Amy McMichael, MD Professor and Chair Department of Dermatology Wake Forest Baptist Health Winston-Salem, NC SC Derm 2019 1 DISCLOSURE/CONFLICTS OF INTEREST Investigator Allergan Intendis Procter & Gamble Samumed Casseopia Concert Alcaris Incyte Consultant Johnson & Johnson Procter & Gamble Stiefel Allergan Bayer Galderma Incyte Samumed Aclaris Anacor Pfizer Nutrafol Bioniz 2 1
Wake Forest Baptist Medical Center Wake Forest School of Medicine 3 GOOD HAIR 4 2
Distributed by Roadside Attractions Special jury prize at 2009 Sundance Film Festival 5 The hair I had last year The hair I had 25 years ago The hair that the rest of my family has In my African American patients, it is hair that grows and shines as well as a measure of acceptance in society 6 3
7 OUTLINE Discuss the most common forms of hair loss Highlight how dermoscopy can be helpful in hair loss Underscore treatment pearls Update treatment paradigms Give special time to hair loss in skin of color patients 8 4
CLASSIFICATION OF AGA IN MALES: THE HAMILTON-NORWOOD SYSTEM Hamilton JB. Ann NY Acad Dermatol. 1951;53:708-828. Norwood OT. South Med J.1975;68:1359-1365. Reprinted with permission from South Med J. 9 10 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. 11 PATTERN HAIR LOSS TYPICAL EXAM FINDINGS Not usually difficult in men In women: Diffuse thinning at vertex, frontal scalp, +/- bitemporally Vellus hair present in areas of thinning, frontal hairline intact +/- positive pull test in active phase Can biopsy to distinguish from telogen effluvium 12 6
frontal occiput Path photo courtesy of Len Sperling 13 Normal density AGA Dermoscopy shows fine hairs mixed with terminal hairs Increase in percentage of single-hair follicular units in the frontal area is also suggestive of early AGA Presence of > 6 short thin hairs in the frontal scalp may be diagnostic 14 7
FEMALE PATTERN HAIR LOSS IN AFRICAN AMERICAN PT hair shaft variability empty follicles peripilar sign Photo courtesy of Fernanda Torres 15 Mild Moderate Minoxidil 5% Low level laserlight Oral minoxidil Finasteride Dutasteride Spironolactone Flutamide Severe Hair restoration surgery Platelet rich plasma Hair piece/wig Botanicals 16 8
Mild Minoxidil 5% Low level laserlight Moderate Finasteride/Dutasteride Oral minoxidil Hair Restoration Severe Platelet rich plasma Hair piece/wig Botanicals 17 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 1. Irwig MS, Kolakula S. J Sex Med. 2011 2. Irwig MS. J Clin Pyschiat. 2012 18 9
Singh MK and Avram M meta-analysis 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: more than 2,500 with no persistent sexual dysfunction Belknap SM et al: questioning adequacy of safety reporting Few side effects of any kind reported in woman 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 MK and Avram M. J of Clin Aesthet Dermatol, 2014 Monpour CM et al. J Natl Ca Inst. 2007 Belknap et al. JAMA Derm, 2015 Seal L, Eginli A, McMichael A JDD 2016 19 113 women with AGA in 24 week single-blinded trial 5% minoxidil foam daily vs. 2% solution 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) Minoxidil 5% foam approved by FDA as daily treatment for women Feb 2014 Blume-Peytavi U et al. JAAD. 2011;65:1126-34 SUCCESS = application techniques + not worse after stopping + expectation of early shedding + expectation of treatment time + possible hypertrichosis 20 10
15 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 of 50 previous patients STE predicted responders to treatment- 100% sensitivity, 71% specificity Commercial testing not available yet -Goren A, Shapiro J, Roberts J, et al. Derm Therapy 2015, Vol 28, 13-16 21 22 11
Oils Butters Lotions Shampoo Pre-poo Conditioners Food Cooking products 23 Data on effectiveness for hair and scalp disease sparse but rampant testimonials on social media Coconut oil 1 Reduced water retention and hair swelling Decreased protein loss incurred from wet combing Comedogenic Jojoba oil Similar properties to sebum in lubricating hair shafts Can induce contact dermatitis Argan oil Some data to suggest good lubrication for hair shafts Allergenicity 1. Rele AS, Mohile RB. J Cosmet Sci. 2003 Mar-Apr;54(2):175-92 24 12
