KEYNOTE ADDRESSA New Understanding of Androgenetic Alopecia George Cotsarelis, MD

Background. Dr. Cotsarelis has been intrigued by the humanhair follicle (HF) ever since he upended conventional wisdom atthe end of the 1980s with his discovery that the HF stem cells (SCs)actually reside up in the then little-known bulge, not down in thebulb. Since then, he has investigated what makes hair grow, whatmakes growth stop in some men and women—especially prema-turely—and how it can be restarted. Male pattern baldness, or AGA(androgenetic alopecia), has been an important focus.

Getting started. Once Cotsarelis demonstrated the sharedstructure and physiology of the mouse and human HF, he was able to benefit from studying mouse hair. It is ideal because the en-tire coat cycles synchronously, and Cotsarelis could also reap the

benefits of the technology emerging then—transgenic mice, flow cytometry for keratinocytes, and techniques to assess the geneticlandscape.

SCs and alopecia. During balding the hair follicle miniatur-izes, shrinking from a 4–5 mm long structure to a microscopic size.Comparing same-patient occiput and balding scalp tissue samplesremaining from transplant procedures, Cotsarelis found SC num-bers in these tiny follicles to be normal, but they produce far fewerdaughter progenitor cells than normal. This apparent defect in SCactivation and proliferation suggested the lack of an activator orpresence of an inhibitor.

Hunt for the cause. Gene expression arrays showed dra-matically elevated levels in balding scalp of the gene for the enzymePGDS (prostaglandin D2 synthase). This enzyme, also higher inbalding scalp, converts prostaglandin H2 to D2 (PGD2), which com-petes with the pro-hair-growth prostaglandins E2 and F2. Baldingscalp also revealed elevated levels of D2, “dwarfing the otherprostaglandin levels in the scalp.” A look at HF cycling in the normalmouse showed increased PGDS expression just as the follicles tran-sition from anagen to catagen and regression. In normal humanhair, expression of L-PGDS (lipocalin-type PGDS, the form of PGDSin humans) likely identifies the small subset of HFs transitioning

DERMATOLOGYFOCUSDERMATOLOGYFOCUS™

DF Clinical Symposia:Proceedings 2016–Part I

VOL. 35 NO. 1 Revised SPRING 2016

A DERMATOLOGY FOUNDATION PUBLICATIONSPONSORED BY VALEANT PHARMACEUTICALS NORTH AMERICA LLC

ADVANCES IN DERMATOLOGYThe Dermatology Foundation presented its annual

3-day symposia series in February. This highly esteemedcutting-edge CME program provides the most clinicallyrelevant knowledge and guidance for making the newest research advances accessible and usable. A daily provocative keynote talk precedes topic-focused, peer-reviewed caliber presentations. (Informal BreakfastRoundtables and evening Therapeutics Forums amplifythe take-home value.) This year’s topics were: TreatmentInnovation and Skin Disease; Pediatric Dermatology; Errors, Complications, and Patient Safety; CPC; DifficultMedical Dermatology Conundrums; Policy, Ethics, andthe Law; and Evolving Evidence: New Knowledge inDermatology. The Proceedings appear in the Spring(Part I) and Summer (Part II) issues.

Janet A. Fairley, MD, andJack S. Resneck, Jr., MD—Program Co-Chairs

Also In This Issue

$2.6 Million in Research Awards for 2016

DF Welcomes 24 New Leaders Society Members

Bruce A. Brod, MD, Honored

Transgenic K14-Cox2 Mouse PhenocopiesAndrogenetic Alopecia

These transgenic mice overexpress COX-2 under control of the human keratin-14 promoter, targeting

overexpression to the epidermis

from anagen to catagen. Mast cells—which also increase in AGA—also express L-PGDS.

Pursuing the path. Applying the PGD2 lipid to normalmouse skin shortened anagen and inhibited hair growth. PGD2binds to 2 different receptors, and using knockout mice the Cot-sarelis lab determined that, of these, the DP2 receptor mediates thisnegative impact on hair growth. So after adding PGD2 to human

HFs—both male and female—in explant culture diminished theirgrowth, adding a DP2 receptor inhibitor restored it in a dose-depen-dent manner. This observation suggested a therapeutic possibility.Because mast cells carry this receptor, several pharmaceutical com-panies had developed receptor inhibitors for treating allergic rhini-tis and asthma. Although ultimately disappointing in that clinicalcontext, Cotsarelis believes such inhibitors might hold potential forAGA. Several he has worked with appear promising.

MINI-SYMPOSIUM: TREATMENT INNOVATION AND SKIN DISEASE

Biologic Therapy for Chronic Urticaria Mary Beth Fasano, MD, MSPH

Introduction. Dr. Fasano reviewed current guideline-basedprotocols for chronic uticaria, then discussed alternative therapiesfor refractory disease. Using a case-based approach, she noted risk-benefit issues and factors to consider when choosing potentialtherapeutic alternatives to try in a given patient.

The challenge. This 44-year-old man with chronic idiopathicurticaria (CIU) had no identifiable triggers and no underlying sys-temic disease or autoimmune component. Skin biopsies indicatedgarden variety urticaria, yet he had failed Steps 1–3 of the U.S. guide-lines (published in 2014). An H1 blocker had failed, as did an addedH2 blocker, then a high-dose combination of second-generation antihistamines, then the leukotriene receptor-antagonist monte-leukast, then the more potent and sedating H1 blockers doxepin +hydroxyzine. High-dose oral glucocorticoids helped, but undesir-able side effects accompanied the long-term dosing needed for disease control.

The alternatives. Anti-inflammatory options include the oraldrugs dapsone (but not with G6PD deficiency), hydroxychloro-quine, and sulfasalazine—all less costly, easy to administer, withsome data suggesting long-term benefit. But onset is slower and theyinvolve toxicities. Immunosuppressants—the calcineurin inhibitors,mycophenolate, and methotrexate—act more rapidly (success/fail-ure is quickly apparent), but associated toxicities require exceed-ingly careful monitoring. In the group Fasano calls “the other,”doxepin may help sleep. IVIG (very costly) and colchicine lack effi-cacy data. Omalizumab—the humanized anti-IgE monoclonal anti-body approved for asthma in 2003 and chronic urticaria in 2014—is often effective. Fasano discussed the omalizumab clinical trials(ASTERIA I AND II, GLACIAL), with similar positive efficacy findingsdespite design differences. Given by subcutaneous injection every4 weeks, improvement is marked and rapid, long-term control is excellent, but full rebound occurs within 8 weeks after stopping.

2 Spring 2016 Rev. Dermatology Foundation

Pathogenesis of Androgenetic Alopecia• Stem cells intact

• Progenitor cells decreased

• Suggests defect in stem cell activation

• Lack of activator or presence of inhibitor?

Omalizumab—Humanized Monoclonal Anti-IgE• Binds circulating IgE– ↓ serum-free IgE within 2 hrs– ↓ FcεRI on basophil & mast cell surface

• Does not bind cell-bound IgE

• Does not activate complement

• Peak serum concentration = 7–8 days

• Half-life = 20–26 days

Prostaglandin D2 pathwayArachidonic Acid

PGS1 (Cox1)PGS2 (Cox2)

Prostaglandin G2/Prostaglandin H2

PGES PGDS

Prostaglandin E2 Prostaglandin D2

PGD2R2 (DP2)

The Mission of the Dermatology

FoundationWho we are: The DF is the leading private

funding source for skin disease research. What we do: The DF provides research

funding that helps to develop and retain newgenerations of teachers, researchers, and master clinicians, enabling advancements in patient care.To learn more, please see dermatologyfoundation.org.

The patient. After failing other Step 4 treatments, omal-izumab brought good control immediately with complete resolu-tion after the third injection. Stopping after 9 months precipitatedbad rebound; restarting reinstituted control. Key points: Rebound isreal, and patients need to know. Although efficacy of omalizumab300 mg appears superior to 150 mg, therapy duration lacks consensus.

Skin Reactions From New Anticancer Therapies Edward Cowen, MD

Introduction. Identifying the culprit medication in a cuta-neous drug reaction is often challenging, and “dealing with the newtargeted cancer treatments can be especially tricky,” Dr. Cowen emphasized. “Reactions are often delayed in onset, and are not thetraditional immunologic reactions.” Going beyond drug names tothe mechanism(s) of action defining their class “will significantlyhelp understand the reactions they cause, and anticipate those youwill see with new agents entering the market.” (Because textbooksand drug eruption manuals do not include medications very recently approved, PubMed can be a helpful resource.) Despiteknowing a drug’s target(s), however, why these reactions occuroften is still unclear.

