PracticeUpdate: Dermatology - Vol 1 - No.1 - 2017

VOL. 1 • NO. 1 • 2017

OUR EXPERTS. YOUR PRACTICE.

ISSN 2207-7006

Increased risk of cutaneous and systemic infections in atopic dermatitis

Opinion

Teledermatology will very likely be a component of the future dermatology landscape, and we should actively participate in its development to ensure a high- quality execution

Conference 2017 AAD Annual Meeting

RESEARCH Burden of skin disease report: implications for dermatology

Wound healing through topical approaches to improve surgical outcomes

Balneotherapy for pain relief, stiffness, and physical function in osteoarthritis of the knee

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CONTENTS 3

RESEARCH Editor’s picks 4 Increased risk of

Cover 4

PracticeUpdate is guided by a world-renowned Editorial and Advisory Board that represents community practitioners and academic specialists with cross-disciplinary expertise. EDITORIAL BOARD Editor-in-Chief Robert Brodell MD FAAD Associate Editors Ashish Bhatia MD FAAD, Eliot Mostow MD, MPH Advisory Board Sarah Chamlin MD, Jane Grant-Kels MD,

Conference 8 2017 American Academy of Dermatology Annual Meeting Increased risk of cutaneous and systemic infections in atopic dermatitis

cutaneous and systemic infections in atopic dermatitis 4 Burden of skin disease report: implications for dermatology 5 Regular use of emollient containing glycerol and paraffin reduces flares in children with atopic dermatitis Medical dermatology 19 Alcohol use disorders are common in patients with eczema and psoriasis General dermatology 20 Wound healing through topical approaches to improve surgical outcomes 20 Depression associated with increased risk of psoriatic arthritis among patients with psoriasis Paediatric dermatology 21 Standard reporting and evaluation guidelines for Stevens-Johnson syndrome and toxic epidermal necrolysis neurofibromatosis type 1 risk among children with isolated café-au-lait macules Rheumatology 24 Celecoxib noninferior to ibuprofen and naproxen for cardiovascular safety 25 Rheumatoid arthritis and risk of ischaemic and nonischaemic heart failure 26 Balneotherapy for pain relief, stiffness, and physical function in osteoarthritis of the knee 26 Advances in the treatment of osteoporosis 22 Predicting 6 A predictive model for diagnosis of lower extremity cellulitis

Christen Mowad MD Editorial Contributor Sarah Churton MD, InYoung Kim MD PhD, Jeffrey Scott MD, Anna Wile MD

PracticeUpdate® is a registered trademark of Elsevier Inc. © 2017 Elsevier Inc. All rights reserved. ABOUT PracticeUpdate Dermatology provides coverage of key research from leading international conferences, and a collection of top journal articles and accom- panying expert commentaries in a convenient print periodical. These and more are also available online at www.practiceupdate.com PracticeUpdate and PracticeUpdate Dermatology are commercially supported by advertising, sponsorship, and educational grants. Individual access toPracticeUp- date.com is free. Premium content is available to any user who registers with the site. While PracticeUpdate is a commercially-sponsored product, it maintains the highest level of academic rigour, objectivity, and fair balance associated with all Elsevier products. No editorial content is influ- enced in any way by commercial sponsors or content contributors. DISCLAIMER PracticeUpdate Dermatology has been developed for specialist medical professionals. The ideas and opinions expressed in this publication do not necessarily reflect those of the Publisher. Elsevier will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. Please consult the full current Product Information before prescribing any medication mentioned in this publication. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publica- tion does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. SALES Fleur Gill fleur.gill@elsevier.com Linnea Mitchell-Taverner l.mitchell@elsevier.com PRODUCTION Editorial Manager Anne Neilson anne.neilson@elsevier.com Editorial Project Manager Carolyn Ng Designer Jana Sokolovskaja

8 Dr Anna Wile’s take-aways 10 Mechanical properties of skin altered significantly in pregnancy 11 Nocturnal pruritus common among pruritic conditions, diminishes quality of life 12 Dr Sarah Chamlin’s take-aways 13 Acne is the most common dermatologic diagnosis in a homeless shelter clinic 14 Dermato-oncologists, oncologists often disagree about dermatologic diagnoses, cancer therapy interruption 16 Modified Fitzpatrick scale promising as tool for grading skin cancer risk in people of colour 17 Dr Jeffrey Scott’s take-aways 18 Patients with haematologic malignancies more likely to seek inpatient oncodermatology consultation 18 Darker skin pigmentation linked with lower serum vitamin D concentrations

Features 23 Potential treatment of pseudoxanthoma elasticum 27 The opioid epidemic

Cover: Cellular skin structure in 3D

PracticeUpdate Dermatology (formerly PracticeUpdate Dermatology&Rheumatology ) is published by Elsevier Australia ISSN 2207-7006 (Print) ISSN 2207-7014 (Online)

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VOL. 1 • NO. 1 • 2017

EDITOR’S PICKS 4

Increased risk of cutaneous and systemic infections in atopic dermatitis Take-home message • This large cohort study using The Health Improvement Network, which is representative of the general UK population, revealed that multiple cutaneous and noncutaneous infections are more common in people with atopic dermatitis (AD) compared with those without. In particular, people with AD had a 55% increased odds of impetigo, 27% increased odds of streptococcal throat infections, a threefold increased odds of molluscum contagiosum, and a twofold increased odds of otitis media. • Individuals with AD are likely to be at increased risk for both cutaneous and noncutaneous infections, highlighting the need for infectious screening and prevention programs aimed at this patient population. Abstract Atopic dermatitis (AD, also known as atopic eczema or eczema), is characterized by skin barrier and immunologic dysfunction. Viral and bacterial super-infection of cutaneous lesions including eczema herpeticum and staphylococcus aureus in patients with severe disease is well documented (Ong and Leung, 2016, Weidinger and Novak, 2016). Whether the general population of patients with AD has an increased risk of these and other types of infections due to an impaired skin bar- rier and/or immunologic dysfunction is unclear. Increased risk of cutaneous and systemic infections in atopic dermatitis – A cohort study. J Invest Dermatol 2017 Feb 12;[EPub Ahead of Print], SM Langan, K Abuabara, SE Henrickson, et al. Journal of Investigative Dermatology

