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Vaccines should be recommended for patients treated with biologics Psoriasis
Psoriasis I The Chronicle
P RACTICAL T HERAPEUTICS and C LINICAL N EWS from the W ORLD of D ERMATOLOGY
n Checking a patient’s vaccine status should be standard before treating with a biologic
O C T./N O V. 2015
by EMILY INNES,
Patients expecting improved outcomes
See page 4
Eczema in first two years of life linked to common food allergies Atopic dermatitis
n Early life events crucial to development of food allergy, tolerance
by JOHN EVANS,
Associate Editor, The Chronicle
czema in the first two years of life appears to be associated with common food allergies, according to results of a case control study published in the International Archives of Allergy and Immunology (May 2015; 166(3):199–207). This study, referred to as the SPAACE study (Surveying Prevalence of Food Allergy in All Canadian Environments), consisted of a cross-
Canada random telephone survey that occurred between Sept. 2010 and Sept. 2011. Participants included in the investigation were 480 individuals with either self-reported convincing symptoms or a physician’s diagnosis of an allergy to any of nine common food allergens to milk, egg, peanut, tree nut, shellfish, fish, wheat, soy, or sesame. A total of 4,950 healthy controls also completed the survey, the authors reported. According to investigators, the
Sunburn art likely to promote new, unusual tanning practices NMSC
n Disturbing trend amplifies deleterious effects of tanning, dermatologist says
by JOHN EVANS, Associate Editor, The Chronicle
he emergence of ‘sunburn art’—creating an image on the skin by applying an adhesive stencil or painting on sunPlease turn to Sunburn art page 12à block before
questions in the survey asked about environmental factors including daycare attendance, pet ownership, whether the individual spent time living on a farm, as well as personal and family history of atopy including Dr. Moshe both eczema and Ben-Shoshan asthma. “We were especially interested in eczema in early life because all [recent] studies suggest that events in the environPlease turn to Eczema page 21à
n The Chronicle is committed to maintaining leadership in environmentally sustainable policies, and to encouraging the adoption of “green-aware” practices in healthcare. We invite your comments via e-mail, at: email@example.com
t is important that dermatologists routinely check patient’s immunization status before starting them on biologic therapies, according to a Markham, Ont.-based dermatologist who spoke at Dermatology Update in Toronto. “We know that patients with different inflammatory diseases may have an increased risk of infection so to consider anything you can do to reduce the risk of those infections would be very important,” said Dr. John Kraft, with the Lynde Centre for Dermatology. “Medications, as well, [such as biologics] that you add on to treat your patient with inflammatoDr. John Kraft ry conditions will also increase the chances of certain infections. Immunizations have their way of decreasing this infection risk.”
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All rights reserved. Chronicle Information Resources Ltd. Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917
Associate Editor, The Chronicle
Patients on biologics more susceptible to infection Dr. Kraft said when clinicians are screening for cardiovascular comorbidities, latent tuberculosis or hepatitis, it it is a good opportunity to also consider immunizations. “We are going to be putting them at a disadvantage in terms of susceptibility to getting infections. Therefore we should consider protecting them by offering vaccinations to our patients.” Vaccines should be administered at least two weeks before biologics
Please turn to Vaccines page 20à
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Vol. 21, No. 7
TOP of the MONTH
Outcomes of continuous sutures equivalent to interrupted sutures for facial wounds No significant differences seen in cosmetic outcomes between continuous or interrupted suture techniques, may save time and materials, according to the results of a Vancouver study . . . . . . . . . . . . . . . . 8
The latest news in pediatric dermatology: Cancer survivors and sun avoidance Childhood cancer survivors, in spite of instruction on sun protection habits, do not generally fully follow these instructions, and additional efforts to improve sun protection behaviour will be needed throughout their lives . . . . . . . . . . . . . . . . 12
Clinical erythema assessment tool for intra- and intra-rating of facial erythema determined reliable Evaluated for the first time, the Clinician Erythema Assessment (CEA) grading scale has been determined to be an effective measure of facial erythema associated with rosacea . . . . . . . . . . . . . . . . .18 Chronicle Postgraduate Educational Supplement In this month’s Chronicle Post graduate Educational Supplement, Spanish researchers investigate how adherence to drug treatments and adjuvant barrier repair therapies play a key role in achieving clinical improvement in patients with mild to moderate acne . . . 23
Do JAKs promote hair growth? From the News Resources of The Chronicle
Janus kinase (JAK) inhibitors, used for treating auto-immune diseases such as rheumatoid arthritis, appear to strongly promote hair growth when applied topically to the skin, say researchers from Columbia University Medical Center in New York. The findings were published in Science Advances (Oct. 2, 2015; 1(9): e1500973). The researchers were testing JAK inhibitors orally for the treatment of alopecia areata. They have also been tested for treating plaque psoriasis. In a press release from the Medical Center on Oct. 23, 2015, study author Angela M. Christiano, PhD, said: “What we’ve found is promising, though we haven’t yet shown it’s a cure for pattern baldness.” Dr. Christiano and her team have been investigating the use of JAK inhibitors to impair the auto-immune response associated with alopecia
October/November 2015 • Vol. 21 No. 7
E-mail: firstname.lastname@example.org ISSN No. 1209-0581
Contents © Chronicle Information Resources Ltd., 2015 except where noted. All rights
A Message from the Medical Editor
areata. In the course of those experiments, Dr. Christiano found that healthy mice grew more hair when the drugs were applied topically than when they were taken systemically. That suggested JAKs were doing more than just reducing the immune system’s attack on the hair follicles— they may be working on the hair follicles directly in some way. Researchers found that JAK inhibitors applied topically were making the hair follicles come out of dormancy rapidly, with some resting hair follicles sprouting a new hair in less than 10 days. “There aren’t many compounds that can push hair follicles into their growth cycle so quickly,” said Dr. Christiano in the release. “Some topical agents induce tufts of hair here and there after a few weeks, but very few compounds have this potent an effect so quickly.”
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Oct./Nov. 2015 · 3
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THE CHRONICLE of S K I N & A L L E R G Y
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n this issue of THE CHRONICLE we cover a multitude of topics ranging from childhood food allergies to an update on the treatment of psoriasis to the best way to repair a Mohs surgical defect. As in every issue, there is significant content related to research across the country. Starting out west Dr. David Zloty’s pioneer research on suture techniques answers an important question “which method will give the best cosmetic outcome”? (see page 8). It’s great to see our Canadian derm surgeons leading the world in this area of research. From Ontario, Dr. Jerry Tan provides readers with insight into the new method for measuring erythema related to rosacea (see page 18). On the psoriasis front Drs. Melinda Gooderham and Julia Carroll weighin on the recent development with respect to brodalumab in suicide risk (page 4). In the same article Dr. Charles Lynde reflects upon the target for treating psoriasis and how we have gone from a target of PASI 50 in 2005 to PASI 90 or 100 in 2015. With the treatments we have in our toolkit and the addition of the anti IL-17s we can help achieve these targets in the majority of our patients. Drs. Lynde and Gooderham also highlight the Please turn to Message page 21à
Editor, Cosmetic Dermatology Sheldon V. Pollack, MD, FRCPC
John P. Arlette, MD, FRCPC Benjamin Barankin, MD, FRCPC Marc Bourcier, MD, FRCPC Eric Goldstein, MD, FRCPC Peter Hull, MD, FRCPC Rod Kunynetz, MD, FRCPC Richard Langley, MD, FRCPC Danielle Marcoux, MD, FRCPC
R.A.W. Miller, MD, FRCPC H. Eileen Murray, MD, FRCPC Kim Papp, MD, FRCPC Yves Poulin, MD, FRCPC Melanie D. Pratt, MD, FRCPC Denis Sasseville, MD, FRCPC Jerry Tan, MD, FRCPC Ronald B. Vender, MD, FRCPC
Founding Editor Colin A. Ramsay, MD, FRCPC (1936-2003)
Publisher Mitchell Shannon Editorial Director R. Allan Ryan Senior Editor Lynn Bradshaw Associate Editors John Evans, Emily Innes
Sales & Marketing Sandi Leckie, RN Production and Circulation Cathy Dusome Comptroller Rose Arciero
Contacting The Chronicle
“If you don’t achieve a target [with a psoriasis therapy] after three to six months, you have not hit the bull’s eye.” Dr. Charles Lynde, medical director at the Lynde Institute for Dermatology in Markham, Ont., and associate professor in the Department of Medicine at the University of Toronto (see page 4)
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4 · Oct./Nov. 2015
THE CHRONICLE of SKIN & A L L E R G Y
Patients expecting more improvement in disease
n PASI 75 was once the gold standard for treatment outcomes. Now PASI 90 or even 100 are the goals by LOUISE GAGNON,
Correspondent, The Chronicle
ew psoriasis treatment choices that do not require monitoring and therapies that address patients with moderate psoriatic disease are encouraging, developments, according to Canadian clinicians who participated in a telephone interview with THE CHRONICLE OF SKIN & A L L E R GY . They also acknowledge that the suspension of studies into one antibody targeting the IL17 receptor has been a disappointment. The manufacturer of the monoclonal antibody brodalumab, designed to treat moderate-to-severe psoriasis, made the decision to cease participating in clinical trial programs after reports of completed suicides led to the U.S. Food and Drug Administration indicating that a restrictive label on the therapy would be required. “It’s well-established that this population is already at risk for an increased risk of suicide,” explained Dr. Melinda Gooderham, a dermatol-
ogist and medical director of the Skin Centre for Dermatology in Peterborough, Ont. “But it is actually a low Dr. Melinda number of cases, Gooderham and it was not a significant number [of cases],” said Dr. Gooderham. “The decision [by the company] was not due to safety concerns, but was a Dr. Julia Carroll business decision.” Other agents that target the IL-17 pathway—secukinumab, which is commercially available, and ixekizumab, which is still under investigation, have not produced similar concerns.
