Psoriasis Treated with Methotrexate: A Case Report
Grade 4 Cystic Acne Managed with Triamcinolone Injection and Isotretinoin: A Case Report
Effectiveness of Various Organic Peels – In Skin Rejuvenation and Sensitive Skin Part-II
Dom
22, Shreeji Bhavan, 275-279, Samuel Street, Masjid Bunder (W), Mumbai-4000 03, INDIA.
EMAIL: theaestheticiansjournalindia@gmail.com
Website: theaestheticiansjournal.com
TEL: +91 22 2345 1404
+91 22 2345 5844
without prior written permission prohibited.
Published for the period of April -2024
Summer can be a challenging season for the skin and there are several risks associated with skin issues during this time. High temperature, high humidity makes the skin vulnerable, prone to sweating and increase the risk of different types of skin infection.
Overall, the combination of increased solar radiation, reduced cloud cover and limited atmospheric moisture during the dry summer season contributes to elevated temperatures on a daily basis. These factors highlight the importance of staying hydrated, seeking shade and practicing sun protection measures to stay safe and comfortable during hot summer days. By incorporating sun protection, some protection measures into daily routine can effectively protect the skin from sun damage and maintain its health and appearance for years to come. it's crucial to follow the dermatologist's recommendations to take proactive steps to safeguard the skin while enjoying the benefits of sunlight responsibly. Remember that sun protection is not just for sunny days; UV rays can penetrate clouds and cause damage even on overcast days. So make sun protection a habit yearround to keep the skin safe and healthy.
To prevent the skin from sun damage, dermatologist’s always recommend the important skincare tips like incorporating sunscreen into daily skincare routine, wearing protective clothing such as hats and sunglasses, seeking shade during peak sun hours and avoiding tanning beds are all effective measures to prevent sun damage. Remember to reapply sunscreen every two hours, especially when swimming or sweating. Prioritize the skin's health by making sun protection a non-negotiable part of lifestyle.
Dermatologists are experts and they have effective strategies to address the skin types and they can recommend specific products or a treatment tailored to the skin’s needs and helps to safeguard the skin from the harmful effects of the sun.
In this issue we got clinical articles on Psoriasis Treated with Methotrexate, Cystic Acne Managed with Triamcinolone Injection and Isotretinoin.
HOPE YOU HAVE A GREAT READ
Thanks & Cheers
- Dom Daniel Executive Editor & PublisherEffectiveness of Various Organic Peels – In Skin Rejuvenation and Sensitive Skin Part-II
Dr. Sowmya N Dogiparthi, MD, DVL, FAM
Psoriasis Treated with Methotrexate: A Case Report
Dr. Pragathi Sankineni, MBBS, MD, DVL
Grade 4 Cystic Acne Managed with Triamcinolone Injection and Isotretinoin: A Case Report
Dr. M. Himabindu, MBBS, DDVL
17th December'2023
28th April'2024
Venue: Hotel Ginger, Near Domestic Airport, Vile Parle (East) Mumbai
Venue: Hotel Orchid, Nr.Domestic Airport, Vile Parle (E) Mumbai
1 Day Hands on Workshop Training by Masters in Aesthetic Dermatology
Dr. Sowmya N Dogiparthi
MD, DVL, FAM
Professor
Department of Dermatology
Shri Sathya Sai Medical College and Research Institute (SSSMC & RI), Chennai Consultant - Apollo Hospitals, Chennai Dermipure Dermaclinic, Chennai.
Dr. Pragathi Sankineni
MBBS, MD, DVL Consultant Dermatologist & Cosmetologist
Pragathi Skin & Cosmetology Clinic
Nizamabad, Telangana
Dr. M. Himabindu
MBBS, MBBS, DDVL Director of Dr. Himabindu's Skin Clinic and Laser Centre, Hyderabad Consultant Dermatologist
Paramitha Children’s Hospital, Kompally, Hyderabad
Dr. Shamanth Murthy
Dr. Satish K.M.
Dr. Vinayak Venktesh
Dr. Sankeerth
Dr. Abdul Samad
Dr. Manjunath Hulmani
Dr. Sanath K.S.
Dr. Nirupa Mary A
Dr. Ashish Shetty
Dr. Pruthviraj
Dr. Shruthi Chikkiah
Dr. Shyam Raj Rao
Dr. Umasree Anne
Dr. M. Krishnarao
Dr. Koushik Kumar
Dr. Samipa Mukherjee
Dr. Harshavardhan Gowda
Dr. Archana Gulur
Dr. Ramesh A . C .
Dr. Haritha R.
Dr. Karthik R.
Dr. Chaitra
Dr. Vinayak Venktesh
Dr. Pavan Kumar
MD, DVL, FAM Professor
Department of Dermatology
Shri Sathya Sai Medical College and Research Institute (SSSMC & RI), Chennai Consultant - Apollo Hospitals, Chennai
Dermipure Dermaclinic, Chennai.
Part - I I
Organic peels results master graphs
Graph 3: Even Coloration
Graph 4: Normal Texture
Graph 5: Clinically evident disease
In current study, among 20 patients with oily skin, 6 patients had black olive peel and 7 each had pumpkin peel and mandelic peel. Firmness, even coloration and normal texture were comparable among the study groups. Smoothness was comparatively significant among patients with mandelic peel (P value 0.041). There was no clinical evidence of disease.
Normal skin:
In current study, among 20 patients with combination skin type, 4 patients each
underwent black olive peel, pumpkin peel, mandelic peel, manuva honey peel and citrus peel. Smoothness, firmness, even coloration and texture was comparable among all the groups with no statistical difference (P value >0.05). One patient with citrus peel had acne after the procedure.
Graph 6: Smoothness
Graph 7: Fairness
Graph 8: Even Coloration
Graph 9 : Normal Texture
Graph 10 : Clinically evident disease
Graph 11 : Smoothness
Graph 12: Fairness
Graph 13: Even Coloration
Graph 14: Normal Texture
Graph 5: Clinically evident disease
Graph 16: Overall score
In current study it was showed that the effectiveness of mandelic peel was more when compared with other organic peels which showed significant difference (P value 0.033).