The drug classes. For each class, Cowen noted old and newentrants, pathway(s) inhibited, relevant cutaneous effects (pro-fusely illustrated), and treatment guidance. EGFR inhibitors:The most familiar targeted drugs to dermatologists, they inhibit theepidermal growth factor receptor. Skin toxicities—which involvethe hair, skin, and nails—are particularly common, including

acneiform eruptions. Many patients end up on an oral antibiotic fortreatment. VEGF inhibitors: This includes selective and multi-pathway (multikinase inhibitors) drugs. Hand-foot skin reaction isthe most frequent cutaneous side effect with these agents. BRAFinhibitors: Squamous cell carcinoma is an established risk, but isreduced when used in combination with a MEK/ERK inhibitor.MEK/ERK inhibitors: Cutaneous side effects appear similar toEGFR inhibitors, but we are still learning the full range. CTLA-4 &

www.dermatologyfoundation.org Spring 2016 Rev. 3

Editors-in-ChiefLindy Fox, MD—Associate Professor of DermatologyUniversity of California, San FranciscoMary M. Tomayko, MD, PhD—Assistant Professor of DermatologyYale School of Medicine, New Haven, CTHeidi A. Waldorf, MD—Director, Laser and Cosmetic DermatologyThe Mount Sinai Medical Center, New York, NYExecutive DirectorSandra Rahn BenzDeputy Executive DirectorChristine M. BorisPlease address correspondence to:Editors-in-Chief, Dermatology Focusc/o The Dermatology Foundation1560 Sherman Avenue, Evanston, Illinois 60201Tel: 847-328-2256 Fax: 847-328-0509e-mail: dfgen@dermatologyfoundation.orgPublished for the Dermatology Foundation byRobert B. Goetz—Designer, ProductionSheila Sperber Haas, PhD—Managing Editor, Writer

This issue of Dermatology Focus is distributed without charge through an educational grant from Valeant Pharmaceuticals North America LLC.The opinions expressed in this publication do not necessarily reflect those of the Dermatology Foundation or Valeant Pharmaceuticals North America LLC.©Copyright 2016 by the Dermatology Foundation

DERMATOLOGY FOCUSA PUBLICATION OF THE DERMATOLOGY FOUNDATION

Sponsored byValeant Pharmaceuticals North America LLC

Omalizumab for CIU—Key Points• Duration of therapy has not been evaluated– Has been used safely for 12–24 weeks in clinical trials– Periodically reassess the need for continued therapy

• “Rebound” urticaria is common after stopping treatment– Omalizumab does not appear to modify underlyingdisease process

• Duration of urticaria suppression is longer with higheromalizumab doses (300 mg vs 150 mg)

• Mechanism of action in refractory CIU is not yet fullyunderstood

Each year, the Foundation honors exceptional dermatologists who have left a lasting imprint on the specialty.The honorary awards provide an opportunity to recognize the formative teachers and clinicians who have inspired generations of dermatologists.Clark W. Finnerud Award—honors the exceptional clinician who has also been a dedicated and highly effective volunteer or part-time teacher for residents and medical students.Practitioner of the Year—recognizes the dermatologist who is an exemplary clinician in private practice with significant involvement in professional organizations and participation in medical teaching and/or research. Your letter, along with your nominee’s CV, are due at the Dermatology Foundation by August 31, 2016.The 2016 Honorary Awards will be presented at the DF Annual Meeting of Membership in March 2017.

Questions? Contact the DF at 847-328-2256.

2016 Honorary AwardsDF Requests Nominations

(Continued on page 6)

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4 Spring 2016 Rev. Dermatology Foundation

Member Support Remains Key to Progress

Dermatology Founda-tion president Dr. MichaelD. Tharp presided at theDF’s annual membershipmeeting in Washington,D.C. this past March.

“The DF remains theonly private organizationcommitted to furtheringthe scientific base of thespecialty, and it’s focusremains on course—to enable advancements

in patient care by providing research funding to tomor-row’s experts.” We are deeply grateful for the supportwe receive from all of our constituents.”

Individual Contributions“Member giving is the key driver in the DF’s ability

to further advancements in the specialty,” Dr. Tharp said, and expressed heartfelt gratitude to everyone whomade the Foundation a priority in 2015. “Your commit-ment has made it possible for the DF to support thisyear’s research award recipients.” He added a specialthank-you to members who had contributed to the DF atespecially high levels. The 18 new Annenberg Circlemembers each pledged $25,000. AC Sustainingmembers each gave an additional $5,000 for the yearfollowing their completed AC commitment. Nine moreSustaining members committed to extending their annual gift for years into the future.

Industry SupportersCorporate funding has declined

as mergers and acquisitions havecontinued to reduce industry giving.Dr. Tharp noted the particular generosity of the eight companiesremaining in the DF CorporateHonor Society. Unilever was thesole Cornerstone Benefactor.Platinum Benefactors are Abbvie;Galderma Laboratories; Merz, NorthAmerica; and Valeant Pharmaceuti-cals. DUSA Pharmaceuticals is theDF’s single Gold Benefactor. The DF’s Silver Benefactorsare Amgen Inc. and Sun Pharmaceuticals.

Society Partners“The Foundation is extremely appreciative of the

contributions it receives from a wide variety of nationaland local societies.” Dr. Tharp had a special note ofthanks to the American Academy of Dermatology andthe Women’s Dermatologic Society for their ongoingsupport.

The 2015 DF Honorary Awardees, left to right: Drs. Warwick L. Morison (Clark W. Finnerud Award), DF PresidentMichael D. Tharp, Maria L. Chanco Turner (Lifetime Career Educator Award), and Bruce A. Brod (Practitioner of theYear Award).

More is Needed“To accomplish its mission in the year

ahead, the Dermatology Foundation will needeven greater contributions from the dermato-logic community,” Dr. Tharp noted. The unre-lentingly fierce competition for research fundingfrom all sources will continue. “Contributing to the DF is so much more than ‘giving back’ to our specialty to help jump-start the work of tomorrow’s highly talented new investigators.These young people will be contributing to thescience of our specialty. That newly uncoveredknowledge—an expanded understanding of diseases, better diagnostic tests, and new treatments—will be valuable to all of us whopractice this great specialty.”

Dr. Tharp encouraged all dermatologists to join the DF. “Start with membership in theLeaders Society. For a simple investment ofonly $4.10 a day, you can help secure our future, and the practice of dermatology.”

www.dermatologyfoundation.org Spring 2016 Rev. 5

2016: $2.6 Million for Research

Young Leader Reception

Many of the Dermatology Foundation’s 74 Young Leaders—dermatologists who made their commitment to Leaders Societymembership within five years of completing their residency—helped to inaugurate the first Young Leader Reception earlier this year. It preceded the Annual Leadership Gala, held at theNational Museum of Women in the Arts in Washington, DC. Dr. Tiffany Scharschmidt, a Young Leader since 2013, welcomedher colleagues,and thanked eachone for making acommitment thatwill serve the specialty well foryears to come.

“I am pleased to announce that the Dermatology Foundationhas awarded $2.6 million in funding to 51 individuals for2016,” Dr. Bruce U. Wintroub, Chairman of the DF Board ofTrustees, told meeting attendees. “This allocation of supportis helping to fund promising projects and people in all areasof dermatology.”

As in prior years, much of the support is devoted to the highly effective career development awards.There are also three Stiefel Scholarawards, “thanks to the extraordinary $1 million gift from Charles and Daneen Stiefel. These awards, plus the 38 CDAs, represent 80% ofthe DF research funding approved for 2016. The list is completed by four fellowships and six grants.

The DF is grateful to Amgen Inc, Novartis Pharmaceutical Corporation, and Valeant Pharmaceuticals North AmericaLLC for their support of the Young Leader Reception andLeadership Gala in March.

6 Spring 2016 Rev. Dermatology Foundation

PD-1 inhibitors: These new immune checkpoint inhibitors augment the normal immune response and produce a variety ofproinflammatory skin reactions.

Caution. Targeted anticancer drugs are dosed differently thanchemotherapy. Patients are on them long-term, and thus managingthe skin toxicities represents a long-term treatment challenge.

Thursday Morning at the Hardware Store…The Right Tools for the Job Suzanne M. Olbricht, MD

Introduction. We go to the hardware store knowing how tochoose the right hook and scissor and hammer for a home project,and this same informed selection for the tools we rely on in ourpractice ensures both the best results for our patients and our ease

and comfort. Dr. Olbricht described and illustrated the variety of relevant design factors, and offered personal recommendationsand take-home pearls.

Scissors. The variety in Olbricht’s office differ with respect tohandles (long or short), blades (straight or curved), tips (sharp orblunt), edges (smooth or serrated), and material (stainless steel ortungsten carbide). The inexpensive and durable Iris scissor is herbasic workhorse, and her favorite for cutting sutures. The very shorthandles of Ragnell scissors—for cutting tissue and undermining—suit her small hands, and their blunt tip will not accidentally punc-ture anything. Olbricht uses the similar but somewhat better Kayescissors ”anywhere tissue requires more delicate care.” She also de-scribed Gradle scissors, and her “new favorite, Supercut scissors”with their very sharp straight tips. Expensive and fairly fragile, sheuses them sparingly.