Biotin highly commercialized in past decade with sales steadily increasing from July 2014 to June 2017 Commercial availability in doses ranging from 30 mcg-10,000 mcg makes supraphysiologic dosing possible 2 assays which are commonly affected by high-dose biotin intake Competitive assay including free T3, free T4, thyroid stimulating hormone receptor antibody, estradiol, testosterone, cortisol, vitamin B12, and folate Sandwich immunometric assay and involves troponin, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), TSH, HCG, SHBG, insulin, LH, and FSH Recommendation: Poor likelihood that biotin helps Stop biotin supplements in patients with hair loss Piketty, Marie-Liesse, et al. Clinical Chemistry and Laboratory Medicine (CCLM) 2017 25 PROPIONATE-- CORTEXOLONE 17Α- Clascoterone competes with DHT for binding to the AR in the scalp Clascoterone bound AR inhibits androgen responsive genes 2 Loss of specific gene expression that results in: Dermal papilla cell survival and normal hair growth cycle 1 Clascoterone DHT Clascoterone is metabolized to cortexolone 21-propionate and cortexolone 2 Metabolites exhibit minimal activity Well-known safety profile DHT can t bind to AR with Clascoterone present Androgen Receptor Clascoterone 1. Figure from: Ellis JA. Expert Rev Mol Med. 2002; https://www.ncbi.nlm.nih.gov/pubmed/14585162 2. Data on File. CB-03-01 Investigator s Brochure. 2017. Cassiopea SpA. 26 13
Both active treatment groups had directionally larger changes from Baseline compared to Vehicle; although results among the three treatment groups were not statistically significant (p=0.0971) 27 ClinicalTrials.gov Identifier: NCT02279823 78 completed the POC study treatment period Clascoterone (CB-03-01) & Minoxidil, the active treatment groups, showed larger TAHC changes from baseline vs. vehicle (p=0.0971) Minoxidil efficacy peaked at Month 4 Skin reactions were mostly minimal/mild No significant systemic AEs were reported The Phase 2 Dose Ranging Study interim results demonstrate the potential as a novel treatment for AGA Note: Clascoterone was referred to as CB-03-01 & cortexolone 17-α propionate POC: Proof-of-Concept; TAHC: Target Area Hair Count; HGA: Hair Growth Assessment; AE: Adverse Events 28 14
Biotin Curcumin Saw Palmetto Vit A, C, D Selenium Resveratrol Zinc L-Methionine L-Lysine L-Cysteine Organic kelp Black pepper fruit Red pepper extract Keratin 29 Oral minoxidil Plasma rich platelets (PRP) Bimatoprost Topical Wnt pathway activation Oral PGD2 receptor antagonist 29 yo man treated with PRP Pietro Gentile et al. Stem Cells Trans Med 2015;4:1317-1323 30 15
Introduced by Rod Sinclair in Australia Doses at 0.25 mg daily (1/4 tab in Austr) Others have begun to use oral dosing in US at 0.625 mg (1/4 of 2.5mg tab) Concerns: Hypertrichosis Postural hypotension Fluid retention Urticaria/rash Telogen effluvium Sinclair R. Int J Dermatol. 2018 Jan;57(1):104-109. doi: 10.1111/ijd.13838. Epub 2017 31 6-month, randomized in men with Norwood Hamilton stages II /V and women w/ Ludwig stage I/II. Two regimens of subdermal platelet-rich plasma injections (27 men and 9 women) 3 monthly sessions with 4th booster session 3 months later 2 sessions every 3 months for 2 sessions Patients in first treatment group - statistically significant increases in hair count. Shaft caliber improvement (+0.024 mm; P <.001). 20% mean increase in hair count and 44.1% increase in caliber Questionnaire results showed patients in first group were likely to be very satisfied 32 16
Many different regimens and costs Mixed platelets with cellular matrix versus platelet injections alone Doses/amounts different in each trial +/- activators Regimen can be weekly for months or monthly with a tapering phase Costs range from $500-1200 per treatment What to tell patients Long-term and costly treatment Need a series of treatments Case series show good outcomes May be helpful, small randomized controlled trials Trials: Gentile P et al. Stem Cells Trans Med 2015;4:1317-1323 Alves R, Grimalt R. Derm Surg 2016;42:491-497 33 Mechanical centrifugation of scalp punch biopsy to isolate human hair follicle stem cells Hair cells counted in each sample 11 patients treated with improvement in hair density 34 17
PGD 2 works via GPR 44 pathway Elevation of PGD 2 levels in certain regions of the male scalp is associated with hair loss in those regions PGD 2 inhibitors found to extend the anagen (growth) phase of the hair cycle, thereby promoting the growth of hair Has already been studied in Phase III study in seasonal allergic rhinitis and Phase II study in asthma Setipiprant is selective oral antagonist to the prostaglandin D 2 (PGD 2 ) receptor Trials for Setipiprant for AGA in men underway 35 36 18
37 Corticosteroids Topical Intralesional Systemic Topical Immunotherapy Minoxidil 5% Anthralin Excimer Laser Other immunosuppressive agents (ie MTX, JAK inhibitors) 38 19