COMMENT By Mark A Bechtel MD T his manuscript suggests a potential link between immune dysfunction in atopic dermatitis and increased susceptibility to cutaneous and non-cu- taneous infections. It is becoming increasingly clear from a research perspective that atopic dermatitis is impacted by both skin barrier and immunologic dys- function. The role of genetic abnormalities in filaggrin and its impact on skin barrier function and atopic der- matitis has been elucidated. Genetic abnormalities in the regulation of the innate and adaptive immune sys- tem and its role in increased risk of infection in atopic dermatitis require further investigation. Dermatologists are fully aware of the increased inci- dence of molluscum contagiosum and Staph aureus infections in our atopic patients. The increased inci- dence of non-cutaneous infections, such as otitis media and streptococcal pharyngitis in atopic patients may be a surprise to many dermatologists. A greater insight into the genetic abnormalities impacting immune dysfunc- tion in atopic dermatitis is critical in determining which patients are at greater risk of developing infections. This will help in developing screening and prevention strategies. Modification in our care and therapeutic management could be necessary. Prevention strategies to diminish the risk of cutaneous and non-cutaneous infections will be important in the future care of our atopic patients.

Dr Bechtel is Professor of Medicine – Clinical and the Director of the Division of Dermatology, Ohio State University College of Medicine, Ohio.

Burden of skin disease report: implications for dermatology

Journal of the American Academy of Dermatology

Abstract The most recent American Academy of Der- matology burden of skin disease report builds on the prior report in 2004 in providing strong evidence of the serious nature of skin disease. With nearly 85 million Americans treated for at least 1 skin condition in 2013 at a direct cost of $75 billion, and an additional indirect cost of $11 billion, the findings of this study highlight the impact of skin disease on patients and our health care system and cannot be ignored. Burden of skin disease report: implications for dermatology. J Am Acad Dermatol 2017 Mar 01;[EPub Ahead of Print], K Edison, B Brod.

Take-home message • This commentary on the recent American Academy of Dermatology (AAD) burden of skin disease report summarises the salient features of the study and its implications for dermatologists. Importantly, the burden of skin disease study revealed that skin disease is serious, highly prevalent, and potentially deadly. Skin disease leads to a direct cost of US$11 billion in lost productivity, as well as significant costs for over-the-counter skin treatment products purchased by patients (US$10 billion). • Given the results of the updated report, the AAD is emphasising three key areas that need attention. There is a need for research on additional prevention and early detection strategies; research is needed into the role of dermatologists in the treatment of skin disease; and data registries are important for future research on outcomes.

PRACTICEUPDATE DERMATOLOGY

EDITOR’S PICKS 5

Regular use of emollient containing glycerol and paraffin reduces flares in children with atopic dermatitis Take-home message • Children from ages 2 to 6 with mild to moderate atopic dermatitis (AD; n = 335) were randomized to receive emollients (15% glycerol, 10% soft paraffin) twice daily vs no emollient. The children treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, and lower IGA and SCORAD scores than those who were not. At 12 weeks, significantly fewer children treated with emollients required corticosteroids or immunosuppressants (23.6%) than patients not treated with emollients (43.3%). • Although emollients are part of standard treatment for AD, there has been limited evidence that they prevent flares. This study suggests that regular emollient use in children with mild to moderate AD can reduce flares and use of corticosteroids. Pediatric Dermatology

COMMENT By Robert Sidbury MD, MPH R egular emollient use is an unambig- uous good for atopic dermatitis. This international, multi-center, parallel, open-label randomized trial of children aged 2-6 years with mild to moderate atopic dermatitis has documented this point anew. Children applying a glycerol and paraffin containing emollient twice daily to their entire bodies, including face, had fewer, delayed flares, used less topical corticosteroids, and had lower global assessment scores than a simi- lar group using a different emollient, or none at all. Any comparative conclusions based upon the specific emollients used are hampered by potential bias, asymmetrical study design, and the universally vexing challenge of defining a disease flare. Nev- ertheless, this study has demonstrated that emollients are beneficial in the short term by improving the skin barrier and decreasing inflammation. Emerging data suggest that if emollients are started early enough, they may likewise have long- term benefit through primary prevention of not only eczema but potentially other atopic co-morbidities.

Abstract BACKGROUND/OBJECTIVES Emollients are part of the standard treatment for atopic dermatitis (AD), although there is limited evidence that regu- lar use of emollients as management therapy reduces the frequency of flares and corticoster- oid consumption. The objective of this study was to evaluate the benefit of emollient use in the management of mild to moderate AD in children by assessing the ability of two different emol- lients (particularly V0034CR) to prevent flares and to reduce the use of corticosteroids. At 12 weeks, significantly fewer children treated with emollients required corticosteroids or immunosuppressants (23.6%) METHODS In this randomized, open-label study, patients with a current flare were treated with a potent topical corticosteroid. After flare res- olution, patients were centrally randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio) for 12 weeks. New flares were medically assessed before being treated with a moderately potent corticosteroid. RESULTS A total of 335 children 2 to 6 years of age were randomized. At 12 weeks, the per- centage of patients with one or more flares was statistically significantly lower with V0034CR (35.1%) than without emollient (67.6%; p < 0.001). Fewer patients treated with V0034CR required any corticosteroids or immunosuppressants (23.6%) than patients with no emollient (43.3%) at 12 weeks. The difference was significant at than patients not treated with emollients (43.3%).

all time points (p = 0.002). Patients treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, lower Investigator Global Assessment scores, and lower Scoring Atopic Dermatitis scores than those who were not. V0034CR was well tolerated, with no spe- cific safety concerns. CONCLUSION Regular emollient use in children with mild to moderate AD reduces flares and corticosteroid consumption. Prevention of flares in children with atopic dermatitis with regular use of an emollient containing glycerol and paraffin: a randomized controlled study. Pediatr Dermatol 2017 Mar 07;[EPub Ahead of Print], GS Tiplica, A Kaszuba, L Malinauskienė, et al.