Other tools. Nail surgery requires a size range of special-ized instruments. Olbricht explained how to use the scissors-likenail splitter to split the nail, then the nail elevator to separate the nail plate from its bed, then the nail puller for easy grasp of the nail.Needles are curved, with any of three tip conformations—tapered,conventional cutting, and reverse cutting. Olbricht uses reverse cut-ting needles, and explained how to match the arc and needlelength to the job at hand. Gloves, originally to protect physiciansfrom HIV infection, now are for patient protection as well. But a re-cent prospective study of sterile vs nonsterile gloves in Mohs surgeryfound identical infection rates. “So use nonsterile gloves and savemoney,” Olbricht counseled.

Laser Tips and Tricks Eva A. Hurst, MD

Introduction. Dr. Hurst devotes 60–70% of her time to Mohssurgery/cutaneous oncology, and the rest to cosmetic work focusedlargely on well-documented laser procedures. She outlined thephysics behind Light Amplification by Stimulated Emission of Radiation, and Rox Anderson’s concept of selective photothermoly-sis introduced over 30 years ago that brought lasers to dermatology.This involved the principles for modifying wavelength, fluence, andespecially pulse duration, to create sufficient heat for destroying thetarget while sparing surrounding tissue. Then Hurst focused on her

My Practice• Reverse cutting needles• Match arc and length to the job at hand• Need large bite in thick dermis of the back? Large diameter arc

• Need small bite in the thin skin of the temple? Small diameter arc

Sterile vs Nonsterile• Prospective study• 1,004 tumors in SG (sterile gloves) and 1,021 tumors in NSG (nonsterile gloves)

• Mohs micrographic surgery and reconstruction• Infection: 0.50% SG, 0.49% NSG p=0.82

D. Mehta et al. Dermatol Surg. 2014;40:234–9.

EGFRI Acneiform EruptionMost common skin reaction

• 43–85% of patients (severe: 10%)

• Cetuximab, panitumumab > erlotinib > gefitinib

• Median onset: 7–10 days after drug initiation (> 3wks)

• Radiation sites often spared

EGFRI Eruption: Treatment• Sun protection/avoidance

• Camouflage cosmetics• Oral antihistamines• Topical antibiotics– Metronidazole– Clindamycin– Erythromycin

• Systemic antibiotics– Doxycycline 100 mg/day

• No standardized treatment– Controlled trials of interventions needed

Tell patients to expect rash, andthat it is not a drug allergy.

Classes of Targeted Anticancer Drugs• EGF Receptor InhibitorsGefitinib LapatinibErlotinib AfatinibCetuximab VandetanibPanitumumab

• VEGF Receptor InhibitorsSorafenib BevacizumabSunitinib RanibizumabAxitinib VandetanibCabozantinib PazopanibCediranib

• BRAF InhibitorsVemurafenib Dabrafenib

• MEK/ERK InhibitorsCobimetinib Trametinib

• CTLA-4 InhibitorsIpilimumab

• PD-1 InhibitorsNivolumabPembrolizumab

www.dermatologyfoundation.org Spring 2016 Rev. 7

primary tools, including substantial guidance on topical numbingand regional nerve blocks for pain control.

Long-pulsed Nd:YAG laser. This versatile laser can functionover a broad duration of pulse times, and Hurst finds it invaluablefor a variety of vascular problems and malformations as well as foreffective hair removal in dark skin. This laser is “really good whenthere are purple or blue colors within a vascular lesion,” and shepresented guidance for port-wine stains, facial telangiectasias, angiomas and venous lakes, and reticular veins around the eyes.Cooling and pain prevention are important.

Resurfacing. Fractionated resurfacing, a fairly easy treatmentpopular for photodamage and sunspots, wrinkles, and acne scars,requires sufficient numbing for an adequate treatment. Hurst dis-covered that reapplying the topical numbing agent twice, 30 min-utes apart, is ideal for a small area like the face. Ablative resurfacing,although the most demanding to do and the most difficult for thepatient, produces dramatically superior results. Injected numbingand nerve blocks are needed, as are ativan or halcion, and carefulmonitoring. Downtime is significant. Hurst discussed the outstand-ing benefits for rejuvenation, actinic cheilitis, and hypertrophicscars. IPL (intense pulsed light) is “a great workhorse machine”—effective for pink and brown dyspigmentation—that Hurst usesalone and combined with other treatments, including fractionatedresurfacing.

Long-Pulsed NdYAG Indications• Port-wine stains

• Facial telangiectasias

• Angiomas

• Venous lakes

• Erythematous scars

• Hemangiomas

• Vascular malformations: venous, lymphatic, mixed

• Leg veins

• Periorbital veins

• Hair (especially in dark skin)

Regional BlocksSensory Innervation of the Central Face

AE – external nasal branch of the anterior ethmoidal nerve (V1)

IO – infraorbital nerve (V2)IT – infratrochlear nerve (V1)M – mental nerve (V3)SO – supraorbital nerve (V1)ST – supratrochlear nerve (V1)

Reprinted with permission from JL Bolognia et al. Dermatology, 2nd ed. NY:Mosby, 2003.

Summary• The long-pulsed NdYAG laser has a variety of indicationsand uses, and perfectly exemplifies the importance of theprinciples of laser physics

• Fractionated resurfacing results can be optimized withaggressive topical anesthesia and consideration of nerveblocks

• IPL is useful in combination with fractionated resurfacing• Fully ablative resurfacing still delivers amazing results,but with more downtime

(As of May 31, 2016)

Mary Altmeyer, MDElias E. Ayli, DO

Sally A. Booth, MDTracy Campbell, MDRoldofo Chirinos, MD

Jonathan A. Cotliar, MDKevin P. Hogan, MD, PhDJohn M. Humeniuk, MD

Nancy Kim, MDAdean A. Kingston, MDBrenda C. LaTowsky, MDRobert Micheletti, MDJesse Olmedo, MDEvan Piette, MD

Abrar A. Qureshi, MD, MPHAllison Readinger, MDKristine A. Romine, MD

Peter Saitta, DOLeah M. Schammel, DO

Peter Teng, MDCaroline S. Wilkel, MDNancy S. Wolfin, MD

Justin Gary Woodhouse, MDRichard D. Wortzel, MD, PhD

New LS MembersGrow Support for the Future

The Dermatology Foundation extends a warm welcome to the 24 dermatologists recognized below who have joined their colleagues in leadership giving. Each newLeaders Society member has contributed$1,500 to further the work of the DF.

(Continued on page 9)

8 Spring 2016 Rev. Dermatology Foundation

2015 Practitioner of the Year:Bruce A. Brod, MDThis annual award recognizes dermatologists for exemplaryservice as a private practitioner combined with significant contributions to the specialty through leadership and teaching.

Dr. Brod is regarded byhis colleagues as, first andforemost, a dedicated andgifted clinician who is thePhiladelphia region’s expertin contact dermatitis (CD).“I have seen first-hand thedirect impact he has on his patients because of hiscompassionate and knowl-edgeable care,” a colleagueobserves. Another says,

“I cannot find a single person who does not have a beautiful story about Bruce. As a clinician and dermatologist, there is none better.”

These outstanding qualities have been recognizedby two Dermatologist of the Year awards, five Patients’Choice Awards, five Compassionate Doctor Recogni-tion awards, and inclusion among the Top 10 Doctorsin Pennsylvania.

Dr. Brod thanks his pediatrician wife for introducinghim to dermatology when they were in the same med-ical school class at the University of Pennsylvania.“She suggested that I take a dermatology elective,” herecalls. “And the rest is history!” Dr. Brod’s fascinationwith immunology also began then, and the final piececame when he “fell in love with pediatric dermatology”early in his residency at the University of Pittsburgh.

There were few fellowships in pediatric dermatol-ogy then, so Dr. Brod began as a clinically oriented educator at Hahnemann University. Once he recog-nized the urgent need for a CD specialist in the greaterPhiladelphia area, he worked to fill it. CD emphasizes

immunology, which he loves. It “bridges the gap between clinical immunology and immunology in thelaboratory setting. And it is an inflammatory diseasethat sometimes we can actually cure.” In addition to his busy clinical practice in Lancaster, PA, Dr. Brod co-directs the CD clinic at the University of PennsylvaniaHospital and teaches dermatology residents and fellows there. Now he is planning a pediatric CD clinic.Childhood CD is real, and children are affected “just ascommonly as adults are,” but there are very few clinicsfocused on this issue even though the need is great.