The images taken after 2 months application of each peel are as follows:
Discussion
Peeling is a dermato-cosmetic method commonly used to remove dead cells from the skin's surface and stimulate the function of deeper skin layers. It is primarily focused on the epidermis, the superficial layer of the skin and generally does not significantly alter the skin's architecture. However, there are more aggressive peeling methods that can even affect the structure of skin proteins. Peels can be classified into two main categories based on their mechanism of action: mechanical peels and chemical peels. Mechanical peels involve the use of creams or masks
containing granules or abrasive particles. These particles, when gently massaged onto the skin's surface, exfoliate and remove dead cells from the epidermis. Mechanical peels provide a relatively easy and superficial form of exfoliation. Whereas chemical peels, rely on the application of chemical substances to achieve exfoliation of the epidermis. Chemical peeling or chemoexfoliation, is a dermatological procedure that involves the application of specific chemical agents to the skin to induce controlled exfoliation and targeted ablation of the damaged skin layers. The goal of a chemical peel is to remove a precise and uniform thickness of damaged skin, promoting the regeneration of new skin cells and improving the overall appearance of the skin. Selection of chemical substances used in the peel depends on the specific skin concerns or issues being addressed. Different substances may be used based on the individual's skin type and the desired outcomes. Chemical peels can be further categorized based on their depth of penetration into the skin. Superficial peels,
also known as light or lunchtime peels, primarily target the outermost layers of the epidermis. They are commonly used for improving skin texture, addressing fine lines, and reducing mild discoloration. Mediumdepth and deep peels involve the penetration of chemical substances into deeper layers of the skin, reaching the papillary dermis or reticular dermis. These peels are more aggressive and may be used to treat more significant skin concerns such as moderate wrinkles, acne scars or pigmentation disorders. They often require more extensive downtime and should be performed by trained professionals.22,23,24,25,26
Common chemical agents used in peels include alpha-hydroxy acids (AHAs) such as glycolic acid and lactic acid, beta-hydroxy acids (BHAs) like salicylic acid and trichloroacetic acid (TCA). By removing the damaged outer layers of the skin, chemical peels can improve the appearance of several skin concerns, such as fine lines and wrinkles, sun damage, acne scars, uneven skin tone and hyperpigmentation.
The exfoliation process stimulates collagen production and promotes cell turnover, resulting in smoother, more youthfullooking skin.
The chemical peels technique should be performed by a qualified dermatologist or skincare professional to ensure proper application, dosage and monitoring. The procedure requires careful evaluation of the patient's skin type and condition to determine the appropriate peel depth and formulation. This helps minimize the risk of complications, such as scarring and post-inflammatory hyperpigmentation.27
The procedure flow of chemical peeling is given as follows:
The chemical peeling, is indeed a valuable method for treating aged skin, photoaging, acne scars and melasma like conditions by applying a mask containing acids to the skin twice a week leading up to the treatment. These acids help exfoliate the skin, remove dead cells, and promote cellular turnover, allowing for better penetration of the peeling agents. Proper postpeeling care is essential which may include avoiding excessive sun exposure, using moisturizers, avoiding harsh skincare products and following a gentle skincare routine as temporary skin issues like redness, sensitive or irritated skin can be observed. Thus chemical peeling though is beneficial still provides side effects to the skin. Organic peels offer an alternative approach to skin rejuvenation, utilizing natural ingredients with potential benefits for improving skin texture, reducing signs of aging and addressing various skin concerns. Fruit enzyme peels, botanical peels and pumpkin enzyme peels are among the organic options commonly used for skin rejuvenation. Their perceived milder properties make them attractive for individuals with sensitive skin. But it is crucial to consider individual skin sensitivities and consult with
a professional to determine the most suitable peel and treatment approach for optimal results and safety. Organic peels alone as basic low strength peels or as a part of medi - facials; as the name suggests, is the new age treatment that combines medicine and facial. They contain Vitamins, Minerals and Antioxidants. It not only imparts an instant glow to the skin but also nourishes it, thereby reducing the effects of ageing without any harmful long-term side effects. They provide long-term nourishment and rejuvenation to the skin. Among all the peels, mandelic, pumpkin peel and black olive peels showed significant results.
References
22. Samargandy S, Raggio BS. Skin Resurfacing Chemical Peels. [Updated 2022 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi. nlm.nih.gov/books/NBK547752/
23. Arif, Tasleem. “Salicylic acid as a peeling agent: a comprehensive review.” Clinical, cosmetic and investigational dermatology vol. 8 455-61. 26 Aug. 2015, doi:10.2147/ CCID.S84765
24. Packianathan, Nilani & Kandasamy, Ruckmani. (2011). Skin Care with Herbal Exfoliants. Functional Plant Science and Biotechnology. Volume 5. 94-97.
25. Soleymani, Teo et al. “A Practical Approach to Chemical Peels: A Review of Fundamentals and Stepby-step Algorithmic Protocol for Treatment.” The Journal of clinical
and aesthetic dermatology vol. 11,8 (2018): 21-28.
26. Liu, JK. Natural products in cosmetics. Nat. Prod. Bioprospect. 12, 40 (2022). https://doi. org/10.1007/s13659-022-00363-y
27. Rendon, Marta I et al. “Evidence and considerations in the application of chemical peels in skin disorders and aesthetic resurfacing.” The Journal of clinical and aesthetic dermatology vol. 3,7 (2010): 32-43.
MBBS, MD, DVL
Consultant Dermatologist and Cosmetologist
Pragathi Skin and Cosmetology Clinic
Nizamabad, Telangana
Introduction
Psoriasis is a chronic, inflammatory, auto-immune disease characterized by the rapid production of skin cells, resulting in the formation of thick, red, scaly patches on the skin. Such patches are also known as plaques and typically appear on the elbows, knees, scalp, lower back and other areas of the body. Exact etiology being unknown, a combination of genetic, immune system and environmental factors are expected to be involved, specifically the immune system plays a key role in the development of psoriasis. The immune system mistakenly attacks healthy skin cells, leading to the increased production of new skin cells and the accumulation of dead skin cells on the surface. This immune system dysfunction that results in chronic inflammation, is a hallmark of psoriasis.
