CLASSIFICATION OF AGA IN MALES: THE HAMILTON-NORWOOD SYSTEM DISCLOSURE OF CONFLICTS OF INTEREST

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1 DISCLOSURE OF CONFLICTS OF INTEREST Investigator: Allergan, Intendis, Procter & Gamble, Abbott, Samumed, Cassiopea, Bayer, Galderma Amy McMichael, MD Professor and Chair Department of Dermatology Wake Forest Baptist Health Winston-Salem, NC Fall Clinical October 2016 Consultant: Procter & Gamble, Johnson & Johnson, Stiefel, Allergan, Galderma, Guthey Renker, Bayer, Healthwise, Merz, Incyte, Samumed, Aclaris, Anacor, Pfizer (A) Grade I (B) Grade II (C) Grade III Ludwig E. British J Dermatol.1977;97:247. Reprinted with permission from British J Dermatol. CLASSIFICATION OF AGA IN MALES: THE HAMILTON-NORWOOD SYSTEM Plasma rich platelets Bimatoprost 29 yo man treated with PRP Topical Wnt pathway activation Oral PGD2 receptor antagonist Hamilton JB. Ann NY Acad Dermatol. 1951;53: Norwood OT. South Med J.1975;68: Reprinted with permission from South Med J. Pietro Gentile et al. Stem Cells Trans Med 2015;4:

2 Recent media and internet attention Study of 71 men reporting persistent sexual side effects, lasting > than 3 mo after stopping finasteride 1 Recruited from website for men experiencing sexual dysfunction Retrospective data on sexual dysfunction or depression Followed these men for 2 more publications 3 rd study evaluated depression and found 75% of 61 patients reports depressive symptoms compared to controls with MPHL on college campus 2 Package insert: added persistent erectile dysfunction 2011 and libido/orgasm disorders 2012 Singh MK and Avram M meta-analysis 1 Prostate trials: more than 17,000 men in one trial looking at sexual dysfunction 2 and >1,300 in other trials with no persistent sexual side effects or depression MPHL trials: more than 2,500 with no persistent sexual dysfunction Belknap SM et al: questioning adequacy of safety reporting 3 Recommendations to patients: discuss outlier data on persistent sexual dysfunction with patients discuss safety seen in large trials discuss pre-existent sexual dysfunction and depression and treat only appropriate patients 1. Irwig MS, Kolakula S. J Sex Med Irwig MS. J Clin Pyschiat MK and Avram M. J of Clin Aesthet Dermatol, Monpour CM et al. J Natl Ca Inst Belknap et al. JAMA Derm, 2015 Corticosteroids Topical Intralesional Systemic Topical Immunotherapy Minoxidil 5% Anthralin Excimer Laser Other immunosuppressive agents (ie MTX, JAK inhibitors) Cytotoxic NKD2+ T cells are necessary and sufficient to induce alopecia in mice Interleukin 15 (required for the growth of natural killer cells) has been identified as a potential therapeutic target Janus kinase (JAK) inhibitors can affect signaling pathway of IL 15 1 Inhibition of JAK-STAT signaling promotes hair growth by stimulating the activation and/or proliferation of HF stem cells 2 1. Xing L et al. Nature Med 2014;20: Harel S, et al. Sci Adv Oct; 1(9) 2

3 King B, Ko J et al poster, WCHR 2015, Miami, FL 47% improved by at least 25% in SALT score Low side effects, ophiasis improved more than totalis/universalis, shorter duration of hair loss better Recommendations to patients: Prescribe these drugs with caution New clinical trials with topical JAK inhibitors are underway Expense and short remissions may outweigh benefits 24 weeks of simvastatin/ezetimibe 40mg/10 mg in 19 patients with 40-70% scalp hair loss 14/19 responders Association of stable remission and on medication significant (p = 0.04) Patchy alopecia areata Topical clobetasol foam BID for 5 day per week Can use clobestasol cream under occlusion 5 nights per week Minoxidil 5% solution or foam daily Intralesional steroids (5-7.5 mg/cc up to 3 cc) every 6-8 weeks Totalis/Universalis Topicals as above Prednisone taper, Methotrexate, Excimer laser, Immunotherapy Lattouf et al. JAAD Variant of lichenplanopilaris INCIDENCE APPEARS TO BE EXPLODING! Exam reveals progressive recession of fronto-temporal hair line with loss of follicular openings Atrophy of frontal scalp/forehead with vessel prominence Perifollicular erythema and hyperkeratosis in active areas Eyebrow loss Facial papules 3

4 TRACTION ALOPECIA Not complete loss Fringe sign FRONTAL FIBROSING ALOPECIA No fringe sign Psuedo-fringe Eyebrow loss Lonely hair Therapeutic ladder: Intralesional corticosteroids every 4-8 weeks Potent and ultrapotent topical steroids Hydroxychloroquine + quinacrine Methotrexate Mycophenylate mofitil P-PAR gamma agonist (pioglitazone, Actos )* 5 alpha reductase inhibitor Oral corticosteroid for severe, progressive disease Cyclosporine *Mirimani P, Karnik P. Arch Derm 2009 Dec;145(12) PPAR gamma important for healthy pilosebaceous units and loss of this function may trigger pathogenesis of LPP -Karnik P et al. J Invest Dermatol May;129(5): Studies N # Remission Sx Improvement s Baibergenova A, Walsh S. J Cutan Med Surg, 2012 Spring et al. JAAD, 2013 Mesinkovska NA et al. JAAD, 2015 Cessation due to side effects patients (343 women, 12 men) Eyebrow loss as initial presenting symptom was associated with milder disease Dutasteride or finasteride used in 111 (31%) patients with improvement in 52(47%) and stabilization in 59(53%) Recommendations to patients: Low side effect profile 50/50 chance of improvement/stabilization Recommendations to patients: 2 nd or 3 rd line drug Few remissions, limited likelihood of improvement High likelihood of side effects 4

