GUEST EDITORIAL Updates in Our Understanding of Central Centrifugal Cicatricial Alopecia Crystal Aguh, MD t has been more than 50 years since central centrifugal other fibroproliferative disorders, in affected scalp of cicatricial alopecia (CCCA) was first defined by LoPresti patients with CCCA.7 Most notably, an expression in gene Iand colleagues1 as hot comb alopecia. Fifty years later, we overlap was noted between fibroids and CCCA in this are only just starting to understand the pathogenesis of study, though the relationship between these two diseases CCCA and its systemic implications. needs to be further explored. Then and Now Gene Variants Identified in CCCA The use of hot combs, a metal device used to straighten More recently, a copynew study has identified a gene variant naturally curly hair, was ubiquitous in the households of of peptidyl arginine deiminase 3, PADI3, that is present black women in the 1960s. It is no surprise then that this in approximately one-quarter of studied patients with styling process was labeled as the culprit of this disease CCCA.8 PADI3 plays a role in hair shaft formation and has that affects black women almost exclusively. As the use of been implicated in another hair disorder, uncombable hair hot combs waned but the prevalence of CCCA persisted, syndrome,not though the latter presents in children, improves its name evolved to chemically induced alopecia—an ode with age, and is not associated with a scarring phenotype.9 to the popular styling product of the 1990s, the chemical However, this study has provided greater insight into our relaxer—and eventually CCCA, a name that reflectsDo its understanding of CCCA by establishing a possible genetic clinical progression and histologic findings.2 predisposition in patients affected with this disease.8 Since then, research has explored the association with systemic diseases, some noting increased rates of type 2 What’s Next for CCCA? diabetes mellitus and thyroid disease, and more recently, For years, many patients with CCCA have been turned an increased rate of fibroids in affected patients.3,4 away with few answers and left thinking that it is their own styling habits that have led to their hair loss, when Clues to Pathogenesis in fact the data we have now suggest a possible link with Compared to other primary cicatricial alopecias, CCCA other systemic diseases and a genetic predisposition for is unique in that active progressionCUTIS is difficult to detect. disease. Armed with this knowledge, we can start working Symptoms, such as pruritus, often are minimal or absent, to identify treatment options and discuss strategies for early rendering clinical assessment quite difficult.5 Unlike other detection of CCCA. Future research should address 1 of forms of scarring hair loss, fibrosis, not inflammation, is 4 large domains: (1) understanding the influence of PADI3 the predominant clinical feature. The clinical presenta- on the scarring pattern seen in CCCA and identifying addi- tion is not unlike a group of disorders termed fibroprolif- tional genetic variants implicated in CCCA; (2) identifying erative disorders, which includes systemic sclerosis, uterine what, if any, inheritance pattern is associated with CCCA; fibroids, atherosclerosis, and keloids, among others. It has (3) identifying other systemic disease associations; and been postulated that diseases of aberrant scarring are more (4) optimizing treatment options for patients with CCCA. common in black individuals due to the protective effect The future is bright for CCCA. Although our under- profibrotic alleles have against endemic helminthic infec- standing of CCCA is still in its infancy, it is my hope that tions of sub-Saharan infections, including oncocerciasis.6 with greater understanding of this disease will come A recent study showed an increased expression of greater empathy for our patients. fibroproliferative genes, particularly those implicated in CONTINUED ON PAGE 340 From Johns Hopkins School of Medicine, Baltimore, Maryland. The author reports no conflict of interest. Correspondence: Crystal Aguh, MD, Johns Hopkins Department of Dermatology, 601 N Caroline St, JHOC 8th Floor, Baltimore, MD 21287. 316 I CUTIS® WWW.MDEDGE.COM/DERMATOLOGY Copyright Cutis 2019. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. GUEST EDITORIAL CONTINUED FROM PAGE 316 REFERENCES 1. LoPresti P, Papa CM, Kligman AM. Hot comb alopecia. Arch Dermatol. 1968;98:234-238. 2. Gathers RC, Lim HW. Central centrifugal cicatricial alopecia: past, present, and future. J Am Acad Dermatol. 2009;60:660-668. 3. Kyei A, Bergfeld WF, Piliang M, et al. Medical and environmental risk factors for the development of central centrifugal cicatricial alopecia: a population study. Arch Dermatol. 2011;147:909-914. 4. Dina Y, Okoye GA, Aguh C. Association of uterine leiomyomas with cen- tral centrifugal cicatricial alopecia. JAMA Dermatol. 2018;154:213-214. 5. Whiting DA, Olsen EA. Central centrifugal cicatricial alopecia. Dermatol Ther. 2008;21:268-278. 6. Hellwege JN, Torstenson ES, Russell SB, et al. Evidence of selection as a cause for racial disparities in fibroproliferative disease. PLoS One. 2017;12:e0182791. doi:10.1371/journal.pone.0182791. 7. Aguh C, Dina Y, Talbot CC Jr, et al. Fibroproliferative genes are prefer- entially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. 2018;79:904.e1-912.e1. 8. Malki L, Sarig O, Romano MT, et al. Variant PADI3 in central centrifugal cicatricial alopecia. N Engl J Med. 2019;380:833-841. 9. Matis WL, Baden H, Green R, et al. Uncombable-hair syndrome. Pediatr Dermatol. 1987;4:215-219. copy not Do CUTIS 340 I CUTIS® WWW.MDEDGE.COM/DERMATOLOGY Copyright Cutis 2019. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher..