Surgical & Cosmetic Dermatology is an official publication of the Brazilian Society of Dermatology (SBD) in partnership with the Brazilian Society of Dermatological Surgery. The technical and scientific content presented in this publication is co-owned by the Brazilian Society of Dermatology.
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SURGICAL & COSMETIC DERMATOLOGY / INSTRUCTIONS TO AUTHORS
GUIDE FOR AUTHORS
Surgical & Cosmetic Dermatology is an interdisciplinary open-access journal dedicated to publishing research on all aspects of Dermatologic Surgery. It also welcomes articles in Cutaneous Oncology, Cosmetic Surgery and Dermatology, Laser, and other Therapy Technologies.
Please see Editorial Policies to:
General information
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Ethical guidelines and research integrity
PREPRINT
We accept the submission of articles deposited in preprints repositories. Authors can share their preprint anywhere at any time.
If a preprint is accepted for publication, we encourage authors to link it to their formal publication through their Digital Object Identifier (DOI).
Authors can update their preprints on bioRxiv (https:// www.biorxiv.org/), medRxiv (https://www.medrxiv.org/) or others with their accepted manuscript.
DISCLAIMER
Statements and opinions expressed in the articles and communications published on Surgical & Cosmetic Dermatology are those of the author(s) and not necessarily those of the Editor(s), Publisher, or Society.
SUBMISSION GUIDELINES
Proper preparation of the manuscript makes the review and publication processes more efficient. Thus, we recommend some precautions that can significantly facilitate the preparation of papers.
Articles must be unpublished and written in the author’s original language (Portuguese or English): the editorial team will provide the necessary versions. The font must be Times New Roman or Arial, 12 points.
The study's title must be concise, informed in Portuguese and English, containing up to 150 characters without spaces, accompanied by a short title.
Abstracts in Portuguese and English must follow the appropriate format for the type of article.
4. Authors must inform full name, abbreviations, and their institutional affiliations, followed by city, state, and country. Links to institutions must be listed in hierarchical order (e.g., first the
Department, second the University). The inclusion of minicurriculums is not allowed.When an author is affiliated with more than one institution, each must be identified separately.When two or more authors are affiliated with the same institution, it should be identified only once. Authors belonging to Private Clinics must cite them as an institution. It is mandatory to mention the ORCID number used to identify researchers for the first and last authors. The author must assume at least one responsibility in the elaboration of the study and must inform the contribution of each one in the submission. One of the authors must be designated as the corresponding author, providing an email address. Authors must also mention the place where the work was conducted. Authors must clearly state any conflicts of interest and financial support.
The keywords must be cited in Portuguese and English, totaling 3 to 10 per language, and they must be included in all types of articles. We recommend that the keywords are obtained from DeCS (Health Science Descriptors) or MeSH (Medical Subject Headings), which can be accessed on the internet.
The limit number of words for texts must follow the type of article and calculated excluding references and abstracts in Portuguese and English.
Extensive and repetitive introductory information should be avoided, giving preference to the most recent, not yet published. Avoid repeating the same information in the abstract, introduction, and discussion.
Weights and measurements must be expressed in the decimal metric system and temperatures in degrees centigrade. Drugs must be mentioned by their generic names, followed by the dose and dosage used, avoiding commercial terms or brands. Descriptions of any equipment, instruments, tests, and reagents must contain the name of the manufacturer and the place of manufacture.
According to the ICMJE, only those who actively participated in the study can be designated as authors, thus assuming public responsibility for its content. Authorship credits must be based solely on substantial contributions to: discussion and planning of the topic and protocol, analysis or interpretation of data; writing of the article or its review; responsibility for final approval for publication.
Other minor contributions such as literature suggestions, data collection and analysis, funding obtaining, technical assistance in conducting routines, patients referral, routine test interpretation, and head of service or department that are not involved in the study do not constitute criteria for authorship. They can be recognized separately in the “Acknowledgments” session, according to the authors’ decision.
ARTICLE TYPES
A Surgical & Cosmetic Dermatology publishes the following article types:
REVIEW ARTICLES
Review articles deepen specific themes in the areas of interest of S&CD, algorithms, compilations, statistics, consensus, and guidelines.These papers have a free format; however, they must contain an unstructured abstract of up to 100 words and conclusions or final considerations. Limit: text up to 6000 words, 10 illustrations, and 60 references. Systematic review articles or meta-analyses must follow relevant guidelines (http://cochrane.org.br).
ORIGINAL ARTICLE
Original articles report original investigative research in Dermatological Surgery, Cutaneous Oncology, Imaging Diagnosis, Dermatology Technology, and Cosmetic Dermatology. Examples: experimental studies, clinical studies, comparisons and descriptions of techniques, or evaluation methods.The text should contain up to 4000 words, 10 illustrations, and 35 references and follow the IMRDC format (Introduction and objective, Methods, Results, Discussion, Conclusion).
Abstract: The abstract must contain up to 250 words and be structured, comprising: Introduction, Objective, Methods, Results, and Conclusions. It is not allowed to state that results or other data will be presented or discussed.
Introduction: State the reasons that motivated the study, describing the current state of knowledge on the subject. Use the last paragraph to specify the central question or objective of the research and the primary hypothesis tested, if any.
Methods: Explain how the study was conducted:
Study type: describe its design specifying the temporal direction (retrospective or prospective), the type of randomization, if any (pairing, drawing, sequencing, etc.), if the study was blind, comparative, placebo-controlled, etc.
Location: indicate where the study was conducted (private or public institution), mentioning the research’s approval by the Research Ethics Committee, the selection procedures, the inclusion and exclusion criteria, and the initial number of patients.
Procedures: describe the main characteristics of the interventions performed, detailing the technique and considering that the investigation study should be reproducible.
Methodology: Description of the methods used to evaluate the results.
Statistical analysis: Inclusion of descriptive and/or comparative statistical analysis describing the sample planning (representative of the universe to be studied), analysis and statistical tests, and presenting the adopted significance levels.We encourage using unusual statistical analyses, but a more detailed description should be made in this case.
Results: Report the main results that point estimates and measures of dispersion should accompany (e.g., mean and standard error) or interval estimates (e.g., confidence intervals), as well as the descriptive levels of the tests statistics used (e.g., “p-value”). Findings must also be interpreted from a clinical point of view.
Discussion: Emphasize the new and essential results found by the study, which will be part of the conclusion. Also, report observations from other relevant studies, mentioning the limitations of the findings and implications for future research.
Conclusions: Clearly and concisely answer the proposed objectives of the study. The same emphasis must be given to studies with positive or negative results.
DIAGNOSTIC IMAGING
Diagnostic Imaging addresses topics or clinical cases where imaging exams (dermoscopy, confocal microscopy, ultrasound, and other methods) are essential for diagnosis or treatment. It must contain unstructured abstract of up to 100 words, text up to 1200 words, 6 illustrations, and 5 references.
HOW I DO IT?
How do I do it? describes new techniques or details of procedures. It must contain unstructured abstract of up to 100 words, an introduction with a literature review, methods, results, discussion, and conclusion. Limit: 1200 words, 8 illustrations, and 30 references.
CASE REPORT
Case report is the description of cases or series of relevant cases in the areas of interest of S&CD, depicting treatments, complications, etc. It must contain unstructured abstract of up to 100 words, an introduction with a literature review, methods, results, discussion, and conclusion, whenever pertinent. Limit: text up to 1200 words, 8 illustrations and 30 references.
LETTERS TO THE EDITOR
Letters to the editor are objective, brief, and constructive comments on previously published studies or research. The text should be up to 600 words, with a maximum of 5 references.
ETHICS COMMITTEE
The authorization certificate by an Ethics Committee is only required for the Original Articles of prospective research.
REFERENCES
Bibliographic references must be listed on the last pages of the article and numbered according to the citation in the text (in sequential numerical order), following the Vancouver style, as indicated by the International Committee of Medical Journal Editors (ICMJE). References cited in table and figure legends must
keep the sequence with the citations in the text. If a document has six or more authors, provide the name of the first six authors followed by "et al".
Below are examples of the most common types of references taken from ICMJE:
Journal articles:
Hallal AH, Amortegui JD, Jeroukhimov IM, Casillas J, Schulman CI, Manning RJ, et al. Magnetic resonance cholangiopancreatography accurately detects common bile duct stones in resolving gallstone pancreatitis. J Am Coll Surg. 2005;200(6):869-75.
Book chapter:
Reppert SM. Circadian rhythms: basic aspects and pediatric implications. In: Styne DM, Brook CGD, editors. Current concepts in pediatric endocrinology. New York: Elsevier; 1987. p .91-125.
Website and online content:
With author: Fugh-Berman A. Pharmed OUT [Internet]. Washington: Georgetown University, Department of Physiology and Biophysics; c2006 [cited 2007 Mar 23]. Available from: http:// www.pharmedout.org/.
When the author is an organization: International Union of Biochemistry and Molecular Biology. Recommendations on Biochemical & Organic Nomenclature, Symbols & Terminology etc. [Internet]. London: University of London, Queen Mary, Department of Chemistry; [updated 2006 Jul 24; cited 2007 Feb 22]. Available from: http://www.chem.qmul.ac.uk/iubmb/
Previous presentation at events:
Bruhat M, Silva Carvalho JL, Campo R, Fradique A, Dequesne J, Setubal A, editors. Proceedings of the 10th Congress of the European Society for Gynaecological Endoscopy; 2001 Nov 22-24; Lisbon, Portugal. Bologna (Italy): Monduzzi Editore, International Proceedings Division; c2001. 474 p.
FIGURES
Figures, charts, and tables must be cited in sequential numerical order in the text in Arabic numerals (example: Figure 3, Chart 7), and the Editor is responsible for suppressing the redundant ones. Figure and charts legends and table titles and footnotes must accurately describe their content in short sentences, but sufficient for understanding, even if the article is not fully read. They must be uploaded in the system in the step corresponding to illustrations, avoiding using the field for the text, so the words within the figures are not counted.
Figures must have a minimum resolution of 300 DPI, minimum width of 1,200 pixels with proportional height, and JPG or TIF formats. The photographs must be in focus, allowing the visualization of the details. Arrows or lines can be used to highlight areas of interest.The legends of histological images must specify staining and magnification. If a figure has been previously published, its source should be cited and included in the references.
The copyright holder's permission for its reproduction must be sent to the journal. The use of pictures that identify patients’ faces requires a written authorization (see the document Consent of Publishing Patient Photographs on the journal’s website).
Regarding videos, it is necessary to insert subtitles containing information such as the title of the manuscript, authorship, institution, and other relevant comments. When using patient images, their identity must be preserved; otherwise, written permission for disclosure must be attached.
Charts must be prepared in Microsoft Excel. Tables do not need to be described in the text because their objective is to supplement it and not augment it. The units used to express the results (m, g, g/100, mL, etc.) should appear at the top of each column. Patients must be identified by numbers or letters, and never by names, initials, or hospital registration numbers.
COVER LETTER
The cover letter must include the following information: An explanation of why your manuscript is suitable for publishing in Surgical & Cosmetic Dermatology.
Confirmation that the manuscript's content is original and has not been published nor is being considered for publication elsewhere.
If the manuscript is being submitted for a particular special issue, its specific name must be mentioned in the cover letter.
If the article reports the results of a health intervention in human participants, Surgical & Cosmetic Dermatology strongly recommends its record in an appropriate registry. The registration number and date must be indicated in this letter.
AUTHORS’ DECLARATIONS
The following final statements must be included in the final version of the manuscript. These declarations are expected to be submitted along with the cover letter since Surgical & Cosmetic Dermatology adopts a double-blind peer review.
‘Acknowledgments’ – list of people who contributed to the article (and does not meet the criteria for authorship), including contributors who provided professional writing services or materials.
‘Availability of data and materials’ – availability statements contain information on where data supporting the results reported in the article can be found, such as hyperlinks to publicly archived datasets. Example sentences are: ‘All data generated or analyzed during this study are included in this article’; ‘The datasets generated and/or analyzed during the current study are available in the [NAME] repository’, ‘The datasets generated during and/ or analyzed during the current study are available from the corresponding author on reasonable request’ or ‘Not applicable’ if no new data were created or analyzed in the study.
‘Financial support’ - all sources of funding of the study
should be disclosed; it is necessary to indicate grants that authors have received in support of the research.
‘Conflict of interest’ – all financial and non-financial competing interests must be declared in this section. If the authors do not have any competing interests, it is necessary to state ‘The authors declare that they have no conflict of interest’.
‘Authors’ contributions’ – Each author is expected to have made substantial contributions to the manuscript, which should be specified in this section. Please use initials to refer to each authors’ contribution. For example: ‘AB, CD, and EF conceived this research and designed experiments. GH participated in the design and interpretation of the data. IJ performed experiments and analysis. KL and MN wrote the paper and participated in the revisions of it. All authors read and approved the final manuscript’.
The maximum acceptable limit of authors is 5 (five); there will only be an exception for more complex works (ex. Original Article, Review) upon justification and approval by the editors.
‘Ethics approval/Ethics approval and consent to participate’: manuscripts reporting studies involving human participants or human data must include a statement on ethics approval and consent and include the name of the ethics committee that approved the study and the committee’s reference number. Studies involving animals must include a statement on ethics approval. If the manuscript does not report on or involve the use of any animal or human data, it is necessary to state ‘Not applicable’.
‘Consent for publication’if the manuscript contains any individual's personal data in any form, consent for publication must be obtained from that person, or in the case of children, their parent or legal guardian. All presentations of case reports must have consent for publication.
SUBMISSION
Manuscripts should be submitted through our online submission system (https://www.gnpapers.com.br/scd/default. asp?lang=en). The submitting author is responsible for the manuscript during the submission and peer-review process. They must ensure that all eligible co-authors have been included in the author list and have all read and approved the submitted manuscript. The following files are required to submit a manuscript:
The main manuscript file, which must not include the names of authors or co-authors (an anonymous file since the journal uses double-blind peer review). References and smaller tables should be included in this file.
A title page, which must contain the names of all authors and co-authors, their affiliations, emails, and all authors’ declarations.
A cover letter.
Figure files.
Any additional files as supplemental material to the manuscript.
All documents such as Copyright, Conflict of Interest, and Consent for Publishing Photographs are available on the journal’s website and in the online submission system. These documents must be signed by all participating authors and attached to the system when submitting the manuscript. Consent for Publishing Patient Photographs is only necessary when the patient’s face is fully identified. The editors will only request the Paper Participation document if necessary.
Table of contents
Official publication of the Brazilian Society of Dermatology
APRIL - JUNE 2025 l Volume 17 l Number 2
ISSN:1984-5510
Online ISSN: 1984-8773
REVIEW ARTICLE
Multidisciplinary consensus on the topical vitamin C benefits
137 Flavia Alvim Sant'anna Addor, Ana Claudia Cavalcante Esposito, Emerson de Andrade Lima, Lucas Portilho, Eliana Mika Yamaguchi, Sylvia Ypiranga
Sodium Deoxycholate - Mechanism of action, application technique, indications and adverse effects
Mar isa Gonzaga da Cunha, Ana Lúcia Gonzaga Cunha, Daphine Tironi Giglio, Débora Terra Cardial, Gabrielle Ellert de Almeida
Treatment of periungual wart: literature review
Emerson Henrique Padoveze, Suelen Montagner, Thamires Prado Dantas, Nilton Gioia Di Chiacchio, Nilton Di Chiacchio
ORIGINAL ARTICLE
Systematic Global Body Assessment - A tool to support optimal patient selection for non-surgical treatment of skin laxity
Vitamin C, or L-ascorbic acid, is the most abundant antioxidant in human skin and its topical replacement has proven relevant, since this reservoir is consumed by external aggression, and it is used in the prevention and treatment of skin aging. This review was based on bibliographic research in the PubMed and LILACS databases and two consensus meetings between the authors to analyze the evidence for its topical use. The highest level of evidence of skin activity has been found in the pure and stabilized form of ascorbic acid. Derivatives, carriers, and nanoformulas are being developed, however further clinical and comparative studies are needed.
A vitamina C, ou ácido L-ascórbico (AA), é o antioxidante mais abundante na pele humana, e sua reposição tópica mostrou-se relevante, pois seu estoque é consumido diante de agressões externas, e por atuar na prevenção e tratamento do envelhecimento cutâneo. Essa revisão baseou-se em pesquisa bibliográfica nas bases PubMed e LILACS e em duas reuniões de consenso entre os autores para análise das evidências sobre seu uso tópico. O AA puro e estabilizado é a forma que apresenta maior nível de evidências de atividade na pele. Derivados, carreadores e nanofórmulas estão sendo desenvolvidos, entretanto mais estudos clínicos e comparativos são necessários. Palavras-chave: Ácido Ascórbico; Antioxidantes; Envelhecimento da Pele; Hiperpigmentação; Cosmecêuticos.
1 Grupo MEDCIN, Centro de Pesquisa Clínica, São Paulo (SP), Brazil
2 Universidade do Oeste Paulista, Dermatologia, Presidente Prudente (SP), Brazil
3 Santa Casa de Misericórdia do Recife, Dermatologia, Recife (PE), Brazil
4 Instituto de Cosmetologia Educacional, Campinas (SP), Brazil
5 Universidade Federal de São Paulo, São Paulo (SP), Brazil
Financing: L'Oréal Brazil provided funds for the in-person author meetings.
Conflicts of interest: Flávia Addor works as a speaker, researcher, and consultant for L'Oréal Brazil, Galderma, Eucerin and Kenvue. Ana Cláudia Cavalcante Espósito has performed scientific activities with L'Oréal Brazil. Sylvia Ypiranga has worked as a speaker for Galderma.
Submitted on: 04/16/2024
Final decision: 07/25/2024
How to cite this article: Addor FAS, Esposito ACC, Lima EA, Portilho L,Yamaguchi EM, Ypiranga S. Multidisciplinary consensus on the benefits of topical vitamin C. Surg Cosmet Dermatol. 2025;17:e20250366.
INTRODUCTION
Given that the skin is the organ most exposed to external factors that accelerate the skin aging process, such as ultraviolet radiation, smoking, pollution, poor diet and stress,1 the skin care market is the leading segment of the cosmetics industry, accounting for approximately 36% of the global market.Vitamin C, or L-ascorbic acid (AA), is an important ingredient in dermocosmetic products due to its multifunctionality.2,3 AA is an essential nutrient obtained exclusively from exogenous sources, and is the most abundant antioxidant in human skin,4 whose biochemical activity is restricted to its levorotatory (L) form, since the dextrorotatory form has no significant biological activity.5 The first publications on the topical use of AA date back to the early 1960s, and this form is essential for increasing cutaneous bioavailability, given that the levels achievable through topical application are 20 to 40 times higher than with oral AA supplementation.6 Moreover, when the skin becomes saturated with AA through topical application, a reservoir effect occurs in which AA tends to stabilize and remain available in the skin for 3 to 4 days.4,6,7 This storage provides prolonged protection against environmental damage, such as UV radiation, pollution, and smoking, which induces oxidative stress in the skin.1,7–9 Although the effectiveness of topical AA has been demonstrated,8,10 developing formulations for topical use is still challenging due to the molecule’s instability, which has stimulated research into AA derivatives and active release technologies. However, although molecular stability has been improved through these innovations, comparative studies on the clinical response and therapeutic action of these new derivatives in comparison with AA are still lacking in the literature. This review will explore the types of AA available for topical use, their proven benefits, and their applicability for clinical dermatology.
METHODS
This article is the result of two consensus meetings between the authors, dermatologists, and pharmacists held in November 2022. Prior to the meetings, a comprehensive bibliographic search was performed in the PubMed and LILACS databases, using a combination of the keywords “vitamin C” or “ascorbic acid” and “skin” and “topical”, to find relevant articles involving three themes: (1) the efficacy, function, and mechanism of action of AA in its different formats; (2) advances in formulation regarding the efficacy, stability, skin penetration, and bioavailability of AA and its derivatives; and (3) the application and clinical efficacy of topical AA in different forms. A third of the selected articles involved authors affiliated with Brazilian institutions, indicating the relevance of the topic in Brazil. In the meetings, the topics were discussed based on the published literature, and while preparing the review’s manuscript, other published articles and relevant technical documentation were included by mutual agreement among the authors.
RESULTS AND DISCUSSION
Biological functions of vitamin C in the skin
The most discussed functions of AA in the literature are its ability to neutralize free radicals (including reactive oxygen species) and its relevance in collagen synthesis. Table 1 summarizes the evidence of these and the other functions of AA and some of its derivatives in the skin, including anti-inflammatory action, photoprotection, its importance in the skin barrier function, antiglycation action, and brightening action.2,8–11
Specificities of topical vitamin C formulation
In topical formulations whose main active ingredients are antioxidants, factors such as compatibility, stability, and penetration must be prioritized, ensuring that their action is synergistic and that the active ingredients are not neutralized in the vehicle.7,20 One of the main challenges in using AA is to ensure its chemical stability and topical bioavailability in a suitable vehicle.23,24 Eight types of serum sold in the Brazilian market were evaluated biweekly for AA content with ultra-high performance liquid chromatography, of which only three had concentrations ≥ 5% at baseline and after 60 days. It was also observed that the cost of the AA serum may be related to the product’s quality and stability, since the most expensive samples had the highest concentrations of AA throughout the study.25 AA is a very unstable molecule that can easily oxidize, losing its antioxidant capacity, either by ionization in water at neutral or higher pH (greater stability is obtained at pH ≤ 4), or by exposure to light, high temperature, contact with air, or the occurrence of metal ions.26 In fact, AA initially degrades to dehydro-L-ascorbic acid in a reversible manner, but can be irreversibly hydrolyzed to 2,3-diketo-L-gulonic acid (Figure 1), losing its activity and degrading into small molecules. The reversible transformation of AA into dehydro-L-ascorbic acid in the skin functions as an oxidation-reduction system that allows cellular interaction and bioactivity of the two molecules.5 In formulations, the AA degradation process is generally accompanied by a gradual change in color,24 However, the isolated darkening of the formula cannot necessarily be considered as loss of dermatological efficacy, since it is also related to the concentration of free AA and bioavailability in the skin.25 Pinnell et al.7 studied the ideal parameters for enabling percutaneous absorption of AA and supplementing the skin’s natural antioxidant reservoir. They found that pure AA (pharmaceutical grade) should be formulated cold in an acidic medium (pH ≤ 3.5) to prevent ionic charge degradation.7 In addition to adjusting the pH, the formulation must contain an ideal concentration of AA (5 to 20%) to promote delivery of the active ingredient through the stratum corneum and hence achieve better results. When testing AA concentrations of 5 to 30% at pH 3.2, skin levels of AA increased, reaching their maximum at 20%, with decreased permeation tending to occur at higher concentrations.2,7 In addition to standardizing the physical-chemical parameters of pure and free AA solution, such as the ideal concentration and pH to ensure stability and dermal penetration,7,20,27 other strategies have
Table 1: Evidence of the main biological actions of L-ascorbic acid and some of its derivatives in the skin
Biological action Study design
In vitro (chemiluminescence)
Antioxidant effect
Moisturizing effect
In vitro (lipid peroxidation)
In vivo (daily application for 4 weeks on the forearm of healthy individuals)
In vitro (keratinocyte culture)
AA 0.000125% to 0.002%;
MAP 0.0021% to 0.0337%; ATIP 0.0082% to 0.1316%
AA 0.6% and 1.5%;
MAP 0.45% and 0.9%; and ATIP 0.45% and 0.9%.
AA 2% at pH 3.5; MAP 2% at pH 7.0; ATIP 2% at pH 5.5
AA 50 μg/ml and 1.2 mM calcium ions
Effect on skin barrier integrity
Effect on collagenesis
In vitro (keratinocyte culture, reconstructed human epidermis and bilayer skin equivalent)
In vitro (keratinocyte culture)
In vivo (biopsy, postmenopausal women) AA 5% at pH 6.0
In vitro (culture of human skin fibroblasts exposed to UV radiation and hydrogen peroxide);
vitro
Anti-inflammatory effect In vitro (keratinocyte and fibroblast cultures)
Antiglycation effect In vitro
Photoprotective effect
Whitening effect
In vivo (topical application to porcine skin for 4 days prior to UV irradiation)
AA 15% + vitamin E 1% at pH 3.2; comparison with isolated actives at the same concentration
AA 15% + vitamin E 1% + ferulic acid 0.5%; comparison with isolated active ingredients in the same concentration
In vitro (culture of UVA-irradiated keratinocytes) 3-O-ethyl ascorbic acid
In vivo (clinical examination, women 23 to 43 years of age)
Antioxidant activity proven by inhibiting the formation of free radicals even at low concentrations; AA showed a better antioxidant effect than the derivatives.
All formulas increased hydration of the stratum corneum;
AA increased transepidermal water loss, indicating increased epidermal cell renewal; MAP, despite penetrating less than AA, increased hydration in the deep epidermis; ATIP had no effect.
Significant increase in ceramide content, helping in the proliferation and differentiation of keratinocytes in the epidermis and improving hydration
Increased content of glucosylceramide and ceramide 6 and 7; improved lipid profile and architecture of the stratum corneum.
Increased keratinocyte differentiation through activation of the protein kinase C-dependent transcription factor activating protein-1.
Increased mRNA levels for procollagens I and III
Cofactor of lysyl and prolyl hydroxylase enzymes that crosslink and stabilize collagen fibers (adequate structure)
Protective effect on degenerative changes that reduce collagen due to decreased superoxide dismutase in the skin
Inhibition of nuclear transcription factor kappa B. Oxidative stress activates nuclear transcription factor kappa B, which is responsible for inducing the production of several pro-inflammatory cytokines, such as TNF-alpha, IL-1, IL-6 and IL-8, which contribute to inflammation and skin aging.
Inhibition of glycation and subsequent end-products.
AA 15% and vitamin E 1% alone protected the skin from UV-induced erythema 2 times more than the vehicle; AA 15% + vitamin E 1% and ferulic acid 0.5% alone protected the skin 4 times more. AA 15% + vitamin E 1% + ferulic acid provided 8 times more protection against UV, which was confirmed by colorimetry of the erythema and sunburn cell count with significant decrease.
Reference
Campos et al 12
12
Kim et al 13
Ponec et al 14
Savini et al 15
Nusgens et al 16
Gegotek et al 17
Lin et al 20
3-O-ethyl ascorbic acid had antimelanogenic effects via Nrf2-mediated a-MSH inhibition and autophagy induction Chen et al 21
AA inhibited tyrosinase through interaction with copper ions at the beginning of the melanin synthesis pathway
Espinal-Perez et al 22
Maia
Maia Campos et al.
Addor18
Farris2
Gkogkolou & Böhm19
been developed to overcome the limitations of topical administration (Figure 2). Efforts to make the topical administration of AA viable are only clinically important when the strategy not only stabilizes AA but ensures its safe penetration into the skin and that it remains free and stable long enough to perform its activity. Adding preservatives and co-antioxidants prevents the degradation of AA. Vitamin E, ferulic acid, and sodium metabisulfite have shown good results, although use of the latter is limited due to its odor.24,28 In addition to ferulic acid, other active plant-based ingredients can be used in synergistic antioxidant systems to stabilize AA.24,29 The flavonoid phloretin stabilizes and increases the cutaneous availability of topically applied AA and ferulic acid.29,30 The lipophilicity of phloretin, which indicates high solubility in skin lipids, can explain its use as a permeation enhancer for other active ingredients.29 Silymarin 0.5%, obtained from the Silybum marianum thistle, synergizes with AA 15% and ferulic acid 0.5% in an aqueous formulation with an acidic pH to reduce lipid peroxidation caused by exposure to UV radiation.31
Degradation of topical AA can also be avoided by using polyol-type humectants and solvents, such as glycerin, propylene glycol, and butylene glycol for non-aqueous vehicles with low oxygen permeability.24 Humectants, such as palmitic acid, propanediol, and glycerin, have also positively influenced the stability of AA in anhydrous vehicles or emulsions.24 Based on these results, polyols have been used in water-in-silicone emulsions, with a formulation prepared in a nitrogen atmosphere, to associate pure AA in concentrations of 5 to 10% with glycerin and
other polyols that, in addition to preventing contact between AA and the water in the emulsion, facilitate penetration and action directly in the dermis, where collagen fibers are formed.16,32 A number of AA derivatives have been proposed, and some are already being used in dermatology, to facilitate the permeation, stability, and bioavailability of AA. Generally, AA derivatives must be enzymatically converted to AA in keratinocytes and fibroblasts to have an effect.28,33 To date, however, no information could be found on the impact of AA derivatives on the skin’s AA reservoir. However, the possibility of numerous combinations of AA derivatives with similar or different solubilities, and even with AA itself in the same formulation, could be advantageous.24 The main AA derivatives used in Brazil, both in industry and in compounding pharmacies, are magnesium ascorbyl phosphate,12,24,26,28 sodium L-ascorbyl-2-phosphate,24,28 ascorbyl tetraisopalmitate,12,24,28,34 ascorbyl methylsilanol pectinate,25,35 ascorbic acid 2-glucoside24,28,36–38 and 3-O-ethyl ascorbic acid21,28,39, which may be known by different trade names. However, the level of scientific evidence for the efficacy of AA is superior to that of derivatives (Table 2). Nanotechnology vectorization and encapsulation have been used to improve topical delivery of the active ingredient and protect AA from degradation.24 These systems include microvectors and nanovectors, liposomes (double lipid membrane with hydrophilic content), microemulsions, and micelles, which can dynamically increase the stability of AA in search of more durable products. However, it is challenging to define the ideal concentration of AA or derivatives and the permeation of AA into the skin.24,28 In general, articles that address
Figure 1: Oxidation of L-ascorbic acid
the vectorization process have not reported the concentration of free AA in the vectors.28,40
AA: L-ascorbic acid; MAP: magnesium ascorbyl phosphate; SAP: Sodium L-ascorbyl-2-phosphate; ATIP: ascorbyl tetraisopalmitate; AMP: ascorbyl methylsilanol pectinate; AA2G: ascorbic acid 2-glucoside and EAA: 3-O-ethyl ascorbic acid. It has been demonstrated that liposomal formulations in vesicles with different lipid compositions containing AA have increased the stability of AA and promoted greater skin retention, suggesting efficacious treatment of skin photoaging.41 The negative liposomal charge favored retention of the active ingredient in the epidermis and dermis.40 Nanotechnology has led to the development of several raw materials for cosmetics (nanovectors, nanocapsules, nanosomes, ethosomes, niosomes, and other nanometric systems) that improve the stability and permeation of AA in the skin, based on different types of materials. Although the supply of dermatological products and ingredients for compounding AA or nanoencapsulated AA derivatives is growing, there are still few studies, especially in vivo studies, regarding the targeting, permeation, and, most importantly, the concentration of free AA delivered to the skin through nanotechnology.33,41,42 In Brazil, magnesium ascorbyl phosphate is available through commercial encapsulation systems in collagen and chondroitin sulfate of marine origin, in both micro- and nanospheres, which reinforce the stability of the derivative to increase skin permeation. However, even with nanotechnology, permeation appears to be limited to the epidermis, with prolonged release of the content through en-
zymatic degradation.24,41 Ultradeformable elastic nanovesicles (spanlastics), formed mainly from alcohol, propylene glycol, polysorbate 80, and surfactants, which were loaded with AA and compared with AA solution at pH 2.38, have shown better permeation and cutaneous concentration at a dose sufficient to demonstrate antioxidant efficacy, lower metalloproteinase expression in vitro, and clinical improvement of UVB-damaged skin according to histological evaluation.33,43 Nanotechnology requires quality control and particle size control during manufacturing. To ensure safety for topical use, vectors > 100 nm are recommended to avoid the risk of systemic permeation. Few articles have demonstrated the cutaneous bioavailability of AA in nanotechnology formulations, and limited information is available about the concentration of either AA or the derivative used in the delivery system. In general, few studies have compared AA and its nanotechnological form, despite evidence that nanoparticles can release AA for > 8 h in vitro 44 Although nanotechnology is promising for cosmetics, there are regulatory and industrial issues that limit its clinical use.24 It is difficult to determine the specificity and clinical efficacy of each nanotechnological formulation of AA and derivatives.24,28,33 RNA or DNA structures with high affinity and specificity for targets of interest, called aptamers, were the subject of a recent study on AA delivery. The DNA and AA aptamer was proposed as a new possibility for stabilizing AA in cosmetics.33
Figure 2: Main strategies for topical viability of vitamin C
Evidence on the relationship between the efficacy and transcutaneous penetration of vitamin C in different formulations
Both the topical application of AA and its delivery to the skin layers are intrinsically dependent on the characteristics of the formulation.7,24,26 However, comparative studies assessing the stability and effective transdermal penetration of different forms of AA are generally limited to in vitro studies.24,26 Pinnell et al.7 tested two products commercially available in the United States that contain AA derivatives (associated with magnesium ascorbyl phosphate 12% and ascorbyl palmitate 10%) in comparison with a formulation of pure AA 15% (free and stabilized at pH 3.2). Unlike ideally parameterized AA, topical application of formulations with AA derivatives did not significantly increase the AA content in the skin.7 Despite being more stable, these AA derivatives appear to have lower skin penetration than free AA and do not have direct antioxidant activity, requiring conversion to AA by enzymatic reaction.24,26 Later studies indicated that esterifying AA with palmitic acid does not guarantee satisfactory stability levels in topical products, despite the lipid nature of ascorbyl palmitate, probably because it interferes with the barrier function and antioxidant action of vitamin E in the skin.24,26,45 One study suggested using AA 2-glucoside, a derivative of AA, in cosmeceuticals, although its antioxidant activity is lower than that of AA.36 In this derivative, a glucose molecule associated with the hydroxyl group of the second carbon atom of AA protects it from high temperatures, pH, metal ions, light, and other degra-
dation mechanisms. In the skin, it reacts with the alpha-glucosidase enzyme to release AA.36 Thus, AA 2-glucoside was shown to be chemically stable and completely metabolized into AA, which guaranteed antioxidant efficacy (in vitro and ex vivo) at concentrations lower than those recommended for pure and free AA, although in vivo it had lower antioxidant action than AA plus vitamin E.28,37 Another study suggested that AA 2-glucoside may protect cells against ionizing radiation by acting against free radicals, reducing initial DNA damage.38 It has been observed that 3-O-ethyl AA is more lipophilic than AA 2-glucoside, which makes it more easily absorbed by the skin than other water-soluble AA derivatives.39 Several mechanisms have been proposed for the antimelanogenic effect of 3-O-ethyl AA: increased autophagy in melanocytes19; inhibition of alpha melanocyte-stimulating hormone and increase in endogenous antioxidants via Nrf2 in keratinocytes21; lower activity of the transcription factor that regulates melanogenesis in melanocytes21; and lower tyrosinase activity through melanocyte cytoplasmic acidification.46 It was also observed that AA plus magnesium ascorbyl phosphate has lower melanin and tyrosinase activity due to cytoplasmic acidification, which could result from increased transportation of AA across the membrane by the sodium-dependent vitamin C transporter-2.46 This mechanism is an efficient way to inhibit tyrosinase without causing cytotoxicity to melanocytes.46 Encapsulating AA 5% in emulsions containing liquid crystals, based on a combination of cetyl alcohol and polysorbate 60, formed a complex colloidal structure at the oil-water interface that ef-
ficiently stabilized AA for 4 months. Subsequently, a controlled clinical trial evaluated the effects of topical application of this stabilized form for 30 days compared to placebo, finding dermal redensification in high-frequency ultrasound measurements.23 Regardless of the strategy used to keep AA stable, the molecule must remain in or be converted into its free form to perform its biological activity.24,32 It has been found that the bioavailability of free AA in the skin layers (up to the dermis) could be increased by optimizing transcutaneous penetration through the following molecule stabilization parameters: AA in pharmaceutical grade purity; concentrations ranging from 5 to 20%, formulation at a low pH (2-4) and the presence of co-antioxidants, such as bioflavonoids and/or vitamin E.7,26 Using a non-invasive method (Raman spectroscopy), a recent study assessed AA penetration in the skin of 10 healthy individuals after topical application of a serum containing 15% pure AA, free and stabilized at a low pH in combination with other antioxidants (vitamin E 1% and ferulic acid 0.5%). There was a significant increase in total AA in the upper layers of the skin 1h and 6h after application, as well as a significant increase of AA in the dermis after 6h, which demonstrated the epidermal and dermal bioavailability of AA in this serum.27 Raman spectroscopy has also been used in vivo to compare an emulsion containing lipophilic derivatives of vitamins A, C (ascorbyl tetraisopalmitate), and E with an emulsion containing nanoparticles of these derivatives. The nanoparticles contributed to greater penetration of ascorbyl tetraisopalmitate and vitamin E derivative in terms of speed and depth, but they did not significantly improve the penetration of the vitamin A derivative. Although, in both emulsions, the three derivatives penetrated rapidly into the stratum corneum, the nanoparticles did not contribute to deeper penetration and, after 6 h, the lipophilic derivatives had penetrated only to the upper layers of the epidermis.47
Clinical evidence on the action of vitamin C
The clinical strategies and applicability of AA in dermatology are quite broad, since the skin requires a high concentration of AA to remain healthy. Topical use (Figure 3) is recommended mainly to treat skin aging, prevent photoaging, and reduce hyperpigmentation, increasing the uniformity of skin tone.1,9
Oxidative damage caused by the exposome
AA has been shown to be a potent topical antioxidant that neutralizes free radicals, which tend to accumulate in the skin due to exposure to exposomal factors, such as UV radiation, pollution, and smoking, which induce or aggravate dermatosis.8,18 This activity is particularly important in the epidermis and corroborates the role of AA as a water-soluble component of the skin’s antioxidant defense system, which is regulated by a complex network of enzymatic and non-enzymatic antioxidants, exogenous or endogenous, that protect the intra- and extracellular spaces from free radicals and, consequently, slow the skin aging process.6,18
Signs of skin aging
In addition to protecting against exposure damage, AA is essential for collagen synthesis and regulation of the collagen/elastin balance in the dermis. In a double-blind, controlled trial of 10 individuals with clinical photodamage to the face, 12 weeks of AA 10% treatment reduced photoaging scores and improved facial wrinkles and skin texture on the AA-treated side compared to the placebo side.9,48 In addition to clinical improvement, biopsies have shown increased collagen in the dermis.16,48 A significant improvement in skin histology and clinical appearance was observed in another double-blind, placebo-controlled trial using topical, free AA 5% stabilized in a cream applied to 20 individuals over a six-month period.16,32 The efficacy of AA and its derivatives for skin rejuvenation can be synergistically enhanced through combination with other active ingredients,49,50 such as amino acids, peptides, growth factors, hyaluronic acid, vitamin E, and other antioxidants.28,33 The patient’s therapeutic routine may require combination with other active ingredients, such as salicylic acid, niacinamide, or retinol.28 Amino acids, in particular glycine, proline, and lysine or their precursors, can facilitate collagen production.33 Reinforcing the relevance of the synergy of active ingredients in anti-aging efficacy, a gel-cream containing AA 5%, mannose 5%, and fragmented hyaluronic acid demonstrated clinical efficacy in reducing fine wrinkles and sagging, while increasing hydration, luminosity, and skin tone uniformity, which was corroborated by an in vitro study in an equivalent dermis model.50 In an ex vivo study, Neves et al. assessed a serum containing AA 15% associated with neohesperidin, Pinus pinaster bark extract (trade name Pycnogenol), tocopherol, and hyaluronic acid, which, compared to the vehicle, reduced mRNA gene expression of inflammatory mediators associated with skin aging induced by air pollution.49 The same formulation was tested for 90 days in a clinical and instrumental study (n=40), and it was found capable of reducing signs of skin aging, improving the structure of the dermoepidermal junction and reducing pigmentation of the basement membrane. Thus, it proved efficient in protecting the skin against pigmentation/skin aging induced by air pollution.49
Hyperchromia
In addition to its effects on signs of skin aging, AA also plays a role in the treatment and prevention of skin hyperpigmentation. Melanocytes are highly susceptible to oxidative damage, since melanogenesis is a pro-oxidative pathway. Thus, AA acts on melanogenesis by combating free radicals and inhibiting tyrosinase. In addition, AA favors the differentiation of keratinocytes and improves dermoepidermal cohesion, contributing to uniform skin tone.8,22 Topical AA can help treat melasma and aid in skin maintenance after procedures for solar melanosis.24,26,28 AA 5% and hydroquinone 4% in water-in-oil emulsions were compared in a for 16-week double-blind trial conducted in 16 individuals with melasma (phototypes IV
and V). Although there was a faster and much better clinical response with hydroquinone (93.75% showed good to excellent improvement), adverse effects occurred in 68.75% of the patients, while on the side treated with AA they occurred in only 6.25% of the patients, which showed positive results (good to excellent improvement) in 62.5% of cases.22
Dermatological procedures and technologies
Topical application of AA and derivatives has been combined with procedures such as ultrasound, iontophoresis, ablative laser, microneedling, and microdermabrasion to increase the penetration and effects of AA.33,51 The use of iontophoresis after topical application of AA increases the percutaneous absorption of the active ingredient in comparison with simple topical application. A controlled trial investigated 24 individuals treated with a serum containing AA 10% to the entire face and, on only one side, used a portable iontophoresis device at home twice a week for 8 weeks. Standardized images and corneometer measurements were made every 2 weeks, showing significant improvement in hydration and pore closure, although the device had less power than the model developed for medical use.52 Previous studies have shown that iontophoresis following topical appli-
cation of AA increases collagen production.33 Fractional lasers have been used by dermatologists to treat signs of skin aging, and these procedures can substantially consume skin antioxidants. Combining the procedure with topical AA may reduce inflammation and help restore the skin.51 A study demonstrated that after a fractional laser procedure, 7 daily applications of a serum containing AA 15% (stabilized at acidic pH) in association with ferulic acid and vitamin E reduced edema and erythema more rapidly than the vehicle (hemifacial; n=15). Overall, the serum was well tolerated immediately after fractional laser treatment, and the acidic pH helped inhibit infection. Furthermore, compared to the vehicle, the AA serum prevented a reduction of basic fibroblast growth factor. This marker is important not only in the proliferation of fibroblasts, but also in the synthesis of extracellular matrix macromolecules (glycosaminoglycans and hyaluronic acid) and inhibition of matrix metalloproteinase-1.51 More recently, an article proposed topical application of a serum with AA 15% stabilized at acidic pH and associated with vitamin E and ferulic acid as an adjuvant treatment with Q-Switched Nd:YAG laser therapy. A comparative controlled trial included 18 men and women with melasma or solar melanosis, who applied the serum twice a day for 2 weeks after the laser
Figure 3: Actions and indications of topical vitamin C
procedure. On the treated side, they presented a significant reduction in melanin index, but not in post-procedure erythema.53 This laser therapy’s brightening potential also enhances the penetration of active topical brightening and antioxidant ingredients for a synergistic effect. A case study on melasma treatment assessed the effect of a topical antioxidant serum containing AA 10% stabilized with phloretin and ferulic acid that was, for 120 days, applied daily and immediately after each biweekly Q-Switched laser session as an adjuvant treatment, due to the role of oxidative stress in this type of dermatosis.54 These practices are consistent with integrated skin care that combines in-office treatments with at-home products to achieve complementary clinical benefits and reduce unwanted side effects. These studies support the efficacy of topical AA application immediately after deliberate barrier-breaking procedures, but the use of cosmetics for post-procedure AA delivery is under investigation by regulatory authorities.33,51
Parameters for prescription
A range of dermocosmetics that include AA is available to dermatologists, featuring different packaging, concentrations, and textures, mainly in serum, gel-cream, and cream forms.3 While product availability makes it easier to adapt to the daily routine of patients, it also requires dermatologists to have in-depth knowledge of pharmacotechnical techniques to best adapt AA therapy to the clinical needs of each patient. In addition to considering the concentration, quality, and molecular form of AA, it is important to select a vehicle that presents a sensory experience adapted to the patient’s skin type and profile, which facilitates treatment adherence. However, the main indication for AA in daily facial care seems to be the stimulation of collagen synthesis, which prevents and reduces signs of skin aging, smoothing fine wrinkles, and promoting perceived improvement in skin vitality, brightness, and firmness.28 To this end, the active form of AA should reach deeper layers of the skin, ideally the dermis. Although AA does not absorb UV radiation, its undeniable ability to neutralize free radicals has justified the use of topical AA as a daily antioxidant (before applying sunscreen) to optimize protection against exposomal damage and, consequently, reduce the degradation of collagen and elastin, preventing signs of skin aging.9 Using topical AA to maintain the skin’s antioxidant reservoir at adequate levels is an adjuvant strategy to the daily use of sunscreen. These are important complementary mechanisms,7 since UV radiation and high ozone levels due to pollution deplete vitamins C and E from the skin’s surface.1,7 Furthermore, laboratory studies have demonstrated a significant reduction in UVB-induced erythema after topical application of AA 10%.2 AA derivatives have been added to sunscreens to prevent lipid peroxidation in oily and acne-prone skin, but the effects of each formula must be verified in vivo. For everyday use, AA has been shown to be a safe active ingredient, even with prolonged use5 in all skin types, including sensitive skin.8,54 However, some products may include warnings about the possi-
bility of skin discomfort due to the high concentration of AA, suggesting a longer interval between applications.5 For sensitive skin, formulations with very low pH should be avoided due to the possibility of irritation. Specific products have been developed for these individuals that combine soothing ingredients, such as acetyl dipeptide-1 cetyl ester (trade name Neurosensine), with 5% to 10% pure and free AA stabilized at pH 4.0 to 6.0 to reduce the possibility of sensitization. Formulations with AA derivatives (stable at pH 5 to 7) or nanoencapsulated AA promise less irritation and also seem suitable for those with sensitive skin. Dermocosmetics with AA are often indicated for use once or twice a day, and deciding about the most suitable product is influenced by several factors, such as a history of sensitive skin, the degree of oiliness, age, the individual needs of each patient, as well as the relationship between AA concentration and skin permeation.9,27,28,40 Clinical trials of topical products containing AA are increasingly important, since different vehicles and combinations with other active ingredients can have different results. The results of AA derivatives can also differ from the free form, even when using the same vehicle. Because interactions between the ingredients can be unpredictable, dermatological studies and clinical evaluations must be performed on each formula to provide clinical confidence. In vitro studies, which indicate possible mechanisms of action, cannot guarantee the same efficacy in vivo. Proof of a product’s efficacy must be based on clinical trials. Table 2 shows that, at present, only free AA has shown clinical efficacy and, thus, is considered the gold standard molecule in dermatology. Furthermore, it has been demonstrated that free AA, stabilized in its active form, has the best penetration in both the epidermis and the dermis, preventing and treating of signs of skin aging and skin hyperpigmentation.7,20,30 There are still few comparative studies between AA and its derivatives or standardized clinical trials on different forms developed to provide greater topical efficacy. Thus, new studies are needed to fill this gap. This review has led to the following conclusions: increasingly higher concentrations of AA do not result in more effective products7; in addition to the concentration, the effectiveness of AA depends on the chemical form, vehicle, and even the packaging; pure AA, although easily oxidizable, can be stabilized at an acidic pH and through association with co-antioxidant active ingredients, as well as through specific technologies (polyols, for example); not all AA derivatives can release AA into the skin, and many only permeate the superficial epidermal layers; although some products report that nanovectors containing AA derivatives are can release AA equivalents, no clinical trials have validated this information.