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;20:1043-1049 2. Harel S, et al. Sci Adv. 2015 Oct; 1(9) 39 40 20
41 Crispin et al (Brett King) JCI Insight 2016 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 FDA fast tracking oral JAK inhibitor by Concert Pharma 42 21
JAK 1/3 product in development Multi-cytokine inhibitors (IL 2, 9, 15) 43 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, JAK inhibitors, Immunotherapy 44 22
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 45 46 23
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49 Case series from South Africa, lichen planus pigmentosus was associated with frontal fibrosing alopecia (FFA) 50% of the time and preceded FFA by years- BJD, 2013 Case report from India- Int J Dermatol 2014 2 Latina women in San Francisco with hyperpigmentation of the face prior to hair loss JAAD 2014 Treatments reported include: topical steroids, topical tacrolimus, Nd:YAG laser, hydroquinone, topical retinoids, sunscreen None extremely successful 50 25
TRACTION ALOPECIA Not complete loss Fringe sign FRONTAL FIBROSING ALOPECIA No fringe sign Psuedo-fringe Eyebrow loss Lonely hair 51 Therapeutic ladder: Intralesional corticosteroids every 4-8 weeks (5 mg/cc) Oral doxycycline 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)1363-6 52 26
53 PPAR gamma important for healthy pilosebaceous units and loss of this function may trigger pathogenesis of LPP -Karnik P et al. J Invest Dermatol. 2009 May;129(5):1243-57 54 27
Studies N # Remission Sx Improvement s Baibergenova A, Walsh S. J Cutan Med Surg, 2012 Cessation due to side effects 24 5 12 4 Spring et al. JAAD, 2013 Mesinkovska NA et al. JAAD, 2015 22 0 7 0 22 0 21 9 Recommendations to patients: 2 nd or 3 rd line drug Few remissions, limited likelihood of improvement High likelihood of side effects 55 355 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 56 28
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Oxybenzone/Avobenzone Sunscreen/moisturizers ~1989 59 First line treatment: Topical tacrolimus ointment or pimecrolimus cream every other day Intralesional corticosteroids every 4-8 weeks for symptoms Mid-potency topical steroids increasing to ultrapotent for severe symptoms Hydroxychloroquine 200 mg twice daily Doxycycline 5-alpha reductase inhibitors (non-childbearing potential) Second line treatment Methotrexate, mycophenylate mofitil P-PAR gamma agonist (pioglitazone, Actos ) Third line treatment: Oral corticosteroid for severe, progressive disease Cyclosporine Nd:YAG laser Sunscreens???? Always combine treatments for best outcome! 60 30
138 articles on hair loss and African Americans in Pub Med from 1968 2017 articles on dissecting cellulitis 77 articles on Central Centrifugal Cicatricial Alopecia 101 articles on Pseudofolliculitis barbae 225 Frontal fibrosing alopecia >40,000 articles on psoriasis > 20,000 articles on atopic dermatitis 61 TOP DIAGNOSES IN AFRICAN AMERICAN PATIENT VISITS TO DERMATOLOGISTS NATIONAL AMBULATORY MEDICAL CARE SURVEY 1993-2009 Diagnosis ICD-9 Code No. of Visits % of Visits Acne 706.1 5,720,000 22.1% Unspec. dermatitis 692.9 3,640,000 14.0% Seb dermatitis 690.10 1,990,000 7.7% Atopic derm 691.8 1,590,000 6.1% Dyschromia 709.0 1,290,000 5.0% Psoriasis 696.1 950,000 3.6% Alopecia 704.00 920,000 3.6% Keloid scar 701.4 830,000 3.2% Viral warts 078.1 780,000 3.0% Sebaceous cyst 706.2 780,000 3.0% Davis SA, et al. J Drugs Dermatol 2012 62 31
TOP DIAGNOSES IN AFRICAN AMERICAN PATIENT VISITS TO DERMATOLOGISTS NATIONAL AMBULATORY MEDICAL CARE SURVEY 1993-2009 Diagnosis ICD-9 Code No. of Visits % of Visits Acne 706.1 5,720,000 22.1% Unspec. dermatitis 692.9 3,640,000 14.0% Seb dermatitis 690.10 1,990,000 7.7% Atopic derm 691.8 1,590,000 6.1% Dyschromia 709.0 1,290,000 5.0% Psoriasis 696.1 950,000 3.6% Alopecia 704.00 920,000 3.6% Keloid scar 701.4 830,000 3.2% Viral warts 078.1 780,000 3.0% Sebaceous cyst 706.2 780,000 3.0% Davis SA, et al. J Drugs Dermatol 2012 63 Hair Fragility Inflammatory Scalp Conditions 64 32
No prevalence data Study: 60 women studied: 30 Caucasian & 30 African American Broken hairs were significantly increased in African women (p = 0.0001) Study:103 African American women surveyed 50% of women between 21-60 years of age have modified their hairstyle to accommodate exercise Nearly 40% avoid exercise at times due to hair-related issues 55% reported breakage of hair shafts with normal styling 65 APPROACH TO HAIR BREAKAGE Correct underlying abnormalities (Iron levels, thyroid, nutrition, etc) Give the hair a rest! Consider stopping chemical relaxer, color, or heat for 6-12 months Place a hair weave that is not tight and will allow scalp care Loose braids Wig Natural hair but do not straighten with heat Serial trimming of hair (every 6-8 weeks) Use heat protectant products on the hair before styling Layering moisturizing regimen Start with moisturizing shampoo and conditioner (should state for dry, damaged hair) Next apply a leave-in conditioner with coating agents to wet hair (dimethicone-coating agents) Add a leave-in conditioner (oils) to dry hair (after washing weekly and then as needed daily) Discuss the long wait for improvement 66 33
