HAIR FOLLICLE STEM CELLS IN THE PATHOGENESIS OF PRIMARY CICATRICIAL ALOPECIA

Abstract

Background: Primary cicatricial alopecia )PCA) is a scarring disease. Although the scarring and deformity may affect any part of the body, such changes have been reported to be most obvious on the face and scalp. The pathogenesis behind this scarring process is not well understood. Once lesions have scarred, recurrent disease tends to occur at the edge of the scarred lesions but not within them. The fact that inflammation in PCA generally involves the bulge area of the hair follicles raises the possibility that damage to the stem cells of the bulge region may be one process leading to the permanent loss of hair follicles. Objective : The aim of this study was to investigate the role of the epithelial hair follicle stem cells which reside in the bulge region in the scarring process in PCA. Methods : We studied the reactivity to Mouse monoclonal antibody, Keratin 15 Ab-1 (LHK15), which recognizes cytokeratin (CK 15) and preferentially immunostains epithelial hair follicle stem cells without staining the remaining hair follicle, on skin biopsies (scalp lesions) from 40 patients with PCA (8 lichen planopilaris, 10 discoid lupus erythematosus, 7 folliculitis decalvans, 5 keratosis follicularis spinulosa decalvans, 10 acne keloid). Reactivity to Mouse monoclonal anti CD8 antibody (cd8-sp16) in cases of prominent inflammatory infiltrate( 16 cases) was studied. Ten normal scalp biopsy specimens served as controls. The correlation between the extent of the cytotoxic inflammatory cell infiltrate(CD8+) and the presence of stem cells was investigated. Results were analyzed semiquantitatively. Results : The expression of CK15 in epithelial hair follicle stem cells was absent at scarred PCA, and in cases of severe inflammation, it was weak or absent. There was normal to moderate CK15 expression at the bulge region of hair follicles when surrounded by mild or moderate inflammatory infiltrate (CD8+). Conclusion : The bulge region appears to be involved in these diseases as a part of a broader involvement of the hair follicles; it is secondarily affected by the surrounding inflammatory cell infiltrate. Expression of CK15 immunostain was diminished and was then absent, indicating either damage to stem cells or differentiation to help in the repair process. Damage to follicular stem cells may help to explain the irreversible alopecia and the scarring process which characterize these diseases.
Key words : cytokeratin 15, primary cicatricial alopecia, hair follicle, scar, stem cell, hair bulge.