PracticeUpdate: Dermatology & Rheumatology

Best of 2016

DECEMBER 2016

RESEARCH NEWS AND VIEWS FROM ELSEVIER

ISSN 2206-4702

Top 2016 research AAD 2016 • • Wounds and ulcers: the good, bad & ugly • • Controversies in managing cutaneous lupus, dermatomyositis

• • Benign vs malignant lesions without biopsy SPD2016 • • Allergic contact dermatitis in paediatric patients • • Phototherapy for childhood vitiligo, atopic dermatitis Summer AAD2016 • • Expert insights on advanced systemic therapeutics ACR 2016 • • RA remission rates improved, earlier diagnosis needed • • Wnt inhibitor improves function in knee OA • • CV event risk similar for RA, T2DM patients

2016 Top Stories in Dermatology

EDITORIAL Managing Editor Anne Neilson anne.neilson@elsevier.com Editor Carolyn Ng carolyn.ng@elsevier.com Designer Jana Sokolovskaja j.sokolovskaja@elsevier.com SALES Commercial Manager Fleur Gill fleur.gill@elsevier.com Account Manager Linnea Mitchell-Taverner l.mitchell-taverner@elsevier.com

PracticeUpdate Dermatology Editorial and Advisory Boardmembers Dr Eliot Mostow and Dr Jane Grant-Kels, as well as Dr Robert Brodell of the University of Mississippi Medical Centre, discuss their top stories in dermatology for 2016, focusing on topical retinoids, shared care to optimise patient outcomes, and exciting advances inmelamona. Dr Robert Brodell on the use of topical retinoids Robert Brodell MD, FAAD, is Professor and Chair of the Department of Dermatology at the University of Mississippi Medical Center. W hile there were many articles involving new treatments, new tech- nologies, and even new diseases, my favourite articles are those that highlight gaps in care for common diseases. The article by Barbieri et al is just such an article ( J Am Acad Dermatol 2016;75:1142-1150.e1). This English study demonstrated that 62% of practitioners did not use a topical retinoid as part of their acne regimen. It validates the work of a team using data from the United States ( J Am Acad Dermatol 2016;74:1252-1254). In 40% of acne patients treated by dermatologists and 70% treated by other physicians, no topical retinoid was used.

DISCLAIMER PracticeUpdate Dermatology & Rheumatology provides highlights of key local and international conferences, timely and relevant news, expert opinions and journal article reviews for specialist medical professionals. The ideas and opinions expressed in this publication do not necessarily reflect those of the Publisher. Elsevier Australia 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 verificationofdiagnosesanddrugdosagesshould 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 publication 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.

This represents a significant gap in patient care. Experts agree that patients with acne should be treated with topical retinoids. Guidelines from the American Acne and Rosacea Society, the American Academy of Pediatrics, and the Global Alliance to Improve Outcomes in Acne support the use of topical retinoids as first-line therapy for acne. Attacking the pathophysiology of acne with strong comedolytics should decrease the length of time systemic and topical antibiotics are needed and minimise the potential for recurrence because the microcomedone is the source of acne infection. If retinoids were used immediately when systemic antibiotics are used to treat acne, the need for prolonged systemic antibiotic use would be reduced, with obvious benefits to society with regard to the development of resistance. Of course, there is an explanation for this behaviour. Topical retinoids are hard for patients to use! They can be drying, irritating, cause redness, and both post-inflammatory hyper- and hypopigmentation. The physician should initiate topical retinoid therapy using milder products (lower concentrations, creams instead of gels, and products with special vehicles to decrease irritation) and prescribing them for use every other night or twice weekly initially for patients with dry skin. Patients develop tolerance to these products and can often increase the frequency of use over time. Using team-based care techniques, the physician and his/her nurse or medical assistant must take the time to educate patients about other approaches to increase the tolerability of topical retinoids. These include application of the topical retinoid at bedtime to a dry face, using a non-comedogenic moisturising lotion in the morning, and using mild soapless cleansers instead of harsher soaps. Finally, patients should avoid other topical products that might be drying. My experience has been that, by using all of these techniques, the vast majority of patients can tolerate a topical retinoid and benefit from its comedolytic and anti-inflammatory effects. This results in acne clearing faster, minimising the time systemic antibiotics are required, and minimising acne recurrences after patients are clear.

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2016 TOP STORIES IN DERMATOLOGY

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Dr Eliot Mostow on shared care to optimise outcomes Eliot Mostow MD, MPH, is Professor and Head of the Dermatology Section at Northeast Ohio Medical University in Ohio, and an Editorial Board Member of PracticeUpdate Dermatology.

The year’s top research, all in one issue Welcome to our special issue, PracticeUpdate Dermatology & Rheumatology: Best of 2016 – bringing you a collection of the best research of 2016 from the world’s top rheumatology and dermatology congresses. You’ll find the best in here plus key clinical commentary on why these studies are practice-changing. Our PracticeUpdate Dermatology advisory and editorial board members share their views on their pick of the top dermatology stories of the year (see left & page 4). On behalf of the Elsevier Australia PracticeUpdate Dermatology & Rheumatology team, I thank you for your continued support and readership. We’ve had some big changes this year with a new name and improved content which we hope helps you in your clinical practice providing the best patient outcomes.