The inflammation causes the skin cells to grow and multiply at an abnormally fast rate, leading to the characteristic plaques. In addition to the skin manifestations, psoriasis can also affect the joints, causing a condition known as psoriatic arthritis. Psoriasis tends to persist over a long period of time, often lasting for years or even a lifetime. Although currently there being no cure for psoriasis, various treatment options can manage the symptoms and reduce inflammation. These treatments includes topical creams and ointments to systemic medications, phototherapy and lifestyle modifications. Psoriasis vulgaris, the most common form of psoriasis, is influenced by a combination of genetic and environmental factors. The clinical presentation of psoriasis is characterized by
erythematous - squamous plaques, typically found on the extensor surfaces of the elbows and knees, scalp and lumbosacral area. These plaques reflect underlying pathogenic mechanisms such as inflammation, hyperproliferation, and angiogenesis. It is important to note that psoriasis is not solely limited to the skin as research has demonstrated that inflammation extends beyond the skin to deeper levels of the body. In moderate-tosevere psoriasis, proinflammatory markers and cytokines are elevated not only in the skin but also in the blood and other biological fluids. Imaging studies, such as FDGPET/CT, have revealed subclinical inflammation in the liver, joints, tendons, subcutaneous tissue and arteries of patients with psoriasis. Psoriasis is also associated with comorbid conditions, similar to other immune-mediated inflammatory diseases. Psoriatic arthritis (PsA) is a common comorbidity, affecting up to 30% of individuals with psoriasis. Other associated conditions include cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and non-alcoholic fatty liver disease that suggest it as a multisystemic disorder, with skin involvement
being the most visibly apparent manifestation of a generalized inflammatory state.1
The histological features of psoriasis and the underlying inflammatory processes includes sustained inflammation that triggers abnormal proliferation and differentiation of keratinocytes. The histology of psoriatic plaques typically reveals acanthosis, which refers to the thickening of the epidermis due to excessive growth and multiplication of keratinocytes. In addition, there is a presence of inflammatory infiltrates in the dermis. These infiltrates consist of various immune cells, including dermal dendritic cells, macrophages, T cells and neutrophils which contribute to the inflammatory response seen in psoriasis. Neovascularization, the formation of new blood vessels, is also a prominent feature of psoriasis were this increased blood vessel formation supports the heightened metabolic demands of the proliferating keratinocytes and contributes to the redness and warmth associated with psoriatic plaques. Since the inflammatory pathways are active in plaque psoriasis, overlap with those in other clinical variants of psoriasis,
there are also distinct differences that contribute to variations in phenotype and treatment outcomes. These differences may explain why certain treatments are more effective for specific types of psoriasis or in certain individuals.2
A 45 year old male patient visited our clinic. He had scaly plaque present bilaterally over upper and lower extremities which were found after clinical examination. Medical history revealed presence of scaly plaque all over scalp since 5 years. No evidence of history of joint pains or other systemic complaints. The total body surface area covered by scaly plaque involved is more than 20%. No evidence of other medical history or medications was found. Some test done such as CBP (complete blood picture), LFT (liver function test) shown normal limits with no variation. The treatment included weekly 10mg tablet of methotrexate (MXT) for a dose regime of 10 weeks. Additionally folic acid tablets (act as folic acid supplements), antihistamines (antiinflammatory), other topicals were given to enhance the effect of MTX. Furthermore phototherapy; specifically NB-UVB phototherapy was given twice a week continued for 6 weeks.
The diagnosis of psoriasis, is typically made based on a combination of clinical examination, medical history and sometimes additional tests. The primary feature is the presence of red, raised and scaly patches of skin known as plaques are typically found on the elbows, knees, scalp and lower back, but they can occur on other areas of the body as well. So the examination may also involve assessing the severity and extent of the disease. The medical history can also reveal any triggering or exacerbating factors which might be involved along with patient's symptoms, including when they first appeared, how they have progressed etc. Psoriasis can sometimes resemble other skin conditions, such as eczema or fungal infections. Hence differential diagnosis can help by performing additional tests if needed to rule out other conditions. Sometimes a skin biopsy may be performed
to confirm the diagnosis or to differentiate psoriasis from other skin disorders. There are no specific blood tests to definitively diagnose psoriasis, but can help to evaluate the levels of certain antibodies, inflammation markers and liver function.3,4
The treatment for psoriasis can vary depending on the severity of the condition, the extent of skin involvement and individual factors. Topical treatments like corticosteroids, coal tar preparations reduces inflammation, retinoids help to normalize the growth of skin cells whereas calcineurin inhibitors, commonly used for sensitive areas such as the face and genitals reduces inflammation thus help to relieve itching and redness. These topical agents are typically used for mild to moderate psoriasis. Systemic medications that are taken orally or by injection and are used for more severe cases of psoriasis or when other treatments have not been effective. Examples include immunosuppressant like methotrexate and cyclosporine that slow down cell turnover, reduces inflammation and suppresses the immune response. A newer class of medications that target specific immune system proteins involved
in psoriasis known as biologics are usually reserved for moderate to severe psoriasis, administered by injection or infusion. Examples include TNF-alpha, IL-17 or IL-23. Sometimes phototherapy that involves exposing the skin to controlled doses of ultraviolet (UV) light, to slow down the growth of skin cells and reduce inflammation can be used. Systemic retinoids, medications related to vitamin A, are used for severe cases of psoriasis that have not responded to other treatments. They reduces inflammation and slow down skin cell growth. Additionally combination of treatments may be used to manage psoriasis and improve its symptoms which could involve using a topical treatment along with phototherapy or combining different systemic medications. Commonly used medication in treatment of psoriasis is methotrexate, an immunosuppressant that helps to reduce inflammation and slow down the overgrowth of skin cells in psoriatic plaques. Methotrexate (MTX) is an antimetabolite, folate antagonist, which works by inhibiting the enzyme dihydrofolate reductase (DHFR) involved in the synthesis of DNA and RNA. It is approved by the FDA for the treatment of moderate
to severe psoriasis and psoriatic arthritis, oftenly used as a first-line systemic therapy for psoriasis when topical treatments are not sufficient. The specific dosing and duration of treatment with methotrexate can vary depending on the individual and their response to the medication, however, a common starting regimen includes methotrexate tablet once a week, orally with often lower initial dose is, such as 5 to 10 mg, and then gradually increased if necessary. The treatment duration may vary, but a common initial course is 10 to 12 weeks, usually taken with a glass of water, taken with or without food, usually prescribed for brief periods, but it can be used for up to six months in some people. Regular monitoring of liver function, blood counts and kidney function is important during MTX treatment to ensure its safety and effectiveness as common side effects include nausea, fatigue, liver toxicity, and decreased blood cell counts.3,5,6,7,8
Additionally to its role as a dihydrofolate reductase (DHFR) inhibitor, it exhibits anti-inflammatory properties by decreasing the synthesis of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-a) and interleukin-1 (IL-1) which play a significant role in
the inflammatory process observed in psoriasis. By reducing their production, MTX helps to dampen the immune response and inflammatory signaling. MTX also acts as an immunosuppressant by inhibiting the activation and proliferation of T cells, which are involved in the pathogenesis of psoriasis. It can decrease the expression of intercellular adhesion molecules by T cells, which are molecules involved in their recruitment to inflammatory sites. It also increases the sensitivity of stimulated T cells to CD95-mediated apoptosis, promoting the elimination of activated T cells. Furthermore, MTX affects purine metabolism, leading to the accumulation of adenosine, has antiinflammatory effects, can modulate immune responses. It inhibits the activation of neutrophils and reduces their chemotaxis, contributing to the suppression of inflammation. While the precise mechanisms of MTX in psoriasis are not fully understood, the combination of its antiproliferative, antiinflammatory and immunosuppressive properties helps to alleviate the symptoms of psoriasis by reducing hyperproliferation of skin cells, modulating immune responses and decreasing