Used Trichometer measurements of hair max index (HMI) Tested Synsepalum dulcificum seed oil (Miracle seed oil) 8 month study Assessed breakage rates on hair shafts (unclear ethniticy) Subjects washed 3 times per week and applied test oil vs argan vs dimethicone vehicle Improvement significant for test oil by HMI and subject evaluation Del Campo R, Zhang Y, Wakeford C, JCAD 2017 67 CENTRAL CENTRIFUGAL CICATRICIAL ALOPECIA 68 34
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 30-65 Often accompanied by traction alopecia Pre-dated chemical relaxers Traction common theme 1. Khumalo NP et al, BJD. 2007 2. Olsen EA et al, JAAD. 2011 3. Yolanda Lenzy, personal communication, AAD 2016 69 Frontal fibrosing alopecia Scleroderma Fibrotic kidney disease Possible pathogenesis of CCCA Beamer et al 2016, Poster, presented at Wake Forest Medical student research day 70 35
487,104 black women older than 18 years of age were seen at Johns Hopkins Hospital during the 4-year study period. 447 women (0.09%) with a medical history of CCCA were identified, 62 of whom had uterine leiomyomas (ULs) Women with CCCA have nearly 5 times increased odds of having uterine leiomyomas compared with race-, age-, and sex-matched controls - Dina et al, JAMA Dermatol 2017 72 African American female subjects with ESRD on hemodialysis were surveyed for CCCA 49/72 subjects (68.1%) had CCCA based on clinical observation unpublished, McMichael et al 71 Dlova et al, Autosomal dominant inheritance of central centrifugal cicatricial alopecia in black South Africans. JAAD, 2014;70:679-682 14 index families with 31 immediate family members Pedigree analysis suggests autosomal dominance 72 36
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) Callender V, Wright D, Davis E, Sperling L Arch Dermatol 2012 73 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 74 37
75 Female pattern hair loss May exist comcomittantly with FPHL 76 38
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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 79 TREATMENT OF CCCA Biopsy for extent of inflammation/alternate diagnosis Often complicated by seb derm and hair fragility Inflammatory Stage Decrease heat to vertex Decrease all traumatic hair styling methods Anti-dandruff shampoos weekly Decrease inflammation via topical and intralesional corticosteroids IL for 8 rounds with 7.5-10 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 80 40
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83 NIGERIAN WOMAN TREATMENT : IL KENALOG AND HAIR RESTORATION Pretreatment Post-treatment 84 42
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Decrease friction and traction behaviors to the area Anti-inflammatory treatments Mid-potency topical steroids 3-4 times per week Intralesional kenalog 5 mg/cc to the affected areas for 2-3 cycles Topical minoxidil 2 or 5% daily Surgical correction Follow improvement with photos 87 Intralesional injections Kenalog 5 mg/cc X 3 Topical minoxidil 5% daily maintenance Gentle hair care 88 44
89 Hair that stays on your head is GOOD HAIR 90 45
Hair that stays on your head is GOOD HAIR Hair that grows in the normal genetically determined density without fragility and inflammatory attack is GOOD HAIR 91 Hair that stays on your head is GOOD HAIR Hair that grows in the normal genetically determined density without fragility and inflammatory attack is GOOD HAIR A pain-free and pruritus-free scalp grows GOOD HAIR 92 46
Hair that stays on your head is GOOD HAIR Hair that grows in the normal genetically determined density without fragility and inflammatory attack is GOOD HAIR A pain-free and pruritus-free scalp grows GOOD HAIR Hair care practices that allow you to live your life healthfully using whatever additions one desires leads to GOOD HAIR 93 THANK YOU FOR YOUR ATTENTION! amcmicha@wakehealth.edu North American Hair Research Society Cicatricial Alopecia Research Foundation National Alopecia Areata Foundation www.nahrs.org www.carfintl.org www.naaf.org 94 47