Best to discuss with patients Some clinicians say the news about brodalumab may lead patients to think twice about initiating therapy with new biologic agents, according to Dr. Julia Carroll, a dermatologist, medical director and co-founder at Compass Dermatology in Toronto, and a lecturer at the University of Toronto. “There is the potential that patients will stumble across [news of reports of suicide], so it’s best that
we address it head on and explain they may see reports of this and explain it to them,” said Dr. Carroll. “It is better that they Dr. Ian Landells don’t come across [the information] themselves and then decide not to use [that category of treatments].” Another new development is Dr. Charles Lynde that established biologic agents are beginning to be studied in the pediatric population. Dr. Ian Landells, medical director at Nexus Clinical Research in St. John’s, Newfoundland and Labrador, and clinical associate professor at Memorial University, is encouraged by data presented in the first quarter of 2015, which demonstrated that ustekinumab produced a favourable response in adolescents with severe plaque psoriasis aged 12 to 17 years and the regular weight-based dose proved more efficacious and had a prolonged effect compared to the half weight-based dose. “The efficacy was outstanding, and there were no new safety sig-
Please turn to Psoriasis page 6à
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THE FIRST AND ONLY † IL-17A INHIBITOR
High efficacy sustained at
PASI 90 scores
achieved at week 12 vs. placebo ‡ (secondary endpoint)
59.2% of patients achieved PASI 90
65.0% of patients achieved PASI 90
vs. 1.2% placebo (p<0.0001, secondary endpoint)
vs. 33.4% etanercept (p<0.0001, secondary endpoint)
81.6% of patients achieved PASI 75
COSENTYX’S SAFETY PROFILE
The most common AEs were nasopharyngitis (11.4%), diarrhea (4.1%), and upper respiratory tract infection (2.5%)
vs. 4.5% placebo (p<0.0001, co-primary endpoint)
Indication and clinical use:
Contraindications: • Severe hypersensitivity to the active substance or any of its excipients
• Caution in patients with active Crohn’s disease • Caution in latex-sensitive patients: natural latex derivatives in the removable cap of the pre-filled syringe/COSENTYX® SensoReady® pen • Should not be used with live vaccinations; can be used with those that are inactivated or non-live • Pregnancy: should not be used unless expected benefits to the mother clearly outweigh potential risks to fetus • Nursing women: Caution should be exercised
Relevant warnings and precautions: • Infections: could potentially increase risk of infections; caution in patients with a chronic infection or recurrent infections; patients should be evaluated for tuberculosis prior to initiation of treatment with COSENTYX®
For more information: Consult the Product Monograph at www.novartis.ca/CosentyxMonograph for important information relating to adverse reactions, drug interactions, and dosing information which have not been discussed in this piece. The Product Monograph is also available by calling 1-800-363-8883.
COSENTYX® (secukinumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. • Geriatric patients ≥65 years: Although limited data, no differences in safety or efficacy observed between older and younger patients • Safety and effectiveness not established in patients below 18 years of age
AE: adverse event. † Clinical significance unknown. ‡ ERASURE was a randomized, multicenter, double-blind, placebo-controlled phase III trial. Patients were randomized in a 1:1:1 ratio to receive COSENTYX® 300 mg (n=245), COSENTYX® 150 mg (n=245), or placebo (n=248). COSENTYX® groups received two 150-mg subcutaneous injections (i.e., 300 mg total) or one 150-mg injection plus one placebo injection. Both injections were administered once weekly at weeks 0, 1, 2, 3, then monthly from week 4 to week 48. § FIXTURE was a randomized, multicenter, double-blind, placebo- and active-controlled phase III trial. Patients were randomized in a 1:1:1:1 ratio to receive COSENTYX® 300 mg (n=327), COSENTYX® 150 mg (n=327), etanercept (n=326), or placebo (n=326). COSENTYX® groups received two 150-mg subcutaneous injections (i.e., 300 mg total) or one 150-mg injection plus one placebo injection. Both injections were administered once weekly at weeks 0, 1, 2, 3, then monthly from week 4 to week 48. Etanercept patients received 50 mg administered subcutaneously twice weekly from baseline until week 12 and then once weekly through week 51, in accordance with the standard dosing regimen. References: 1. COSENTYX® Product Monograph. Novartis Pharmaceuticals Inc., February 27, 2015. 2. Langley RG, Elewski BE, Lebwohl M et al. Secukinumab in plaque psoriasis – results of two phase III trials. N Engl J Med 2014;371(4):326–38. 3. Data on file. Novartis Pharmaceuticals Canada Inc.
COSENTYX and SensoReady are registered trademarks. Product Monograph available on request. Printed in Canada 15COS020E © Novartis Pharmaceuticals Canada Inc. 2015
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6 · Oct./Nov. 2015
Indication and clinical use: ROSIVER (ivermectin) Cream, 1% is for the topical treatment of inflammatory lesions (papules and pustules) of rosacea in adults 18 years of age or older. Relevant warnings and precautions: • Risk of local skin reactions, allergic reactions, and skin irritation • Avoid concomitant use of potentially irritating topical products or procedures • Caution in pregnant women • Risk of serious adverse reactions in nursing infants (nursing women should discontinue nursing or the drug) For more information: Please consult the Product Monograph at http://galderma.ca/ Portals/4/pdf/ROSIVER_productmonograph.pdf for important information relating to adverse reactions, drug interactions, and dosing/administration information which have not been discussed in this advertisement. The Product Monograph is also available by calling us at 1-800-467-2081. References: 1. ROSIVER™ Product Monograph. Galderma Canada Inc. April 22, 2015. 2. Stein Gold L et al; Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehiclecontrolled pivotal studies. J Drugs Dermatol. 2014;13(3):316–323. A phase 3, multicentre, randomized, double-blind, 12-week, vehiclecontrolled, parallel-group study assessing the efficacy and safety of ROSIVER once daily in 683 patients with moderate to severe papulopustular rosacea (IGA score of 3 or 4). The co-primary efficacy endpoints were the success rate based on the IGA outcome (percentage of patients “clear” and “almost clear” at Week 12 of the study) and absolute change from baseline in inflammatory lesion counts. 3. Taieb A et al; Ivermectin Phase III Study Group. Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial. Br J Dermatol. 2015;172(4):1103–10. An investigator-blinded, multicentre, randomized, parallel-group study comparing the efficacy and safety of ROSIVER once daily with metronidazole 0.75% cream twice daily in 962 patients with moderate to severe papulopustular rosacea (IGA score of 3 or 4) over a 16-week treatment period. The primary efficacy endpoint was percent change in inflammatory lesion counts from baseline to week 16. IGA: Investigator Global Assessment.
THE CHRONICLE of SKIN & A L L E R G Y
Psoriasis: Patients expect improvement
Continued from page 4 nals,” said Dr. Landells. “The European regulatory authority gave a favourable response for the use of ustekinumab in adolescents based on these data. We are hoping it will lead to a similar decision in North America.”
Outcome goals changing Dr. Charles Lynde, medical director at the Lynde Institute for Dermatology in Markham, Ont. and associate professor in the Department of Medicine at the University of Toronto, said the other two agents that target IL-17 do not appear to present the same concern as brodalumab. “The other two companies are distancing themselves and saying [their agents] are different,” said Dr. Lynde. While brodalumab proved more effective than ustekinumab in clinical studies, a restrictive warning for its use would mean in practical terms that dermatologists would likely have to screen patients for psychiatric health before initiating them on brodalumab, explained Dr. Lynde. “It would be a roadblock [to prescription of brodalumab],” Dr. Lynde said. As with other goals in medicine, practitioners of dermatology are eager to see improved outcomes in their patients, which has given rise to the concept of treating to target. “Ten years ago, we felt the target was PASI (Psoriasis Area and Severity Index) 50,” said Dr. Lynde. “Then the FDA asked for PASI 75 as the gold standard. Now in clinical trials, people are talking about PASI 90 or PASI 100 or near clear or essentially clear. That is what we are trying to achieve, and that is what many patients want. “If you don’t achieve an [expected] target after three to six months, you have not hit the bull’s eye,” said Dr. Lynde. “Either you can look at maximizing the dosage of the drug or changing to a different drug with a different mechanism of action. We have many more therapies [available to us]. It was not so long ago that we just had methotrexate and before that we only had tar and light. With a bigger armamentarium, we can mix and match to achieve good results for our patients.” Some patients may prefer oral agents such as the phosphodiesterase-4 inhibitor apremilast, noted Dr. Lynde. “This is for a population that is not ready for biologics but wants more than topical agents,” said Dr. Lynde during an interview. “Apremilast requires no monitoring, and it is very safe.”
Dr. Gooderham agreed that apremilast is very palatable for many patients and while she described it as less efficacious than a biologic, it is not a fair comparison to pit the oral agent against a biologic with respect to its place in the therapeutic armamentarium. “Patients may have five per cent body surface area [affected by psoriasis], but they may not want to put on ointment regularly,” explained Dr. Gooderham. “A therapy like [apremilast] is great for that patient, and it is less expensive than a biologic.” According to Dr. Gooderham, there is a whole “middle ground” of patients with psoriasis for whom a biologic is not indicated, but whose condition remains uncontrolled with traditional topical therapies or who would opt not to take methotrexate. Such patients are suitable candidates for an oral therapy like apremilast. Other oral therapies, such as tofacitinib, a Janus kinase inhibitor, have been studied against the biologic etanercept, and it was concluded the novel therapy was non-inferior to the biologic, noted Dr. Gooderham.
Studying inflammation pathways Psoriasis is a condition that is illustrative of inflammation that is present in the body. Indeed, research presented by Dr. Wayne Gulliver at the annual meeting of the American Academy of Dermatology concluded cardiovascular health was compromised in psoriatic patients in Newfoundland, particularly when they had early onset of disease, and that exposure to a biologic helped protect the cardiovascular health of these patients. Specifically, there was an 83% decreased risk of having a myocardial infarction in the psoriatic population with exposure to biologic therapy lasting at least one month. “Decreasing inflammation in the
skin and the rest of the body gives these people longer and more fruitful lives,” said Dr. Lynde. The economic burden of psoriasis should not be underestimated, noted Dr. Lynde, pointing to a review that placed direct costs at $51.7 billion to $63.2 billion in the U.S. annually, with indirect costs estimated at a price tag of as high as $35.4 billion annually (JAMA Dermatol 2015; 151(6):651–658). “There are direct costs, and there are indirect costs,” Dr. Lynde said. “There are the direct costs of drugs and seeing doctors. Absenteeism from work, for example, is an indirect cost.” Adjunctive therapies important The use of adjunctive therapies such as effective moisturizers can ward off exacerbation of psoriasis through minimizing the potential for the Koebner phenomenon induced by scratching, noted Dr. Carroll. “For some, psoriasis is very itchy,” said Dr. Carroll. “It’s important that individuals with psoriasis try not to scratch because they can induce psoriasis due to the trauma of repeated scratching.” Other new molecules under development include BI 655066, a biologic which selectively blocks IL23. Phase II data demonstrated patients were clear or almost clear after 12 weeks of therapy and had mild side effects. “It is moving into Phase III, and it looks like a very promising drug,” said Dr. Lynde. “It gives very high efficacy [PASI 90 and 100], and it seems to be very clean in terms of safety.”