inflammation. Folic acid can commonly be coadministered with MTX to mitigate certain adverse effects of the medication while still maintaining its effectiveness. There is no clear consensus on the ideal dose of folic acid to be taken with MTX but The primary goal of folic acid supplementation in this context is to prevent adverse reactions in the hematopoietic system (which produces blood cells) and reduce hepatotoxicity (liver toxicity). This supplementation of folic acid has been shown to alleviate various symptoms associated with MTX treatment, such as nausea and mucosal ulcerations whereas the role in reducing the risk of pulmonary fibrosis (a lung condition) has not been definitively established. The recommended dose is 15 mg per week, typically administered at least 12 hours after the last dose of MTX, although waiting 24 to 48 hours is more common. Another option is to take 5 mg of folic acid daily, except on the days when MTX is taken. Though providing such advantages, efficacy concerns still prevails as conclusive supporting evidence has not been wellestablished.8
Antihistamines are primarily used to treat allergic reactions and symptoms like itching, sneezing and
runny nose associated with allergy. It may also help relieve itching associated with psoriasis, indirectly by treat the underlying cause of the condition. Phototherapy, specifically Narrowband Ultraviolet B (NB-UVB) phototherapy, is also a commonly used treatment for psoriasis that involves exposing the affected skin to a specific wavelength of ultraviolet B light to reduce the symptoms of psoriasis. Treatment sessions are usually scheduled two to three times per week, depending on the severity of the psoriasis and the patient's response. The duration of each session depends on the patient's skin type and the intensity of the light used. NB-UVB phototherapy works by slowing down the abnormal growth of skin cells and reducing inflammation. The specific wavelength of light used in NB-UVB phototherapy (around 311-312 nanometers) has been found to be effective in treating psoriasis while minimizing the risk of side effects. NB-UVB phototherapy has shown significant efficacy in reducing the symptoms of psoriasis. It can help improve the appearance of the skin, reduce redness and scaling, and alleviate itching and discomfort. The treatment is well-tolerated by most patients, and
the risk of side effects is relatively low compared to other treatments.9
Psoriasis is a chronic inflammatory skin disease that affects a significant number of people worldwide. It is characterized by various skin manifestations, with the classical form presenting as red, scaly plaques on the extensor surfaces of the elbows, knees and scalp. However, there are also pustular variants of psoriasis, which display localized or generalized pustulosis and have different clinical behaviors and relative treatment resistance compared to plaque-type variants. Additionally, around 20% of individuals with psoriasis suffer from psoriatic arthritis, which affects the distal extremities and large joints. Recent research shows that psoriasis should be considered a systemic disease, sharing similarities in pathogenesis with other chronic inflammatory conditions like rheumatoid arthritis, Crohn's disease and lupus erythematosus. An ongoing discussion whether psoriasis can be classified as an autoimmune disease is going on as it exhibits mechanisms of chronic inflammation, involves TNF-a in its pathogenesis and shares genetic loci associated with other
autoimmune disorders. Although a candidate autoantigen has been identified for psoriasis, its clinical relevance is still not fully understood. Psoriasis is known to have a strong genetic component and it is closely linked to the immunophenotype. Studies have demonstrated a higher risk of developing psoriasis in siblings of affected individuals compared to siblings of non-affected individuals. Genetic associations have been found for the major histocompatibility complex (MHC) locus on chromosome 6, which contains the human leukocyte antigen (HLA) genes and other immune genes such as TNF-a. Additionally, genome-wide association studies have identified several other psoriasis risk variants in common alleles of the general population, involving genes related to the TNF-a and IL-23/IL17 pathways, as well as epidermal/ antimicrobial genes. The pathogenesis of psoriasis involves interactions between various cell types, including epidermal keratinocytes, antigen-presenting cells and T cells, which create a pro-inflammatory environment. The exact initiation phase of psoriasis is not fully understood, but antimicrobial peptides (AMP) and dendritic cells
have been implicated. Trigger factors such as traction forces, chemicals and microbes activate epidermal keratinocytes, leading to the production of pro-inflammatory molecules. This, in turn, activates plasmacytoid dendritic cells, which produce cytokines like IFN-a and IFN-a, along with TNFa and IL-1a. These cytokines further activate myeloid dendritic cells and trigger a cascade of downstream cytokines, including IL-23, IL-17, IL-22 and IFNa, which continue to activate keratinocytes. The activated keratinocytes exhibit high proliferation rates and produce a range of proinflammatory chemokines and antimicrobial peptides. The European Society of Neurology/Peripheral Nerve Society (EFNS/PNS) 2021 guidelines for chronic inflammatory demyelinating polyneuropathy (CIDP) recommend using electrophysiological diagnosis, neuroimaging, cerebrospinal fluid (CSF) analysis, and nerve biopsy to accurately diagnose CIDP. The guidelines also recommend firstline therapies such as corticosteroids, intravenous immunoglobulin (IVIg) and plasma exchange (PE). Corticosteroids have multiple immunemodulatory effects, including anti-inflammatory,
anti-immune, anti-allergic and anti-shock properties. IVIg can interfere with complement activity, production of proinflammatory cytokines and signal transduction of phagocytes and B cells. Both IVIg and PE can remove pathogenic factors from the blood, such as autoantibodies, activated complement and inflammatory mediators, leading to rapid and sustained treatment responses. In the case of the patient described, they received multiple rounds of IVIg and IA (intravenous immunoadsorption) treatments. Each IVIg treatment resulted in symptom improvement and an increase in the Medical Research Council (MRC) sum scores by at least 6 points (on a scale of 0-60). IA treatments also provided significant relief of clinical symptoms, allowing the patient to walk independently with some assistance in daily life. However, the symptoms recurred severely after a short period and the patient was readmitted to the hospital. The patient had a history of psoriasis and discontinuation of psoriasis medications led to a worsening of the condition, suggesting a potential immunopathogenic mechanism shared between CIDP and psoriasis, possibly related to
the activation of Th17 cells and production of IL-17 and other inflammatory factors. The patient's symptoms have stabilized for a longer period of time with the use of secukinumab, a medication that targets IL17, but long-term efficacy still needs to be evaluated. It is important to consider that individuals susceptible to autoimmune diseases may develop multiple autoimmune conditions depending on the costimulatory environment. However, further clinical and basic research is necessary to confirm the relationship between CIDP and psoriasis and understand the underlying mechanisms.10
CIDP, chronic inflammatory demyelinating polyneuropathy that involves progressive weakness and reduced senses in the arms and legs. There are challenges associated with the pathogenesis and treatment of CIDP were the precise underlying mechanism remain unclear and the clinical symptoms can vary widely among individuals. If patients with CIDP do not respond well to first-line treatments or if the disease follows a relapse-remission pattern, it is important to consider possibilities such as misdiagnosis, other immune diseases,
or insufficient doses of immunotherapy. The combination of CIDP and psoriasis is clinically rare but serves as a reminder to clinicians that CIDP can manifest in diverse ways. Early treatment intervention and close monitoring of relapse-remission instances along the treatment journey are crucial.11
The immune-mediated and inflammatory nature of psoriasis, as well as the evolving treatment landscape with the introduction of biologics. It is indeed true that psoriasis is a chronic relapsing-remitting disease that affects a significant percentage of the global population. Advancements in understanding the inflammatory pathways involved in psoriasis have led to the identification of key molecules in the inflammatory cascade of the disease. This knowledge has paved the way for the development of targeted therapies, particularly biologics, that can specifically modulate these pathways and modify the natural course of psoriasis. Biologics have demonstrated their ability to reduce the inflammatory background of the disease, thereby preventing irreversible organ damage and systemic complications.