Dr. Brod’s patient advocacy involvement, whichbegan quite unexpectedly about 15 years ago, hassince become what he calls “my other life.” Learning of state efforts to prohibit children from using tanningsalons, he became involved and ended up leading thatproject to a successful conclusion. Dr. Brod’s interest in health policy and patient safety mushroomed. Hebegan working with organized medicine and getting involved in the legislative process, and is now a volun-teer in key organizational leadership roles. More recentaccomplishments include truth in advertising andphysician credentialing. Transparency in drug pricing is one of Dr. Brod’s current targets. He has been honoredas Dermatology Advocate of the Year by the AAD andnamed Physician Safety Patient Hero by the AmericanSociety for Dermatologic Surgery Association.

Dr. Brod’s patients remain at the heart of hiswork. He regards “truly listening to them” as themost important part of his ability to gain their trust and to “get a sense of the big picture and priorities.” Sometimes, he shares, it starts with the power of a simple touch. “Patients with visiblediseases—like vitiligo and psoriasis—are oftenstigmatized and shunned by the public. But as adermatologist, literally reaching out and touchingtheir skin changes their lives.”

DF Honors Excellence in Dermatology

The Dermatology Foundation pays yearly tribute to dermatologists whose exemplary capabilities and dedication have helped to make the specialty what it is today. Presentation of the 2015 awards was a highlight of the DF Annual

Meeting on Saturday, March 5 in Washington, D.C. The leaders and role models honored by their peers were:Practitioner of the Year—Bruce A. Brod, MD

Lifetime Career Educator Award—Maria L. Chanco Turner, MDClark W. Finnerud Award—Warwick L. Morison, MD

(Drs. Morison and Turner were highlighted in the Winter 2015/16 issue.)

Dr. Brod

Spring 2016 Rev. 9www.dermatologyfoundation.org

MINI-SYMPOSIUM:PEDIATRIC DERMATOLOGY

Hot Topics in Pediatrics for the Dermatologist Maria C. Garzon, MD

Immunosuppression and immunization. Patients whoare highly immunocompromised or immunosuppressed—includingthose on >20 mg of prednisone a day for at least 14 days, or a biologicdrug inhibiting the immune response—cannot be given a live-virusimmunization and should avoid exposure to others who have recently received one: rotavirus, MMR, varicella zoster, intranasal flu,and yellow fever. Because live virus is shed in the stool and the rotavirus vaccine is given during infancy, the highly immunosup-pressed parent/grandparent should temporarily avoid close contactand changing diapers. Any patient of any age about to begin im-munosuppressive therapy should complete needed immunizationsbefore starting. The American Academy of Pediatrics’ Red Book(http://redbook.solutions.aap.org/book.aspx?bookid=1484) pro-vides full guidance.

Unusual immunization site reactions. “These childrenhave often seen multiple physicians before we arrive at the diagno-sis,” Dr. Garzon noted. She used a 7-month-old infant—with inflam-

matory pruritic nodules at his multiple immunization sites and anoverlay of scratching-induced changes—to discuss the type 4 reac-tion to aluminum and how to diagnose it (including patch testingwith empty Finn Chambers). Aluminum—high on the list of immu-nization allergens—is difficult to avoid because of wide use as a response-boosting adjuvant. These nodules usually develop onlyafter multiple immunizations and can appear days to months afterthe critical one. They can persist for years. Treatment with potenttopical corticosteroids under occlusion can help alleviate symp-toms, with periodic reassessment for adverse side effects.

Selected Cutaneous ReactionsVaccine/Component Skin ReactionMany types Localized redness, swelling,

discomfort ~80% resolve in few daysMMR 5% rash (modified viral exanthem)

Rare: erythema multiformeVaricella • Generalized vesicular 51%(when reported) • Nonspecific 41%

• Injection site vesicular 8%Many types Prolonged site reactions

• Localized nodules (not itchy)• Sterile abscesses• Pruritic nodules (granulomatous)Type IV reaction/DTH

Immunization Summary• Bring up to date on immunizations prior to starting immunosuppressant

• Avoid live-virus vaccines– Contraindication for many

• Many suggest avoiding “contacts” who received live-virus immunization– Varicella vaccine (Oka strain): secondary transmissionis very rare, but described in close household contacts– Zoster vaccine contains more virus than Varicella vaccine

– Rotavirus viral sheds for at least 14 days– Transmission risk from recently immunized householdcontact is relatively low

– Practice hand washing, avoid stool contact

• Data on effectiveness of influenza and pneumococcalvaccines while on therapy variably reported

Aluminum Hypersensitivity• Develops after multiple vaccinations• Lesions appear days to months after exposure• Nodules may persist for years• Exacerbations with re-exposure or URI• Pruritus becomes less intense after a few years– Topical corticosteroids with occlusion

Vaccines and Adjuvants • Contains Aluminum

– DTaP, Tdap– Hepatitis A– Hepatitis B– Hib– HPV– Pneumococcus

• No Aluminum– IPV– Influenza– MMR– Rotavirus– Varicella

http://www.cdc.gov/vaccinesafety/Concerns/adjuvants.html

Consider a gift to the DF honoring a cherished colleague or mentor and—at the same time—support advancements in patient care. The Dermatology Foundation is proud to

accept memorial and tribute gifts. This effectiveway to honor special friends and colleagues increases the DF’s capacity for funding promisingphysician-scientists’ research projects that willstrengthen the specialty’s future—and is deeply appreciated.

For further information, call 847-328-2256 ordfgen@dermatologyfoundation.org.

The DF is a 501(c)3 organization and all contributions are tax deductible to the extent provided by law.

Memorial and Tribute Gifts

10 Spring 2016 Rev. Dermatology Foundation

Anesthesia and the young brain. This “very hot topic inpediatrics” currently raises far more questions than answers. Neuro-transmitters are important for normal brain development, espe-cially in the first several years of life, yet the anesthetics andsedatives used in infants and children are believed to alter neuro-transmitter receptors. Although animal studies document neuraldamage with consequent behavioral and learning abnormalities,the relevance to humans is uncertain and critical studies are stillseveral years from completion. Garzon discussed the timing of earlyvs later laser treatment of port-wine stains to illustrate the attendantcomplexities and controversy. Multiple anesthesia-requiring treat-ments may be needed, but delaying treatment of facial lesions mayhave psychosocial impact. Additional research to clarify optimaltiming is critical. The SmartTots organization (smarttots.org) is avaluable resource for risks-benefits discussions with parents.

Integrative Pediatric Dermatology: Practical Tips for Those Who Seek “Natural”Peter A. Lio, MD

Introduction. Dr. Lio, who is also a member of the AmericanAcademy of Medical Acupuncture, practices integrativemedicine. Heexplained what this is, why he believes that it is, in reality, a definition ofgoodmedicine, and provided examples of its value in his practice.

Perspectives. Lio finds that the “mountain of evidence-build-ing” encouraged by the dominant perspective in medicine createsa false sense of security about what we know and what we need totell our patients. “The older and wiser I get, the more humble I become about dermatology and about my understanding. It is im-portant to embrace those limits of our knowledge, to address thishead on, in the open.” Integrative healthcare is how Lio does this.The NIH’s National Center of Complementary and IntegrativeHealth defines complementary treatment as something non-main-stream used together with—rather than as an alternative to—conven-tional medicine, and integrative healthcare brings complementaryand conventional approaches together in a coordinated way. “Thisintegration brings together the best of both worlds—which I think iswhat all good clinicians do naturally.”

Mutual benefits. Lio underlines the importance of learningone’s patients’ fears and reassuring them rather than dismissingthem. He also notes the benefits of the positive, supportive vocabu-lary of complementary practitioners—they heal, balance, and tonifyrather than attack and destroy. Dermatologists can also frame theirapproach in a supportive, healing way. Lio’s main passion is atopic

dermatitis, and he talks with patients and parents about the skin bar-rier, the need to strengthen it and to rebalance the bacteria on theskin. And that they can talk about curcumin—or whatever the patienthas raised—once that is accomplished. The standard treatment Lioprescribes—bleach baths and moisturizer—is welcomed because itwas framed in “a language of connection, caring, and personaliza-tion. The holistic approach is, at the heart, just really really goodmedicine.”

KEYNOTE ADDRESS Life as a (Dermatologist) Surgeon General Boris D. Lushniak, MD, MPH, RADM, USPHS (Ret)

Background. Dr. Lushniak, after training in family, preven-tive, and occupational medicine, and dermatology, was part of theU.S. Public Health Service (USPHS) Commissioned Corps for 27years (he retired to private life this past October 1*). Appointed toDeputy Surgeon General in 2010 under Regina Benjamin, he be-came Acting Surgeon General when she retired unexpectedly inJuly 2013. Told his time at the helm would be brief, it actually lasteduntil mid-December 2014, long enough to leave his mark and relishhis unique experiences. Lushniak recapped the history, structure,and accomplishments of this office, then spoke of his time as itshead, especially his skin cancer prevention program and his com-mendation-earning response to the ebola crisis.