A lthough difficult to pick one article that was a favourite, a study by Lui and colleagues “Modeling the effect of shared care to optimise acne re- ferrals from primary care clinicians to dermatologists” published this past year in JAMA Dermatology rises to the top for me as top story of the year! ( JAMA Dermatol 2016;152:655-660) A recent keynote lecture by Marty Makary at the American Dermatological Association annual meeting (July 28–31, 2016, Boston, Massachusetts) brought this into focus. Dr Makary is the co-developer of theWorld Health Organization checklist outlined in Atul Gawande’s bestseller The Checklist Manifesto (NewYork, NY. Metropolitan Books; 2009). He is a surgeon and professor of public health at Johns Hopkins, and has written his own book, Unaccountable: What Hospitals Won’t Tell You and How Transparency Can Revolutionize Health Care (Makary M. New York, NY. Bloomsbury Press; 2012). He believes that many of the issues we face in medical care (eg, cost containment, efficient delivery of care) can be addressed by acknowledging that the way we “always did it” might not be the best approach from the standpoint of our patients and society as a whole. Related to this, he advocates “accountability” in the form of data that show what is being done and allowing one to compare the care provided by physicians and institutions. His message is not specifically pro-government or pro-regulation. He favours physicians identifying problems and working to improve systems that will protect our patients. He suggests that physicians are generally competitive. Once the data become transparent, we will work harder than ever to be the best we can be. This message resonates when I think about this particular article and the com- mentary that was written with my colleagues Drs Brodell and Bhatia. We can address patient needs with respect to acne most effectively with a team approach. Let’s start by working with our primary care colleagues (and patients) to promote evidence-based medicine (eg, safe and effective use of topical retinoids in acne). There is a plethora of data to support earlier use of topical retinoids because it has been shown to improve outcomes in young patients with acne. So-called “shared care” has the potential to optimise outcomes and minimise costs and inconveniences for our patients. Of course, it is not just about acne. There are many other conditions for which access to board-certified dermatologists can be problematic! Earlier diagnosis of skin cancers will surely help to reduce morbidity and mortality. In my opinion, this will depend on everyone within the “house of medicine” keeping their eyes open for potential melanomas and non-melanoma skin cancers. Other conditions can also be attacked with better communication and education focused on the improvement of outcomes. This should not be perceived as “giving up” our turf in the realm of evidence-based care of acne. On the contrary, it extends the reach of the dermatologist to serve the needs of a population through data generated from studies in our literature. Advanced disease will still be funnelled to specialists; but, at least at the popu- lation level, perhaps much psychological and physical scarring may be addressed sooner and avoided altogether with primary care physicians addressing the issue and providing proven first-line therapies. This article spoke to me as an example of one way to improve outcomes, reduce costs, and ensure that dermatologists continue to contribute to the “house of medicine.” This requires individual effort focusing on professionalism and ethics. Let’s roll up our sleeves and work together to improve the dermatologic health of our patients.

I wish you well for 2017 – and to the breakthroughs next year will bring. Happy summer reading! Anne Neilson

Managing editor, PracticeUpdate Dermatology & Rheumatology (Australian Edition)

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2016 TOP STORIES IN DERMATOLOGY 4

Dr Jane Grant-Kels onmelanoma

Jane Grant-Kels MD is Professor and founding Chair of the Department of Dermatology at the University of Connecticut Health Center and Medical School, and an Advisory Board Member of PracticeUpdate Dermatology. She specialises in cutaneous oncology and pigmented lesions of the skin.

T here continues to be incredible excitement in the melanoma field due to a constant flow of advances and discoveries. I have chosen three to share with you. In the area of therapy, last year’s approval of ipilimumab as adjuvant therapy for stage  III melanoma opened the door to a new era in melanoma treatment. This approval was based on the pivotal study by Eggermont et al ( Lancet Oncol 2015;16:522-530). For a long time, there has been an unmet need for an approved adjuvant therapy for stage III melanoma patients besides interferon, which is only marginally helpful and very toxic. This multicentre and international group performed a double-blind phase 3 trial with 951 patients with stage III cutaneous melanoma who had not received previous therapy except surgery. Patients were randomised to receive intravenous ipilimumab (10 mg/kg) or saline every 3 weeks for four doses and then every 3 months for 3 years. The group who received the adjuvant ipilimumab had significantly improved recurrence-free survival (median survival was 26.1 months, and 3-year survival was 46.5%) versus the placebo group (median survival was 17.1 months, and 3-year survival was 34.8%). Adverse events were immune-related and resulted in discontinuation of therapy by 52% of the patients receiving active therapy and 5 deaths. Despite the toxicity of ipilimumab, the adjuvant therapy clearly improved recurrence-free survival. The dosage used of 10 mg/kg is higher than the approved dose of 3 mg/kg that is used in patients with stage IV disease. Further investigation on dosing is ongoing in the ECOG 1609 (NCT 01274338) study that is comparing 1 year of ipilimumab at 10 mg/kg versus 3 mg/ kg versus high-dose interferon. So, stay tuned. More information to come to help our stage III melanoma patients!