Dr Sidbury is Associate Professor at the Department of Pediatrics, Chief, Division of Dermatology, University of Washington School of Medicine and at Seattle Children’s Hospital,

Seattle, Washington.

VOL. 1 • NO. 1 • 2017

EDITOR’S PICKS 6

Journal of the American Academy of Dermatology A predictive model for diagnosis of lower extremity cellulitis COMMENT By Boris D Lushniak MD, MPH T he word diagnosis is derived through Latin from Greek from a word meaning “to dis- cern, distinguish.” Since the time of our

Take-home message • In this cross-sectional study of 259 patients admitted through the emergency department between 2010 and 2012 with a diagnosis of lower extremity cel- lulitis, 30.5%were ultimately found to have beenmisdiagnosed with cellulitis. Variables associated with a true diagnosis of cellulitis included asymmetric involvement, leukocytosis, tachycardia, and an age >70. These variables were converted into a predictive model named the ALT-70 cellulitis score (asymmetry, 3 points; leukocytosis, 1 point; tachycardia, 1 point; age >70 years, 2 points). A score of 0–2 points indicates >83.3% likelihood of pseudocellulitis, and a score of >5 points indicates >82.2% likelihood of cellulitis. • A novel model incorporating the four variables of asymmetry, leukocytosis, tachycardia, and age >70 years is capable of predicting pseudocellulitis and cellulitis with a likelihood of >80%. This model may be useful in the emergency department for early identification and may reduce healthcare costs by precluding hospital admissions for pseudocellulitis. Abstract BACKGROUND Cellulitis has many clinical mimickers (pseudocellulitis), which leads to fre- quent misdiagnosis. OBJECTIVE To create a model for predicting the likelihood of lower extremity cellulitis. METHODS A cross-sectional review was performed of all patients admitted with a diag- nosis of lower extremity cellulitis through the emergency department at a large hospital between 2010 and 2012. Patients discharged with diagnosis of cellulitis were categorized as having cellulitis, while those given an alternative diagnosis were considered to have pseudocellulitis. Bivariate associations between predictor variables and final diagnosis were assessed to develop a 4-variable model. RESULTS In total, 79 (30.5%) of 259 patients were misdiagnosed with lower extremity cellulitis. Of the variables associated with true cellulitis, the 4 in the final model were asymmetry (unilateral involvement), leukocytosis (white blood cell count ≥10,000/uL), tachycardia (heart rate ≥90 bpm), and age ≥70 years. We converted these variables into a points system to create the ALT-70 cellulitis score as follows: Asymmetry (3 points), Leukocytosis (1 point), Tachycardia (1 point), and age ≥70 (2 points). With this score, 0–2 points indicate ≥83.3% likelihood of pseudocellulitis, and ≥5 points indicate ≥82.2% like- lihood of true cellulitis. LIMITATIONS Prospective validation of this model is needed before widespread clinical use. CONCLUSION Asymmetry, leukocytosis, tachycardia, and age ≥70 are predictive of lower extremity cellulitis. This model might facilitate more accurate diagnosis and improve patient care. A predictive model for diagnosis of lower extremity cellulitis: a cross-sectional study. J Am Acad Dermatol 2017 Feb 16;[EPub Ahead of Print], AB Raff, QY Weng, JM Cohen, et al.

initial training in medical school, we have been primed to follow an odyssey to become mas- ter diagnosticians. The goal to “getting it right” is critical because of the myriad repercussions of being wrong. For example, incorrect diagno- ses can lead to unnecessary treatment (one of the concerns in the issue of antimicrobial resist- ance) or a pathway of delayed treatment and potential increased morbidity or mortality. Using the skills of history taking, the physical exam, diagnostic procedures, and laboratory tests, we are at times awed by our acumen and success in getting it right and perhaps humbled by the opposite. In the practice of medicine, we are committed to the ongoing pursuit to improve our diagnostic skills using any variety of new tools. In this endeavour to do our jobs better, we have been blessed with high tech (and oftentimes very costly) advancements and cutting-edge labora- tory techniques. Yet, there is plenty to learn from population-based pattern recognition, which then allows us to establish diagnostic criteria. In this article, the authors delineate the impact of this common infection as well as the impact of misdiagnosis, which is attributed to a lack of “accurate or reliable diagnostic studies.” Using a retrospective, cross-sectional chart review of emergency department patients, comparisons were made between admitting and discharge diagnoses. The end product of the analyses was a point system taking into account asym- metry, leukocytosis, tachycardia, and age ≥70 (ALT-70), with proposed cutoff points and clini- cal interpretation. So, can we add this to our diagnostic tool kit? Well, consider it a work in progress. Two points to consider: 1) the threshold is set at 80% positive or negative predictive value – that is, nothing is per- fect; and 2) further validation is needed before widespread clinical use. Yet this shows that pop- ulation-based pattern recognition can play a part in expanding our diagnostic tools.

Dr Lushniak is Professor and Chair of the Department of Preventive Medicine and Biostatistics and Professor of Dermatology, F. Edward Hébert School of Medicine at the Uniformed Services University of the Health Sciences in Bethesda, Maryland.