The Office. One of the smallest of the seven U.S. uniformedservices, the USPHS comprises over 6,800 officers spread across theglobe, assigned and supervised by the Surgeon General from a surprisingly minimalist office in terms of staff and assigned budget.The genesis of today’s comprehensive and far-flung Corps was the1798 act providing care for sick and injured merchant seamen,evolving into the Public Health Service by 1912. The mission in-forming the Surgeon General’s spectrum of duties—each of whichLushniak described—is to protect, promote, and advance the healthand safety of the nation, and the Corps played a role in the 10 land-mark public health achievements that spanned the 20th century

”Tips”1. Being open to integrative medicine may signal kindess,strength, and wisdom

2. Reassurance of fears may be better than dismissal3. It may be in our best interest to help guide this movement rather than simply reject it

4. A “holistic” approach to the patient is good medicine

10 Great U.S. Public Health Achievements: 1900–1999

• Vaccination• Motor-vehicle safety• Safer workplaces• Control of infectious diseases

• Decline in deaths fromheart disease and stroke

• Safer and healthier foods• Healthier mothers and babies

• Family planning• Fluoridation of water• Recognition of tobacco as a health hazard

MMWR 1999 Apr 2;48(12):241–3.

Facial Port Wine Stains: One Approach• We discuss data and unknowns with parents• We discuss controversy regarding optimal timing fortreatment– Majority of parents report they have heard about these concerns.

• In-office treatments with PDL with cooling device andtopical lidocaine cream (dose appropriate for infant’sage/size)– Bundle/swaddle requires additional assistance– I do not treat the immediate periocular area at that time

• Delay treatment of lid area until older• Delay larger procedures requiring anesthesia/sedationsuntil the children are older?

www.dermatologyfoundation.org Spring 2016 Rev. 11

(including vaccination, motor-vehicle safety, family planning, andrecognition of tobacco’s health hazard). The 50th anniversary re-port of the Surgeon General’s report on smoking and health waspublished during Lushniak’s tenure, and he discussed its content.

Preventing skin cancer. The National Prevention Strategy—embedded within the Affordable Care Act—created the National Pre-vention Council under the Surgeon General’s leadership “to move thenation from a focus on sickness to one of wellness—our 21st centuryconcept.” The U.S. has a great “sick care” system, but the large majorityof problems we see are, in fact, preventable, and we want to “increasethe number of Americans who are healthy at every stage of life.” Thedermatologist in Lushniak realized that the office had never addressedpreventing skin cancer—“and now is the time.” He described his stepsto use this “bully pulpit” to full advantage, releasing a report in July,2014 that took the media by storm, and “America listened—at least fora little bit.” The critical first steps were effectively taken.

Responding to Ebola. Designing and implementing “thestrategy to diminish the threat of ebola in the U.S. and the world bydefeating it at its source” quickly became “perhaps the most excitingpart of my year and a half.” Although the initial USPHS response inLiberia was small, caring for infected healthcare workers quickly be-came “an important imperative” that was green-lighted on Septem-ber 14, 2014. Lushniak described his planning and implementationphases for the Monrovia Medical Unit (MMU), their various partners,

the personnel, physical setup and logistics erected from scratch,their treatment approach, and their first patients. This work was recognized by the first ever presidential citation to the Corps. *He is currently 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, Bethesda, MD.

MINI-SYMPOSIUM: ERRORS, COMPLICATIONS, AND PATIENT SAFETY

When Eczema Isn’t Just Eczema: How Not to Miss Immune Disorders Mary Beth Fasano, MD, MSPH

Background. The skin’s importance in immune disordersmakes dermatology’s role critical in diagnosing and caring for patients with inherited primary immunodeficiencies (PID). Al-though the hallmark of a primary immune deficiency is recurrent,unusual, or severe infections, roughly 80% of patients have associ-ated skin manifestations. (Examples are eczema in Wiskott-Aldrichsyndrome and hyper-IgE syndrome; erythroderma with or withoutalopecia in babies with SCID [severe combined immunodefi-ciency].) These disorders are secondary to a plethora of mutationsin genes affecting a variety of pathways impacting immune func-tion. Dr. Fasano discussed the critical initial evaluation of these infants and young children, illustrating with “examples of wheneczema is not just eczema,” highlighting pattern recognition, and offering practical tips.

Clinical patterns. Wiskott-Aldrich syndrome: The patient ismale (this syndrome is X-linked). In addition to his eczema, a petechial rash reflects profound, possibly life-threatening, thrombo-cytopenia with abnormally small platelets, and he has recurrent infections. Older patients may develop lymphoma. Hyper-IgE syndrome (aka Job’s syndrome): In addition to eczema, skin find-ings can be infectious in nature. Of the known mutations, Fasano

The Surgeon General’s Call to Action to Prevent Skin Cancer

A science-based document to stimulate action nationwide to solve a major public health problem

• Raises the issue of skin cancer prevention to a higher level of priority and attention

• Provides clear action steps tomove the issue forward

http://www.surgeongeneral.gov/library/calls/prevent-skin-cancer/index.html

MMU MissionProvide hope through care to healthcare workers inLiberia who may have the Ebola Virus Disease; continueefforts with the Liberian government and internationalpartners to build capacity for additional care

USPHS Staffing• ~10 Medical Providers (MDs/NP or PAs)• ~20 nurses• ~4 pharmacists• ~3 laboratorians• ~10–15 safety officers• ~5 behavioral health providers• ~15–20 admin, logistics, planning staff• Command: officer in charge, executive officer, commanding officer

Calls To Action: 5 Strategic Goals1. Increase Opportunities forSun Protection in OutdoorSettings

2. Provide Individuals withthe Information They Need to Make Informed,Healthy Choices about UV Exposure

3. Promote Policies that Advance the National Goalof Preventing Skin Cancer

4. Reduce Harms from Indoor Tanning

5. Strengthen Research, Surveillance, Monitoringand Evaluation Related toSkin Cancer Prevention

12 Spring 2016 Rev. Dermatology Foundation

focused on STAT3 and DOCK8, contrasting their respective expres-sions and noting the diagnostic challenges. SCID: Fasano discussedOmenn syndrome, a hypomorphic form linked to autologous,oligoclonal, autoreactive T cells. B-cell deficiencies: a broad discus-sion included infectious skin lesions, vitiligo, and alopecia espe-cially in IgA deficiency and common variable immunodeficiency.

Cases: Fasano presented the evaluation process and clinicalpatterns for 3 patients with skin findings—a 22-month-old male diag-nosed with hypomorphic SCID secondary to the NEMO mutation; a6-month-old male with SCID secondary to mutations affecting T-celland NK-cell development; a 5-year-old female with the autosomaldominant sporadic form of hyper-IgE syndrome.

Practical tips. Ask questions—about infections (severity, nature, source), about possible failure to thrive, about family history(including death from overwhelming infection). Physical exam—also look: inside the mouth, at the skin, for failure to thrive, for dysmorphic features. Screening tests—ideal to do before referral to immunologist.

Filler Complications—Avoid First, Deal Second Eva A. Hurst, MD

Introduction. Dr. Hurst reviews all potential filler complica-tions with each patient, then does her best to prevent them. Be-cause problems can occur despite one’s best efforts, she discussedhow she handles them. (Hurst also recommends two recent journalsupplements with helpful information, one with the Nov. 2015 Plastic and Reconstructive Surgery (vol 136), the other with the Dec. 2015 Dermatologic Surgery (vol 41).

Less serious. Bruising. Apply ice and topical arnica—ananti-inflammatory compound from the Arnica montana flower thathas some supporting data—immediately following a procedure. Advise to skip exercise for several days. A significant bruise can beeradicated the following day with a 5-minute pulsed-dye laser treat-ment. The Tyndall effect can occur with some hyaluronic acid(HA) fillers, most commonly in the tear trough (where makeuphides it). This scattering of light by fine particles in suspension appears as a very subtle lightening and grayish color beneath the

(Continued on page 15)

Primary Immunodeficiencies• Diverse group of inherited disorders– >150 known primary immunodeficiencies

– Different molecular mechanisms

• May present at any age– 80% diagnosed by age 20 yrs– 58% diagnosed by age 15 yrs

• Overall incidence – 1:2,000– Male predominance (70–80%)

What Should You Do?Key Questions• Infections? nature/pattern • Is this patient failing to thrive?• Family history – Known immune deficiency?– Recurrent, unusual, severe infections?

