6/30/2015. Many patients with more than one form of alopecia, but they think of it as one entity. and Gamble, Galderma, Sanumed

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1 Amy McMichael, MD Professor and Chair Department of Dermatology Wake Wk Forest Baptist i Medical l Center Winston Salem, NC Pacific Dermatology Meeting 2015 Investigator: Consultant: Allergan, Intendis/Bayer, Procter and Gamble, Galderma, Sanumed Procter and Gamble, Johnson and Johnson, Stiefel, Allergan, Up to Date, Galderma, Gunthy Renker, Merz Patients devasted and emotional Patients want to discuss long and often unrelated historical info Physical exam not always helpful hlfl Physicians taught to consider only one overarching diagnosis at a time Many patients with more than one form of alopecia, but they think of it as one entity 1

2 Historical information Age, duration of hair loss, location of hair loss, symptoms, previous treatment Verbal history vs. questionnaire Examination Determine pattern, extent, health of hair shafts, health of background scalp To biopsy or not to biopsy Accuracy of previous biopsy, best location of biopsy Determine treatment course Female pattern hair loss and telogen effluvium Scarring hair loss and female pattern hair loss Scarring hair loss and telogen effuvium Scarring hair loss and breakage Seborrheic dermatitis, breakage, scarring hair loss, and female pattern hair loss 2

3 Increased shedding of telogen hairs associated with physiologic stress to the body Perhaps the most difficult alopecia to diagnose since it is constantly changing Acute phase:sudden shedding hdd Pull test + for >2 hairs/30 hair pull Mid phase:constant shedding Late phase: Slowed shedding with prominent bitemporal and fronto vertex thinning on exam Bitemporal area may have positive pull test Diffuse thinning all over the scalp (patient may not be aware of this) Patients have one episode starting before 1 st episode ending Ex:Childbirth, hair loss, weight loss, hair loss, start new oral contraceptive, hair loss over course of 1.5 years Existing female pattern hair loss with TE complicating clinical findings long term hair loss with sudden worsening Common causes include: Medications Iron deficiency Thyroid abnormalities Post partum alopecia Weight loss Protein calorie malnutrition Physiologic stress (fever, systemic illness, surgery) 3

4 Thorough history for time period 3 9 months prior to start of hair loss If no identifiable event, consider labs: Iron panel including ferritin CBC with diff TSH If normal labs and history, consider nutrition consultation Eating disorders, supplement use, seb derm Male pattern hair loss is the most common form of hair loss in men, unclear for women Frequency and severity increase with age At the age of 70 and beyond, around 80% of men and 42% women report pattern hair loss Asian population have lower prevalence of pattern hair loss No info on African Americans 1. Blume Peytavi U et al. Br J Dermatol 2011;1649(1): Messenger A. Androgenic Alopecia in men. In Hair Growth and disorders. Springer Verlag 2008:

5 (A) Grade I (B) Grade II (C) Grade III Ludwig E. British J Dermatol.1977;97:247. Reprinted with permission from British J Dermatol. Notice diffuse thinning on parietal and temporal (sides) of scalp 5

6 Pattern Hair Loss Minoxidil 2% solution Minoxidil 5% solution or foam Wigs and hair pieces Surgical hair restoration 5 alpha reductase inhibitors Dutasteride Finasteride Low level light laser Diameter increasers Combinations of above Women Only Antiandrogens Flutamide Spironolactone Cyproterone acetate (not in US) +oral contraceptives Minoxidil 5% foam approved as q day txt for women Feb women with AGA in 24 week single blinded trial 5% minoxidil dlfoam daily vs. 2% solutions BID Greater, but not significant improvement in 5% foam group Significantly lower rates of local irritation for 5% foam vs. 2% solution (p=.046) Less interference in hair styling for 5% foam (p=.002) Blume Peytavi U et al. JAAD. 2011;65: patients in a study (7 women, 8 men) Plucked hairs tested in sulfotransferase enzyme (STE) assay before and after minoxidil 6 mo twice daily treatment Data combined in meta analysis analysis of 50 previous patients STE predicted responders to treatment 100% sensitivity, 71% specificity Commercial testing not available yet Soon, may be able to predict who will be a responder to topical minoxidil Goren A, Shapiro J, Roberts J, et al. Derm Therapy 2015, Vol 28,

