Gene expression profiling suggests severe, extensive central centrifugal cicatricial alopecia may be both clinically and biologically distinct from limited disease subtypes.

The natural history of central centrifugal cicatricial alopecia (CCCA) is widely variable. Some patients experience rapid progression to extensive, end-stage disease while others never approach extensive involvement over decades, suggesting heterogeneity in CCCA disease phenotype. To better characterize clinically severe disease in CCCA, tissue samples were obtained from the peripheral, hair-bearing lesional scalp of women with clinically focal, limited and extensive CCCA disease involvement. A microarray analysis was conducted to identify differential expression of genes previously identified to be preferentially expressed in the lesional scalp vs. non-lesional scalp of CCCA patients. Clinically extensive, severe CCCA was characterized by increased expression of MMP9, SFRP4 and MSR1 when directly compared with focal and limited disease. These biomarkers correspond to dysregulated pathways of fibrosis, Wnt signalling and macrophage-mediated inflammatory processes respectively. These findings hold significance for both possible targets for future study of prognostic markers of disease severity and new potential therapeutic targets. In summary, this study suggests clinically extensive, severe CCCA may have a differential gene expression pattern in the lesional scalp of affected patients, in addition to its clinical distinction.

Disorders of Hypopigmentation

Hypopigmentation and depigmentation of the skin can be due to multiple causes and has a broad differential diagnosis. The most common cause of depigmentation worldwide is vitiligo. This disorder affects 1-2% of the world's population and is seen in all races. Vitiligo is an autoimmune disorder in which the predominant cause is an attack by CD8+ cytotoxic T cells on melanocytes in the epidermis. This condition can have a significant negative impact on the quality of life of affected individuals. Treatment options currently include psychological counseling, topical therapy, systemic therapy, phototherapy, surgical therapy, and depigmentation. In patients with stable, refractory disease, successful repigmentation has been achieved using mini-punch grafting, blister grafting, and non-cultured epidermal suspension (NCES) grafting. Emerging therapies include the Janus kinase (JAK) inhibitors ruxolitinib and tofacitinib. Further studies exploring the pathogenesis of vitiligo are warranted in order to optimize treatment for affected patients. J Drugs Dermatol. 2019;18(3 Suppl):s115-116.

Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is a primary cicatricial alopecia that most commonly affects women of African descent. Like CCCA, fibroproliferative disorders (FPDs) such as keloids, atherosclerosis, and fibroids are characterized by low-grade inflammation and irritation, resulting in end-stage fibrosis. OBJECTIVE: We sought to determine whether fibroproliferative genes were up-regulated in patients with CCCA. METHODS: A total of 5 patients with biopsy-proven CCCA were recruited for this study. Two scalp biopsy specimens were obtained from each patient; 1 from CCCA-affected vertex scalp and 1 from the unaffected occipital scalp. Microarray analysis was performed to determine the differential gene expression patterns. RESULTS: There was an upregulation of genes implicated in FPDs in patients with CCCA. Specifically, we noted increased expression of platelet derived growth factor gene (PDGF), collagen I gene (COL I), collagen III gene (COL III), matrix metallopeptidase 1 gene (MMP1), matrix metallopeptidase 2 gene (MMP2), matrix metallopeptidase 7 gene (MMP7), and matrix metallopeptidase 9 gene (MMP9) in affected scalp compared with in unaffected scalp. Significant overlap in the canonic pathways was noted between patients with CCCA and patients with both atherosclerosis and hepatic fibrosis (P < .001). LIMITATIONS: Small sample size and the use of whole skin tissue for analysis. CONCLUSION: We have identified the upregulation of critical genes implicated in FPDs in the gene expression profile of patients with CCCA. These findings may help identify future therapeutic targets for this otherwise difficult-to-treat condition.

Presence of Uterine Leiomyomas Has No Significant Impact on Gene Expression Profile in the Scalp of Patients with Central Centrifugal Cicatricial Alopecia.

Central centrifugal cicatricial alopecia (CCCA) is associated with increased expression of genes implicated in fibroproliferative disorders and a higher prevalence of uterine leiomyomas (ULs) among affected individuals. We sought to examine the effect of UL status on the gene expression profile of the lesional scalp in patients with CCCA. Scalp biopsy was obtained from 16 patients with a confirmed diagnosis of CCCA between 2017 and 2020. Microarray analysis was used to identify differential gene expression between patients with CCCA with a history of UL and those without the history. Of more than 20,000 genes analyzed, 23 of 25 genes with the highest expression in patients with CCCA with UL held no statistical significance. No genes previously implicated in fibroproliferative disorders were found among the upregulated transcripts. Of all genes analyzed, only eight upregulated genes and zero downregulated genes had a fold change in expression >2 in patients with CCCA with UL compared with those in patients with CCCA without UL. Our findings highlight similar gene expression patterns in the lesional scalp of patients with CCCA with and without a history of UL. This analysis is key in highlighting no evidence of causational or linked mechanobiology that accounts for the increased prevalence of UL seen in patients with CCCA that previous studies have not addressed.