Physical Exam• General appearance– Failure to thrive– “Syndromic” features

• Mouth– Thrush, gingivitis, oral ulcers, abnormal teeth, periodontal disease

• Skin– “eczema,” petechiae, abscesses, candida, warts, molluscum, vitiligo, poor wound healing

Lab Tests• CBC with differential & platelet count; smear• Quantitative immunoglobulins: IgG, IgA, IgM, IgE• Flow cytometry with lymphocyte subset analysis

• ↑ Susceptibility to infection– Chronic/recurrent– Unusual pathogen– Unusual severity– Unusual complication

• ↑Autoimmune disease• ↑Malignancy• Syndrome complex• Cutaneous findings in most

Skin Manifestations in Primary Immunodeficiencies

• In 79% of PID patients, skin findings preceded &were the basis for immune evaluation & diagnosis

• Only 2 of 130 patients did not have skin findings • 49% of PID patients had skin findings• WAS & HIES = 100% with “eczema”• SCID = erythroderma & alopecia• AT = 100% with telangiectasia

A. Berron-Ruiz et al. Pediatr Dermatol. 2000;17:91–6; W. Al-Herz et al. Pediatr Dermatol.2011;28:494–501.

Cutting edge research in dermatology oftenhas its roots in career development awards provided by the DF. To disseminate this researchas widely as possible, the Dermatology Founda-tion and the Journal of the American Academy of Dermatology (JAAD) have partnered to create a new section in the journal. Initiated in the Mayissue, From the Dermatology Foundationfeatures clinically relevant manuscripts from investigators whose research was sponsored by the DF.

The journal welcomes submissions from DF-sponsored researchers, as well as commentsand suggestions from JAAD readers.

New JAAD Section: “From the Dermatology

Foundation”

®/TMs are trademarks of Valeant Pharmaceuticals International, Inc. or its affiliates. All other product or brand names are trademarks of their respective owners. ©2016 Valeant Pharmaceuticals North America LLC. JUB.0058.USA.16 Printed in US

*For the treatment of onychomycosis of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes.

AT THE SITE OF INFECTION1

STEALING THE SHOW?

FIGHT IT

*

JUBLIA allows some patients to have clearer toenails grow back. Individual results may vary.

INDICATIONJUBLIA (efinaconazole) topical solution, 10% is indicated for the topical treatment of onychomycosis (tinea unguium) of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes.

IMPORTANT SAFETY INFORMATION• JUBLIA is for topical use only and is not for oral, ophthalmic, or intravaginal use.

• Patients should be instructed to contact their health care professional if a reaction suggesting sensitivity or severe irritation occurs.

• The most common adverse reactions (incidence >1%) were (vs vehicle): ingrown toenail (2.3% vs 0.7%), application-site dermatitis (2.2% vs 0.2%), application-site vesicles (1.6% vs 0%), and application-site pain (1.1% vs 0.2%).

• JUBLIA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and should be used with caution in nursing women. The safety and effectiveness in pediatric patients have not been established.

Please see Brief Summary of full Prescribing Information on the adjacent page.Reference: 1. JUBLIA [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2015.

Find out more by visiting www.JubliaRx.com.

8 mLLARGER

Rx OnlyAVAILABLE

size

Trim: 8.5"x11" File Format: PDF Carling Communications 4/19/2016 B

BRIEF SUMMARY OF PRESCRIBING INFORMATION

This Brief Summary does not include all the information needed to use JUBLIA safely and effectively. See full prescribing information for JUBLIA.

JUBLIA® (e�naconazole) topical solution, 10%

For topical useInitial U.S. Approval: 2014

INDICATIONS AND USAGEJUBLIA (e�naconazole) topical solution, 10% is an azole antifungal indicated for the topical treatment of onychomycosis of the toenail(s) due to Trichophyton rubrum and Trichophyton mentagrophytes.

DOSAGE AND ADMINISTRATIONApply JUBLIA to affected toenails once daily for 48 weeks, using the integrated �ow-through brush applicator. When applying JUBLIA, ensure the toenail, the toenail folds, toenail bed, hyponychium, and the undersurface of the toenail plate, are completely covered.

JUBLIA is for topical use only and not for oral, ophthalmic, or intravaginal use.

CONTRAINDICATIONSNone.

ADVERSE REACTIONSClinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not re�ect the rates observed in practice.

In two clinical trials, 1227 subjects were treated with JUBLIA, 1161 for at least 24 weeks and 780 for 48 weeks. Adverse reactions reported within 48 weeks of treatment and in at least 1% of subjects treated with JUBLIA and those reported in subjects treated with the vehicle are presented in Table 1.

Table 1: Adverse Reactions Reported by at Least 1% of Subjects Treated for up to 48 Weeks

Adverse Event, n (%)JUBLIA

N = 1227Vehicle N = 413

Ingrown toenail 28 (2.3%) 3 (0.7%)

Application site dermatitis 27 (2.2%) 1 (0.2%)

Application site vesicles 20 (1.6%) 0 (0.0%)

Application site pain 13 (1.1%) 1 (0.2%)

DRUG INTERACTIONSIn vitro studies have shown that JUBLIA, at therapeutic concentrations, neither inhibits nor induces cytochrome P450 (CYP450) enzymes.

USE IN SPECIFIC POPULATIONSPregnancyPregnancy Category CThere are no adequate and well-controlled studies with JUBLIA in pregnant women. JUBLIA should be used during pregnancy only if the potential bene�t justi�es the potential risk to the fetus.

Systemic embryofetal development studies were conducted in rats and rabbits. Subcutaneous doses of 2, 10 and 50 mg/kg/day e�naconazole were administered during the period of organogenesis (gestational days 6-16) to pregnant female rats. In the presence of maternal toxicity, embryofetal toxicity (increased embryofetal deaths, decreased number of live fetuses, and placental effects) was noted at 50 mg/kg/day [559 times the Maximum Recommended Human Dose (MRHD) based on Area Under the Curve (AUC) comparisons]. No embryofetal toxicity was noted at 10 mg/kg/day (112 times the MRHD based on AUC comparisons). No malformations were observed at 50 mg/kg/day (559 times the MRHD based on AUC comparisons).

Subcutaneous doses of 1, 5, and 10 mg/kg/day e�naconazole were administered during the period of organogenesis (gestational days 6-19) to pregnant female rabbits. In the presence of maternal toxicity, there was no embryofetal toxicity or malformations at 10 mg/kg/day (154 times the MRHD based on AUC comparisons).

In a pre- and post-natal development study in rats, subcutaneous doses of 1, 5 and 25 mg/kg/day e�naconazole were administered from the beginning of organogenesis (gestation day 6) through the end of lactation (lactation day 20). In the presence of maternal toxicity, embryofetal toxicity (increased prenatal pup mortality, reduced live litter sizes and increased postnatal pup mortality) was noted at 25 mg/kg/day. No embryofetal toxicity was noted at 5 mg/kg/day (17 times the MRHD based on AUC comparisons). No effects on postnatal development were noted at 25 mg/kg/day (89 times the MRHD based on AUC comparisons).

Nursing MothersIt is not known whether e�naconazole is excreted in human milk. After repeated subcutaneous administration, e�naconazole was detected in milk of nursing rats. Because many drugs are excreted in human milk, caution should be exercised when JUBLIA is administered to nursing women.

Pediatric UseSafety and effectiveness of JUBLIA in pediatric subjects have not been established.

Geriatric UseOf the total number of subjects in clinical trials of JUBLIA, 11.3% were 65 and over, while none were 75 and over. No overall differences in safety and effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identi�ed differences in responses between the elderly and the younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

NONCLINICAL TOXICOLOGYCarcinogenesis, Mutagenesis, Impairment of FertilityA 2-year dermal carcinogenicity study in mice was conducted with daily topical administration of 3%, 10% and 30% e�naconazole solution. Severe irritation was noted at the treatment site in all dose groups, which was attributed to the vehicle and confounded the interpretation of skin effects by e�naconazole. The high dose group was terminated at week 34 due to severe skin reactions. No drug-related neoplasms were noted at doses up to 10% e�naconazole solution (248 times the MRHD based on AUC comparisons).

E�naconazole revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and Chinese hamster lung cell chromosome aberration assay) and one in vivo genotoxicity test (mouse peripheral reticulocyte micronucleus assay).

No effects on fertility were observed in male and female rats that were administered subcutaneous doses up to 25 mg/kg/day e�naconazole (279 times the MRHD based on AUC comparisons) prior to and during early pregnancy. E�naconazole delayed the estrous cycle in females at 25 mg/kg/day but not at 5 mg/kg/day (56 times MRHD based on AUC comparisons).

PATIENT COUNSELING INFORMATIONSee FDA-Approved Patient Labeling (Patient Information).