However, they have shown remarkable efficacy, there are still several important considerations and unanswered questions regarding their use, particularly in patients with systemic comorbidities. Understanding the longterm risks associated with continuous use of biologics and optimizing their administration in special populations are areas that require further research and exploration. The efficacy and safety profile of biologics in psoriasis is a topic of significant interest. Clinical studies and realworld evidence have provided valuable insights into the effectiveness of biologics in managing psoriasis symptoms and improving patients' quality of life. Additionally, safety data have been collected and monitored to assess potential risks associated with biologic therapies. This narrative review aims to shed light on both the efficacy and safety aspects of biologics in psoriasis as it covers the pathophysiology of the disease, the role of biologics in modulating inflammatory pathways, and their clinical application in treating psoriasis. By synthesizing this information, the review aims to provide a comprehensive understanding of the benefits and considerations related to the use of biologics
in the management of psoriasis.
1. Campanati, Anna et al. “Psoriasis as an ImmuneMediated and Inflammatory Systemic Disease: From Pathophysiology to Novel Therapeutic Approaches.” Biomedicines vol. 9,11 1511. 21 Oct. 2021, doi:10.3390/ biomedicines9111511
2. Rendon, Adriana, and Knut Schäkel. “Psoriasis Pathogenesis and Treatment.” International journal of molecular sciences vol. 20,6 1475. 23 Mar. 2019, doi:10.3390/ijms20061475
3. Kim, Whan B et al. “Diagnosis and management of psoriasis.” Canadian family physician Medecin de famille canadien vol. 63,4 (2017): 278-285.
4. Kimmel, Grace W., and Mark Lebwohl. “Psoriasis: Overview and Diagnosis.” EvidenceBased Psoriasis: Diagnosis and Treatment 1–16. 1 Jul. 2018, doi:10.1007/978-3-319-901077_1
5. da Silva, Carolina AP et al. “Methotrexate for psoriasis.” The Cochrane Database of Systematic Reviews vol. 2019,4 CD010498. 9 Apr. 2019, doi:10.1002/14651858. CD010498.pub2 www.ncbi. nlm.nih.gov/pmc/articles/ PMC6454986/
6. Laura C. Coates et al, Methotrexate in Psoriasis and Psoriatic Arthritis, The Journal of Rheumatology Supplement Jun 2020, 96 31-35; DOI: 10.3899/ jrheum.200124
7. Torsekar, R, and Manjyot M Gautam. “Topical Therapies in Psoriasis.” Indian dermatology online journal vol. 8,4 (2017): 235-245. doi:10.4103/22295178.209622
8. Czarnecka-Operacz, Magdalena, and Anna SadowskaPrzytocka. “The possibilities and principles of methotrexate treatment of psoriasis - the updated knowledge.” Postepy dermatologii i alergologii vol. 31,6 (2014): 392-400. doi:10.5114/ pdia.2014.47121
9. Randall, Katrina L, and Carolyn A Hawkins. “Antihistamines and allergy.” Australian prescriber vol. 41,2 (2018): 41-45. doi:10.18773/ austprescr.2018.013
10. Saalbach A and Kunz M (2022) Impact of Chronic Inflammation in Psoriasis on Bone Metabolism. Front. Immunol. 13:925503. doi: 10.3389/fimmu.2022.925503
11. Jin, Yan et al. “Chronic inflammatory demyelinating polyneuropathy and psoriasis comorbidity with significantly alleviated in symptoms after secukinumab: case report.” BMC neurology vol. 22,1 400. 2 Nov. 2022, doi:10.1186/ s12883-022-02928-3
MBBS, DDVL
Director of Dr. Himabindu's Skin Clinic and Laser Centre, Hyderabad
Consultant Dermatologist
Paramitha Children’s Hospital, Kompally, Hyderabad
Introduction
Acne vulgaris or simply acne, is a common human skin disease of the pilosebaceous unit and occurs in areas of skin with large numbers of sebaceous follicles, which are found on the cheek, forehead and back. Acne is generally characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules and possibly scarring. The precise mechanism of acne is not known but is thought to involve four main pathogenic factors: follicular keratinization, increased sebum production, the presence of Propionibacterium acnes and inflammation. Apart from these factors, genetic predisposition, fluctuations in hormone levels, particularly during puberty, menstrual cycles, or hormonal disorders, birth control pills, certain medication, stress and use of oily cosmetics that can create a favorable environment for the colonization of Propionibacterium acnes, in the follicles. Acne occurs due to blockage in the follicles resulting in the formation
of comedones. The earliest microscopic lesion observed is the microcomedones, which are characterized by follicular plugging caused due to follicular keratinization and reduced desquamation of keratinocytes in the pilosebaceous unit. Over time, the microcomedones develop into comedones that further develop into blackheads and whiteheads. Lack of oxygen in these plugged follicles creates an anaerobic environment suitable for the growth of P. acnes. The cell wall and the biological by-products of these flourishing bacteria act as chemo-attractants and proinflammatory mediators leading to inflammation. The inflammatory cells diffuse from the follicle to the surroundings, secreting enzymes that rupture the follicular walls. These inflammatory mediators stimulate a localized immune response resulting in the formation of pustules, while a more intense inflammation is accompanied by the formation of comedonal acne.