FINAL CONSIDERATIONS
Numerous forms of AA are already available for topical use in dermatology, being recommended for the prevention and treatment of signs of photoaging, either as monotherapy or in combination with other active ingredients or in-office procedures. Clinical practice should be based on published evidence
and should encourage research, in addition to transparency regarding technical information, efficacy and safety. For each formulation, the stability, penetration, and bioavailability of AA in the skin must be assessed, and data on clinical efficacy and pa-
tient adaptation to the product must be provided. AA is still the gold standard molecule for clinical practice (Figure 4) due to the higher level of evidence16,22,23,32,48–50,52,53 regarding its mechanisms of action and clinical activity than other derivatives34,55–60 and molecules available through nanotechnology. l
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57. ascorbyl phosphate shows in vitro and in vivo efficacy in the prevention and treatment of acne vulgaris. Int J Cosmet Sci. 2005;27(3):171-6.
58. Huh CH, Seo KI, Park JY, Lim JG, Eun HC, Park KC. A randomized, double-blind, placebo-controlled trial of vitamin c iontophoresis in melasma. Dermatology. 2003;206(4):316-20.
59. Ishikawa Y, Niwano T, Hirano S, Numano K, Takasima K, Imokawa G. Whitening
60. effect of l-ascorbate-2-phosphate trisodium salt on solar lentigos. Arch Dermatol Res. 2019;311(3):183-91.
61. Yokota M, Yahagi S. Evaluation of the anti-wrinkle effect of a lipophilic pro-vitamin c derivative, tetra-isopalmitoyl ascorbic acid. J Cosmet Dermatol. 2022;21(8):3503-14.
62. Valacchi G, Pecorelli A, Belmonte G, Pambianchi E, Cervellati F, Lynch S, et al. Protective effects of topical vitamin c compound mixtures against ozone-induced damage in human skin. J Invest Dermatol. 2017;137(6):1373-5.
AUTHOR’S CONTRIBUTION:
Flavia Alvim Sant'anna Addor 0000-0003-1851-7342
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, critical review of the literature, critical review of the manuscript.
Ana Claudia Cavalcante Esposito 0000-0001-9283-2354
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, critical review of the literature, critical review of the manuscript.
Emerson de Andrade Lima 0000-0002-6132-5031
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, critical review of the literature, critical review of the manuscript.
Lucas Portilho 0000-0001-9399-1664
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, critical review of the literature, critical review of the manuscript.
Eliana Mika Yamaguchi 0009-0002-0241-3928
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, critical review of the literature, critical review of the manuscript.
Sylvia Ypiranga 0009-0002-8440-0214
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, critical review of the literature, critical review of the manuscript.
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Sodium deoxycholate - mechanism of action, application technique, indications, and adverse effects
Desoxicolato de sódio - mecanismo de ação, técnica de aplicação, indicações e efeitos adversos
Techniques for removing adipose tissue are always of great interest, and among many described, the applications of sodium deoxycholate (DS) or deoxycholic acid, known as intralipotherapy, have stood out in recent years, following approval by the FDA for the treatment. of submental fat, due to the ease of application and short downtime. The objective of this study was to elucidate, through the available literature, the most frequently asked questions in this regard, and demonstrate that it is an effective and safe alternative for the treatment of localized fat.
Keywords: Atrophy; Adipose Tissue; Fat Body.
RESUMO
As técnicas de remoção do tecido adiposo são sempre de muito interesse, e entre muitas descritas, as aplicações de desoxicolato de sódio (DS) ou ácido deoxicólico, conhecida como intralipoterapia, têm se destacado nos últimos anos, após a aprovação pelo FDA para o tratamento da gordura submentoniana, devido a facilidade de aplicação e o curto tempo de inatividade. O objetivo deste estudo foi elucidar, através da literatura disponível, as questões mais frequentes a esse respeito e demonstrar que se trata de uma alternativa eficaz e segura para o tratamento da gordura localizada.
1 Faculdade de Medicina do ABCFMABC, Cosmiatry department of the Dermatology course at FMABC, Santo André (SP), Brazil
Correspondence:
Marisa Gonzaga da Cunha E-mail: dramarisagonzaga@yahoo. com.br / daphinegiglio@gmail. com
Financial support: None. Conflict of interest: None.
Submitted on: 10/16/2023
Approved on: 10/03/2024
How to cite this article:
Cunha MG, Cunha ALG, Giglio DT, Cardial DT, Almeida GE. Sodium deoxycholate - mechanism of action, application technique, indications, and adverse effects. Surg Cosmet Dermatol. 2025;17:e20250307.
INTRODUCTION
Adipose tissue has been a subject of growing interest, as new surgical and nonsurgical removal techniques have been proposed. Anatomical and histological research has enabled more rational and effective procedures to be developed. In addition, adipose tissue has become of major interest in the study of the anatomy of aging and dermatology.1 Anatomically, adipose tissue is divided into hypodermis or areolar/superficial adipose tissue (SAT) and lamellar/deep adipose tissue (DAT). In some areas of the body, both layers are present, while in others, it is only the hypodermis that covers the entire integument.1 Subcutaneous adipose tissue or DAT originates embryologically in the mesoderm and functions to store energy, protect against mechanical shocks, and allow mobility over deeper structures. It also has an important cosmetic effect, shaping the body contour and presenting significant variation in fat content and thickness among individuals. The location of DAT is determined mainly by genetics and hormones, being responsible for sexual dimorphism.2 It is present only in certain areas of the body, mainly in the abdomen, flanks, trochanteric region, inner upper thighs, knees, and back of the arms. Proportionally, during weight loss, it reduces less in thickness than SAT, since its adipocytes are predominantly α2 adrenergic receptors (antilipolytic).3 The areas of lipodystrophy are organized as follows from the surface: skin (epidermis and dermis), hypodermis or SAT, a horizontal fibrous layer of connective tissue (membranous layer or superficial fascia), DAT, which covers the deep fascia and muscles.3,4
DAT differs from the hypodermis in appearance: it has larger, flatter, and less defined adipose tissue lobules, with less evident fibrous septa, generally oriented obliquely and connected to the membranous layer of the deep fascia of the muscles (Figures 1A and 1B). Sbarbati et al. describe this layer from the peri-adipocyte collagen network as incomplete, extremely fragile, and finely adherent, with few vascular components, which apparently characterizes it as an area of high lipid deposition (Figures 2A and 2B).4 The low structural stability, limited elasticity properties to stretching, and low resistance to compression explain the sliding of this subcutaneous tissue over the deep fascia.3
There are few nonsurgical therapeutic options for the treatment of DAT, and among them, the application of sodium deoxycholate (SD) or deoxycholic acid has stood out in recent years, after FDA approval for the treatment of submental adipose tissue, due to its ease of application and short downtime. Its application is indicated for small areas of lipodystrophy, often not amenable to other forms of treatment,5 through a technique called intralipotherapy. SD is a synthetic bile salt with a chemical structure identical to the endogenous one, but it does not contain substances of human or animal origin. It causes dose-dependent lysis of mature adipocytes with necrosis, rupture, and dissolution of the adipose architecture and inflammatory response, preserving adjacent structures.5-8 The destruction of fat cells causes a local tissue inflammatory response involving
BAFigure 1: A - Anatomy of superficial and deep adipose tissue. B - Schematic drawing1
fibroblast infiltration, localized neocollagenesis, and macrophage recruitment to eliminate lipids and cellular debris.9 This article aims to elucidate the mechanism of action of DS, its best indications for the treatment of facial and body adipose tissue, application technique, and adverse effects.
BACKGROUND
The combination of sodium deoxycholate and phosphatidylcholine is marketed under the trade name Lipostabil®. It is produced and distributed in Europe by Aventis Pharma, and its intravenous application is indicated for the treatment of fat embolism and dyslipidemia.5 Since 2001, it has been used in Brazil for the treatment of lipodystrophy, but the manufacturer never requested its registration with the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária [ANVISA]). In April 2011, the sale and distribution of Lipostabil® and its active ingredient phosphatidylcholine were banned in Brazil.10 However, ANVISA still allowed the active ingredient sodium deoxycholate to be compounded. In 2004 and 2005, the first studies showed that the lipolytic activity of the combination was due to sodium deoxycholate and not phosphatidylcholine, which only acted as a diffuser.12 In 2015, ATX-101 (Kythera
MECHANISM OF ACTION OF SODIUM DEOXYCHOLATE
Biopharmaceuticals, a subsidiary of Allergan, West Lake Village, California) was approved by the FDA at a concentration of 10 mg/mL for subcutaneous application in the treatment of submental adipose tissue and has been marketed under the name Kybella in the US and Belkyra in Canada. In Brazil, as of 2018, DS was approved for use to reduce adipose tissue—the opinion concluded that studies showed the safety and effectiveness of the drug in eliminating submental adipose tissue and that, given its legal registration, it is a product approved for the intended purposes (ANVISA/MS—1.1047.0185). However, the injectable use of phosphatidylcholine is prohibited in Brazil (ANVISA Resolution No. 30 of January 8, 2003). It is currently approved in the United States and Canada and, according to the product label, only for the treatment of submental adipose tissue. In Brazil, there are no specifications regarding the areas indicated for its use, therefore its use on the body is not considered off-label.
After questions regarding the association of phosphatidylcholine and DS, studies initiated by Rotunda in 2004 revealed that this was the truly active ingredient, acting in a dose-dependent manner as a biological detergent, solubilizing cellular phospholipid bilayers and leading to adipocyte lysis.10 SD disrupts the integrity of membranes by introducing its polar hydroxyl groups into the hydrophobic core of the bilayer, solubilizing the membrane. The cell collapses into micelles of phospholipids and detergent molecules.11 Experiments using cell culture, metabolic assays, and histological evaluations have independently verified, by testing isolated DS, that it was capable of inducing cell lysis and resulting necrosis, with most cells destroyed within 15 minutes of incubation with the solution in vitro. These experiments also revealed that mature adipocytes were more resistant to detergent-induced cell lysis in vitro, raising the issue of safety in the event of accidental injections outside the adipose tissue compartments.12 Subsequent studies with histological examinations revealed that DS does not affect the muscle layer, dermis, and epidermis, despite intense necrosis and fibrosis of the subcutaneous cellular tissue.13 DS is insoluble in aqueous solutions, and serial histological studies have demonstrated marked differences in patients treated with mixtures when compared to isolated DS. After injection, specimens have shown small areas of adipose tissue with scattered necrotic and fibrotic effects, with minimal changes after injection of the mixture, as opposed to focal areas of adipose tissue necrosis when DS is used alone.12 Areas injected 1 week before microscopic examination showed small areas of adipose tissue necrosis in the tissue exposed to the solution, while intense inflammation and fibrosis were observed in areas treated with DS alone. After 2 weeks, histological examinations showed large areas of necrosis in the buccal pouch, with inflammation, neovascularization, adipose lysis, and macrophage infiltration with DS alone and more organized adipose necrosis with the solution. After 1 month, a fibrotic appearance was seen in the subcutaneous tissue treated with DS alone, while the areas treated with the combined solution showed a fractional response, with small areas of adipose necrosis separated by islands of normal-appearing adipose tissue. The treatment areas exhibited sterile cellulitis with neutrophil-rich infiltrate in the deep reticular dermis in all patients.12,13 In summary, when injected into subcutaneous adipose tissue, DS causes adipocytolysis and stimulates the local tissue response with macrophage infiltration that removes cellular debris and released lipids, fibroblast recruitment, and neocollagenesis. The process begins 15-20 minutes after application.5,15 Studies have shown that DS alone enters the circulation within a few days after injection, binds to albumin present in plasma, and undergoes fecal elimination in a manner similar to endogenous bile acids.5,13,14
INDICATIONS
The application of DS, preferably in isolation, is indicated for small and medium-sized areas of lipodystrophy in patients
FIGURE 2: Adipocytes of the DAT characterized by large adipocytes and poor collagen component. A - optical microscope B - scanning microscopy (Scale bars: 50 μm).2
with low BMI (20-25). On the face, the most suitable areas are submental adipose tissue and the jaw. On the body, the most suitable areas are located on the abdomen, waist, flanks, upper outer thighs, upper back of the thighs, below the infragluteal fold, inner knees and arms, back, and anterior and posterior axillary folds.15 These areas have little therapeutic response to other forms of treatment, including liposuction, which can leave residual sagging.15 In addition to the treatment of lipodystrophy itself, other indications in the literature are for liposuction touch-ups and for the treatment of paradoxical adipose tissue after cryolipolysis.16
CONTRAINDICATIONS
Infection at the application site, pregnancy, and breastfeeding. No studies in patients under 18 or over 65 have confirmed its safety.
AVAILABLE PRESENTATIONS
In Brazil, DS must be compounded upon individualized prescription with the patient’s name. The most commonly used concentrations are 1% for the face and 2.44% for the body. Studies have not shown any advantages in the 6% concentration.16,17,20 Combinations with other active ingredients do not increase the performance of DS and, furthermore, there is no standardization for these preparations. It should be noted that the numerous products distributed in Brazil, containing phosphatidylcholine or other active ingredients, are registered for cosmetic use only and are not indicated for injectable use.
APPLICATION
Before each application, photos taken from the front, at a 45º angle and at a 90º angle are recommended to evaluate the treatment results. To each 6 mL vial of 2.44% DS for body use, 1.0 mL of lidocaine can be added to reduce discomfort during application. The injection technique is important to avoid technical adverse events, and it should be noted that this is intralipotherapy and not mesotherapy (or intradermotherapy). The main difference is that in mesotherapy, the application is performed in the dermis, and in intralipotherapy, in the localized adipose tissue, which is a deeper application.16,17,19,20 The application can be performed with 30G 13 mm needles for the body and 9 mm needles for the face. Small amounts should be injected at each application point: 0.1 mL or less per 1 cm on the face and up to 0.2 mL per 2 cm on the body should be observed. Studies have shown that doses greater than 4 mg/cm2 did not produce greater efficacy and resulted in more frequent and severe adverse effects.18,19 The maximum amount recommended by Amore
et al. is 5 vials with 10 mL of 1.22% solution.18 The depth should be 9 to 13 mm in most areas of the body and around 6 mm on the face and neck, with the needle always positioned vertically to the skin. It is mandatory to wait a few seconds before removing the needle to avoid superficialization of the product. The application is virtually painless, but erythema and local burning begin a few minutes later. Massaging the area helps to relieve the symptoms. After application, the use of a compression bandage for a few days can reduce edema and local soreness. The use of oral analgesics is generally unnecessary. The application can be done at 4-week intervals, and studies have shown that up to 6 sessions are necessary for complete improvement of adiposity, although most patients improved with 4 sessions or less.18
ADVERSE EFFECTS AND COMPLICATIONS
Studies have not shown any systemic effects with the recommended doses of DS used alone. 12 Edema, erythema, hardening, and local soreness are expected adverse effects caused by panniculitis resulting from the application of DS. These effects appear shortly after application and are self-limiting, requiring no treatment. Edema lasts 9-10 days and hardening lasts 17-25 days and tends to be proportional to the degree of lipolysis. In combinations with DS, nausea, dizziness, and malaise were observed shortly after injection. 12 True complications include dysphagia, temporary asymmetry of the smile due to paresis of the marginal nerve of the mandible, focal necrosis, and irregularities due to superficial injections, nodules due to increased focal necrosis, and transient alopecia of the treated area, probably due to local inflammation. Comparative studies with DS alone and in combination showed no differences in adverse effects and complications. Septal and lobular panniculitis were noted with thickening of the fibrous septa, adipose necrosis, and formation of persistent granulomas when doses greater than 0.2 mL were used at each site and when DS alone was applied in high concentrations. 13 Treatment with DS had no effect on serum glucose, lipid, and plasma inflammation marker levels when used within the recommended doses. 21
CONCLUSION
DS has proven to be an effective and safe alternative for the treatment of lipodystrophy (localized adipose tissue) when applied correctly using the intralipotherapy technique (injection into the subcutaneous adipose tissue), with few and self-limiting adverse effects.21,22 Combination with other active ingredients has not shown improved performance, and combination with phosphatidylcholine is prohibited for injectable use in Brazil. l
REFERENCES:
1. Illouz,YG. Complications of liposuction. Clin Plastic Surg 2006;33(1):129–63.
2. Cunha MG, Cunha ALG, Machado CA. Hypodermis and subcutaneous adipose tissue two. Diferente structures. Surg Cosmet Dermatol 2014;6(4):355-9.
3. Paschoal LHC, Cunha MG, Ciporkin H. Fisiopatologia e atualização terapêutica da lipodistrofia ginóide - celulite. 2nd rev. ed. Rio de Janeiro: Di Livros; 2012.
4. Sbarbati A, Accorsi D, Marchetti L, Orsini G, Rigotti G, Panettiere P. Subcutaneous adipose tissue classification. Eur J Histochem.2010;54(4):226-30.
5. Kamalpour S, Leblanc Jr K. Injection adipolysis: mechanisms, agents, and future directions. J Clin Aesthet Dermatol. 2016;9(12):44–50.
6. Rotunda AM, Suzuki H, Moy RL, Kolodney MS. Detergent effects of sodium deoxycholate are a major feature of an injectable phosphatidylcholine formulation used for localized fat dissolution. Dermatol Surg. 2004;30(7):1001-8.
7. Rose PT, Morgan M. Histological changes associated with mesotherapy for fat dissolution. J Cosmet Laser Ther. 2005;7(1):17-9.
8. Rotunda AM. Injectable treatments for adipose tissue: terminology, mechanism, and tissue interaction. Lasers Surg Med. 2009;41(10):714–20.
9. Duncan D, Rubin JP, Golitz L, Badylak S, Kesel L, Freund J, et al. Refinement of technique in injection lipolysis based on scientific studies and clinical evaluation. Clin Plast Surg. 2009;36(2):195–209.
10. Ministério da Justiça e Segurança Pública (BR). Relatório 2022 – produtos farmacêuticos. 2023.
11. Lichtenberg D, Ahyayauch H, Goñi Fm. The mechanism of detergent solubilization of lipid bilayers. Biophys J. 2013;105(2):289–99.
12. Gupta A, Lobocki C, Singh S, Robertson M, Akadiri OA, Malhotra G, et al. Actions and comparative efficacy of phosphatidylcholine formulation and isolated sodium deoxycholate for different cell types. Aesthetic Plast Surg. 2009;33(3):346–52.
14. Saluja SS, Avram MM. Overview of non-invasive treatments for submental fat reduction. The PMFA J. 2018;5(6).
15. Sykes JM, Allak A, Klink B. Future applications of Deoxycholic acid in body contouring. J Drugs Dermatol. 2017;16(1):43-6.
16. Herreros FOC, Velho PENF, Moraes AM. Mesoterapia: uma revisão biliográfica. An Bras Dermatol. 2011;86(1):96-101.
17. Amore R, Pinto H, Gritzalas K, Hernández C, Skwara-Guzikowska K, Amuso D, et al. Intralipotherapy, the state of the art. Plast Reconstr Surg Glob Open. 2016;4(10):e1085
18. Georgesen C, Lipner SR. The development, evidence, and current use of ATX-101 for the treatment of submental fat. J Cosmet Dermatol. 2017;16(2):174-9.
19. Pinto H, Hernandez C, Turra C, Manzano M, Salvador L, Tejero P. Evaluation of a new adipocytolytic solution: adverse effects and their relationship with the number of vials injected. J Drugs Dermatol. 2014;13(12):1451–5.
20. Amore R, Amuso D, Leonardi V, Leva F, Sibaud AC, Guida A, et al. Evaluation of safe and effectiveness of an injectable solution acid deoxycholic based for reduction of localized adiposities. Plast Reconstr Surg Glob Open. 2018;6(6):e1794.
21. Reeds DN, Mohammed BS, Klein S, Boswell CB, Young VL. Metabolic and structural effects of phosphatidylcholine and deoxycholate injections on subcutaneous fat: a randomized, controlled trial. Aesthet Surg J. 2013;33(3):400-8.
22. Duncan DI, Palmer M. Fat reduction using phosphatidylcholine/sodium deoxycholate injections: standard of practice. Aesth Plast Surg. 2008;32(6):858-72.
AUTHOR’S CONTRIBUTION:
Marisa Gonzaga da Cunha 0000-0002-4186-0643
Statistical analysis, approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, data collection, analysis, and interpretation, effective participation in research guidance, intellectual participation in the propaedeutic and/or therapeutic conduct of the cases studied, critical literature review, critical review of the manuscript.
Ana Lúcia Gonzaga Cunha 0000-0001-8431-3386
Statistical analysis, approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, data collection, analysis, and interpretation, effective participation in research guidance, intellectual participation in the propaedeutic and/or therapeutic conduct of the cases studied, critical literature review, critical review of the manuscript.
Daphine Tironi Giglio
0009-0005-9775-614X
Approval of the final version of the manuscript, effective participation in research guidance.
Débora Terra Cardial 0000-0003-2482-4234
Preparation and writing of the manuscript, data collection, analysis, and interpretation, intellectual participation in the propaedeutic and/or therapeutic conduct of the cases studied, critical literature review, critical review of the manuscript.
Gabrielle Ellert de Almeida 0000-0002-4707-1100
Approval of the final version of the manuscript, preparation and writing of the manuscript, data collection, analysis, and interpretation, intellectual participation in the propaedeutic and/or therapeutic conduct of the cases studied, critical literature review, critical review of the manuscript.
www.surgicalcosmetic.org.br/
Treatment of periungual wart: a literature review
Tratamento da verruga periungueal: revisão da literatura
Review Article
Authors:
Emerson Henrique Padoveze1,2 Suelen Montagner3
Thamires Prado Dantas2 Nilton Gioia Di Chiacchio4,5 Nilton Di Chiacchio4
1 Universidade Estadual de Campinas, Dermatology, Campinas (SP), Brazil
Periungual warts are the most common tumors of the periungual region, primarily affecting children and adolescents. Caused by human papillomavirus (HPV), they can lead to cosmetic disfigurement in patients. There are several therapeutic options for the treatment of this condition, and the choice of treatment depends on the number of warts, patient age, immune status, and skill of the dermatologist. Given the high recurrence rate and numerous therapeutic possibilities, this review article provides a comprehensive summary of the condition, with a particular focus on treatment modalities.
Keywords: Warts; Nail Diseases; Papillomavirus Infections.
RESUMO
As verrugas periungueais são os tumores mais comuns da região periungueal, acometendo principalmente crianças e adolescentes. São causadas pelo papilomavírus humano (HPV) e podem levar a uma desfiguração estética nos pacientes. Existem diversas opções terapêuticas para o tratamento dessa patologia, e a escolha do tratamento depende do número de verrugas, da idade do paciente, do estado imunológico e da habilidade do dermatologista. Devido ao alto índice de recidiva e às inúmeras possibilidades terapêuticas, este artigo de revisão fornece um resumo abrangente da patologia, com foco principal nas formas de tratamento. Palavras-chave: Verrugas; Doenças da Unha; Infecções por Papilomavírus.
2 Faculdade de Medicina São Leopoldo Mandic, Dermatology, Campinas (SP), Brazil
3 Private practice, Dermatology, Campinas (SP), Brazil
4 Hospital do Servidor Público Municipal de São Paulo, Dermatology, São Paulo (SP), Brazil
5 Faculdade de Medicina do ABC, Dermatology, São Paulo (SP), Brazil
How to cite this article: Padoveze EH, Montagner S, Dantas TP, Di Chiacchio NG, Di Chiacchio N. Treatment of periungual warts: a literature review. Surg Cosmet Dermatol. 2025;17:e20250402.
INTRODUCTION
Periungual warts are the most common tumors of the periungual region, primarily affecting children and adolescents. Caused by human papillomavirus (HPV), they can lead to cosmetic disfigurement in patients. There are several therapeutic options for the treatment of this condition, and the choice of treatment depends on the number of warts, patient age, immune status, and skill of the dermatologist. Given the high recurrence rate and numerous therapeutic possibilities, this review article provides a comprehensive summary of the condition, with a particular focus on the available treatment modalities.
PERIUNGUAL WARTS
Warts caused by HPV can appear anywhere on the body.1 Those located around the nail are known as periungual warts, while those found under the nail are called subungual warts. There are approximately 218 types of HPV, and genotypes 1, 2, 4, 27, and 57 are most commonly associated with periungual warts.2,3 They most frequently affect children and adolescents (peak between 12 and 16 years of age),4 reaching an estimated prevalence of 33% in this age group and 22% in the general population.5,6 HPV enters the skin through abrasions or maceration,4,7 which expose the keratinocytes of the basal layer, facilitating virus penetration.8,9 This explains the higher prevalence of periungual warts in individuals who bite their nails, suck their fingers, or work in humid environments. Warts are acquired through direct or indirect contact with HPV, and the development of infection depends on local and systemic factors, including host predisposition and immunity. Patients with HIV, hematologic malignancies, and transplant recipients tend to have larger and multiple lesions.10 In general, warts are not highly contagious,11 and clinical lesions can appear from a few weeks to 1 year after infection.4 The presence of viral DNA in apparently normal skin indicates the existence of subclinical viral infections.12 Most patients with periungual warts require treatment due to cosmetic disfigurement, as well as functional and social concerns. There are various treatment approaches for this condition, including the use of cytotoxic agents, cryotherapy, electrosurgery, immunotherapy, and laser. However, despite these treatment options, many lesions are resistant and recalcitrant, making their cure a challenge. Among all viral warts, those located in the periungual and plantar regions have the highest recurrence rates.13,14 In response to this challenge, this review article provides a comprehensive summary of the condition, with a particular focus on treatment modalities. We have categorized treatment modalities into 3 groups based on their mechanisms of action: destructive treatments, characterized by epidermal destruction or keratolysis; immunotherapy, focused on the production of antiviral cytokines and stimulation of cell-mediated immune responses; and cytotoxic agents, designed to interfere with viral replication. Doses, drug administration intervals, and potential adverse events will be discussed for each modality.
CLINICAL FEATURES
Periungual warts may originate from the proximal nail and lateral folds or hyponychium. They initially appear as 1-mm hyperkeratotic normochromic papules, which can later grow up to 1 cm in diameter or coalesce into plaques. When the proximal nail fold is affected, it may simulate a hyperkeratotic cuticle. Changes to the nail plate are uncommon, as HPV does not usually affect the nail matrix. However, external compression can lead to grooves and ridges. When the nail bed is affected, onycholysis and splinter hemorrhages may occur. In rare cases, hypercurvature of the nail plate may be observed4 (Figure 1). Dermoscopy is a useful diagnostic tool, revealing the typical punctate rough surface and dilated capillaries15 (Figure 2).
Figure 1: Subungual wart causing hypercurvature of the nail plate
Figure 2: Dermoscopy showing punctate rough surface and dilated capillaries
HISTOLOGY
Pathology reveals epithelial hyperplasia with acanthosis, papillomatosis, and hyperkeratosis with parakeratotic stratum corneum. Thrombi within dilated capillaries and mononuclear cells may be present in the dermis.8
Confirming the diagnosis
The diagnosis of periungual warts is usually clinical. The classic clinical sign of warts is the pinpoint bleeding resulting from trauma to the capillaries.4 In doubtful cases, dermoscopy and biopsy can assist in diagnosis. In situ hybridization and polymerase chain reaction (PCR) allow viral identification.16,17 In older patients with long-standing single lesions or in cases refractory to conventional treatment, the diagnosis of squamous cell carcinoma should be ruled out with biopsy. HPV 16 is the most common subtype in malignant cases.
TREATMENT
Treatment of periungual warts is challenging compared to other types of viral warts due to high recurrence and treatment-related pain. While it was believed that 65% of warts could disappear spontaneously,18 spontaneous resolution is more common in children. In adults and adolescents, these lesions are less likely to disappear spontaneously. Furthermore, untreated lesions can spread to other sites, increase in size, and even become a source of infection to other individuals. Several treatment modalities are available, which can be divided into destructive, immunotherapeutic, and cytotoxic. The choice of treatment depends on the number, location (periungual or subungual), and duration of the warts, age and immune status of the patient, and skill of the dermatologist.4 Below, we will address the specific characteristics of each treatment modality.
I - DESTRUCTIVE TREATMENT
Topical treatments
These are considered a good conservative treatment option, especially for children, as some lesions may regress spontaneously in this age group.18 This category includes keratolytic agents and caustics such as cantharidin, trichloroacetic acid, and fuming nitric acid.
Keratolytic agents
These are the most popular treatment for periungual warts and are particularly suitable for children due to their safety profile, reduced pain, and topical application as creams, ointments, or quick-drying acrylate lacquers.4 They act by destroying and irritating virus-infected keratinocytes in the epidermis.19 Salicylic acid, at concentrations of 16% to 50%, is the most commonly used agent. It should be applied 5-7 times per week for 12 weeks to provide a clearance better than placebo (15% and 8%, respectively).8
Cantharidin
Cantharidin is a vesicant that causes acantholysis and blistering within the epidermis. It is isolated from the insect Cantharis vesicatoria. At a concentration of 0.7%, it is applied to the wart using a cotton swab, while protecting the surrounding healthy skin. Patients should cover the treated area for 4 to 8 hours before washing it with soap and water. Blister formation at the application site is common and usually resolves within 1 to 2 weeks. The reported efficacy in the literature is approximately 80%.20 Pain and a burning sensation may occur as adverse events. This medicine is not available in Brazil.
Cryotherapy
The treatment involves applying liquid nitrogen at −196 °C to lesions for approximately 10 to 15 seconds. This process induces irreversible damage to keratinocyte cell membranes through freezing and stimulates cellular immune response. For hyperkeratotic lesions, prior curettage can be performed to enhance the penetration of liquid nitrogen.4 Cryotherapy has an efficacy rate of approximately 70% and is generally well tolerated.21 Adverse events include pain at the application site, which may persist for up to 72 hours, hypochromia or hyperchromia, and scarring.Warts located in the proximal nail fold treated with cryotherapy may develop leukonychia, Beau’s lines, and onychomadesis. Severe matrix damage may lead to irreversible nail atrophy.8
Laser
The 585 nm pulsed dye laser targets hemoglobin. The mechanism of action is attributed to thermal injury to HPV and the destruction of blood vessels supplying the warts.22 Studies generally indicate clearance rates comparable to those of conventional methods, and this treatment is considered safe for both adults and children.22 Potential adverse events include hypopigmentation, scarring, purpura, pain, and burning sensation at the application site.23,24 The CO2 laser emits at 10,600 nm, a wavelength absorbed by water, which causes thermal injury and vaporization of HPV-infected epidermal cells. For subungual lesions, removal of the nail plate is required before laser application.4 Lim & Goh25 reported a 57.4% clearance rate using power settings from 3 to 15 W and a spot size of 2 mm. Pain is the most common adverse event, but nail changes such as onycholysis, thinning of the nail plate, and transient changes in sensitivity may also occur.26 The Er:YAG laser emits at 2,940 nm, a wavelength also absorbed by water, and acts similarly to the CO2 laser. However, it is more selective, resulting in less tissue damage and, consequently, fewer adverse events. While there are reports of the use of the Er:YAG laser for facial flat warts with a 62.5% clearance rate,27 no published studies exist on its use for periungual warts.
Electrosurgery
Electrosurgery should be avoided for tissue destruction in wart-affected areas due to the risk of scarring and permanent
nail matrix damage.8 In addition, it is associated with prolonged healing times and postoperative pain. In general, regardless of the selected method, the aggressiveness of the technique is not related to the clearance rate.
II – IMMUNOTHERAPY
Imiquimod
It acts as an immunomodulator due to its ability to stimulate the production of cytokines (especially interferon) and the migration of Langerhans cells.28,29 The literature shows varying dosing regimens, typically ranging from 3 to 5 times per week. Some authors use imiquimod under occlusive dressing or in combination with keratolytics,30 because, when used alone, its efficacy is reduced due to the difficulty of penetration of the medication into the keratotic surface of warts.31 Micali et al.32 reported an 80% clearance rate for periungual and subungual warts applying 5% imiquimod for 5 consecutive days per week over 6 weeks, combined with 50% salicylic acid in white petrolatum (Figure 3). Furthermore, the literature also indicates that the combined use of imiquimod and ablative lasers for recalcitrant warts yields superior results compared with the use of imiquimod alone.10
Contact immunotherapy
Diphencyprone is a sensitizer used in weekly applications, with dilutions ranging from 0.001% to 3% according to the patient’s response. The goal of treatment is to induce mild contact dermatitis.33 Rampen et al., 34 in a study of periungual and palmoplantar warts, applied a diphencyprone solution of 0.1%-3% to the warts once a week for 8 weeks, in 154 patients.The results showed a clearance rate of 8% after 2 months and 44% after a 4-month follow-up. Adverse events were considered mild.
Intralesional and topical immunotherapy
Another immunotherapy option is the application of vitamin D3 (calcipotriol), topically or by injection. Vitamin D is believed to regulate the proliferation and differentiation of epidermal cells and to modulate cytokine production.35 Topical calcipotriol can be applied 1 to 3 times a day, with a treatment duration of 3 to 18 months, as reported in the literature.36-38 For injectable vitamin D, the described dose is 0.2 mL of vitamin D at a concentration of 15 mg/mL, administered at the base of the periungual wart after injecting local anesthetic.10,39 Adverse events such as mild pain, edema, and erythema may occur at the application site.40 A recent study comparing intralesional vitamin D and purified protein derivative (PPD) for the treatment of extragenital warts showed slightly lower efficacy in the vitamin D group (21.7% vs. 59%).10 The application of PPD antigen provides an increase in interleukin (IL)-12 and IL-14 levels, contributing to a cell-mediated reaction. Cure rates with this treatment modality range from 23% to 77%. Clearance rates with this treatment modality range from 23% to 77%.40-42 Adverse events include pain, blistering, and erythema.
Systemic immunotherapy – cimetidine
Cimetidine, a histamine H2 receptor antagonist, has demonstrated variable efficacy in the treatment of warts. Its action is attributed to an increase in T cells, leading to cellular immune response. The reported dosage in the literature is 25-40 mg/kg/ day, divided into 3 daily doses.8 This medication is generally well tolerated, and the most frequently reported adverse events are gastrointestinal disturbances, dizziness, and drowsiness.43 A major drawback of cimetidine treatment is the need for multiple daily administrations over months, which may impact treatment adherence.44 For children with multiple, extensive, or recalcitrant warts, treatment with cimetidine has reported cure rates ranging from 56% to 82%.29,45
Figure 3: Patient treated with imiquimod. Left view, before treatment and after 3 months
HPV vaccines
HPV vaccines, which contain noninfectious virus-like particles of the L1 capsid protein, have shown well-established efficacy in the prevention of HPV-related diseases, such as anogenital warts and cervical, vulvar, vaginal, and anal cancers. Currently, 3 types of HPV vaccines are available: bivalent – against HPV 16 and 18; quadrivalent – against HPV 6, 11, 16 and 18; and nonavalent – against HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58. These vaccines are associated with strong cellular immune responses and the production of HPV type-specific neutralizing antibodies.46 In the treatment of warts caused by HPV strains other than those contained in the vaccines, it is believed that a cross-immune response occurs, leading to the resolution of non-genital lesions.47,48 Studies have explored the use of bivalent,47 quadrivalent,49,50 and nonavalent51 HPV vaccines (administered at 0, 2, and 6 months) for the treatment of periungual warts. In the treatment of common warts, a comparative study of intralesional versus intramuscular bivalent HPV vaccine showed a clearance rate of 81.8% in the intralesional group and 63.3% in the intramuscular group, with no significant difference between the groups.47 Shin et al.51 treated 45 patients with recalcitrant extragenital warts, primarily plantar and periungual, using the nonavalent HPV vaccine. A dose of 0.5 mL was injected intramuscularly at 0, 2, and 6 months, resulting in a 62.2% clearance rate. Potential adverse events included pain at the application site, pruritus, and fatigue.
III - CYTOTOXIC TREATMENT
Bleomycin
It has been a safe and effective antimitotic agent in the treatment of periungual warts for over 5 decades.52 It acts primarily on DNA cleavage53 and promotes endothelial damage,54 resulting in high clearance rates of 92% to 96%. Most studies suggest an optimal dose between 0.1 and 0.3 U/lesion, with a maximum recommended dose of 3 U per session. The medication can be administered by needle injection at the base of the lesion or by applying a drop of bleomycin solution to the surface of the lesion, followed by multiple punctures. Typically, 2 to 3 sessions are required, with intervals of 3 to 4 weeks between them55 (Figure 4).
The main limiting factor of this treatment is pain, which can range from moderate to severe during application.11 However, pain can be alleviated by adding an anesthetic during medication dilution or by performing a digital nerve block before infiltration. Other side effects include erythema, edema, ulceration, hemorrhagic crusting, transient hypopigmentation or hyperpigmentation, atrophic or hypertrophic scars, and hematoma. Less common adverse events include Raynaud’s phenomenon, tissue necrosis, nail dystrophy, and nail loss (Figure 5).
Cidofovir
Cidofovir is a nucleoside analog antiviral agent that resembles cytosine. After intracellular phosphorylation, the active metabolite cidofovir diphosphate serves as a substrate for viral
application
DNA polymerase, being incorporated into viral DNA and terminating its replication. It has a 25- to 50-fold higher affinity for viral over cellular DNA polymerase and, unlike other nucleoside analogs (acyclovir and ganciclovir), it does not require viral enzymes for molecular activation, making it effective against viral strains resistant to tyrosine kinase.56,57 Due to poor oral bioavailability, cidofovir is often administered intravenously, topically, and intralesionally. The intralesional route provides the highest clearance rates for the treatment of viral warts (75.9%100%), with a recommended dose of 15 mg/mL every 15-30 days, which may be preceded by local anesthesia with lidocaine. Potential adverse events include erythema, pruritus, and blistering at the application site.58 Cidofovir cream (1%-3%), applied twice daily with or without occlusive dressing, can achieve a 55.2% clearance rate. It is suitable for both adults and children, whether immunocompromised or not.59,60 Due to a possible de-
Figure 4: Patient treated with bleomycin. Left view, before treatment and after 3 months
Figure 5: Hemorrhagic necrosis after bleomycin
layed response, treatment may be prolonged for at least 10-12 weeks.61 Adverse events include erythema, pruritus, and burning sensation. Injectable cidofovir, administered at a dose of 3.5-5 mg/kg for 2 weeks to 4 months, can achieve a 75% clearance rate. However, caution is advised due to potential nephrotoxicity and immunosuppression.10 Overall, despite the promising results, the use of cidofovir is limited by its high cost.
CONCLUSION
The treatment of periungual warts poses a challenge in dermatological practice, primarily due to the risk of scarring
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and pain associated with the procedures. While several treatment modalities are currently available, selecting the most suitable method requires careful consideration of factors such as the number of lesions, patient age, degree of immunosuppression, and the availability and cost of treatment. Among the existing options, bleomycin has been our treatment of choice due to its high clearance rates and good tolerability. Immunotherapies have emerged as a promising, safe, and less invasive alternative. However, further studies are needed to fully demonstrate the efficacy of these new treatment options. l
19. Sterling J. Treatment of warts and molluscum: what does the evidence show? Curr Opin Pediatr. 2016;28(4):490-9.
20. Wolverton SE, Comprehensive dermatologic drug therapy. Philadelphia: W.B Saunders Company; 2001. p.524-36.
21. Walkzuk I, Eertmans F, Rossel B, Cegielska A, Stockfleth E, Antunes A, et al. Efficacy and safety of three cryotherapy devices for wart treatment: a randomized, controlled, investigator- blinded, comparative study. Dermatol Ther (Heidelb). 2018;8(2):203-16.
22. Jacobsen E, McGraw R, McCagh S. Pulsed dye laser efficacy as initial therapy for warts and against recalcitrant verrucae. Cutis. 1997;59(4):206-8.
23. Nguyen J, Korta DZ, Chapman LW, Kelly KM. Laser treatment of nongenital verrucae: a systematic review. JAMA Dermatol. 2016;152(9):1025-34.
24. Park HS, Choi WS. Pulsed dye laser treatment for viral warts: a study of 120 patients. J Dermatol. 2008;35(8):491-8.
25. Lim JT, Goh CL. Carbon dioxide laser treatment of periungual and subungual viral warts. Australas J Dermatol. 1992;33(2):87-91.
26. Street ML, Roenigk RK. Recalcitrant periungual verrucae: the role of carbon dioxide laser vaporization. J Am Acad Dermatol. 1990;23(1): 115-20.
27. Balevi A, Ustuner P, Ozdemir M. Use of Er:YAG for the treatment of recalcitrant facial verruca plana. J Dermatolog Treat. 2017;28(4):368-71.