Non-proprietary and brand names of therapies: brodalumab (not available in Canada); secukinumab (Cosentyx, Novartis); ustekinumab (Stelara, Janssen); apremilast (Otezla, Celgene); tofacitinib (Xeljanz, Pfizer Canada); etanercept (Enbrel, Amgen).
THERAPEUTIC INDEX Canadian Dermatology Industry Association. . . . . . . . . . . . . 18 Galderma Canada Inc. Rosiver. . . . . . . . . . . . . 7, 6 GlaxoSmithKline Spectro. . . . . . . . . . . . . 2 LEO Pharma
Picato. . . . . . 9
Novartis Cosentyx . . . . . . . . . . . . . 5 Pfizer Corporate. . . . . . . . . . . . . 27 Pierre Fabre Dermo Cosmetique Avéne XeraCalm AD . . . . 19 Procter & Gamble Gillette Venus Swirl. . . . . . . . 28
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NEW ROSIVER (ivermectin) Cream, 1% for the ™
topical treatment of papulopustular rosacea in adults • Demonstrated a powerful and rapid reduction in inflammatory lesions vs. vehicle ° Median percent reduction from baseline in inﬂammatory lesion counts at Weeks 2 and 12 was 30.0% and 76.0% vs. 16.5% and 50.0% for once-daily 2 ROSIVER vs. vehicle cream, respectively; both P<0.001 (secondary endpoint)* • Provided superior efficacy vs. metronidazole 0.75% cream ° Percent reduction from baseline in inﬂammatory lesion counts at Weeks 3 and 16 were 32.5% and 83.0% vs. 30.5% and 73.7% for once-daily ROSIVER vs. twice-daily metronidazole 0.75% cream, respectively; †1,3 both P ≤0.04 (primary endpoint) • Demonstrated an excellent safety and tolerability profile ° Most common adverse reactions were: skin burning sensation, skin irritation, pruritus, and dry skin (1.0% vs. 2.2%, 0.9% vs. 2.4%, 0.8% vs. 1.1%, and 1 0.5% vs. 0.7% for ROSIVER vs. vehicle cream, respectively) ° The safety proﬁle remained stable under conditions of long-term use as observed 1 with treatment for up to one year
ROSIVER (ivermectin) Cream, 1% is for the topical treatment of inﬂammatory lesions (papules and pustules) of rosacea in adults 18 years of age or older. Refer to the page in the bottom right icon for additional safety information and for a web link to the Product Monograph discussing: • Relevant warnings and precautions regarding skin reactions, allergic reactions, and skin irritation; concomitant use of potentially irritating topical products or procedures; use in pregnant women; and serious adverse reactions in nursing infants • Conditions of clinical use, adverse reactions, drug interactions, and dosing/administration instructions The additional safety information page contains the reference list and study parameters relating to this advertisement. *Mean inﬂammatory lesion counts at baseline: ROSIVER 31.0; vehicle 30.5.1 † Mean inﬂammatory lesion counts at baseline: ROSIVER 32.9; metronidazole 0.75% cream 32.1.3 See page XX for additional safety information.
ROSIVER™ is a trademark of Galderma Canada Inc.
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8 · Oct./Nov. 2015
THE CHRONICLE of S K I N & A L L E R G Y
Outcomes of continuous sutures equivalent to interrupted sutures for facial wounds Research
n No significant differences seen in cosmetic outcomes between techniques, Vancouver study reports
by JOHN EVANS,
Associate Editor, The Chronicle
oth interrupted and continuous 5–0 nylon sutures used to close facial wounds from Mohs micrographic surgery (MMS) produced equivalent cosmetic outcomes at all examined time points in a large, randomized trial published in Dermatologic Surgery (Aug. 2015; 41(8):919–928). A total of 105 individuals with facial defects from MMS surgery were enrolled, and 101 of them completed assessment at all time points. All studied scars were at least 4 cm in length. Participants who were randomly selected had half of their scar sutured with interrupted 5–0 nylon stitches, and the other half sutured with running 5–0 nylon stitches. Unblinded scar evaluation was done at one week, eight Dr. David Zloty weeks, and six months by the principal investigator. Blinded photographic assessments were done at one week and six months by both a plastic surgeon and a general dermatologist using three different scar assessment scales.
Photo by Lynn Bradshaw
First of a series of studies The study was the first of a series of studies undertaken by senior author Dr. David Zloty, clinical associate professor, Department of Dermatology and Skin Science, University of British Columbia,
Vancouver, and his colleagues in order to test com- to-side closure, rotation flap, or transposition flap. monly-accepted ideas about skin surgery that may “We also looked at sites,” said Dr. Zloty. “Were be insufficiently supported. “There are concepts there different sites where you are better off using that everybody believes to be true, but when you interrupted versus running?” Again, because of the look at the evidence it numbers and the power is either non-existent, here are concepts of the analysis, there was weak, or of poor qualino perceived difference that everybody ty,” said Dr. Zloty. “One in cosmetic outcome— of the biggest ones was believes to be true, forehead, cheek, lip, or the idea that interruptnose. “That was also but when you look ed sutures were going quite exciting for us,” Dr. to give a better longZloty said, “because at the evidence it is either term final cosmetic some people were saying non-existent, weak, result compared to a that you could use runrunning suture, espening [sutures], maybe, on or of poor quality.” cially on a facial site.” the lateral cheek but you —Dr. David Zlotyq In contrast to this certainly would not want common wisdom, the to use them on the nose. trial found no statistical difference in cosmetic out- Findings a boon to surgeons comes between the two suturing techniques at any Dr. Zloty there has long been debate about experitime point, by any assessor, on any of three differ- ence and how those with more experience might ent scar assessment scales. have better use and handling of instruments and “We were very happy with the findings better suture handling to deal with the limitations because we enrolled a large number of patients of running sutures and still obtain great results. which allowed for a very high degree of statistical Conversely, an inexperienced practitioner using power,” said Dr. Zloty. A statistician from the running sutures may get a compromised cosmetic University of British Columbia was employed to result. However, that did not seem to be case. “We look at the data and to ensure enough patients were able actually to separate my repairs—and I were enrolled so that the study had the statistical had 18 years of experience at that time—vs. my felpower to answer the questions the investigators low’s repairs. She just had one year. And again, we were asking, he said. did not find any difference,” said Dr. Zloty. The data also showed no difference in outcome “This is the largest, randomized clinical trial from different types of reconstruction, whether side- looking to answer this question. There is nothing
The International League of Dermatological Societies (ILDS) recognized the International Albinism Awareness Day on June 13, during the World Congress of Dermatology in Vancouver. This marked the first International Albinism Awareness Day, which was adopted by the United Nations' General Assembly in Nov. 2014. The ILDS initiative was launched at a press conference during the WCD, featuring speakers who described the disease and new research into its physical and social effects. (l-r) Dr. Margot Whitfield (Australia), Dr. Jerry Shapiro (Canada), Prof. Roderick Hay (U.K.), Dr. Henning Grossman (former head of the Regional Dermatology Training Centre [RDTC] in Moshi, Tanzania), Paul Ash (founder, with his brother Peter, of Vancouver-based Under the Same Sun, an albinism awareness group), Dr. Claire Fuller (U.K.) and Dr. Harvey Lui (Canada).
else in the literature that we were aware of that was this large, this well powered, this robust statistically in a randomized, prospective, blinded fashion,” Dr. Zloty said. “I think our results as we have outlined are very strong and I think the results are very valid.” Finding no difference in cosmetic outcomes between the two suturing techniques is a boon to surgeons, said Dr. Zloty, who noted that there are a number of advantages to using running sutures compared to interrupted. “One, you probably use less suture material. With interrupted you may go through more suture, and if you are paying for these sutures there can be a cost saving using the running suture compared to interrupted.” Potentially more important though, he said, is the saving of time. The additional motions needed to tie and cut the additional knots, as well as reload the suture material can add significant time to a procedure. However, Dr. Zloty cautions that this study focused entirely on facial scars of at least 4 cm, so the findings cannot be generalized to other sites on the body or to short scars. “I personally use running [sutures]” even when operating on patients with benign nevi who are concerned about the cosmetic effects, said Dr. Zloty. “Those cosmetic results have been excellent. So my own bias has been that even for shorter scars, or shorter wounds on the face, running will still give you at least equivalent if not better results than interrupted. But that is my own personal bias, not supported by the data from our study.”
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10 · Oct./Nov. 2015
THE CHRONICLE of S K I N & A L L E R G Y
Cancer survivors, sun
n Sun avoidance drops off soon after diagnosis
From the News Resources of The Chronicle
n Fumaric acid esters trialled as alternate Tx From the News Resources of The Chronicle
Childhood cancer survivors, in spite of instruction on sun protection habits, do not fully follow these instructions, and additional efforts to improve sun protection behaviour is needed throughout their lives, according to research published in PLoS One (Sept. 8, 2015). The authors conducted a case-control study of 143 pediatric patients (average age 11.2±4.6 years) who had histories of malignancy, as well as 150 healthy controls (average age 10.4±4.8 years). The mean interval from diagnosis in the patients was 4.4±3.8 years. Validated questionnaires were used to assess sun exposure and protection habits. Both groups reported similar weekday sun exposure time—94±82 minutes a day for patients and 81±65 minutes a day for controls (p=0.83). Only on weekends did patients spend significantly less time outside—103±85 minutes per day compared to 124±87 minutes a day for controls (p=0.02). The longer it had been since patient diagnosis also correlated with time spent outdoors during weekdays and weekends (r=0.194, p=0.02; r=0.217, p=0.01, respectively). Sun exposure also increased noticeably three years after diagnosis, and age positively correlated with sunburns per year and tanning-specific sun exposure, and negatively with use of sun protection. No significant difference in composite sun protection score was seen between the two groups.
Fumaric acid esters (FAE) produced an improvement in both disease severity and quality of life (QoL) in pediatric patients with recalcitrant psoriasis, with generally mild, transient side effects, suggesting the treatment may be a viable alternative systemic treatment in these patients, according to a paper published online in the Journal of Dermatological Treatment (Oct. 9, 2015; 1-7). To investigate the efficacy, impact on QoL, and safety of FAE in these patients, investigators examined 14 patients (mean age 13.7 years, ranging from eight to 17 years) with recalcitrant plaque psoriasis. The patients were treated for a mean duration of 48.6 weeks (ranging from 12 to 124 weeks), and a mean dosage of 564 mg per day (ranging from 180 to 1200 mg maximum daily dose). At baseline, their mean Psoriasis Area and Severity Index (PASI) scores were 10.5 (±1.0 SEM). These compared to 8.6 (±1.1) at week 12, 6.2 (±1.6) at week 24, and 4.9 (±1.5) at week 36. A total of nine (64.3%) patients saw an improvement in their PASI scores. Mean CDLQI at weeks zero, 12, 24, and 36 were 8.9 (±1.4), 6.8 (±1.2), 3.7 (±1.4), and 3.1 (±2.0). Gastrointestinal complaints occurred in 13 patients, flushes in 10, lymphocytopenia in five, and eosinophillia in four.
