An update of the pathogenesis of frontal fibrosing alopecia: What does the current evidence tell us?

Frontal fibrosing alopecia (FFA) is a primary patterned cicatricial alopecia with a complicated pathogenesis yet to be fully understood. FFA appears to be increasing in incidence worldwide, especially in the last decade. In order to consider current treatment options, we reviewed current evidence for its pathogenesis comprising immune-mediated, genetic, hormonal and environmental factors. Th1-mediated inflammation with collapse of hair follicle immune privilege and bulge epithelial stem cell destruction, peroxisome proliferator-activated receptor gamma (PPAR-γ) depletion and epithelial-mesenchymal transition are key events leading to permanent hair follicle destruction in FFA. Although the vast majority of cases are sporadic, familial reports of FFA implicate genetic or epigenetic mechanisms in its pathogenesis. The frequent onset of FFA in post-menopausal women, similar patterning and co-existence with female pattern hair loss, together with a reportedly good response to 5α-reductase inhibitors suggest a role for sex steroid hormones. The reported increasing incidence invites speculation for, yet unproven, environmental triggers such as sun exposure and topical allergens. More robust research into this unique entity is required to help understand the complexity of the pathogenesis of FFA in order to find satisfactory therapeutic targets for this often distressing condition.