28. Suzuki H, Wang B, Shivji GM, Toto P, Amerio P, Tomai MA, et al. Imiquimod, a topical immune response modifier, induces migration of Langerhans cells. J Invest Dermatol. 2000;114(1):135-41.
29. Veasey JV, Miguel BAF, Campaner AB, Manzione TS. Imiquimod use for the treatment of extramammary Paget disease: series of four cases. Surg Cosmet Dermatol. 2018;10(4):309-13.
30. Ahn CS, Huang WW. Imiquimod in the treatment of cutaneous warts: an evidence-based review. Am J Clin Dermatol. 2014;15(5):387-99.
31. Edwards L. Imiquimod in clinical practice. J Am Acad Dermatol. 2000;43:S12-7.
32. Micali G, Dall’Oglio F, Nasca MR. An open label evaluation of the efficacy of imiquimod 5% cream in the treatment of recalcitrant subungual and periungual cutaneous warts. J Dermatolog Treat. 2003;14(4):233-6.
33. Silverberg NB, Lim JK, Paller AS, Mancini AJ. Squaric acid immunotherapy for warts in children. J Am Acad Dermatol. 2000;42(5 Pt 1):803–8.
34. Rampen FH, Steijlen PM. Diphencyprone in the management of refractory palmoplantar and periungual warts: an open study. Dermatology. 1996;193(3):236-8.
35. Osborne JE, Hutchinson PE. Vitamin D and systemic cancer: is this relevant to malignant melanoma? Br J Dermatol. 2002;147(2):197-213.
36. Egawa K, Ono T. Topical vitamin D3 derivatives for recalcitrant warts in three immunocompromised patients. Br J Dermatol. 2004;150(2):374-6.
37. Moscarelli L, Annunziata F, Mjeshtri A, Paudice N, Tsalouchos A, Zanazzi M, et al. Successful treatment of refractory wart with a topical activated vitamin d in a renal transplant recipient. Case Rep Transplant. 2011:2011:368623.
38. Imagawa I, Suzuki H. Successful treatment of refractory warts with topical vitamin D3 derivative (maxacalcitol, 1alpha, 25-dihydroxy-22-oxacalcitriol) in 17 patients. J Dermatol. 2007;34(4):264-6.
39. Jain Sk, Mohta A. Recalcitrant periungual warts in a paediatric patient treated with intralesional vitamin D3. Indian J Med Res. 2020;152 (Suppl 1):S44.
40. Abd-Elazeim FM, Mohammed GF, Fathy A, Mohamed RW. Evaluation of IL-12 serum level in patients with recalcitrant multiple common warts, treated by intralesional tuberculin antigen. J Dermatolog Treat. 2014;25(3):264-7.
41. Amirnia M, Khodaeiani E, Fouladi DF, Masoudnia S. Intralesional immunotherapy with tuberculin purified protein derivative (PPD) in recalcitrant wart: a randomized, placebo- controlled, double-blind clinical trial including an extra group of candidates for cryotherapy. J Dermatolog Treat. 2016;27(2):173-8.
42. Kus S, Ergun T, Gun D, Akin O. Intralesional tuberculin for treatment of refractory warts. J Eur Acad Dermatol Venereol. 2005;19(4):515-6.
43. Jafarzadeh A, Nemati M, Khorramdelazad H, Hassan ZM. Immunomodulatory properties of cimetidine: its therapeutic potentials for treatment of immune-related diseases. Int Imunopharmacol. 2019;70:156-66.
44. Arancibia NR, Varas C, Munoz ER. Severe and recalcitrant periungual warts in a child successfully treated with cimetidine. Dermatol Therap. 2021;34(6):151-4.
45. Chern E, Cheng YW. Treatment of recalcitrant periungual warts with cimetidine in pediatrics. J Dermatolog Treat. 2010;21:314-6.
46. Ahn J, Best SRA & Tunkel DE. Advances in Vaccine Technology. In: Campisi P. editor. Recurrent Respiratory Papillomatosis. Springer: Cham. 2018; p.45-58.
47. Nofal A, Marei A, Ibrahim Al-Shimaa M, Nofal E, Nabil M. Intralesional versus intramuscular bivalent human papillomavirus vaccine in the treatment of recalcitrant common warts. J Am Acad Dermatol. 2020;82:94-100.
48. Lowe J, Panda D, Rose S, Jensen T, Hughes WA, Tso FY, et al. Evolutionary and structural analyses of alpha-papillomavirus capsid proteins yields novel insights into L2 structure and interaction with L1. Virol J. 2008;5(1):150.
AUTHOR’S CONTRIBUTION:
Emerson Henrique Padoveze 0009-0001-3025-0372
49. Waldman A, Whiting D, Rani M, Alam M. HPV vaccine for treatment of recalcitrant cutaneous warts in adults: a retrospective cohort study. Dermatol Surg. 2019;45(12):1739-41.
50. Yang MY, Son JH, Kim GW, Kim HS, Ko HC, Kim MB, et al. Quadrivalent human papilloma virus vaccine for the treatment of multiple warts: a retrospective analysis of 30 patients. J Dermatolog Treat. 2019;30(4):405-9.
51. Shin JO, Son JH, Lee J, Kim HS, Ko HC, Kim BS, et al. Nonavalent human papilloma virus vaccine for the treatment of multiple recalcitrant warts: an open-label study. J Am Acad Dermatol; 86(4):940-1.
52. Umenzawa H, Maeda K, Takeuchi T. New antibiotics, bleomycin A and B. J Antibiot. 1966;19:200–9.
53. Saitta P, Krishnamurthy K, Brown LH. Bleomycin in dermatology: a review of intralesional applications. Dermatol Surg. 2008;34(10):1299-313.
54. Lee JH, Burm JS, Yang WY, Kang SY, Byun SW. Treatment of verruca vulgaris in both external auditory canals using bleomycin injections. Clin Exp Otorhinolaryngol. 2015;8(3):295-7.
55. Noriegal LF, Valandro LS, Di Chiacchio NG, Vieiral ML, Di Chiacchio N. Treatment of viral warts with intralesional bleomycin. Surg Cosmet Dermatol. 2018;10(1):16-20.
56. Zabawski J, Cockerell CJ. Topical and intralesional cidofovir: a review of pharmacology and therapeutic effects. J Am Acad Dermatol 1998;39(5 Pt 1):741-5.
57. Gnann JW, Salvaggio MR. Drugs for herpesvirus infections. Infect Dis. 2010;2:1454-63.
58. Cook Mk, Hagen EM, Feldman SR. Cidofovir in the management of non-genital warts: a review. J Drugs Dermatol. 2023;22(10):1009-16.
59. Cha S, Johnston L, Natkunam Y, Brown J. Treatment of verruca vulgaris with topical cidofovir in an immuno- compromised patient: a case report and review of the literature. Transpl Infect Dis.2005;7(3-):158–61.
60. Gupta M, Bayliss SJ, Berk DR. Topical cidofovir for refractory verrucae in children. Pediatr Dermatol. 2013;30(1):131–4.
61. Spaña LP, Boz J, Morano TF, Villafranca JA, Troya M. Successful treatment of periungual warts with topical cidofovir. Dermatol Therap. 2014;27(6):337-42.
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript.
Suelen Montagner 0000-0002-6597-2981
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript.
Thamires Prado Dantas 0009-0002-8379-1401
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript
Nilton Gioia Di Chiacchio 0000-0001-5944-7737
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript.
Nilton Di Chiacchio 0000-0001-9536-2263
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript.
www.surgicalcosmetic.org.br/
Systematic Global Body Assessment: a tool
to support optimal patient selection for
nonsurgical treatment of skin laxity
Avaliação Corporal Sistemática e Global: uma ferramenta para seleção de pacientes para tratamento não cirúrgico de flacidez cutânea
Introduction: The search for minimally invasive aesthetic procedures to improve non-facial skin laxity has been increasing annually. The biostimulator poly-L-lactic acid stands out as one of the most versatile products for aesthetic procedures in this field.
Objective: To develop a systematic assessment framework tool to guide treatment decision-making for skin laxity in extra-facial areas, since there are no reports regarding how to select the most appropriate patients for non-invasive body shaping with biostimulators to date.
Methods: The authors developed the tool described herein based on their collective experience with treatment of extra-facial skin laxity with poly-L-lactic acid.
Results: This assessment method collates input from four fundamental factors: somatotype/morphotype, skin quality/severity of laxity, distribution and quantity of adipose tissue, and nutritional and hormonal profile.
Conclusions: Each aspect of the framework has been developed to optimize decision-making and tailor the clinical experience for each patient, enabling clinicians to select the most favorable candidates for biostimulator use, leading to more predictable and optimized outcomes.
Introdução: A busca por procedimentos estéticos minimamente invasivos para melhora da flacidez cutânea corporal tem aumentado anualmente. O bioestimulator ácido poli-L-lático destaca-se como um dos produtos mais versáteis para melhora da flacidez.
Objetivo: Desenvolver uma ferramenta sistemática de avaliação estruturada para orientar a seleção de pacientes com flacidez cutânea em áreas extrafaciais, uma vez que ainda não existem critérios publicados para indicar tratamentos não invasivos de contorno corporal com bioestimuladores.
Métodos: Os autores desenvolveram a ferramenta descrita, baseada na experiência coletiva do tratamento de flacidez cutânea em áreas extrafaciais com ácido poli-L-lático.
Resultados: Este método de avaliação integra quatro fatores fundamentais: somatótipo/morfotipo, qualidade da pele/ grau de flacidez, distribuição e quantidade de tecido adiposo, e perfis nutricional e hormonal.
Conclusões: Cada componente da avaliação foi elaborado para otimizar a tomada de decisão e personalizar a experiência clínica, permitindo aos médicos identificar os pacientes mais adequados ao uso de bioestimuladores e alcançar resultados mais previsíveis e eficazes.
Palavras-chave: Envelhecimento da Pele; Rejuvenescimento; Classificação.
2 Hospital Israelita Albert Einstein, Coordinator, Graduate Program in Laser, Cosmetic Medicine and Procedures, São Paulo (SP), Brazil
3 Dermatologist. Private practice, Belo Horizonte (MG), Brazil
4 Endocrinology, Metabology and Nutrology, Private practice, São Paulo (SP), Brazil
Financial support: Galderma financially supported the writing of this manuscript.
Conflict of interest: Dr. Haddad is a speaker, consultant, advisor, and investigator for Galderma Brazil. Dr. Sarubi is a speaker and consultant for Galderma Brazil. Dr. Assaly has no conflict of interest to declare.
Submitted on: 10/07/2024
Approved on: 15/08/2024
Authors' abbreviations: Haddad A, Sarubi J, Assaly V. How to cite this article: Haddad A, Sarubi J, Assaly V. Systematic Global Body Assessment - a tool to support optimal patient selection for non-surgical treatment of skin laxity. Surg Cosmet Dermatol.2025;17:e20250388.
INTRODUCTION
As skin ages, collagen and elastic fibers degrade, and the consequent loss of structural support and subcutaneous fat results in the development of wrinkles and ptosis, changing the contour and reducing the projection of extra-facial areas.1–3 Skin laxity becomes increasingly prominent in the arms, knees, thighs, buttocks, and abdomen, and is one of the main reasons patients seek aesthetic treatments.4 The search for effective and safe non-surgical aesthetic procedures to improve body appearance and contour has increased significantly in recent years, especially with respect to injectable treatments; an increase of 55% in non-surgical treatments for cellulite and 18% for skin laxity was reported in 2019.5 Poly-l-lactic acid is a biodegradable, biocompatible collagen biostimulator that increases dermal collagen content.6–8 Its facial use has been widely described9,10 and recent reports have also demonstrated its application in extra-facial areas,11 such as the buttocks,12,13 thighs,14 arms,13,15 chest/ neck,16,17 and back of the hands.18 However, adequate treatment planning tailored to each individual patient’s profile is essential. The objective of this paper is to propose a global and systematic body assessment framework and associated tool to assess which patients with sagging skin in extra-facial areas might be eligible for the use of poly-L-lactic acid. This framework is based on four factors: muscle constitution (somatotype/morphotype), skin laxity and quality, adipose tissue, and hormonal/nutritional profile.
METHODS
The authors developed the tool described herein through experience sharing.The components of the assessment tool were defined based on the authors’ collective experience of treating skin laxity in extra-facial areas with poly-L-lactic acid
RESULTS
Muscle constitution
The assessment of somatotypes, also known as morphotypes, classifies the individual’s physical structure profile through three primary components: muscle, bone, and body fat. This classification is one of the five clinical items of the global and systematic assessment tool (Table 1). Somatotype influences not only to the concept of weight gain or fat location, but also to how we age, and is determined by racial, genetic and epigenetic factors.19 In clinical practice, this assessment consists
of a general inspection of the patient’s body in front, lateral and posterior views, seeking to determine the predominant somatotype of the patient (Figure 1).20-22 Based on over 15 years of clinical experience, the authors suggest tailoring poly-L-lactic acid treatment to the patient’s predominant somatotype. Overall, the mesomorphic somatotype is usually associated with the best clinical outcomes after poly-L-lactic acid injection, followed by the endomorphic and ectomorphic somatotypes, as summarized in table 1.
Skin quality and severity of laxity
Type I and type III collagen are the most abundant types found in human skin, with type I responsible for skin elasticity and resistance.23 From the age of 30, there is a reduction of around 1% per year in type I collagen, increasing the degree of skin laxity.23–25 Therefore, we selected the degree of laxity and skin quality as the second key consideration when conducting a systematic body assessment. This factor has a direct impact on treatment success: it defines the limits of sagging and the degree of the expected clinical response, as well as helps physicians estimate the number of sessions and vials that will be required. To define eligibility for treatment with poly-L-lactic acid, the authors suggest using a visual analogue scale to grade the severity of body skin laxity (Figure 2). The best and most evident results from poly-L-lactic acid application are obtained in candidates with grade 1 and 2 skin laxity, who usually require only 1 or 2 sessions, while those with grade 3 or 4 will require more treatments (3 to 4 sessions) to achieve satisfactory results.
Adipose tissue
Adipose tissue contributes substantially to body contouring.26 Although the recommended modality to define the distribution of body fat in gynoid or android patterns is bioimpedance or dual-energy X-ray absorptiometry, this may not be available in all clinics.27 For in-office evaluation, the authors suggest the use of a body fat caliper, which measures skinfold thickness from the superficial subcutaneous cellular tissue. Measurements should be performed on the right side of the body by pinching the skin with the index finger and thumb, while trying to differentiate subcutaneous tissue from muscle tissue. Three measurements should be averaged: the higher the value, the
Somatotype Use of poly-L-lactic acid and expected results
Ectomorph During treatment, protein and vitamin supplements should be prescribed alongside appropriate exercises to maintain the musculature.
Mesomorph Good clinical response is expected.
Endomorph Laser and/or other technologies, such as micro- and macro- focused ultrasound, radiofrequency, and acoustic wave therapy, should be considered alongside poly-L-lactic acid treatment.
All types General lifestyle changes should be discussed, such as improved diet and physical activity.
Table 1: Additional recommendations for the use of poly-L-lactic acid according to the patient’s somatotype
greater the amount of subcutaneous adipose tissue. We suggest a 4-grade classification system according to the amount of adipose tissue present in the treatment area (Table 2).
Hormonal and nutritional profile
Hormonal profile
Sex hormones are key determinants of body fat distribution. Estrogen is the main hormone implicated in metabolic regulation, providing protection against the accumulation of adipose tissue28 as well as stimulating collagen production and maintaining skin elasticity.24,25,29,30 Thus, it would be interesting to measure serum levels of sex hormones, transport proteins (sex-hormone binding protein), gonadotropins, and sex steroids; however, these tests are not common in dermatologic clinical practice. We suggest an indirect evaluation by visual determination of body shape (Figure 3).31 Based on the authors’ clini-
cal experience, the hourglass and triangle body shapes are most appropriate for treatment with PLLA, as they are likely to denote higher levels of estrogen.28
Nutritional profile
The body mass index (BMI) is a validated tool widely used to assess for obesity or undernourishment.32 The authors’ clinical experience suggests that the ideal BMI for PLLA treatment is in the range of 18.5–24.9 kg/m2; individuals with a BMI <18.4 kg/m2 may not have the expected result due to low levels of body fat and muscle.
DISCUSSION
This article proposes a standard framework which has been developed into a tool to evaluate patients who seek treatment for extra-facial skin laxity by applying systematic assess-
Figure 1: Definition of somatotypes according to distribution of bone, muscle, and fat structure
1: Normal appearance, no sagging
2: Mild skin sagging. Indication for biostimulator injection
3: Moderate skin sagging. Good candidates for biostimulator injection
4: Severe (or intense) skin sagging. Poor results. Realistic patient expectations are essential
ments based on four key factors (Figure 4). Although each of the classic somatotypes has distinctive characteristics, this classification may be considered on a spectrum.21 Most patients have a predominance of two components, which can make it difficult to determine somatotype. Therefore, it is recommended to consider both visual evaluation and anthropometry/adipometry to define somatotype. It is important to emphasize that we are not suggesting that any one somatotype has a greater or lesser response to poly-L-lactic acid treatment, but rather that body constitution may influence the appearance of the skin and body contour, leading to a more or less apparent aesthetic result. Further studies are required to better understand these aspects
and their relationship with the results obtained with the use of biostimulators. The objective analysis of skin laxity has been studied previously.33,34 Evaluating the patient’s muscle condition is equally important, since muscle mass and tone can interfere with skin laxity in certain body areas; adequate muscle tone enhances aesthetic results, while weak muscles with significant hypotrophy can exacerbate skin laxity.21 The results of treatment will be less visible in these patients, and their expectations should be aligned accordingly. One way to differentiate skin laxity from muscle flaccidity is to evaluate the area using the manual skinfold (pinch) test. In cases of skin laxity, in addition to slow return of the skin, ptosis and formation of spontaneous skinfolds (Grade
Figure 2: Visual grading of skin sagging
Grade
Grade
Grade
Grade
Table 2: Presence of subcutaneous adipose tissue in the body region to be treated
Grade Condition of subcutaneous cellular tissue
Grade 1 Normal appearance; smooth subcutaneous tissue without localized fat.
Grade 2 Mild subcutaneous component in the area to be treated (skinfold: 0–3 cm).
Grade 3
Moderate subcutaneous component in the area to be treated (skinfold: 3–5 cm).
3–4) will be observed. Muscle laxity/hypotrophy, in turn, is characterized by a lack of well-defined contours and mobility of the muscle on palpation upon muscle contraction. Regarding adipose tissue, in the authors’ experience, grade 1–2 skinfolds (up to a maximum of 4 cm) yield the most favorable results after poly-L-lactic acid application. Nevertheless, studies have shown that gradual weight loss improves the histological structure of the hypodermis, improving skin quality and retractability.26 Thus, patients with Grade 4 adipose tissue or a BMIs in the overweight/obese range should be encouraged to seek professional nutritional guidance and increase the intensity and frequency of physical activity to obtain better results following biostimulator application. Since patients presenting with grade 3/4 fat deposits are less likely to achieve visible results, treatments with other technologies can be considered, either in parallel or instead of poly-L-lactic acid. It is important to note that low food intake and very intense physical activity can also interfere with
the outcome of treatment, and more sessions may be required to obtain satisfactory results. Furthermore, post-bariatric surgery patients may have delayed responses to treatment due to changes in adipose tissue structure and skin condition;35 nutritional supplementation is often required in these cases.
CONCLUSION
Aesthetic procedures, especially the use of poly-L-lactic acid , have been increasingly sought by patients who want to improve skin laxity in non-facial areas of the body. Having a method that enables a systematic and individualized evaluation of patients can further improve their satisfaction with poly-L-lactic acid treatment, align expectations, and optimize outcomes. The authors believe that the use of the proposed tool, based on four key factors, can facilitate the selection of candidates for the application of poly-L-lactic acid in extra-facial areas. l
REFERENCES :
1. El Khatib HA. Classification of brachial ptosis: strategy for treatment. Plast Reconstr Surg. 2007;119:1337–42.
2. Lin MJ, Dubin DP, Khorasani H. Poly-L-lactic acid for minimally invasive gluteal augmentation. Dermatol Surg. 2020;46:386–94.
3. Hart DR, Fabi SG, White WM, Fitzgerald R, Goldman MP. Current concepts in the use of PLLA: clinical synergy noted with combined use of microfocused ultrasound and poly-l-lactic acid on the face, neck, and décolletage. Plast Reconstr Surg. 2015;136:180S–7S.
4. Kaminer MS, Casabona G, Peeters W, Bartsch R, Butterwick K, Chao YYY, et al. Validated assessment scales for skin laxity on the posterior thighs, buttocks, anterior thighs, and knees in female patients. Dermatol Surg. 2019;45(Suppl 1):S12–S21.
5. American Society of Plastics Surgeons. 2019 Plastic Surgery Statistics Report. 2019.
6. Brown SA, Rohrich RJ, Baumann L, Brandt FS, Fagien S, Glazer S, et al. Subject global evaluation and subject satisfaction using injectable poly-l-lactic acid versus human collagen for the correction of nasolabial fold wrinkles. Plast Reconstr Surg. 2011;127:1684–92.
7. Haddad A, Kadunc BV, Guarnieri C, Noviello JS, Cunha MG, Parada MB. Current concepts in the use of poly-L-lactic acid for facial rejuvenation: literature review and practical aspects. Surg Cosmet Dermatol. 2017;9:60–71.
8. Stein P, Vitavska O, Kind P, Hoppe W, Wieczorek H, Schürer NY. The biological basis for poly-l-lactic acid-induced augmentation. J Dermatol Sci. 2015;78:26– 33.
9. Bohnert K, Dorizas A, Lorenc P, Sadick NS. Randomized, controlled, multicentered, double-blind investigation of injectable poly- l -lactic acid for improving skin quality. Dermatol Surg. 2019;45:718–24.
10. Vleggaar D. Facial volumetric correction with injectable poly-l-lactic acid. Dermatol Surg. 2005;31(11 Pt 2):1511–8.
11. Haddad A, Menezes A, Guarnieri C, Coimbra D, Ribeiro E, Sarubi J, et al. Recommendations on the use of injectable poly-l-lactic acid for skin laxity in off- face areas. J Drugs Dermatol. 2019;18:929–35.
12. Mazzuco R, Sadick NS. The use of poly-l-lactic acid in the gluteal area. Dermatol Surg. 2016;42:441–3.
13. Cunha MG, Daza F, Rezende FC, Machado Filho CDS. Poly-l-lactic acid injections in sagging body skin. Surg Cosmet Dermatol. 2016;8:322–9.
14. Vleggaar D. Soft-tissue augmentation and the role of poly-l-lactic acid. Plast Reconstr Surg. 2006;118:46S-54S.
15. Coimbra DD, Amorim AGF. New techniques poly-l-lactic acid in the rejuvenation of the medial and anterior arms. Surg Cosmet Dermatol. 2012;4:182–5.
16. Melo F, Carrijo A, Hong K, Trumbic B, Vercesi F, Waldorf HA, et al. Minimally invasive aesthetic treatment of the face and neck using combinations of a PCL-based collagen stimulator, PLLA/PLGA suspension sutures, and cross-linked hyaluronic acid. Clin Cosmet Investig Dermatol. 2020;13:333–44.
17. Mazzuco R, Hexsel D. Poly-l-lactic acid for neck and chest rejuvenation. Dermatol Surg. 2009;35:1228–37.
18. Rendon MI, Cardona LM, Pinzon-Plazas M. Treatment of the aged hand with injectable poly-l-lactic acid. J Cosmet Laser Ther. 2010;12:284–7.
19. Carter JEL, Ross WD, Duquet W, Aubry SP. Advances in somatotype methodology and analysis. Am J Physical Anthropol. 1983;26:193–213.
20. Bolonchuk WW, Siders WA, Lykken GI, Lukaski HC. Association of dominant somatotype of men with body structure, function during exercise, and nutritional assessment. Am J Hum Biol. 2000;12:167–80.
21. Olds T, Daniell N, Petkov J, Stewart AD. Somatotyping using 3D anthropometry: a cluster analysis. J Sports Sci. 2013;31:936–44.
22. Ryan-Stewart H, Faulkner J, Jobson S. The influence of somatotype on anaerobic performance. PLoS ONE. 2018;13:1–11.
23. Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure. J Drugs Dermatol. 2008;7:12–6.
24. Chaudhary M, Khan A, Gupta M. Skin ageing: pathophysiology and current market treatment approaches. Curr Aging Sci. 2020;13:22–30.
25. Ganceviciene R, Liakou AI, Theodoridis A, Makrantonaki E, Zouboulis CC. Skin anti-aging strategies. Dermato-Endocrinol. 2012;4:308–19.
26. Silva SL. Anatomic variations of the subcutaneous tissue after ponderal weight lost. Rev Bras Cir Plast. 2010;25:675–8.
27. Kuriyan R. Body composition techniques. Indian J Med Res. 2018;148(5):648–58.
28. Rettberg JR, Yao J, Brinton RD. Estrogen: a master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol. 2014;35:8–30.
29. Dao H, Kazin RA. Gender differences in skin: a review of the literature. Gend Med. 2007;4:308–28.
30. Rahrovan S, Fanian F, Mehryan P, Humbert P, Firooz A. Male versus female skin: what dermatologists and cosmeticians should know. Int J Womens Dermatol. 2018;4:122–30.
31. Mcainch AJ, Scott D, Armamento-Villareal R, Aguirre LE, Qualls C, Villareal DT, et al. Fat mass follows a u-shaped distribution based on estradiol levels in postmenopausal women. Front Endocrinol. 2018;9:315.
32. World Health Organization. Body mass index (BMI). 2023.
33. Alam M, Pongprutthipan M, Nanda S, Kim NA, Swary JH, Roongpisuthipong W, et al. Quantitative evaluation of skin shrinkage associated with non-invasive skin tightening: a simple method for reproducible linear measurement using microtattoos. Lasers Med Sci. 2019;34:703–9.
34. Hexsel D, Dal’Forno Dini T, Hexsel C. Skin distension test: a new simple tool to evaluate skin laxity. Dermatol Surg. 2021;47(7):1026–7.
35. Light D, Arvanitis GM, Abramson D, Glasberg SB. Effect of weight loss after bariatric surgery on skin and the extracellular matrix. Plast Reconstr Surg. 2010;125(1):343–51.
AUTHOR’S CONTRIBUTION:
Alessandra Haddad 0000-0002-5552-7251
Approval of the final version of the manuscript, Study design and planning, Preparation and writing of the manuscript, Data collection, analysis, and interpretation, Effective participation in research guidance, Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, Critical literature review, Critical review of the manuscript
Juliana Sarubi 0009-0000-4189-6235
Approval of the final version of the manuscript, Study design and planning, Preparation and writing of the manuscript, Data collection, analysis, and interpretation, Effective participation in research guidance, Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, Critical literature review, Critical review of the manuscript
Vania Assaly 0000-0002-4115-2081
Approval of the final version of the manuscript, Study design and planning, Preparation and writing of the manuscript, Data collection, analysis, and interpretation, Effective participation in research guidance, Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, Critical literature review, Critical review of the manuscript
www.surgicalcosmetic.org.br/
Double-blind randomized trial comparing commercial and compounded topical anesthetics for diode laser hair removal
Ensaio randomizado duplo-cego entre formulação anestésica comercial e magistral para depilação com laser diodo
IntroductIon: The demand for laser procedures in dermatology is increasing, and topical anesthetics are widely used to reduce pain, enhance patient comfort, and improve treatment outcomes. Despite their frequent use, the evaluation of pain perception during diode laser hair removal using topical anesthetics has not been extensively studied.
objectIve: This study aimed to compare the analgesic effects of a commercial 4% lidocaine formulation (Dermomax®, Aché Pharmaceutical Company, São Paulo, Brazil) with a compounded formulation containing 23% lidocaine and 7% tetracaine (Artpharma Pharmaceutical Company, São Paulo, Brazil) during LightSheer® diode laser hair removal procedures.
Methods: A total of 74 women aged between 14 and 65 years underwent a total of 256 laser hair removal procedures. Sixty minutes before the procedure, the two anesthetic formulations were applied: the commercial 4% lidocaine on one half of the treatment area, and the compounded 23% lidocaine with 7% tetracaine on the other half. The treated areas included axillae, face, legs, and groin. The side of the body on which each formulation was applied, as well as the side to be treated first with the laser, were randomly assigned in a double-blind manner. Pain intensity was assessed using a Visual Analog Scale (VAS). Data were analyzed by comparing VAS scores across the different treatment areas.
results: Statistically significant differences in pain perception were found in all evaluated regions. The compounded formulation resulted in lower pain scores compared to the commercial formulation. No adverse effects were reported.
conclusIons: The compounded anesthetic formulation containing 23% lidocaine and 7% tetracaine was more effective in providing analgesia than the commercial 4% lidocaine product (Dermomax®) for diode laser hair removal.
Keywords: Pain; Anesthetics; Laser Therapy.
RESUMO
Introdução: A busca por procedimentos a laser em dermatologia é crescente e os anestésicos tópicos são amplamente utilizados para reduzir a dor, oferecendo conforto e melhores resultados no tratamento. Apesar desse uso comum, a avaliação da percepção da dor durante o laser com anestésicos tópicos para depilação não foi amplamente estudada. Objetivo: O objetivo deste estudo foi comparar o efeito analgésico da lidocaína comercial a 4% (Dermomax® Aché farmacêutica, São Paulo, Brasil) e da formulação magistral de lidocaína a 23% associada a tetracaína a 7% (farmácia Artpharma, São Paulo, Brasil), utilizados em procedimentos com laser diodo LightSheer® para depilação. Métodos: Analisaram-se 77 pacientes num total de 256 procedimentos. Anestésicos tópicos foram aplicados 60 minutos antes do procedimento, sendo a lidocaína comercial a 4% aplicada de um lado e a formulação magistral do outro lado das áreas a serem tratadas: axilas, face, pernas ou virilha. O lado do corpo em que o laser deveria ser aplicado primeiro foi escolhido aleatoriamente, como num estudo duplo-cego. A intensidade da dor foi avaliada através da utilização da escala visual analógica.
Resultados: Houve diferença estatisticamente significativa em todas as regiões corporais avaliadas. Os dados sugerem que a formulação anestésica magistral proporcionou maior alívio da dor em comparação à comercial. Não houve efeitos colaterais no estudo.
Conclusão: O uso da formulação magistral é mais eficiente na produção de analgesia do que a lidocaína comercial a 4%.
Palavras-chave: Dor; Anestésicos; Terapia a Laser.
Original Article
Authors:
Yara Martins Ortigosa Leonardo1
Luciena Cegatto Martins Ortigosa1 Edmundo Pereira de Souza Neto2,3
1 Clínica Triune, Dermatology, Presidente Prudente (SP), Brazil
2 SCP d'Anesthésie, Clinique du Pont de Chaume, Anesthésie, Mountauban – Tarn-et-Garonne, France
3 Hôpital d'instruction des armées Robert Picqué, Anesthésie, Villenave d'Ornon – Gironda, France
The term “laser” stands for “light amplification by stimulated emission of radiation.” In practical terms, lasers are devices that generate electromagnetic radiation with specific characteristics and have a wide range of applications in dermatology.1 Their variety of wavelengths makes these systems highly versatile for procedures such as hair removal, skin rejuvenation, treatment of vascular lesions, and removal of pigmented lesions and tattoos.2
Unwanted hair growth is a common cosmetic concern for both men and women. In recent years, laser hair removal has emerged as a highly effective, long-lasting solution with minimal side effects.3 Among the lasers used for epilation are the ruby (695 nm), alexandrite (755 nm), diode (800 nm), and Nd:YAG (1064 nm). The most widely used diode laser for hair removal is the LightSheer®, manufactured by Lumenis® (Santa Clara, California, USA), which emits energy in the 800-810 nm range of the electromagnetic spectrum.3 It offers a selectable pulse duration between 5 and 400 ms and fluences ranging from 10 to 100 J/cm2
The LightSheer® laser has been shown to be a highly effective method for hair removal. Like other long-pulse lasers, it operates based on the principle of selective photothermolysis, which targets specific tissue structures while minimizing damage to surrounding tissue.4,5
The number of cosmetic and surgical procedures has grown considerably, along with the demand for effective, fast, and safe methods of analgesia. This trend has led to an increased use of topical anesthetics in such procedures to enhance patient comfort and improve treatment outcomes.6 Many topical anesthetics are available for use prior to minor outpatient procedures and laser treatments.6-8
Adverse events depend on the chemical structure and concentration of the anesthetic, the extent of application, and the duration of skin contact. Topical anesthetics may trigger type I (immediate hypersensitivity) or type IV (contact dermatitis) allergic reactions.6 Systemic complications can result from toxic effects on the central nervous and cardiovascular systems, especially when high concentrations are applied over large areas, leading to rapid systemic absorption. These reactions may include agitation, paresthesia, metallic taste, nausea, vomiting, disorientation, tremors, loss of consciousness, atrioventricular block, bradycardia, and seizures, and may progress to respiratory depression, coma, hypotension, heart failure, and death.6,9
Lidocaine is an amide-type anesthetic that rarely causes severe allergic reactions. However, systemic absorption may lead to dose-dependent adverse effects.6,9-10 Tetracaine, an ester-type anesthetic, is more lipophilic than lidocaine and prilocaine, allowing it to penetrate the cornea more effectively and form deposits that are released gradually. This reduces systemic absorption and prolongs the anesthetic effect.8-9 Allergic contact reactions to ester anesthetics are relatively common.8-9 Tetracaine is hydrolyzed in the dermis by nonspecific tissue esterases into para-aminobenzoic acid (PABA), which is responsible for many of these reactions. Its use on mucous membranes is not recom-
mended due to the lack of safety data.6,9-10
The ideal topical anesthetic should provide effective anesthesia within a short period, act on intact skin, and avoid both systemic and local adverse effects or discomfort. These pharmacological characteristics are found in commercially available eutectic and liposomal formulations, although only at lower concentrations.9,11 In contrast, compounded formulations containing higher concentrations of ester- and amide-type anesthetics have been used in cosmetic procedures to achieve stronger anesthetic effects. However, there are no comparative studies to confirm whether these higher-concentration combinations are more effective. As such, these agents and their formulations require further investigation.
OBJECTIVE
The aim of this study was to compare the analgesic effects of a commercial 4% lidocaine formulation (Dermomax®, Aché Pharmaceutical Company, São Paulo, Brazil) and a compounded formulation containing 23% lidocaine and 7% tetracaine (Artpharma Pharmaceutical Company, São Paulo, Brazil) in patients undergoing hair removal with the LightSheer® diode laser.
MATERIALS AND METHODS
This study was conducted at a private dermatology clinic over a period of 2 years. Following approval by the Research Ethics Committee (protocol number 1255) and the signing of informed consent forms, we performed a randomized, controlled, blinded trial with a single operator. Adult patients undergoing hair removal procedures on one or more of the following body areas were included: axillae, face, legs, and groin (trial registration: RBR-373nm7). A single patient could undergo multiple sessions and have one or more areas treated.
Exclusion criteria included a history of allergic reactions to any of the products used in the study, the presence of keloids, or sun exposure within four weeks prior to treatment. After providing informed consent, eligible patients were referred for laser hair removal sessions using the LightSheer® diode laser device.
TREATMENT PROCEDURE
To eliminate potential bias in treatment techniques, all procedures were performed by the same dermatologist using identical laser settings. Randomization was conducted using sealed envelopes to determine which anesthetic formulation would be applied to each side of the body as well as which side would be treated first. Both the patient and the dermatologist were blinded to the treatment allocation. Double blinding was maintained throughout the study unless unblinding was deemed necessary for clinical reasons — which did not occur. The coordinating investigator remained blinded until the study was completed and ready for analysis.
A total of 60 minutes prior to the laser procedure, patients received a single oral dose of 10 mg ketorolac trometha-
mine (Toragesic®, Sigma Laboratories, São Paulo, Brazil). At the same time, the treatment area was cleansed with a mild emollient and water to remove any residues from moisturizers or other home-use products. Topical anesthetics were then applied in equal amounts (approximately 2 mm thick). The average treatment area was estimated to be less than 500 cm2 per patient, calculated using the surface area of the palm (excluding fingers).12
Commercial 4% lidocaine was applied to one half of the treatment area, and the compounded formulation containing 23% lidocaine and 7% tetracaine was applied to the other half. Treated regions included the axillae, face, legs, and groin. After 60 minutes, the anesthetics were removed, and the laser procedure was performed using identical parameters on both sides of each treatment area. Settings were individualized according to the body area, hair thickness and color, and the patient’s Fitzpatrick skin type, with pulse durations ranging from 5 to 100 ms and fluences between 30 and 60 J/cm2. No cooling was used.
Pain intensity was assessed using the Visual Analog Scale (VAS). At the end of each session, patients were asked to rate their pain on a scale from 0 to 10, where 0 represented no pain and 10 indicated the highest level of pain. Data analysis was performed by comparing pain scores between the two sides of the body within the same treated area. Adverse events were monitored on the day of the procedure and again at a follow-up visit 2 days later. No significant changes were made to the study methods or outcome measures after the trial began.
STATISTICAL ANALYSIS
Power analysis indicated that 80 procedures were required to detect a 1-point difference in VAS scores between the two products, with a 5% type I error rate, an 80% power, and a two-tailed test. Results were expressed as medians ± standard deviation (SD) of the median.The median absolute deviation (MAD), a variation of mean absolute deviation, was used because it is less influenced by outliers; extreme values have less impact on the median than on the mean. For datasets with extreme values, the MAD or interquartile range generally provides a more robust estimate of variability than the SD.
The nonparametric Wilcoxon signed-rank test was used to compare VAS scores. Qualitative variables were analyzed using Fisher’s exact test. Linear correlations were assessed using Spearman’s rank correlation coefficient. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed by using StatView® for Windows (Abacus® Concepts Inc., Berkeley, CA, USA; version 4.57, 1996).
RESULTS
A total of 77 patients were included in the study, of whom 64 underwent more than one procedure. There were no losses or exclusions after randomization (Figure 1). Table 1 presents the patients’ anthropometric characteristics according to the number of procedures performed per treatment area.
Figure 1: Double-blind randomized trial comparing commercial and compounded topical anesthetics for diode laser hair removal
Table 1: Anthropometric characteristics per area
Fitzpatrick classification (I/II/III/IV/V/VI)
Results are expressed as median ± standard deviation of the median. BMI: Body mass index; kg: kilogram; m: meter
DISCUSSION
2: Visual Analog Scale (VAS) scores by treatment area at the end of the laser session
None of the participants had previously undergone light-based or laser therapy, and all were free of systemic diseases. Throughout routine follow-up, no adverse effects related to the laser procedure or topical anesthetics were reported by any patient.
A total of 256 laser hair removal procedures were performed, distributed across four body areas in the following manner: 69 axillary, 88 facial, 36 legs, and 63 groin treatments. A statistically significant difference in pain control was observed between the two anesthetic formulations used with the LightSheer® diode laser. The compounded formulation resulted in significantly lower pain scores compared to the commercial product, demonstrating greater anesthetic efficacy across all evaluated body regions (Figure 2).
Pain can reduce patient satisfaction and compromise the efficacy of laser procedures, often requiring the use of lower laser settings. Patients undergoing diode laser hair removal frequently report pain, described as burning or stinging sensations.This discomfort can be distressing for both the operator and the patient. In our pain management approach, we combined topical anesthetic creams with ketorolac, a potent nonsteroidal anti-inflammatory drug (NSAID) with both anti-inflammatory and analgesic properties. Indeed, ketorolac pretreatment has been shown to be a safe, effective method for pain relief prior to procedures such as chemical peeling, without adverse reactions.13,14 The combination of topical anesthetics and NSAIDs can be useful in minimizing treatment-related discomfort. Topical anesthetics are painless to administer and reduce the risk of systemic exposure.15
Figure
A systematic review of noninvasive anesthetic methods for dermatologic laser procedures included several studies involving the use of topical anesthetics during laser hair removal.15-23 Although these agents were associated with pain reduction, the overall quality of evidence was low. Many studies failed to report or perform statistical analyses and did not provide p-values or confidence intervals.12 Additionally, randomization was not always employed, and blinding was often not feasible — particularly relevant since that pain is a subjective outcome measure.15
In addition to the low quality of existing studies, no previous research has compared commercial preparations to compounded formulations across different body regions. This gap underscores the relevance of our study, which statistically compared both anesthetic types across four body areas.
The anesthetics evaluated in our study were lidocaine and tetracaine. Tetracaine is a highly potent, long-acting ester-based anesthetic. Its prolonged action is due to its high hydrophobicity, which allows sustained interaction with sodium channel binding sites, conferring greater potency than lidocaine. In contrast, lidocaine is a moderately hydrophobic, amide-based anesthetic with a rapid onset of action and a moderate duration of effect (approximately 1-2 hours). It also has a lower risk of triggering allergic reactions.24
Compounded anesthetic formulations — such as the one evaluated in our study — are commonly used before dermatologic procedures to enhance anesthetic efficacy. These formulations allow for higher concentrations and combinations of multiple anesthetic agents.25,26 Our study assessed the efficacy of a compounded formulation containing 23% lidocaine and 7% tetracaine and found it to be superior to the commercial 4% lidocaine product (Dermomax®) in terms of pain control.
However, the use of high-concentration compounded topical anesthetics requires additional precautions. Reports of systemic toxicity have typically involved application of such formulations under occlusion to large surface areas.27 Some studies advise against applying large quantities, under occlusion, for extended durations, or on irritated or broken skin.28-30 Caution is also advised when using these formulations in conjunction with laser procedures — particularly resurfacing techniques.29 Moreover, it is recommended to use the same compounding pharmacy consistently to reduce variability in product composition.26
Although adverse events reported in research highlight the importance of proper education regarding the use and risks of compounded topical anesthetics, our study did not identify any side effects. These findings support the efficacy and apparent safety of the compounded formulation containing 23% lidocaine and 7% tetracaine when used appropriately.
STUDY LIMITATIONS
This study presents several limitations. First, we did not measure plasma levels of lidocaine, monoethylglycinexylidide, or tetracaine. Elevated serum levels of lidocaine have been associated with higher topical concentrations, longer exposure times, larger application areas, and the use of occlusive dressings. Some studies suggest that combining ester- and amide-type anesthetics may present a higher risk of toxicity than combining two amides, such as lidocaine and prilocaine.32-34 However, Spiegel et al. found no evidence of synergistic central nervous system toxicity between lidocaine and tetracaine in a rat model.35
As noted by Oni et al. (2010), there is significant interindividual variability in lidocaine absorption through the skin. Moreover, systemic levels are not always directly correlated with the applied dose or exposure time.33 In our study, exposure time was minimized, no occlusive dressings were used, and the same compounding pharmacy was consistently employed to ensure formulation consistency. Additionally, a trained health professional — familiar with the warning signs of lidocaine toxicity — was present during all procedures and prepared to manage any adverse reactions. No clinical signs of toxicity were observed in any of the participants.
Second, this was a single-center study, which may limit the generalizability of the findings to other clinical settings. Third, the compounded formulation used in this study may differ from similar formulations prepared by other institutions. The efficacy of a topical anesthetic depends not only on concentration and dosage, but also on the vehicle used for delivery.30-32
CONCLUSION
The findings suggest that the compounded formulation containing 23% lidocaine and 7% tetracaine is more effective in providing analgesia across all treated areas compared to the commercial 4% lidocaine cream (Dermomax®). No allergic reactions or other adverse effects were observed during the study. Nevertheless, proper administration is essential to avoid potential, though rare, serious complications.
In conclusion, the compounded formulation of 23% lidocaine and 7% tetracaine proved to be an effective, noninvasive, well-tolerated option for topical anesthesia during laser hair removal. It represents a promising choice for patients who are likely to undergo repeated procedures requiring topical anesthesia. l
REFERENCES:
1. Gianfaldoni S, Tchernev G, Wollina U, Fioranelli M, Roccia MG, Gianfaldoni R, et al. An overview of laser in dermatology: the past, the present and… the future (?). Open Access Maced J Med Sci. 2017;5(4):526-30.