Several factors influence the development of acne, including infection of P. acnes and Staphylococcus epidermidis, natural environmental insults that produce free radical scavenging activity, skin type and hormonal imbalance.1,2,3
Treating cystic acne often requires a comprehensive approach and may involve a combination of oral and topical medications. Antibiotics are commonly prescribed to reduce inflammation and control bacteria. Oral isotretinoin is another potent medication that is reserved for severe cases of cystic acne. It effectively reduces oil production and prevents future breakouts but has potential side effects and requires close monitoring. Topical treatments, such as retinoids, benzoyl peroxide or antibiotic creams, corticosteroid injections etc, are some of the treatment options available for treatment. Maintaining a consistent skincare routine, avoiding picking or squeezing the cysts, managing stress levels, eating a balanced diet and keeping the skin clean can contribute to overall skin health.3,4,5,6
Grade 4 cystic acne is the most severe form of acne vulgaris. It is a chronic skin disorder characterized by the presence of deep, inflamed nodules or cysts that extend deep into the skin layers resulting in significant redness, swelling and warmth around the affected, typically larger in size and more tender or painful compared to milder forms of acne. They often affects a larger surface area of the skin,
including the face, chest, back and shoulders were the lesions may be widespread and may occur in clusters or individually. These acne carries a higher risk of scarring due to the deep nature of the lesions, potential for inflammation and tissue damage which can be permanent if appropriate treatment is not provided.3,4,5,6
A 24 year old patient was presented to our clinic. She came with the complaints of swelling over face for 2 months of duration. She was initially suffering from acne since 3 years and was on topical creams and antibiotics for a while when treated elsewhere. After thorough clinical examination and reviewing the medical history, at present stage she was diagnosed with grade 4 cystic acne. Since she initially had some treatment done, we suggested a combination therapy of tablet Isotretinoin 10mg and gave 1 shot of Triamcinolone acetonide injection intra lesional 10mg/ml; single injection for cystic acne. The problem of lesions was resolved in 3 weeks of time and significant improvement was seen within weeks. She still is pursuing the treatment of the same. Took 2 more injection for cystic lesions in gap of 2 weeks now the cysts have resolved presently she is taking laser treatment for acne scars.
After single injection of Triamcinolone 10 mg/ml for Cystic Acne
After 3 weeks of treatment with Isotretinoin 10mg and Triamcinolone 10 mg/ml
The diagnosis of cystic acne is typically involves a combination of a physical examination, medical history review and assessment of the characteristic signs and symptoms. Clinical examination of affected areas such as face, chest and back which has specific features including the presence of large, inflamed and painful nodules or cysts beneath the skin's surface to be done. Since genetic factors can trigger acne development, reviewing family history, including any previous or current skin conditions, duration and severity of acne symptoms and any treatments received has to be considered. These signs and symptoms has to be assessed properly as scarring or hyperpigmentation can result from previous acne outbreaks. In some cases, other skin conditions that may mimic cystic acne such as folliculitis, rosacea or hidradenitis suppurativa can be ruled out with the help of differential diagnosis. Additional tests or procedure may not be necessary in case of cystic acne as diagnosis is typically made based on the characteristic appearance and clinical features. However in certain situations skin biopsy may be required to confirm the diagnosis or to rule out other underlying conditions.3
Oral antibiotics, such as tetracycline, doxycycline, minocycline or isotretinoin (Accutane/ Roaccutane), corticosteroid injections, injected directly into the cysts helps to reduce inflammation, control bacterial growth. Isotretinoin is a powerful oral medication, also known as accutane, typically reserved for severe cases of cystic acne, requires close monitoring due to potential side
effects and is not suitable for pregnant women. Topical treatments like creams, gels or ointments containing ingredients like retinoids, benzoyl peroxide or antibiotics like clindamycin or erythromycin may be applied directly to the affected areas. Topical retinoids, such as tretinoin, adapalene or tazarotene, can help unclog pores, reduce inflammation, and promote skin cell turnover. Azelaic acid helps unclog pores, reduce inflammation and has antibacterial effects. Oral contraceptives can help regulate hormones and decrease sebum production, leading to improvements in acne symptoms. Combination therapy can be used to maximize the effectiveness of treatment, for e.g. a combination of oral antibiotics and topical retinoids or oral contraceptives and topical treatments may be prescribed. Safe extraction of contents from large cysts, usage of chemical peels for exfoliating the skin, reducing oil production and promoting new skin cell growth or laser/ light therapies that targets bacteria, reduce inflammation and promote skin healing are some procedures which can be performed by the health care professinals to treat acne. Along with any treatment a consistent
skincare routine, such as gently cleansing the affected areas, avoiding harsh scrubbing or picking at the skin and using noncomedogenic (non-poreclogging) skincare products etc should be followed to get effective result.7,8,9,10
Triamcinolone injection, a type of corticosteroid injection, have been used as an off-label treatment for cystic acne for many years. It shows anti-inflammatory action by suppressing the immune response helps to reduce inflammation, swelling and redness associated with the acne when injected directly into the cystic acne lesions using a small needle. It can provide quick relief, rapidly reduce the size and inflammation of cystic acne lesions and promote faster healing of the affected area. It also helps to calm the skin, alleviate pain or discomfort associated with the cysts and prevents the formation of scars in some cases. The effectiveness of triamcinolone injections may vary from person to person.
Triamcinolone injections are generally well-tolerated and may have adverse effects which are typically minimal and transient. Some potential local side effects include temporary skin discoloration at the injection site, thinning of the skin and rarely, infection which are relatively uncommon.