PRACTICEUPDATE DERMATOLOGY

BRENZYS etanercept ®

The first available etanercept biosimilar in Australia 1

QUALITY * SUPPORT † VALUE ‡

PBS Information: This product is not listed on the PBS. PLEASE REVIEW THE PRODUCT INFORMATION BEFORE PRESCRIBING – AVAILABLE FROM WWW.MSDINFO.COM.AU/BRENZYSPI. BRENZYS [etanercept (rch)] Indications: rheumatoid arthritis; psoriatic arthritis; plaque psoriasis; ankylosing spondylitis; non-radiographic axial spondyloarthritis in adults ( ≥ 18 years); not indicated for use in children under 18 years. Contraindications: Hypersensitivity to any component of this product; patients with, or at risk of sepsis; patients with serious active infection including chronic or localised infections; concurrent treatment with Interleukin-1 antagonists. Precautions: Infections: tuberculosis, reactivation of hepatitis B, worsening of hepatitis C; alcoholic hepatitis; hypoglycaemia in patients treated for diabetes; concurrent administration of TNF inhibitors and anakinra; concurrent administration with abatacept; haematological reactions; allergic reactions; congestive heart failure; neurological disorders; concurrent use in psoriasis; lymphomas, leukaemia, other malignancies, melanoma and non-melanoma skin cancer; immunosuppression; vaccinations; autoantibody formation; fertility effects, use in pregnancy, lactation; not indicated in children under 18 years;use in elderly. Pregnancy Category: D. Interactions: methotrexate; abatacept; anakinra; cyclophosphamide; live vaccines; sulfasalazine; digoxin; warfarin. Adverse Effects: injection site reactions; infections; malignancies and lymphoproliferative disorders; autoantibody formation; psoriasis; headache; rhinitis; dizziness; pharyngitis; cough; asthenia; abdominal pain; rash, respiratory disorder; sinusitis; allergic reactions; fever see full PI. Dosage: rheumatoid arthritis, psoriatic arthritis, non-radiographic axial spondyloarthritis and ankylosing spondylitis: 50mg per week SC. Plaque psoriasis: 50mg per week once weekly or initially 50mg twice weekly for 12 weeks then 50mg per week thereafter. See full PI. Based on PI approved 14 October 2016 References: 1. Australian Register of therapeutic Goods. ttps://www.tga.gov.au/australian-register-therapeutic-goods. Accessed 5 January 2017. 2. Emery P et al. Ann Rheum Dis 2015;0:1–7. 3. Data on file. 4. Department of Health. Pharmaceutical Benefits Scheme to be reformed (Available at: http://www.health.gov.au/internet/ministers/ publishing.nsf/Content/health-mediarel-yr2015-ley063.htm, accessed: January 2017). *BRENZYS demonstrated equivalent efficacy and comparable safety and immunogenicity to originator etanercept 2 † MSD will provide comprehensive support for patients prescribed BRENZYS as well as support and education for health care professionals 3 ‡ Biosimilars have the potential to deliver greater affordability to the Australian healthcare system 4

Copyright © 2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA. All rights reserved. Merck Sharp & Dohme (Australia) Pty Limited. Level 1, Building A, 26 Talavera Road Macquarie Park, NSW 2113 Australia. BIOS-1209351-0000. February 2017. MSDBIO0011RC

CONFERENCE COVERAGE 8

2017 American Academy of Dermatology Annual Meeting 3–7 MARCH 2017 • ORLANDO, FLORIDA, USA

The 2017 AAD Annual Meeting sawmore than 1100 speakers present new research and clinical information on the diagnosis and treatment of skin, hair and nail conditions. The PracticeUpdate editorial team and contributors Dr Anna Wile, Dr Sarah Chamlin and Dr Jeffrey Scott, present highlights from the meeting.

2017 AADANNUALMEETING Dr AnnaWile’s take-aways

S068 – Therapeutic and diagnostic pearls What’s new in infectious disease – T Rosen • We could be facing a Zika outbreak this summer in the US. Although there are no FDA-approved treat- ments for Zika, a recent screen of FDA-approved drugs found several that could inhibit Zika infection. These drugs included mycolic acid (pregnancy category D), ivermectin (pregnancy category C), sertraline (pregnancy category C), and daptomycin (pregnancy category B). 1 Areas predicted to be affected are the Gulf Coast and lower Atlantic sea- board. Commercial tests for Zika are now available. The FDA is debating releasing genetically modified male Aedes mosquitoes into the Florida Keys, which would yield nonviable larvae. This has been a suc- cessful tactic in the Cayman Islands and Brazil. • New vaccines to be on the lookout for are the dengue fever vaccine, which is nearly 100% effec- tive, and the nonavalent HPV vaccine. • Syphilis is on the rise and there is a national Bicillin shortage. Minocycline 100 mg twice daily for 28 days is 87.3% effective and a good alternative. • Omadacycline is the first antibiotic in the aminomethyl- cycline class. It has a broad spectrum that includes CRE, VRE, MRSA, VRSA, and clindamycin- and erythro- mycin-resistant strep. It will be available as a single-day oral or IV dosing. It will be highly resistance resistant. 2

Dr Wile, a regular contributor to PracticeUpdate Dermatology , offers her key “take-aways” from the 2017 AAD Annual Meeting.

S045 – Teledermatology working for you: customizing use in the changing healthcare environment. Teledermatology and the future of medicine – C Kovarik • Teledermatology will very likely be a component of the future dermatology landscape, and we should actively participate in its development to ensure a high-quality execution. Preferred modalities include live-interactive and store and forward. • Teledermatology will be a means to deliver care in areas of poor dermatology access and in under- served subspecialties (eg, inpatient dermatology) to improve outcomes. However, we must be vigi- lant to detect poor-quality teledermatology, which could compound our access problems. Unsavoury teledermatology providers could compromise potential opportunities. • We as dermatologists must advocate for payments to us as providers to care for our patients instead of corporate telemedicine dominating the market.

