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Alopecia areata pathogenesis: known genetic background, unknown environmental triggers

Presented By
Prof. Rodney Sinclair , University of Melbourne, Australia
SPIN 2022

Alopecia areata (AA) is a polygenic and multifactorial autoimmune disease that results in non-scarring hair loss. Both local and systemic environmental factors can trigger the disease.

As Prof. Rodney Sinclair (University of Melbourne, Australia) pointed out, AA is a multifactorial disease with a known genetic background and unknown environmental triggers [1]. Both innate and acquired immunity are involved in the pathogenesis of AA. In a genome-wide association study, 139 single nucleotide polymorphisms could be identified that are significantly associated with AA [2]. Unknown environmental triggers can be divided into local and systemic factors. Local factors are a loss of hair follicle immune privilege causing inflammatory cells to swarm and attack the hair bulb in what is known as the “swarm of bees”. Both intrafollicular CD8 cells and multiple cytokines and chemokines are involved in this process. Systemic factors that might trigger AA are increased serum IFN-γ and serum autoantibodies.

Regrowth within 12 months in most cases of AA

According to textbooks, in 50% of patients, hair will regrow spontaneously within 6 months. In 70% of cases, recovery will occur within 12 months. “But what we notice is that the 30% of patients who have persistent AA over 12 months come back to us,” Prof. Sinclair said, signalling an unmet need. According to an Australian expert consensus statement, patients with a solitary stable patch of AA <12 months have only a 13% risk of developing chronic AA. However, 30.6% of patients with chronic AA will progress to alopecia totalis if not on treatment [3]. As Prof. Sinclair pointed out, the question is whether therapy can alter the risk of progression in chronic AA. This seems to be the case with systemic corticosteroids. “Systemic steroids are the treatment most commonly used, but 50% will relapse if the dose is reduced or stopped,” Prof. Sinclair concluded.

  1. Sinclair R. Alopecia areata. Real World Data. FS4, SPIN 2022 Congress, 06–08 July, Paris, France.
  2. Petukhova L, et al. Nature. 2010;466:113-7.
  3. Cranwell WC, et al. Australas J Dermatol. 2019:60:163-70.


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