Pediatric dermatology update
URTICARIA, SYSTEMIC LUPUS ERYTHEMATOSUS LINK Chronic spontaneous urticaria (CSU) may be linked to childhood-onset systemic lupus erythematosus (cSLE), occurring primarily at disease onset and associated with moderate to high lupus activity without major organ involvement, according to research published in International Archives of Allergy and Immunology (2015; 167(3):186-192). The study involved 852 cSLE patients. Guidelines from the European Academy of Allergy and Clinical Immunology, the Global Allergy and Asthma European Network, the European Dermatology Forum, and the World Allergy Organization were used to diagnose CSU. Patients with CSU—determined at urticaria diagnosis—and those without—evaluated at last visit—were assessed for the clinical and laboratory features of lupus, as well as treatment. CSU was seen in 10 cSLE patients (1.17%), with the mean duration of cSLE at diagnosis of urticaria being zero years (-3 to 5 years). Patients with CSU vs. those without had a greater frequency of constitutional symptoms (40% vs. 8%, p=0.006), involvement of the reticuloendothelial system (30 vs.. 3%, p=0.003, mucocutaneous and musculoskeletal manifestations (90% vs 28%; 50% vs. 6%, respectively, both p<0.0001), and use of methylprednisolone pulse therapy (60% vs. 9%, p<0.0001). Those patients with CSU also had higher median SLE Disease Activity Index 2000 (12 vs. 2, p<0.0001), and erythrocyte sedimentation rate (40 vs 19 mm/1st hour, p=0.024).
MALIGNANT VS. NON-MALIGNANT NON-MELANOMA SKIN CANCERS In pediatric patients with non-melanomic skin tumours, the ratio of malignant to benign skin tumours is small, with the most common such lesions being pilomatricoma, pyogenic granuloma, and nevus sebaceous, researchers report in the Journal of Clinical Medicine Research (Oct. 2015; 7(10):770-774). All skin punch and excisional biopsies done in children up to 16 years of age at a single dermatology department between Jan. 2007 and Jan. 2012 were investigated, excluding melanocytic tumours and cystic and infectious lesions. Patient age, sex, location, and histopathologic diagnosis were recorded and their tumours were categorized. Of the 203 lesions in children up to age 16, 97 lesions in 91 patients were nonmelanocytic tumours. Of those 91, 47 (51.64%) were male and 44 were (48.36%) female, and the mean age was 10.55±4.31 years. One (1.03%) of the tumours was malignant while the remaining 96 (98.97%) were benign. Of the non-melanocytic tumours, the most common types were pilomatricoma (22 lesions, 22.68%), pyogenic granuloma (18, 18.54%), and nevus sebaceous (10, 10.3%). The malignant lesion was cutaneous leukemic infiltrate. Children over age 13 were most frequently affected, up to and including 16 years, with 38 (41.7%) patients in that range. Most of the lesions were found on the head or scalp (32 lesions, 32.96%), the trunk (28, 28.84%), and the upper limbs (22, 22.75%).
SURGICAL EXCISION BEST TX FOR HOBNAIL HEMANGIOMA While hobnail hemangioma—also known as targetoid hemosiderotic hemangioma—is typically benign and does not require treatment, complete surgical excision appears to be the most effective approach in cases where intervention is indicated, researchers report online ahead of print in the Journal of Cutaneous Medicine + Surgery (Oct. 16, 2015). The authors conducted a retrospective chart review of all histopathologically confirmed cases of hobnail hemangioma at The Hospital for Sick Children in Toronto between May 2000 and Dec. 2014. Demographic data, as well as clinical characteristics and immunohistochemical staining results were collected. A total of six patients were identified—four male and two female—three of whom had congenital lesions. The lesions were most commonly found on the extremities, and treatment options employed included observation and surgical excision.
ELEVATED RISK OF ARTERIAL PLAQUES SEEN IN PEDIATRIC PSORIASIS PATIENTS Pediatric patients with psoriasis appear to have a higher atherogenic cardiometabolic risk profile, findings which may support the observed link later in life between psoriasis and cardiovascular disease as well as demonstrating a need for screening and education of young patients to minimize later complications, investigators report online in the Journal of Investigational Dermatology (Sept. 30, 2015). Researchers measured lipoprotein composition and function in 44 pediatric patients (mean age 13.0 years) with psoriasis, as well as 44 age- and sex-matched controls, using NMR spectroscopy to measure high density lipoprotein (HDL) cholesterol efflux capacity (CEC). Individuals with psoriasis had higher waist-hip ratios (0.85 vs. 0.80; p<0.002) than controls, as well as higher insulin resistance measures (log transformed HOMA-IR 0.65 vs. 0.41; p=0.07). Both groups had similar traditional lipid values, but having psoriasis was associated with higher concentrations of apolipoprotein B (72.4 vs. 64.6; p=0.02), a decrease in large HDL particles (5.3 vs. 6.7; p<0.01), and a reduced CED after adjusting for age, sex, fasting glucose, HOMA-IR, systolic blood pressure, body mass index, apolipoprotein A-1, and HDL cholesterol concentration (beta 0.22, p=0.02).
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THE CHRONICLE of S K I N & A L L E R G Y
Sunburn art not a harmless practice, dermatologist says Continued from page 1 tanning—is a disturbing trend, says Vancouver clinical and cosmetic dermatologist Dr. David Zloty. The practice, he feels, could encourage people to engage in indoor tanning who might not otherwise, as a form of personal artistic expression.
G N I EE M R O C TH IN S O E T TI 6 1 I C 20
Tanning salon as art studio Dr. Zloty, the medical director of The Dermatologic Surgery Centre in Vancouver, said that while he has not seen patients in his own clinic sporting these ‘artistic’ tan patterns since his patients tend to comprise an older demographic, his staff have
spoken with individuals who have developed suntan ‘tattoos’ at indoor tanning salons. “In fact, [the tanners who were questioned] said it is sometimes standard practice when you go to a tanning salon now,” Dr. Zloty says. “[The salon] will give you
stickers of your choice so that you can decorate your body in whatever way you choose. So I think [the practice of sunburn art] is quite common now.” To date, Dr. Zloty has not observed the practice among outdoor tanners on Vancouver’s popular beach-
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es. “I think right now it is probably primarily with home tanners with sun lamps or sun beds in a salon. “But I think that if the trend becomes more visible, and there is more media exposure, I would not be surprised if this translates to people putting [stickers] on while they are doing their outdoor tanning,” Dr. Zloty added.
Tanning in non-tanners Everyone he is aware of who reported engaging in this decorative behaviour has already been a chronic tanner, says Dr. Zloty, but he is concerned that media attention may draw new tanners. “If the decorative look becomes more accepted in youth culture, will that entice others to specifically go to a salon to get this decorative look? Not so much that they are interested in the appearance of their skin in terms of getting a tan, but in terms of the appearance of this socalled art on their skin,” he says. “That would be my concern long-term, but I do not think we have any evidence that is happening now, not yet.” Regarding the utilization of public education about sun safety in response to this trend, Dr. Zloty suggests there may not be much that can be done to dissuade individuals who are already chronic tanners. The best approach, he thinks, might be to target individuals who are looking at this practice first as a method of self-expression rather than as a way to add a flourish to existing tanning behaviour. “For a certain percentage of the population, I think our messages are falling on deaf ears. “Most of them are aware of the risks but they still feel they look healthier, and they feel better with the tan,” he says. “If they are looking for decorative options, I would rather have them dye their hair and have nice jewellery and do their nails, because those are all solutions that still draw decorative attention to them but carry no longterm consequences to their overall health and the health of their skin.”
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Vol. 20, No. 5
THE CHRONICLE of S K I N & A L L E R G Y
Surveying the current
Dermatologic literature Topical liposomal tranexamic acid has potential in Tx of melasma
PDT investigated for possible treatment of abnormal skin scarring
Index may help caregivers assess healing time of chronic and acute wounds
Oct./Nov. 2015 · 17
Recently come across something from the peer-review literature that you consider to be interesting or impactful? Share it with your colleagues. E-mail your clippings, along with your comments, to: email@example.com
(TA) appears to be a safe, promising new agent for the treatment of melasma, according to research published in the Journal of Cosmetic Dermatology (Sept. 2015; 14(3):174–177). OPICALLY APPLIED LIPOSOMAL TRANEXAMIC ACID
The authors note that although there are several existing treatment approaches for the common skin darkening disorder, none are satisfactory in the management of melasma. As the plasmin inhibitor TA has been reported to improve melasma when either injected locally, or used orally or topically, they set out to compare topical liposomal TA to conventional hydroquinone therapy in the treatment of melasma. A split-face, 12-week trial was conducted with 30 women who had bilateral melasma. Participants blindly applied 5% topical liposomal TA and 4% hydroquinone cream to the assigned sides of their faces, twice daily. Patients also used an assigned sun screen once daily in the morning. Melasma area and severity index (MASI) scores were taken to measure skin pigmentation at baseline and at each visit, separately for each side of the face. MASI scores were also recorded at a follow-up visit one month after end of the treatment period. Of the initial 30 enrollees, 23 completed the study. Mean MASI scores had significantly reduced on both treated sides of the face by the 12 week mark (p<p=0.001). A slightly larger decrease was seen on the sides treated with 5% liposomal TA, but the difference was not significant. Three patients experienced irritation with hydroquinone, and there were no serious adverse events with TA. —For more information visit http://tinyurl.com/nud4g6t
investigators have shown morphological and cellular effects from the application of photodynamic therapy (PDT) in the treatment of skin fibrosis correlating with the degree and severity of the fibrosis, which they suggest indicates that PDT may be ideal for the treatment of abnormal skin scarring, according to research published in Photodermatology, Photoimmunology & Photomedicine (Sept. 2015; 31(5):239–251).