2. Callaghan DJ 3rd, Bonati LM, Alam M, Jerdan K, Taylor MB, Dover JS. Sound levels and safety in cosmetic laser surgery. Lasers Surg Med. 2019;51(6):491-4.
3. Shapiro J, Lui H. Treatments for unwanted facial hair. Skin Therapy Lett. 2005;10(10):1-4.
4. Ataie-Fashtami L, Shirkavand A, Sarkar S, Alinaghizadeh M, Hejazi M, Fateh M, et al. Simulation of heat distribution and thermal damage patterns of diode hair-removal lasers: an applicable method for optimizing treatment parameters. Photomed Laser Surg. 2011;29(7):509-15.
5. Gan SD, Graber EM. Laser hair removal: a review. Dermatol Surg. 2013;39(6):823-38.
6. Sobanko JF, Miller CJ, Alster TS. Topical anesthetics for dermatologic procedures: a review. Dermatol Surg. 2012;38(5):709-21.
7. Kundu S, Achar S. Principles of office anesthesia: part II. Topical anesthesia. Am Fam Physician. 2002;66(1):99-102.
8. Boyce RA, Kirpalani T, Mohan N. Updates of topical and local anesthesia agents. Dent Clin North Am. 2016;60(2):445-71.
9. Lee HS. Recent advances in topical anesthesia. J Dent Anesth Pain Med. 2016;16(4):237-44.
10. Catterall W, Mackie K. Local anesthetics. In: Goodman & Gilman's editors. The pharmacological basis of therapeutics. New York: McGraw-Hill; 2006. p.369-86.
12. Scarisbrick JJ, Morris S. How big is your hand and should you use it to score skin in cutaneous T-cell lymphoma? Br J Dermatol. 2013;169(2):260-5.
13. Kim JH, Whang KK, Hahm JH. The Effect of Premedication with Ketorolac on Pain Relief During Chemical Peeling. Ann Dermatol. 2002;14(1):18-21.
14. Esparza-Villalpando V, Ortiz-Barroso G, Masuoka-Ito D. Evidence-based safety profile of oral ketorolac in adults: systematic review and meta-analysis. Pharmacol Res Perspect. 2024;12(6):e70033.
15. Greveling K, Prens EP, Liu L, Van Doorn MBA. Non-invasive anaesthetic methods for dermatological laser procedures: a systematic review. J Eur Acad Dermatol Venereol. 2017;31(7):1096-110.
16. Akinturk S, Eroglu A. Effect of piroxicam gel for pain control and inflammation in Nd:YAG 1064-nm laser hair removal. J Eur Acad Dermatol Venereol. 2007;21(3):380-3.
17. Akinturk S, Eroglu A. A clinical comparison of topical piroxicam and EMLA cream for pain relief and inflammation in laser hair removal. Lasers Med Sci. 2009;24(4):535-8.
19. Eremia S, Newman N. Topical anesthesia for laser hair removal: comparison of spot sizes and 755 nm versus 800 nm wavelengths. Dermatol Surg. 2000;26(7):667-9.
AUTHOR’S CONTRIBUTION:
Yara Martins Ortigosa Leonardo
0000-0001-9892-2887
20. Guardiano RA, Norwood CW. Direct comparison of EMLA versus lidocaine for pain control in Nd:YAG 1,064 nm laser hair removal. Dermatol Surg. 2005;31(4):396-8.
21. Ke M. Pain inhibition with pneumatic skin flattening (PSF) in permanent diode laser hair removal. J Cosmet Laser Ther. 2007;9(4):210-2.
22. Nahm WK, Tsoukas MM, Falanga V, Carson PA, Sami N, Touma DJ. Preliminary study of fine changes in the duration of dynamic cooling during 755-nm laser hair removal on pain and epidermal damage in patients with skin types III-V. Lasers Surg Med. 2002;31(4):247-51.
23. Rashidi T, Hoseinzade N. Comparison of pain reduction between lidocaine-prilocaine cream and diclofenac gel in patients treated with the alexandrite laser. Iran J Dermatol 2012;15:109-10.
24. Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012;59(2):90-101.
25. Railan D, Alster TS. Use of topical lidocaine for cosmetic dermatologic procedures. J Drugs Dermatol. 2007;6(11):1104-8.
26. Carruthers JA, Carruthers JD, Poirier J, Oliff HS, Mordaunt J, Schreiber WE. Safety of lidocaine 15% and prilocaine 5% topical ointment used as local anesthesia for intense pulsed light treatment. Dermatol Surg. 2010;36(7):1130-7.
27. Neal JM, Bernards CM, Butterworth JF 4th, Di Gregorio G, Drasner K, Hejtmanek MR, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35(2):152-61.
28. Kapes B. Media microscope analyzes misuse of topicals. Dermatol Times 2005;26:22.
29. Kumar M, Chawla R, Goyal M. Topical anesthesia. J Anaesthesiol Clin Pharmacol. 2015;31(4):450-6.
30. Tayeb BO, Eidelman A, Eidelman CL, McNicol ED, Carr DB. Topical anaesthetics for pain control during repair of dermal laceration. Cochrane Database Syst Rev. 2017;2(2):CD005364.
31. Berkman S, MacGregor J, Alster T. Adverse effects of topical anesthetics for dermatologic procedures. Expert Opin Drug Saf. 2012;11(3):415-23.
32. McCleskey PE, Patel SM, Mansalis KA, Elam AL, Kinsley TR. Serum lidocaine levels and cutaneous side effects after application of 23% lidocaine 7% tetracaine ointment to the face. Dermatol Surg. 2013;39(1 Pt 1):82-91.
33. Oni G, Brown S, Burrus C, Grant L, Watkins J, Kenkel M, et al. Effect of 4% topical lidocaine applied to the face on the serum levels of lidocaine and its metabolite, monoethylglycinexylidide. Aesthet Surg J. 2010;30(6):853-8.
34. Oni G, Brown S, Kenkel J. Comparison of five commonly-available, lidocaine-containing topical anesthetics and their effect on serum levels of lidocaine and its metabolite monoethylglycinexylidide (MEGX). Aesthet Surg J. 2012;32(4):495-503.
35. Spiegel DA, Dexter F, Warner DS, Baker MT, Todd MM. Central nervous system toxicity of local anesthetic mixtures in the rat. Anesth Analg. 1992;75(6):922-8.
Approval of final version of the manuscript, Study conception and planning, Manuscript preparation and writing, Data collection, analysis, and interpretation, Critical review of literature, Critical review of manuscript.
Luciena Cegatto Martins Ortigosa
0000-0002-3541-9456
Approval of final version of the manuscript, Study conception and planning, Manuscript preparation and writing, Data collection, analysis, and interpretation, Active participation in research supervision, Intellectual contribution to the diagnostic and/or therapeutic management of studied cases, Critical review of literature, Critical review of manuscript.
Edmundo Pereira de Souza Neto
0000-0001-6921-235X
Statistical analysis, Approval of final version of the manuscript, Study conception and planning, Manuscript preparation and writing, Data collection, analysis, and interpretation, Active participation in research supervision, Intellectual contribution to the diagnostic and/or therapeutic management of studied cases, Critical review of literature, Critical review of manuscript.
www.surgicalcosmetic.org.br/
Study of the antimicrobial and antioxidant activity of anti-acne face wash, hand sanitizer gel, and soap containing phycocyanin and phycoerythrin
Estudo da atividade antimicrobiana e antioxidante de gel de limpeza facial antiacne, gel desinfetante para as mãos e sabonete feitos com ficocianina e ficoeritrina
Introduction: The use of natural ingredients in skincare products has gained increasing attention due to the harmful effects and environmental risks associated with synthetic compounds.
Objective: This growing concern has driven research into photosynthetic organisms as sustainable and eco-friendly sources of effective ingredients. Natural extracts — particularly those derived from plants, algae, and cyanobacteria — have drawn significant interest in the cosmetics industry. Cyanobacteria stand out for their low cultivation requirements, rapid growth, and ability to produce a wide range of bioactive metabolites, making them a sustainable and cost-effective resource.
Methods: This study evaluated the effects of natural pigments — phycocyanin and phycoerythrin — extracted from Spirulina platensis and Nostoc sp. on three cosmetic products: soap, anti-acne face wash, and hand sanitizer gel. After culturing the cyanobacteria, the pigments were extracted, purified, and coated with chitosan as a stabilizer. These coated pigments were then used to formulate the cosmetic products, which were assessed for viscosity, pH, stability, antioxidant activity, and antibacterial properties.
Results: The results showed that phycocyanin and the combined pigment content were higher in the anti-acne face wash and soap, whereas phycoerythrin and the total pigment concentration were greater in the hand sanitizer gel.
Conclusion: This study demonstrates the potential of cyanobacterial pigments to produce stable, enriched cosmetic products, offering sustainable and effective alternatives to synthetic ingredients.
Introdução: O uso de ingredientes naturais em produtos de cuidados com a pele tem ganhado grande interesse devido aos efeitos adversos dos compostos sintéticos.
Objetivo: Essa preocupação crescente impulsionou a pesquisa sobre organismos fotossintéticos como fontes sustentáveis e ecológicas de ingredientes eficazes. Extratos naturais, especialmente os derivados de plantas, algas e cianobactérias, têm atraído grande interesse da indústria de cosméticos. As cianobactérias se destacam por suas baixas exigências culturais, crescimento rápido e capacidade de produzir diversos metabólitos bioativos, tornando-as um recurso sustentável e econômico.
Métodos: Este estudo avaliou os efeitos de pigmentos naturais — ficocianina e ficoeritrina — extraídos de Spirulina platensis e Nostoc sp. em três produtos cosméticos: sabonete, gel de limpeza facial antiacne e gel desinfetante para as mãos. Após o cultivo das cianobactérias, os pigmentos foram extraídos, purificados e revestidos com quitosana como estabilizante. Esses pigmentos revestidos foram então utilizados para formular os produtos cosméticos, que foram avaliados quanto à viscosidade, pH, estabilidade, atividade antioxidante e propriedades antibacterianas.
Resultados: Os resultados mostraram que a ficocianina e o conteúdo combinado de pigmentos foram maiores no gel antiacne e sabonete, enquanto a ficoeritrina e a concentração total de pigmentos foram maiores no gel desinfetante. Conclusão: Este estudo demonstra o potencial de produzir produtos cosméticos estáveis e enriquecidos com pigmentos de cianobactérias, oferecendo alternativas sustentáveis e eficazes aos ingredientes sintéticos.
Funding support: None. Conflicts of interest: None.
Submitted on: 19/08/2024
Approved on: 16/01/2025
How to cite this article: Nowruuzi B, Alibabaei M. Study of the antimicrobial and antioxidant activity of anti-acne face wash, hand sanitizer gel, and soap containing phycocyanin and phycoerythrin. Surg Cosmet Dermatol. 2025;17:e20250396.
INTRODUCTION
Cyanobacteria have been used for over 2,000 years, dating back to their application by the Chinese during periods of malnutrition. Since the 1950s, they have been increasingly utilized in biotechnology.1,2 Their chemical composition enhances the nutritional value of food and animal feed, plays a crucial role in aquaculture, and supports the development of cosmetic products.2 Microalgal biomass, including that of cyanobacteria, is used to produce a variety of valuable products, particularly high-protein dietary supplements for human nutrition, aquaculture, and nutraceutical applications.3
Cosmetics have become an essential part of daily routines, with growing consumer demand driven by concerns for skin health and aesthetics. Ethical issues surrounding the use of animal-derived ingredients, as well as the potential adverse effects of synthetic substances — such as allergies and environmental risks — have led to increased interest in cosmetic products formulated from photosynthetic organisms.4 Among these, microalgae stand out for their ability to promote skin healing and repair, along with anti-blemish and anti-inflammatory properties.5-7
The cyanobacterial genera Nostoc, Spirulina (also known as Arthrospira), and Aphanizomenon are particularly well-studied due to their high content of calcium, beta-carotene, phosphorus, iron, biotin, folic acid, pantothenic acid, and vitamin B12.8 Extracts and bioactive compounds derived from these species are under investigation for their protective effects on skin and hair.9 For example, beta-carotene from Desmonostoc muscorum, Leptolyngbya foveolarum, and Arthrospira platensis has demonstrated the ability to regulate UV-A-induced gene expression in human keratinocytes.10 It also modulates biological targets such as NF-κB, COX-2, and matrix metalloproteinase-9, owing to its anti-inflammatory activity.5
Cyanobacterial phycobiliproteins (PBPs), such as phycocyanin (PC), exhibit antioxidant, anti-inflammatory, and anti-aging properties and are already being utilized in cosmetics.7-11 These hydrophilic proteins, found in cyanobacteria and certain red algae, offer promising commercial applications as natural cosmetic ingredients.12 Structurally similar to bilirubin, PBPs are efficient scavengers of reactive oxygen species, making them potential antioxidant agents. They are composed of three main components: phycoerythrin (PE; a red pigment), allophycocyanin (a bluish-green pigment), and PC (a blue pigment).These fluorescent protein-pigment complexes have diverse commercial potential.13
Spirulina contains several key phytopigments — including PC, gamma-linolenic acid, phycocyanobilin, and phycoerythrobilin — which contribute to its antioxidant, anti-melanogenic, anti-wrinkle, and anti-aging properties.11 These compounds are already incorporated into cosmetic products such as lipsticks, eyeliners, and eyeshadows as natural colorants. In addition to its dermatological benefits, Spirulina is also recognized for its anti-inflammatory, neuroprotective, and hepatoprotective effects. It has been shown to reduce serum levels of alanine aminotransfe-
rase, aspartate aminotransferase, and malondialdehyde.4,14
Cyanobacterial extracts also contain peptides and proteins that are suitable for use in hair care products, including lotions, shampoos, permanent wave solutions, and hair coloring agents.15,16 Studies on Chlorogloeopsis sp. and Spirulina extracts have reported benefits such as increased shine, easier combing, improved hair restoration, and enhanced moisturization. For example, the Blue Green Algae Hair Rescue Conditioning Mask by Aubrey Organics has shown effectiveness in strengthening hair and preventing breakage and split ends.6
Active cyanobacterial extracts, such as Spirulina-derived Spiralin®, are currently in use in the cosmetics industry for skin protection. Products like Skinicer® Repair Cream and Spirularin® contain these extracts, which have demonstrated regenerative effects on damaged skin cells and collagen, as well as protection against UV radiation. Additionally, the PBP C-phycocyanin (C-PC), derived from Aphanizomenon flos-aquae, is used in NaturCyanin Bioactive® as a natural alternative to synthetic colorants, due to the attractive pink-purple hue it imparts.17
There remains limited research on cosmetic applications of other cyanobacterial genera, thus presenting a valuable opportunity for further exploration. This study evaluates the antioxidant and antimicrobial effects of soap, anti-acne face wash, and hand sanitizer gel formulated with chitosan-coated PC and PE.
METHODS
Culture conditions of Nostoc sp. and Spirulina sp. Cyanobacterial strains Spirulina platensis and Nostoc sp., isolated from the cyanobacteria culture collection (CCC) of the ALBORZ Herbarium at the Science and Research Branch, Islamic Azad University, Tehran, were cultivated in modified Zarrouk and BG110 media, respectively. Cultures were maintained in illuminated growth chambers (300 µmol m-2 s-1) at 28 ± 2 °C for 30 days.18,19
Extraction and purification of analytical-grade
PC and PE
PC and PE were extracted and purified from 14-day-old log-phase cultures.20 The cyanobacterial cultures were centrifuged at 4,000 rpm to collect the biomass pellet. The pellet was resuspended in a specific buffer for PC and in potassium phosphate buffer for PE.The extraction procedure was repeated daily for four days until the cell biomass turned dark purple.
Crude pigment extracts were obtained by centrifugation at 5,000 rpm for 10 minutes. Purification followed the method of Afreen and Fatma, which involves the addition of solid ammonium sulfate to the crude extract to achieve 65% saturation.21 The mixture was centrifuged at 4,500 × g for 10 minutes, and the resulting pellet was resuspended in 50 mM acetic acid–sodium acetate buffer, followed by overnight dialysis. The dialyzed extracts were then filtered through a 0.45 μm membrane filter.
The absorption spectra of the purified pigments were measured using a Specord 200 spectrophotometer (Analytik Jena, Germany), scanning the samples across wavelengths ranging from 300 to 750 nm. Concentrations of PC and PE were determined based on absorbance measurements at 620 and 650 nm (for PC) and at 565 nm (for PE), using standard equations. Pigment purity was assessed at each step by calculating the purity ratios: A620/ A652 for PC and A555/A280 for PE (Figure 1).22
Stabilization and coating of pigments with chitosan
PC and PE were encapsulated by combining them with a water-soluble chitosan (WSC) solution, using sodium tripolyphosphate as a cross-linking agent. The WSC solution was prepared by dissolving oligochitosan in distilled water at a concentration of 1 mg/mL. This mixture was maintained at 4 °C for 24 hours to ensure complete hydration. Subsequently, 1 mL of PC + PE solution (in deionized water) was slowly added to 1 mL of WSC solution (1 mg/mL) under constant stirring at 25 °C. Sodium tripolyphosphate (2 mg/mL) was then added in 0.5 mL aliquots, followed by pH adjustment to 7.0 using 1% HCl. Finally, 0.5 mL of polyethylene glycol (PEG) was added to complete the stabilization process.23
A C B D
E F G H
Formulation of soap, anti-acne face wash, and hand sanitizer gel
A series of experimental trials were conducted to optimize the laboratory formulations of soap, anti-acne face wash, and hand sanitizer gel. The final compositions were developed based on the best-performing ingredient combinations (Table 1). Four control treatments were included in the formulation process for all three products: (1) a formulation without any pigment, (2) a formulation containing only PC (1.5 g), (3) a formulation containing only PE (1.5 g), and (4) a formulation containing a combination of both pigments (1.5 g total) (Figure 2).24-26
Evaluation tests of anti-acne face wash
Viscosity
The viscosity of the anti-acne face wash was evaluated using a digital Brookfield viscometer (spindle No. 64), operating at 10 rpm and a controlled temperature of 25 °C. A predetermined amount of the product was transferred to a beaker, and the viscometer spindle was immersed in the sample to perform the measurement. All tests were conducted in triplicate to ensure accuracy and reproducibility.27
pH
The pH of a 1% aqueous solution of the formulation was measured at a constant temperature of 25 °C using a calibrated digital pH meter.28
Figure 1: Different stages of separation and purification of phycocyanin (A to D) and phycoerythrin (E to H) pigments. A - primary culture of Spirulina cyanobacteria, B - preparation of crude extract, C - dialysis, D - freeze-drying and preparation of phycocyanin powder, E - primary culture of Nostoc cyanobacteria, F - preparation of crude extract, G - dialysis, H - freeze-drying and preparation of phycoerythrin powder
sanitizer gel
Table 1: Composition of anti-acne face wash gel, soap, and hand sanitizer gel
Physical evaluation
A visual inspection was conducted to assess the physical characteristics of the formulation, including color, appearance, and consistency.29
Gel stability
The stability of the gel formulations was evaluated using the freeze–thaw cycle method. Samples were stored at 4 °C, 25 °C, 37 °C, and 40 °C for a period of 7 days, and any changes in physical appearance or texture were recorded.30
Gel homogeneity
Homogeneity was assessed visually after transferring the gel into a designated container. Each sample was examined for uniformity in appearance, presence of any lumps or phase separation, and density distribution.31
Antimicrobial assay of anti-acne face wash
The antimicrobial activity of the anti-acne face wash was evaluated using the turbidimetric method. A sterile nutrient agar medium was prepared aseptically and spread evenly onto Petri dishes. The acne-affected area on a volunteer’s face was first cleansed with distilled water and allowed to air dry. By using a sterile cotton swab, distilled water was applied to a ruptured
pimple to collect microbial content, which was then transferred onto the agar medium to inoculate it. Following incubation at 37 °C for 24 hours, six sterile cotton balls (1 cm in diameter) were immersed for 5 minutes in various formulations — including a standard drug, the test formulations, and distilled water (control). A 50 mL volume of nutrient broth was prepared and sterilized; 5 mL of this broth was used as a blank reference in a UV spectrophotometer. The remaining broth was inoculated with the microbial culture from the Petri plate and divided into six sterile test tubes, each containing one of the cotton ball samples. Test tubes were incubated at 37 °C for 24 hours. After incubrpmation, the absorbance of each sample was measured at 600 nm to assess microbial growth inhibition.32
Evaluation tests of soap
Moisture content
A 10 g sample of soap was weighed immediately and recorded as the wet weight. The sample was then dried at a temperature below 115 °C by using appropriate drying equipment until a constant weight was achieved. After cooling, the sample was reweighed and recorded as the dry weight. The moisture content was calculated using the following equation:
Figure 2: Preparation of anti-acne gel A - (a): without pigment, (b): with phycoerythrin, (c): total of phycoerythrin and phycocyanin, (d): with phycocyanin; Hand gel B - (a): total of phycoerythrin and phycocyanin, (b): with phycoerythrin, (c): with phycocyanin, (d): without pigment; Soap C - (a): without pigment, (b): with phycocyanin, (c): phycoerythrin + phycocyanin, (d): with phycocyanin
%W = 100 A – B/B × 100.
Where:
%W = Percentage of moisture in the sample
A = Weight of wet sample (g)
B = Weight of dry sample (g)33
Soap viscosity
A 40 mL portion of the soap solution was transferred into a 100 mL beaker. The spindle of a Brookfield digital visco-
meter was immersed into the solution, and viscosity was measured under standard conditions.34
Total fatty matter
An accurately weighed 5 g sample of soap was transferred to a 250 mL beaker. A volume of 100 mL of hot distilled water was added to completely dissolve the soap.Then, 40 mL of 0.5 N nitric acid was added until the solution reached a mildly acidic pH. The mixture was heated in a water bath to promote the separation of fatty acids, which formed a distinct upper layer. After cooling, the fatty acids were isolated using ice.
To extract residual fatty acids, 50 mL of chloroform was added to the remaining solution and transferred to a separating funnel.The mixture was shaken and allowed to separate into two phases. The lower aqueous layer was discarded. Another 50 mL of chloroform was added to the remaining solution to repeat the extraction process. The chloroform layers containing the fatty acids were combined.
The lipid content was transferred to a pre-weighed porcelain dish, evaporated, and the remaining residue was weighed. The percentage of total fatty matter was calculated by determining the mass difference.35
pH
A 10% soap solution was prepared by dissolving 1 g of soap in 10 mL of distilled water in a volumetric flask. The pH was measured using a pre-calibrated digital pH meter.33
Foam height
A 0.5 g soap sample was dispersed in 25 mL of distilled water and transferred to a measuring cylinder. The solution was diluted to a total volume of 50 mL.The mixture was then shaken manually with 25 strokes. The height of the foam formed above the aqueous solution was measured.33
Foam retention
A 25 mL sample of 1% soap solution was placed in a 100 mL graduated cylinder. The cylinder was manually sealed and shaken 10 times. Foam volume was recorded at 1-minute intervals over a 4-minute period.33
Alcohol insoluble content
A 5 g sample of soap was dissolved in 50 mL of hot ethanol. The solution was filtered through a filter paper previously coated with tar and rinsed with an additional 20 mL of warm ethanol. The filter paper and retained residue were dried at 105 °C for 1 hour. After drying, the weight of the residue was measured, and the percentage of alcohol-insoluble matter was calculated using the following formula: % Alcohol-insoluble matter = (Weight of residue × 100) / Weight of sample36
High temperature stability
Liquid soap samples were stored at temperatures of 25 °C, 37 °C, 40 °C, and 50 °C for a period of 1 month. Stability was monitored over this time frame. Samples that remained homogeneous and free of precipitation or crystallization were classified as stable. In contrast, samples that developed roughened crystals or visible precipitation were deemed unstable.37
Percentage free alkali
Approximately 5 g of the soap sample were placed into a conical flask and mixed with 50 mL of neutralized alcohol. The mixture was subjected to reflux in a water bath for 30 minutes, then cooled to room temperature. Afterward, 1 mL of phenolphthalein indicator solution was added, and the mixture was titrated immediately with 0.1 N hydrochloric acid (HCl) until the pink color disappeared.37
Saponification value determination
The saponification value represents the number of mg of potassium hydroxide (KOH) required to saponify 1 g of fat or oil. Approximately 2 g of the soap sample were placed into a conical flask, followed by the addition of 0.5 M KOH solution. The mixture was stirred continuously and heated in a water bath at approximately 55 °C. The temperature was then increased by an additional 100 °C, and the mixture was boiled for about 1 hour.
Titration was performed using phenolphthalein as an indicator and 0.5 M HCl. The endpoint of the titration was determined by the disappearance of the pink color.38
The saponification value was calculated using the following formula:
Saponification value = (Average volume of KOH × 28.056) / Weight of oil (g)
Antimicrobial assay of soap
Antimicrobial tests were conducted to evaluate the biological activity of the optimized soap formulations. The agar well diffusion method was used to assess their efficacy against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Sterile nutrient agar plates were inoculated with the respective test organisms, and wells were created in the agar. Each formulation was placed into individual wells and allowed to diffuse for 2 hours.The plates were then incubated at 37 °C for 24 hours. After incubation, the zones of inhibition (ZOI) around each well were measured and compared to assess antimicrobial effectiveness.39
Evaluation tests of hand sanitizer gel
Physical analysis
Physical characteristics of the hand sanitizer gel were assessed through pH and viscosity measurements. pH was determined by using a pre-calibrated digital pH meter (Mettler Toledo, Philippines).Viscosity was measured with a Brookfield digital viscometer by immersing the spindle in a measured volume of gel placed in a glass container.26
Antibacterial activity by agar well diffusion assay
The antibacterial efficacy of the hand sanitizer gel was evaluated against five bacterial species: two gram-positive bacteria (S. aureus and Enterococcus faecalis) and three gram-negative bacteria (E. coli, P. aeruginosa, and Salmonella typhi). Bacterial cultures were maintained on tryptone soya agar at 40 °C.
Inoculum preparation followed the Clinical and Laboratory Standards Institute (CLSI) guidelines (M02-A12).39 Isolated colonies of each bacterial strain were selected from freshly prepared agar plates and incubated for 18–24 hours. These colonies were then transferred into tryptone soy broth to prepare bacterial suspensions. Turbidity of each suspension was adjusted to achieve a concentration of 1.0 to 2.0 × 108 CFU/mL, verified using a UV-Visible spectrophotometer at 600 nm.
For the assay, 0.1 mL of each bacterial suspension was spread evenly onto Mueller-Hinton agar plates using a sterile spreader. Wells with a diameter of 6 mm were created using sterile borers. Into each well, 50 µL of the formulated gel and commercial hand sanitizer gels were introduced. Positive and negative controls were included using 70% ethanol and dimethyl sulfoxide (DMSO), respectively.
After a 5-minute diffusion period at room temperature, plates were incubated at 37 °C for 18 to 24 hours. Following incubation, the ZOI surrounding each well were measured using an automatic colony counter set to inhibition zone mode.40
Determination of minimum inhibitory concentration (MIC)
MIC of the hand sanitizer formulations was determined using the macrodilution method in sterile test tubes following the guidelines of the CLSI (M07-A08).41
The laboratory-prepared gel was serially diluted in Mueller-Hinton broth using a 1:2 ratio, resulting in a concentration range from 100% to 0.195%. The test inoculum was prepared in three steps: i) a cell suspension of each bacterial strain was prepared as described in the agar well diffusion assay, adjusted to a concentration of 1 to 2 × 108 CFU/mL; ii) the suspension was diluted at a ratio of 1:150 to reach an intermediate density of 1 × 106 CFU/mL; and iii) this suspension was further diluted 1:2 to obtain the final inoculum concentration of 5 × 105 CFU/mL.
Each test tube in the dilution series received 1 mL of the hand sanitizer formulation and 1 mL of the bacterial inoculum, with the procedure performed within 15 min of inoculum preparation. The contents were mixed thoroughly. Serial dilution was conducted by transferring 1 mL from one tube to the next, maintaining a 1:2 dilution factor across the series. The final tube in the series contained the lowest concentration (0.195%).
The same procedure was followed to determine MIC for different pigment concentrations within the hand sanitizer. All tubes were incubated at 37 °C for 16 to 20 hours. MIC was defined as the lowest concentration of the formulation at which no visible microbial growth was observed, as determined without the aid of instrumentation.40
Determination of minimum bactericidal concentration (MBC)
MBC was determined by inoculating 0.1 mL of the bacterial suspension from each tube used in the MIC assay onto Mueller-Hinton agar plates using the spread plate technique. Following inoculation, plates were incubated at 37 °C for 18 to 24 hours.
After incubation, the MBC was identified as the lowest concentration of the hand sanitizer gel at which no bacterial growth was observed. The absence of colony formation on the agar surface indicated complete bactericidal activity, confirming that the formulation effectively eliminated viable bacterial cells in the absence of antibiotics. MBC values were recorded for all pigment-containing hand sanitizer formulations against the five tested bacterial strains.40
Hand sanitizer gel stability test
Stability testing was performed by storing the hand sanitizer gel samples at three different temperatures (25 °C, 37 °C, 40 °C) for a period of 1 month. Samples were routinely monitored for changes in physical characteristics such as color, odor, and phase separation.26
Antioxidant activity assay
The antioxidant activity of extracts and products derived from cyanobacterial strains was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. This method assesses the ability of antioxidant compounds to neutralize DPPH free radicals.
For the assay, 1 mL of Andrographis paniculata extract was mixed with 2 mL of a 0.1 mM DPPH solution prepared in methanol. The reaction mixture was incubated in the dark for 30 minutes to allow free radical scavenging activity to occur. Following incubation, an aliquot of the mixture was transferred into a cuvette, and absorbance was measured at 517 nm using a UV-Visible spectrophotometer.
A control sample was prepared by mixing 2 mL of the DPPH methanolic solution with 1 mL of methanol. All absorbance measurements were performed in triplicate for each sample.
The percentage of free radical scavenging activity (% inhibition) was calculated using the following formula42:
Experimental data were analyzed using analysis of variance (ANOVA) in the IBM SPSS Statistics for Windows, version 24 (IBM Corp., Armonk, N.Y., USA). A 95% confidence
level was applied to determine statistical significance. When significant differences were identified by ANOVA (p ≤ 0.05), the Tukey post-hoc test was used to compare the means. Each treatment was tested in triplicate, and the results were expressed as mean values ± standard error of the mean (SEM).43
RESULTS
Determination of coated pigments concentration and purity
Spectrophotometric analysis revealed that PE exhibited maximum absorbance at 562 nm, with a secondary peak at 617 nm. PC showed its maximum absorbance at 621.9 nm. The calculated purity values were 0.845 for PE and 0.401 for PC (Figure 3).
Anti-acne face wash gel containing PE and PC pigments
Viscosity
One-way ANOVA followed by Tukey’s post-hoc test indicated no statistically significant differences in viscosity among the different treatments over a 30-day period. However, formulations containing PC alone and PC + PE pigments exhibited the highest viscosity compared to the control.
pH
Analysis of pH values using one-way ANOVA and Tukey’s test showed no significant difference between treatments over the 30-day observation period. Notably, the control formulation recorded the highest pH value.
Physical
properties
Gels formulated with PE, PC, and PC + PE displayed distinct coloration: pale pink, blue, and green, respectively, while the control gel remained colorless. All formulations were shiny, transparent, and exhibited a light, cooling sensation upon application to the skin (Figure 2).
Foamability of anti-acne face wash gel
One-way ANOVA followed by Tukey’s test revealed no statistically significant differences in foamability among the various formulations over the 30-day evaluation period.
Stability of anti-acne face wash gel at different temperatures
Assessment of physical stability — including color, odor, and consistency — at 4 °C over 30 days showed that all formulations received the maximum score (5 out of 5) for all parameters. At 25 °C and 37 °C, no significant differences in consistency were observed between the pigment-containing formulations and the control. However, on day 30 at 40 °C, the control formulation showed a significant reduction in consistency compared to the pigment-containing treatments.
Color retention analysis at 25 °C demonstrated that pig-
DataStream - Scan DataStream - Scan
Absorbance [A]
Wavelength [nm]
ment-containing formulations maintained a significantly higher color intensity than the control throughout the 30-day period. At 37 °C and 40 °C, a significant difference in color intensity between the control and the pigment-treated samples was observed starting from day 20.
In contrast, odor assessments at 25 °C, 37 °C, and 40 °C showed no significant differences between treatments and the control group over the entire 30-day period.
Homogeneity of the anti-acne gel
Visual inspection of the anti-acne gel formulations confirmed that all samples remained homogeneous throughout the entire evaluation period. No signs of phase separation, sedimentation, or texture inconsistencies were observed on any of the measurement days. According to one-way ANOVA followed by Tukey’s post-hoc test, no significant difference in antimicrobial activity was observed between the control and the PE-containing gel until day 30. However, formulations containing PC and PC + PE showed significantly enhanced antimicrobial activity on days 15 and 5, respectively. Among all treatments, gels formulated with the combined pigments and those containing PC alone exhibited the highest bacterial inhibition rates.
Antioxidant activity of anti-acne face wash gels
(ferric reducing ability of plasma [FRAP] method)
Analysis using one-way ANOVA and Tukey’s test showed that the highest antioxidant activity was observed on day 10 in gels formulated with PC + PE.
Results of soap evaluation tests
Moisture content
Results of one-way ANOVA and Tukey’s test showed a
Absorbance [A]
Wavelength [nm]
significant decrease in moisture content over the 30-day period. Notably, on days 25 and 30, soaps enriched with PE alone and with the combination of both pigments retained significantly higher moisture content compared to the other formulations.
Total fat content and pH
Both total fat content and pH levels showed a significant decrease over the 30-day period, according to one-way ANOVA and Tukey’s test. However, no statistically significant differences in fat content were observed among the soaps prepared with different types of pigment.
Foam formation and height
One-way ANOVA and Tukey’s test revealed a significant decline in foam height over the 30 days. However, no significant differences were observed between days 25 and 30. Additionally, there was no statistically significant difference in foam height among soaps formulated with different pigments on days 25 and 30.
Soap foam shelf life
One-way ANOVA and Tukey’s test showed that foam height decreased significantly over the 30-day observation period. However, no statistically significant differences were found in foam retention between the various pigment-containing treatments and the control across different time points.
Alcohol-insoluble matter
The analysis revealed a significant increase in alcohol-insoluble content compared to the control. However, no significant differences were observed between the different pigment-treated formulations.
Figure 3: The results of spectrometry of pigment extracted and purified from A - Nostoc sp. and B - Spirulina sp.
Stability
One-way ANOVA followed by Tukey’s test showed no significant differences in color or odor stability among the soap formulations over the 30-day period. Additionally, there were no statistically significant differences between pigment-containing treatments and the control in terms of color stability. At 25 °C over 30 days, stable soap formulations showed no visible color changes or phase separation. Homogeneous samples were classified as stable, while those exhibiting sediment-like separation were considered unstable. Throughout the 30-day evaluation period, all soap formulations maintained structural integrity and received the maximum score of 5 for form stability.
Percentage of alkali
No statistically significant differences were found in the percentage of alkali among the treatments when compared to the control, as determined by one-way ANOVA and Tukey’s test.
Saponification rate
Saponification value showed a statistically significant decrease compared to the control group, which indicates a reduction in the degree of saponification in pigment-treated soap formulations.
Antibacterial properties of soap
The antibacterial activities of soap formulations against E. coli, S. aureus, and P. aeruginosa were evaluated over a 30-day period using one-way ANOVA followed by Tukey’s test. The soaps were prepared under four conditions: control (no pigment), PC, PE, and PC + PE (Table 2).
For E. coli, no significant differences in antibacterial activity were observed over the 30 days, indicating stable efficacy across treatments. However, soaps formulated with PC alone and PC + PE consistently exhibited significantly higher antibacterial activity than the control and PE-only treatments (Table 2a).
Regarding S. aureus, no significant differences were found between the control and PE-only soaps throughout the 30day period. Soaps containing both pigments showed the highest antibacterial activity up to day 20. After day 20, however, a significant reduction in activity was observed (Table 2b).
Against P. aeruginosa, there were no significant differences in antibacterial activity between the control and individual pigment treatments during the 30-day period. Soaps containing both pigments demonstrated the highest antibacterial activity up to day 10, after which their efficacy declined significantly (Table 2c).
Antioxidant activity of soap
One-way ANOVA and Tukey’s test indicated that the antioxidant activity of all soap formulations significantly decreased over the 30-day period. Despite this decline, all treatments demonstrated significantly higher antioxidant activity compared to the control. No statistically significant differences were observed between the different pigment-treated soaps.
Psychrophilic bacteria count
The presence of psychrophilic (cold-loving) bacteria was evaluated over 30 days. One-way ANOVA and Tukey’s test showed that bacterial growth was detected in the control soap on day 20, in PC-containing soap on day 25, and in PE-containing soap on day 30. However, no psychrophilic bacteria were detected in soaps formulated with both pigments. The control soap exhibited a significantly higher psychrophilic bacterial count compared to all other treatments.
Colorimetry of soaps
Colorimetric analysis was performed using L*, a*, b*, and ΔE values. One-way ANOVA and Tukey’s test showed the following:
l L* (lightness): Soaps containing PE and the combination of both pigments had significantly higher brightness than the other formulations.
l a* (red-green scale): No significant differences were observed among treatments or between treated and control soaps over time. However, PE-treated soaps consistently exhibited the highest a* values throughout the evaluation period.
l b* (yellow-blue scale): No significant differences were noted over time among treatments or versus the control, although PE-containing soaps showed the lowest b* values on day 30, with a statistically significant difference.
l ΔE (total color difference): No significant differences in ΔE were found between treatments and control during the observation period. However, soaps containing PC and PC + PE exhibited the lowest ΔE values, with a significant difference noted on day 30.
Results of hand sanitizer gel tests
pH
One-way ANOVA and Tukey’s test showed that pH levels decreased significantly over the 30-day period, particularly in the control gels. On day 30, the lowest pH value was observed in gels enriched with PC.
Viscosity
Viscosity also showed a significant decrease over 30 days, as indicated by one-way ANOVA and Tukey’s test. On day 30, the highest viscosity values were recorded in gels formulated with PE and PC + PE. The control gel exhibited the lowest viscosity.
Antimicrobial activity of hand sanitizer gel
According to one-way ANOVA and Tukey’s test of ZOI diameters, the highest antimicrobial activity against S. aureus was observed in gels enriched with PC + PE. For E. faecalis and E. coli, no statistically significant differences in ZOIs were found among the pigment-treated gels. However, the highest inhibi-
Table 2: Results of one-way analysis of variance and Tukey’s test evaluating the antibacterial properties of soaps against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa over 30 days under four different conditions: control, phycocyanin (PC), phycoerythrin (PE), and PC + PE (a) Escherichia coli
Treatment Day 1 Day 5 Day 10 Day 15 Day 20 Day 25 Day 30 Control
Lowercase letters indicate significant differences in rows; uppercase letters indicate significant differences in columns (Tukey’s test, p ≤ 0.05).
tion against P. aeruginosa and S. typhi was noted in gels containing PE and PC + PE (Table 3).
MIC of hand sanitizer gel
One-way ANOVA and Tukey’s test revealed that the lowest MIC against S. aureus was observed in gels enriched with PE and PC + PE. For E. faecalis, E. coli, P. aeruginosa, and S. typhi, the lowest MIC values were consistently recorded in gels containing PC + PE.
MBC of hand sanitizer gel
Analysis of MBC levels using one-way ANOVA and Tukey’s test showed that the lowest MBC values against S. aureus, P. aeruginosa, E. faecalis, and S. typhi were found in gels enriched with either PE, PC, or PC + PE. For E. coli, the lowest MBC was observed in formulations containing PC + PE.
Table 3: Results of one-way analysis of variance and Tukey’s test for growth inhibition diameters (in mm) of hand sanitizer
(B)
± 0.33 (B)
±
(A) PC + PE
± 0.33 (D)
± 0.33 (B)
± 0.58 (B)
± 0.33 (B)
Lowercase letters indicate significant differences in rows; uppercase letters indicate significant differences in columns (Tukey’s test, p ≤ 0.05).
± 0.58 (B)
Table 4: Results of one-way analysis of variance and Tukey’s test to determine the antioxidant activity (measured by DPPH assay) of hand sanitizer gels prepared with four different conditions: control, phycocyanin (PC), phycoerythrin (PE), and PC + PE, over 30 days
Control 4.39±0.10 (Aa) 5.21±0.10 (Aab) 5.83±0.13 (Ab) 7.38±0.16 (Ac)
PC + PE 2.39±0.04 (Ba) 2.44±0.02 (Bab) 2.47±0.02 (Bab) 2.48±0.02 (Bbac) 2.55±0.01 (Bcb) 2.59±0.04 (Bcb) 2.63±0.05 (cB)
Lowercase letters indicate significant differences within rows (between time points), and uppercase letters indicate significant differences within columns (between treatments) according to Tukey’s test (p ≤ 0.05).
Hand
sanitizer gel stability test
Stability was evaluated under various storage conditions (4 °C, 25 °C, 40 °C) by monitoring odor, color, and phase separation. One-way ANOVA and Tukey’s test indicated that all samples scored 5 out of 5 for all three parameters at 4 °C, 25 °C (up to day 15), and 40 °C.
Although a significant reduction in odor and color stability was observed over 30 days, no significant differences were found between the control and pigment-enriched gels. For phase separation, significant differences were observed on days 25 and 30 at 25 °C, 37 °C, and 40 °C. However, no statistically significant differences were found between control and treated samples. All gels received a score of 5 for phase separation and color on days 10 and 15 at 40 °C, and on days 15 and 20 at 25 °C.
Antioxidant activity of hand sanitizer gel (DPPH method)
According to one-way ANOVA and Tukey’s test, antioxidant activity significantly declined over the 30-day period. On the final day, the highest antioxidant activity was observed in gels enriched with PE and PC + PE (Table 4).
Foaming ability of hand sanitizer gel
The foaming ability did not differ significantly between control and pigment-treated gels, as indicated by one-way ANOVA and Tukey’s test.
Lethality percentage of hand sanitizer gel
The lethality rate of the sanitizer gel significantly decreased over the 30-day period. The greatest differences were found in gels enriched with PC + PE (Table 5).
DISCUSSION
The use of natural ingredients for cosmetic purposes dates back to ancient times, long before the formal establishment of the cosmetics industry.44 In recent years, the rise of cosmeceuticals has emphasized the potential of cyanobacteria as a promising source of bioactive components due to their capacity to synthesize a wide variety of functional compounds. Cyanobacteria produce numerous bioactive molecules, including fatty acids, polyphenols, peptides, polysaccharides, and pigments, many of which have applications in health, nutrition, and skincare.45 Among these, cyanobacterial pigments — such as chlorophylls, carotenoids, and PBPs — stand out for their diverse physicochemical properties and broad color range, from blue to red. These pigments have gained increasing attention for their
Treatment Day 1 Day 5 Day 10 Day 15 Day 20 Day 25 Day 30
Control
PE
(aA)
(BCa)
±
±
PC 76.54 ± 0.00 (Ba)
(Aab)
(Bab)
±
± 0.40 (Bab)
PC + PE 78.19 ± 0.41 (ACa) 75.90 ± 0.70 (Bb)
(Abc)
(Bab)
± 0.74 (Bab)
± 0.00 (Bb)
(Bbc)
± 0.43 (Bbc)
± 0.43 (Bbc)
(Bc)
± 0.44 (Bcd)
± 0.44 (Bcd)
±
(BCcd)
(Bde)
±
± 0.44 (ACcd)
±
(BCd)
± 0.00 (Be)
71.86 ± 0.43 (ACd)
Lowercase letters indicate significant differences within rows (across time points), and uppercase letters indicate significant differences within columns (across treatments) based on Tukey’s test (p ≤ 0.05).
potential applications in food, animal feed, nutraceuticals, and cosmetics.46 In particular, carotenoids and PBPs possess notable antioxidant, moisturizing, and skin-stabilizing properties, making them highly desirable in natural cosmetic formulations.6,47
Carotenoids are commonly incorporated into sunscreens, anti-aging products, and antioxidant-enriched cosmetics due to their excellent free radical scavenging abilities. In cyanobacteria, these pigments help dissipate excess energy generated during photosynthesis, thereby preventing oxidative damage at the cellular level.48 This photoprotective mechanism has clear parallels in human skin, which is similarly susceptible to oxidative stress caused by UV radiation and intense light exposure.49
PBPs are associated with a broad spectrum of bioactivities, including anticancer, antiviral, antimicrobial, and antioxidant effects.50 These properties make them highly valuable as functional additives in cosmetic formulations. In addition to their biological activities, PBPs function as natural colorants, offering a safer alternative to synthetic dyes that are often linked to skin irritation, allergic reactions, and potential toxicity. Their hydrophilic nature and water solubility further enhance their suitability for use in topical skincare applications, particularly in products such as serums and lotions.46
This study aimed to evaluate the effects of chitosan-coated PC and PE on the antioxidant and antimicrobial activity of three cosmetic products: soap, anti-acne face wash, and hand sanitizer gel. The results of the anti-acne face wash gel tests revealed that pigment composition significantly influenced several parameters. Gels enriched with PC and PC + PE exhibited higher viscosity, enhanced antioxidant activity, and stronger antimicrobial activity against acne-causing microorganisms compared to other formulations. In contrast, the control formulation displayed the highest pH.
