863 Central centrifugal cicatricial alopecia gene expression analysis revealed cholesterol, fatty acid, and mast cell pathways

Abstract

Central centrifugal cicatricial alopecia (CCCA) is a primary lymphocytic scarring alopecia that presents as inflammation, pain and scarring hair loss at the scalp vertex primarily in women of African descent. It is estimated that between 6-8% of individuals of African descent have CCCA with the incidence rising in populations over 50 years of age, although CCCA is thought to be grossly underreported. Its onset has been associated with the use of hair straightening practices, suggesting mechanical factors in the hair shaft may predispose in part to CCCA. Current standard treatments are largely guided by expert opinion and include topical and injection corticosteroid therapies as well as oral tetracycline. To initiate a molecular analysis of CCCA, RNAseq analysis was performed on scalp biopsies of 5 CCCA patients compared to healthy control subjects. We identified three major pathways associated with CCCA: 1) downregulation of steroid/cholesterol/fatty acid pathways (ACAA1 and FASN); 2) upregulation of fibrosis and hypertrophic scarring pathways (COL1A1, BMP10, and CLDN5); and 3) upregulation of a mast cell signature (TPSAB1, MS4A2, and CMA1). Consistent with the molecular analysis, the histology of CCCA lesions displayed infiltration of mast cells, especially around the fibrotic tissue surrounding the remaining hair follicles. Current treatments involving immunomodulatory modalities are not clinically efficacious, consistent with the lack of immune and inflammatory pathway dysregulation in our analyses. Since the same three core pathways are shared among all cicatricial alopecias, rational development of therapies focusing on restoring cholesterol and fatty acid metabolism, and downregulation of fibrosis and mast cells may hold promise for improved clinical outcomes. Leveraging this core set of pathways to inform new therapies, these findings provide a paradigm in which to develop new treatments for CCCA as well as other primary cicatricial alopecias.