SING AN EX VIVO MODEL,
The authors used PDT combining either 5-aminolevulinic acid (5ALA) or methyl ALA (MALA) with red light illumination at 40 J/cm2 to treat striae alba, fine line, hypertrophic and keloid scars ex vivo. In total, 18 scars were treated. Both H&E and Herovici’s and Weigert’s differential staining methods were used to assess general morphology, while apoptosis, proliferation, metalloproteinase 3, and tropoelastin expression immunohistochemically quantified. Realtime quantitative reverse transcription polymerase chain reaction was used to assess differential gene expression of proliferating cell nuclear antigen (PCNA), types I and III collagen (COL), matrix metalloproteinase 3 (MMP3), and tropoelastin (ELN). They found that apoptosis increased, correlating with decreased proliferation and expression of the PCNA gene. After PDT, matrix components were observed to be re-organized both in hypertrophic and keloid scars. Expression of COL I and COL III genes decreased, but expression of both MMP3 and ELN increased significantly compared to both normal skin and untreated controls (p<0.05). No significant differences were seen between PDT treatments using 5ALA and MALA. —For more information visit http://tinyurl.com/npr9a4n
that can contribute to prolonged healing of complex acute wounds, potentially helping caregivers to predict wound healing time and increasing their ability to detect, refer, and focus on patients who have wounds that require higher levels of care, according to findings published in International Wound Journal (Oct. 2015, 12(5):531–536). ESEARCHERS HAVE DEVELOPED A MODEL OF FIVE FACTORS
Noting that while knowing which wounds are at elevated risk of prolonged healing times is important to enable timely treatment and communication with medical specialists, the authors point out that existing wound healing prognostic models are for chronic ulcers and not acute wounds such as those from trauma or surgery. To address this missing element, the authors developed a model to attempt to detect which factors could impact the duration of healing in complex acute wounds, and trialed it in a large wound expertise centre (WEC). Some 563 patients with acute wounds were included in the study, who were documented in the WEC registry between 2007 and 2012. Patients’ wounds had existed for a median of 19 days (ranging from six to 46 days). Most of the wounds (52%) were located on the leg. The authors identified five significant, independent predictors of prolonged wound healing. These included the wound being located on the trunk (hazard ratio (HR) 0.565, 95% confidence interval (CI) 0.405–0.788, p=0.001), wound infection (HR 0.728, 95% CI 0.534–0.991, p=0.044), wound size (HR 0.993, 95% CI 0.988–0.997, p=0.001), wound duration (HR 0.998, 95% CI 0.996–0.999, p=0.005), and patient age (HR 1.009, 95% CI 1.001–1.018, p=0.020). However, diabetes was not a significant predictive factor. —For more information visit http://tinyurl.com/pfoyrch
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THE CHRONICLE of S K I N & A L L E R G Y
Clinical erythema assessment tool for facial erythema determined to be reliable Rosacea
n Study evaluates inter- and intra-rater effectiveness of scale for erythema associated with rosacea
by EMILY INNES,
Associate Editor, The Chronicle
he Clinician Erythema Assessment (CEA) grading scale has been deemed an effective way to assess facial erythema of rosacea by Canadian and American dermatologists, according to a study published in The Journal of the American Academy of Dermatology (Oct. 2014; 71(4):760– 763). The reliability of the assessment scale has never been evaluated previously. The objective of this study was to evaluate the inter-rater and intrarater reliability of the CEA. “Currently, there is only one Food and Drug Administration-approved pharmacologic treatment that directly targets erythema of rosacea, leaving a potential unmet need among patients with rosacea,” stated the authors in the study. “The development of clinical therapies necessitates reliable, responsive, discriminatory, and validated outcome measure to standardize diagnosis, evaluation, and treat-
ment.” Twelve U.S. board-certified dermatologists participated in the study to rate 28 patients with facial erythema. Of these, three were male and 25 female, between the ages of 18 and 61 years and were all Dr. Jerry Tan Caucasian with Fitzpatrick skin phototype ranging from I to III. The dermatologists all underwent a consensus training program before evaluating the patients. They were provided with reference photographs on the use of the CEA and discussed the results of the evaluations to achieve consensus. During the rating process, each dermatologist evaluated each subject twice with at least a two-hour interval between evaluation sessions. The inter-rater reliability for session one was a weighted 6 of 0.74 and for session one and session two was 0.673. This, according to the
“The high inter-rater reliability found in this study for the CEA was reassuring—demonstrating that different raters could consistently grade severity of redness.” Dr. Tan said the scale is simple to use with its five grades—clear, almost clear, mild, moderate, and severe— High level of reliability reassuring that have a descriptive text to match “The level of intra-rater reliability was each grade. The clinician needs to previously unknown. This is an impormatch the grade of erythema that tant concept of any measurement most closely resembles that of the scale as it determines how well other patient. He said the scale is also easy raters achieve the same outcome,” to teach because of the descriptions stated Dr. Jerry Tan, a Windsor, Ont.and the visual he high inter-rater guides. “Accurate and reliability found in reliable means to this study for the CEA evaluate skin redness is critical in was reassuring— determining the demonstrating that different raters could effect of medications and/or proconsistently grade severity of redness.” cedures on red—Dr. Jerry Tanq ness of various skin conditions,” said Dr. Tan regarding the clinical based dermatologist and the study’s importance of an effective grading lead author, in an e-mail to T H E scale. CHRONICLE OF SKIN & ALLERGY. A limitation of the study noted by the researchers was that all the raters were all experienced dermatologists who were trained. Dr. Tan said other dermatologists and general physicians would likely yield the same reliability if they have been trained to use the tool. Another limitation of the study was the short time interval of two hours between ratings, which according to the authors could lead to recall bias because clinicians may have been able to remember previous scores. As well, using photographs for the training can be problematic because photos can distort light reflection, colour and depth. However, the investigators added that it was necessary to use them for convenience in the training module. Landis and Koch score, is considered a fair to good reproducibility where perfect is 1.0. For intra-rater reliability, the overall weighted 6 statistic between session one and session two was 0.692, reported the investigators in their study.
One more severity level needed While the authors concluded that they support the CEA as a tool for evaluating facial erythema in rosacea, Dr. Tan noted that he might propose two changes to the scale and training: “An added grade of very severe may have been useful to ensure that the entire spectrum of redness was represented. More images of redness in people with different skin colour may be useful in the future.” More information is available at: http://ow.ly/FdN17
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20 · Oct./Nov. 2015
THE CHRONICLE of S K I N & A L L E R G Y
Vaccines recommended for patients on biologic therapy Continued from page 1 are started, but for a live vaccine ideally four weeks should be allotted before starting the therapy (J Rheumatol 2012: 39:1583–1602). Immunocompromised individuals who are underimmunized are vulnerable to serious infections and even
death; however, healthcare providers should also consider that inappropriate administration of live vaccines can lead to serious adverse events in the immunocompromised host,” stated Dr. Claire Bombardier, professor of medicine at the University of Toronto, et al in the Journal of
Rheumatology paper. Vaccines can be either in a live or killed/inactive form and Dr. Kraft said it is critical to find out which vaccine a patient is receiving and which brand. Another consideration is live virus shedding, noted Dr. Kraft. The probability of acquiring a vaccine virus
after close contact with a single live attenuated influenza virus recipient is estimated at 0.58% to 2.4%. Even though the risk is generally low, he said, “it is still worthwhile to consider isolating your immunosuppressed patient from the patient who received the live vaccine, or at
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least holding off on the live vaccine in the household context of someone who is immunosuppressed.”
Tx should be stopped before adminstering live vaccine Treatment can continue if a patient requires an inactive vaccine while on a biologic. However, Dr. Kraft said if a patient requires a live vaccine then the therapy should be stopped for two to five halflives of the biologic before the vaccine is administered. This ranges anywhere from eight to 21 days for etanercept (4.3 mean half-life, days) to 92 to 230 days for ustekinumab (46 mean halflife, days) (J Rheumatol; 2012:39:1583–1602). “It seems like a long time to stop the drug, but I think it is worthwhile to consider because you want to make the [live] vaccine as safe as possible when it is administered,” said Dr. Kraft. After the vaccine is administered it is recommended to wait two to four weeks before restarting the biologic. Dr. Kraft said some routine vaccinations to consider before starting on biologics include the influenza vaccine (yearly); pneumococcal vaccine (every three to five years); hepatitis B vaccine (vaccine if serology test is negative); diphtheria, pertussis, and tetanus (Tdap) vaccine (every 10 years); measles, mumps, and rubella (MMR) vaccine (adult dose is live so preferably before biologic is started); and zoster vaccine (live). Dr. Kraft said inflammatory disease patients have been found to have an increased risk of developing herpes zoster from the general population. While the risk does not usually increase until after the age of 60 years, for some patients, such as rheumatoid arthritis or lupus patients, their risk is increased over the age of 50 years. Other vaccines to consider include the human papillomavirus vaccine in young females and males, and vaccines for travelling patients. Dr. Kraft said the U.S. Centers for Disease Control and Prevention’s website (cdc.gov) is a good resource tool for travellers. It provides recommended vaccines based on the risk of those diseases in the country the patient is visiting.
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THE CHRONICLE of S K I N & A L L E R G Y
Oct./Nov. 2015 · 21
Eczema in first two years linked to common food allergens Continued from page 1 food allergy and is associated large amounts through the ment that occur in early life with higher risk of food aller- mouth, you are more likely to are crucial to the develop- gy, especially peanut and tree induce tolerance. But when ment of food allergy and tol- nuts, but less likely to milk.” the skin is impaired and the erance,” says study lead This supports the dual first introduction is through author Dr. Moshe Ben- allergen exposure hypothe- the impaired skin barrier, you Shoshan, assistant professor, sis, he says. “So if you have do not have the same tolerDivision of Pediatric Allergy early onset of eczema then ance-inducing mechanism and Clinical Immunology, you are more likely to be and you might induce allerDepartment of house Pediatrics, gy,” says introduced to food allergens 7/16/2015 dermcity ad 07-16-15_WCD_Daily_2015_Rates+Data 3:36Dr. PMBen-Shoshan Page 1 McGill University Health in an undesirable way—a regarding the hypothesis. Center in Montreal. The study way that will lead more to Previous research pubwas supported by AllerGen allergy rather than toler- lished in The Journal of and Health Canada. Allergy and Clinical ance.” Data showed that for all Immunology (Jan. 2013; Dual allergen exposure of the included allergens, 131(1):135–143.e1–12) from The dual allergen exposure there was an increased risk of U.K. investigators showed hypothesis was proposed by probable allergy associated that in children at higher risk Dr. Gideon Lack in 2008 in a with three factors: a personal of food allergy—and children report published in The history of eczema in the first with eczema are at higher Journal of Allergy and Clinical two years of life, asthma, or risk of developing food allerImmunology (June 2008; hay fever (odds ratio (OR) gy—early introduction of 121(6):1331–1336). 2.3, 95% CI 1.6–3.5; OR 2.8, peanut is better for inducing “When you introduce 95% CI 2.2–3.6, OR 2.3, 95% CI tolerance instead of allergy, something early in life in 1.8–3.0 respectively); food allergy in parents or siblings (OR 3.7, 95% CI 2.5–5.6 for mother, OR 3.0, 95% CI 1.8– 5.1 for father, and OR 3.1, 95% Continued from page 3 CI 2.2–4.2 for siblings), and role of the phosphodiesterase-4 inhibitors and how it is prefhigh household income (top erential treatment for some of our patients. Comments from the Rock include Dr. Ian Landells’ 20%, OR 1.5, 95% CI 1.2–2.0). It is not surprising to find update on the importance of treating pediatric psoriasis and atopy and generalized Dr. Lynde and others on the importance of targeting inflameczema associated with food mation to decrease cardiovascular risk in moderate-toallergy, says Dr. Ben-Shoshan, severe psoriasis patients. As well they introduce you to “but the interesting part is that some of the newer biologic agents under development, we showed that eczema in including IL-23, which in phase 2 has excellent efficacy. the first two years of life is cru- Soon patients may be offered treatment which is one injeccial for the development of tion per year.