PRACTICEUPDATE DERMATOLOGY

2017 AAD ANNUAL MEETING 9

It is not likely that use of SPF sunscreen contributes to less vitaminDproduction in the skin with sun exposure. >17 Topical ELMA and LMX are commonly used for topical anesthesia in pediatric procedures, and Glad Press’n Seal food wrap was suggested to cover the application site. >12

S069 – What’s new in dermatology What’s new in dermatologic surgery – B Coldiron • Nicotinamide 500 mg twice daily was shown to reduce the risk of new nonme- lanoma skin cancer by 23% in patients with a history of skin cancer. 3 • A large review found skin cancer screening did decrease the incidence of invasive melanoma; however, the USPSTF still does not recommend skin cancer screening due to a lack of evi- dence, an inauspicious decision as the incidence and mortality of melanoma continues to rise. 4–6 Self skin examina- tion with a partner could help with early melanoma detection. 7 • Sentinel lymph node biopsy for inter- mediate-thickness melanoma remains controversial, and Dr Coldiron reminds us that there is no survival benefit. 8 The Castle test provides a prediction similar to that with sentinel lymph node biopsy and is less invasive. • Multiple studies have linked HPV to oro- pharyngeal cancers, and HPV in smoke plumes is an under-recognised source of infection.

What’s new in pediatric dermatology – S Friedlander

• The regular use of emollients from birth may decrease the risk of atopic derma- titis (AD) by 50%. 9 • Crisaborole, a topical PDE4 inhibitor, and dupilumab, a monoclonal antibody against inflammatory mediators in the AD pathway, were approved for AD this year. • The LEAP study shifted the food allergy paradigm, and we now know that early exposure to peanuts can reduce the risk of peanut allergy. 10 References 1. Barrows NJ, Campos RK, Powell ST, et al. Cell Host Microbe 2016.20(2):259-270. 2. Heidrich CG, Mitova S, Schedlbauer A, et al. Antibiotics (Basel). 2016. 22;5(4):E32. 3. Chen AC, Martin AJ, Choy B, et al. N Engl J Med 2015;373(17):1618-1626. 4. Brunssen A, Waldmann A, Eisemann N, Katalinic A. J Am Acad Dermatol 2017;76(1):129-139.e10. 5. Screening for skin cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;150(3):188-193. 6. Glazer AM, Winkelmann RR, Farberg AS, et al. JAMA Dermatol 2017;153(2):225-226. 7. Hultgren BA, Turrisi R, Mallett KA, et al. JAMA Dermatol 2016;152(2):184-190. 8. Bigby M, Popescu C. BMJ 2015;351:h5940. 9. Simpson EL, Chalmers JR, Hanifin JM, et al. J Allergy Clin Immunol 2014;134(4):818-823. 10. Du Toit G, Sayre PH, Roberts G, et al. N Engl J Med 2016;374(15):1435-1443.

The findings reinforce the

importance of inpatient oncodermatology

collaboration in optimising care of hospitalised cancer patients and survivors. >18

VOL. 1 • NO. 1 • 2017

CONFERENCE COVERAGE 10

Mechanical properties of skin altered significantly in pregnancy

S kin mechanical properties change significantly during pregnancy and remain altered 4 months post delivery, results of a clinical comparative study show. Caroline Baudouin, PhD, of Labo- ratoires Expanscience, Epernon, France, explained that pregnancy is a particular physiological state that induces major physical changes. From a mechanical point of view, the abdomen is the most affected area by continuous and progres- sive stretching of the skin. Except for stretch marks, no comparison of mechanical properties of nonle- sional skin between nonpregnant

and pregnant women and women in delivery has been performed. Dr Baudouin and colleagues set out to investigate skin mechanical properties of the highly-stressed abdomen and the less stressed thigh in pregnant women and women before and after delivery. Fifteen nonpregnant and 26 preg- nant women in their eighth month of pregnancy and 4 months after delivery participated. Mechanical properties of nonlesional skin were measured under suction stress with a Cutometer MPA580 with a 2mm diameter aperture. On the abdomen, under a one-cy- cle strain-time test, nonlesional skin in pregnant women was sig- nificantly less extensible and more viscous than in nonpregnant women. After delivery, a loss of tonicity was also observed vs non- pregnant and pregnant conditions.

Repetitive measurements con- firmed these results and showed that nonlesional skin extensibil- ity of women post delivery was higher than in pregnant and non- pregnant conditions. On the thigh, a decrease in tonicity was also observed during pregnancy and after delivery. Dr Baudouin concluded that skin mechanical properties changed significantly during pregnancy and remained altered 4 months post delivery. As expected, mechanical properties of abdominal skin were impacted during pregnancy. Inter- estingly the team also measured mechanical changes on thigh skin, which is less subject to stretching. The results underlined the fact that pregnancy exerts profound changes in skin properties at vari- ous sites.

The results underlined the fact that pregnancy exerts profound changes in skin properties at various sites.

PracticeUpdate Editorial Team

DETECT THE BRAF MUTATION EARLY

References: 1. Pharmaceutical Benefits Scheme. Available from www.pbs.gov.au, accessed July 2016. 2. Dummer R et al. Ann Oncol 2015; 26 (Suppl 5): 126–32. 3. Kakavand H et al. Pathology 2016;48(2):194–202. Novartis Pharmaceuticals Australia Pty Ltd, ABN 18 004 244 160, 54 Waterloo Road, Macquarie Park, NSW 2113. Phone (02) 9805 3555. Item No.: MEL0168. Date of preparation: September 2016.