7 5 alpha reductase inhibitor Type I (finasteride) Type I and II inhibition (dutasteride) Work by decreasing serum and scalp dihydrotesterone Trials in women with Finasteride 1 mg showed progression of the hair loss, few side effects Meta analysis by Stout and Stumpf suggests one year of treatment may be needed with 1 mg dose* No trials with higher dosing, only small case series Not safe in women of child bearing potential Side effects: typical for any medication breast tenderness and enlargement decreased libido Stout SM, Stumpf JL. Ann Pharmacother 2010;44: women on both finasteride 2.5 mg/day and OC s with drospirenone and ethinyl estradiol Followed for 12 months 24/37 (62%) with improvement via global photography Significant increase in hair density in 12 subjects (p=.002) No adverse reactions Iorizzo M, et al. Arch Dermatol Mar;142(3): Recent media and internet attention re: these side effects Study of 71 men reporting persistent sexual side effects, lasting > than 3 mo after stopping finasteride* Recruited from website for men experiencing sexual dysfunction, patient referral, and a practice 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 1 Package insert changed in 2011 to add persistent erectile dysfunction, changed in 2012 to reflect libido/orgasm disorders *Irwig MS, Kolakula S. J Sex Med Irwig MS. J Clin Pyschiat

8 Singh MK and Avram M. J of Clin Aesthet Dermatol, Best review of the data on the topic Prostate trials: more than 17,000 men in one trial looking at sexual dysfunction* and >1,300 in other trials with no persistent sexual side effects or depression MPHL trials: il more than 2,500 with ih no persistent sexual dysfunction 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 *Monpour CM et al. J Natl Ca Inst Flutamide Pure selective antiandrogen with nonsteroidal structure Few studies Study of 101 Caucasian women with FPH over 14 yrs Given flutamide with or without OC s for with 125 mg BID for one yr and decreasing dose to 62.5mg Biochemical assays of hormones Ludwig scores improved after 6 mo and cont. 2 yr Similar drop out rate for both groups, only (4%) with sig. increased transaminase and only in starting dose Flutamide hepatotoxicity appears dose dependent Other side effects: nausea, diarrhea, dry skin, decreased libido Paradisi R, et al. Ann Pharmacother Apr ;45(4): FDA cleared for males in 2007 FDA clearance for women in models approved ranging from $295 $495 Used 3 times per week Randomized, double blind, sham devicecontrolled, multicenter trial with HairMax Lasercomb* 26 week trial in 110 males Increase in terminal hair density vs. sham group No serious adverse events *Leavitt M, et al. Clin Drug Investig. 2009;29(5):

9 Insufficient evidence for: Iron Ginseng Saw palmetto Green tea Biotin Minerals Mesotherapy Caffeine Botulinum toxin Bimatoprost Wnt stimulating agents New measuring instruments being designed for photos, dermascopy for clinical studies and possibly for patient care Plasma rich platelets no randomized clinical trials *Karzan G et al. FASEB Journal 2013;27(2): *Valente Duarte de Sousa IC, Tosti A. Expert Opin Investig Drug

10 Variant of lichenplanopilaris Exam reveals progressive recession of frontotemporal hair line with loss of follicular openings Atrophy of frontal scalp/forehead with vessel prominence Perifollicular erythema and hyperkeratosis in active areas Incidence appears to be exploding 13 patients(11 postmenopausal) Performed clinical and pathologic exam from scalp, eyebrows (6), and body (5) All patients with clinical lloss of eyebrows and 10/13 subjects with body hair loss Pathology showed similar findings from eyebrows, upper limb, and scalp Perifollicular lymphoid infiltrates and fibrosis Marked reduction in number of hair follicles *Chew AL et al. J Am Acad Dermatol 2010 Oct 63(4);