Another major development in treating melanoma is our new understanding of the regulatory pathways and immune checkpoints in the adaptive immune response to melanoma. A wonderful review from the Moffitt Cancer Center (United States) details how inhibitors of these checkpoints can be utilised to treat melanoma ( Semin Oncol 2015;42:363-377). Blockades by an antibody to CTLA-4 or an antibody to PD-1 have now been shown to be successful strategies either alone or in combination in melanoma patients. Other emerging checkpoint proteins (BTLA, VISTA, CD 160, LAG3, TIM3, CD244, and others) are also being investigated as potential targets for inhibition. Finally, a recent paper by Kaisaki et al presents data that may transform the way we diagnose and follow our melanoma patients ( PLoS One 2016;11:e0162809). Imagine if we could draw the blood of our melanoma patients to see how they have responded to therapy. This study suggests that might not be too far in the future. This group studied circulating tumour DNA of melanoma patients and lung cancer patients. Solid tumours often release DNA into the circulation and therefore the blood could be a source for a “liquid” biopsy. The 21 known melanoma patients were studied retrospectively to confirmwhether themutations in the primary melanoma would also be detectable in the circulating tumour DNA. Blood samples were drawn within 1 year of biopsy or before treatment. Circulating DNA showed good concordance with the primary melanoma mutations. Of note was that circulating DNA sequenced after targeted melanoma therapy demonstrated that in 9 out of 10 patients, the mutations were no longer found. This suggests that circulating DNA could be a way to follow therapeutic responses in our melanoma patients!

A recent paper by Kaisaki et al

presents data that may transform the way we diagnose and follow our melanoma

patients. Imagine if we could draw the blood of our

melanoma patients to see how they have responded to therapy. This study suggests that might not be too far in the future.

PRACTICEUPDATE RHEUMATOLOGY & DERMATOLOGY

SIMPONI GOES THE DISTANCE 1,2 † † Durable efficacy ‡ and established safety to 5 years in bio-naïve patients with rheumatoid arthritis ‡ 49% ACR50 responders 2 2

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SIMPONI (golimumab, rmc). Indications: Moderate to severely active rheumatoid arthritis (RA) in adult patients, in combination with methotrexate; active and progressive psoriatic arthritis (PsA) in adult patients, alone or in combination with methotrexate; active ankylosing spondylitis (AS) in adult patients, active non-radiographic axial spondyloarthritis (nr-Axial SpA), active ulcerative colitis (UC) in adult patients. Contraindications: Severe infections such as tuberculosis (TB) and sepsis, opportunistic infections; concurrent anakinra or abatacept; moderate or severe heart failure (NYHA class III/IV), hypersensitivity to golimumab or any excipients. Precautions: May affect immune response; chronic, current, history or risk of infections, TB; Hep B reactivation; Hep B screening; surgery (infection risk); history or current malignancies *and lymphoproliferative disorders development of lymphomas, leukaemia or other malignancies in patients treated with a TNF-antagonist cannot be excluded, *hepatosplenic T-cell lymphoma; colon dysplasia/carcinoma; skin cancers, periodic skin examination, risk of malignancies in children, especially with concurrent immunosuppressants; CNS demyelinating disorders; haematological cytopaenias; live vaccines not recommended; concurrent therapeutic infectious agents not recommended; hypersensitivity reactions, latex sensitivity; autoimmunity. Not recommended in pregnancy (Category C) or while breastfeeding. Contraception recommended and discontinue breastfeeding including at least 6 months after last dose. Interactions with other medicines: Use with abatacept or anakinra is not recommended. Combination with other biologics used to treat the same condition is not recommended. Live vaccines should not be given concurrently with SIMPONI.Therapeutic infectious agents should not be given concurrently with SIMPONI. Use with methotrexate does not require dose adjustment. Adverse Effects: URTIs, *LRTIs infections (bacterial, viral and superficial fungal), allergic reactions, GI effects, increased ALT and AST, dizziness, headache, *paraesthesia, pyrexia, asthenia, hypertension, pruritus, *alopecia, rash, dermatitis, *asthma and related symptoms, anaemia, depression, insomnia, bone fractures, injection site reaction, chest discomfort. For others see full Product information. Dosage: RA, PsA, AS *and nr-Axial SpA: 50 mg subcutaneous injection once a month, on the same date each month; UC: 200 mg at Week 0, 100mg at Week 2 then 100 mg every 4 weeks. Presentation: Solution for injection containing 50 mg golimumab in Smartject Injector pen or pre-filled syringe; Solution for injection containing 100 mg golimumab in Smartject Injector pen or pre-filled syringe. Date of preparation: 20 September 2016.