For the hand sanitizer gel, a decline in both viscosity and pH was observed over time, with the lowest values recorded in the control and PC-enriched formulations, respectively. Antioxidant activity in hand sanitizers was lower overall, particularly in gels containing only PE or the combined pigments, suggesting
reduced stability or effectiveness of the pigments in this formulation type. However, all gel formulations maintained full homogeneity throughout the study period. The anti-acne face wash gels were also noted for their appealing physical characteristics — they remained shiny and transparent, and upon application, provided a light and cooling sensation on the skin. Among the tested formulations, the highest antimicrobial lethality in the face wash gel was recorded in those containing PC + PE and PC alone.
However, among the hand sanitizer gel formulations, PC +PE demonstrated the best overall performance. Optimal cultivation conditions are essential for maximizing the production of secondary metabolites in extremophilic cyanobacteria. Zucchi and Necchi51 studied the growth and pigment content of freshwater algal cultures and found that temperature was the primary factor influencing pigment synthesis. In contrast, variations in irradiance, photoperiod, and their interactions contributed less significantly to pigment variation. Their findings also indicated that PC was generally more abundant than PE, and PBPs were more concentrated than chlorophyll a.
In contrast, Rizzo et al.52 reported no variation in total protein content or penicillin-binding protein production under different light conditions. Ma et al.53 showed that PBP content peaked at light intensities below 90 μmol m-2 s-1. However, PC and allophycocyanin levels increased with greater light intensity, while PE levels declined. Furthermore, the study found that exposure to blue and red light led to the highest increases in fresh weight, protein content, and PBP levels, which were associated with higher concentrations of dry matter, PC, and chlorophyll a.
PE has demonstrated versatile applications in the pharmaceutical, antioxidant, and food industries.54-55 However, its limited stability remains a significant barrier to its widespread use. PE is highly sensitive to factors such as pH, salt concentration, temperature, water activity, and light exposure as well as to in vitro processes including extraction, purification, storage, and formulation. These conditions often compromise its structural integrity and bioactivity. Size and protein composition of the PE
Table 5: Results of one-way analysis of variance and Tukey’s test to determine the lethality percentage of hand sanitizer gels prepared under four different
complex also vary in response to environmental conditions. For instance, low light intensity improves PE synthesis and leads to the elongation of rod-like structures.
Numerous purification and characterization techniques have been developed for isolating PE from various cyanobacterial and red algal strains.14
The stability analysis of color, odor, and consistency for both the anti-acne face wash and hand sanitizer gels revealed that all formulations consistently received the maximum score of 5. In the case of the anti-acne face wash gel, color stability measurements at 25 °C, as well as at 37 °C and 40 °C (from day 20 onward), were highest in the control group. However, no significant differences in odor were observed between treatments and the control across all temperatures over the 30-day evaluation period. Similarly, all hand sanitizer gel formulations maintained full stability — receiving scores of 5 out of 5 for odor, color, and absence of phase separation at 4 °C, 25 °C (until day 15), and 40 °C. The soap formulations also maintained physical integrity and form stability, with all receiving the maximum score of 5.
Foamability remained unchanged throughout the evaluation period for both the anti-acne face wash and hand sanitizer gels. In soaps, parameters such as total fat content, pH, foam formation and height, shelf life, alkalinity, and antioxidant activity gradually declined over time; however, no statistically significant differences were observed. Although insoluble alcohol content increased over the 30 days, this change was not statistically significant.
Cyanobacteria naturally possess protective mechanisms against dehydration, which makes them promising candidates as moisturizing agents in cosmetic formulations. Several studies have demonstrated their ability to improve skin hydration and elasticity.56-57 For example, topical application of microalgae has been shown to enhance skin moisture and elasticity.4 Research on Nostoc commune further revealed that cells containing extracellular polymeric substances (EPS) displayed significantly greater desiccation tolerance, highlighting their superior water-retention capacity when compared to urea and chitosan.58,59
EPS are high-molecular-weight biopolymers composed of hydrated sulfate groups, neutral sugars (e.g., glucose, galactose, mannose, fructose, ribose, xylose, arabinose, fucose, rhamnose), non-carbohydrate components (e.g., phosphate, lactate, acetate, glycerol), and various uronic acids (e.g., glucuronic and galacturonic acids). The strong water-binding ability of these polysaccharides is attributed to the interactions between water molecules and hydrophilic –OH groups. Notably, the composition of EPS varies depending on environmental conditions and species.60 For example, Chroococcidiopsis modifies the composition of its cellular envelope under water stress, producing compounds such as sporopollenin-like materials, proteins, beta-linked polysaccharides, acid sulfates, and lipids. These metabolites contribute to reduced water loss and enhanced regulation of hydration.61
In the current study, both moisture content and saponification rate decreased in soaps over time, with the most substantial reduction in moisture observed in soaps enriched with PE and PC + PE on days 25 and 30. Additionally, the presence of psychrophilic bacteria was highest in the control soap, further emphasizing the protective effect of pigment-enriched formulations against microbial contamination under cold conditions. Based on the colorimetry results for the soap formulations, the highest brightness levels (L*) were observed in soaps containing PE and PC + PE.The highest a* values, which reflect redness, were found in soaps enriched with PE alone. In contrast, the lowest b* values (indicating yellowness) were associated with PE-treated soaps, and the lowest total color difference (ΔE) values were recorded in soaps containing PC and PC + PE. Regarding the antibacterial properties of the soaps, no significant differences were observed over the 30-day period in the inhibition of E. coli, S. aureus (in control and PE-treated soaps), and P. aeruginosa (in control and soaps enriched with PE and PC). For the hand sanitizer gel formulations, the highest ZOI against S. aureus was found in gels enriched with PC + PE. No significant differences were observed in ZOI diameters for E. faecalis and E.coli among the pigment-enriched gels. However, the highest inhibition rates against P. aeruginosa and S. typhi were recorded in gels containing PE and PC + PE. The MIC results for the hand sanitizer gels showed that the lowest inhibitory concentrations were achieved with PE and PC + PE against S. aureus, and with PC + PE against E. faecalis, E. coli, P. aeruginosa, and S. typhi Regarding MBC, the lowest bactericidal concentrations against S. aureus, P. aeruginosa, E. faecalis, and S. typhi were observed in gels enriched with the combined pigments (PC + PE), as well as with either PE or PC alone. For E. coli, the lowest MBC values were recorded in gels containing PC + PE.
CONCLUSION
The increasing focus on skin health, particularly in relation to aesthetics and aging, has driven the demand for innovative cosmetic products derived from natural sources. These products offer the advantages of reduced adverse effects and greater environmental sustainability. Cyanobacteria are promising candidates for the cosmetic and cosmeceutical industries due to their natural ability to resist dehydration, radiation, and oxidative stress through the production of specialized bioactive compounds. This study demonstrated the potential of cyanobacterial pigments, particularly PC and PE, in the formulation of three cost-effective and sustainable cosmetic products: soap, anti-acne face wash, and hand sanitizer gel. These formulations not only exhibited desirable physicochemical and antimicrobial properties but also aligned with biotechnological strategies for enhancing the efficiency and environmental compatibility of cosmetic production. The findings support the use of cyanobacteria as a valuable resource in the development of next-generation, naturally derived cosmetic products. l
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41. MA W. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. Clsi (Nccls). 2006;26:M7-A.
42. Vieira MV, Pastrana LM, Fuciños P. Microalgae encapsulation systems for food, pharmaceutical and cosmetics applications. Marine Drugs. 2020;18(12):644.
43. Nowruzi B, Khavari-Nejad R, Sivonen K, Kazemi B, Najafi F, Nejadsattari T. Optimization of cultivation conditions to maximize extracellular investments of two Nostoc strains. Arch Hydrobiol Suppl Algol Stud. 2013;142(1):63-76.
44. Scott DA. A review of ancient Egyptian pigments and cosmetics. Studies Conserv. 2016;61(4):185-202.
45. Guedes AC, Amaro HM, Malcata FX. Microalgae as sources of high added‐value compounds — a brief review of recent work. Biotech Progress. 2011;27(3):597-613.
46. Pagels F, Guedes AC, Vicente AA, Vasconcelos V. Cyanobacteria-based bioprocess for cosmetic products — cyanobium sp. as a novel source of bioactive pigments. Phycology. 2023;3(1):47-64.
47. Morone J, Alfeus A, Vasconcelos V, Martins R. Revealing the potential of cyanobacteria in cosmetics and cosmeceuticals — a new bioactive approach. Algal Res. 2019;41:101541.
48. Anunciato TP, Rocha Filho PA. Carotenoids and polyphenols in nutricosmetics, nutraceuticals, and cosmeceuticals. J Cosmet Dermatol. 2012;11(1):51-4.
49. Pagels F, Vasconcelos V, Guedes AC. Carotenoids from cyanobacteria: biotechnological potential and optimization strategies. Biomolecules. 2021;11(5):735.
50. Pagels F, Guedes AC, Amaro HM, Kijjoa A, Vasconcelos V. Phycobiliproteins from cyanobacteria: chemistry and biotechnological applications. Biotech Adv. 2019;37(3):422-43.
51. Zucchi MR, Necchi Jr O. Effects of temperature, irradiance and photoperiod on growth and pigment content in some freshwater red algae in culture. Phycol Res. 2001;49(2):103-14.
52. Rizzo RF, Santos BNCd Castro GFPS, Passos TS, Nascimento MA, Guerra HD, et al. Production of phycobiliproteins by Arthrospira platensis under different lightconditions for application in food products. Food Sci Technol. 2015;35:247-52.
53. Ma R, Lu F, Bi Y, Hu Z. Effects of light intensity and quality on phycobiliprotein accumulation in the cyanobacterium Nostoc sphaeroides Kützing. Biotechnol Lett. 2015;37:1663-9.
54. Mishra SK, Shrivastav A, Pancha I, Jain D, Mishra S. Effect of preservatives for food grade C-Phycoerythrin, isolated from marine cyanobacteria Pseudanabaena sp. I J Biol Macromol. 2010;47(5):597-602.
55. Soni B, Visavadiya NP, Dalwadi N, Madamwar D, Winder C, Khalil C. Purified c‐phycoerythrin: safety studies in rats and protective role against permanganate‐mediated fibroblast‐DNA damage. J App Toxicol. 2010;30(6):542-50.
56. Warren‐Rhodes KA, McKay CP, Boyle LN, Wing MR, Kiekebusch EM, Cowan DA, et al. Physical ecology of hypolithic communities in the central namib desert: the role of fog, rain, rock habitat, and light. J Geophys Res Biogeosci. 2013;118(4):1451-60.
57. Smith HD, Baqué M, Duncan AG, Lloyd CR, McKay CP, Billi D. Comparative analysis of cyanobacteria inhabiting rocks with different light transmittance in the mojave desert: a mars terrestrial analogue. I J Astrobiol. 2014;13(3):271-7.
58. Li H, Xu J, Liu Y, Ai S, Qin F, Li Z, et al. Antioxidant and moisture-retention activities of the polysaccharide from Nostoc commune. Carbohydrate Polymers. 2011;83(4):1821-7.
59. Tamaru Y, Takani Y, Yoshida T, Sakamoto T. Crucial role of extracellular polysaccharides in desiccation and freezing tolerance in the terrestrial cyanobacterium nostoc commune. App Environ Microbiol. 2005;71(11):7327-33.
60. Nowruzi B, Khavari-Nejad R, Sivonen K, Kazemi B, Najafi F, Nejadsattari T.Optimization of cultivation conditions to maximize extracellular investments of two Nostoc strains. Algologic Stud. 2013;142(1):63-76.
61. Caiola MG, Billi D, Friedmann EI. Effect of desiccation on envelopes of the cyanobacterium Chroococcidiopsis sp. (Chroococcales). Eur J Phycol. 1996;31(1):97-105.
AUTHOR’S CONTRIBUTION:
Bahareh Nowruzi 0000-0001-6656-777X
Statistical analysis, Final approval of the manuscript, Study conception and design, Manuscript drafting and writing, Active participation in research supervision, Intellectual contribution to the clinical management of studied cases, Critical literature review, Critical manuscript revision. Mahshid Alibabaei 0009-0000-3743-226X
Statistical analysis, Final approval of the manuscript, Study conception and design, Manuscript drafting and writing, Active participation in research supervision, Intellectual contribution to the clinical management of studied cases, Critical literature review, Critical manuscript revision.
www.surgicalcosmetic.org.br/
Topical potassium hydroxide 40% versus trichloroacetic acid 40% in the treatment of plantar warts: a randomized controlled trial
Hidróxido de potássio tópico 40% versus ácido tricloroacético 40% no tratamento de verrugas plantares: ensaio clínico randomizado
Introduction: Warts are a viral skin condition caused by the human papillomavirus (HPV), which can lead to disfigurement, embarrassment, and frustration. No single treatment has been shown to guarantee complete eradication.
Objective: To evaluate and compare the effectiveness of topical potassium hydroxide (KOH) 40% and trichloroacetic acid (TCA) 40% in the treatment of plantar warts, based on clinical and dermoscopic outcomes, as well as to assess side effects and patient satisfaction.
Methods: An interventional comparative study was conducted involving 33 patients with plantar warts. Lesions were divided into two groups: Group A received topical TCA 40%, and Group B received topical KOH 40%. All patients were evaluated both clinically and through dermoscopy.
Results: Both treatment groups showed statistically significant clinical and dermoscopic improvement (p < 0.001 for both). Complete dermoscopic clearance without recurrence over a 2-month follow-up period was more frequent in the KOH group (88.6%).
Conclusion: Topical TCA and KOH were similarly effective. KOH, in particular, proved to be both effective and safe, making it a promising adjunct treatment for plantar warts alongside destructive and immunotherapeutic methods.
Background: As verrugas são uma doença viral da pele causada pelo vírus do papiloma humano (HPV) que pode ser desfigurante, causando constrangimento e frustração aos pacientes. Nenhum tratamento pode garantir a erradicação total.
Objetivo: Avaliar e comparar a eficácia do hidróxido de potássio (KOH) tópico 40% versus ácido tricloroacético (TCA) tópico 40% no tratamento clínico e dermatoscópico de verrugas plantares, bem como relatar os efeitos colaterais e a satisfação do paciente.
Métodos: Este estudo intervencionista comparativo incluiu 33 pacientes com verrugas plantares. As lesões foram divididas em dois grupos: o Grupo A recebeu TCA tópico 40%, o grupo B recebeu KOH tópico 40%.Todos os pacientes foram submetidos a avaliação clínica e dermatoscópica.
Resultados: Ambos os grupos de tratamento apresentaram melhora significativa avaliada tanto clínica quanto dermatoscopicamente (p < 0,001 para ambos). A resolução dermatoscópica completa das verrugas sem recorrência durante um período de acompanhamento de 2 meses foi mais frequente no grupo KOH (88,6%).
Conclusão: TCA e KOH tópicos apresentaram eficácia semelhante. O KOH, em particular, demonstrou ser eficaz e seguro, tornando-se um tratamento complementar promissor para verrugas plantares, juntamente com métodos destrutivos e imunoterapêuticos.
1 Cairo Hospital of Dermatology and Venereology, Egyptian Ministry of Health and Population, Dermatology Department, Cairo, Egypt.
Correspondence: Shaimaa Farouk E-mail: dr.shaimaafarouk@gmail. com
Financial support: None. Conflicts of interest: None.
Submitted on: 17/11/2024
Approved on: 16/01/2025
How to cite this article: Farouk S, Tarek E, Hossam D, Sadek A. Topical potassium hydroxide 40% versus trichloroacetic acid 40% in the treatment of plantar warts: a randomized controlled trial. Surg Cosmet Dermatol. 2025;17:e20250423.
Farouk S, Tarek E, Hossam D, Sadek A.
INTRODUCTION
Plantar warts are benign skin manifestations caused by human papillomavirus (HPV) infection, most commonly types 1, 4, 57, 60, 63, 65, and 66. The myrmecia-type wart appears as a smooth-surfaced, deep, often inflamed, and tender papule or plaque. These lesions typically develop on the palms or soles, but can also occur near or under the nails, and less frequently on the fingertips. They are characteristically dome-shaped and extend deeper beneath the surface than they appear clinically. Warts are transmitted either through direct person-to-person contact or indirectly via contaminated surfaces.Verruca vulgaris accounts for approximately 70% of all cutaneous warts and occurs primarily in children.1 Skin warts are estimated to affect up to 10% of children and young adults, with the highest incidence between 12 and 16 years of age. This prevalence increases by 50 to 100 times in immunocompromised individuals.2
Spontaneous clearance rates of warts are generally low and require extended periods of time, with reported rates of 23% at 2 months, 30% at 3 months, and 65%-78% after 2 years.3 Cutaneous warts are estimated to affect up to 10% of children and young adults, with the highest incidence between 12 and 16 years of age. This prevalence increases by 50 to 100 times in immunocompromised individuals.2
The primary goals of treatment are to remove the wart without scarring, prevent recurrence — particularly at the same site — and, if possible, induce long-term immunity. Because of the variability of treatment outcomes, multiple therapeutic options, including combination therapies, may be considered. Treatment selection should be based on the size, location, and morphological type of the wart.4 Destructive treatments, including chemical and surgical methods, function by damaging the epithelium and inducing infected cell death, which leads to antigen exposure and presentation,2 thereby potentially triggering an immune response.
Superficial viral destruction can be induced by a variety of agents; however, such treatments may not reach virus-infected cells in the deeper layers of the epidermis. Direct stimulation of the immune system at the site of the wart may enhance the likelihood of an effective immunological response against infected keratinocytes.5 Destructive procedures can be inconvenient, especially for large or multiple warts, as they may leave extensive areas of raw skin that require prolonged healing and carry an increased risk of secondary infection. Consequently, immunotherapy has emerged as a more favorable treatment option for resistant warts.Various agents have been utilized in immunotherapy, including systemic treatments such as H₂ receptor blockers, zinc, and interferons. Intralesional injections of the MMR (measles, mumps, rubella) vaccine, Candida antigen, purified protein derivative (PPD), and Trichophyton skin antigen have also been employed. Additional modalities include auto-implantation and the topical application of imiquimod.
Potassium hydroxide (KOH) solution is a promising treatment for cutaneous warts due to its keratolytic effect and
ability to deeply penetrate the skin, resulting in the destruction of virus-infected cells. Its irritant properties may also stimulate an inflammatory response, contributing to wart resolution. KOH is associated with minimal side effects and is inexpensive.6
Trichloroacetic acid (TCA) is a topical destructive agent that induces hydrolysis of cellular proteins, leading to cell death. When applied to the skin, it causes coagulative necrosis of epidermal cells, precipitates proteins, and leads to necrosis of collagen from the papillary to upper reticular dermis. Within a few days, unaffected adnexal structures regenerate the skin, and the necrotic tissue peels away. TCA produces results similar to those of cryotherapy and is effective in treating anal, genital, cervical, and common warts when used at concentrations of 70-80%.3 For common warts, lower concentrations (10-30%) are typically used. TCA offers the advantage of having no systemic toxicity, though local side effects such as burning, discomfort, hyperpigmentation, and, less commonly, scarring may occur.7
The aim of this study was to evaluate and compare the effectiveness of topical TCA 40% versus topical KOH 40% in the treatment of plantar warts, both clinically and dermoscopically, and to report on associated side effects and patient satisfaction.
MATERIALS AND METHODS
This interventional comparative study included 33 patients aged over 10 years. Each patient had two plantar warts: one lesion was treated with KOH and the other with TCA. Patients were excluded if they had autoimmune diseases, symptoms suggestive of inflammation or infection, were receiving immunosuppressive therapy, were pregnant or lactating, or had received wart treatment in the preceding months.
Following approval by the Research Ethics Committee of the Central Directorate for Research and Health Development, Egyptian Ministry of Health (IORG0005704/IRB0000687; Com. No./Dec. No: 7-2023/31), the study was conducted in the outpatient procedures department of the Cairo Hospital of Dermatology and Venereology, from December 2022 to July 2023. Written informed consent was obtained from each participant or from a parent/guardian in cases involving minors under 18 years of age.
Patients underwent a complete medical history to document name, age, sex, address, contact information, duration of the warts, and any previous therapeutic attempts and their outcomes. This was followed by a thorough clinical examination of the warts4 to record their size, location, and surface characteristics. Each patient had two plantar warts: one lesion was treated with KOH and the other with TCA. The lesions were randomly assigned into two groups: Group A (33 lesions) received topical TCA 40%, and Group B (33 lesions) received topical KOH 40%. A piece of cotton soaked with the respective solution was gently applied to each wart and left in place for 1-2 hours. Both treatments were administered on the same day.
Treatment sessions were performed weekly until complete improvement or for a maximum of six sessions. All patients were evaluated through both clinical and dermoscopic assessments. Treatment efficacy was evaluated based on the following criteria:
Clinical photography
Photographs were taken at baseline, after every two treat¬ment sessions, and two months following the final treatment session. All images were evaluated by two dermatology consul¬tants who were blinded to patient identity and treatment details. The improvement of plantar warts was assessed using a three-point scale: i) non-responder (0): <25% improvement; ii) mild improvement (1): 25-75% improvement; and iii) complete im¬provement (2): >75% improvement. Images were captured using a smartphone camera (Samsung A7), featuring a 24-megapix¬el primary sensor, an 8-megapixel wide-angle sensor, and a 5-megapixel depth sensor.
Dermoscopic evaluation
Dermoscopic findings included thrombosed blood ves¬sels interrupting the cutaneous dermatoglyphics. A handheld dermoscope (DermLite DL4, 3Gen, USA) was used for exam¬ination. Evaluations were performed at baseline, after every two treatment sessions, and 2 months after the final session. Two inde-pendent dermatologists, blinded to treatment details, assessed the images using the following three-point scale: i) nonresponder (0); ii) mild improvement (1); and iii) complete improvement (2).
Patient satisfaction:
Patient satisfaction was evaluated after the final treatment session using a 6-point scale ranging from 0 (not satisfied) to 5 (very satisfied).
Adverse effects were monitored and included post-inflammatory hyperpigmentation, hypopigmentation, bullae, erythema, infection, and scarring. Patients who experienced adverse effects received detailed post-treatment wound care instructions and were prescribed a topical antiseptic solution and antibiotic cream as needed.
Statistical analysis:
Data were collected, edited, coded, and entered using IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, N.Y., USA). Quantitative data were presented as the mean, standard deviation (SD), and range for parametric variables, or as the median and interquartile range (IQR) for non-parametric variables. Categorical variables were expressed as frequencies and percentages.
The chi-square test was used to compare qualitative variables between groups. For quantitative data, the independent t-test was applied to compare two groups with parametric distribution, while the Mann-Whitney U test was used for non-parametric comparisons.
A margin of error of 5% was accepted, and 95% confi-
dence interval. The following thresholds were used to interpret p-values:
Not significant: p > 0.05
Significant: p < 0.05
Highly significant: p < 0.01
RESULTS
The study included 33 individuals: 12 men (36.4%) and 21 women (63.6%), all with multiple plantar warts. Participants’ ages ranged from 14 to 50 years, with a mean age of 32.42 ±
1: Demographic and clinical characteristics of patients
33
of warts (months)
Table
S, Tarek E, Hossam D, Sadek A.
Table 2: Follow-up of clinical photography assessment at different time points in both groups
P > 0.05 = Not significant (NS); p < 0.05 = Significant (S); p < 0.01 =
3:
P > 0.05 = Not significant (NS); p < 0.05 = Significant (S); p < 0.01 = Highly
*Chi-square test
8.96 years. The duration of warts ranged from 2 to 4 months, with a mean of 2.48 ± 0.76 months (Table 1).
A statistically significant improvement in clinical photographic assessment was observed throughout the treatment sessions in both the KOH and TCA groups, with p-values < 0.001 and 0.001, respectively (Table 2).
(HS)
Dermoscopic photographic assessment also revealed statistically significant improvement during treatment in both groups, with p-values < 0.001 for each (Table 3).
Complete dermoscopic clearance of warts without recurrence during the 2-month follow-up period was achieved in 88.6% of the KOH group, compared to 66.7% of the TCA group. There was no statistically significant difference between the two groups in terms of the number of sessions required for improvement or patient satisfaction scores. Both groups had a median of 6 sessions (IQR 3-6) (Table 4).
Table 5: Comparison between KOH and TCA groups regarding side effects
No statistically significant differences were found between the groups regarding the occurrence or types of side effects, with p-values of 0.099 and 0.132, respectively. Side effects were reported in 9.1% (3 patients) in each group. In the KOH group, the side effects included burning sensation (66.7%, 2 patients) and subcorneal hemorrhage (33.3%, 1 patient). In the TCA group, side effects included ulceration, subcorneal hemorrhage, and peeling—each reported in 33.3% of the affected patients (Table 5).
No statistically significant difference was found between the two groups regarding final dermoscopic and clinical responses. Both groups showed similar rates of mild clinical improvement: 24.2% in the KOH group and 21.2% in the TCA group. Regarding final dermoscopic response, complete improvement was observed in 81.8% of the KOH group and 78.8% of the TCA group (Table 6).
TABLE 4: Comparison between KOH and TCA groups regarding number of improvement sessions and patient
S, Tarek E, Hossam D, Sadek A.
Table 6: Comparison between KOH and TCA groups regarding
Figure 1: A - 26-year-old female patient with two plantar warts present for 3 months, each treated with KOH 40% and TCA 40% over six sessions. A1 - Wart near the big toe treated with KOH, showing complete clinical improvement (score 2). A2 - Dermoscopic image of the same wart, showing complete improvement (score 2). The patient reported a satisfaction score of 5 and minimal side effects. B1 - Wart on the heel treated with TCA, showing mild clinical improvement (score 1). B2 - Dermoscopic image of the same wart, showing mild improvement (score 1). The patient reported a satisfaction score of 4 and no side effects
Figure 2: A - 22-year-old female patient with two plantar warts present for 1 month, treated with KOH 40% and TCA 40% over fivesessions. A1 - Wart on the tip of the big toe treated with TCA, showing mild clinical improvement (score 1). A2 - Dermoscopic image of the same wart, showing complete improvement (score 2). The patient reported a satisfaction score of 3 and no side effects. B1 - Wart at the base of the big toe treated with KOH, showing complete clinical improvement (score 2). B2 - Dermoscopic image of the same wart, showing complete improvement (score 2). The patient reported a satisfaction score of 5 and no side effects
DISCUSSION
A highly statistically significant correlation was found between dermoscopic and clinical assessments in the KOH group (p = 0.007). A statistically significant correlation was also observed in the TCA group (p = 0.022).
Final dermoscopic and clinical outcomes are illustrated in figure 1 and figure 2.
HPV is the primary cause of common warts, which often affect children and immunocompromised individuals. Warts can be disfiguring, leading to embarrassment and frustration, which motivates most patients to seek treatment.8
Although various treatment options are available — including topical medications, cryotherapy, laser therapy, photodynamic
therapy, surgical excision, and immunotherapy — no single method guarantees complete eradication or prevention of recurrence.9
Due to their destructive nature, many of these treatments can leave scars. Less invasive approaches, while minimizing scarring, may produce suboptimal responses or increase the likelihood of recurrence, particularly in patients with large or multiple lesions. For these reasons, immunotherapy has gained increasing attention and popularity.10
KOH has been investigated for its efficacy and tolerability in wart treatment. It has been shown to be a safe and effective option for treating plane warts. Its keratolytic properties promote the destruction of virus-infected cells, facilitating wart resolution.11
TCA is a topical destructive agent that induces cell death through the hydrolysis of cellular proteins. When applied to the skin, TCA causes protein precipitation, coagulative necrosis of epidermal cells, and collagen necrosis extending from the papillary to the upper reticular dermis. Within a few days, the epidermis regenerates from adnexal structures that were unaffected by the chemical injury, and the necrotic layers peel off. At various concentrations, TCA has been shown to be effective in treating anal, genital, cervical, and common warts, with response rates comparable to those achieved with cryotherapy.11
The aim of this study was to evaluate and compare the effectiveness of topical TCA 40% and KOH 40% in the treatment of plantar warts, using both clinical and dermoscopic assessments, while also documenting any side effects and levels of patient satisfaction.
This interventional comparative study included 33 patients over the age of 10 with multiple plantar warts. Exclusion criteria included autoimmune disease, signs of active inflammation or infection, use of immunosuppressive therapy, pregnancy or lactation, and receipt of wart treatment in the preceding months.
Patients underwent a complete medical history, including documentation of name, age, sex, address, contact information, duration of warts, and any previous therapeutic attempts and their outcomes. A thorough clinical examination of the warts was then performed to assess their size, location, surface characteristics, and number. Each patient’s lesions were randomly divided into two groups: Group A received topical TCA 40%, and Group B received topical KOH 40%. The topical solutions were applied using a cotton swab and left in place for 1-2 hours. Both treatments were administered on the same day.
Treatment sessions were conducted weekly until complete improvement or for a maximum of six sessions. All patients were evaluated through clinical and dermoscopic assessments. Dermoscopic findings included the presence of thrombosed blood vessels interrupting the cutaneous dermatoglyphics.
Assessments were performed at baseline, after every two sessions, and two months after the final treatment session, using a three-point scale: i) non-responder (0); ii) mild improvement (1); and iii) complete improvement (2).
Among the studied patients with plantar warts, 63.6% were female and 36.4% were male.
Similarly, gender distribution in a study conducted by Hanif et al. (2022) showed that 48.65% of participants were male and 51.35% were female, all presenting with plantar warts.11 In our study, participant age ranged from 14 to 50 years, with a mean ± SD of 32.42 ± 8.96 years. This was comparable to the findings of Al Mokadem et al. (2022), who reported an age range of 18 to 50 years in their study.12
No statistically significant difference was observed between the two groups regarding final dermoscopic and clinical responses. Based on final dermoscopic evaluation, complete improvement was recorded in 81.8% of the KOH group and 78.8% of the TCA group.
Complete dermoscopic clearance of warts without recurrence during the 2-month follow-up period was achieved in 88.6% of patients in the KOH group, compared to 66.7% in the TCA group.
Both groups showed statistically significant improvement in clinical and dermoscopic assessments across successive treatment sessions, with p-values of <0.001 for the KOH group and 0.001 for the TCA group.
The time required for complete wart resolution ranged from 3 to 6 weeks. Patient satisfaction scores ranged from 2 to 5, with a median of 4 in both the KOH and TCA groups.
No statistically significant difference was observed between the KOH and TCA groups regarding the incidence and type of side effects, with p-values of 0.099 and 0.132, respectively.
Since there were no significant differences between the KOH- and TCA-treated groups in terms of treatment response, number of sessions required for clearance, or patient satisfaction, these findings suggest that KOH has a therapeutic effect comparable to that of TCA. Both agents appear capable of achieving similar clinical outcomes.
Similarly, Khan et al. (2017) enrolled 100 patients with palmoplantar warts and treated them with 10% topical KOH applied once daily at night. The efficacy was comparable for both palmar and plantar warts (p = 0.85). Notably, a significantly better outcome (p = 0.04) was observed in patients with a single lesion, with 90.91% (20 out of 22) showing complete clearance. The study concluded that 10% KOH is highly effective for the treatment of palmoplantar warts, especially in cases involving a single lesion.13
Likewise, Bodar et al. (2020) reported that TCA needling was an effective technique for treating palmoplantar warts in a study involving patients aged 4 to 50 years. After obtaining informed consent, participants received weekly applications of 100% TCA followed by needling using an insulin syringe. Total wart clearance was achieved within a minimum of three weeks and a maximum of eight weeks.11,14
In contrast, Hanif et al. (2022) compared 148 cases of palmoplantar warts in patients of both sexes, aged 3 to 12 years.The
Farouk S, Tarek E, Hossam D, Sadek A.
participants were divided into two groups of 74 each: Group A received topical TCA 35%, and Group B received topical KOH 10%. Efficacy was observed in 28 cases (37.84%) in Group A and 57 cases (77.03%) in Group B. Group B demonstrated significantly superior results compared to Group A (p = 0.0001).11 According to their findings, 10% KOH was substantially more effective than 35% TCA, even after accounting for confounding variables such as age, site, size, and duration of the warts. These results suggest that higher concentrations of TCA may be required to achieve clearance of plantar warts, whereas lower concentrations of KOH can be equally effective.
Similarly, Attia et al. (2020) reported that both KOH 30% and TCA 30% were equally effective in the treatment of plane warts, with no statistically significant differences between the groups at the end of the treatment period or during follow-up. The study included 60 patients with plane warts, divided into two groups: Group A (TCA) and Group B (KOH). Complete clearance was observed in seven patients (23.3%) in each group. After 12 weeks, partial improvement was achieved in 15 patients (50%) in Group A and 16 patients (53.3%) in Group B. Non-response was noted in eight patients (27.6%) in Group A and seven patients (23.3%) in Group B.15
In contrast, Al-Hamdi et al. (2012) reported that topical KOH at lower concentrations (5% and 10%) provided a safe, effective treatment for plane warts, with minimal adverse effects. The study involved 250 patients with plane warts, divided into two equal groups based on age and sex. Group A received topical KOH 5% once nightly, while Group B received KOH 10% once nightly. By the end of the second week, complete wart clearance was observed in 9.3% of patients in Group A and 66.3% in Group B. At the end of the fourth week, complete response was achieved in 82.1% of Group B and 80.3% of Group A. Reported side effects included itching, burning sensation, erythema, and transient dyspigmentation, affecting 77.6% of patients in Group A and 90.5% in Group B. During the 3-month follow-up, re-
currence rates were low in both groups: 5.8% in Group A and 5.1% in Group B.16
Patient-related variables such as age, gender, occupation, and wart location did not significantly influence treatment response in any of the study groups. However, larger-scale studies are warranted to confirm these findings.
In our study, side effects were minimal. Burning sensation was the most frequently reported adverse effect in the KOH group, consistent with findings by Attia et al. (2020).15
Limitations
The limitations of this study include the small sample size, the lack of long-term post-treatment follow-up, and the absence of correlation between long-term response and treatment outcome.
CONCLUSION
Both TCA and KOH demonstrated comparable effectiveness in the treatment of plantar warts. Notably, patients with a wart duration of less than 6 months showed a better therapeutic response.13 Burning sensation was more frequently reported in the KOH group, along with pain and black eschar formation. Overall, topical TCA 40% and KOH 40% are effective and moderately safe options for the treatment of plantar warts and may be considered viable therapeutic alternatives.
Recommendations
Further prospective studies with larger sample sizes are recommended to validate the findings.
Additional investigations using different concentrations of both TCA and KOH are needed to assess their impact on clinical response in patients with plantar warts.
Future studies should include detailed documentation of side effects after each individual treatment session. l
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9. Graham S, Faizo AA. Control of human papillomavirus gene expression by alternative splicing. Virus Res. 2017;231:83-95.
10. Mitra A, MacIntyre DA, Lee YS. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep. 2015;5:1–11.
11. Hanif N, Tahir R, Hassan T. Comparing Efficacy of 35% Trichloroactetic acid versus 10% potassium hydroxide in topical treatment of palmoplantar warts in patients upto 12 years of age. Pak J Medical Health Sci. 2022;16:261.
12. Al Mokadem SMAEF, Elfazani SEA, Khater MH. Intralesional methotrexate versus curettage and application of 100% trichloroacetic acid in planter warts. Egypt J Hosp Med 2022;89:5345–9.
13. Khan S, Zeeshan H. Efficacy of 10% KOH in palmoplantar warts. Pak J Medical Health Sci. 2017;11(2):553-5.
14. Bodar P, Agarwal P, Saikia S. Evaluating the efficacy of 100% trichloroacetic acid needling in the treatment of palmoplantar warts. Indian J Drugs Dermatol. 2020;6(1):13.
15. Attia A, Alawady AA, Abdo HM. Evaluation of topical 30% potassium hydroxide versus 30% trichloroacetic acid in the treatment of plane warts. Al-Azhar Med J. 2020;49(4):2053–64.
16. Al-Hamdi K. Evaluation of topical potassium hydroxide solution for treatment of plane warts. Indian J Dermatol. 2012;57(1):38-41.
AUTHOR’S CONTRIBUTION:
Shaimaa Farouk
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied.
Eman Tarek
Statistical analysis, acquisition, analysis and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied.
Dalia Hossam
Approval of the final version of the manuscript, conception and design of the study, critical review of the literature.
Ahmed Sadek
Approval of the final version of the manuscript, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical revision of the manuscript.
www.surgicalcosmetic.org.br/
Autologous melanocyte grafting by micropunch technique in patients with stable vitiligo: a pilot study in a tertiary hospital in Brazil
Enxerto autólogo de melanócitos por técnica de micropunch em pacientes com vitiligo estável: estudo piloto em um hospital terciário no Brasil
Introduction: Vitiligo is a dermatological condition that causes loss of skin pigmentation, significantly affecting patients’ quality of life due to social stigma. Despite various therapeutic approaches, including topical treatments, systemic therapies, and phototherapy, many cases remain refractory.
Objective: To report a series of cases to evaluate the effectiveness of autologous melanocyte grafting using the micropunch technique.
Methods and Results: We selected 9 patients with stable and refractory vitiligo, totaling 15 surgeries. Of these, 93.3% showed some degree of repigmentation in the treated area, with the formation of a pigmentation halo around the grafts, as observed in post-surgical photographic follow-up. The inner arm was the most frequently used donor area (60%). The complications were minimal: 1 patient (6.7%) developed hypertrophic scarring in the donor area; 3 patients (20%) developed the “cobblestone appearance” in the recipient area, with 1 case resolving spontaneously after 6 months. There was also partial graft loss in 1 patient (6.7% of surgeries).
Conclusion: The results indicate that the micropunch technique is a viable and safe alternative for managing stable vitiligo, offering a new therapeutic option for cases refractory to conventional treatments.
Introdução: O vitiligo é uma condição dermatológica que causa a perda de pigmentação da pele, afetando significativamente a qualidade de vida dos pacientes devido ao estigma social. Apesar das várias abordagens terapêuticas, incluindo tratamentos tópicos, sistêmicos e fototerapia, muitos casos permanecem refratários.
Objetivo: Relatar uma série de casos para avaliar a eficácia do enxerto autólogo de melanócitos utilizando a técnica de micropunch.
Métodos e Resultados: Foram selecionados 9 pacientes com vitiligo estável e refratário, totalizando 15 cirurgias. Desses, 93,3% apresentaram algum grau de repigmentação na área tratada, com formação de um halo de pigmentação ao redor dos enxertos, conforme observado no seguimento fotográfico pós-cirúrgico. A face interna do braço foi a área doadora mais utilizada (60%). As complicações foram mínimas: 1 paciente (6,7%) apresentou cicatriz hipertrófica na área doadora; 3 pacientes (20%) desenvolveram o “efeito de pedra em calçamento” na área receptora, sendo que, em 1 dos casos, a condição se resolveu espontaneamente após 6 meses. Também houve perda parcial dos enxertos em 1 paciente (6,7% das cirurgias).
Conclusão: Os resultados indicam que a técnica de micropunch é uma alternativa viável e segura para o manejo do vitiligo estável, oferecendo uma nova opção terapêutica para casos resistentes aos tratamentos convencionais. Palavras-chave: Vitiligo; Transplante de Pele; Pigmentação da Pele; Transplante Autólogo.
Original Article
Authors:
Carlos Gabriel Sánchez Urresta1
Vivian Nunes Arruda1
Ana Cristina Fortes Alves1
Nelson Marcos Ferrari1
Maria Victória Quaresma1
1 Hospital das Clínicas, FMUSP - USP Medical School, Dermatology Division, São Paulo (SP), Brazil
Correspondence:
Carlos Gabriel Sánchez Urresta E-mail: carlosgs797@gmail.com / carlos.sanchez@hc.fm.usp.br
Funding source: None. Conflict of interest: None.
Submission date: 11/18/2024
Final decision: 01/16/2025
How to cite this article: Urresta CGS, Arruda VN, Alves ACF, Ferrari NM, Quaresma MV. Autologous melanocyte grafting by micropunch technique in patients with stable vitiligo: a pilot study in a tertiary hospital in Brazil. Surg Cosmet Dermatol. 2025;17:e20250424.
INTRODUCTION
Vitiligo is an autoimmune pigmentation disorder characterized by selective destruction of melanocytes, resulting in achromic patches on the skin that can affect any region of the body, including mucous membranes.1,2 Global prevalence of vitiligo ranges from 0.5% to 2.3%, and the condition is known to significantly impact the quality of life of individuals due to the social stigma associated with visible lesions.3,4 Vitiligo is classified into 2 main variants: segmental vitiligo (SV), which affects a single area or follows a dermatome, and nonsegmental vitiligo (NSV), which presents with scattered lesions in various regions.5,6 Studies indicate that SV tends to respond more favorably to surgical interventions due to its restricted distribution, whereas NSV tends to have a more unpredictable course.7 Treatments for vitiligo include drug therapies (topical and systemic), physical therapies (laser and phototherapy), and surgical interventions, each with its own limitations and specific indications.8,9 However, many patients achieve unsatisfactory results with these conventional approaches, especially those with SV and stable lesions. Given this limitation, punch micrografting has been explored as a viable alternative for skin repigmentation, offering an easy-to-perform option with the potential for good aesthetic results.1,10 This study aims to assess the degree of repigmentation of autologous melanocyte transplantation using punch micrografting in the treatment of achromic areas in patients with SV who are refractory to conventional clinical approaches.
METHODS
This research was approved by the Research Ethics Committee (CAPPesq) of the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP)
on February 9, 2024, Opinion No. 6,644,970 and CAAE No. 76811824.6.0000. 0068. A pilot study was conducted in a series of cases to assess the degree of repigmentation in areas treated with punch micrografting in adult patients aged 18 years or older diagnosed with SV. Patients were seen at the Inaesthetics Outpatient Clinic of the Dermatology Division of the HCFMUSP from November 2023 to December 2024. The inclusion criteria were: patients aged 18 years or older; clinical diagnosis of SV; patches with an area equal to or greater than 2 cm², previously measured with a millimeter ruler; disease stability for at least 1 year, with no new lesions, increased depigmentation in existing lesions, or Koebner phenomenon; and cases that were refractory to conventional therapies, including topical and systemic medications and phototherapy, for at least 6 months. The exclusion criteria were: patients currently using physical therapies or topical or systemic corticosteroid therapy, and those who had used these therapies in the past 3 months; pregnant women; individuals with a history of hypertrophic scars and/or keloids; and patients who declined to sign the informed consent form.