59459 BRAF Half pg Dermatology Update Ad v1HR.indd 1 P CTICEUP ATE DERMATOLOGY

during the day (P < 0.0001). The severity of nocturnal pruritus was significantly cor- related with overall itch severity (r = 0.22, P = 0.006). Of the 146 subjects with nocturnal pruritus, 90% reported sleep disturbance. Furthermore, for subjects with nocturnal pruritus, the severity of itch at night corre- lated significantly with the severity of sleep disturbance (r = 0.35, P < 0.0001). The severity of nocturnal pruritus corre- lated significantly with total Itchy Quality of Life score (r = 0.22, P = 0.006), indicating that nocturnal pruritus was associated with an overall reduced quality of life. Specifically, the severity of nocturnal pruri- tus correlated with two of the Itchy Quality of Life subscales: functioning (r = 0.29, P = 0.0004) and emotions (r = 0.18, P = 0.03). Dr Lavery concluded that nocturnal pruri- tus was found to be a common complaint among a wide range of pruritic conditions, and exerts a negative impact on quality of life. The results highlight the need for tar- geted clinical interventions for patients with chronic pruritus. 2017 AAD ANNUAL MEETING 11

Nocturnal pruritus common among pruritic conditions, diminishes quality of life N octurnal pruritus was found to be a common complaint among a wide range of pruritic conditions, and The results highlight the need for targeted clinical interventions for patients with chronic pruritus.

exerts a negative impact on quality of life, report results of a retrospective analysis. Michael Lavery, MD, of Lewis Katz School of Medicine at Temple University, Philadel- phia, and colleagues set out to assess the prevalence, characteristics, and impact on quality of life of patients with noctur- nal pruritus. Patients who attended an “itch clinic” from 2015 to 2016 were surveyed. Patients with chronic itch (≥6 weeks) were asked to complete a validated questionnaire assess- ment of pruritus. This itch questionnaire assessed the severity of itch on a numeric rating scale of 0–10 and several associated character- istics, including the presence and severity of nocturnal pruritus and sleep disturbance on a scale of 0–4. A validated quality of life

questionnaire (ItchyQ) was also completed. Questionnaires from 160 subjects were analysed. Mean subject age was 57 ± 16. Ninety-seven (60.6%) of the cohort were female and 63 (39.4%) were male. A total of 146 of the 160 subjects (91.3%) reported suffering from nocturnal pruritus. The most common conditions that co-occurred with nocturnal pruritus were atopic dermatitis, prurigo nodularis, brachioradial pruritus, and psoriasis. Mean itch intensity severity was signifi- cantly high (8.2 ± 2.1). Subjects reported significantly higher itch severity at night vs

PracticeUpdate Editorial Team

REQUEST THE BRAF TEST FOR YOUR PATIENTS WITH MELANOMA.

PATIENTS WHO TEST POSITIVE FOR THE BRAF MUTATION MAY BE ELIGIBLE FOR TARGETED MELANOMA THERAPIES 1,2 BRAF mutation tests are recommended for the following patients: 2 MANDATORY • Unresectable stage III or IV HIGHLY RECOMMENDED • High-risk resected stage IIc or stage IIIb–IIIc

~40% OF PATIENTS WITH MELANOMA HARBOUR THE BRAF MUTATION 3

CONFIRM BRAF MUTATION STATUS EARLY HELP EXPEDITE ACCESS TO TARGETED THERAPIES FOR ADVANCED MELANOMA

10/4/17 3:34 pm

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2017 AADANNUALMEETING Dr Sarah Chamlin’s take-aways

Dr Chamlin, Associate Professor of Pediatrics and Dermatology at Northwestern University Feinberg School of Medicine and member of the Advisory Board for PracticeUpdate Dermatology , offers her key “take-aways” from the pre-ADD meeting sponsored by The Society for Pediatric Dermatology.

New tools for your therapeutic toolbox – Erin Mathes Use of – and FDA approval of – both systemic and topical agents for pediatric skin disease most often lag behind use and approval for adults. Dr Mathes presented many new cutting-edge options for the treatment of skin dis- ease in children. This talk was practical and rich with useful information. • The use of crisaborole ointment and dupilumab injec- tions for children with atopic dermatitis was presented. Many practitioners treating atopic dermatitis struggle with patient and parent steroid phobia, and many chil- dren are undertreated because of the fear of potential steroid side effects. Topical crisaborole, a phosphodi- esterase-4 inhibitor, is now available as an ointment for use in children and is approved for children 2 years of age and older. Of note, very promising phase III trials were reviewed with more than 1500 study participants. Highlights include the indication for mild-moderate atopic dermatitis, and a high vehicle response rate possibly due to its petrolatum base. There may be prescribing limitations due to potentially cumbersome prior authorisation requirements. Dr Mathes proposes that crisaborole will likely be a useful addition to, but will not replace, topical steroids. Data from two randomized double-blind placebo-controlled trials of dupilumab in adults were reviewed, and significant improvements in all atopic dermatitis parameters including disease severity, itch, anxiety and depression were noted. With this therapy, patients got better quickly and had fewer skin infections in the treatment group vs the placebo group. A pediatric trial has been completed, with no results yet available. • Can we prevent atopic dermatitis in high-risk infants? Data from a study by Dr Eric Simpson and colleagues suggest that we can. Emollient use within 3 weeks of birth in high-risk infants significantly reduced the inci- dence of atopic dermatitis at 6 months of age. 1 • Oral tofacitinib and topical bimatoprost were sug- gested as possible therapy for children with alopecia areata. 2 A trial of tofacitinib in teens with alopecia areata reported 9 responders and 4 nonresponders. Unfortunately, relapse was common in this trial, with an average time to relapse of 8.5 weeks after stopping the drug, and chronic long-term systemic therapy is harder to accept in children until long-term side effects are known. Topical bimatoprost is another treatment option, albeit an expensive one, which is unproven in large studies for alopecia areata. • Both topical and oral ivermectin, used in adults with rosacea, can also be useful for therapy of perioral dermatitis and rosacea in children. • Topical compounded sirolimus 1% cream may be of

therapeutic benefit for superficial type of microcystic lymphatic malformations. It also may be effective for use in conjunction with pulsed dye laser treatment for more recalcitrant port wine stains. • Consider topical timolol 0.5% GFS with occlusion for treatment of pyogenic granulomas. While case reports show efficacy, consider systemic absorption, which can limit use in young children. Pediatric pain management & procedural pain control – Amy Baxter Pearls for performing procedures in children were offered by Dr Baxter, a pediatric emergency department physician. • Needle phobia has increased in children and directly cor- relates with the greatly increased number of vaccinations given to children since 1983. Before 1983, approximately six vaccines were administered early in life. Currently, over 30 vaccinations are given by the age of 6 years. • Topical ELMA and LMX are commonly used for topical anesthesia in pediatric procedures, and Glad Press’n Seal food wrap was suggested to cover the application site. This plastic wrap can be removed from skin and hair-bearing areas with less pain than a Tegaderm dressing. • EMLA cream takes 60 minutes to work, vasoconstricts for the first 1.5 hours, and provides deeper skin pen- etration than other topical anesthetics. Approximately 2% of users have a petechial skin reaction. • LMX, lidocaine in a liposomal delivery cream, works in about 20 minutes and diffuses away in about 20 min- utes. For improved efficacy, rub this on when applying and occlude for 20 to 30 minutes.