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AMERICAN ACADEMY OF DERMATOLOGY 73RD ANNUAL MEETING 6

Dr Robert Brodell discusses wounds and ulcers, controversies inmanaging cutaneous lupus and dermatomyositis patients Robert Brodell MD, FAAD, is Professor and Chair of the Department of Dermatology at the University of Mississippi Medical Center in Jackson, and Editor-in-Chief of PracticeUpdate Dermatology .

AAD 2016 4–8 MARCH 2016 • WASHINGTON, USA PracticeUpdate

Dermatology ’s Editor- in-Chief and Editorial/ Advisory Board members weigh in on controversies in managing cutaneous lupus and

dermatomyositis patients, as well as treating and preventing herpes zoster; discussions on Zika-linked skin

SYM S056 – Wounds and ulcers: the good, the bad and the ugly. Robert S. Kirsner Eliot Mostow noted that the exact cost of wound care and the number of ulcers treated annually in the US needs further clarification. While 6.5 million chronic wounds at a cost of US$25 billion dollars per year have been a statistic cited multiple times, Dr Mostow proposes more focus on extrapolation from defined “closed healthcare” systems to flesh out these numbers more accurately and adjust for population changes. Multiple studies suggest that the costs may be higher even with (potentially) lower numbers of wounds. It is possible that the number exceeds that of non-melanoma skin cancers treated in a year. This is not a condition that dermatologists should cede to physicians from other specialties. Hadar Lev-Tov’s lecture stressed the importance of choosing the correct test to assess arterial insufficiency in patients with diabetic leg ulcerations. Transcuta- neous oxygenation measure and toe pressures can be a more accurate reflection of oxygenation and flow when compared withABI (ankle-brachial pressure index) because of collateral blood flow in the legs. Adam Friedman noted that he no longer uses silver sulfadiazine because the agent can impede wound healing. Silver dressings, however, are effective antimicrobials

eruptions; and insights on emerging technology in dermatology, from AAD 2016.

and improve healing rates when used appropriately. They are unlikely to cause argyria because of the small amount of silver actually used in the products. Manuka honey is helpful for wounds because of osmotic effects and by keeping the wound moist. However, honey that has not been irradiated (medical grade) may create risk for bacterial infections. Nitric oxide accelerates wound healing, but not all nitric oxide donors and generators perform equally. There are no products currently on the market harnessing this technology, but a number of promising studies suggest that new products will be available within a few years. FOC U067 – Controversies inmanagement and treatment of cutaneous lupus and dermatomyositis patients. Benjamin F. Chong When dermatomyositis (DM) is suspect- ed based on dermatologic signs, several

© 2016 AMERICAN ACADEMY OF DERMATOLOGY PRACTICEUPDATE RHEUMATOLOGY & DERMATOLOGY

AAD 2016 7

tests are indicated. First, test for muscle strength and order creatine kinase (CK) and aldolase to showmuscle damage. In patients with clear-cut dermatomyositis, further diagnostic tests are often not warranted. However, in patients in whom the diagnosis is considered, but not at all certain, a panel of myositis antibodies in the patient’s serum can now be ordered at certain reference labs (eg, Oklahoma Medical Research Founda- tion Clinical Immunology Laboratory and the Mayo Clinic). Be prepared for the results to take up to 2 months since the tests are batched before they are run. Also, the panel may detect 70% to 80% of cases, but not all. The panels include: • Mi2 – Patients with this antibody commonly have skin findings including the “shawl” sign, less muscle weakness, and generally a good prognosis. • Anti-tRNA synthetase (Jo 1 and others are in this class) – These patients commonly have interstitial lung disease and Raynaud’s phenomenon, but this antibody is rare. • MDA-5 (10–20% of DM patients) – These patients have rapidly progressive interstitial lung disease, painful palmar papules, and ulcerations in place of Gottron’s papules, although they are in the same locations. • TIF1-gamma (13–20% of DM patients) – This can be malignancy-associated. Extensive skin disease is present, including psoriatic lesions and hyperkeratotic lesions of the palms and soles. • NXP2 (2–30% of DMpatients) – This can be malignancy-associated and is seen in juvenile DM. An approximate 20% of patients with DM have interstitial lung disease. Three ap- proaches can be taken to assess for this in DM patients. • Pulmonary function tests. • High-resolution CT; often read as interstitial pneumonia. This has the added benefit of screening for lung cancer (DM is associated with a threefold increased risk of internal malignancy). • Refer to pulmonary physician. With regard to the question does smoking decrease the effectiveness of antimalarial agents in patients treated for discoid lupus? • One study said “yes.” • Three retrospective studies said “no.” • Recent JAAD meta-analysis suggested a two-fold decrease in disease response in patients who smoke.

Dr Eliot Mostow discusses herpes zoster and the Dermatology Teachers Exchange Group

Eliot N Mostow MD, MPH, is Professor and Head of the Dermatology Section at Northeast Ohio Medical University, and an Editorial Board Member of PracticeUpdate Dermatology.