5 Therapeutic ladder: Intralesional corticosteroids every 4-8 weeks * Potent and ultrapotent topical steroids * Hydroxychloroquine * +quinacrine Methotrexate * Mycophenylate mofitil * P-PAR gamma agonist (pioglitazone, Actos ) 5 alpha reductase inhibitor * Oral corticosteroid for severe, progressive disease Cyclosporine 105 articles on hair loss and African Americans in Pub Med from articles on dissecting cellulitis 65 articles on Central Centrifugal Cicatricial Alopecia 101 articles on Pseudofolliculitis barbae >40,000 articles on psoriasis > 20,000 articles on atopic dermatitis TOP DIAGNOSES IN AFRICAN AMERICAN PATIENT VISITS TO DERMATOLOGISTS NATIONAL AMBULATORY MEDICAL CARE SURVEY Diagnosis ICD-9 Code No. of Visits % of Visits Acne ,720, % Unspec. dermatitis ,640, % TOP DIAGNOSES IN AFRICAN AMERICAN PATIENT VISITS TO DERMATOLOGISTS NATIONAL AMBULATORY MEDICAL CARE SURVEY Diagnosis ICD-9 Code No. of Visits % of Visits Acne ,720, % Unspec. dermatitis ,640, % Seb dermatitis ,990, % Seb dermatitis ,990, % Atopic derm ,590, % Dyschromia ,290, % Psoriasis , % Alopecia , % Keloid scar , % Viral warts , % Sebaceous cyst , % Atopic derm ,590, % Dyschromia ,290, % Psoriasis , % Alopecia , % Keloid scar , % Viral warts , % Sebaceous cyst , % Davis SA, et al. J Drugs Dermatol 2012 Davis SA, et al. J Drugs Dermatol 2012 CENTRAL CENTRIFUGAL CICATRICIAL ALOPECIA CENTRAL CENTRIFUGAL SCARRING ALOPECIA EPIDEMIOLOGY Prevalence ranges from 2.7% in 604 South African women to 5.6% in 529 US women 1,2 Wide range of clinical severity Symptoms range from none to severe pruritus and pain Mostly women of African descent, ages Often accompanied by traction alopecia Pre-dated chemical relaxers Traction common theme 1. Khumalo NP et al, BJD Olsen EA et al, JAAD Yolanda Lenzy, personal communication, AAD

6 Central Scalp Alopecia Photographic Scale in African American Women Olsen EA, Callender V, Sperling L, McMichael A, Anstrom KJ, Bergfeld W, Durden F, Roberts J, Shapiro J and Whiting DA Derm Therapy Vol 21, 2008 CENTRAL HAIR LOSS IN AFRICAN AMERICAN WOMEN: INCIDENCE AND POTENTIAL RISK FACTORS JAAD 2011;64(2): ELISE A OLSEN, MD, VALERIE CALLENDER, MD, AMY MCMICHAEL, MD, LEONARD SPERLING, MD, KEVIN J. ANSTROM, PHD, JERRY SHAPIRO, MD, JANET ROBERTS, MD, FAITH DURDEN, MD, DAVID WHITING, MD AND WILMA BERGFELD, MD Incidence and patterns of central hair loss and the relationship of hair care practices, family history of hair loss and underlying medical conditions Extensive central scalp hair loss was seen in 5.6% in 529 subjects at 4 sites No association of extensive hair loss with relaxer, hot comb use, prior history of seborrheic dermatitis, reaction to a hair care product, bacterial infection, male pattern hair loss in fathers of subjects, however there was an association with a history of tinea capitis. Supported by the NAHRS and an unrestricted educational grant from Procter and Gamble Inflammation Hormonal? Inflammation Inflammation 6

7 TRACTION ALOPECIA Not complete loss Fringe sign FRONTAL FIBROSING ALOPECIA No fringe sign Psuedo-fringe Eyebrow loss Lonely hair Epidemiology not known Can occur alone or with other forms of hair loss Often requires biopsy to diagnose Retrospective study of patients staged at beginning and end of treatment Treatment = IL Kenalog, topical steroids, +/- minoxidil N = 15 After treatment: 5/15 (33.3%) had decreased severity scores (Improved) 8/15 (53.3%) had increased severity scores (Worsened) 2/15 (13.3%) had no change in severity scores FPHL FPHL with CCCA TREATMENT OF CCCA Biopsy for extent of inflammation/alternate diagnosis Inflammatory Stage Decrease heat to vertex Decrease all traumatic hair styling methods Decrease inflammation via topical and intralesional corticosteroids IL for 8 rounds with mg/cc for max 3 cc/visit (q 6-8 weeks) Oral/topical antibiotics for pustular disease Push treatment until symptom free Post-inflammatory treatment Monixidil solution for prolongation of anagen Surgical restoration 7

8 NIGERIAN WOMAN TREATMENT : IL KENALOG AND HAIR RESTORATION Pretreatment Post-treatment Dlova et al, Autosomal dominant inheritance of central centrifugal cicatricial alopecia in black South Africans. JAAD, 2014;70: index families with 31 immediate family members Pedigree analysis suggests autosomal dominance EXCITING RESEARCH 47% of nearly 6,000 African American women participants had crown hair loss in the Black Women s Health Study at Boston University 1 THANK YOU FOR YOUR ATTENTION! 1. Yolanda Lenzy, personal communication, AAD