Skin Health Spring/Summer 2015

THANK YOU TO OUR SUPPORTERS OF 2014 (CONTINUED FROM PAGE 4) Sherry Shieh, MD Mr. and Mrs. William Silver Mr. Robert B. Silvers and Ms. Grace Dudley Dana K. Stern, MD Mr. and Mrs. John H. Szalkay Mark F. Tesser, MD Jack P. Tom, MD Eileen Q. Trokhan, MD Susan L. Ungar, MD Ms. Zenia R. Wand Robert L. Warner, MD Debra Wattenberg, MD Mr. and Mrs. Eric C. Woglom Ms. Evelyn Zafran

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Skin Health FROM THE KIMBERLY AND ERIC J. WALDMAN DEPARTMENT OF DERMATOLOGY

SPRING/SUMMER 2015

Blazing the Trail of

Scientific Discovery

By Sharon E. Rose, MD

I

t is an exciting time at Mount Sinai Dermatology, as the department continues its long tradition of clinical and scientific breakthroughs. The work done here has led to hundreds of publications and countless presentations around the world.

Dr. Sharon Rose is a Dermatopharmacology Fellow in the Kimberly and Eric J. Waldman Department of Dermatology of the Icahn School of Medicine at Mount Sinai.

Our research is made possible by grants and charitable gifts. The following are just a few of the many advances made possible by the generous supporters to whom we dedicate this issue of Skin Health.

Physician-scientists in our department have been among the first to develop disease models that have paved the way for novel pharmaceutical agents for atopic dermatitis (commonly known as eczema) and psoriasis. Our work on new biologic drugs and nonsteroidal oral and topical medications is filling an important gap in the management of these two common and often devastating skin disorders.

Our work with the class of drugs called biologics is worth a special mention. These medications have revolutionized therapy for moderate-to-severe psoriasis (see photos). Members of our department not only spearheaded this breakthrough but were the first to propose the use of biologics for other serious skin conditions, including pyoderma gangrenosum and hidradenitis suppurativa, two chronic conditions that are painful and can be emotionally debilitating. Previously, there were no effective treatments for these disorders.

Our department has been at the forefront of treating precancerous growths and skin cancer. Thanks in part to numerous studies performed here, the use of imiquimod (Aldara™ & Zyclara®) and ingenol mebutate (Picato®) are now standard therapies for the common precancerous lesions called actinic keratoses (AKs).

The use of these topical agents to enhance the immune system's ability to eradicate AKs was discovered and first tested here. At the current time, we are investigating the efficacy of less irritating formulations and the effects of one on AK genomic markers.

More than a decade ago, Mount Sinai dermatologists were the first to use excimer lasers to treat vitiligo, a distressing skin disorder that causes loss of pigmentation. This year our clinical research team reported exciting results with a new vitiligo treatment called afamelanotide (SCENESSE® Implant Drug), a hormone that stimulates pigment production by melanocytes. The department's latest advance in procedural dermatology was our study that led to the recent FDA-approval of injectable KybellaTM to dissolve underchin fat, producing a more youthful jawline and upper neck.

The impact of the department’s laboratories is just as extraordinary as that of the clinical domain. One of our faculty members demonstrated the impact of chromatin, the material around our genes, on the evolution of malignant melanoma and also elucidated the mechanisms of drug resistance in melanoma. Our melanoma research team is identifying the genetic mutations that distinguish melanoma from benign moles and those that signal the metastatic potential of melanomas. These discoveries are major steps in the quest to improve melanoma prevention and treatment.

Please see the following article for more details about discoveries made by Mount Sinai dermatologists. We are excited to see what advances await – and hope you are, too.

A case of psoriasis (left), which cleared after 2 months of treatment with an experimental biologic drug and remained clear during 10 months of treatment.

REVIEW OF HIGHLIGHTS

Discoveries and Breakthroughs

TEENAGE ACNE & ACNE SCARS In 1982, the drug that has been called a “miracle” for severe acne, isotretinoin (Accutane®) was approved by the FDA. A Mount Sinai research team led by dermatologists Susan Bershad, MD and Susana Poliak, MD characterized the metabolic side effects of isotretinoin and guided its monitoring by the professional community. More recently, Dr. Bershad discovered and led successful trials of the short-contact method of topical retinoid therapy, a new way to treat acne successfully without the typical skin irritation caused by retinoid drugs (see photos).

A case of facial acne before (left) and after 12 weeks of short-contact retinoid therapy.

leading treatment for AKs. Mount Sinai was also a key center in the international clinical trials of ingenol mebutate (Picato®), now another leading topical agent for AKs. Our clinical research team led by Giselle K. Singer deserves much of the credit.”

Acne scarring is a therapeutic challenge that often requires a combination of lasers and cosmetic filler injections. Before lasers, the mainstay of treatment was dermabrasion, invented by Abner Kurtin, MD and first described in his landmark Mount Sinai lecture.

Dermabrasion was later refined for acne scars by a vanguard of procedural dermatologists that included his son, our professor Stephen B. Kurtin, MD.

SubcisionTM is a procedure that lifts acne scars by breaking up fibrous tissue.

The discovery of genistein, a soybean isoflavone, as a photoprotective agent to prevent AKs was made at Mount Sinai

by Huachen Wei, MD, who holds a patent on this treatment.

Our faculty member Gary Goldenberg, MD is a leading thought leader and educator for AK treatment who has helped introduce physicians and patients to effective treatment with the new drug Picato®.

Another of our faculty, David S. Orentreich, MD and his father, Norman Orentreich, MD recognized that no prior acne scar treatment lifted depressed scars, and together they came up with the solution: a procedure called Subcision™, trademarked

by Dr. David Orentreich (see figure).