FRM F015 – Herpes zoster: controversies and conundrums in treatment and prevention. Lorraine L. Rosamilia This was an excellent case-based session moderated by Dr Lorraine Rosamilia. She did a great job framing the “real world” questions related to herpes zoster as an effective set-up and closure to covering reviews on diagnostics given by: • Dr Whitney High – While Tzanck preps can still play a role, newer diagnostics such as polymerase chain reaction (PCR) are not too expensive and are relatively quick and accurate. The options for these will vary with locale. • Dr Vikash Oza – In paediatric cases, zoster can occur post vaccination, but it is often attenuated compared with wild-type cases except in the immunocompromised. • Dr Stephen Tyring – Vaccine is safe, and “moderately” effective in adults, although vaccination, once someone’s had shingles, is likely of minimal benefit. • Dr Ken Tomecki – Reviewed drug options and data. Searching for zoster in the AAD program shows that this was the only mention of it, although I hope there were lectures in other sessions that covered some of this material! FRM F029 – Dermatology Teachers Exchange Group. Tammie C. Ferringer, Roy Mitchell Colven I loved the overall session known as the Dermatology Teachers Exchange Group. I always leave inspired to think about new ways to advance the teaching of dermatology. This year, I’m going to use ideas proposed to “force” students to use accurate terms by filling in the blanks (sort of like a Mad Libs) of a script I’m going to compose…something like, “This patient has a___________(primary lesion) that is_________(descriptor of color, texture, etc) on the_________(location)…” with additional scripts that will help them improve their communication with me and to enter the medical record in a more defined fashion. I also liked the lecture by Allison Cruse from the University of Mississippi Medical Center. She talked about efforts to increase hand hygiene in outpatient clinics by having medical students, residents, nurses, and faculty make a single knock on the desk or wall if anyone

enters a patient room without using hand hygiene within 20 seconds. Their centre went from about 40% hand hygiene to 80% in 6 months and 90% a year later. Nonthreatening immediate feedback can have dramatic results in improving behaviour, even when in- grained in faculty over decades! Time and space do not permit more comments on this ses- sion; but, if you like teaching, this is a great session every year.

© 2016 AMERICAN ACADEMY OF DERMATOLOGY

DECEMBER 2016

AMERICAN ACADEMY OF DERMATOLOGY 73RD ANNUAL MEETING 8

Dr Sarah Chamlin discusses Zika-linked skin eruption, systemic drug therapy in children, cognitive behavioural therapy for eczema Sarah Chamlin MD, is Associate Professor of Pediatrics and Dermatology at Northwestern University Feinberg School of Medicine, and a member of the PracticeUpdate Dermatology Advisory Board.

Zika virus and paediatric derm update. Scott Norton Dermatologists need to be alert for the skin eruption of Zika virus infection. Zika virus, a Flavivirus, is part of a family of mosquito-borne viruses which includes West Nile virus and is transmitted by Aedes mosquitos, specifically A. aegypti and A. albopictus . Zika virus infection was first reported in the Zika forest in Uganda in 1947, which later spread to the Micronesian island of Yap, then French Polynesia. Further spread to Mexico, Central America, the Caribbean, and South America followed; the current epicentre is Brazil. Most often – 80% of the time – infection is asymptomatic, but 20% of individuals experience a mild viral illness that may include a rash, conjunctivitis, and arthralgia. Fever, myalgia, and headache may also be noted. The rash has been described as a generalised, erythematous morbilliform eruption. The differential diagnosis includes dengue and Chikungunya, although the rash and conjunctivitis are more prominent with Zika. Zika is also thought to cause lissencephaly – leading to the microcephaly reported in Brazil – Guillain-Barré syndrome, and acute disseminated encephalomyelitis. While only approximately 100 cases of Zika have been identified in the US, more are anticipated, possibly this summer; dermatologists may be on the front line to make this diagnosis. Controversies involving systemic drug therapy in children. Stephen Wolverton Clinical decision-making about drug use in paediatric patients with skin disease is often based on limited data that are extrapolated from adult data or paediatric data for another disease (eg, use of systemic drugs for juvenile idiopathic arthritis or Crohn’s disease). A few lecture pearls are listed below. • As a general rule, mg/kg dosing starts to roughly equal adult doses at around 45 kg. • While subcutaneous methotrexate dosing has approximately the same bioavailability as the oral formulation, subcutaneous avoids the first-pass effect in the liver and higher doses can be used. Unfortunately, the use of subcutaneous drugs is more limited in children due to pain. • A methotrexate test dose, 5 to 10 mg, with labs in 5 to 6 days may minimise pancytopenia risk. The paediatric dosing range for methotrexate is 0.2 to 0.7 mg/kg, and many patients respond at lower doses, even the test dose. • A FibroScan should be considered in children with a high BMI on methotrexate to reassure clinicians of long-term safety. While this scan is not routinely done