Surgical technique
The donor and recipient sites were marked prior to surgery, followed by antisepsis with 2% alcoholic chlorhexidine solution (Figure 1 - A). Local anesthesia was administered with 2% lidocaine and adrenaline diluted 1:200,000. Punch micrografting, a technique first described by Falabella in 1978,1 involves transplanting epidermal and dermal tissue from a donor site to a recipient site using small-diameter punches (1 to 2 mm).1,7,10 In this study, a 2-mm punch was used to obtain the micrografts (Figure 1 - B, C). Following collection, the grafts were stored in
FIGURE 1: A - marking and antisepsis; B, C - obtaining grafts; D - creation of recipient beds; E, F - placement of grafts and fixation with internal dressin
a 0.9% saline solution. In the recipient site, a smaller diameter punch (1 mm) was used to create the recipient beds for the grafts (Figure 1 - D). The donor sites were protected with petrolatum and gauze and micropore® dressings (Figure 1 - E, F). The number of grafts removed and beds created varied according to the extent of the area to be repigmented, and beds were spaced approximately 0.5 to 1.0 cm apart, allowing the pigment halos generated by each graft to merge (Figure 1 - D). The grafts were gently placed into position using curved Adson forceps, always ensuring that the dermal side of the graft was in contact with the bed (Figure 1 - E). After placing all the grafts, a 2-layer dressing was applied: the internal dressing, just above the grafts, made with petrolatum and micropore®, and the external dressing, with gauze and surgical tape (Figure 1 - F). Immediately after the completion of the surgical procedure, patients were instructed to keep the external dressing on the recipient site and the dressing on the donor site for 48 hours. Patients were also instructed to perform daily hygiene, removal of blood crusts, and dressing changes at home. The internal dressing in the recipient site was kept in place and removed 14 days postoperatively (Figures 2 and 3), when the results were assessed according to the protocol, monitoring the evolution and degree of repigmentation through photographic records on postoperative day 14, and subsequently on a monthly basis (Figures 2 and 3).
RESULTS
A total of 9 patients were included in the study, 6 women (66.7%) and 3 men (33.3%), with a mean age of 33.6 years. SV was predominant in the sample, present in 8 patients (88.9%), while only 1 patient (11.1%) had NSV. All participants had a history of disease stability, with a mean duration of 5.5 years, ranging from 2 to 11 years. In addition, all had received previous treatments, such as topical corticosteroids, calcineurin inhibitors, phototherapy, and systemic corticosteroid therapy for more than 3 years prior to surgery. However, these treatments failed to result in satisfactory repigmentation, which qualified them as candidates for autologous melanocyte transplantation. A total of 15 surgeries (100%) were performed among the 9 patients. Of these, 1 patient underwent 3 surgeries, 4 patients underwent 2 surgeries each, and 4 patients underwent only 1 surgery. Among the 15 interventions performed, 14 (93.3%) showed some degree of repigmentation in the treated site, evidenced by the formation of a pigmented halo around the grafts, as recorded during photographic follow-up. The inner arm was the most frequently used donor site, chosen in 9 surgeries (60%), followed by the gluteal region on 2 occasions (13.3%), the lumbosacral region in 1 (6.7%), the retroauricular region in 1 (6.7%), and the inner thigh in 1 (6.7%). Few complications were recorded in the donor and recipient sites. Only 1 patient (6.7% of surgeries) developed hypertrophic scarring in the donor site (Figure 4 - A),
FIGURE 2: A, B - before the surgery; C, D - 15 days after surgery; E, F - 3 months after surgery; G, H - 6 months after surgery
which demonstrates that the procedure is safe in most cases. In the recipient site, 3 patients (20% of surgeries) presented with a “cobblestone appearance” (Figure 4 - C), which is when the skin graft has an uneven texture with small bumps that look like stones. In 1 case (6.7% of surgeries), the condition resolved spontaneously after 6 months of follow-up. In addition, 1 patient (6.7% of surgeries) had grafts that failed to repigment (Figure 4 - B), a complication known as static grafts. Finally, 1 patient (6.7% of surgeries) had significant graft loss, with more than 50% in the first surgery (Figure 4 - D) and less than 50% in the second.
DISCUSSION
FIGURE 3: A - before the first surgery; B - 15 days after the first surgery; C - 3 months after the first surgery; D - before the second surgery; E - 15 days after the second surgery; F - donor site 15 days after the first surger
FIGURE 4: A - hypertrophic scarring in the donor site; B - static grafts; C - grafts with cobblestone appearance; D - grafted site with loss of more than 50% of the grafts
The results of this pilot study suggest that punch micrografting may be a viable alternative for the treatment of stable, refractory vitiligo. The predominance of SV in the sample (88.9%) is in line with other studies that indicate a more favorable response of this subtype of vitiligo to surgical interventions due to the smaller extent and distribution of lesions.1,7 The average duration of disease stability (5.5 years in our study) reinforces the importance of careful selection of candidates for surgery. Patients with stable vitiligo for a long period have a lower risk of
developing new lesions after the intervention, an essential factor for the success of the treatment.3,6 In relation to complications, hypertrophic scarring in the donor site in only 1 patient reinforces the safety of the technique in most cases. Complications in the recipient site, such as “cobblestone appearance” and partial loss of grafts, are consistent with the findings of other studies, which indicate that these events are relatively common in punch micrografting. However, these issues can be minimized by improving graft placement techniques, such as using micropunches with a diameter smaller than 2 mm, creating thin grafts composed only of the epidermis and superficial dermis, using appropriate instruments, and performing rigorous postoperative follow-up.8,9 The predominant use of the inner arm as the donor site (60%) demonstrates its sufficiency for the procedure, considering its accessibility and compatibility with the characteristics of the recipient site. Other sites, such as the gluteal and retroauricular region, were chosen for patients with specific needs, suggesting that the selection of the donor site should be customized according to the anatomical and aesthetic characteristics of each
case.4,5 This study has limitations, including the small sample size and the absence of a control group, which hinders the generalization of the results. However, the data obtained provide an important basis for future studies and reinforce the potential of the punch micrografting as a therapeutic option for stable and refractory SV.
CONCLUSION
Vitiligo is a dermatological condition with significant prevalence, especially in a country like Brazil. Although it is not physically disabling, its lesions are highly stigmatizing, having a great impact on the quality of life of individuals. Despite the various clinical treatments available, many cases remain refractory to conventional therapies. In this context, melanocyte micrografting using a micropunch emerges as a promising alternative, combining efficacy and ease of execution. This procedure can bring substantial benefits to the quality of life of patients with stable vitiligo, providing a therapeutic option for those refractory to traditional treatments. l
REFERENCES:
1. Falabella R, Barona MI. Surgical approaches for stable vitiligo: an overview. J Am Acad Dermatol. 2009;60(3):474-91.
2. Alghamdi KM, Kumar A, Taïeb A, Ezzedine K. What patients with vitiligo have to say about their condition: a qualitative study. Br J Dermatol. 2019;180(3):564-70.
3. Sehgal VN, Srivastava G, Aggarwal AK. Vitiligo: prevalence, distribution and related aspects in rural community of Haryana. Indian J Dermatol Venereol Leprol. 2019;70(3):187-90.
4. Passeron T, Ortonne JP. Physiopathology and genetics of vitiligo. J Autoimmun. 2005;25(Supplement):63–8.
5. Desai S, Dhamanaskar D, Gohil A. Segmental vitiligo and its surgical treatment. Int J Dermatol. 2020;59(5):593-600.
6. Kumar R, Mehta R, Sharma N. Advances in vitiligo surgical techniques. J Cutan Aesthet Surg. 2021;14(1):55-63.
AUTHOR’S CONTRIBUTION:
Carlos Gabriel Sánchez Urresta
0000-0002-7332-9435
7. Lahiri K. Vitiligo management update: a consensus view from expert vitiligo academicians in India. Indian J Dermatol. 2012;57(6):383-90.
8. Mehta NR, Shah KC. Long-term outcome of various surgical modalities in the management of stable vitiligo. J Cutan Aesthet Surg. 2017;10(3):140-6.
10. Grochocka M, Welniak A, Bialczyk A, Marek-Jozefowicz L, Tadrowski T, Czajkowski R. Management of stable vitiligo—a review of the surgical approach. J Clin Med. 2023;12(5):1984.
Conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, critical review of the literature, critical revision of the manuscript
Vivian Nunes Arruda 0000-0002-7114-1869
Approval of the final version of the manuscript, effective participation in the conduct of the study, critical revision of the manuscript
Ana Cristina Fortes Alves 0009-0009-0485-6205
Author’s contribution: Approval of the final version of the manuscript, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied
Nelson Marcos Ferrari 0009-0008-3556-4611
Effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied.
Maria Victória Quaresma 0000-0003-2891-1650
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, effective participation in the conduct of the study, critical review of the literature, critical revision of the manuscript.
www.surgicalcosmetic.org.br/
Giant Merkel cell carcinoma: report of an atypical case
Carcinoma de célula de Merkel gigante: relato de um caso atípico
Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine cancer that occurs on sun-damaged skin in older White patients. It typically manifests as a solitary plaque or nodule in the head and neck region. We report an unusual presentation of Merkel cell carcinoma in a black patient who simultaneously developed two primary tumors located in the trunk region.
1 Hospital Universitário, State University of Londrina, Dermatology Service, Londrina (PR), Brazil
RESUMO
O carcinoma de células de Merkel é um câncer neuroendócrino cutâneo raro e agressivo que acomete a pele fotodanificada de pacientes brancos e idosos, apresentando-se geralmente como uma placa ou nódulo solitário na região da cabeça e do pescoço. Relatamos uma apresentação incomum do carcinoma de Merkel, com o surgimento simultâneo de dois tumores primários na região do tronco, em paciente negro. Palavras-chave: Carcinoma de célula de Merkel; Carcinoma neuroendócrino; Imuno-histoquímica; Tronco
Correspondence:
Ana Carolina Cechin de Mello E-mail: anacechin@hotmail.com
Funding: None.
Conflict of interest: None.
Submitted on: 10/22/2023
Final decision: 02/27/2025
How to cite this article:
Mello ACC, Kondo RN, Samesina e Singh B, Gon AS. Giant Merkel cell carcinoma: report of an atypical case. Surg Cosmet Dermatol. 2025;17:e20250314.
Dear Editor,
A 78-year-old black man, who works as a gardener, presented with two nodules on his back that had been rapidly growing over the past 3 months. He denied fever, weight loss, or other related symptoms. His medical history includes prostate adenocarcinoma, treated with an orchiectomy in 2019. Dermatological examination revealed two indurated nodules measuring 12 and 16 cm in the dorsal region (Figure 1), with no
associated lymph node enlargement. Histopathological examination of both nodules revealed basaloid cells with oval nuclei, scant cytoplasm, and numerous mitoses, suggestive of Merkel cell carcinoma (MCC). Immunohistochemistry was positive for cytokeratin 20 (CK20) and negative for prostate-specific antigen (PSA) and thyroid/lung transcription factor-1 (TTF-1) (Figures 2 and 3).
Figure 1: A - Two nodules in the dorsal region. B - Detail of the nodule on the left: basaloid cells, oval nucleus, scant cytoplasm, and numerous mitoses.
Figure 3: Immunohistochemistry showing that the cells stained positive for the cytokeratin 20 marker
MCC is a rare and aggressive neuroendocrine cancer that primarily affects sun-exposed skin in older White individuals, with a rare incidence in black individuals. It commonly appears as a solitary plaque or nodule on the head or neck.1,2 Although MCC accounts for less than 1% of all malignant skin tumors, it is the third leading cause of skin cancer-related deaths.2 It was first described by Toker et al. in 1972 as trabecular carcinoma of the skin, suggesting, at the time, a possible glandular origin. In 1978, the same authors identified electron-dense granules in the cytoplasm of tumor cells, indicating a neuroendocrine origin similar to epidermal Merkel cells.2 The pathogenesis of MCC remains unclear, but ultraviolet (UV) radiation, immunosuppression, and, recently, the presence of Merkel cell polyomavirus in the tumor genome appear to play key roles.2,3 The acronym “AEIOU” was developed to aid in considering a diagnosis of MCC, corresponding to: A = asymptomatic, E = expanding rapidly, I = immunosuppression, O = older than 50 years, and U = UV-exposed site.2 Histopathology shows a dermal lesion consisting of clusters of monomorphic, round, basophilic cells with large vesicular nuclei with finely granular chromatin, pyknotic nuclei, and abundant mitotic figures.4 While CK20 is a key immunohistochemical marker for diagnosis, it can be negative in up to 20% of cases.2 The TTF-1 marker is typically positive in lung and thyroid cancers, and a negative result can support the diagnosis of MCC.2 The differential diagnosis for MCC includes
REFERENCES:
1. Coggshall K, Tello TL, North JP, Yu SS. Merkel cell carcinoma: An update and review: Pathogenesis, diagnosis, and staging. J Am Acad Dermatol. 2018;78(3):433-42.
2. Llombart B, Requena C, Cruz J. Atualização em carcinoma de células de Merkel: Epidemiologia, etiopatogenia, características clínicas, diagnóstico e estadiamento. Actas Dermosifiliogr. 2017;108(2):108-19.
3. Góes HFO, Lima CS, Issa MCA, Luz FB, Pantaleão L, Paixão JGM. Carcinoma de células de Merkel em um paciente imunossuprimido. An Bras Dermatol. 2017;92(3):395-7.
AUTHOR’S CONTRIBUTION:
Ana Carolina Cechin de Mello
0009-0007-6862-6287
epidermal cysts, dermatofibroma, basal cell carcinoma, squamous cell carcinoma, amelanotic melanoma, lymphoma, skin metastases, and adnexal tumors.2 Staging, for determining prognosis and treatment strategies, adheres to the American Joint Committee on Cancer criteria: stage 1 (primary tumor < 2 cm); stage 2 (primary tumor ≥ 2 cm); stage 3 (regional lymph node involvement); and stage 4 (distant metastasis).2 Surgical excision with 1 cm margins is the treatment of choice. Inoperable or recurrent tumors can be treated with radiotherapy. Chemotherapy serves as a palliative treatment option for patients in stage 4.5 In the case reported here, tomography revealed bone metastases and lymph node involvement in the mediastinum, pelvis, and abdomen. However, no neuroendocrine tumor was identified at any other site or primary focus. The two lesions observed in this case are presumed to be synchronous due to their concurrent appearance without a known primary focus and their size. Nevertheless, the authors do not rule out the possibility that these are two metastases originating from an undetected primary tumor, given the patient’s stage 4 presentation and the extremely aggressive nature of MCC, which often metastasizes even from small primary lesions. Regardless, this case has an unusual presentation, with the emergence of two large synchronous lesions in a black individual.The patient has been referred to an oncology hospital in the city for chemotherapy treatment. l
4. Walsh NM, Cerroni L. Merkel cell carcinoma: a review. J Cutan Pathol. 2021;48(3):411-21.
5. Tétu P, Baroudjian B, Madelaine I, Delyon J, Lebbé C. Update in treatment for Merkel cell carcinoma and clinical practice guide. Bull Cancer. 2019;106(1):64-72.
Preparation and writing of the manuscript, effective participation in the conduct of the study, intellectual participation in propaedeutic and/or therapeutic approach to studied cases, critical review of the literature.
Rogerio Nabor Kondo
0000-0003-1848-3314
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in propaedeutic and/or therapeutic approach to studied cases, critical review of the literature, critical revision of the manuscript.
Betina Samesima e Singh 0000-0002-6055-0341
Acquisition, analysis and interpretation of data, effective participation in the conduct of the study, critical review of the literature, critical revision of the manuscript.
Airton dos Santos Gon 0000-0003-1219-5581
Approval of the final version of the manuscript, conception and design of the study, effective participation in the conduct of the study, intellectual participation in propaedeutic and/or therapeutic approach to studied cases, critical revision of the manuscript.
www.surgicalcosmetic.org.br/
Transfollicular subcutaneous forehead and brow lift
Lifting transfolicular subcutâneo do terço superior da face
The appearance of the upper third of the face is a key indicator of aging and plays a significant role in communication by conveying non-verbal information. Different surgical techniques have been described for the rejuvenation of this region, with transfollicular subcutaneous forehead and brow lift enabling excellent results by lowering the hairline, reducing forehead height, softening forehead and glabellar rhytids, raising the eyebrows, and improving pseudodermatochalasis. This technique offers the advantages of reduced risk of nerve injury and excellent scalp scar camouflage.
1 Santa Casa de Misericórdia do Rio de Janeiro, Instituto de Dermatologia Professor Rubem David Azulay, Rio de Janeiro (RJ ), Brazil
RESUMO
A aparência do terço superior da face é um dos principais indicadores de envelhecimento e desempenha um papel significativo na comunicação ao transmitir informações não verbais. Diferentes técnicas cirúrgicas têm sido descritas para o rejuvenescimento dessa região, com o lifting transfolicular subcutâneo do terço superior da face possibilitando excelentes resultados ao abaixar a linha de implantação capilar, reduzir a altura da fronte, atenuar rítides frontais e glabelares, elevar as sobrancelhas e melhorar a pseudodermatocálase. Essa técnica apresenta as vantagens de menor risco de lesão nervosa e excelente camuflagem da cicatriz no couro cabeludo. Palavras-chave: Cirurgia Plástica; Envelhecimento da Pele; Procedimentos Cirúrgicos Dermatológicos; Rejuvenescimento; Ritidoplastia.
Correspondence:
Anna Karoline Gouveia E-mail: a.karolineoliveira@gmail.com
Funding: None.
Conflict of interest: None.
Submitted on: 05/15/2024
Final decision: 07/15/2024
How to cite this article: Gouveia AK, Loda G, Benez M, Loda AB. Transfollicular subcutaneous forehead and brow lift. Surg Cosmet Dermatol. 2025;17:e20250372.
INTRODUCTION
The appearance of the upper third of the face is a key indicator of aging, characterized by rhytids, forehead and brow ptosis, and changes in the periocular region, which result from bone resorption, transmission of muscle action to the skin surface, and skin-ligamentous laxity. The upper third of the face also plays a significant role in communication by conveying non-verbal information. Regarding the aesthetics of this region, young men typically have straighter horizontal brows positioned at the level of the orbital rim. In young women, the brows are usually positioned above the level of the orbital rim, featuring a fuller, more quadrangular medial portion and becoming progressively arched and thinner toward the lateral portion, with the brow apex often coinciding with a vertical line drawn from the lateral corneal limbus. Aging leads to a progressive descent of the eyebrows, which can be positioned below the orbital rim, depending on the degree of aging.
Different surgical techniques have been described for the rejuvenation of this region, each with its own advantages and limitations, which, combined with the surgeon’s experience, will determine the choice of technique for each patient. While non-surgical treatments can be beneficial and used in combination, the most substantial and long-lasting results are only achieved with surgical lifting.We describe the transfollicular subcutaneous forehead and brow lift (TSFBL), a technique that allows rejuvenation of the eyebrow, glabellar, and forehead regions.
SURGICAL TECHNIQUE
With the patient seated, the incision line is marked. In the lateral third, a line with superior concavity below the eyebrow delineates the area of maximal elevation, where the detachment will be performed in the subcutaneous plane. In the medial region, where the supraorbital and supratrochlear nerves are located, a line with inferior concavity is marked above the eyebrow, serving as the lower limit of the detachment, with the aim of reducing the risk of nerve injury and avoiding over-elevation of the medial brow portion. In the glabellar region, a line with superior concavity is marked as a reference point for the lower limit of the detachment (Figure 1). The lateral limits are marked with a vertical line drawn at the level of the temporal crest.The scalp incision is marked approximately 5 mm posterior to the hairline, drawn in a jagged fashion to simulate the shape of the natural hairline (Figure 2). The procedure is performed under tumescent local anesthesia using an anesthetic solution consisting of 80 mL of 0.9% sodium chloride, 20 mL of 2% lidocaine, and 0.4 mL of 1 mg/mL epinephrine. The solution is injected subcutaneously along the previously marked area, and the total volume to be used depends on the extent of the frontal region. In our experience, this volume ranges from 60 to 80 mL. The incision and dissection plane give the procedure its name, TSFBL. The incision is made using a No. 11 blade, angled between 10 and 20 degrees relative to the horizontal plane. This angle allows for the hair follicles to be sectioned at different
Figure 1: Skin marking. Area of maximal elevation marked in the lateral third and inferior to the eyebrows with a line with superior concavity, indicating the inferior limit of the detachment in the subcutaneous plane. In the medial region, where the supraorbital and supratrochlear nerves are located, the inferior limit of the detachment is marked with a line with inferior concavity above the eyebrow. In the glabellar region, the limit of detachment is marked with a line with superior concavity. The lateral limits are marked with a vertical line drawn at the level of the temporal crest
heights, preserving part of the bulbs, which will allow for the most anterior follicles to grow in front of the scar (Figure 3), promoting effective scalp scar camouflage. These incision characteristics also produce very thin wound edges, contributing to a better aesthetic outcome. The dissection is performed in the subcutaneous plane, maintaining fat both on the roof and floor, thus creating an adipocutaneous flap and avoiding damage to the underlying frontalis muscle. By respecting the uppermost marking line in the proximal region of the eyebrows, over-elevation of their medial portion is avoided, while the lower dissection of the glabella and lateral portions allows elevation of the tail of the brow and correction of glabellar ptosis, restoring a more you-
thful appearance. Because this subcutaneous technique allows direct visualization, there is a lower risk of injury to the primary sensory and motor nerves in the glabellar region compared with endoscopic and supraperiosteal techniques. The lateral limit of Surg Cosmet Dermatol. 2025;v.17: n.2 apr-Jun. p.206-11.
the detachment should not exceed the temporal crest to avoid injury to the temporal nerve. The superficial musculoaponeurotic system (SMAS) fibrous septa connect the frontalis muscle to the forehead skin. During dissection in the subcutaneous plane, most of these septa are disrupted, resulting in a significant improvement in forehead and glabellar rhytids. While the depressor supercilii muscles can be sectioned under direct visualization, we have chosen not to approach them due to the lack of superiority in the observed results, as well as not to increase the risk of complications. Once the dissection is complete, the flap is pulled over the scalp and 3 vertical incisions are made (back cut): one in the central region of the forehead, which corresponds inferiorly to the glabella; and two paramedian incisions, which correspond to the point of maximal brow elevation, often coinciding with a vertical line drawn from the lateral corneal limbus. The length of these incisions ranges from 15 to 30 mm, depending on the eyebrow position, the distance between the scalp and eyebrows, and the surgeon’s experience. In our practice, a length between 20 and 25 mm is adequate in most cases.The flap is secured with key sutures placed between the distal part of these incisions and the scalp, using simple 5.0 nylon sutures (Figure 4). Excess skin is then removed using a No. 11 blade, following the same design and angle of the scalp incision, and the wound edges are gently closed using simple 5.0 nylon sutures (Figure 5). The procedure is completed with the application of a pressure dressing, and the patient is reassessed within 48 hours. After this period, dressings are no longer required. The sutures are removed after 10 to 14 days (Figure 6).
4: Three vertical incisions (back cut) and flap fixation with key sutures placed between the distal part of these incisions and the scalp, using simple 5.0 nylon sutures
Figure 2: The scalp incision is marked approximately 5 mm posterior to the hairline, drawn in a jagged fashion to simulate the shape of the natural hairline
FIGURE 3: Dermoscopy showing hair growth in front of the scar
Figure
DISCUSSION
There are several surgical options for the treatment of brow ptosis, which can be didactically divided into direct visualization, transblepharoplasty, and endoscopic techniques. The di-
rect visualization techniques vary based on the incision location, including excisions performed just above the eyebrows (Castañares technique), in the mid-forehead, pretrichial, coronal, and transfollicular. Endoscopic brow lift is performed in the subgaleal or subperiosteal plane and uses bone fixation materials, resulting in smaller incisions and reduced postoperative edema, dysesthesia, and alopecia. However, this technique requires specialized equipment, is more expensive, has a steeper learning curve, and may offer less long-lasting results compared with direct methods, since the amount of elevation is determined by flap release and fixation, without direct skin excision.1 It is particularly indicated when there is brow asymmetry.2 The transpalpebral approach involves securing the brow tissue, muscles, and subcutaneous fat to the periosteum through an upper blepharoplasty incision. This can be performed intraoperatively during an upper blepharoplasty when a traditional brow lift is not planned. Mokhtarzadeh et al., evaluating 98 patients who underwent internal fixation during blepharoplasty, identified an average elevation in central/ lateral brow position of 1.47 to 2.29 mm over a follow-up of 4-5 months.3 The direct brow lift includes variations of bilateral elliptical incisions just above the eyebrows (including the Castañares technique), hiding the scar along the hairline, or midfrontal incisions to camouflage scars within horizontal forehead rhytids. These two types are particularly suitable for patients with unstable hairlines. The technique can be modified to address lateral ptosis alone or to compensate for asymmetries.These techniques may also lower the hairline by shortening the forehead. While dissection in the subcutaneous plane can be performed medially
Figure 5: After excess skin removal, following the same design of the scalp incision
Figure 6: Results on postoperative day 15
Figure 7: Results 1 year after treatment (same patient as in figure 1). Note the significant improvment in forehead and glabellar rhytids, eyebrow position, and pseudodermatochalasis. The resultant scar is a thin hypochromic line, only visible with the hair pulled back
to improve glabellar rhytids, it does not improve forehead rhytids, and the scar may remain visible for a long period.3 The coronal brow lift, an open technique using an ear-to-ear scalp incision, elevates the hairline but can cause alopecia and nerve damage. The pretrichial approach involves an incision on the forehead, just outside and below the scalp. Unlike the coronal brow lift, this technique lowers the hairline by shortening the forehead, but it can lead to the same complications as the other methods, with the added disadvantage of leaving a more visible scar. The transfollicular approach can lower the hairline, reduce forehead height, and soften forehead and glabellar rhytids, elevating the entire upper third of the face, with improvement in pseudodermatochalasis. If excess upper eyelid skin persists after TSFBL, an upper blepharoplasty can be performed in the same surgical procedure to complement the results. In our experience, we prefer performing blepharoplasty at a later stage to obtain a more accurate assessment of the amount of excess skin. The appearance of the resultant scar is satisfactory, resulting in a thin hypochromic line, only visible with the hair pulled back (Figure 7). Overall, all surgical brow elevation techniques have a low incidence of complications, with the most common being hematoma, dama-
ge to sensory and motor nerves leading to dysesthesia, paresis, asymmetry, alopecia, and unsightly scarring. Currently available data do not demonstrate the superiority of one technique over another, nor of endoscopic techniques over direct visualization techniques.4,5
CONCLUSION
The various brow lifting techniques have their own peculiarities regarding specific indications, execution methods, and contraindications, which will determine the choice of the optimal procedure for each patient. In patients with high hair density in the frontotemporal region, our technique of choice is the transfollicular subcutaneous approach due to the satisfactory and long-lasting results in lifting the entire upper third of the face, associated with improvements in rhytids, excellent scalp scar camouflage, safe dissection in the subcutaneous plane under direct visualization, and the possibility to be performed with low-cost materials, compared with endoscopic techniques.The main contraindications to this approach are unstable hairlines and alopecia in the frontotemporal region. l
Gouveia AK, Loda G, Benez M, Loda AB.
REFERENCES:
1. Holck DE, Ng JD, Wiseman JB, Foster JA. The endoscopic browlift for forehead rejuvenation. Semin Ophthalmol. 1998;13(3):149-57.
2. Karimi N, Kashkouli MB, Sianati H, Khademi B. Techniques of eyebrow lifting: a narrative review. J Ophthalmic Vis Res. 2020;15(2):218-35.
3. Mokhtarzadeh A, Massry GG, Bitrian E, Harrison AR. Quantitative efficacy of external and internal browpexy performed in conjunction with blepharoplasty. Orbit. 2017;36(2):102–9.
4. Graham DW, Heller J, Kirkjian TJ, Schaub TS, Rohrich RJ. Brow lift in facial rejuvenation: a systematic literature review of open versus endoscopic techniques. Plast Reconstr Surg. 2011 Oct;128(4):335e-341e. Erratum in: Plast Reconstr Surg. 2011;128(5):1151. Kirkjian, T Jonathan [corrected to Kurkjian, T Jonathan].
5. Byun S, Mukovozov I, Farrokhyar F, Thoma A. Complications of browlift techniques: a systematic review. Aesthet Surg J. 2013;33(2):189-200.
AUTHOR’S CONTRIBUTION:
Anna Karoline Gouveia 0000-0001-6258-9824
Conception and design of the study; preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic approach to studied cases; critical review of the literature.
Guillermo Loda 0000-0003-0511-0025
Approval of the final version of the manuscript; conception and design of the study; effective participation in the conduct of the study; intellectual participation in propaedeutic and/or therapeutic approach to studied cases; critical revision of the manuscript.
Marcela Benez 0000-0003-0289-5656
Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic approach to studied cases.
Anna Beatriz Loda 0009-0000-7319-2531
Intellectual participation in propaedeutic and/or therapeutic approach to studied cases.
www.surgicalcosmetic.org.br/
Target nevus: dermoscopy and reflectance confocal microscopy
Nevo em alvo: dermatoscopia e microscopia confocal de reflectância
Halo, cockade, eczematous, and targetoid hemosiderotic nevi are known as target nevi, classified as melanocytic nevi with special features and often mimic melanoma. This communication aims to demonstrate clinical manifestations, dermoscopic patterns, and reflectance confocal microscopy findings in 4 patients with different types of target nevi.
Os nevos halo, cocar, eczematoso e hemossiderótico targetoide são conhecidos como nevo em alvo, classificados como nevos melanocíticos especiais e frequentemente simulam melanoma. A presente comunicação tem como objetivo demonstrar as manifestações clínicas, os padrões dermatoscópicos e os achados na microscopia confocal de reflectância de quatro pacientes com diferentes tipos de nevos em alvo. Palavras-chave: Dermoscopia; Microscopia Confocal; Melanoma; Nevo com Halo.
1 Hospital Universitário de Brasília, Dermatology, Brasília (DF), Brazil
2 Hospital Regional da Asa Norte, Dermatology, Brasília (DF), Brazil
Correspondence:
Inês Stafin E-mail: inesstafin@gmail.com
Funding: None.
Conflict of interest: None.
Submitted on: 08/08/2024
Final decision: 12/09/2024
How to cite this article: Stafin I, Brandão FV, Pinheiro AMC. Target nevus: dermoscopy and reflectance confocal microscopy. Surg Cosmet Dermatol. 2025;17:e20250395.
Some melanocytic nevi are classified dermoscopically as special nevi, exhibiting distinct clinical and histopathologic features. They are considered “melanoma mimics” and include target nevi, such as halo, cockade, eczematous, and targetoid hemosiderotic nevi.1 While the dermoscopy and reflectance confocal microscopy (RCM) patterns of typical nevi are well-documented, there are limited data on this specific category of nevi.2 This communication aims to demonstrate clinical manifestations, dermoscopic patterns, and RCM findings in different cases of target nevi. We present 4 patients (2 men and 2 women), aged 24 to 39 years with phototypes 1-3, with distinct presentations of target nevi: halo, cockade, eczematous, and targetoid hemosiderotic nevi, detailing their clinical, dermoscopic, and RCM structures. Dermoscopy was performed using the FotoFinder medicam 1000 imaging system, and RCM was performed using the VivaScope 1500. We report 4 different benign melanocytic nevi, termed target nevi: halo, cockade, eczematous, and targetoid hemosiderotic. The halo nevus, also known as Sut-
ton nevus,3 presents as a pigmented lesion located on the patient’s lower back, surrounded by a peripheral white halo. Dermoscopically, the nevus exhibits a globular pattern, surrounded by a white rim of depigmentation. RCM mosaic image shows dense bright nests at the dermoepidermal junction (DEJ) and in the dermis (Figure 1 A, B, C). The cockade nevus, located on the patient’s neck, features a central pigmented papular nevus,4 surrounded by a depigmented inner rim and a pigmented outer rim. Dermoscopically, the nevus exhibits a central globular pattern, a lighter homogeneous inner ring, and a peripheral darker reticular ring. RCM mosaic image shows, at the level of the DEJ, a central dense nest and a ringed pattern at the periphery (Figure 2 D, E, F). The eczematous nevus,1 also known as Meyerson’s phenomenon, presents as an eczematous halo surrounding a pigmented nevus, located on the patient’s back. Clinically, it appears as a small brown papule with an erythematous halo and evident overlying scales. Dermoscopically, the phenomenon does not modify the characteristics of the nevi, maintaining a re-
A E B F C D
D, E and F
nevus: papular nevus surrounded by 2 halos, depigmented and pigmented; dermoscopy: globular pattern, lighter homogeneous inner halo, and peripheral darker reticular halo; reflectance confocal microscopy: central dense nest surrounded by a ringed pattern
Figure 1: A, B and C - Sutton nevus: papule surrounded by a peripheral white halo; dermoscopy: central globular pattern and peripheral white depigmentation; reflectance confocal microscopy: dense bright nest
Figure 2:
- Cockade
A
D B E
Figure 3: A, B and C - Eczematous nevus: small brown papule with an erythematous halo and overlying scales; dermoscopy: reticular pattern, but blurred due to a yellowish serocrust; reflectance confocal microscopy: roundish to oval spaces in the epidermis filled with small bright round particle
C F
Figure 4: D, E and F - Hemosiderotic nevus: violaceous, ecchymotic halo surrounding a flat central nevus; dermoscopy: homogeneous pattern with vascular hemorrhage, red to purple; reflectance confocal microscopy: ringed patter
ticular pattern, although it may appear blurred due to yellowish serocrusts. RCM mosaic image shows roundish to oval spaces in the epidermis filled with small bright round particles, indicative of inflammatory cells (Figure 3 A, B, C). The targetoid hemosiderotic nevus5 was reported by the patient as a sudden change in the pigmentation of a preexisting nevus, clinically resulting in an asymptomatic, violaceous, ecchymotic halo surrounding a flat central nevus. Dermoscopically, the lesion shows a homogeneous pattern with hemorrhagic vascular features, ranging from
red to purple, superimposed on and surrounding the nevus. RCM mosaic image reveals the presence of a ringed pattern at the level of the DEJ (Figure 4 D, E, F). Recognizing the clinical, dermoscopic, and RCM features of melanocytic nevi with special features is crucial for improving diagnostic accuracy in unusual clinical and dermoscopic cases. This recognition helps to avoid unnecessary excisions in cases that are frequently misdiagnosed as melanoma. l
REFERENCES:
1. Larre Borges A, Zauladek I, Longo C, Dufrechou L, Argenziano G, Lallas A et al. Melanocytic nevi with special features: clinical-dermoscopic and reflectance confocal microscopic- findings. J Eur Acad Dermaol Venereol 2014;28(7):833-45.
2. Porto AC, Blumetti TP, Castro RPR, Pinto CALP, Mendes ASPM, Duprat Neto, et al. Recurrent halo nevus: dermoscopy and confocal microscopy features. J Am Acad Dermatol Case reports. 2017;3(3):256-8.
3. Aouthmany M, Mhsa BS, Weinstein M, Zirwas JZ, Brodell RT. The natural history of halo nevi: a retrospective case series. J Am Acad Dermatol 2012;67(4):582-6.
4. Kessides MC, Puttgen KB, Cohen BA. No biopsy needed for eclipse and cockade nevi found on the scalps of children. Arch Dermatol 2009;145(11);1334-6.
5. Patrizi A, Giacomini F, Savoia F, Miscialli C, Neri I. Targetoid hemosiderotic naevus. J Am Acad Dermatol. 2009;23(4):493-4.
AUTHOR’S CONTRIBUTION:
Inês Stafin 0000-0003-0518-0066
Preparation and writing of the manuscript; acquisition, analysis and interpretation of data; critical review of the literature; critical revision of the manuscript.
Flávia Vieira Brandão 0000-0003-3809-9774
Conception and design of the study; acquisition, analysis and interpretation of data; critical review of the literature; critical revision of the manuscript.
Ana Maria Costa Pinheiro 0000-0002-7804-3567
Author contribution: Approval of the final version of the manuscript; conception and design of the study; acquisition, analysis and interpretation of data; effective participation in the conduct of the study; critical review of the literature; critical revision of the manuscript.
www.surgicalcosmetic.org.br/
Periorbital eruptive vellus hair cyst: a challenging treatment in an atypical location
Cisto veloso eruptivo periorbital: tratamento desafiador em localização atípica
Eruptive vellus hair cyst is a rare condition resulting from the abnormal development of vellus hair follicles, leading to the formation of multiple follicular papules. While it can appear on the face, only five cases specifically located in the periorbital region have been described in the literature. Its treatment is challenging, particularly in the case we report here due to the peculiar location of the lesions, which increases the risk of postoperative scarring and dyschromia. We present a report that addresses the challenging diagnosis and successful treatment of a rare case of eruptive vellus hair cyst located in the periorbital region.
O cisto veloso eruptivo é uma entidade rara decorrente do desenvolvimento anormal dos folículos vellus, que se manifesta na forma de múltiplas pápulas foliculares. Eventualmente, pode localizar-se na face, sendo descritos na literatura apenas cinco casos na região periorbital. Seu tratamento é desafiador, especialmente neste relato de caso, devido à peculiaridade da localização das lesões, com risco de cicatriz e discromia pós-procedimento. Relata-se o diagnóstico desafiador e o tratamento satisfatório de um caso raro de cisto veloso eruptivo localizado na região periorbital. Palavras-chave: Cisto folicular; Pálpebras; Procedimentos cirúrgicos menores
Antônio Moraes, Department of Clinical Medicine, Dermatology Course, Vitória (ES), Brazil
Correspondence:
Bruna dos Anjos Bortolini E-mail: bdabortolini@gmail.com
Funding: None.
Conflict of interest: None.
Submitted on: 03/04/2024
Final decision: 04/18/2024
How to cite this article: Bortolini BA, Fraga RC, Nogueira PSE, Grippa TA, Ferreira VA. Periorbital eruptive vellus hair cyst: a challenging treatment in an atypical location. Surg Cosmet Dermatol. 2025;17:e20250356.
INTRODUCTION
Eruptive vellus hair cyst (EVHC), a rare condition first described in 1977,1 arises from the abnormal development of vellus hair follicles at the infundibular level, leading to retention of hairs, cystic dilation of the proximal part of the follicle, and secondarily, atrophy of hair bulbs.2,3 EVHC is most commonly observed in children and young adults, with no sex or race predilection. Its pathogenesis remains unknown, and it may be associated with either the sporadic form of the disease or autosomal dominant inheritance with incomplete penetrance,2,3 based on numerous reports of families in which two or more members are affected.4 Typically, these lesions are asymptomatic but may sometimes be associated with mild pruritus or altered sensitivity. Occasionally, they can appear on the face.2 Treatment can be challenging, and currently, there is no consensus on the optimal treatment. We report the case of a patient with EVHC located on the eyelids, which, due to its unusual location, was initially
misdiagnosed as milia during childhood. This case report aims to illustrate and demonstrate a treatment approach that resulted in a satisfactory aesthetic outcome.
METHODS
A 19-year-old male patient with no known comorbidities presented with asymptomatic normochromic and hypochromic papules of firm consistency on the upper and lower eyelids, present since the age of 6 years.There was no family history of similar lesions. Previous medical consultations resulted in a diagnosis of milia, and topical exfoliants were prescribed without improvement. Due to the progressive increase in the number of lesions, eventually forming clustered papules (Figure 1), an excisional biopsy was performed. Histopathological analysis revealed cysts lined by keratinized squamous epithelium filled with laminated keratin and occasional vellus hair shafts (Figure 2), confirming the
Figure 1: Normochromic and hypochromic papules of firm consistency, some clustered, located on the upper and lower eyelids
Figure 2: Anatomopathologic examination: cyst located in the dermis lined by keratinized squamous epithelium filled with laminated keratin and vellus hair shafts (HE, 100x)
diagnosis of EVHC. Given the patient’s significant aesthetic discomfort, we opted for needle evacuation in some lesions using a 30G needle. To minimize the risk of post-inflammatory hyperchromia, the patient’s skin was prepared topically for 14 days with Kligman’s formula (hydroquinone 40 mg/g + tretinoin 0.5 mg/g +fluocinolone acetonide 0.1 mg/g cream) prior to the procedure.
Description of the technique:
Infiltrative anesthesia using 2% lidocaine with vasoconstrictor.
Incision of the lesions with a 30G needle (Figure 3a).
Needle evacuation using a 30G needle or manual drainage (Figure 3b).
Hemostasis achieved with local compression using gauze.
Local cleaning with a 0.9% saline solution.
RESULTS
The patient experienced mild edema in the first postoperative days.Two months post-procedure, the patient has shown good healing and achieved a satisfactory aesthetic outcome, with no recurrence of the lesions to date (Figure 4).
DISCUSSION
EVHC manifests clinically as multiple follicular papules, flat or dome-shaped, ranging from 1 to 5 mm in diameter, characterized by a smooth surface and firm consistency, with variations of color (erythematous, normochromic, hyperchromic, or even whitish and yellowish). The papules may also exhibit a central hyperkeratotic crust and umbilication.2,3 While these lesions are mostly located on the thorax and upper and lower extremities, they can occasionally affect the abdomen, neck, axillae, groins, and face.2 This distribution is unlikely to be random and appears to overlap with that of pilosebaceous and apocrine units.4 Given its clinical resemblance to other conditions, the definitive diagnosis of EVHC relies on anatomopathologic examination. In the case reported here, this clinical similarity led to misdiagnosis and a prolonged treatment for milia.2,3,5 In addition to milia, the differential diagnosis includes molluscum contagiosum, keratosis pilaris, steatocystoma multiplex, folliculitis, multiple adnexal tumors, and syringomas.2,3,5 Histopathological analysis of EVHC typically reveals its presence in the middle or upper dermis, lined by multiple layers of keratinized stratified squamous epithelium (up to 12 layers). The cyst’s contents consist of varying amounts of laminated keratin, along with numerous vellus hairs that are cut both obliquely and transversely, causing occlusion and dilation of the follicular unit. Usually, no sebaceous gland is found in the cyst wall.2,3,5 EVHC in the periorbital region, as reported in this case, is rare, with only five cases described in the literature.4-7 While treatment approaches for EVHC are not well-established, it is estimated that spontaneous remission occurs in approxima-
Figure 3: A - Incision of lesions with a 30G needle
B - Manual drainage of lesion contents
Figure 4: Reduction in size and number of lesions after needle extraction
tely 25% of cases by transepidermal elimination or destruction secondary to the local inflammatory process.2,3,5 Currently, there is no universally accepted treatment. Reports mention the use of lactic acid and retinoids (tretinoin and isotretinoin), but their results are still insufficient.2,3 Dermabrasion, erbium:YAG laser, carbon dioxide laser vaporization, and needle evacuation have also been noted as potential treatments. However, these methods have limitations, including the risk of scarring and the high rate of early recurrence.2,3,8
CONCLUSION
We report this case of periorbital EVHC due to its rarity, particularly in this atypical location. Furthermore, this report aims to increase awareness of this often underdiagnosed condition, as its primary differential diagnoses correspond to more common entities. Although benign, EVHC can cause considerable aesthetic concerns and even psychological distress for patients, making appropriate and effective treatment essential. Therefore, despite the challenges in treating this condition, the satisfactory response to the approach used in this case is noteworthy. l
8. Kaya TI, Tataroglu C, Tursen U, Ikizoglu G. Eruptive vellus hair cysts: an effective extraction technique for treatment and diagnosis. J Eur Acad Dermatol Venereol. 2006;20(3):264-8.
Conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, critical review of the literature, critical revision of the manuscript.
Rafael Cavanellas Fraga 0009-0001-1869-128X
Approval of the final version of the manuscript, effective participation in the conduct of the study, intellectual participation in propaedeutic and/ or therapeutic approach to studied cases, critical revision of the manuscript.