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• The use of a J-Tip, CO 2 -powered, lidocaine-loaded syringe is reported to greatly reduce injection pain and provide a 2-cm radius of numbing. • Other pearls for pain reduction include use of a Buzzy Bee vibration device and an ice pack. • Reducing fear in a child during a procedure can be done by thorough preparation (tell the child what is being done before it is done), reducing chaos (having only one person in the room talk), and preparing trays outside of the room. The use of iPads or other tablets during the actual procedure are very helpful as well. Lastly, restraining the child leads to fear and anxiety; being held in a comfortable position by a parent proves to be more helpful. Managing hidradenitis suppurativa in the pediatric population – Chris Sayed Dr Sayed reviewed the management of hidradenitis sup- purativa (HS) in pediatric patients, and, like in adults, it is very challenging. Pediatric patients are more likely to have a family history of HS, and disease comorbidities include metabolic syndrome and other inflammatory dis- eases, which are on par with adult disease. • Of note, young children with HS should be evaluated for androgen excess , specifically precocious puberty. Evaluation for metabolic syndrome or other systemic disease is dictated by physical exam and findings. • A treatment algorithm with clindamycin and rifampin, hormonal therapy for women (drospirenone-containing oral contraceptives), laser for follicular destruction, and deroofing vs local excision can be considered. • Immunomodulators such as etanercept, adalimumab, infliximab, and ustekinumab are considered in adults with HS but have limited use in children. • The use of retinoids to treat HS signs and symptoms is not promising in children or adults with HS. References 1. Simpson EL, Chalmers JR, Hanifin JM, T, et al. J Allergy Clin Immunol 2014;134(4):818-823. 2. Craiglow BG, Liu LY, King BA. J Am Acad Dermatol 2017;76(1):29-32.

Acne is themost common dermatologic diagnosis in a homeless shelter clinic Though unexpected, the most common dermatologic diagnosis at a homeless shelter clinic was acne, with approximately one in five patients presenting with the condition, finds a retrospective chart review. M ichael J. Murphy, MD, of the University of Connecticut, Farmington, explained that

The top 10 diagnoses per total number of patients over 8 years were: • Acne, 19.78% • Atopic dermatitis, 9.89% • Tinea pedis, 9.16% • Xerosis, 8.06% • Folliculitis, 5.13% • Post-inflammatory hyperpig- mentation, <5% • Seborrheic dermatitis, <5% • Tinea infection of the body and head, <5% • Psoriasis, <5% • Verruca vulgaris, <5% Surprisingly, only acute cold injury and two foot lacerations were treated. Additionally, the rate of suspected malignancy per total patients seen was 2.6%, with seven patients presenting with lesions concerning for melanoma (n=5) and basal cell carcinoma (n=2). Diagnostic trends were also analysed based on gender, eth- nicity, age, and season of the year. Dr Murphy concluded that though unexpected, the most common diagnosis at the clinic was acne, with approximately one in five patients in the homeless shel- ter clinic presenting with the condition. The most common diagnoses will advise decisions about diagnostic and treatment supplies ordered for future clinics in order to best care for these homeless individ- uals. Results of the study will be published in an upcoming issue of Connecticut Medicine . The studywas limited by the lack of clinics during the summer months and diagnosis variability between attending dermatologists.

among the homeless, dermato- logic conditions are very common due to the exposure of skin to environmental elements and often inadequate clothing and hygiene. The University of Connecticut South Park Dermatology Clinic was founded in 2008 to reduce barriers to care and increase con- venience in these patients. The clinic is part of a general med- ical clinic founded in 1987 by a group of University of Connecti- cut medical students. Their goal was to provide critical health- care services to this underserved population. Dr Murphy and colleagues set out to identify the most common dermatologic diagnoses among all patients seen at the clinic from 2008 to 2016. Particular attention was paid to age, gender, season of the year, and the rate of malig- nancy. The data will be used to generate a robust supply of treat- ment options to best care for homeless patients. Patient charts from 45 derma- tology clinics held at the shelter clinic were reviewed and demo- graphics, diagnosis, and treatment data were recorded. Overall, 273 patients, 1–67 (mean 37, median 39 years of age were seen for dermatologic concerns. Demographically, 54% were male and 46% were female, with 30% identifying as African-American/ black, 29% Hispanic, and 25% Caucasian. Sixteen percent did not disclose their race. A total of 363 diagnoses were recorded, encompassing 90 separate der- matologic conditions, with 26% of patients presenting with more than one complaint.

PracticeUpdate Editorial Team

© 2017 American Academy of Dermatology Association.

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Dermato-oncologists, oncologists often disagree about dermatologic diagnoses, cancer therapy interruption Dermato-oncologists and oncologists have been found to disagree often about dermatologic diagnoses and cancer therapy interruption, reveal results of a retrospective chart review.

G regory Phillips, MD, of Memorial Sloan Kettering Cancer Center, New York, explained that admin- istration of anticancer therapies often results in dermatologic adverse events, which can negatively impact quality of life and patient outcomes. Dr Phillips and colleagues set out to compare antican- cer therapy interruption due to dermatologic adverse events, as well as diagnostic concordance patterns between referring clinicians and dermatologists at their centre. One-hundred thirty dermatology consultations over a 2-month period in 2015 were reviewed. Consultations were identified using a consult log. The final analysis included 113 patients.

