Alopecia Areata: A Review of Disease Pathogenesis

F. Rajabi; L.A. Drake; M.M. Senna; N. Rezaei


The British Journal of Dermatology. 2018;179(5):1033-1048. 

In This Article

Abstract and Introduction


Background: Alopecia areata is a disorder that results in nonscarring hair loss. The psychological impact can be significant, leading to feelings of depression and social isolation.

Objectives: In this article, we seek to review the pathophysiological mechanisms proposed in recent years in a narrative fashion.

Methods: We searched MEDLINE and Scopus for articles related to alopecia areata, with a particular emphasis on its pathogenesis.

Results: The main theory of alopecia areata pathogenesis is that it is an autoimmune phenomenon resulting from a disruption in hair follicle immune privilege. What causes this breakdown is an issue of debate. Some believe that a stressed hair follicle environment triggers antigen presentation, while others blame a dysregulation in the central immune system entangling the follicles. Evidence for the latter theory is provided by animal studies, as well investigations around the AIRE gene. Different immune-cell lines including plasmacytoid dendritic cells, natural killer cells and T cells, along with key molecules such as interferon–γ, interleukin–15, MICA and NKG2D, have been identified as contributing to the autoimmune process.

Conclusions: Alopecia areata remains incurable, although it has been studied for years. Available treatment options at best are beneficial for milder cases, and the rate of relapse is high. Understanding the exact mechanisms of hair loss in alopecia areata is therefore of utmost importance to help identify potential therapeutic targets.


Alopecia areata (AA) is a nonscarring hair loss disorder with an unpredictable course and a wide spectrum of manifestations. It affects both sexes equally, with a cumulative lifetime incidence of about 2% and no significant racial predominance.[1–3] The condition is known to carry a considerable impact on health-related quality of life.[4–6]

AA is usually diagnosed clinically by the characteristic narrowing of the hair shaft near the scalp (exclamation mark hair). Histopathological studies may be required in some cases in which the lesions reveal peribulbar lymphocytic infiltration.[7] The infiltration consists of CD8+ T cells in the follicular epithelium and CD4+ T cells around the hair follicles (HFs).[8]

Currently, available treatments for AA have limited responses, with success rates varying from 23% to 75%.[9,10] Detailed knowledge of the pathophysiological events is a prerequisite for an effective target-oriented treatment with fewer side-effects. In this review, we seek to understand the precise mechanisms involved in the pathophysiology of AA.