The Pathogenesis of Primary Cicatricial Alopecias

Abstract

Cicatricial (scarring) alopecia results from irreversible damage to epithelial stem cells located in the bulge region of the hair follicle, generally as a result of inflammatory mechanisms (eg, in the context of autoimmune disease). In primary cicactricial alopecia (PCA), the hair follicle itself is the key target of autoaggressive immunity. This group of permanent hair loss disorders can be classified into distinct subgroups, characterized by the predominant peri-follicular inflammatory cell type. In none of these PCA forms do we know exactly why hair follicles begin to attract such an infiltrate. Thus, it is not surprising that halting or even reversing this inflammation in PCA is often extremely difficult. However, increasing evidence suggests that healthy hair follicle epithelial stem cells enjoy relative protection from inflammatory assault by being located in an immunologically "privileged" niche. Because this protection may collapse in PCA, one key challenge in PCA research is to identify the specific signaling pathways that endanger, or restore, the relative immunoprotection of these stem cells. After a summary of pathobiological principles that underlie the development and clinical phenotype of PCA, we close by defining key open questions that need to be answered if more effective treatment modalities for this therapeutically very frustrating, but biologically fascinating, group of diseases are to be developed.

Eradication of damaged keratinocytes in cutaneous lichen planus forms demonstrated by evaluation of epidermal and follicular expression of CK15, indices of apoptosis and regulatory protein S100

“…TUNEL reaction findings obtained by us are in accordance with evidence demonstrated by Bloor et al and confirmed by Harries et al reporting on increase of TUNEL positive epithelial cells in LP [14,24,40]. The results of TUNEL reaction supported by AI counting and ultrastructural analysis performed suggest that among patient groups analyzed in this study the basal and suprabasal keratinocyte damage was especially pronounced in the LPP of the scalp region, thus with high probability explaining hair loss.…”

“…Various triggers have been proposed as potential -infections, drug reactions, reactions to metal [9,10], vaccinations [11] and stress [12,13]. The role of genetic factors in the pathogenesis of primary cicatricial alopecias (PCA) including those related to autoimmune matter has been studied as well [7,14].…”

“…These multipotent stem cells, called epithelial hair follicle stem cells (eHFSCs), are located in the bulge region -specifically, at the insertion site of the arrector pili muscle in the outermost layer of the outer root sheath [14,15] -and contribute to repopulation of the epidermis after injury. According to the results published by Abbas et al (2009Abbas et al ( , 2011, Kloepper et al (2008), and Sabeti et al (2013) [16,17,18,19] cytokeratin 15 (CK15), a stem cell marker, labels the cells in the bulge region of the human hair follicle, the outermost layer of the outer root sheath, the basal layer of the epidermis and eccrine glands, whereas other researchers found that the basal layer of normal epidermis is usually negative for CK15, and the bulge stem cells do not contribute to the interfollicular epidermis reconstitution [20].…”

Lichen planopilaris: Demographic, clinical and histopathological characteristics and treatment outcomes of 25 cases

“…LPP'nin patogenezi tam olarak aydınlatılamamıştır 1,2 . Ancak, erektör pili kasının kıl follikülünün fibröz kök kılıfına tutunma noktası olan ve "bulge" adı verilen bölgedeki folliküler epitelyal kök hücrelerin bilinmeyen bir nedene bağlı olarak oluşan otoimmün hasarının rol oynadığı öne sürülmüştür 12 . LPP'nin klinik formlarının klasik klinik özellikleri olmakla birlikte bunlar alopesiye neden olan diğer hastalıklarla iç içe geçebilir ve/veya hastalık ilerledikçe değişime uğrayabilir 4,13 .…”

Primary cicatricial alopecia: diagnosis and treatment

“…3 Hair regeneration is prevented because of destruction of epithelial stem cells in the bulge of the outer root sheath at the level where the arrector pili muscle inserts ( Figure 1). 4,5 Secondary cicatricial alopecia is also irreversible, though destruction of the hair follicle is incidental to a non-follicle-directed cause, such as thermal burns, metastatic cancer, trauma or radiation. 4 This article will focus on primary cicatricial alopecia.…”