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says Dr. Ben-Shoshan. “Our study supports that and extends it to most food allergens, except milk, because I think milk is introduced early in life even before eczema starts to appear,” he says. “[The findings] show that you probably need to protect the skin at the same time you introduce food through the mouth. I think it has practical implications.”
Eczema on the rise The findings of the study are particularly important because other research has shown that the rate of eczema in the world is increasing, particularly in North America, says Dr. Ben-Shoshan. “So the question is now why is eczema rising in prevalence?” Colder, drier
environments are known to be associated with increased loss of moisture from the skin, he says. Dr. Ben-Shoshan questions whether the increase in eczema prevalence could be related to environmental factors such as more people staying indoors being exposed to air-drying central heating and air-conditioning or immigrants having skin that is not used to the Canadian climate. More research is needed, said Dr. Ben-Shoshan, who added that in the future he would like follow up this research with a study in twins to investigate how genetic factors interplay with environmental factors in the development of food allergy.
In Montreal, Dr. Moshe Ben-Shoshan studies the role of skin barrier function in atopic dermatitis with respect to the development of food allergies (see page 1). Dr. Craig Elmets and others have pointed out that while we are making progress in the treatment of melanoma with the molecules that target MEK and BRAF, the use of sunscreen still needs some advocacy. Case in point: Dr. Zloty highlights the ways our patients continue to devise new and innovative ways to increase their risk of melanoma, most recently that of decorative tanning (see page 1). Many of us, including Drs. Elmets and Zloty, are sounding a little discouraged by this behaviour. Who can blame them? —Wayne P. Gulliver, MD, FRCPC Medical Editor
Share your knowledge and opinions with worldwide peers. Visit www.
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POSTGRADUATE EDUCATIONAL SUPPLEMENT
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Adherence to drug treatments and adjuvant barrier repair therapies are key factors for clinical improvement in mild to moderate acne: the ACTUO observational prospective multicenter cohort trial in 643 patients Raúl de Lucas,1 Gerardo Moreno-Arias,2 Montserrat Perez-López,3 Ángel Vera-Casaño,4 Sonia Aladren,5 Massimo Milani,5,* and on behalf of ACTUO Investigators study group
from 1Hospital Universitario La Paz, Madrid, Spain, 2Hospital Quirón Teknon, Barcelona, Spain, 3Clínica Dermatológica de Moragas, Barcelona, Spain, 5Isdin S.A. Medical Department, Provençals 33, Barcelona, Spain, *Corresponding author.
Background: In acne, several studies report a poor adherence to treatment. We evaluate, in a real-life setting and conditions, the impact of compliance to physician’s instructions, recommendations and adherence to treatments on clinical outcome in patients with mild to moderate acne in an observational, non-interventional prospective study carried out in 72 dermatologic services in Spain (ACTUO Trial). Methods: Six-hundred-forty-three subjects were enrolled and 566 patients (88%) completed the three study visits. The study aimed to evaluate the impact of adherence (assessed with ECOB scale) on clinical outcome, as well as how the use of specific adjuvant treatments (facial cleansing, emollient, moisturizing and lenitive specific topical products) influences treatment adherence and acne severity (0–5 points score). Recommendation of specific adjuvant skin barrier repair products was made in 85.2%. Results: Overall, clinical improvement was observed throughout follow-up visits with an increased proportion of patients who reported reductions of =>50% on the total number of lesions (two months: 25.2%; three months: 57.6%) and reductions of severity scores (2.5, 2.0 and 1.3 at one, two and three months after treatment, respectively). Adherence to treatment was associated with a significant reduction on severity grading, a lower number of lesions and a higher proportion of patients with =>50% improvement. Conclusion: Good adherence to medication plus adherence to adjuvants was significantly associated with a higher clinical improvement unlike those that despite adherence with medication had a low adherence to adjuvants. A good adherence to adjuvant treatment was associated with improved adherence and better treatment outcomes in mild to moderate acne patients. (ISRCTN Registry: ISRCTN14257026).
cne is a common chronic skin disease that very often requires prolonged treatments. 1 With a chronic course2 and an episodic pattern of presentation,3 acne vulgaris lesions occur mainly in exposed areas like the face and the presternal region. The effect of the scarring may be
notable and the functional, social and emotional impact on the patient’s quality of life may be significant. 4,5 Adherence to doctor prescriptions has a major impact on treatment outcome.6 Several studies conducted over the past few years suggest that adherence to acne medications is particularly low3,7 and has been associated with inadequate response to therapy,8 especially
Reprinted with permission from: de Lucas, et al: BMC Dermatology 2015; 15:17. © 2015 de Lucas, et al; licensee BioMed Central Ltd. http://www.biomedcentral.com/1471-5945/15/17
when both topical and systemic treatments are prescribed to the same patient.9 The treatment plan and the choice of specific active ingredients should take into account not only the individual characteristics of the patient and/or the disease but also their preferences and expectations with treatment as well as questions of convenience.10 The adverse effects of the various therapies available should also be borne in mind in order to increase adherence to the physician’s instructions and recommendations, thus promoting what are known as health-related behaviours.7 Specific systemic and topical acne treatments are often associated with local side effects such as dry, burning and itching sensations,7 hence poor tolerability that further worsens compliance.11 Based on the evidence and clinical experience obtained with topical treatments and their possible irritant effects,12 adjuvant skin barrier repair therapies such as specific emulsion and detergent products, hydrating and emollients are often prescribed in order to reduce these side effects, all in search of improving adherence to therapeutic strategies. 13,14 Other factors such as a good and efficient physicianpatient relationship are also crucial for improving adherence to therapeutic strategy 15 since this interaction includes specific roles and motivations16 that might be essential to the healing of many patients, particularly so for patients with chronic disease or disease having a negative impact on quality of life and self-esteem such as acne. 17 Adherence to acne therapies has been evaluated mainly in subjects irrespective to grading severity of the condition (from mild to severe forms)8, 18 but, so far, few data are available regarding this conduct in patients with mild to moderate forms. In a real-life setting, we evaluated the impact of adherence to dermatologist instructions and recommendations and adherence to the treatments (specific anti acne treatments and adjuvant therapies) on the clinical outcome in patients with mild to moderate acne. The participating physicians of the ACTUO trial were practicing, experienced Spanish dermatologists working in hospital outpatient dermatology services.
ACTUO was a multicentre, prospective, observational, epidemiological study of patients with mild to moderate acne treated at 72 dermatology services throughout Spain between Oct. 2011 and Nov. 2012. All study materials were evaluated and approved by a Clinical Research Ethics Committee before the study start. Approval (Ethics Committee of “Centro Medico Teknon” Barcelona, Spain) was obtained Aug. 1, 2011. Subjects A total of 643 subjects with mild to moderate acne, after they provided
written informed consent, were enrolled in the study. Eligibility criteria were men and women with mild to moderate acne vulgaris eligible for a specific acne treatment (topical retinoid agents or antiseptics and/or systemic antibiotics) willing to participate in the study. The study was conducted at three visits carried out in a period of three months (V1: baseline, and two follow-up visits: V2 and V3). In all three visits, data on acne severity was recorded on the Case Report Form (CRF) by the dermatologist using the global ranking system of the U.S. FDA19 (0: no lesions, 4: severe) and the total number of acne lesions. Acne severity was also evaluated by the patient. In addition, adherence to antiacne treatments and adjuvant therapies was also assessed trough study. Primary outcome
The main objective of this analysis was to evaluate the impact of adherence to the treatments on the clinical outcome in patients with mild to moderate acne. A secondary outcome was to evaluate the impact of the use of specific adjuvant treatments (facial cleansing products, emollient moisturizing and lenitive specific topical cream products containing mainly rhamnosoft as emollient and antinflammatory agent) on adherence level and entity of the clinical outcome obtained. Acne severity was assessed at each visit with a 5point score system (from 0 to 4), absolute count of lesions and percentage of patient reaching a =>50% reduction in lesion numbers. Adherence to treatment was evaluated at visit 2 and visit 3 by means of validated four-item questionnaire (ECOB) with a dichotomous classification: good adherence (ECOB score=4) and poor adherence (ECOB <4). Poor adherence to treatment was defined as a different to expected answer on the ECOB questionnaire. The four questions of ECOB were according to Pawin, et al.20 The degree of adherence to the adjuvant measures prescribed by the doctor (application of cleansers and moisturizers for facial skin care) was assessed using the data provided by the patients attending all three study visits. It was considered that patients who followed all their doctor’s instructions and recommendations in at least three of the four assessments showed compliance with the medical advice. The effects of adherence to adjuvant treatment on the doctor’s and patient’s final assessments of acne severity was compared in patients “without/practically without lesions” (FDA scores=0–1) and patients “with lesions” (FDA scores=>2–4). The ACTUO study has evaluated also the impact of acne and acne treatments on quality of life evaluated by means of Cardiff Acne Disability Index21 (CADI) and Dermatology Life Quality Index (DLQI).22 However these data would be presented elsewhere.