Paulo Sergio Emerich Nogueira 0000-0003-1528-1100
Approval of the final version of the manuscript, effective participation in the conduct of the study, intellectual participation in propaedeutic and/ or therapeutic approach to studied cases, critical revision of the manuscript.
Tiago de Almeida Grippa 0000-0002-9729-7757
Approval of the final version of the manuscript, effective participation in the conduct of the study, intellectual participation in propaedeutic and/ or therapeutic approach to studied cases, critical revision of the manuscript.
Vitor Angelo Ferreira 0000-0003-2672-5897
Approval of the final version of the manuscript, effective participation in the conduct of the study, intellectual participation in propaedeutic and/ or therapeutic approach to studied cases, critical revision of the manuscript.
www.surgicalcosmetic.org.br/
Keloid surgery on the earlobe by total excision with fistulectomy: two case reports
Cirurgia de queloide em lóbulo de orelha por excisão total com fistulectomia: relato de dois casos
Several surgical techniques are available for the treatment of keloids on the earlobes. Depending on the size, depth, duration, and morphology of the lesion, the procedure can pose significant challenges for the dermatologic surgeon, as these factors are associated with a higher risk of recurrence and local deformities. We report two cases in which total excision with fistulectomy was performed, yielding favorable aesthetic outcomes.
Keywords: Keloid; Ear; Case Reports; Ambulatory Surgical Procedures.
RESUMO
Existem várias técnicas cirúrgicas para o tratamento de queloides em lóbulos de orelhas. Dependendo do tamanho, da profundidade, do tempo de evolução e da forma do queloide, a cirurgia pode ser desafiadora para o cirurgião dermatológico, pois, nessas situações, as recidivas e as deformidades locais podem ocorrer mais frequentemente. Relatamos dois casos em que realizamos excisão total com fistulectomia, apresentando resultados estéticos favoráveis. .
Palavras-chave: Queloide; Orelha; Relatos de Casos; Procedimentos Cirúrgicos Ambulatórios.
1 Universidade Estadual de Londrina, Clínica Médica, Londrina (PR), Brazil
Correspondence:
Rogerio Nabor Kondo
E-mail: kondo.dermato@gmail. com / kondo.dermato@uel.br
Funding: None. Conflicts of interest: None.
Submitted on: 28/04/2024 Approved on: 08/08/2024
How to cite this article: Kondo RN, Pereira BM, Miyazawa B, Souza JMF, Gubert M. Keloid surgery on the earlobe by total excision with fistulectomy: two case reports. Surg Cosmet Dermatol. 2025;17:e20250367.
INTRODUCTION
Keloids are benign, dense, and disorganized overgrowths of type I and III collagen fibers that develop in response to skin trauma.1 Earlobe keloids (ELK) are relatively common and may affect up to 2.5% of individuals who wear earrings in this region.2 The surgical removal of ELK can be challenging for dermatologic surgeons due to high recurrence rates, the potential for unaesthetic scarring, and the risk of local disfigurement.3
Several treatment options are available, including partial or total excision, intralesional corticosteroids, excision combined with corticosteroid injection, cryotherapy, silicone sheeting, pressure dressings, immunosuppressive or antitumor agents, laser therapy, and radiotherapy.2,3 Combined therapies have demonstrated better outcomes and lower recurrence rates compared to monotherapy.2
We report two cases in which patients underwent multiple sessions of intralesional triamcinolone followed by total excision with fistulectomy, resulting in satisfactory cosmetic outcomes. The aim of this case report is to illustrate a possible surgical approach for treating ELK that yielded high patient satisfaction.
METHODS
Two patients with ELK were treated. Both received monthly intralesional injections of triamcinolone (10 mg), totaling four applications prior to surgery.
Patient 1: Male, 23 years old, White, presented with a 9-millimeter (mm) papule connected to a 35 mm plaque on the anterior and posterior aspects of the left earlobe, respectively (Figure 1).
Surgical Technique (Patient 1):
The patient was placed in the right lateral decubitus position.
Antisepsis was performed using 10% topical povidone-iodine.
Sterile surgical drapes were applied.
Local infiltrative anesthesia was administered with 2% lidocaine containing a vasoconstrictor.
An incision was made with a no. 15 scalpel blade on the anterior portion of the keloid, followed by full-thickness excision through the earlobe (fistulectomy) extending to the posterior region. The keloid was removed en bloc (Figure 2).
Hemostasis was achieved.
The wound was closed using simple interrupted sutures with 5-0 mononylon on both the anterior and posterior aspects of the left earlobe (Figure 3).
An additional intralesional injection of triamcinolone (10 mg) was administered (Figure 2).
Patient 2: Male, 47 years old, Brown, presented with a 33-millimeter (mm) plaque on the anterior aspect of the right earlobe, connected to a 54 mm plaque on the posterior aspect (Figure 4).
Figure 1: Patient 1.
A - Anterior view of the earlobe keloid.
B: Posterior portion of the keloid.
Kondo RN, Pereira BM, Miyazawa B, Souza JMF, Gubert M.
2: Patient
A - Defect on the anterior portion of the earlobe. B - Defect on the posterior portion of the earlobe.
C - Enucleated keloid showing anterior and posterior segments connected by an abnormal tract (“fistula”)
3: Patient 1. A - Completed suturing of the anterior region of the earlobe.
B - Completed suturing of the posterior region of the earlobe.
Figure
1.
Figure
RESULTS
Surgical Technique (Patient 2):
The patient was placed in the left lateral decubitus position.
Antisepsis was performed using 10% topical povidone-iodine.
Sterile surgical drapes were applied.
Local infiltrative anesthesia was administered with 2% lidocaine containing a vasoconstrictor.
An incision was made with a no. 15 scalpel blade on the anterior portion of the keloid, followed by full-thickness excision through the earlobe (fistulectomy) extending to the posterior region. The keloid was removed en bloc (Figure 5).
Hemostasis was achieved.
The wound was closed using simple interrupted sutures with 5-0 mononylon on both the anterior and posterior aspects of the left earlobe (Figures 6A and 6B).
An additional intralesional injection of triamcinolone (10 mg) was administered.
A second-stage procedure was performed three weeks later to correct the earlobe shape. This involved excision of a semi-fusiform strip of skin, followed by closure with simple interrupted sutures using 5-0 mononylon.
Both patients had an uneventful recovery during the early postoperative period. Wound healing was satisfactory, and the late postoperative phase showed good aesthetic outcomes (Figures 7 and 8).
DISCUSSION
Earlobes are common sites for keloid formation. The management of ELK can be particularly challenging for dermatologic surgeons, especially when the lesion exceeds 2 cm in size, due to the increased risk of anatomical deformity.3 Monotherapy is associated with higher recurrence rates, ranging from 40% to 100%. Combined treatments involving corticosteroids, pressure earrings, radiotherapy, and surgical excision appear to reduce recurrence rates.2
Some surgical techniques preserve the keloid margins through intralesional excision, aiming to avoid injury to surrounding non-keloidal skin and the deep dermis, focusing instead on removing only the central, most proliferative fibroblastic component. However, current literature does not provide sufficient evidence that this approach is superior to extralesional (total) excision.1
In 2015, Zhu et al. described the use of total excision with fistulectomy. This technique involves complete removal of the lesion and a full-thickness incision through the earlobe (anteroposterior perforation) at the site of the abnormal con-
FIGURE 4: Patient 2. A - Lateral view. B - Posterior view. C - Anterior view
nection between the anterior and posterior portions of the keloid — the so-called “fistula” and the keloid core. In their study, 11 ELKs were treated, and no recurrences were observed after 12 months.3
In the present report, we replicated the total excision with fistulectomy technique in two cases. Based on this experience, we suggest that in ELKs larger than 50 mm — such as
in Case 2 — excess skin should not be removed during the initial procedure to avoid anatomical distortion. Lobe reshaping should be performed after 3 weeks. In both cases, four monthly intralesional triamcinolone injections were administered prior to surgery, as well as an additional dose during the procedure. The objective was to suppress inflammatory processes and mitigate secondary effects such as collagen and glycosaminoglycan
Figure 5: Patient 2. A - Posterior view of keloid enucleation. B - Anterior view of the enucleation defect, showing the central “fistula.” C - Immediate postoperative appearance
Figure 6: A - Two weeks postoperative. B - Second-stage procedure: correction of the earlobe shape by excising excess skin in a semi-fusiform pattern. C - Immediate postoperative appearance following the second-stage procedure
Figure 7: Patient 1, 12 months after surgery. A - Anterior view of the earlobe.
B - Posterior view of the earlobe
synthesis as well as to inhibit growth factors that may contribute to keloid recurrence.2
Radiotherapy is also a recognized adjuvant treatment for ELK surgery,4,5 helping control fibroblast proliferation, disrupt the cell cycle, and induce premature cellular senescence. Although it can be combined with intraoperative corticosteroid
Figure 8 : Patient 2, 2 years after the second-stage procedure.
A - Lateral view. 8 - Posterior view
injections, it was not used in these cases due to its limited availability and high cost.
Neither patient experienced recurrence: Patient 1 at 1 year and Patient 2 at 2 years of follow-up. Although Patient 2 had a visibly smaller earlobe postoperatively, he reported satisfaction with the aesthetic outcome and an improvement in quality
Kondo RN, Pereira BM, Miyazawa B, Souza JMF, Gubert M.
of life, having previously experienced distress due to the appearance of the keloid.
Despite the existing knowledge of extralesional excision with fistulectomy for ELK, few cases have been reported in the literature. Based on our experience, we consider this surgical technique a viable, effective treatment option, as demonstrated in the two cases presented.
CONCLUSION
Total excision with fistulectomy combined with adjuvant corticosteroid infiltration appears to be a promising treatment option for ELK, providing satisfactory aesthetic outcomes. l
REFERENCES:
1. Olewinski L, Khodaee M. Posterior Earlobe Mass. Am Fam Physician. 2018;98(10):603-4.
2. Mascarenhas MRM, Paiva JMG, Mutti LA, Vivan MM, Yarak S. Efeito da terapia combinada no tratamento do queloide auricular. Surg Cosmet Dermatol 2015;7(3):253-6.
3. Zhu Z, Shan Y, Ying L, Zheng J, Mohamed S, Ma Z. Complete earlobe keloid resection with fistulectomy. Dermatol Surg. 2015;41(1):83-6.
4. Ekstein SF, Wyles SP, Moran SL, Meves A. Keloids: a review of therapeutic management. Int J Dermatol. 2021;60(6):661-71.
5. Cheraghi N, Cognetta A Jr, Goldberg D. Radiation therapy for the adjunctive treatment of surgically excised keloids: a review. Clin Aesthet Dermatol. 2017;10(8):12-5.
AUTHOR’S CONTRIBUTION:
Rogerio Nabor Kondo 0000-0003-1848-3314
Final approval of the manuscript, study conception and design, manuscript drafting and writing, active participation in research supervision, intellectual contribution to the diagnostic and/or therapeutic management of the cases, critical manuscript revision
Barbara Messias Pereira 0000-0002-1180-7438
Final approval of the manuscript, manuscript drafting and writing, critical literature review, critical manuscript revision
Bianca Miyazawa 0009-0003-0561-8504
Final approval of the manuscript, manuscript drafting and writing, critical literature review, critical manuscript revision
João Marcos Franco de Souza 0000-0002-9297-7841
Final approval of the manuscript, manuscript drafting and writing, critical literature review, critical manuscript revision
Marina Gubert 0000-0002-9293-5019
Final approval of the manuscript, manuscript drafting and writing, critical literature review, critical manuscript revision
www.surgicalcosmetic.org.br/
Secondary correction of prominent ears with closed otoplasty
Correção secundária da orelha em abano com otoplastia fechada
Case Report
Authors:
Cinthia Trisóglio1 Silvia Maria de Souza Quaggio2
1 Faculdade de Ciências Médicas de Belo Horizonte, Medical Sciences School, Belo Horizonte (MG), Brazil
Prominent ears are a common congenital deformity, affecting around 5% of the population, in addition to harming self-esteem and psychological well-being.To report a case of closed otoplasty in a 37-year-old patient who was dissatisfied with the results of an open otoplasty performed in childhood, with recurrence and erasure of the antihelix. The closed, incisionless technique was performed with local anesthesia and Mustardé percutaneous sutures, creating the antihelix with no need for incisions. The procedure was performed in an outpatient setting, with sutures buried under the skin and no apparent stitches, followed by the use of an immobilization bandage at night for 2 months. The surgery was completed in approximately 30 minutes per ear, with no complications. The patient reported mild to moderate pain in the first few days, which was relieved with analgesics. No complications, such as hematomas or keloids, were observed at the 2- and 24-month follow-up visits.The patient was highly satisfied with the aesthetic result and modeling of the antihelix. Closed otoplasty proved to be an effective and safe alternative for correcting prominent ears, with significant aesthetic and psychological benefits. It is suitable for cases of mild to moderate deformity.
Keywords: Surgery, Plastic; Anesthesia; Minor Surgical Procedures.
RESUMO
A orelha em abano é uma deformidade congênita comum, afetando cerca de 5% da população, além de prejudicar a autoestima e o bem-estar psicológico. Relatar um caso de otoplastia fechada em uma paciente de 37 anos, insatisfeita com o resultado de uma otoplastia aberta realizada na infância, com recidiva e apagamento da anti-hélice. A técnica fechada, sem incisão, foi realizada com anestesia local e suturas percutâneas Mustardé, criando a curva anti-helicoidal sem necessidade de incisões. Procedimento realizado em ambiente ambulatorial, com suturas enterradas sob a pele e sem pontos aparentes, seguido de uso noturno de faixa para imobilização por 2 meses. A cirurgia foi concluída em cerca de 30 minutos por orelha, sem intercorrências. A paciente relatou dor leve a moderada nos primeiros dias, aliviada com analgésicos. Não foram observadas complicações, como hematomas ou queloides, nos retornos de 2 e 24 meses. A paciente apresentou alta satisfação com o resultado estético e modelação da anti-hélice. A otoplastia fechada mostrou-se uma alternativa eficaz e segura para correção de orelhas proeminentes, com benefícios estéticos e psicológicos significativos, sendo adequada para casos de deformidade leve a moderada. Palavras-chave: Cirurgia Plástica; Anestesia; Procedimentos Cirúrgicos Menores.
2 Faculdade Estadual de Medicina de São José do Rio Preto, Medical Sciences School, Ribeirão Preto (SP), Brazil
Correspondence: Cinthia Trisóglio E-mail: cinthia.trisoglio@gmail. com
Funding source: None. Conflict of interest: None.
Submission date: 10/25/2024
Final decision: 01/30/2025
How to cite this article: Trisóglio C, Quaggio SMS. Secondary correction of prominent ears with closed otoplasty. Surg Cosmet Dermatol. 2025;17:e20250416.
INTRODUCTION
Prominent ears are the most common congenital deformity of the outer ear, affecting approximately 5% of the general population. A harmonious face goes far beyond skin care alone. Correcting prominent ears to their ideal anatomy makes all the difference in improving the appearance of the face, in addition to alleviating psychological issues, boosting self-esteem, and increasing self-confidence. Several authors have described techniques for treating prominent ears. Prominent ears are mainly caused by the absence of an antihelix and/or conchal hypertrophy and anterior rotation of the lobe. More than 200 techniques have been suggested to surgically correct prominent ears. The existence of so many approaches highlights that no single technique can correct all cases and that new techniques and modifications will continue to be developed. There are 3 main groups of surgical techniques used to correct prominent ears: cartilage-cutting techniques (CCT), cartilage-sparing techniques (CST), and incisionless or closed techniques. Mustardé1 and Furnas2 were pioneers in the use of concha-scapha and concha-mastoid sutures with little or no cartilage incision, forming the basis for incisionless otoplasty, which inspired Fritsch3 and Peled4 to describe the incisionless otoplasty technique, in which permanent sutures are used to recreate the antihelix, placed percutaneously and buried through the needle holes along the way, making surgical treatment more versatile, simpler, and safer. In recent years, there have been increasing requests for minimally invasive methods to perform otoplasty. The reasons behind this development are the search for methods to minimize invasive surgical techniques and, on the other hand, to reduce postoperative risks, including hematoma and increased scarring. Peled4 published the idea of knifeless otoplasty and Fritsch3 described incisionless otoplasty in 1995. Fritsch applied his technique to prominent ears, a suture-only technique, creating a new antihelix fold with horizontal mattress sutures placed percutaneously and subcutaneously. A modification of this technique is described by Peled as “incisionless otoplasty,” combining a suture technique similar to Fritsch’s with blind puncture of the anterior antihelix through a small skin incision in the anterior tail area of the antihelix. Serdev5 stated that “Serdev Suture® transcutaneous closed approach lifts encompass the main concept of suspension and/or suture repositioning.” Nikolay uses a Deschamps aneurysm needle (30G), which is more traumatic than the custom curved syringe needle (28G) used in the reported technique. Both needles could be used to pass sutures and score the cartilage. Merck6 adopted Peled’s method with modification of the guide wire, dorsal placement of the knots, and no cartilage processing, but this technique, 4 in 1 mattress suture to fold the poorly defined antihelix, did not correct other ear deformities such as conchal hypertrophy or concha-mastoid angle. The choice of surgical technique should be customized for each patient according to a meticulous preoperative evaluation. Therefore, we report the case of a 37-year-old female patient who had previously undergone open otoplasty at the age of 7. Even so, she was still dissa-
tisfied, as the open surgery did not provide complete correction of the prominent ear. We opted for a secondary approach using the closed otoplasty technique to treat the antihelix.
METHODS
The closed otoplasty technique consists of a closed surgical approach to correct prominent ears. We perform tumescent anesthesia to promote anterior and posterior displacement of the cartilage, performing permanent percutaneous subcutaneous horizontal nonabsorbable sutures via the anterior approach and no incision. Percutaneous Mustardé mattress sutures are appropriately placed, forming the antihelix. To ensure that each suture is buried under the skin, the needle must re-enter the skin at the exact point where it exits. (Figure 1) The main indication is to correct the changes that caused the antihelix of the auricle to disappear without the need for incisions. After undergoing anamnesis, the selected patient, in an outpatient setting, with no need for sedation or general anesthesia, underwent rigorous antisepsis and placement of disposable sterile drapes. A surgical pen with a fine/thick double tip
Figure 1: Principle of closed otoplasty: whenever the suture needle enters, it must exit the skin between the surface and the perichondrium through the same puncture site and needle tract
and methylene blue ink was used to mark the new antihelix, and 3 marks were made. The anesthesia injected into the antihelix was a 1% lidocaine solution with 1/200,000 adrenaline, achieving adequate blanching and distribution of the solution in the anterior and posterior aspects of the ear, with one of the objectives being the expansion and displacement of the skin from the cartilage. A 10-minute wait was observed between the application of the anesthetic in order to increase the efficiency of the vasoconstrictive action. A 22G hypodermic needle is then used on the previous markings to percutaneously mark the cartilage at the level where the antihelix fold is to be created, being placed percutaneously following a type of horizontal Mustardé mattress suture, which we numbered points 1-2-3-4, to recreate the antihelix fold and reduce the prominence of the concha. The first point was transfixed into the skin of the posterior surface of the auricle at point 1 and passed through the subcutaneous tissue, emerging in the skin at mark 2. It then re-entered the same puncture site, now transfixing the cartilage deeply, going to point 3, emerging at 3, re-entering the same puncture site, and going to point 4 in the subcutaneous tissue. It exits at point 4, passes the suture deeply through the cartilage, without exiting the skin anteriorly, continuing to point 1, closing the suture, and ending by cutting the knot. Transfixing only the skin, it returns to the initial region, forming a “rectangular design,” Mustardé U-shaped sutures (Figure 2) and (Figure 3). It is important to note that the suture
2: Marking where the new Mustardé U-shaped sutures will be made on the erased antihelix, to create the new curvature in the cartilage
needle always enters and exits the skin between the surface and the perichondrium through the same puncture site and needle tract (Figure 1). Transfixation of the subdermal needle to hide the stitch and cut close to the skin. Note the positioning and posterior displacement of the auricle and formation of the new antihelix. We performed 2-3 sutures in the posterior region and in the anterior region along the erased antihelix. Compressive gauze and sterile micropore tape were inserted into the dressing. This technique does not involve skin resection, scraping, or incisions in the cartilage, nor does it leave visible stitches or require stitch removal. Postoperatively, the use of bandage is recommended to immobilize the ear against the head to prevent accidental folds, only at night for 2 months. Follow-up was performed through photos and patient visits to assess changes and complications, such as recurrence and infections, at 15 days, 2 months, and 24 months. The entire procedure is performed with a minimally invasive needle. For this reason, complications are minimized, as no dissection planes or skin flaps are created, nor is there any skin resection, scraping, or incisions in the cartilage, nor are there any visible stitches, and no need for stitch removal. Postoperatively, the use of bandage is recommended to immobilize the ear against the head to prevent accidental folds, only at night for 2 months. For this reason, postoperative care is minimal.
Figure 3: Demonstration of the technique (beginning in the posterior region, where 4 marks are made to perform Mustardé’s U-shaped suture. The procedure is initiated at point 1, an entry puncture is made with a 22G needle, the black 3.0 nylon suture is inserted into the subcutaneous tissue at mark 1, exits with the needle at 2, enters the same exit puncture as 2, passes the surgical thread deeply through the cartilage, exits at 3, enters the same exit point at 3, now passes the suture thread into the subcutaneous tissue, exits at 4, enters the same exit point, now passing the suture deeply into the cartilage, without transfixing the skin in the anterior portion, and closes the suture at 1, finishing with surgical knot amputation)
Figure
RESULTS
The otoplasty was performed with no incisions and, therefore, no scars, with a mean operative time of 30 minutes per ear. The entire procedure was performed with local anesthesia and no sedation. The patient reported mild to moderate pain in the first 3 days postoperatively, which was alleviated with analgesics. Healing ointment was applied to the wire entry sites for 15 days, and oral antibiotics were prescribed for 7 days. At the 2-month follow-up, no complications or adverse events such as ecchymosis, edema, necrosis, hyperesthesia, keloid, recurrence, exposure of stitches, or asymmetry were observed. Good modeling of the antihelix was observed even after 24 months, and the patient was very satisfied.
DISCUSSION
There are more than 200 techniques for correcting prominent ears. The main treatment is to correct the hypertrophic concha and shape the antihelix. In 1992, Fritsch modified the techniques from open to closed otoplasty.This surgical treatment provides many advantages for patients and surgeons due to its lower risk of complications and minimally invasive approach to correcting the ears. This new surgical approach has simplified otoplasty and made it more versatile in treating a wide range of ear deformities, especially those requiring antihelix correction. This study reports a secondary surgical case using the closed otoplasty technique in a 37-year-old female patient who had previously undergone unsuccessful open otoplasty surgery. At the time, the patient did not seek repair of the open otoplasty surgery because she had experienced trauma from the surgery in childhood, had experienced severe pain for 3 months, and had edema in her ear. She learned about this new approach and sought clarification. During the consultation, the patient was wary of the new surgical approach, but as her prominent ears still bothered her, it was explained to her that it would be a different technique, which reassured her, making her feel safe and satisfied. A new surgery was scheduled, now secondary with a closed approach. No complications occurred during the surgical procedure, and postoperatively, the patient only experienced pain within 24 hours of the procedure, which was resolved with analgesics. The results were evaluated subjectively after 15 days, 2 months, and 24 months, using preoperative and postoperative photos (Figures 4, 5, and 6), and the patient was very satisfied. (Figure 7)
CONCLUSIONS
We believe that different ear deformities should be corrected by different techniques, thus providing greater naturalness and harmony to overall appearance. The closed otoplasty technique is not a solution for all types of prominent ears, but rather for the correction of antihelix erasure, mainly in malleable cartilage with no conchal hypertrophy. This is a conservative procedure, easy to perform, easily reproducible, with low patient discomfort, and relatively no major complications. It has
Figure 4: Before performing secondary open otoplasty repair and immediately after antihelix correction using the closed otoplasty technique, i.e., incisionless
Figure 5: Lateral view of the ear before closed otoplasty and immediately after closed otoplasty
Figure 6: Postoperative results 2 months after closed otoplasty
excellent applicability in all age groups. Otoplasty goes beyond facial aesthetics. It is a procedure that promotes the patient’s well-being, restoring their self-esteem, self-confidence, and quality of life. Considering the benefits of a rapid and painless postoperative period, incisionless otoplasty clearly represents a valuable tool for promoting the individual’s overall health.This technique is intended to be another asset in the arsenal of dermatological surgery. l
REFERENCES:
1. Mustardé JC. The correction of prominent ears using simple mattress sutures. Br J Plast Surg 1963;16:170-8.
2. Furnas DW. Correction of prominent ears by concha-mastoid sutures. Plast Reconstr Surg. 1968;42(3):189–93.
4. Peled IJ. Knifeless otoplasty: how simple can it be? Aesth Plast Surg. 1995;19(3):253-5.
5. Serdev NP. Scarless serdev suture method in prominent ears. Int J Cosmet Surg. 2006;6(2):184–90.
6. Merck W. Ohrmuschelkorrektur ohne hautschnitt – die Fadenmethode von Merck. Korrektur und Rekonstruktion der Ohrmuschel. Berlim: Springer; 2017. p.153–69.
AUTHOR’S CONTRIBUTION:
Cinthia Trisóglio 0000-0001-8288-2518
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript.
Silvia Maria de Souza Quaggio 0000-0001-8199-3961
Approval of the final version of the manuscript, conception and design of the study, preparation and writing of the manuscript, acquisition, analysis and interpretation of data, effective participation in the conduct of the study, intellectual participation in the propaedeutic and/or therapeutic approach to the cases studied, critical review of the literature, critical revision of the manuscript.
Figure 7: Postoperative results 24 months after closed otoplasty
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Transposition flap for reconstruction of lower eyelid wounds adjacent to the tarsus after Mohs micrographic surgery: a case series
Retalho de transposição para reconstrução de feridas da pálpebra inferior adjacentes ao tarso após cirurgia micrográfica de Mohs: uma série de casos
Case report
Authors:
Bruna Cabral Meira Chaves1
Luciana Ballardin2
Felipe Bochnia Cerci2,3,4
1 Centro Médico Lúmen, Curitiba (PR), Brazil
2 Hospital Universitário Evangélico Mackenzie, Serviço de Dermatologia, Curitiba (PR), Brazil
3 Clinica Cepelle Mohs Curitiba, Curitiba (PR), Brazil
Skin cancers affecting the eyelid can be a reconstructive challenge due to the complexity of the local anatomy. In addition to precise eradication of the tumor, maximal preservation of the skin is essential for both functional and cosmetic outcomes. Transposition flaps represent an excellent reconstructive option, as they require few incisions and, when well planned, do not cause ectropion, a key consideration in this topography. We describe a case series of lower eyelid reconstructions adjacent to the tarsus following Mohs micrographic surgery, using transposition flaps.
Cânceres de pele que acometem a pálpebra podem ser um desafio para reconstrução devido à complexidade anatômica local. Além da erradicação precisa do tumor, deve-se também prezar pela conservação máxima da pele, tanto por razões funcionais quanto cosméticas. Os retalhos de transposição se destacam como ótima opção de reconstrução, pois exigem poucas incisões e, quando bem planejados, não causam ectrópio, o que é a prioridade nessa topografia. Descrevemos aqui uma série de casos de reconstrução de feridas da pálpebra inferior adjacentes ao tarso após cirurgia micrográfica de Mohs utilizando retalhos de transposição.
4 Universidade Federal do Paraná, Programa de Pós-Graduação em Medicina Interna e Ciências da Saúde, Curitiba (PR), Brazil
Correspondence:
Bruna Cabral Meira Chaves
E-mail: brunacabralmeira@gmail. com / brunacabral.dermato@ gmail.com
Financial support: None. Conflicts of interest: None.
Submitted on: 13/06/2024
Approved on: 25/06/2024
How to cite this article: Chaves BCM, Ballardin L, Cerci FB. Transposition flap for reconstruction of lower eyelid wounds adjacent to the tarsus after Mohs micrographic surgery: a case series. Surg Cosmet Dermatol. 2025;17:e20250379.
INTRODUCTION
One in ten skin cancers occur in the periorbital region. Within this topography, the lower eyelid is the most commonly affected subunit, representing 55% of cases.1,2 Mohs micrographic surgery (MMS) is indicated in this region because, in addition to providing a higher oncologic remission rate, it maximizes preservation of healthy tissue and reduces surgical morbidity.3 The primary objective of eyelid reconstruction is to preserve function while achieving a good aesthetic result. In this area, primary horizontal closures are rarely feasible due to the risk of ectropion. Among the various flap options, transposition flaps offer a key advantage in free-margin regions, as they redirect the tension vectors involved in the closure, helping to prevent distortion of the eyelid margin. In addition, they require less tissue displacement compared to advancement or rotation flaps, further reducing surgical morbidity.4
CASE REPORTS
We present a case series of reconstructions of surgical defects of the lower eyelid adjacent to the tarsus, involving the anterior lamella (partial thickness). In some cases, the wound also involved a small portion of the tarsus. All reconstructions were performed using transposition flaps encompassing defects located in various regions of the lower eyelid, thereby demonstrating the versatility of this technique. Twelve patients with basal cell carcinoma underwent MMS, including 11 women and 1 man, with a mean age of 55 years (range: 43 to 80). All surgeries were performed in an outpatient setting under local anesthesia with 1% lidocaine and epinephrine. In cases involving the ciliary margin, 0.5% proxymetacaine hydrochloride anesthetic eye drops were added for greater patient comfort due to the proximity to the cornea. After achieving tumor-free margins with MMS, reconstruction was planned by designing the transposition flap
to redirect vertical tension vectors into horizontal ones, thereby minimizing the risk of ectropion.
The classic rhomboid transposition flap, described by Limberg, is used to repair primary rhomboid defects with internal angles of 60º and 120º. DuFourmentel later modified Limberg’s flap by reducing the internal angles of the rhombic defects to between 60º and 90º, thereby increasing its versatility and decreasing the size of the standing cones excised.4 Due to the pronounced elasticity of periocular tissue, modifying the flap into a triangular or Banner flap—with acute internal angles between 30º and 60º, without converting the defects into a rhomboid—preserves healthy tissue and offers the additional advantage of allowing greater flexibility in positioning the donor flap. The flap can thus be designed in the orientation best suited to the local tension vectors.5 In practical terms, the lobe of the transposition flap should be designed with consideration for how the donor area will be closed. In other words, the closure vector of the donor site must not create downward traction on the eyelid.
After appropriate planning, the flap was elevated in the subdermal or subcutaneous plane, when the donor area extended into the malar region. Whenever possible, the donor site was kept within the eyelid subunit due to the similarity in skin characteristics. The secondary defect was sutured in the subcutaneous and dermal planes with 5-0 poliglecaprone and in the superficial plane with 6-0 polypropylene. Due to the limited dermal thickness in the eyelid region, the flap was primarily sutured in the superficial plane. When the wound affected the ciliary margin, closure was performed using the minimum number of sutures necessary to avoid contact with the cornea. In these cases, the suture ends were left longer and directed inferiorly to reduce ocular discomfort. All the cases showed satisfactory
A B C
Figure 1: A - Vertical tension vectors (red arrows) pull the free eyelid edge inferiorly. In this case, primary closure carries a high risk of ectropion. B - Planning of the transposition flap:B - leading edge, C - secondary arm, BAC - internal angle of approximately 30º. C - The transposition flapredirects the closure tension to the secondary defect and reorients these forces horizontally (green arrows), parallel to the tarsus, thereby eliminating downward vertical traction and reducing the risk of ectropion
Figure 2: A - Surgical wound. B - Design of the transposition flap (Banner type). C-E - Flap movement. F - Immediate post-operative appearance. G-H - Late post-operative outcome
A E B F C G D H
Figure 3: A - Surgical wound in the anterior lamella. B - Flap design. C-E - Flap movement. F - Immediate post-operative appearance. G-H - Late post-operative outcome outcomes, with preservation of both eyelid function and cosmetic appearance. No intraoperative or postoperative complications occurred, and no surgical revisions were required. Figures 1 to 6 illustrate some of these reconstructions.
DISCUSSION
In eyelid topography, beyond the precise eradication of the tumor, maximal preservation of the skin and soft tissues is essential for both functional and cosmetic reasons.1,3 However, Surg Cosmet Dermatol. 2025;v.17: n.2 apr-Jun. p.232-7.
Figure 4: A - Surgical wound in the anterior lamella at the medial canthus. B - Flap design. C-E - Flap movement. F- Immediate post-operative appearance
D E B F C D
due to the limited availability of redundant tissue in this area, there may be a temptation to reduce surgical margins when operating without intraoperative margin control, which increases the risk of inadequate excision. MMS is the recommended treatment for skin cancer of the eyelid. This technique allows for
Figure 5: A - Surgical wound in the anterior lamella in the lateral canthus.
B - Flap design.
C - Immediate post-operative appearance.
D - Late post-operative outcome
complete excision of the lesion through precise histologic control of surgical margins, resulting in higher oncologic cure.4 At the same time, MMS preserves healthy tissue, reducing wound size and facilitating reconstruction. In addition, it can help avoid full-thickness excision in smaller lesions, safely removing poorly
Figure 6: A - Delimitation of the lesion. B - Operative wound on the anterior flap. C - Flap design. D - Immediate post-operative period. E - Late postoperative period
defined tumors and reserving enucleation or exenteration for more complex cases.1-8
There are several reconstructive options following MMS in this region. The choice of repair and the surgical outcome depend, in part, on the surgeon’s knowledge of eyelid anatomy and their ability to assess the reconstructive requirements of the post-MMS defect.2 In complex full-thickness cases, a multidisciplinary approach may be necessary. Transposition flaps are a safe option, as they require few incisions and, when well planned, do not lead to ectropion—an essential consideration in this anatomical region. Furthermore, they are quick and simple to perform and, when properly executed, yield excellent results.
Transposition flaps typically recruit skin from the same eyelid subunit and, due to the characteristic movement of this technique, redirect the closure tension vectors. The leading edge of the flap should be positioned perpendicularly to the eyelid edge, as the movement of the flap toward the primary defect causes a shift in the tension vectors, distributing the tensile forces to the secondary defect (Figure 1). To close the flap, the first suture should be placed at the proximal portion of the donor area, projecting the flap into the primary defect. To avoid ectropion, the primary tension vector must be oriented horizontally, parallel to the free eyelid margin.4 Flap preparation must be meticulous to preserve adequate vascularization, but thinning the flap is essential for an optimal outcome. Thick flaps may develop trapdoor deformity, and if this does not resolve after a few months,
treatment with intralesional corticosteroid infiltration or surgical revision may be necessary.
Secondary intention healing can be useful for small defects, especially near the medial canthus. In other eyelid locations, this approach must be selected with caution, as wound contraction can lead to ectropion. Primary closure, may be appropriate for small to medium-sized defects if the tension vector is oriented parallel (or even oblique) to the eyelid margin; otherwise it is relatively contraindicated due to the risk of ectropion.2
Another reconstructive option is the full-thickness skin graft; however, contraction during the healing process may result in ectropion.2,8 Additional options include advancement and rotation flaps,2,6,7,9 which—due to vector dynamics—require larger incisions and more extensive dissection to recruit skin from the lateral face, thereby increasing surgical complexity and the risk of postoperative complications such as hematomas and bleeding, particularly in anticoagulated patients.
CONCLUSION
Transposition flaps are an important option for the repair of partial-thickness eyelid wounds adjacent to the tarsus and should be familiar to dermatologic surgeons. These flaps are safe, easy to perform, and, when properly planned, avoid extensive tissue dissection, provide adequate vascularization, and yield excellent functional and aesthetic outcomes, as demonstrated in this study. l
REFERENCES:
1. Blumenthal SR, Swick M, Bayan CA, Ramanathan D, Maher I. Complex eyelid reconstruction: a practical guide for the Mohs surgeon. Dermatol Surg. 2022;48(9):916-23.
2. Archibald LK, Gupta R, Shahwan KT, Swick M, Bakker C, Mattox AR, et al. Periorbital reconstructive techniques following Mohs micrographic surgery or excisions: a systematic review. Arch Dermatol Res. 2023;315(7):1853-61.
3. Bittner GC, Cerci FB, Kubo EM, Tolkachjov SN. Mohs micrographic surgery: a review of indications, technique, outcomes, and considerations. An Bras Dermatol. 2021;96(3):263-77.
4. Scott JF, Bordeaux JS. A conceptual approach to designing transposition flaps. Dermatol Surg. 2020;46(1):9-19.
5. Teske SA, Kersten RC, Devoto MH, Kulwin DR. The modified rhomboid transposition flap in periocular reconstruction. Ophthalmic Plast Reconstr Surg. 1998;14(5):360-6.
6. Harvey DT, Taylor RS, Itani KM, Loewinger RJ. Mohs micrographic surgery of the eyelid: an overview of anatomy, pathophysiology, and reconstruction options. Dermatol Surg. 2013;39(5):673-97.
7. Monheit G, Hrynewycz K. Mohs surgery for periocular tumors. Dermatol Surg. 2019;45 Suppl 2:S70-S8.
8. Sanchez FH, Lerner E. Mohs micrographic surgery in periocular tumors. Surg Cosmet Dermatol 2014;6(4):226-32
9. Yüce S, Demir Z, Selçuk CT, Celebioğlu S. Reconstruction of periorbital region defects: a retrospective study. Ann Maxillofac Surg. 2014;4(1):4550.
AUTHOR’S CONTRIBUTION:
Bruna Cabral Meira Chaves
0009-0009-8158-2017
Approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, data collection, analysis, and interpretation, literature review, critical review of the manuscript
Luciana Ballardin 0009-0000-2015-0629
Approval of the final version of the manuscript, preparation and writing of the manuscript, data collection, analysis, and interpretation, literature review
Felipe Bochnia Cerci
0000-0001-9605-0798
Approval of the final version of the manuscript, study design and planning, data collection, analysis, and interpretation, effective participation in research orientation, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, literature review, critical review of the manuscript
www.surgicalcosmetic.org.br/
Upper and lower blepharoplasty combined with phenol-croton oil peel for facial rejuvenation: a clinical case report
Blefaroplastia superior e inferior associada ao tratamento com peeling de fenol-cróton no rejuvenescimento facial: relato de caso clínico
Blepharoplasty is often the first facial aesthetic surgery sought by patients. However, in cases of more advanced aging, blepharoplasty alone may not achieve the desired aesthetic result, requiring the combination of additional rejuvenation techniques. Phenol-croton oil peeling is an excellent adjunct to eyelid surgery, as it effectively addresses deep rhytides.This case report describes a patient treated with combined upper and lower blepharoplasty and full-face phenol-croton oil peel, resulting in a highly satisfactory facial rejuvenation outcome.
A blefaroplastia é, frequentemente, a primeira cirurgia estética facial procurada pelos pacientes. Porém, em casos de envelhecimento mais pronunciado, a blefaroplastia isolada não é capaz de oferecer o resultado estético desejado, sendo necessária a associação com outras técnicas de rejuvenescimento. Assim, o peeling de fenol-cróton é uma alternativa excelente para complementar a cirurgia plástica palpebral, uma vez que trata as rítides profundas. Esse trabalho traz um relato de caso de paciente tratada com associação de blefaroplastia superior e inferior com peeling de fenol-cróton de face total com resultado muito satisfatório no rejuvenescimento facial. Palavras-chave: Blefaroplastia; Abrasão Química; Fenol; Óleo de Cróton; Rejuvenescimento.
3 Hospital de Olhos Hilton Rocha , Soebras, Departamento de Oftalmologia, Belo Horizonte (MG), Brazil
4 Clínica Completa, Dermatologia e Cosmiatria, Belo Horizonte (MG), Brazil
Funding support: None. Conflicts of interest: None.
Submitted on: 20/06/2024
Approved on: 21/11/2024
How to cite this article: Barbil JSF, Queiroz MVR, Santana KKR, Nogueira GC. Upper and lower blepharoplasty combined with phenol-croton oil peel for facial rejuvenation: a clinical case report. Surg Cosmet Dermatol. 2025;17:e20250381.
INTRODUCTION
Blepharoplasty is a surgical procedure aimed at rejuvenating the upper and/or lower eyelids. It is often one of the first aesthetic interventions sought by patients pursuing facial rejuvenation. Technically delicate, blepharoplasty requires careful planning and meticulous execution to achieve optimal results and minimize complications.1 Upper eyelid blepharoplasty is typically performed for both aesthetic and functional reasons, whereas lower eyelid blepharoplasty is more commonly indicated for cosmetic purposes.2
However, improving the periocular region alone may be insufficient for full facial rejuvenation, and adjuvant aesthetic treatments are often necessary. In this context, phenol-croton oil peel is an effective option for treating deep facial rhytides.3 This technique involves a deep chemical peel whose level of skin penetration depends on factors such as the volume applied and the concentration of phenol and croton oil in the formulation. When appropriately indicated and correctly performed, this procedure yields marked improvements in skin quality and wrinkle reduction compared to other methods.3
Because it reaches the reticular dermis, phenol-croton oil peel promotes the formation of a dense dermal neocollagenesis zone, where newly organized elastic fibers replace elastosis and melanin granules are reduced.4 Histologic studies of skin treated with phenol-croton oil peel have shown increased collagen density in the papillary and reticular dermis, due to the stimulation of type I and III collagen.5 As such, phenol-croton oil peels are effective in softening or eliminating deep wrinkles and may serve as valuable adjuncts to facial rejuvenation surgery.6
This report presents a clinical case of a patient with significant facial aging who was treated with combined upper and lower blepharoplasty and full-face phenol-croton oil peel, resulting in substantial aesthetic improvement. This study was reviewed and approved by the Human Research Ethics Committee (CEP) under approval number 5.608.414.
CASE REPORT
N.P.D., a 67-year-old White female from Belo Horizonte, MG, was evaluated at the oculoplastic surgery outpatient clinic of the Hilton Rocha Eye Hospital with complaints of excess skin on the upper and lower eyelids of both eyes, as well as facial wrinkles. She had a history of hypertension, type 2 diabetes, and dyslipidemia, and was taking losartan 100 mg/day, metformin 850 mg/day, and simvastatin 20 mg/day.
Dermatologic assessment revealed a pattern of aging characterized predominantly by extrinsic factors, with significant photoaging. The patient exhibited minimal facial deflation and well-defined mandibular contour (Figure 1). Oculoplastic examination showed upper and lower eyelid dermatochalasis, with prolapse of the medial fat pads in the upper eyelids and medial, central, and lateral fat pads in the lower eyelids, as demonstrated in figure 1. Snap-back and distraction tests indicated horizontal laxity of the lower eyelids.
On January 25, 2022, upper and lower blepharoplasty was performed using radiofrequency (Wavetronic 5000 – 110 volts) in “cut” mode for skin incisions (80% cut, 20% coagulation) and “blend” mode for dissection (50% cut, 50% coagulation). After asepsis, local anesthesia was administered with lidocaine and bupivacaine combined with a vasoconstrictor at 2%.
For the upper eyelids, skin incisions were made along premarked lines, preserving the orbicularis muscle, followed by resection of the medial fat pad. For the lower eyelids, a subciliary incision was made to excise a myocutaneous flap (excess skin and a band of preseptal orbicularis muscle). The medial, central, and lateral fat pads were resected. Canthopexy was performed using 5-0 polypropylene sutures, and skin closure was completed with 6-0 nylon sutures. The procedure lasted one hour and was uneventful. Sutures were removed on postoperative day 10. The result 30 days after surgery is shown in figure 2.
After 105 days, the patient underwent full-face phenol-croton oil peel. The procedure was performed in an operating room under appropriate cardiorespiratory monitoring, intrave-
Figure 1: Patient before undergoing treatment
nous hydration with Ringer’s lactate, and conscious sedation using a combination of midazolam, fentanyl, and ketamine, under the supervision of an anesthesiologist.
The phenol-croton oil solution used was Hetter’s 1.6% formula, consisting of 2.75 mL distilled water, 0.25 mL Novisol, and 2 mL of stock solution (0.08 mL croton oil and 1.92 mL of 88% phenol solution), yielding a total of 5 mL for facial application.
