Alopecia Areata: a historical perspective on the role of infectious agents

Alopecia Areata (AA) is a skin condition that causes sudden and patchy hair loss. The cause of this disease has been a subject of continuous debate and study since its earliest discovery. The history of AA is as fascinating as it is complex, particularly due to the initial hypothesis proposed by Gruby in 1843 that an infectious agent could be the cause of the disease.

Gruby, a prominent scientist in the 19th century, introduced the idea that AA could be the result of a fungal infection. He discovered a fungus, which he named Microsporum audouini, residing around the hairs of patients diagnosed with “porrigo decalvans”, the old name for alopecia areata that was in use at the time. Based on this discovery, Gruby published a medical journal article claiming that AA must be an infectious disease. This hypothesis was based on the discovery of the fungus and the the observation that the hair loss in AA patients expanded slowly, similar to how local skin infections typically progress.

Additional support for idea that a fungal agent was causing AA came from the resemblance between the rapid, patchy hair loss observed in AA and conditions known to be infectious, such as ringworm and syphilis. Secondary (chronic) syphilis produces skin lesions over the body including the scalp and can also cause patchy hair loss. Furthermore, the secondary effects of AA, such as its impact on nail development, also mirrored those observed in syphilis patients. Reports of AA “epidemics” in institutions such as schools and orphanages during the 19th and early 20th centuries further bolstered the argument for an infectious cause.

At the time, the infectious theory (sometimes called the parasitic theory) of AA was widely accepted, and the fear of contagion even led to development of AA being considered a valid reason for military service exemption in France. However, as more data was collected, the infectious agent hypothesis slowly started to lose credibility.

For instance, several dermatologists identified different fungi, but none found Microsporum audouini. Others identified bacteria associated with AA, leading one author to rename the condition as “bacterium decalvans.” However, some dermatologists found no infectious agents that couldn’t also be found on the scalps of non-AA affected people. Moreover, attempts to transfer the disease via inoculation consistently failed. Some of the school and orphanage epidemics of AA were investigated in more depth and found to be more likely due to ringworm or children pulling their own and others hair out (trichotillomania or traction alopecia).

Eventually, dermatologists suggested the most likely explanation for Gruby’s data was that the original differential diagnosis between AA and ringworm may have been confused. Later articles concluded that Gruby was probably studying patients with ringworm, and not AA. Over time, the consensus among dermatologists shifted against an infectious cause for AA. While most dermatologists thought AA was caused by something other than an infectious agent by the turn of the century, the idea that AA was infectious did persist in some parts of the world into the 1930s and early 40s. By the early 1950s however, pretty much everyone favored a hypothesis of stress or trauma as a cause of AA.

Interestingly, that was not quite the end of the idea that infectious agents could cause AA. In the 1990s cytomegalovirus (CMV) infection was hypothesized as a potential inducer of alopecia areata. Initially, the suggestion was based on the observation that CMV can promote strong immune responses and has a predilection for infecting cells in a latent state, which could theoretically trigger the autoimmune reactions seen in AA. However, subsequent research failed to consistently demonstrate a direct correlation or causal relationship between CMV infection and the development of AA. Studies that attempted to identify CMV DNA in alopecia areata lesions often yielded negative results, and the presence of CMV in patients with AA was found to be comparable to that in the general population. Consequently, the scientific consensus shifted away from considering CMV as a causative agent for AA.

Today, while the idea of an infectious agent as the cause of AA has largely been dismissed, there is still a possible role for pathogen superantigens. These molecules are produced by certain types of bacteria and viruses and are known to increase the general activity of the immune system. There is a possibility that these superantigens could activate AA via a process known as antigen epitope mimicking.

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