in children, it helps to decrease the number of liver biopsies done in adult psoriasis patients. • Evidence for use of methotrexate, azathioprine, and cyclosporine for severe and recalcitrant atopic dermatitis is present in the literature. Much less evidence is published for use of mycophenolate mofetil, which is probably the safest to use. Research options emerging for this population are omalizumab and dupilumab. • Several biologics are available for use in children with severe, recalcitrant psoriasis, including etanercept, adalimumab, infliximab, ustekinumab, and secukinumab. • Recent articles suggest less frequent laboratory monitoring for patients taking isotretinoin. Pregnancy testing in women is an exception to this, and triglyceride testing is the most volatile lab to follow, especially if elevated at baseline. The approach to lab testing that was reviewed was to stop monthly labs if stable after 2 months of testing. • There is no strong and supportive evidence proving an increased risk of depression and suicide or inflammatory bowel disease with isotretinoin use. Anecdotally, there may be a very small subpopulation at risk for quickly reversible depression. Cognitive behavioural therapy & biofeedback in the management of eczema. Carisa Perry-Parrish Children with atopic dermatitis may experience excessive itching, sleep disturbance, diminished quality of life, poor self-image, and peer teasing. Involvement of a paediatric psychologist in the care of severely affected patients may improve patient and family disease knowledge, treatment adherence, and coping. In addition, scratching reduction can improve disease severity. Behavioural treatment examples for scratching reduction include: • Habit reversal – Keep hands busy! Instead of scratching, squeeze hands together, sit on hands, draw or colour. • Praise children for behaviours incompatible with scratching – This will increase positive habits and reduce inadvertent reinforcement of bad habits. Saying “stop scratching” just doesn’t work. • Token system – Provide points or stickers for applying moisturisers or taking a bath. Earn points for engaging in habit-reversal techniques. • Stress reduction – Older children may benefit from stress-reduction techniques such as deep breathing, visualisation, and muscle relaxation.

PRACTICEUPDATE RHEUMATOLOGY & DERMATOLOGY

AAD 2016 9

Dr Jane Grant discusses new and emerging technologies in dermatology

SYM S035 – New and emerging technologies in dermatology. Jane Grant-Kels This session reviewed current and evolving technologies available to help us differentiate benign from malignant lesions without performing a biopsy. Reflectance confocal microscopy In vivo reflectance confocal microscopy (RCM) is a noninvasive optical imaging technique that provides a high-resolution image of the skin to a depth of 200 to 300 μm (0.2–0.3 mm). RCM relies on a low-power laser that emits near infrared light projected through a lens system. To obtain an image of skin, RCM uses the different reflection indices of various structures to produce a horizontally sectioned (ie, sections parallel to the skin surface) black-and-white image. The resulting images are comparable to histopathology images but are obtained in vivo, without performing a biopsy. I reviewed clinical applications of the VivaScope 1500, or the wideprode traditional RCM that has recently been awarded CPT codes and can be used to evaluate 8 mm x 8 mm areas on the skin. Dr Harold Rabinovitz from the University of Miami reported on the handheld VivaScope 3000, which provides stacks of images through the skin that are only 1 mm x 1 mm in size. The handheld adaptor is most applicable to evaluate tumours on the eyes, periorbital skin, mucosal surfaces, and curved surfaces of the face, which are difficult to capture with the larger head of the VivaScope 1500. Both I and Dr Rabinovitz gave many examples of how this technology can spare our patients unnecessary biopsies and improve our malignant to benign biopsy ratio. Electrical impedance spectroscopy Dr Peter Mohr from Buxtehude, Germany, reviewed his data on the use of electrical impedance spectroscopy (EIS) to differentiate benign from malignant lesions of the skin without biopsy. EIS measures the overall resistance within tissue at alternating currents of various frequencies. The resulting different measurements detect changes in cellular structure, cellular orientation, cell sizes, and cell types. The ultimate score is calculated by the computer and reflects the degree of atypia, helping to establish the difference between a benign nevus and melanoma with a sensitivity of 97% and specificity of 35% and without a painful procedure. Of interest is that the sensitivity for dermatopathology was 85% and the sensitivity for dermoscopy was 71% on the same lesions. Dr Mohr suggested that this new technology would be particularly helpful in those melanomas that defy clinical and dermatoscopic diagnosis. The use of EIS in dermatology clinics in Europe has been shown to reduce excisions by 40% to 50%. Raman spectroscopy and photoacoustic tomography Dr Eric Tkaczyk from Vanderbilt University reviewed the exciting future roles for Raman spectroscopy and photoacoustic tomography. Raman spectroscopy is a technique that measures inelastic scattering of monochromatic light. The light interacts with molecular vibrations that

Jane Grant-Kels MD, is Director of Dermatopathology and Chair of the Melanoma Signature Program at the University of Connecticut Health Center, and an Advisory Board Member of PracticeUpdate Dermatology .

result in a “fingerprint” of the biochemical compo- sition of the tissue. Clinical applications include imaging of topical drug delivery. Photoacoustic tomography allows deep detection of melanin, hae- moglobin, and oxygenation. Three-dimensional im- aging of tissue results from light that is absorbed by biological tissue and converted to transient heating, which is then converted into ultrasonic waves. De- tection of the ultrasonic waves yields a tomographic image based on the photoacoustic effect. Dr Tkaczyk demonstrated how photoacoustic microscopy could identify melanoma metastases in lymph nodes in lieu of sentinel lymph node biopsies! This new and exciting technology is still only in the research lab but someday will be applied in the clinic to reduce procedures and enhance accuracy in early diagnosis.