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12 Therapeutic ladder resembling that for chronic cutaneous lupus Intralesional corticosteroids every 4 8 weeks Potent and ultrapotent topical steroids Hydroxychloroquine+ quinacrine Oral corticosteroid for severe, progressive disease Cyclosporine Methotrexate Mycophenylate mofitil P PAR gamma agonist (pioglitazone, Actos )* 5 alpha reductase inhibitor Aggressive therapy for quickly progressive disease *Mirimani P, Karnik P. Arch Derm 2009 Dec;145(12) Clinical review of 36 patients* Used quantitative activity score called Lichenplanopilaris activity index (LPPAI) Evaluated response to hydroxychloroquine, doxycycline, mycophenylate mofetil Results: Most subjects were women (97%), white (92%), postmenopausal (83%) Scalp pruritus (67%) and perifollicular edema (86%) Significant reduction in signs and symptoms at 6 and 12 months in patients treated with hydroxychloroquine Small study, scoring scale validation? * Samrao A. Chew AL, Price V. Br J Dermatol Dec;163(6): Targeted deletion of PPAR gamma in follicular stem cells in mice causes a skin and hair phenotype of scarring alopecia PPAR gamma may be 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): LPP patients treated with pioglitazone* 20/24 were females 3 patients: no change 4 patients: discontinued treatment due to side effects Side effects included leg pain, lightheadedness, nausea, hives, dizziness 5 patients: achieved remission 12 patients: improvement 12

13 Spring et al. JAAD, patients with LPP/FFA at 15 mg/day for 1 year (cont d other txt) 3 patients with cessation of disease activity 4 with improvement, relapse after d/c of drug 5 with cessation of symptoms, still active disease Judged as a negative outcome Mesinkovska NA et al. JAAD, 2015 Retrospective evaluation of 22 patients No remissions, 16 marked improvement, 5 stable, 1 progression,2 of the responders relapsed after d/c of drug 9 stopped due to side effects Recommendations to patients: 2 nd or 3 rd line drug Few remissions, limited likelihood of improvement High likelihood of side effects 19 patient study showing the majority of patients on dutasteride stabilized, but none of the other therapies stabilized disease* Combined review evaluating 114 patients 1 45% with good clinical results on 5 alpha reductase inhibitors 30% of the 29 treated showed good clinical response on hydroxychloroquine *Ladzinski B et al. JAAD Racz E et al. JEADV patients (343 women, 12 men) Eyebrow loss as initial presenting symptom was associated with milder disease Dutasterideor finasterideused d 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 13

14 Cicatricial Alopecia Research Foundation Brochures currently available for scarring hair loss and for CCCA Funding is available for studies on cicatricial alopecias 103 African American women surveyed Fifty percent of women between years of age have modified their hairstyle to accommodate exercise Nearly 40% avoid exercise at times due to hair related issues Respondents who exercised less due to hair concerns were 2.9 times less likely to exercise >150 minutes/week (p=0.08; 95% CI = ). 14

15 Over half of study participants reported symptoms at baseline 55% reported breakage of hair shafts with normal styling 55% reported itching 32% reported flaking/scaling 23% hair coming out at the root 10% reported pustules/bumps 8% had pain/burning Prevalence unknown Wide range of clinical severity Symptoms range from none to severe pruritus and pain Mostly African American women, ages Frontal scalp variety vs. vertex variety Often accompanied by traction alopecia Pre dated chemical relaxers Occurs in patients who have never used hot comb or relaxers Traction common theme 15

16 874 adults in Capetown Questionnaire and scalp exam 30.9% men and 69.1% women Most women had chemical treated hair (53%) Prevalence of CCCA was 1.9% overall, 2.7% in the women in the study Higher prevalence in women over age 50 (6.7% vs. 1.2%) 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 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 16

17 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 Pdi analysis suggests autosomal dominance Patient recommendations: Discuss research on CCCA Tell patients there may be an interaction between hair care practices and genetics May be able to predict likelihood of disease at some point 9 patients with vertex hair breakage 8/9 with biopsy results 5 showed typical CCCA changes 1 showed advanced end stage scarring alopecia 2 showed premature desquamation of inner root sheath (suggestive of early CCCA) 17

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19 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 Oral/topical antibiotics for pustular disease Push treatment until symptom free Post inflammatory treatment and Female pattern Monixidil solution for prolongation of anagen Oral meds:flutamide, finasteride Surgical restoration Pretreatment Posttreatment Pretreatment Post treatment 19

20 New treatments in hair disorders arriving slowly, but they are arriving Low level laser light might be a new focus New uses for Excimer laser Genetics are becoming more important and may help for long term recommendations in alopecia areata, scarring alopecia Approaches for scarring hair loss are increasing New molecules for scalp hair loss, like bimatoprost 20