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POSTGRADUATE EDUCATIONAL SUPPLEMENT Statistical methods The FDA ratings made by the physician and patient after three months were grouped into two categories: presence of lesions (FDA=>2-4), or absence or near absence of lesions (FDA=0–1). Using the parameters severity and total number of lesions, improvement was assessed by classifying patients into two groups based on the reduction of acne severity (=>50% improvement vs. improvement <50%) and the percentages of reduction of comedones and papules/pustules. Statistical analysis was performed using the statistical software SPSS ver.19. Continuous variables were expressed as mean (SD). Categorical binary variables were expressed as proportions (%). The Mann–Whitney, Wilcoxon and the chi-square tests were used for inference statistical analysis tests. A multivariate logistics regression analysis was performed in order to assess the correlation between improvement of acne severity score, percentage of patients with 50% or more in acne lesion number reduction, and the following variable: demographic data, adherence to specific treatments and to adjuvant treatments.
Table 1 gives information about patients’ characteristics at the time of enrollment. A total of 643 cases were enrolled. A total of 566 patients (88%) completed the three-visit study. Data are presented as per protocol analysis. At baseline, adjuvant products were prescribed in 83.8% of the patients. The application frequency was 1.3/day. Prescription for specific adjuvant products was made for 85.2% of the patients. Severity of acne assessed by the physician was 2.5±0.6 and mean number of comedones was 18.9±2. Severity acne score was significantly (p<0.001) reduced in comparison with baseline after one month (2.0±0.8) and after three months (1.3±0.9). At the end of the study period patients scoring 0 (complete cure of acne) were 17%. In general, significant reductions in the severity scores vis-à-vis the baseline visit were observed in both doctor's and patients’ assessment (2.1±0.9 at one month and 1.4±0.9 at three months; p<0.001). Figure 1 shows the evolution of acne severity score in the population as a whole. Percentage of patients showing at least 50% of lesion reduction was 25.2% at visit 2 and 57.6% at visit 3. According to the ECOB scores, good adherence to treatment was documented in 50.0% of the patients at visit 2 and in 66.3% at visit 3. Good adherence to treatment was associated with a significant (p<0.05) acne improvement in comparison with poor adherence group at both control visits. At visit 3 acne severity score was 1.19±0.8 in patients with good adherence to adjuvants vs. 1.4±0.9 in poor adherence group. Good adherence to specific acne treatments (facial cleansers) was documented in 83.6% at visit 2 and in 89.9% at visit 3. At the end of study, patients with good
adherence to treatment presented a significant improvement of acne both in term of acne severity score (1.2 vs. 1.7; p=0.001) and regarding the proportion of patients whom reduction of lesions was =>50% (60.9% vs. 32.8%; p<0.001) when compared to those with poor adherence (Fig. 2). In patients for whom the dermatologist had prescribed adjuvant therapies, a good adherence to this treatment was documented in 36.2%. Adherence to adjuvant treatment improves acne thus it was associated with a significant reduction of score grading severity at visit 3 (1.2 vs. 1.4; p=0.002), with a higher percentage of reduction of average lesions number vs. baseline (50.8% vs. 43.7%; p=0.015) and with more patients obtaining a =>50% reduction in acne lesions’ number (65.9% vs. 51.5%; p=0.003) in comparison with the low adherence group (Fig. 2). Adherence to adjuvant treatments was associated with a greater proportion of patients with a complete cure of acne (defined as no or very few acne lesions) at the final visit in comparison with poor-adherers (66.5% vs. 52.6%; p=0.004). In particular, good adherence to adjuvant treatments improved the adherence to topical retinoid therapy therefore influencing clinical improvement of acne showing a higher proportion patients with adherence to treatment in adherers to adjuvants when compared to non-adherers (85.5% vs. 70.7%; p<0.001). In addition, in patients with a good adherence toadjuvants were significantly more frequently considered with an =>50% improvement on clinical outcome in comparison with those that did not adhere to adjuvants (65.9% vs. 51.5%; p=0.003). Multiple logistic regression analysis was performed to identify factors influencing clinical improvement of acne. Adherence to specific treatments, adherence to adjuvant treatments and good adherence to treatment are significantly (p=0.001) correlated with clinical improvement of acne. In accordance with previous studies, sex (women vs. men) and the fact of being accompanied (by parents/tutor or relative) or not at the medical visit are also independent factors affecting improvement clinical outcome of acne. Other analysis allowed observing an association between the patient’s assessment of quality of life based on the DLQI scale and the adherence to adjuvant treatment since rates of improvement on QoL were lower in non-compliers (43% vs. 56.1%, p=0.007).
Low adherence to treatments is still a relevant problem in the treatment of mild to moderate acne.23 The definition of strategies to improve adherence with both pharmacological and behavioural treatment remains a major challenge. Suboptimal medication adherence is one of the major reasons for treatment failure in subject with acne vulgaris.24 Our findings reveal that dermatologists
Table 1: Sociodemographic data and acne severity at baseline visit
in Spain frequently prescribe specific adjuvant treatment for acne. They recommend the use of specific products including non-comedogenic soaps and moisturizers in over 80% of acne patients. The synergy between the effects of drug treatment and adjuvant products can improve comfort during the various stages of treatment and can encourage patients to continue the application of the products. Adherence
to adjuvant treatment was associated not only with a 2.4-fold increase in the probability of adherence to pharmacological treatment, but also with a significant reduction in acne severity, in the number of lesions as assessed by both the treating physician and the patient, and a higher percentage of patients whose severity improved by 50% or more. In the ACTUO study low adherence to treatment was found in 50% of
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ments medicamenteux CRF: Case report form FDA: Food and Drug Administration
Figure 1: Acne severity score
Sonia Aladren and Massimo Milani are ISDIN employees. The ACTUO study was supported by an unrestricted grant of ISDIN SA.
RDL, GMA, MPL, AVC participated in the study design, coordination and patients enrollment. MM and SA participated in the design of study protocol and data analysis. All authors read and approved the final manuscript.
the patients (at one month) and this result is in line with previous published data. Low adherence to adjuvant treatments was observed in up to 63.8% of subjects after three months. In addition we have to consider that these data derived from a per protocol analysis, not including 12.4% of patients not attending to control visits which therefore could be considered as “non-complier” by definition. In line with previous experiences,3 we have observed that adherence to pharmacological treatment is a key factor for the improvement of acne both in terms of reduction of severity grading, number of lesions and percentage of patients obtaining at least a 50% acne improvement. Good adherence to adjuvant treatments also improves clinical evolution of acne with a greater reduction of severity of grading and number of lesions and with a significant greater percentage of patients obtaining a 50% or more improvement of acne in comparison with patients with poor adherence to adjuvant treatments. Furthermore, patients with good adherence with drug and those with adherence to adjuvant treatments presented the highest percentage of patients with improvement of acne lesions =>50%. In addition, in the present study it was shown that adherence to adjuvant products is the second most important factor (just after adherence to drug treatment) influencing the degree of acne improvement. A good adherence to adjuvant treatment is associated with an improved adherence to acne treatments and with a better treatment outcome in mild to moderate acne
patients. Some limitations should be taken in account in evaluating the results of our study. In particular the evaluation of compliance was based on self-reporting questionnaire. This approach however was used in other studies assessing the same outcome and the ECOB questionnaire is considered a validated tool.3,18 On the other hand, we believe that the sample size and the study design adopted, quite close to “real life” conditions of acne treatment strategies, could be considered as aspects increasing the external validity and the generalization of the observed results of the ACTUO.
The ACTUO observational study results confirm that adherence to pharmacological treatment and adjuvant therapies are both key factors of acne improvement in terms of reduction of severity, number of lesions and percentage of patients with at least a 50% acne improvement. In addition, adherence to adjuvant treatment with specific cleansers and moisturizers for patients with acne is the second most important factor in achieving symptom improvement, after completion of drug treatment. Good adherence to adjuvant treatment is associated with a 2.2-fold increase in the probability of adherence to topical pharmacological treatment and with significant reductions in the severity and number of acne lesions.
ECOB: Elaboration de un outil de evaluación de l’observance des traita-
Actuo Study Group Investigators: Abellaneda Fernández, Cristina; Aguayo Leyva, Ingrid Rocío; Alcaraz León, Inmaculada; Alonso García, Ignacio; Arechalde Pérez, Ana; Balbín Carrero, Eva; Ballestero Corominas, Alejandro; Bilbao Badiola, Ibon; Boada García, Aram; Ciudad Blanco, Cristina; De Lucas, Raúl; Del Pozo Hernando, Luis Javier; Del Rio Reyes, Rosa; Eguino Gorrochategui, Patricia; Escalas Taberner, Juan; Espelt Otero, Jorge Luis; Fernández Angel,Isabel; Fernández Casado, Alex; Fernández Torres, Rosa Mª; Gallego Álvarez, Silvia; Galvany Rosell, Loida; Gamo Villegas, Reyes; Ginarte Val, Manuel; Gómez Fernández, Cristina; Gómez Vázquez, Mercedes; Gutiérrez De La Peña, Javier; Hernandez Cano, Natalia; Houmani Houmani, Manmoud; Ibargoyen Esnal, Jesús; Iglesias Sancho, Maribel; Izquierdo Herce, Noelia; Jeremías Torruella, Javier; Latorre Fuentes, José Mª; Llambrich Mañes, Alex; López Ferrer, Ana; Mariscal Polo, Amaia; Márquez Balbas, Gemma; Martin Ezquerra, Gemma; Martin Urda, Maria Teresa; Martinez Escala, Maria Estela; Martinez Fernández, Matilde; Mieras Barceló, Caterina; Molina Ruiz, Ana; Montero Pérez, Iria; Moreno Arias, Gerardo A.; Nadal Llado, Cristina; Naranjo Díaz, Maria José; Nasarre Calvo,Jaume; Navajas Pinedo, Belén; Oleaga Morante, José Manuel; Perelló Llinas, Guillermo; Pérez Losada, Mª Eugenia; Pérez-López, Montserrat; Pérez-Beato De Cos, Mª Paz; Pestoni Porven, Carmela; Poza Magdalena, Olga; Rocamora Duran, Vicenc; Rodriguez Caruncho, Clara; Rodriguez Granados, Mª Teresa; Roe Crespo, Esther; Ruiz Carrascosa, José Carlos; Salgado Boquete, Laura; Sanchez Muros, Virginia; Sanz De Galdeano Palacio,Carmen; Taberner Ferrer, Rosa; Trasobares Marugan, Lidia; Uria García, Mª Carmen Valle Martin, Mª Del Mar; Valle Santana, Pilar; Vázquez García, Juan; Velasco Pastor, Manuel; Vera Casaño, Angel; Vilarrasa Rull, Eva; Waadad Waadad, Tamim.