Patients’ demographics, reason for referral, tumour and anticancer therapy agents, dermatologic diagnoses, and anticancer therapy interruption due to derma- tologic adverse events were abstracted from each patient’s electronic medical record. Kappa statistic was estimated for agreement between clinicians in hold- ing anticancer therapy due to dermatologic adverse events. Diagnostic concordance between the referring clini- cian and dermatologist was determined based on the following definition: in instances where the referring clinician underdiagnosed (for example, identified one correct and missed three other conditions). This was considered concordance; and in instances where the referring clinician overdiagnosed (for exam- ple, diagnosed three conditions, only two of which were agreed by the dermatologists), this was consid- ered discordant. Overall, referring clinicians and dermatologists agreed diagnostically only on 26% of referred cases (n=113). Of 79 patients receiving treatment for solid or haema- tologic cancers, dermatologic adverse event-induced therapy interruption was documented in 41 patients (52%).

The results underscore the importance of a dermatologic evaluation for the diagnosis, attribution, and management of anticancer therapy-induced dermatologic adverse events.

For the 10 cases in which the referring clinician recom- mended holding therapy, the dermatologist agreed only once (10%). A kappa value of 0.14 was reported. Fifteen patients (19%) harboured dermatologic conditions attributable to anticancer ther- apy by the referring clinician vs 27 (34%) by the dermatol- ogist. Attribution was unclear in 73% and 58% of cases, respectively. Dr Phillips concluded that the study showed a high dis- cordance between referring clinicians and dermatologists. In addition, a weak agreement between referring clinicians and dermatologists holding anticancer therapy was found. The results underscore the importance of a dermatologic evaluation for the diagnosis, attribution, and management of anticancer therapy-induced dermatologic adverse events.

PracticeUpdate Editorial Team

© 2017 American Academy of Dermatology Association.

PRACTICEUPDATE DERMATOLOGY

Cosentyx Efficacy

He was so excited to have been given a greater opportunity to achieve clear skin *1

*At week 52, PASI 100 responses to secukinumab and ustekinumab were 45.9% and 35.8% respectively ( p =.0103). Primary study endpoint was achieved with secukinumab demonstrating superiority in PASI 90 response (79%) to ustekinumab (57.6%; p <.0001) at Week 16.

See approved Product Information before prescribing. Approved Product Information available on request. For the most up-to-date Product Information, go to: https://www.novartis.com.au/products/healthcare-professionals PBS Information: Section 85 Authority Required for the treatment of severe chronic plaque psoriasis, active ankylosing spondylitis and severe psoriatic arthritis. Refer to PBS Schedule for full Authority information. COSENTYX ® (secukinumab) Indication: Treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. Treatment of adult patients with active psoriatic arthritis when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate. Treatment of adult patients with active ankylosing spondylitis. Dosage and administration: Plaque psoriasis: The recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg. Psoriatic arthritis: The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. For patients who are anti-TNF α inadequate responders or patients with concomitant moderate to severe plaque psoriasis, the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg. Ankylosing spondylitis: The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Contraindications: Severe hypersensitivity reactions to the active substance or to any of the excipients. Clinically important, active infections. Precautions: Infections: Caution in patients with chronic or history of recurrent infection. If a patient develops a serious infection, the patient should be closely monitored and Cosentyx should not be administered until the infection resolves. Anti-tuberculosis therapy should be considered prior to initiation in patients with latent tuberculosis. Cosentyx should not be given to patients with active tuberculosis. Crohn’s disease: Caution should be exercised, when prescribing to patients with inflammatory bowel disease. Exacerbations, in some cases serious, occurred during clinical trials in plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. In addition, new onset inflammatory bowel disease cases occurred in clinical trials. Patients should be monitored for signs and symptoms of inflammatory bowel disease. Hypersensitivity reactions: Rare cases of anaphylactic reactions have been observed during clinical trials. Administration should be discontinued immediately and appropriate therapy initiated if an anaphylactic or other serious allergic reaction occurs. Latex-sensitive individuals: The removable cap of the Cosentyx pre-filled syringes/pen contains a derivative of natural rubber latex. Vaccinations: Cosentyx should not be given concurrently with live vaccines. Pregnancy: Cosentyx should be used during pregnancy only if the benefits clearly outweigh the potential risks. Breast-feeding: Caution should be exercised when Cosentyx is administered to a woman who is breast-feeding. Interactions: Live vaccines should not be given concurrently with Cosentyx. Side effects: Very common ( ≥ 10%): nasopharyngitis. Common (1 to 10%): upper respiratory tract infection, rhinitis, pharyngitis, oral herpes, diarrhoea, urticaria, rhinorrhoea, headache, nausea, hypercholesterolemia. Uncommon (0.1 to 1%): sinusitis, tonsillitis, oral candidiasis, neutropenia, tinea pedis, otitis externa, conjunctivitis. In clinical trials, major adverse cardiovascular events were rarely observed in patients receiving secukinumab. In the overall secukinumab program, the exposure adjusted incidence rates of adjudication-confirmed cases per 100 patient-years for secukinumab

was 0.40 versus 0.39 for placebo. Elevations (mainly CTCAE Grade 1 and Grade 2) in cholesterol, triglycerides and hepatic transaminases were also observed during clinical trials in patients with psoriatic arthritis and ankylosing spondylitis. (cos171016m). Reference: 1. Blauvelt A, et al. JAAD 2016. http://dx.doi.org/10.1016/j.jaad.2016.08.008. ® Registered trademark of Novartis. Novartis Pharmaceuticals Australia Pty Limited ABN 18 004 244 160. 54 Waterloo Road, Macquarie Park NSW 2113. Ph (02) 9805 3555. Date of preparation: March 2017. AU-1489. CRD2756.