© 2016 AMERICAN ACADEMY OF DERMATOLOGY

DECEMBER 2016

AMERICAN ACADEMY OF DERMATOLOGY 73RD ANNUAL MEETING 10

Hirsutism, acanthosis nigricans themost reliablemarkers of polycystic ovary syndrome

Hirsutism and acanthosis nigricans are the most reliable cutaneous markers of polycystic ovary syndrome and require a comprehensive skin examination to diagnose, results of a retrospective, cross-sectional study show.

T imothy Hunter Schmidt, MD, PhD, of the University of California, San Francisco, explained that the understanding of the associations among cutaneous findings, systemic abnormalities, and fulfilment of diagnostic criteria in women suspecting of having polycystic ovary syndrome is incomplete. Dr Schmidt and a research team led by Kanade Shinkai, MD, PhD set out to identify cutaneous and systemic features of polycystic ovary syndrome to help distinguish women who do and do not meet diagnostic criteria. Dr Shinkai said, “We undertook the study to better understand the skin manifestations of polycystic ovary syndrome. It was the first study to system- atically characterise the detailed skin findings of this disease in a large, racially diverse cohort of women.” The team studied a racially diverse referred sample of women seen at their polycystic ovary syndrome multidisciplinary clinic over a 6-year period be- tween 2006 and 2012. Four hundred one women were referred for suspected polycystic ovary syn- drome, 68.8% (n=276) who met the Rotterdam polycystic ovary syndrome diagnostic criteria. Twelve percent (n=48) did not. Overall, 11.5% (n=46) had insufficient data to render a diagnosis, 1.7% (n=7) were excluded, and 6.0% (n=24) declined to participate in the study. Patients underwent comprehensive skin examination and transvaginal ultrasonography and were tested for total testosterone, free testosterone, dehydroepiandrosterone (DHEA-S), androstene- dione, as well as a number of additional hormone levels. Serum cholesterol, high density lipoprotein choles- terol (HDLC), low density lipoprotein cholesterol (LDLC), and triglyceride levels were also meas- ured, as well as 0- and 2-h oral glucose tolerance test (DGTT) results, along with glucose and insulin levels. Median patient age was 28 years. Compared with women who did not meet diagnostic criteria for polycystic ovary syndrome, women who met cri- teria had higher rates of hirsutism (53.3% [144 of 270] vs 31.2% [15 of 48], P = 0.005) (with higher mean modified Ferriman-Gallwey scores of 8.6 vs

5.6, P = 0.001), acne (61.2% [164 of 268] vs 40.4% [19 of 47], P = 0.004) and acanthosis nigricans (36.9% [89 of 241] vs 20.0% [9 of 45], P = 0.03). Cutaneous distributions also varied. Women who met criteria for polycystic ovary syn- drome demonstrated more severe hirsutism (espe- cially on the trunk) and higher rates of acanthosis nigricans (especially axillary). Women who met criteria for polycystic ovary syndrome had elevated total testosterone levels, (40.7% [105 of 258] vs 4.3% [2 of 47], P < 0.001). Among women with polycystic ovary syndrome, the presence of hirsutism (43.9% [54 of 123] vs 30.9% [34 of 110], P = 0.04) or acanthosis nigri- cans (53.3% [40 of 75] vs 27.0% [40 of 148], P < 0.001) was associated with higher rates of elevated free testosterone levels, as well as several metabolic abnormalities, including insulin resistance, dyslip- idaemia, and increased body mass index. Though the prevalence of acne was increased among women with polycystic ovary syndrome, acne types and distribution differed minimally between women meeting versus not meeting pol- ycystic ovary syndrome criteria. The team concluded that hirsutism and acanthosis nigricans are the most reliable cutaneous markers of polycystic ovary syndrome and require a com- prehensive skin examination to diagnose. When present, hirsutism and acanthosis nigricans should raise clinical concern that warrants further diagnostic evaluation for metabolic comorbidities that may lead to long-term complications. Acne and androgenic alopecia are prevalent but unreliable markers of biochemical hyperandrogenism in this population. Dr Shinkai said, “A significant result of the study is that it helps identify key skin features that distin- guish women with polycystic ovary syndrome from those suspected of having the syndrome but do not have the disease. This information will hopefully improve the diagnostic accuracy of clinicians as- sessing these patients (and also avoid unnecessary diagnostic workup of women who do not need it).” She added, “Future directions include understand- ing the skin findings in subtypes of polycystic ovary syndrome and also, the best medical and surgical treatments for the syndrome.”

A significant result of the study is that it helps identify key skin features that distinguishwomen with polycystic ovary syndrome from those suspected of having the syndrome but do not have the disease.

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WHAT IS REALLY IMPORTANT TO PATIENTS?