1. Kligman AM: An overview of acne. J Invest Derm 1974; 62:268-287. 2. Bhate K, Williams HC: Epidemiology of
acne vulgaris. Br J Dermatol 2013; 168:474-485. 3. Thiboutot D, Gollnick H, Bettoli V, Dréno B, et al: New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad Dermatol 2009; 60:S1-S50. 4. Lasek RJ, Chren MM: Acne vulgaris and the quality of life of adult dermatology patients. Arch Dermatol 1998; 134:454-458. 5. Goulden V: Guidelines for the management of acne vulgaris in adolescents. Pediatr Drugs 2003; 5:301-313. 6. Weiden PJ, Rao N: Teaching medication compliance to psychiatric residents: placing an orphan topic into a training curriculum. Acad Psychiatry 2005; 29:203-210. 7. Haider A, Shaw JC: Treatment of acne vulgaris. JAMA 2004; 292:726-735. 8. McDonald HP, Garg AX, Haynes RB: Interventions to enhance patient adherence to medication prescriptions: scientific review. JAMA 2002; 288:2868-2879. 9. Dréno B, Layton A, Zouboulis CC, et al: Adult female acne: a new paradigm. J Eur Acad Dermatol Venereol 2013; 27:1063-1070. 10. Russell JJ: Topical therapy for acne. Am Fam Physician 2000; 61:357-365. 11. Snyder S: Medical adherence to acne therapy: a systematic review. Am J Clin Dermatol 2014; 15:87. 12. Weiss JS: Current options for the topical treatment of acne vulgaris. Pediatr Dermatol 1997; 14:480-488. 13. Herane MI, Fuenzalida H, Zegpi E, et al: Specific gel-cream as adjuvant to oral insotretinoin improved hydration and prevented TEWL increase—a double blind, randomized, placebo-controlled study. J Cosmet Dermatol 2009; 8:181-185. 14. Del Rosso JQ: Clinical relevance of skin barrier changes associated with the use of oral isotretinoin: the importance of barrier repair therapy in patient management. J Drugs Dermatol 2013; 12:626-631. 15. Renzi C, Picardi A, Abeni D, et al: Association of dissatisfaction with care and psychiatric morbidity with poor treatment compliance. Arch Dermatol 2002; 138:337-342. 16. Tsou AY, Creutzfeldt CJ, Gordon JM: The good doctor: professionalism in the 21st century. Handb Clin Neurol 2013; 118:119-132. 17. Farin E, Gramm L, Schmidt E: Predictors of communication preferences in patients with chronic low back pain. Patient Prefer Adherence 2013; 7:1117-1127. 18. Zaghloul SS, Cunliffe WJ, Goodfield MJ: Objective assessment of compliance with treatments in acne. Br J Dermatol 2005; 152:1015-1021. 19. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry; AcneVulgaris: Developing Drugs for Treatment. 2005. 20. Pawin H, Beylot C, Chivot M, et al: Creation of a tool to assess adherence to treatments for acne. Dermatology 2009; 218:26-32. 21. Motley RJ, Finlay AY: Practical use of a disability index in the routine management of acne. Clin Exp Dermatol 1992; 17:1-3. 22. De Tiedra AG, Mercadal J, Badía X, et al: Adaptación transcultural al español del cuestionario Dermatology Life Quality Index (DLQI): El índice de calidad de vida en dermatología. Actas Dermatosifilogr 1998; 89:692-700. 23. Jones-Caballero M, Pedrosa E, Peñas PF: Self-reported adherence to treatment and quality of life in mild to moderate acne. Dermatology 2008; 217:309-314. 24. Miyachi Y, Hayashi N, Furukawa F, et al: Acne management in Japan: study of patient adherence. Dermatology 2011; 223:174-181.
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NEW SEVERITY SCORE FOR HIDRADENITIS SUPPURATIVA
esearchers have developed a new composite, dynamic disease severity score tailored for hidradenitis suppurativa (HS) called the Acne Inversa Severity Index (AISI). The scale includes a physician-rated assessment of the types of lesions appearing as well as what body sites are involved. A zero to 10 visual analogue scale (illness-VAS) is also included to assess pain, discomfort, and disability arising from HS. To assess the validity of the new scale, it was compared to Hurley staging classification, modified Sartorius score, and the Dermatology Life Quality Index (DLQI). In 46 patients with HS, the authors demonstrated a significant correlation between AISI and Hurley staging (r: 0.70856, p=0.0021), modified Sartorius score (r: 0.9730, p<0.00001), and DLQI (r: 0.8257, p=0.221). In the new scale, HS may be categorized as mild, moderate, or severe (AISI <10, 10>18, or >18, respectively). AISI was also faster to administer than the Sartorius score, taking an average of 46.44±19.24 seconds vs. 83.2±19.04 seconds, p=1.31x10-6. Chiricozzi A, Faleri S, Franceschini C, Caro RD, Chimenti S, Bianchi L: AISI A new disease severity assessment tool for hidradenitis suppurativa, in Wounds (Oct. 2015; 27(10):258-264).
HDR PLESIOTHERAPY FOR NON-MELANOMA SKIN CANCER
retrospective institutional study of non-melanoma skin cancer (NMSC) treated using two hypofractionated high-dose-rate (HDR) plesiotherapy techniques looked at 134 basal cell or squamous cell skin carcinomas treated in the same radiation oncology department between Nov. 2006 and Dec. 2011. Lesions were treated with the HDR plesiotherapy using either a fixed (Leipzig) applicator or a customized mold. The median follow up was 33 months, with overall disease-free survival 95.12% at three years, and 93.36% at five. With the applicator, disease-free survival was 94.9% at both three and five years, while with the custom mold it was 93.1% at three years and 88% at five. 98% of lesions completely regressed, two persisted after treatment (both Leipzig), and six had local recurrence (five Leipzig and three molds, p=0.404). Acute toxicity below Grade 2 was seen in 57.3% of patients, and only 2.2% of lesions had Grade 4. Custom molds were borderline significantly associated with elevated toxicity (p=0.067). Larger tumours were associated with greater skin toxicity. Cosmeisis outcomes were excellent or good in 82% of patients, fair in 13%, and were not available in 5%. Arenas M, Arguis M, Diez-Presa L, et al: Hypofractionated high-dose-rate plesiotherapy in nonmelanoma skin cancer treatment, in Brachytherapy (Oct. 17, 2015 online edition).
Diagnostic Quiz Image courtesy: http://ow.ly/UQvR4
Research of Note
THE CHRONICLE of S K I N & A L L E R G Y
A. Epidermolysis bullosa B. Urticaria pigmentosa C. Lentigo D. Linear IgA dermatosis
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What THE LAY PRESS is saying about . . .
ANTIOXIDANTS FUEL MELANOMA? An antioxidant commonly used in nutritional supplements doubled the spread of melanoma in a mouse model, adding evidence to the idea that antioxidants may fuel the growth of cancer cells, reports The Wall Street Journal (Oct. 8, 2015). Researchers from the Sahlgrenska Academy in Gothenburg, Sweden, found that the antioxidant N-acetylcysteine (NAC) doubled the rate at which malignant melanoma spread to the animals’ lymph nodes. As well, when the investigators repeated the experiment with human cells cultured in the lab, the cancerous cells became better at invading adjacent tissue, the news outlet reports. The study’s lead author, professor Martin Bergö of the Sahlgrenska Cancer Center, noted the study only looked at antioxidants from nutritional supplements, according to the Journal, so the findings can not be extrapolated to antioxidants from food. Professor Bergö was quoted saying that the findings are part of a growing body of evidence that suggests antioxidant supplements are not helpful for the prevention of cancer, and may be harmful, so that individuals who have cancer or are at risk of developing cancer should avoid using them.
PHARMACISTS ASSESSING AND TREATING SKIN AILMENTS IN NEWFOUNDLAND AND LABRADOR Pharmacists in Newfoundland and Labrador are now allowed to both prescribe for and treat minor ailments, including many skin conditions, reports CBC News (Sept. 22, 2015). At a news conference, the province’s health minister, Steve Kent, introduced new regulations that would expand pharmacists’ scope of practice. “You don’t need to go to the emergency room or your doctor anymore to treat acne or heart burn or a minor headache or joint pain,” Kent was quoted saying. According to the CBC, skin conditions included in the regulations include acne, mild to moderate atopic dermatitis, callouses and corns, cold sores, contact dermatitis, and fungal infections of the skin. Pharmacists will need to be authorized with the provincial pharmacy board in order to be able to treat patients under the new rules, according to the news outlet. “It’s about patient choice and access because access has been a real problem, especially in rural areas,” Richard Coombs, past president of the provincial pharmacists’ association said.
CONFIRMED: PSORIATICS AT HIGHER RISK OF DEPRESSION Patients with psoriasis, regardless of its severity, are at elevated risk for depression, reports U.S. News & World Report (Oct. 1, 2015). A study published online in JAMA Dermatology (Sept. 30, 2015), that examined disease data on more than 12,000 men and women, collected between 2009 and 2012 by the U.S. National Health and Nutrition Examination Survey. The investigators identifyed psoriasis among nearly 3% of respondents and major depression among nearly 8%, and almost 17% of psoriasis patients also had depression. Study author Dr. Roger Ho, assistant professor in the department of dermatology at New York University School of Medicine, said the risk of depression in psoriasis patients may be driven more by worry about appearance than skin status. However, Dr. Gary Goldenberg, assistant professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York City, said it is possible that depression and psoriasis may share physiological pathways, and that the next step in research into the link may be to see if treatment with psoriasis medications have an impact on depressive symptoms.
Correct answer: Urticaria pigmentosa
26 · Oct./Nov. 2015
NUMBER OF MOLES ON RIGHT ARM MAY INDICATE MELANOMA RISK Having 11 or more moles on your right arm may be a simple indicator of being at high risk of melanoma, reports CTV News (Oct. 20, 2015). Reporting on research published in the British Journal of Dermatology on Oct. 19, the news outlet noted that the investigators found that the number of moles on a person’s right arm was a good predictor of that person’s total mole count, and that the higher the total mole count the higher the person’s risk of skin cancer. The study looked at 3,594 sets of female Caucasian twins who had the moles on 17 body areas counted, reported CTV. Similar counts were done on a group of approximately 400 men and women with melanoma. The new outlet quoted the study’s lead author, Simone Ribero of the department of twin research and genetic epidemiology at King’s College, London, U.K., saying that the findings could have a “significant impact”, and allow doctors to quickly and accurately estimate a patient’s total number of moles via an easily accessible body part.
Department Editor: John Evans
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Skin_OctoberNovember_2015,rar11_ms_rar1_Skin_March_2014,rar1.qxd 27/11/2015 4:34 PM Page 32
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The Chronicle of Skin & Allergy October/November 2015