Manufactured for:Valeant Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA

Manufactured by: Kaken Pharmaceutical Co. Ltd, Shizuoka, Japan

Product of Japan

U.S. Patents 8,039,494; 7,214,506

Based on 9391902 DM/JUB/15/0076 Issued: 02/2015

Trim: 8.5"x11" File Format: PDF Carling Communications 4/19/2016 B

www.dermatologyfoundation.org Spring 2016 Rev. 15

skin. If in the lower face, placement was too high; dissolve withhyaluronidase, or change technique. Nodules of several types canoccur. With HA fillers, they occur in the tear trough area from too

much material or lack of a submuscular injection plane, and are im-mediately responsive to hyaluronidase (30–50 units—undiluted—ina nodule). The conjugated HA filler Voluma, injected in the uppercheek area, can cause delayed (by several months) inflammatorynodules. Cause and management are unclear; try prednisone for 3days. Improper Sculptra placement can induce nodules. In patientswith many layers of fillers, the biofilm (bacteria growing in a stickyslime-enclosed aggregate) can cause nodules that should betreated with 2–3 antibiotics, prednisone, and close monitoring.

More serious. Minimize infections by not injecting in areaswith active bacterial infections or acne. Prophylax zoster in the site.(Biopsy any suspected infection for culture.) Vascular occlu-sion and necrosis require an immediate injection ofhyaluronidase; see any patient complaining of pain without delay.Blindness is very rare (98 reported cases) but the most frighteningcomplication. Most involve injections in areas communicating withthe ophthalmic system, especially the glabellar nasal dorsum. Hurstlisted precautions, and stressed the critical need for immediateaction if this worst fear is realized.

MINI-SYMPOSIUM: CPCEva A. Hurst, MD

Case 1. A former resurfacing patient showed Dr. Hurst her tat-tooed eyebrows (done many years earlier, then repeated ~2 yearspreviously), which had become thickened in the past 5 months.Biopsy showed confluent verruca. This has been reported with tat-toos, but not previously with a cosmetic tattoo. Hurst suspected thecause was a combination of factors. The plan is to resurface her eye-brows, then treat with imiquimod, or possibly curettage. Asking foraudience experience elicited: PDT with red light; intralesionalbleomycin; topical imiquimod.

Case 2. A 72-year-old significantly immunosuppressed manwas referred to Hurst for Mohs excision of a moderately differenti-ated SCC (squamous cell carcinoma) of the cheek. The referringdermatologist often does both biopsy and ED&C at the initial visit,and there was no visible tumor by the time this patient saw Hurst.She still did the surgery, and found tumor cells in the first stage ofMohs. “The key point is the significant clinical challenge of detect-ing residual or recurrent SCC under a scar, especially in the im-munosuppressed patient,” and Hurst recommends omitting ED&Cfor invasive SCC in the immunosuppressed patient appropriate for surgery.

Case 3. In the debilitated elderly patient, healing can be diffi-cult after removing a large tumor resulting in exposed bone. Granu-lation tissue is difficult to achieve, and grafts often will not take overexposed bone. Hurst’s less-well-known but far more reliable approach is bone decortication, a pain-free in-office procedure typically followed by sudden granulation and healing within 2weeks. Hurst reviewed bone anatomy and the tools and procedure.

Potential Filler Complications• Injection site pain, erythema, edema are common– Usually resolve within a few days

• Bruising is also common, particularly in muscular areas– Avoid NSAIDS 2–3 days, ASA, and vitamin E 10–14 days if possible

– Ice post-treatment in-office and at home– Consider arnica – Consider exercise avoidance

• Hypersensitivity versus allergies—hard to classify– Rare with HAs– Hard to determine etiologic agent

• Adverse events– Nodules and Tyndall effect– Nodules can be more of problem with non-HA fillers

– Necrosis– Infection– Blindness

Safety Recommendations to Safeguard Eyesight

• Appropriate consent• Use caution with glabellar, nasal, and deep upper nasolabial fold injections

• Use small needles and apply slow minimal pressure• Consider the use of blunt tipped microcannulas• Aspirate for backflow• Inject small volumes at a time and move needle/cannulaslightly with injections

• Always have hyaluronidase in-office• If symptoms occur, consider the diuretic acetazolamideand consult your ophthalmologist immediately

Hyaluronidase• Soluble protein enzyme that acts at site of local injection• Splits glucosaminidic bond of glucuronic acid– Breaks down and hydrolyzes HA– Decreases viscosity and promotes diffusion and absorption

• Dose is 30–50 units into a nodule• Comes as 200 units/mL• Recommend skin test– 3 units intradermal– 20-minute observation– Rare sensitivity to animal-derived hyaluronidase enzyme

Origins of Warts Within Tattoos• Koebner phenomenon• Inoculation with virally contaminated tattoo dyes/needles• Latent verruca in area of tattoo• Saliva• Local immune dysregulation induced by carbon pigment,especially black/dark blue

16 Spring 2016 Rev. Dermatology Foundation

Case 4. A 72-year-old otherwise healthy man (with a priormelanoma) had an asymptomatic 6-mm red papule for 1 month.Histology showed a dermal-based tumor with 2 cell populations:large highly mitotic epithelioid cells and an intense lymphoplasma-cytic (B and T cell) infiltrate—ie, lymphoepithelioma-like carci-noma of the skin (first identified in 1988), now regarded as aninteresting variant of SCC. Metastasis from a nasopharyngeal carci-noma was ruled out, as were SCC-relevant high-risk features. Hehealed beautifully after a 3-stage Mohs procedure, with no recur-rence at 6 years.

George Cotsarelis, MD Case 1. On call last August, we transferred a woman to the

Hospital of the University of Pennsylvania in the middle of the nightbecause of what appeared to be a severely worsening and blisteringrash after treatment with high-dose corticosteroids plus cyclo-sporine for what was regarded to be a lupus flare (the patient had ahistory of lupus), and then was thought to be evolving TEN. Anemergency biopsy with frozen sections revealed a split in the granular layer that was consistent with a staph-mediated toxin

causing the blistering (staphylococcal scalded skin syndrome). Shecultured out staph—both MRSA and methycillin-sensitive—from several areas. The immune-suppressing drugs, added to the mycophenolate mofetil and hydroxychloroquine she had been taking, produced this rampant staph overgrowth and resultant blistering that had raised the possibility of TEN, but she improveddramatically on IV antibiotics.

Case 2. In atrichia with papules—which resembles alopeciauniversalis—children are born with hair that goes into catagen andtelogen and falls out, then never regrows. Follicles under the mi-croscope appear truncated, and remnants eventually form cyststhat increase with age. Both mice and humans with mutations inthe hairless gene develop this phenotype, as the dermal papillacells lose their connection with the stem cells at the base of the tel-ogen follicle and the follicle can no longer cycle. Some mutationsin the vitamin D receptor can cause the same phenotype, but ac-compianied by rickets. (An article in Science wrongly associatesalopecia universalis with a patient who has one of these hairlessmutations.)

Case 3. Cotsarelis described a 12-year-old boy and his sisterwith a genetic disorder they call hereditary mucoepithelial dyspla-sia. Identified in just one other known family so far, the responsiblegene is under exploration. He described the cyclical, patchy hairloss and fiery red gums, which are key. (The other family also has

(Continued on page 18)

Mark Your Calendar!2017 DF Clinical Symposia—

Advances in Dermatology, January 18–22, Naples, FL

Here is why so many dermatologists never miss this meeting: “Concentrated presentation of new, pertinent information.”

“Great coverage of the modern scope of derm.”“Best meeting I attend all year.”A spectrum of Mini-Symposia provides the latest dermatology advances that will benefit your practice:

Registration begins in September 2016: visit dermatologyfoundation.org

• Monitoring for Malignancy• Pediatric Dermatology• CPC Session• Inflammatory Diseases• Care Delivery, Practice Improvement, and Politics

• Skin Cancer• Infectious Disease• What’s New: Therapeutic Updates

Bone Decortication—Anatomy

1. Outer Table (lamellar bone) avg thickness: 2.5−3.0 mm

2. Diploic Layer (spongy bone) avg thickness: 1.5−2.0 mm

3. Inner Table (lamellar bone) avg thickness: 3.2−0.5 mm

Photo courtesy of faculty.ivytech.edu NA Ebraheim et al. Spine J. 2007;7:689–93.

1.

2.

3.

Diagnosis: Staphylococcal Scalded Skin Syndrome

• Cultures from the perianal and abdominal skin erosionsgrew both methicillin-sensitive Staphylococcus aureus(MSSA) and methicillin-resistant Staphylococcus aureus(MRSA)

• Profound immunosuppression likely contributed• Staph toxin cleaves desmoglein 1• Patient improved with IV antibiotics (empiric intravenous clindamycin and vancomycin, changed to clindamycin and linezolid in light of severe penicillin allergy)

www.dermatologyfoundation.org Spring 2016 Rev. 17

2015 Corporate Honor SocietyPartners in Shaping Dermatology’s Future

The Dermatology Foundation is grateful to the following corporations for their generouscontributions last year. Their support furthers the DF’s mission to develop and retain tomorrow’s leaders in the specialty, enabling advancements in patient care.

