Central centrifugal cicatricial alopecia: A common but under‐recognized and under‐treated disease finally comes of age

Most healthcare providers have not heard of central centrifugal cicatricial alopecia (CCCA). This is a common condition most familiar to those dermatologists and dermatopathologists involved in the care of African Americans, but it has received little attention in the general medical literature. Perhaps this is because the disease is confined to the scalp, is often considered only of cosmetic importance, and can be easily hidden from view by the use of wigs or other hairstyles. Early treatment is key to preventing severity and progression. A recent article in the New England Journal of Medicine focusing on CCCA is remarkable because it represents the first time that CCCA has been discussed in a prestigious journal catering to a global audience of healthcare providers. Also, it represents one of the few times that bench science has been utilized to study the condition. Finally, this article about the PADI3 gene and CCCA suggests a possible heritable basis for CCCA. CCCA was first described in 1968. The pioneer authors correctly identified the condition as a form of inflammatory scarring (cicatricial) hair loss affecting African Americans. They attributed the inflammation to the use of traumatic hair styling with hot combs, and thus called it “hot comb alopecia. ” Subsequently, hot comb alopecia was largely ignored in the medical literature for decades, but was then revisited by two dermatology-trained dermatopathologists, and renamed “the follicular degeneration syndrome (FDS). ” Pathologists have long used histopathologic findings to create hypotheses regarding disease pathogenesis, and this became true for CCCA. By 1992, the use of chemical hair relaxers had largely replaced hot combs in the African-American community. The authors of the FDS paper described the histopathologic features of the disease, debunked the notion that hot combs were causative, and proposed a hypothesis for pathogenesis based on histopathologic findings. In 1994, the condition was expanded to include men as well as women, and an effective treatment regimen was described. Eventually, the name of the condition was altered to the clinically descriptive term “central centrifugal cicatricial alopecia,” a name that is now familiar to a new generation of dermatologists and dermatopathologists. Numerous papers have been published in the dermatology literature about CCCA, but few have applied the tools of bench science to understand the disease. Some studies have implicated the inner root sheath (IRS) of the hair follicle as underlying CCCA, a hypothesis already proposed in 1992 (Figure 1). In simplified terms, the IRS interlocks tightly with the hair shaft, serving as a cornified “gasket” to seal off the lowermost portion of the hair follicle from environmental/ external insults (eg, shampoos, permanent dyes, bacteria, yeast, hair relaxers, etc.). The most specific and consistent histopathologic feature of CCCA is premature desquamation of the IRS (PDIRS), opening a potential route for external irritants to penetrate deep into the follicle. In CCCA, unlike other forms of cicatricial alopecia (such as discoid lupus erythematosus or lichen planopilaris), only follicles showing PDIRS are susceptible to inflammation and eventual destruction (Figures 2 and 3). External factors such as traction and chemical styling play an important role in CCCA, but the underlying problem is an anatomical abnormality under genetic control. At long last, researchers have applied modern scientific approaches to identify a genetic variant associated with CCCA. Using exome sequencing of DNA isolated from women with CCCA, they identified mutations in PADI3 in 5 of 16 individuals. These variants The opinions and assertions expressed herein are those of the authors and do not necessarily reflect the official policy or position of the Uniformed Services University or the U.S. Department of Defense. Received: 16 June 2021 Revised: 19 August 2021 Accepted: 31 October 2021