Recently, noninvasive detection of skin cancer has been revolutionized by optical coherence tomography (OCT), a procedure pioneered by our faculty member Orit Markowitz, MD. Dr. Markowitz was the first president of the International Optical Coherence Tomography Society. Her current research is directed toward new ways to diagnose and treat skin cancer without invasive surgery.

Dermatology professor Julide Celebi, MD directs our melanoma research laboratory at the Tisch Cancer Institute at Mount Sinai. Dr. Celebi’s team, in collaboration with the Icahn Institute of Genomics and Multiscale Biology at Mount Sinai, uses DNA sequencing to predict melanoma risk and to develop personalized therapy for this deadly form of skin cancer.

ACTINIC KERATOSES & SKIN CANCER When asked to decribe the groundbreaking work of the department to treat precancerous lesions called actinic keratoses (AKs), Sol and Clara Kest Professor and Chair Mark G. Lebwohl, MD explained, "Approximately fifteen years ago, we realized that immune mediators called interferons were responsible for successful eradication of warts by imiquimod cream. It occurred to us that other types of skin growths might respond similarly. We then designed a bilateral controlled trial in which patients had symmetrical AKs on both sides of the hands and face and showed that imiquimod cream was highly effective, whereas the vehicle was ineffective on the matching control side.

Using this data, we convinced the drug’s manufacturer to launch a national multicenter study. Over 80% reduction in AKs was seen using imiquimod cream, which has subsequently become a

ATOPIC DERMATITIS & ECZEMA Emma Guttman-Yassky, MD, PhD leads a research team in the Department of Dermatology and The Immunology Institute. She was the first to describe a critical immune-mediated pathway responsible for atopic dermatitis (AD), the condition commonly known as eczema. Her discovery of the role of Th22 cells, which secrete a chemical messenger protein known as IL-22 cytokine, established AD as a reversible, immune-driven skin disorder. In 2014 Dr. Guttman-Yassky's team showed dramatic improvement in the barrier and immune defects of AD using an investigational drug, dupilumab. The new treatment could reach the market by continued on page 3 2

2017, opening the door to a new era of target treatments for AD. "It brings hope to patients who have tried everything," says Dr. Guttman-Yassky.

Hospital in 1999. It has become the leader among academic dermatology centers focused on medical care and procedures for diverse skin types. Under its current Director for the more than a decade, Andrew F. Alexis, MD, MPH, The Skin of Color Center continues to make headlines for its advances in the treatment of skin and hair disorders that preferentially affect deeper skin tones.

COSMETIC PROCEDURES

VITILIGO [LOSS OF PIGMENTATION]

Mount Sinai dermatologists have been among the earliest adopters and educators in the fields of cosmetic fillers, botulinum toxin injections, liposuction, and laser therapy. To name just a few – Patricia Wexler, MD was one of the earliest physicians to learn the technique of botulinum injections for forehead wrinkles, and she is also an internationally respected expert in the areas of liposuction and fillers. Heidi Waldorf, MD, who teaches her special cosmetic techniques to dermatologists around the world, was the lead investigator of Kybella TM, the new FDA-approved injectable treatment for under-chin fat.

Hooman Khorasani, MD is the founder and co-chair of an annual international conference at Mount Sinai entitled Advances in Facial Reconstruction & Cosmetic Surgery.

No reliable treatments for the disfigurement of vitiligo existed when Mount Sinai dermatologists James Spencer, MD and Suhail Hadi, MD published their discovery of excimer laser treatment in 2004 (see photos). Their dramatic results showed excimer laser to be safer and more effective than any previously used drug or device.

One of the latest triumphs of our research appeared in the January 2015 issue of JAMA Dermatology describing success with a new treatment for vitiligo using a melanocyte-stimulating hormone implant (SCENESSE®) combined with phototherapy. Madelaine Haddican, MD and Rita Linkner, MD led the Mount Sinai team in the multi-center study of this breakthrough therapy.

PSORIASIS & PSORIATIC ARTHRITIS Mark G. Lebwohl, MD is a world-recognized authority in the field of psoriasis. Under his direction, the department has pioneered virtually every new psoriasis treatment, including a vast array of biologic drugs that have dramatically improved the prognosis of psoriasis and psoriatic arthritis. Dr. Lebwohl and our research team led by Giselle K. Singer have helped bring to market many novel agents in this class, including adalimumab (Humira®), etanercept (Enbrel®), infliximab (Remicade®), ustekinumab (Stelara®), and soon-to-be-released drugs that hold even greater promise.

THE SKIN OF COLOR CENTER Vincent A. DeLeo, MD and Susan C. Taylor, MD founded the first center of its kind for skin of color at Mount Sinai Roosevelt

A patient with vitiligo before (top) and after excimer laser treatment.

Skin Health FROM THE KIMBERLY AND ERIC J. WALDMAN DEPARTMENT OF DERMATOLOGY

SUSAN V. BERSHAD, MD

Editorial Board

ALAN KLING, MD

Editor

DOUGLAS D. ALTCHEK, MD

ANGELA J. LAMB, MD

YVONNE B. MEYERS

JANET NEZHAD BAND, ESQ.

DAVID S. ORENTREICH, MD

Managing Editor

DAVID COLON

STEPHEN VANCE WALL

MARK G. LEBWOHL, MD

JOSÉ GONZALEZ

PATRICIA WEXLER, MD

Sol and Clara Kest Professor and Chair, Kimberly and Eric J. Waldman Department of Dermatology; President, Editorial Board

GERVAISE L. GERSTNER, MD

VICTORIA F. WHITE

KRISTINA GOLDENBERG, MD

The editors thank Mount Sinai Printing Services.

BRUCE E. KATZ, MD

3

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