Alopecia areata: from pathophysiology to therapeutic innovation

Abstract

Alopecia areata (AA) is a chronic disease characterized by non-scarring hair loss, ranging from patches on the scalp to total body hair loss. The major event in the pathophysiology of AA is the breakdown of the immune privilege of the hair follicle caused by increased local production of interferon-gamma (IFN-γ). As a result, in the majority of the cases, there is autoantigen recognition with infiltration of autoreactive T cells, and a series of inflammatory changes in the hair follicle microenvironment, largely mediated by the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Based on these pathophysiological findings, the JAK-STAT pathway has been defined as a therapeutic target in AA, with JAK inhibitors emerging as an alternative to traditional nonspecific treatments. Initially, first-generation oral JAK inhibitors (baricitinib, tofacitinib, and ruxolitinib) and, more recently, second-generation oral JAK inhibitors (ritlecitinib, brepocitinib, upadacitinib, and abrocitinib) have demonstrated efficacy and safety in the treatment of AA. Following positive results from the BRAVE-AA1 and BRAVE-AA2 studies, oral baricitinib (Olumiant) became the first drug ever approved for the treatment of AA on 13 th June 2022. In contrast, topical JAK inhibitors, as well as other novel therapies such as phosphodiesterase-4 inhibitors (apremilast) and biologics (dupilumab, secukinumab, and aldesleukin), appear to have limited efficacy in the treatment of AA, with the possible exception of dupilumab. Thus, the aim of this article is to review the pathophysiological mechanisms and new targeted treatments in AA, with a special focus on JAK inhibitors.

Exploring Phytotherapy For Alopecia: Efficacy, Mechanisms, And Future Directions

“…Telogen effluvium is often triggered by stress, hormonal changes, or illness, leading to an increased number of hairs entering the resting phase (telogen) of the hair cycle. Anagen effluvium is typically caused by the interruption of the anagen (growth) phase due to toxins, such as chemotherapy drugs (Peter et al, 2013, Lourenço & Gonçalo, 2023Fukuyama et al, 2022). Other forms of alopecia, such as telogen effluvium, are characterized by a disruption in the normal hair growth cycle, often triggered by stress, illness, or hormonal changes.…”