Cornerstone Benefactor ($500,000 or more)

Platinum Benefactor ($200,000 or more)

Gold Benefactor ($100,000 or more)

DUSA Pharmaceuticals

Silver Benefactor ($50,000 or more)

Amgen Inc.Sun Pharmaceuticals

18 Spring 2016 Rev. Dermatology Foundation

lung involvement.) The hair shaft has increased fragility and ispoorly anchored to the follicle. Hair loss can be cyclical, reappear-ing after several seemingly normal years. (Inform Cotsarelis of similar cases.)

Ruth Ann Vleugels, MD, MPH Case 1. A 25-year-old man, previously healthy and a dedicated

runner, presented after seeing multiple other physicians with an 8-month history of lower right leg changes that had begun with anerythematous patch on the upper thigh and extended over weeks toinvolve the lower leg. Within several months, the patient developeda prominent knee contracture and lost substantial bulk of the lowerleg, and he presented with a prominent limp. His clinical examina-tion was classic for linear morphea. The first treatment goal with thisentity is halting disease progression, the second is softening the mostrecently affected areas. Working to improve any associated jointcontracture is critically important. Although many physicianschoose to treat this entity with topical therapy, this by itself is inade-quate and consensus data from the pediatric literature support theroutine use of systemic therapy. When there is involvement over ajoint, it is imperative to use both systemic corticosteroids andmethotrexate. With no joint involvement, methotrexate alone maybe considered. Physical therapy is also an imperative component oftherapy when a patient with linear morphea has involvement over ajoint. Following aggressive combination therapy, the patient has hadsignificant improvement with reduction of the knee contracture andimproved ambulation. Despite this, he has permanent limb-lengthdiscrepancy and disfigurement as well as challenging-to-heal ulcerations given the delay in his receiving adequate treatment.

Case 2. An otherwise healthy 54-year-old man, working actively as a police officer, presented with a cutaneous eruption.Pathology confirmed the suspected diagnosis of sarcoidosis. Thenext critical step in management of any patient diagnosed with sarcoid affecting the skin is an extensive workup (see Misha Rosenbach: Am J Clin Dermatol. 2014;15:283–97). This patient wasfound to have low vitamin D, pulmonary involvement, and cardiacinvolvement. His cardiac involvement required placement of an implantable cardiac defibrillator to avoid sudden cardiac death.This reminds all dermatologists of the role they can play in caringfor patients with serious systemic disease. This patient’s skin diseaseimproved significantly with a combination of hydroxychloroquineand methotrexate. �

2016 DF Clinical Symposia Faculty Disclosures (Part I)George Cotsarelis, MD: Johnson & Johnson, Kythera/Allergan, Follica. Edward Cowen, MD: UpToDate®. Mary Beth Fasano, MD, MSPH: none. Maria C. Garzon, MD: Astellas Pharma USA, CUMC Department of Dermatology Clinical Research. Eva A. Hurst, MD: none. Peter A. Lio, MD: Anacor Pharmaceuticals, Inc., Derm Tap, Inc., Ferndale Laboratories, Inc., Galderma Laboratories, LP, IntraDerm Pharmaceuticals, Johnson & Johnson Consumer Products Company, La Foundation pour la Dermatite Atopique, Modernizing Medicine, Pierre Fabre Dermatologie, Regeneron, Valeant Pharmaceuticals International,Valeant Pharmaceuticals North America LLC. Boris D. Lushniak, MD, MPH, RADM, USPHS (Ret): none.Suzanne M. Olbricht, MD: none. Ruth Ann Vleugels, MD, MPH: none.

Sarcoid—Initial Evaluation

• Hx (occupational/environmental exposure, sx)• Physical exam• Chest X-Ray, PA & lateral• Pulmonary Function Tests with DLCO• Ophthalmologic examination• CBC w/ diff, CMP, Ca• Urine analysis • EKG– If history of palpitations, additional testing (cardiac MRI or PET and/or 24h Holter)

• Tuberculin skin test or IFNγ release assay• Thyroid testing• Vitamin D 25, Vitamin D 1,25

Courtesy of Misha Rosenbach, MD

Linea Morphea

Because of delay in adequate treatment, aggressive combination therapy achieved significant progress

but with limitations.

www.dermatologyfoundation.org Spring 2016 Rev. 19

2016 CLINICAL SYMPOSIA FACULTYProceedings—Part I

Janet A. Fairley, MDProfessor and Chair

Department of DermatologyUniversity of Iowa

Jack S. Resneck, Jr., MD*Associate Professor and Vice Chair

Department of DermatologyCore Faculty, Philip R. Lee Institute

for Health Policy StudiesUniversity of California, San Francisco

George Cotsarelis, MD*Professor and ChairmanDepartment of DermatologyUniversity of Pennsylvania

Edward Cowen, MDSenior Clinician

Dermatology Branch, NCI, NIHNational Cancer Institute

Mary Beth Fasano, MD, MSPHClinical Professor

Department of Internal MedicineUniversity of Iowa

Maria C. Garzon, MDProfessor

Department of DermatologyColumbia University Medical CenterDirector, Pediatric Dermatology

New York Presbyterian–Morgan Stanley Children’s Hospital of New York

Eva A. Hurst, MDAssociate Professor

Department of DermatologyWashington University

Peter A. Lio, MDAssistant Professor

Department of DermatologyNorthwestern University

Boris D. Lushniak, MD, MPH, RADM, USPHS (Ret)Professor

Department of DermatologyChair of Preventive Medicine

Uniformed Services University of the Health Sciences

Suzanne M. Olbricht, MDAssociate Professor

Department of DermatologyHarvard University

Ruth Ann Vleugels, MD, MPH*Associate Professor

Department of DermatologyBrigham and Women’s Hospital, Harvard University

Corporate Supporters2016 DF Clinical Symposia

Diamond Supporter($100,000)

Galderma Laboratories, LPMerz, North America

UnileverValeant Pharmaceuticals

North America LLC

Emerald Supporters($50,000)AbbVie

DUSA Pharmaceuticals, Inc.Sun Pharmaceutical Industries, Inc.

Sapphire Supporter($25,000)Amgen

Anacor Pharmaceuticals, Inc.Bayer HealthcarePromius Pharma

Taro Pharmaceuticals U.S.A. Inc.

DF CLINICAL SYMPOSIAPROCEEDINGS 2016—PART II

Will Appear in the Summer “Dermatology Focus”

Difficult Medical Dermatology Conundrums

Policy, Ethics, and the Law

Evolving Evidence: New Knowledge in Dermatology

Keynote Talk

PROGRAM CO-CHAIRS

Educational Grant($300,000)

The DF is pleased to recognize Unilever for

their support of the 2016 DF Clinical Symposia Resident Program.

*DF Research Award Recipient

In 2015, surgeonand scientist H. WilliamHiggins II, MD, MBE,completed his Mohsfellowship at Yale andbecame a junior facultymember at the WarrenAlpert Medical School

of Brown University. He also carried out his plan tojoin the Dermatology Foundation’s Leaders Societyas soon as he had finished his training. In very short order he also became a DF volunteer in RhodeIsland’s LS campaign. “I wanted to help contribute tothe greater good of the specialty,” Dr. Higgins says.

Dr. Higgins was first impressed by the Founda-tion when he learned about it during his residency at Brown. “I really appreciated the quality of the re-search coming out of DF grants and career develop-ment awards (CDAs).” Then at Yale, “I realized thatall of the people I respected in the research commu-nity had a common thread—they supported the DF.”

Now, when Dr. Higgins invites colleagues to jointhe Leaders Society, he talks about the widespreadclinical impact of research enabled by DF support,such as better understanding of inherited skin diseases, the use of lasers and light therapy, the development of retinoids, biologics, antifungals, corti-costeroids, and targeted treatments for melanoma. “I also mention the results coming to light from mycurrent DF CDA, which is a very large, well-poweredepidemiologic study to elucidate characteristics oflentigo maligna.”

“Once we are out in clinical practice,” Dr. Higginsreflects, “we make a choice about where we want todonate our money and effort. The DermatologyFoundation was an easy decision for me. Ilooked at their aim, at their terrific track record,and at the dermatologists I admire—who all contribute. I chose to become a DF member forthe long term. It’s one of the few ways we can really promote the growth of the field.”

Giving Back—Profile of a DF Volunteer“Contributing to the greater good.”

The DF is exceptionally grateful to its many volunteers who give generously of their time and inspiration to keep dermatology at the forefront of medicine.

VOL. 35 NO. 1 Revised SPRING 2016

A DERMATOLOGY FOUNDATION PUBLICATIONSPONSORED BY VALEANT PHARMACEUTICALS NORTH AMERICA LLC

ADDRESS SERVICE REQUESTED

Dermatology Focusc/o Dermatology Foundation1560 Sherman Avenue Evanston, Illinois 60201-4808

Non-ProfitU.S. Postage

PAIDPermit No. 236 Melrose Park, IL

Dr. Higgins