The risk of systemic side effects, such as suppression of the adrenal glands or other hormonerelated complications, is generally low due to the localized nature of the injection. However, repeated or excessive use of corticosteroid injections can increase the risk of systemic effects. It's important to note that while triamcinolone injections can be beneficial in specific cases, they are not recommended as a first-line treatment for cystic acne. They are typically reserved for severe cases or when other treatment options have proven ineffective. A comprehensive treatment approach, including other topical or systemic medications, may be necessary for long-term management of cystic acne. Regular monitoring and follow-up visits are necessary to monitor the progress of the injected cystic acne lesions.7,8,9,10
Isotertinoin being a highly effective oral medication for treating severe cystic acne, including grade 4 acne is typically prescribed in a dose range of 0.5 to 1 mg/ kg of body weight per day. The dosage and the duration of treatment can vary based on individual factors, such as body weight, response to treatment and the judgment of the prescribing healthcare professional.
The duration of isotretinoin treatment can vary, but it is generally taken for a course of several months. In some cases, a total cumulative dose may be targeted (e.g., 120-150 mg/kg), while in others, the treatment duration may be based on individual response and the resolution of acne symptoms. It reduces sebum production, controlling inflammation and preventing the formation of new acne lesions and can have a significant impact on improving severe cystic acne and reducing the risk of scarring. However, isotretinoin is a potent medication and can have potential side effects, including dryness of the skin and mucous membranes, increased sensitivity to sunlight and in rare cases, more serious side effects affecting the liver, blood lipids or mental health. Therefore, it requires close monitoring and regular follow-up appointments with the prescribing healthcare professional. 7,8,11,12,13,14,15
Acne vulgaris is a common chronic skin disorder that presents with comedones, cystic structures forming within the distal hair follicle and in most cases, inflammatory skin lesions on the face and upper torso. Cystic acne grade 4 is a severe form of acne vulgaris
that can have a significant impact on a person's physical appearance, selfesteem and overall wellbeing that is characterized by the presence of large, deep and inflamed cysts beneath the skin's surface, often accompanied by widespread skin involvement and a higher risk of scarring. The severity of grade 4 cystic acne sets it apart from milder forms of acne. The deep cysts are typically painful, tender and slow to heal. The inflammation and redness associated with these cysts can be intense and may cause discomfort or even distress which can lead to frustration, anxiety and even depression due to the persistent nature of the condition and its impact on their daily lives. The lesions often occur in clusters and can affect areas such as the face, chest, back and shoulders. A genomewide association study and meta-analysis of data from 34,422 individuals with acne and 364,991 controls from three independent European-ancestry cohorts have been performed. The study replicated 19 previously implicated genome-wide significant risk loci and identified four novel loci [11q12.2 (FADS2), 12q21.1 (LGR5), 17q25.3 (FASN), and 22q12.1 (ZNRF3-KREMEN1)], bringing the total number of reported acne risk loci
to 50. The meta-analysis results explain 9.4% of the phenotypic variance of acne. A polygenic model of acne risk variants showed that individuals in the top 5% of the risk percentiles had a 1.62-fold (95% CI 1.47-1.78) increased acne risk relative to individuals with average risk (2080% on the polygenic risk score distribution). The study highlights the Wnt and MAPK pathways as key factors in the genetic predisposition to acne vulgaris, together with the effects of genetic variation on the structure and maintenance of the hair follicle and pilosebaceous unit. Two novel loci, 11q12.2 and 17q25.3, contain genes encoding key enzymes involved in lipid biosynthesis pathways. Other studies have also been conducted to identify genetic factors associated with acne vulgaris. For example, a genome-wide association analysis in the United Kingdom identified three genome-wide significant associated loci with severe acne. Another study performed a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts and identified 29 novel genome-wide significant loci and replicated 14 of the 17 previously identified risk loci, bringing the total number of reported acne
risk loci to 46. A systematic review and meta-analysis of gene variants associated with acne vulgaris presentation and severity also revealed that the genes and loci associated with acne are involved in various biological pathways, including inflammation, lipid metabolism, androgen metabolism and extracellular matrix remodeling.4,5,6
Treatment options provided includes oral medications like isotretinoin, that helps to reduce sebum production, control inflammation and prevent the formation of new acne lesions. Antibiotics may also be prescribed to control bacterial infection and inflammation. Topical medications, professional procedures like corticosteroid injections to quickly reduce inflammation and promote healing of individual cysts, chemical peels, laser therapy or extraction of comedones may be considered to improve overall skin condition and reduce scarring. Adopting a healthy skincare routine, avoiding harsh or irritating products, practicing good hygiene and managing stress can all contribute to the improvement of acne symptoms.3,16
Global severity grading systems assess the overall appearance of
acne and categorize it into different levels. The severity levels are usually represented numerically or using sequential grading such as mild, moderate and severe. This system provides a comprehensive assessment of the overall impact of acne on the patient's skin. On the other hand, lesion counting grading systems focus on the number of specific acne lesions were each type of lesion, such as comedones, papules, pustules and nodules, is counted and a severity index is assigned to each type. The total severity score is then calculated by multiplying the number of each type of lesion by the respective severity index. This method provides a detailed evaluation of the specific types and quantities of acne lesions present. Proper classification of acne severity is essential for determining the appropriate individualized treatment plan based on the severity of the disease. Treatment plans should be individualized, taking into consideration factors such as the patient's age, hormonal status, medical history and response to previous treatments. A comprehensive approach that addresses the underlying causes of acne, including sebum production, follicular hyperkeratinization and inflammation, is key to
effectively managing the disease and minimizing its consequences, such as scarring and psychological impact. Hence even though grading systems provide a standardized approach to assess acne severity, it's important to remember that acne is a complex and multifactorial condition.17
