Alopecia areata: Current understanding of the pathophysiology and update on therapeutic approaches, featuring the Japanese Dermatological Association guidelines

Abstract

Alopecia areata (AA) is a relatively common nonscarring hairloss disease characterized by an autoimmune response to anagen hair follicles (HFs). Accumulated evidence suggests that collapse of the HF immune privilege subsequent to triggering events, represented by viral infection, leads to autoimmune response in which autoreactive cytotoxic CD8+NKG2D+ T cells mainly target exposed HF autoantigens. AA had been recognized as type 1 inflammatory disease, but recent investigations have suggested some roles of type 2‐ and Th17‐associated mediators in AA pathogenesis. The significance of psychological stress in AA pathogenesis is less emphasized nowadays, but psychological comorbidities, such as depression and anxiety, attract greater interest in AA management. In this regard, the disease severity may not solely be evaluated by the extent of hair loss. Use of trichoscopy markedly improved the resolution of the diagnosis and evaluation of the phase of AA, which is indispensable for the optimization of treatment. For the standardization of AA management, the establishment of guidelines/expert consensus is pivotal. Indeed, the Japanese Dermatological Association (JDA) and other societies and expert groups have published guidelines/expert consensus reports, which mostly recommend intralesional/topical corticosteroid administration and contact immunotherapy as first‐line treatments, depending on the age, disease severity, and activity of AA. The uniqueness of the JDA guidelines can be found in their descriptions of intravenous corticosteroid pulse therapy, antihistamines, and other miscellaneous domestically conducted treatments. Considering the relatively high incidence of spontaneous regression in mild AA and its intractability in severe subsets, the importance of course observation is also noted. Evidenced‐based medicine for AA is currently limited, however, novel therapeutic approaches, represented by JAK inhibitors, are on their way for clinical application. In this review, the latest understanding of the etiopathogenesis and pathophysiology, and update on therapeutic approaches with future perspectives are summarized for AA, following the current version of the JDA AA management guidelines.

Lifestyle Factors Involved in the Pathogenesis of Alopecia Areata

“…Alopecia areata is a common form of immune-mediated alopecia in which the autoimmune attack of the hair follicle results in non-scarring hair loss, which is characterized by a range of circular patches on the scalp. The estimated lifetime risk of alopecia areata has been reported to be 1.7-2.1% [9]. Approximately 20% of cases are children, with 60% of alopecia areata patients recognizing their first hair loss patch before 30 years of age [10].…”

“…Because of the immunological pathogenesis of alopecia areata, various therapeutic options are currently available to regulate hair follicle inflammation. Consistently, topical steroid and immunomodulator therapy with squaric acid dibutylester (SADBE) are effective treatments [9]. Environmental factors influence immunological actions in various inflammatory diseases; therefore, daily lifestyle factors are also associated with the development of alopecia areata.…”

How Our Microbiome Influences the Pathogenesis of Alopecia Areata

“…Viral infections, as with other autoimmune diseases [ 88 ], have also been implicated in the pathogenesis of alopecia areata, especially infections of Epstein-Barr virus, hepatitis B and C [ 89 ], and even recently SARS-CoV-2 [ 90 ]. As discussed in previous sections, the activation of IFN-α-producing PDCs by viral infection is an important mechanism that establishes this relationship [ 50 , 52 ].…”

Comparative study between topical steroid alone versus combined fractional Erbium:YAG laser with topical steroid in treatment of alopecia areata

“…Topical corticosteroids act as an anti-in ammatory agent decreasing the dense peribulbar in ltrate allowing the hair follicle to restore the normal hair growth cycle 19 . Due to its easy and painless application and wide safety margin, it is considered the rst line of treatment in children.…”