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

Abstract

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.

Keywords: alopecia; central centrifugal cicatricial alopecia; cicatricial alopecia; fibroproliferative disorders; fibrosis.

FIGURE 1

Spectrum of CCCA disease severities: Patients with stage 1B (focal, (A)), stage 3B (limited, (B)) and stage 5B (extensive, (C)) disease