Alopecia areata: a review of disease pathogenesis

Br J Dermatol. 2018 Nov;179(5):1033-1048. doi: 10.1111/bjd.16808. Epub 2018 Sep 9.

Abstract

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.

Publication types

  • Review

MeSH terms

  • AIRE Protein
  • Alopecia Areata / drug therapy
  • Alopecia Areata / immunology*
  • Alopecia Areata / pathology
  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / pathology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Hair Follicle / cytology
  • Hair Follicle / immunology*
  • Hair Follicle / pathology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immune Privilege*
  • Immunologic Factors / therapeutic use*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism
  • Keratinocytes / immunology
  • Keratinocytes / pathology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K / immunology
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Recurrence
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / immunology
  • Treatment Outcome

Substances

  • Histocompatibility Antigens Class I
  • Immunologic Factors
  • Interleukin-15
  • MHC class I-related chain A
  • NK Cell Lectin-Like Receptor Subfamily K
  • Transcription Factors
  • Interferon-gamma