Based on the review and suggestions mentioned, a modified classification system for acne lesions can be proposed as Acne Type 1 that includes noninflammatory lesions such as comedones (open or closed) and skin-colored dome-shaped papules, Acne Type 2, comprises moderately inflamed acne lesions characterized by faint red or pink papules, Acne Type 3, are red papules and papulopustular lesions, indicating more pronounced inflammation whereas Acne Type 4; encompasses nodules, nodulocystic lesions and cystic lesions, representing the most severe and deep inflammatory lesions. By classifying acne lesions based on their stage and appearance, this modified classification system aims to provide a more comprehensive understanding of the disease's clinical presentation. It acknowledges that different stages of inflammation may require different treatment
approaches. This proposed classification system takes into account the pathology and clinical features of acne lesions, allowing for a more targeted and individualized treatment algorithm. Based on the information have presented, it is evident that acne lesions, regardless of clinical signs of inflammation, exhibit an inflammatory response. Early-stage acne lesions show a lymphoid perivascular infiltrate, with lymphocytes and macrophages releasing various inflammatory cytokines. P. acnes, through the release of lytic enzymes and lipases, disrupts the follicular epithelium, leading to inflammation. In the late stage, neutrophilic response occurs, with myeloid cells phagocytizing P. acnes in the dermis. Polymorphonuclear leukocytes (PMN) infiltrate the lesion, resulting in pustule formation and eventual rupture. These inflammatory processes involve the release of inflammatory cytokines, vasodilation of vessels, and melanogenesis. Different cell types and depths within the lesions, as well as variations in the severity of ruptures in the affected infundibular wall, can be observed histologically. Considering the differences in histology, immunohistochemistry and clinical characteristics
of various acne lesions, it is reasonable to suggest that different types of lesions may respond differently to acne therapies and may require distinct treatment approaches. While current guidelines often recommend applying anti-acne products or systemic medications to the entire face, the response of inflammatory and non-inflammatory lesions to therapy may differ in terms of timing and effectiveness. Further research and discovery of targeted therapies based on the pathophysiology of individual lesion types may contribute to more effective and precise treatment strategies for acne vulgaris.17
Genetic factors play a significant role in the development of acne vulgaris and several studies have identified various genetic loci associated with the condition. These findings provide insights into the biological pathways involved in the pathogenesis of acne and may help in developing effective acne treatments. An improved acne classification system that takes into account clinical, molecular biological and histological features is needed even though, the existing classifications, including the European
Dermatology Forum (EDF) guideline, have provided valuable frameworks for assessing and managing acne, they may not fully capture the complexity and varied stages of acne lesions. By incorporating a classification system that considers the individual stages of acne lesions and their underlying causes, it may be possible to enhance identification and treatment strategies for each stage of acne. Such a classification system could potentially provide a more comprehensive understanding of the disease process and enable targeted therapies that address the specific pathophysiological mechanisms at play. To develop an improved classification, it would be necessary to integrate clinical observations with molecular and histological findings. This could involve incorporating molecular markers, genetic factors, inflammatory cytokine profiles and histopathological characteristics into the classification system. By doing so, a more precise and personalized approach to acne management could be achieved. Further research and collaboration among dermatologists, researchers and clinicians would be essential in developing and validating an improved acne
classification system. By combining clinical, molecular biological and histological features, we may be able to advance our understanding of acne and improve the identification and management of each stage of the condition. Hence consulting with a dermatologist or healthcare professional who stays up-to-date with the latest research and guidelines would be advisable for personalized acne management.
1. Toyoda M, Morohashi M. Pathogenesis of acne. Med Electron Microsc. 2001 Mar;34(1):29-40. doi: 10.1007/ s007950100002. PMID: 11479771.
2. Leung, Alexander Kc et al. “Dermatology: how to manage acne vulgaris.” Drugs in context vol. 10 2021-8-6. 11 Oct. 2021, doi:10.7573/dic.2021-8-6
3. Sutaria AH, Masood S, Schlessinger J. Acne Vulgaris. [Updated 2023 Feb 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK459173/
4. Mitchell, B.L., Saklatvala, J.R., Dand, N. et al. Genomewide association metaanalysis identifies 29 new acne susceptibility loci. Nat Commun 13, 702 (2022). https://doi. org/10.1038/s41467-02228252-5
5. Navarini, A., Simpson, M., Weale, M. et al. Genome-wide association study identifies three
novel susceptibility loci for severe Acne vulgaris. Nat Commun 5, 4020 (2014). https://doi. org/10.1038/ncomms5020
6. Heng, A.H.S., Say, YH., Sio, Y.Y. et al. Gene variants associated with acne vulgaris presentation and severity: a systematic review and metaanalysis. BMC Med Genomics 14, 103 (2021). https://doi. org/10.1186/s12920-02100953-8
7. Sang Ju Lee, Moo Yeol Hyun, Kui Young Park, Beom Joon Kim, A tip for performing intralesional triamcinolone acetonide injections in acne patients, VOLUME 71, ISSUE 4, E127, DOI:https://doi.org/10.1016/j. jaad.2014.04.030
8. Kraft, John, and Anatoli Freiman. “Management of acne.” CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne vol. 183,7 (2011): E430-5. doi:10.1503/ cmaj.090374
9. Gallagher, Tara et al. “Dermatologist Use of Intralesional Triamcinolone in the Treatment of Acne.” The Journal of clinical and aesthetic dermatology vol. 13,12 (2020): 41-43.
10. National Guideline Alliance (UK). Intralesional corticosteroids for the treatment of individual acne vulgaris lesions: Acne vulgaris: management: Evidence review K. London: National Institute for Health and Care Excellence (NICE); 2021 Jun. (NICE Guideline, No. 198.) Available from: https://www. ncbi.nlm.nih.gov/books/ NBK573050/
11. COMMENTARY to Kwon et al. on p. 241, Diet in Acne: Further Evidence for the Role of Nutrient Signalling in Acne Pathogenesis, volume 92, issue 3 , Acta Derm Venereol 2012; 92: 228–231 ,https://www.medicaljournals. se/acta/content/ html/10.2340/00015555-1325
12. Layton, Alison. “The use of isotretinoin in acne.” Dermato-endocrinology vol. 1,3 (2009): 162-9. doi:10.4161/ derm.1.3.9364
13. Del Rosso, James Q. “Face to face with oral isotretinoin: a closer look at the spectrum of therapeutic outcomes and why some patients need repeated courses.” The Journal of clinical and aesthetic dermatology vol. 5,11 (2012): 17-24.
14. Agarwal US, Besarwal RK, Bhola K. Oral isotretinoin in different dose regimens for acne vulgaris: A randomized comparative trial. Indian J Dermatol Venereol Leprol 2011;77:688-694
15. Sardana K, Garg VK. Efficacy of low-dose isotretinoin in acne vulgaris. Indian J Dermatol Venereol Leprol 2010;76:7-13
16. Zaenglein, A. L., Pathy, A. L., Schlosser, B. J., Alikhan, A., Baldwin, H. E., Berson, D. S., … Bhushan, R. (2016). Guidelines of care for the management of acne vulgaris. Journal of the American Academy of Dermatology, 74(5), 945–973.e33. doi:10.1016/j. jaad.2015.12.037
17. Prapapan et al. Proposal for a 4-type Classification of Acne: An Evidence-Based Review of the Literature. Volume: 14, 2020, Pages 38-43, Open Dermatology Journal DOI: 10.2174 / 1874372202014010038