The technique began with facial degreasing using pure acetone, followed by demarcation of treatment zones using a white pencil or surgical marker. The face was divided into five zones: forehead, nose, perioral region, malar area, and periocular region, with careful delineation of the mandibular line.
A handmade applicator, which was a wooden stick wrapped with cotton at one end, was dipped into the solution.Then, the excess was removed, and the applicator was applied to the face. The solution was spread generously to keep the area moist, and the applicator was gently rubbed across the skin while the other hand stabilized the area. In regions with deep rhytides,
more vigorous rubbing was performed to enhance penetration. Each facial zone was treated sequentially with a 15- to 20-minute interval between applications, resulting in a total procedure time of at least one hour, which helps minimize systemic phenol toxicity.
Immediately after application, a solid white frost appeared on the skin, followed by a light gray hue. A thick layer of petroleum jelly was applied to the entire face intraoperatively. The patient was instructed to reapply petroleum jelly frequently until complete reepithelialization.
Prophylactic antiviral therapy (for herpes simplex) was initiated the day before the procedure and continued for 10 days. The peak period of discomfort typically occurs 1 to 4 hours after the procedure and may last up to 8 hours.4 For relief, the use of cool, moist compresses and fans was recommended. Reepithelialization occurred approximately 1 week after the procedure.
It is common for residual erythema to persist for 3 to 6 months following treatment, as shown in Figure 3.4 6 months after completing treatment, the patient exhibited a highly satisfactory outcome (Figure 4).
Figure 2: Patient one month after upper and lower blepharoplasty
Figure 3: Thirty days after full-face 1.6% phenol-croton oil peel.
DISCUSSION
In patients with deep periocular and facial rhytides, isolated upper and lower blepharoplasty may not provide the desired level of facial rejuvenation. Therefore, combining eyelid surgery with other aesthetic procedures is often necessary to enhance overall outcomes. Full-face phenol-croton oil peel is an excellent adjunctive treatment option; however, it should be reserved for patients with lower Fitzpatrick phototypes (I, II, or III) and fixed deep rhytides that no longer respond to conventional therapies such as botulinum toxin injections.
Importantly, phenol is cardiotoxic. It can prolong the QT interval (>450 ms or an increase of 20-30 ms from baseline) and may trigger minor arrhythmic events (e.g., isolated atrial extrasystoles) as well as more significant ventricular arrhythmias such as ventricular bigeminy and nonsustained ventricular tachycardia.7 The risk of cardiotoxicity increases when phenol is applied to an area greater than one cosmetic unit, or more than 0.5% of total body surface area. Although phenol-croton oil peel has been associated with transient intraoperative QT prolongation, no clinically significant arrhythmias were observed. Nevertheless, due to the potential interaction of phenol with various medications – including analgesics, antibiotics, diuretics, antifungals, antipsychotics, and antidepressants – further investigation is warranted to establish clear safety parameters.7 In such cases, it is recommended that the procedure be performed in an operating room under continuous electrocardiographic monitoring and with appropriate air ventilation or exhaust systems. Substantial intravenous hydration during the procedure is also advised.4
Full-face phenol-croton oil peel may be safely performed in conjunction with blepharoplasty as long as transcutaneous lower eyelid surgery is not performed. This precaution is due to the risk of postoperative eyelid retraction resulting from the combined effect of surgical skin excision and anterior lamella contraction induced by the peel. Thus, phenol-croton oil peeling is best combined with either isolated upper blepharoplasty or with lower blepharoplasty performed via a transconjunctival approach, where only the prolapsed fat pads are excised, and skin treatment is exclusively managed by the peel.
Additionally, for patients with prominent periocular rhytides who do not wish to undergo full-face peeling, a phenol-croton oil peel can be applied to the periocular region in a localized fashion. Because the area involved is smaller, this localized approach can be safely performed in an outpatient setting.
CONCLUSION
Full facial rejuvenation is an increasingly common demand in dermatology, plastic surgery, and oculoplastic practice. To achieve more effective outcomes, a combination of treatments is often required to address skin laxity, improve skin quality, and, in some cases, restore volume in areas affected by the aging process. Thus, the present case demonstrated the effectiveness of combining blepharoplasty with phenol-croton oil peel for achieving significant facial rejuvenation in the patient described. l
Figure 4: Patient six months after phenol-croton oil peel
1. Alghoul M. Blepharoplasty: anatomy, planning, techniques, and safety. Aesth Surg J. 2019;39(1):10–28.
2. Bhattacharjee K, Misra DK, Deori N. Updates on upper eyelid lepharoplasty. Indian J Ophthalmol. 2017;65(7):551–8.
3. Cortez EA, Fedok FG, Mangat DS. Chemical peels: panel discussion. Facial Plast Surg Clin North Am. 2014;22(1):1–23.
4. Wambier CG, Lee KC, Soon SL, Sterling JB, Rullan PP, Landau M, et al. Advanced chemical peels: phenol- croton oil peel. J Am Acad Dermatol. 2019;81(2): 327–36.
5. Cardoso F, Moura RD, Pilar E, Moura I, Miot HA, Costa A. Phenol-croton oil peel enhances type-1 and type-3 collagen amounts by stimulating SIRT-6 and SIRT-7. Int J Dermatol. 2022;61(2):e71– 4.
6. Ozturk CN, Huettner F, Ozturk C, Bartz-Kurycki MA, Zins JE. (2013). Outcomes assessment of combination face lift and perioral phenol-croton oil peel. Plast Reconstr Surg. 2013;132(5):743e–53e.
7. Wambier CG, Wambier SPF, Pilatti LEP, Grabicoski JA, Wambier LF, Schmidt A. Prolongation of rate-corrected QT interval during phenol-croton oil peels. J Am Acad Dermatol. 2018;78(4):810-2.
AUTHOR’S CONTRIBUTION:
Juliana Senna Figueiredo Barbi
0000-0001-6888-0495
Final approval of the manuscript, study conception and design, active participation in research supervision, critical revision of the manuscript.
Marina Vieira Rodrigues Queiroz
0000-0001-5544-458X
Final approval of the manuscript, study conception and design, manuscript drafting and writing, intellectual contribution to the diagnostic and/ or therapeutic approach, critical literature review, critical revision of the manuscript.
Karoline Kalinca Rabelo Santana
0000-0002-6744-8112
Final approval of the manuscript, manuscript drafting and writing, data acquisition, analysis, and interpretation, critical literature review.
Gustavo Carneiro Nogueira
0000-0002-0602-3241
Final approval of the manuscript, data acquisition, analysis, and interpretation, intellectual contribution to the diagnostic and/or therapeutic approach.
www.surgicalcosmetic.org.br/
Case report: the importance of nail transillumination in the diagnosis and topographic assessment of subungual glomus
tumor
Relato de caso: a importância da transiluminação ungueal no diagnóstico e avaliação topográfica do tumor glômico subungueal
Case report
Authors:
Micaelly Samara Meneses Santos1
José Roberto Pegas1
Raissa Piagentini de Andrade1
Leonardo Silva Grassi1
Vanessa Cristina Coimbra1
Bianca Sousa de Almeida Neves1
1 Complexo Hospitalar Padre Bento de Guarulhos, Serviço de Dermatologia, Guarulhos (SP), Brazil
Glomus tumor is a rare, benign neoplasm typically found in areas with a high concentration of glomus bodies. It presents with a characteristic clinical triad: paroxysmal pain, cold sensitivity, and localized tenderness. We report the case of a patient with clinical suspicion of a glomus tumor, in which transillumination played a crucial role in diagnosis, surgical planning, and rapid pain relief. This case highlights the importance of maintaining a high index of clinical suspicion and the utility of transillumination for both diagnosis and therapeutic planning – particularly in settings where high-frequency ultrasound or magnetic resonance imaging is not readily available.
Keywords: Glomus Tumor; Transillumination; Nail Diseases; Surgical Procedures, Operative.
RESUMO
O tumor glômico é uma neoplasia benigna e rara, em geral, localizada em áreas com grande quantidade de corpos glômicos. A clínica é a tríade característica: dor paroxística, sensibilidade ao frio e dor a palpação local. Relatamos o caso de um paciente com suspeita clínica de tumor glômico, no qual o método de transiluminação foi ímpar para auxílio diagnóstico, planejamento cirúrgico e rápido controle álgico. Ressalta-se a importância da alta suspeição clínica e da transluminação no diagnóstico e planejamento terapêutico, podendo ser útil principalmente em serviços em que a ultrassonografia de alta frequência ou a ressonância magnética são de difícil acesso. Palavras-chave: Tumor Glômico; Transiluminação; Doenças da Unha; Procedimentos Cirúrgicos Operatórios.
Funding support: None. Conflicts of interest: None.
Submitted on: 24/06/2024
Approved on: 15/08/2024
How to cite this article: Santos MSM, Pegas JR, Andrade RP, Grassi LS, Coimbra VC, Neves BSA. Case report: the importance of nail transillumination in the diagnosis and topographic assessment of subungual glomus tumor. Surg Cosmet Dermatol. 2025;17:e20250382.
INTRODUCTION
Glomus tumor was first described by William Wood in 1812. It is a rare, benign, slow-growing tumor derived from structures known as glomus bodies. These are neuromyoarterial structures composed of arteriovenous anastomoses responsible for thermoregulation by controlling blood flow to the skin. They are found in the dermis throughout the body, but are most concentrated in the digital pulp, particularly in the subungual nail beds.1,5
Glomus tumors are considered tumors of young individuals, with a higher prevalence among females and an average age at diagnosis of around 40 years. Studies show that the time from symptom onset to diagnosis typically ranges from 3.3 to 5 years. Clinically, these tumors are characterized by hyperesthesia and well-localized pain, which intensifies with exposure to cold temperatures. The classic triad suggestive of diagnosis includes paroxysmal lancinating pain, cold sensitivity, and precise localization of tenderness on palpation. Nail dystrophy and/or mild discoloration of the nail plate (bluish or pinkish hue) may also be observed.2,3
Definitive diagnosis is made through histopathological examination. Auxiliary methods for preoperative identification include transillumination, onychoscopy, high-frequency ultrasound, and magnetic resonance imaging (the gold standard).3,4
This study aims to report the case of a young patient with clinical suspicion of a glomus tumor, in which transillumination — a method considered highly specific — was instrumental for diagnostic support, prompt tumor excision, and effective pain control.
METHOD AND RESULTS
Information was obtained through medical record review and photographic documentation, with the patient’s consent.
A 22-year-old male patient reported pain in the left fifth digit for 6 years, with progressive worsening. Initially, the pain occurred only during movement but later evolved to occur even at rest. On physical examination, he presented with intense pain upon palpation of the nail plate of the left fifth digit, which prevented precise tumor localization during the preoperative assessment.
In the operating room, transillumination using a mobile phone flashlight revealed a translucent, spherical structure measuring approximately 4 mm in diameter (Figure 1). Based on clinical history and physical examination, a glomus tumor was suspected. Nail transillumination proved essential for preoperative localization, eliminating the need for additional imaging tests.
The patient underwent surgical exploration of the area guided by the light-assisted technique. A pinkish, rounded lesion with a smooth and regular surface — consistent with a glomus tumor — was identified (Figures 2 and 3). The lesion was excised, and the specimen was sent for histopathological analysis to confirm the diagnosis.
DISCUSSION
Glomus tumor is an uncommon neoplasm with benign behavior. It is a neurovascular mass derived from glomus bodies located in the reticular dermis. These bodies are arteriovenous anastomoses found throughout the body and are involved in thermoregulation.8 Although they may also be found in the central nervous system, gastrointestinal tract, and genital organs, glomus bodies are most commonly located in the digital pulp — especially within the subungual nail beds of the hands. Approximately 65% of glomus tumors are found in this region.2
The typical presentation is a solitary lesion in the subungual or periungual region. Clinically, it is defined by the classic triad of paroxysmal lancinating pain, localized tenderness, and hypersensitivity to cold. Except for subtle changes in nail color, the lesion usually has a normal macroscopic appearance. The pathophysiological mechanism of pain is not yet fully understood; however, it may involve myofilament contraction in response to temperature changes as well as the involvement of nerve fibers, mast cells, and cyclooxygenase-2. Indeed, the tumor’s pathogenesis remains poorly understood.9,10
Figure 1: Nail transillumination
Diagnosis is essentially clinical and may be supported by complementary tests such as X-ray, magnetic resonance imaging (MRI), arteriography, ultrasound, and transillumination. The clinical signs and symptoms are typically sufficient to raise suspicion and justify surgical intervention.11 In a case series (2007–2009) involving 21 patients who underwent surgical excision, a variety of tests were used, including the “pin test” (pain upon percussion of the tumor area), thermal sensitivity test, and nail transillumination. In the latter, 85.7% of cases presented a bluish-violet or pink nodule in the subungual bed.2
The transillumination technique involves the use of a bright light source placed beneath the nail in a completely dark room. The tumor area appears as a distinct image, helping to estimate its size.4,8 In the present case, this method enabled visualization of a well-defined, rounded, lighter-colored image compared to the surrounding nail bed, indicating the probable tumor location without the need for further imaging. Intraoperatively, the lesion was found precisely in the area identified through transillumination, demonstrating the practicality, low cost, and
Despite its advantages, transillumination is less effective in detecting multiple overlapping lesions and cannot differentiate the etiology of lesions, unlike imaging techniques such as ultrasound or MRI.15,16 There are reports of patients undergoing surgery only after MRI evaluation, and in one-third of these cases, the imaging failed to identify the tumor, resulting in false-negative outcomes. This reinforces the importance of clinical evaluation over reliance on imaging in cases of suspected glomus tumor.12
Differential diagnoses include hemangiopericytoma, neuroma, schwannoma, gout, osteoarthritis, subungual melanoma, and chronic paronychia. The treatment is primarily surgical. Two main techniques are described in literature: transungual and periungual approaches. Both are performed under local and regional anesthesia. The periungual approach, used in this case, is indicated for lesions located in the nail pulp or superficially in the subungual bed.
Possible surgical complications include nail deformity and tumor recurrence.14 In this case, the procedure was preceded by digital block anesthesia with 2% lidocaine at the base of the finger, along with distal wing block. A subtotal nail detachment was performed, preserving adherence on the contralateral nail fold. After trimming the nail at the level of the distal matrix (lunula), the nail bed became visible. A semilunar incision was made
at the hyponychium, followed by dissection of the bed toward the lunula, where a single, well-circumscribed, rounded lesion was identified. It was carefully separated from the surrounding tissue.
Simple sutures were used to close the nail bed and to reposition and secure the detached nail fragment (Figure 4). The excised lesion was sent for histopathological examination, which later confirmed the diagnosis of glomus tumor.
CONCLUSION
Glomus tumor is a rare, benign neoplasm typically found in areas with a high concentration of glomus bodies, such as the subungual region and digital pulp. It presents with the classic clinical triad of paroxysmal pain, cold sensitivity, and localized tenderness. Nail dystrophy and/or slight discoloration (ranging from pink to violet) may also be observed.
Diagnosis is based on clinical suspicion and must be confirmed by histopathological examination. This tumor type often causes significant discomfort, requiring prompt management. As demonstrated in our case, the transillumination test — a practical, quick, and low-cost tool — can be highly valuable for supporting diagnosis and guiding early therapeutic planning in patients with clinical suspicion. It is especially useful in settings where advanced imaging techniques such as high-frequency ultrasound or magnetic resonance imaging (the gold standard) are not readily available. l
REFERENCES:
1. Kim SW, Jung SN. Glomus tumour within digital nerve: a case report. J Plas Reconstr Aesthet Surg. 2011; 64(7):958-60.
2. Puentes Buendia GP, Jimenez Uribe WA, Facciolli D, Rodriguez Florez JM, Gervais J. Tumor glômico: um diagnóstico fácil ou difícil? Rev Bras Cir Plast. 2010;25(3):439- 42.
3. Grover C, Jayasree P, Kaliyadan F. Clinical and onychoscopic characteristics of subungual glomus tumor: a cross‐sectional study. Int J Dermatol.2021;60(6):693-702.
4. Tang CY, Tipoe T, Fung B. Where is the lesion? Glomus Tumours of the hand. Arch Plast Surg. 2013;40(5):492-5.
5. McDermott E, Weiss A. Review Glomus Tumors. J Hand Surg. 2006;31(8):1397-1400.
6. Lin YC, Hsiao PF, WuYH, Sun FJ, Scher RK. Recurrent digital glomus tumor: analysis of 75 cases. Dermatol Surg. 2010;36(9):1396-1400.
7. Lin S, Dumanian G. Benign hand tumors. Medscape; 2011.
8. Honsawek S, Kitidumrongsook P, Luangjarmekorn P, Pataradool K, Thanakit V, Patradul A. Glomus tumors of the fingers: expression of vascular endothelial growth factor. World J Orthop. 2016;7(12):843–6.
9. Samaniego E, Crespo A, Sanz A. Key diagnostic features and treatment of subungual glomus tumor. Actas Dermosifiliogr. 2009;100(10):875-82.
10. Sun Y, Ruiqun QI, Wu Z, Zhang X, Niu J. The clinicopathologic and immunohistochemical features of 60 cutaneous glomus tumor: a retrospective case series study. An Bras Dermatol. 2024;99(2):238-24.
11. Cigna E, Carlesimo B, Bistoni G, Conte F, Palumbo F, Scuderi N. The value of clinical diagnosis of digital glomus tumors. Acta Chir Plast. 2008;50(2):55-8.
12. Trehan SK, Athanasian EA, DiCarlo EF, Mintz DN, Daluiski A. Characteristics of Glomus Tumors in the hand not diagnosed on magnetic resonance imaging. J Hand Surg. 2015;40(3):542-5.
13. 13. Suhett RP, Ger vais Filho J, Souza MMC, Buttner AA, Janin B, Santos EA. Tumor Glômico: o que é e como tratar? Rev Bras Cir Plast. 2012;27(3 SUPPL.1):96.
14. Abidin MA, Kitta MI, Nong I, Rahmansyah N, Johan MP. Diagnosis and surgical approach in treating glomus tumor distal phalanx left middle finger: a case report. Int J Surg Case Reports. 2023:108:108426.
15. Quinto-González KL, Espinosa-Gutiérrez A, Hernández-Méndez-Villamil E, Borjón-Cisneros AE. [Glomus Tumor of subungual presentation in the thumb and use of ultrasound in its diagnosis. Case report and literature review]. Acta Ortop Mex. 2023;37(6):368-71. Spanish.
16. Tsiogka A, Belyayeva, Sianos S, Rigopoulos D. Transillumination: a diagnostic tool to assess Subungual Glomus Tumors. Skin Appen Dis.2021;7(3):231-3.
17. Chen L, Gao YH, Chen J, Yao YJ, Wang R, Yu Q, et al. Diagnosis of Subungual Glomus Tumors with 18MHz ultrasound and CDFI. Sci Rep. 2020;10(1):17848.
18. Saaiq M. Presentation and management outcome of Glomus Tumors of the hand. Arch Bone Joint Surg. 2021;9(3): 312.
AUTHOR’S CONTRIBUTION:
Micaelly Samara Meneses Santos
0009-0001-0314-9033
Final approval of the manuscript; study conception and design; manuscript drafting and writing; data collection, analysis, and interpretation; intellectual contribution to diagnostic and/or therapeutic management of the case; critical review of the literature; critical review of the manuscript.
José Roberto Pegas
0000-0002-2541-6008
Final approval of the manuscript; study conception and design; manuscript drafting and writing; data collection, analysis, and interpretation; active research supervision; intellectual contribution to diagnostic and/or therapeutic management of the case; critical review of the literature; critical review of the manuscript.
Raissa Piagentini de Andrade
0009-0003-9250-9065
Final approval of the manuscript; study conception and design; manuscript drafting and writing; data collection, analysis, and interpretation; intellectual contribution to diagnostic and/or therapeutic management of the case; critical review of the literature; critical review of the manuscript.
Leonardo Silva Grassi
0000-0003-1629-9476
Final approval of the manuscript; study conception and design; manuscript drafting and writing; data collection, analysis, and interpretation; intellectual contribution to diagnostic and/or therapeutic management of the case; critical review of the literature; critical review of the manuscript.
Vanessa Cristina Coimbra
0009-0009-2583-0178
Final approval of the manuscript; study conception and design; manuscript drafting and writing; data collection, analysis, and interpretation; intellectual contribution to diagnostic and/or therapeutic management of the case; critical review of the literature; critical review of the manuscript.
Bianca Sousa de Almeida Neves 0000-0002-2921-6281
Final approval of the manuscript; study conception and design; manuscript drafting and writing; data collection, analysis, and interpretation; intellectual contribution to diagnostic and/or therapeutic management of the case; critical review of the literature; critical review of the manuscript.
www.surgicalcosmetic.org.br/
Late-onset complication after polymethyl methacrylate (PMMA) injections: diagnosis
and treatment
Complicação tardia após aplicação de PMMA: diagnóstico e tratamento
Case report
Authors:
Célia Luiza Petersen Vitello Kalil1,2
Augusto Casagrande1,3
Clarissa Reinehr1,4
Julia Frota Variani1
1 Dermatological Clinic Dr. Celia Kalil, Dermatologist Physician, Porto Alegre (RS), Brazil
2 Director of the Dermatological Clinic Dr. Celia Kalil, Director of the Dermatological Clinic Dr. Celia Kalil, Porto Alegre (RS), Brazil
At the beginning of dermal filler use, which started with fat grafts, a variety of products were tested for this purpose, from temporary to permanent fillers. The decision to use polymethyl methacrylate (PMMA) as a permanent dermal filler should be considered with caution. Keywords: Polymethyl Methacrylate; Plastics; Cosmetic Industry.
RESUMO
Desde o início do uso de preenchedores, cujo primeiro representante foi enxerto de gordura corporal, diferentes produtos foram testados para esta proposta: tanto substâncias temporárias, quanto substâncias permanentes. A escolha da aplicação do polimetilmetacrilato (PMMA) como um preenchedor permanente deve ser cautelosa. Palavras-chave: Polimetil Metacrilato; Cirurgia Plástica; Indústria Cosmética.
3 Hospital de Pronto Socorro de Porto Alegre, Plastic Surgeon, Porto Alegre (RS), Brazil
4 Federal University of Rio Grande do Sul, Postgraduate Program in Medicine: Medical Sciences, MSc, PhD in Medical Science at Federal University of Rio Grande do Sul, Porto Alegre (RS), Brazil
Correspondence: Julia Frota Variani E-mail: jfvariani@gmail.com
Funding: None.
Conflicts of interest: None.
Submitted on: 06/26/2024
Final decision: 07/25/2024
How to cite this article: Kalil CLPV, Casagrande A, Reinehr C, Variani JF. Late-onset complication after polymethyl methacrylate (PMMA) injections: diagnosis and treatment. Surg Cosmet Dermatol. 2025;17:e20250383.
CASE REPORT
A 67-year-old woman presented with facial edema in areas previously treated with polymethyl methacrylate (PMMA) injections 16 years earlier by another physician (Figure 1). The patient reported that the edema had started 6 months previously, when she sought medical attention and was treated with antibiotics and corticosteroids, with poor clinical response. The patient was evaluated by a plastic surgeon for surgical removal of the PMMA, which was scheduled to be performed in two consecutive sessions. Histopathological analysis of the excised tissue revealed marked chronic inflammation with amorphous material, connective tissue fibrosis, and muscle and salivary ac-
Figure 1: Facial edema in the area of PMMA injections, 16 years after application
Figure 2: Histopathological analysis showing marked chronic inflammation with amorphous material (hematoxylin and eosin, 40X)
Figure 3: Two-year follow-up examination showing complete resolution in the surgically treated area
cessory glands covered with squamous mucosa (Figure 2). Forty days after the first surgical session, the patient experienced a recurrence of edema and erythema, and an oral corticosteroid was restarted (prednisone 60 mg for 3 days, tapered to 40 mg for 7 days, 30 mg for 7 days, and finally 20 mg for 7 days). After the symptoms were controlled, the second procedure was performed. At the 2-year follow-up examination after completion of both procedures, the patient showed no signs of facial edema or erythema (Figure 3).
DISCUSSION
Following the initial use of dermal fillers, which started with fat grafts, a variety of products have been used for this purpose, from temporary to permanent fillers. PMMA is a low-cost thermoplastic material composed of microspheres suspended in a collagen matrix that offers long-lasting results. Within 1 to 3 months post-PMMA injection, the collagen carrier is absorbed, and new collagen is deposited by the host to encapsulate and engulf the remaining PMMA particles (fibroplasia).1,2 The main issue with PMMA is its permanence, which increases patient susceptibility to foreign body reactions, with an approximate
1.5% probability of granuloma formation, which can be triggered by systemic illness or orofacial infection/surgery. Treatment options for filler reactions include systemic anti-inflammatories, antibiotics, hyaluronidase, intralesional triamcinolone with 5-fluorouracil, and surgical excision.3 Our patient’s clinical response to oral and intralesional corticosteroids was not sustained, prompting a discussion with the patient about the possibility of surgical removal of PMMA in an attempt to promote a sustained response. We identified only one previously published study that addressed the surgical excision of facial inflammatory nodules caused by PMMA. This retrospective review described 9 cases of periorbital PMMA nodules that were successfully treated with surgical excision, improving edema, erythema, and nodularity.4 The choice of PMMA injection as a dermal filler requires careful consideration, and nonpermanent fillers should generally be favored. Patients with a history of PMMA injections should be carefully evaluated before any subsequent cosmetic procedures, and imaging techniques should be used whenever possible, such as ultrasonography. It is also essential for dermatologists to be aware of the clinical management of PMMA injection complications and to refer patients to plastic surgeons for surgical removal if necessary. l
REFERENCES:
1. Ibrahim O, Dover JS. Delayed-onset nodules after polymethyl methacrylate injections. Dermatol Surg. 2018;44(9):1236-8.
2. Jones DH. Semipermanent and permanent injectable fillers. Dermatol Clin. 2009;27(4):433-44.
3. Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E. Adverse reactions to injectable soft tissue permanent fillers. Aesthetic Plast Surg. 2005;29(1):34-48.
4. Limongi R, Tao J, Borba A, Pereira F, Pimentel A, Akaishi P, et al. Complications and management of polymethylmethacrylate (PMMA) injections to the midface. Aesthet Surg J. 2016;36(2):132-5.
Conception and design of the study, Intellectual participation in propaedeutic and/or therapeutic approach to studied cases, Critical review of the literature
Augusto Casagrande
0009-0008-3364-751X
Intellectual participation in propaedeutic and/or therapeutic approach to studied cases
Clarissa Reinehr
0000-0003-1811-4519
Approval of the final version of the manuscript, Preparation and writing of the manuscript, Effective participation in the conduct of the study, Intellectual participation in propaedeutic and/or therapeutic approach to studied cases
Julia Frota Variani 0000-0002-3420-6352
Conception and design of the study, Preparation and writing of the manuscript, Effective participation in the conduct of the study
www.surgicalcosmetic.org.br/
Foreign body reaction to the stinger of mandi (Pimelodus maculatus) simulating squamous cell carcinoma
Reação de corpo estranho ao ferrão do mandi (Pimelodus maculatus) simulando carcinoma espinocelular
Fish-related injuries (ichthyism) are common among fishermen. The mandi catfish (Pimelodus maculatus) is a freshwater species that uses, as a defense mechanism, the insertion of spines equipped with venom glands, characterizing an active venomous ichthyism. In a series of 200 ichthyism cases recorded in rivers and lakes across Brazil, approximately 40% were caused by mandi catfish and other catfish species. We report the case of a patient with a “nonhealing wound” on the left leg for 5 months following local trauma. The initial diagnosis of squamous cell carcinoma was later revised to a foreign body reaction caused by the spine of the mandi catfish.
1 Universidade de Taubaté, Medicina, Taubaté (SP), Brazil
2 HUMANITAS - Faculdade de Ciências Médicas, Medicina - São José dos Campos (SP), Brazil
3 Hospital Municipal Universitário de Taubaté, Dermatologia, Taubaté, (SP), Brazil
RESUMO
Acidentes com peixes (ictismo) são frequentes entre pescadores. O mandi (Pimelodus maculatus) é um bagre de água doce que utiliza, como mecanismo de defesa, a introdução de ferrões dotados de glândulas de peçonha, caracterizando um ictismo ativo e peçonhento. Em uma série de 200 casos de ictismo registrados em rios e lagos do Brasil, aproximadamente 40% foram provocados por mandis e bagres. Relatamos o caso de um paciente com uma “ferida que não cicatrizava” na perna esquerda há 5 meses, após trauma local. O diagnóstico inicial de carcinoma espinocelular foi posteriormente redefinido como reação de corpo estranho ao ferrão do mandi. Palavras-chave: Reação a Corpo Estranho; Carcinoma de Células Escamosas; Ferimentos e Lesões; Peixes Venenosos.
Correspondence:
Pedro Henrique Ramalho Bafume E-mail: bafumepedro@gmail.com
Funding: None.
Conflict of interest: None.
Submission date: 05/26/2024
Final decision: 07/15/2024
How to cite this article: Bafume PHR, Burgos Ghirello GA, Azevedo JLS, Silva MF, Lima EMA, Ferreira FR. Foreign body reaction to the stinger of mandi (Pimelodus maculatus) simulating squamous cell carcinoma. Surg Cosmet Dermatol. 2025;17:e20250374.
INTRODUCTION
Fish-related accidents are common among both recreational and professional fishermen. 1 Known as ichthyism, these accidents can be classified as either active or passive. Venomous, or acanthotoxic, ichthyism occurs when the fish inserts a spine into the victim. This spine, typically serrated, is covered by a tegumentary sheath beneath which venom glands are located.
In Brazil, venomous fish-related injuries caused by spines located on the tail are mainly attributed to stingrays. However, there are also species with spines on the dorsal and pectoral fins, such as catfish, scorpionfish, and the toadfish (niquim), all marine species, as well as the mandi catfish, which is freshwater.2
In a series of 200 fish-related accidents documented by Haddad Junior in rivers and lakes across Brazil, approximately 40% were caused by mandi catfish and other catfish species.3 Pimelodus maculatus, also known as mandi-amarelo, mandi-guaçu, mandiuva, mandi-pintado, or mandiú, is a freshwater catfish species belonging to the family Pimelodidae. Although literature describes it as native to the São Francisco and Paraná river basins, this species is found in nearly all Brazilian hydrographic basins.4
Clinically, lesions may range from simple skin lacerations to arterial and nerve damage, potentially leading to symptoms such as vertigo, edema, erythema, local hemorrhage, and even late manifestations such as infections.5
We report the case of a patient with a “nonhealing wound” on the left leg for 5 months following local trauma, initially diagnosed as squamous cell carcinoma (SCC), but later redefined as a foreign body reaction to the spine of mandi catfish.
CASE REPORT
A 62-year-old white male patient, retired, born and residing in the city of Taubaté, state of São Paulo (SP), sought care at the Dermatology Department complaining of a “lump” on his left leg for approximately 30 to 40 days. He reported a “sting” at the site 5 months earlier, which occurred while fishing on the banks of the Paraíba do Sul River. Since then, the lesion had not healed, progressing with recurrent episodes of inflammation and, more recently, the appearance of a verrucous, friable nodule (Figure 1).
The patient had undergone two courses of systemic antibiotic therapy but was unable to recall the specific medications used. He had also undergone drainage at an urgent care facility. Because of initial clinical suspicion of SCC, with possible differential diagnoses including deep mycoses and other cutaneous granulomatous diseases, surgical excision of lesion was proposed.
During the surgical procedure, a tract leading to the subcutaneous tissue was observed. The initial nodule was excised and sent for histopathological examination, and the procedure was subsequently interrupted. The patient was referred for radiography and ultrasonography, which revealed a linear structure measuring approximately 2.5 × 0.2 cm, highly echogenic, with a well-defined posterior acoustic shadow, consistent with a foreign body (Figure 2).
Figure 1: Verrucous, friable nodule partially covered by a hemorrhagic crust on the left leg
Histopathological examination revealed an exuberant chronic suppurative inflammatory process, associated with areas of old hemorrhage and scar fibrosis in the dermis and subcutaneous tissue, thereby supporting the diagnosis of a foreign body reaction and ruling out neoplasia.
A new surgical approach was performed, this time broader and deeper, guided by imaging findings. During the procedure, a serrated structure with an osseocartilaginous consistency was identified and recognized by the patient himself as the spine of a mandi catfish (Figures 3 and 4).
DISCUSSION
Ichthyism is the term used to describe accidents involving marine or freshwater animals. In addition to the main forms — active (caused by stings or bites) and passive (through ingestion) — other mechanisms have also been described, such as those involving electric discharges or the entry of these animals into natural orifices of bathers.5,6
The fish involved in this case report — the mandi catfish — use venom inoculation as a defense mechanism and belong to a subgroup of species classified as venomous. These fish possess three serrated spines located on the dorsal fin and both pectoral
Figure 2: Ultrasound image – A - Linear structure measuring approximately 2.5 × 0.2 cm, highly echogenic, with a well-defined poterior acoustic shadow, consistent with a foreign body.
B - Enlarged detail
fins, covered by a tegumentary sheath beneath which venom glands are located.6
Accidents involving aquatic animals are medical emergencies and represent a public health issue in Brazil, with a high incidence among fishermen due to the nature of their work. The severity of these accidents varies according to several factors, including the extent of the lesion, the affected site, secondary infections, and envenomation — this last one being more common with certain species.5
The lack of knowledge, inadequate dissemination of information, and absence of preventive measures contribute to the persistence of this condition, which stands as the main occupational hazard among fishermen. Fish-related injuries typically occur when victims step on the animals, remove hooks or harpoons, or handle them.7
In this case, the patient’s inability to recall the exact moment of accident and the confusion with a sting from another venomous animal contributed to a delayed diagnosis and greater complexity in treatment. The clinical course of ichthyism vic-
tims can be highly variable, including inflammation, recurrent infections, chronic pain, nodules, abscesses, and granulomas — often associated with the persistence of foreign bodies.5
A foreign body granuloma is an inflammatory reaction to immunologically inert materials, which may be exogenous (e.g., suture threads, talc, cotton fibers, metals) or endogenous (e.g., keratin, cholesterol, hair fragments).8
Figure 3: Spine of Pimelodus maculatus
Figure 4: Immediate postoperative appearance
The patient in this case presented a foreign body reaction to the spine of a mandi catfish, which, in its clinical course, mimicked SCC, manifesting as a verrucous, friable nodule. This scenario highlights the importance of histopathological examination for diagnostic clarification. Since cutaneous lesions caused by ichthyism can mimic various other dermatoses and present in different forms,4 this case report emphasizes the importance of persistence in diag-
nostic investigation and the critical role of the physician in conducting a thorough medical history and physical examination. Among the differential diagnoses, the local epidemiology and characteristics of the population being treated must be included.
Acknowledgments
We thank Dr. Rui Fernando Faria de Assis for kindly providing the ultrasound images used in this study. l
REFERENCES:
1. Kaar CRJ, Nakanishi AK. Recreational and commercial catfishing injuries: a review of the literature. Wilderness Environ Med. 2017;28(4):348-54.
2. Nogueira T. Ictismo - acidentes causados por peixes [Internet]. InfoEscola. 2024.
3. Haddad Jr V. Animais aquáticos de importância médica no Brasil. Rev Soc Bras Med Trop. 2003;36(5):591-7.
5. Ajmal N, Nanney LB, Wolfort SF. Catfish spine envenomation: a case of delayed presentation. Wilderness Environ Med. 2003;14(2):101-5.
6. Manual de diagnóstico e tratamento de acidentes por animais peçonhentos. 2nd ed. - Brasília: Fundação Nacional de Saúde; 2001.
7. Haddad Jr V. Atlas de animais aquáticos perigosos do Brasil: guia médico de identificação e tratamento. São Paulo: Roca; 2000.
8. Meyer TN, Oliveira LR, Almeida SMCG, Ribeiro-Silva A. Reação de corpo estranho ao preenchimento de poliamida na face. Rev Bras Cir Plast. 2016;31(3):433-5.
AUTHOR’S CONTRIBUTION:
Pedro Henrique Ramalho Bafume
0009-0005-6624-3667
Approval of final version of the manuscript, Study conception and design, Manuscript drafting and writing, Data collection, analysis, and interpretation, Critical review of literature
Guilherme Andretta de Burgos Ghirello
0009-0000-9923-6782
Approval of final version of the manuscript, Manuscript drafting and writing.
João Lucas Samaha de Azevedo
0009-0005-2781-0171
Author contributions: Approval of final version of the manuscript, Study conception and design, Manuscript drafting and writing, Data collection, analysis, and interpretation, Critical review of literature
Mariana Ferreira da Silva 0009-0006-8085-7662
Approval of final version of the manuscript, Manuscript drafting and writing 2HUMANITAS - Faculdade de Ciências Médicas, Medicina - São José dos Campos (SP), Brazil
Elisangela Manfredini Andraus de Lima 0000-0002-2390-0410
Approval of final version of the manuscript, Study conception and design, Intellectual contribution to the diagnostic and/or therapeutic management of the studied cases, Critical review of manuscript.
Flávia Regina Ferreira 0000-0001-5679-4282
Approval of final version of the manuscript; manuscript drafting and writing, Active participation in research supervision, Intellectual contribution to the diagnostic and/or therapeutic management of studied cases, Critical review of manuscript.
www.surgicalcosmetic.org.br/
Scrotodynia successfully treated with botulinum toxin
Escrotodinia tratada com toxina botulínica: relato de sucesso terapêutico
Case report
Authors: Taciana Dal´Forno Martina Souilljee Birck1
1 Clinical practice, Dermatology, Porto Alegre (RS), Brazil
Scrotodynia, or genital dysesthesia, is characterized by chronic scrotal pain lasting at least 3 months, with no identifiable etiology despite thorough investigation. Although it is considered a relatively common condition, the lack of effective therapeutic options significantly impacts the quality of life of affected patients. We report a successful and sustained treatment for scrotodynia with botulinum toxin in a 69-year-old patient who had not responded to appropriately dosed oral medications for chronic pain.
Keywords: Male Urogenital Diseases; Botulinum Toxins; Pain, Intractable.
A escrotodinia ou disestesia genital é caracterizada por dor escrotal crônica (superior a 3 meses de duração) sem etiologia definida mesmo após investigação criteriosa. Embora seja considerada uma condição relativamente comum, a ausência de opções terapêuticas eficazes compromete significativamente a qualidade de vida dos pacientes acometidos. Relatamos um caso de sucesso terapêutico e resposta sustentada com uso de toxina botulínica no tratamento da escrotodinia em um paciente de 69 anos, refratária ao uso de medicações orais em doses adequadas para dor crônica.
Palavras-chave: Genitália Masculina; Escroto; Toxinas Botulínicas Tipo A.
Funding: None. Conflicts of interest: None.
Submitted on: 04/16/2024 Approved on: 08/01/2024
How to cite this article: Dal’Forno, Birck MS. Scrotodynia successfully treated with botulinum toxin. Surg Cosmet Dermatol. 2025;17:e20250376.
INTRODUCTION
Chronic scrotal pain, termed scrotodynia or genital dysesthesia, if no etiology is defined after careful investigation, is a relatively common condition. Although still poorly understood, it has a significant impact on patients’ quality of life and causes frustration given the limitations of the therapeutic options currently available. This condition is characterized by unilateral or bilateral, constant or intermittent scrotal pain or discomfort lasting more than 3 months.1 This report aims to describe the therapeutic success in managing scrotodynia in a 69-year-old patient using injectable botulinum toxin.
CASE REPORT
A 69-year-old male patient presented with discomfort, stinging, and superficial itching in the scrotum and right inguinal region, which had been going on for approximately 6 years. He had no history of genital herpes or other conditions in the region. No specific etiology was identified after extensive investigation by a urologist. The patient showed no improvement following the use of oral medications for chronic pain, including anticonvulsants, prescribed by a clinical physcian. On physical examination, no skin lesions were observed in the affected area, nor any other alterations, except for the presence of 2 acrochordons. In view of the refractory nature of the conventional medication, it was decided to treat the patient with botulinum toxin (Dysport®), at a total dose of 90 units (U). The application was made intradermally, at a rate of 2 U per point, distributed over 45 points, with a spacing of 0.5 cm between them, covering the entire symptomatic area, previously identified with the help of the patient, who indicated the areas of greatest discomfort, including the scrotum and part of the right inguinal region (Figure 1). The patient reported a significant improvement in symptoms 2 weeks after the procedure and expressed satisfaction with the therapeutic approach, no longer requiring the use of oral medication for pain relief. In addition, no adverse effects related to the application of the toxin were observed. The patient maintained satisfactory symptom control for a period of 10 months, using this intervention exclusively, with no need for complementary therapies during follow-up.
DISCUSSION
The management of scrotodynia represents a clinical challenge because, in addition to the need to exclude acute and chronic causes associated with scrotal pain syndrome, there is no consensus to date on the most effective therapeutic approach.2 The available literature mainly addresses the use of drugs used to control neuropathic pain, a pathophysiological mechanism potentially involved in genital dysesthesia, including antibiotics, tricyclic antidepressants, and anticonvulsants.3
As second-line options, surgical procedures such as epididymectomy, vasovasostomy, vasectomy, orchiectomy, and testicular denervation have been described, although they are associated with significant risks, such as infertility, and often unpredictab-
le results.2 Given these limitations, minimally invasive measures with a better long-term safety profile have been progressively explored. There are reports, although based on small series of cases, on the use of radiofrequency spermatic cord ablation, with symptomatic relief for periods ranging from 6 to 9 months.1
On the other hand, botulinum toxin has been consolidated as a therapeutic drug in the management of various pain syndromes of neuropathic origin, including pain located in the genital region, such as anal fissures, vulvodynia, and vaginismus.
In these conditions, significant clinical improvement is observed a few days after application, with a sustained response for periods ranging from 12 to 24 weeks.3 The literature also describes the use of botulinum toxin at a dose of 100 U for the management of genital dysesthesia.4
In this context, we decided to apply 90 U of botulinum toxin in this case, distributed in the delimited area of dysesthesia, as indicated by the patient. Significant clinical improvement was observed within 2 weeks of the procedure, and the response was maintained up to the time of writing this report. The absence
of adverse effects, coupled with the possibility of discontinuing the oral medications previously used, reinforces the beneficial potential of this intervention in the management of scrotodynia.
CONCLUSION
This report shows that injectable botulinum toxin can be an effective and safe therapeutic option in the management of scrotodynia, especially in cases refractory to conventional drug
therapies. The patient’s active participation in delimiting the affected area, as well as the adequate definition of the dose, seem to be determining factors in the success of the treatment. Despite the favorable results observed, studies with a larger number of patients and long-term follow-up are needed to validate the efficacy, safety, and lasting effects of botulinum toxin in the treatment of scrotodynia. l
2. Gordhan CG, Sadeghi-Nejad H. Scrotal pain: evaluation and management. Korean J Urol. 2015;56(1):3-11.
3. Raef HS, Elmariah SB. Treatment of male genital dysesthesia with botulinum toxin. JAAD Case Rep. 2021;10:60-2.
4. Khambati A, Lau S, Gordon A, Jarvi KA. Onabotulinum toxin A (Botox) nerve blocks provide durable pain relief for men with chronic scrotal pain: a pilot open-label trial. J Sex Med. 2014;11(12):3072-7.
AUTHOR’S CONTRIBUTION:
Taciana Dal´Forno 0000-0003-0848-9042
Statistical analysis, approval of the final version of the manuscript, study design and planning, preparation and writing of the manuscript, data collection, analysis, and interpretation, effective participation in research guidance, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, critical literature review, critical review of the manuscript.
Martina Souilljee Birck 0000-0001-9281-7744
Author’s contribution: Study design and planning, preparation and writing of the manuscript, data collection, analysis, and interpretation, intellectual participation in propaedeutic and/or therapeutic conduct of studied cases, critical literature review.