CLEAR SKIN *1-3

*PASI 100 was achieved in 41.6% and 36.8% of patients with Cosentyx 300 mg at week 16. 1,3

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 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 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). References: 1. Cosentyx ® TGA Approved Product Information. Novartis Pharmaceuticals Australia Pty Limited. 17 October 2016. 2. Thaci D et al. J Am Acad Dermatol 2015;73:400–9. 3. Langley RG et al. N Engl J Med 2014;371:326–38. ® 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: December 2016. SKM0416. CRD2720. 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.

AMERICAN ACADEMY OF DERMATOLOGY 73RD ANNUAL MEETING 12

Melanoma diagnosed earlier from 2001 through 2011 Early detection of melanoma improved significantly, as measured by stage at diagnosis, over the decade 2001–2011, report results of a crossover registry study.

G iselle Prado, BS, of the Herbert Wertheim College of Medicine, Florida International University, Miami, explained that it is estimated that over 73,000 new cases of melanoma will be diagnosed in the US this year. While melanoma accounts for less than 2% of skin cancer cases, it will account for most skin cancer related deaths. Early detection of this highly aggressive cancer is the cor- nerstone of treatment. “We undertook this study,” said Ms Prado, “because we know that melanoma incidence has been increasing. It’s important to implement public health programs that help increase early detection. Excising a superficial melanoma is much simpler than dealing with the morbidity and mortality associated with higher stages of melanoma. In addition, rising healthcare costs are another important reason to detect melanomas at an early stage.” Ms Prado and colleagues employed data from 18 registries reporting to the Surveillance, Epidemiology, and End Re- sults (SEER) program from 2001–2011. They performed multivariate logistic regression to obtain unadjusted and adjusted associations between year of diagnosis and stage at the time of diagnosis (in situ/localised vs regional/distant). Demographic traits, age at diagnosis, primary site, laterality, histologic subtype, and tumour size were used as predictors. A total of 115,913 cases of melanoma were identified from 2001–2011. Men constituted 56.6%. Age at diagnosis was evenly split between persons 40-64 years of age (45.4%) and those >65 years of age (43.4%). Primary site was distributed as follows: head and face 28.1%, trunk 29.8%, upper limb 25.0%, and lower limb 17.0%. More primary melanomas were located on the left side (51.8%).

Most cases were in situ or localised (92.5%) versus regional and distant (7.5%). A significant unadjusted association was observed be- tween year and stage of diagnosis (odds ratio 0.95, 95% CI 0.95–0.96). After adjusting for sex, age at diagnosis, primary site, and histology code subtype, the significant association between year of diagnosis and stage remained (odds ratio 0.94, 95% CI 0.93–0.95). Adjusted analysis also demonstrated that females were less likely to be diagnosed at a higher stage than men (odds ratio 0.69, 95% CI 0.65–0.73). Persons >65 years of age were more likely to be diagnosed with regional and distant cancer (odds ratio 1.24, 95% CI 1.13–1.35) than those age 18–39 years. Melanomas located on the trunk (odds ratio 0.77, 95% CI 0.71 - 0.82) and upper limb (odds ratio 0.64, 95% CI 0.60–0.69) were less likely to be a higher stage than those located on the face and head. Nodular melanoma was more likely to be widespread at diag- nosis than superficial spreading melanoma (odds ratio 10.63, 95% CI 9.77–11.57). Acral lentiginous melanoma was more likely to be staged higher (odds ratio 6.75, 95% CI 5.70–8.00). Ms Prado said that early detection improved significantly as measured by stage at diagnosis. Men and older patients were more likely to be diagnosed at a higher stage. Education and interventions aimed at early detection are critical to reduce the incidence of regional and distant melanoma. “In the future,” she said, “we need more studies detailing exactly why earlier detection occurred over this time period, whether it was increased awareness, increased surveillance by dermatologists, or other factors.”

Over a third of emergency department patients admitted for cellulitis are misdiagnosed Over a third of patients admitted through the emergency department with a diagnosis of cellulitis were misdiagnosed, outcome of a retrospective chart review performed in a large urban hospital show. A dam B. Raff, MD, PhD, of Harvard Medical School, Boston, Massa- chusetts, explained that cellulitis is

emergency department costs. Cellulitis is frequently misdiagnosed due to numerous clinical entities with similar pres- entations, so-called pseudocellulitis, such as chronic venous stasis. Thirty to ninety percent of patients referred to an inpatient dermatologist for presumed severe lower limb cellulitis were misdiagnosed in a study. In an effort to better characterise the overall

impact of misdiagnosis, Dr Raff and col- leagues analysed of the healthcare burden of pseudocellulitis, including delay of effective care, inappropriate use of antibiotics, unnec- essary hospital admissions, complications, and increased medical costs. Dr Raff said, “I was challenged by patients I was seeing as an inpatient dermatologist. Many patients referred to me for cellulitis

a common diagnosis, with 2.3 million visits annually to the emergency department and an estimated at 15.2% admission rate. Cel- lulitis accounts for 10% of infectious disease – related US hospitalisations. Cellulitis ac- counted for US$3.7 billion in outpatient and

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