Central Centrifugal Cicatricial Alopecia

Amy McMichael, MD Professor and Chair Department of Dermatology Wake Forest Baptist Health Winston-Salem, NC SEC 2019 DISCLOSURE/CONFLICTS OF INTEREST

Investigator Consultant

Allergan Johnson & Johnson Intendis Procter & Gamble Procter & Gamble Stiefel Samumed Allergan Casseopia Bayer Concert Galderma Alcaris Incyte Incyte Samumed Aclaris Anacor Pfizer Nutrafol Bioniz 157 articles on “hair loss and African Americans” in Pub Med from 1968 – 2019 99 articles on Central Centrifugal Cicatricial Alopecia 101 articles on Pseudofolliculitis barbae 349 Frontal fibrosing alopecia (225 articles in 2017) 4214 articles on alopecia areata >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 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 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%

Davis SA, et al. J Drugs Dermatol 2012 CENTRAL CENTRIFUGAL SCARRING ALOPECIA EPIDEMIOLOGY

▪ Prevalence ranges from 2.7% in 604 South African women to 5.6% in 529 US women1,2 ▪ 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 • Hopkins study of 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

• Microarray data from 5 CCCA patients suggesting upregulation of critical genes implicated in fibroproliferative disorders in the gene expression profile of patients with CCCA – Aguh et al, JAAD 2018 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 ▪ 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) ▪ CallenderV, Wright D, Davis E, Sperling L Arch Dermatol 2012 Tosti and Miteva, Skin Appendage 2015 My patient  Dermatoscopic evaluation: can be followed with treatment

 Perifollicular scale and erythema activity  Significant loss of follicular openings burnt out disease  Miniaturization of hair shafts possible ability to recruit and have regrowth ▪ 10 women with bx-proven CCCA ▪ Clinical and dermatoscopic photographs obtained from clinically active alopecic site and clinically- unaffected posterior scalp ▪ All 10 patients with histologic changes of CCCA 4 cm below clinical changes ▪ Dermatoscopic findings suggest early changes of CCCA and correlate with path ▪ Dermoscopy may be reliable, less invasive option to visualize CCCA changes ▪ Early treatment in proximal areas may reduce disease severity and improve quality of life for CCCA patients

▪ 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

▪ Collaborative study with U.S. and S. African patients and Genetics group in Israel ▪ 16 patients, identified one splice site and three heterozygous missense mutations in PADI3 ▪ PADI3 encodes peptidyl arginine deiminase, type III (PADI3), an enzyme that post- translationally modifies other proteins essential to hair-shaft formation ▪ Uncombable hair syndrome shown in some cases to involve mutations in PADI3- (no alopecia) ▪ Mutations resulted in reduced PADI3 expression, abnormal intracellular localization of the protein, and decreased enzymatic activity ▪ Immunofluorescence staining showed decreased expression of PADI3 in biopsy samples of scalp skin from patients with CCCA ▪ Replication set of 42 patients was directly sequenced. Combining data sets, we found pathogenic variants in 14 out of 58 affected patients (24%). Liron Malki et al, New England Journal of Med, Feb 2019 Stained with anti-PADI3 specific antibodies ▪ 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  Discuss Genetic predisposition with patients to increase awareness  +/- Biopsy for extent of inflammation/alternate diagnosis  Decrease all traumatic styling methods and heat behaviors to vertex scalp

 Inflammatory Stage ▪ Moisturizing anti-dandruff shampoos weekly ▪ Decrease inflammation via topical and intralesional corticosteroids ▪ IL Kenalog for 8 rounds with 5.0-7.5 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 ▪ Long term topical steroids ▪ Minoxidil solution for prolongation of anagen ▪ Surgical restoration ▪ ?PRP  Discuss Genetic predisposition with patients to increase awareness  +/- Biopsy for extent of inflammation/alternate diagnosis  Decrease all traumatic styling methods and heat behaviors to vertex scalp  CARF – Cicatricial Alopecia Research Foundation  Skin of Color Society short film (www.skinofcolorsociety.org)

 Post-inflammatory treatment ▪ Long term topical steroids ▪ Minoxidil solution for prolongation of anagen ▪ Surgical restoration ▪ ?PRP ▪ Scarring alopecia difficult to treat ▪ Treatment often leads to disappointing outcomes for patients ▪ Idea is to rescue and recruit hairs that are undecided in their fate ▪ Must rescue hairs that are under inflammatory attack but have not succumbed to fibrosis ▪ Stabilization may be the outcome but may see improved density

Pre-treatment Post-medical treatment Post-surgical treatment DINA Y, AGUH C. DERMATOL SURG. 2018 NIGERIAN WOMAN TREATMENT : IL KENALOG AND HAIR RESTORATION

Pretreatment Post-treatment

6 mo weave in 9 mo/treatment place

Pre-treatment 3 mo/treatment ▪ Use your dermatoscope to look for early disease ▪ Discuss known genetics with CCCA patients to encourage family members to share their experience ▪ Manage traction-related hair care practices ▪ Aggressively manage anti-inflammatory treatments ▪ In post-inflammatory stage, use minoxidil (off-label) and continue topical steroids ▪ Follow these patients yearly to ensure stable disease ▪ Refer for surgical restoration in appropriate cases THANK YOU FOR YOUR ATTENTION!

[email protected]

North American Hair Research Society www.nahrs.org Cicatricial Alopecia Research Foundation www.carfintl.org National Alopecia Areata Foundation www.naaf.org