A “hair‐raising” history of alopecia areata

Abstract

A 3500‐year‐old papyrus from ancient Egypt provides a list of treatments for many diseases including “bite hair loss,” most likely alopecia areata (AA). The treatment of AA remained largely unchanged for over 1500 years. In 30 CE, Celsus described AA presenting as scalp alopecia in spots or the “windings of a snake” and suggested treatment with caustic compounds and scarification. The first “modern” description of AA came in 1813, though treatment still largely employed caustic agents. From the mid‐19th century onwards, various hypotheses of AA development were put forward including infectious microbes (1843), nerve defects (1858), physical trauma and psychological stress (1881), focal inflammation (1891), diseased teeth (1902), toxins (1912) and endocrine disorders (1913). The 1950s brought new treatment developments with the first use of corticosteroid compounds (1952), and the first suggestion that AA was an autoimmune disease (1958). Research progressively shifted towards identifying hair follicle‐specific autoantibodies (1995). The potential role of lymphocytes in AA was made implicit with immunohistological studies (1980s). However, studies confirming their functional role were not published until the development of rodent models (1990s). Genetic studies, particularly genome‐wide association studies, have now come to the forefront and open up a new era of AA investigation (2000s). Today, AA research is actively focused on genetics, the microbiome, dietary modulators, the role of atopy, immune cell types in AA pathogenesis, primary antigenic targets, mechanisms by which immune cells influence hair growth, and of course the development of new treatments based on these discoveries.

Integration of a single-step genome-wide association study with a multi-tissue transcriptome analysis provides novel insights into the genetic basis of wool and weight traits in sheep

“…Several genes associated with wool traits were also significantly associated with immune-related traits in humans, such as the reticulocyte fractions of red blood cells ( SPHK1 ) and white blood cells ( NPTX1 ) (Fig. 4 ), which is consistent with previous findings that indicated that the immune system is involved in hair follicle development [ 53 , 54 ]. Many genes associated with LW in sheep exhibited significant associations with traits related to metabolism and skeletal tissues in humans, such as ADSL (body mass index), RAPSN (height), PSKH1 (height), PPP1R3D (standing height), SHISA4 (heel bone mineral density), ADSL (standing height) and CHRNB1 (body mass index).…”

Hair follicle immune privilege and its collapse in alopecia areata

“…Through its long history, a link between AA and inflammation has been well recognized 262 . It presents with a wide array of clinical and aetiological variations, 263,264 but in all instances it is a non‐scarring alopecia 265,266 .…”

New developments in hair research

“…Alopecia areata (AA) as a non‐scarring alopecia, has held the attention of physicians and those afflicted for at least 3500 years and probably for much longer. In the context of George Santayana's famous quote; "Those who cannot remember the past are condemned to repeat it", Broadley and McElwee's review of AA history provides a reminder that long‐forgotten research investigations contain information still relevant today . Of particular note, Giovannini's detailed histological investigation of AA, his identification of follicular inflammation, and conclusion that inflammatory cells likely drove alopecia, was 70 years ahead of its time .…”

“…In the context of George Santayana's famous quote; "Those who cannot remember the past are condemned to repeat it", Broadley and McElwee's review of AA history provides a reminder that long-forgotten research investigations contain information still relevant today. [9] Of particular note, Giovannini's detailed Herz-Ruelas et al, examine the secretion of stress hormones in AA in response to ultra-violet A (UVA-1) phototherapy. [20] These studies suggest that we need to look well beyond the lymphocyte infiltrate and investigate the role of the innate immune system, and the dynamics of hair follicle biology, to fully understand the mechanism(s)…”