Hair loss is frequent in patients with IBD and often multifactorial, but in a small proportion of patients it may be from immune-mediated AA. In this case-control study, we note that AA development was more common in patients with IBD on anti-TNF therapy. We also demonstrate that overall, the severity of AA in patients with IBD tended to be mild and only around one quarter of patients with AA saw no improvement following diagnosis.
An interesting finding from our study is the higher frequency of anti-TNF use in patients with IBD developing AA compared to controls. This was not solely a reflection of disease severity as evidenced by the lack of difference in use of other advanced biologic or small molecule treatment or need for prior IBD related surgery. Prior studies investigating the association between IBD-related medication use and alopecia have yielded mixed results. A 10-year population-based cohort study of 11,442 patients on anti-TNF found a significantly elevated risk of vitiligo but not AA when comparing anti-TNF users against controls 30. One of the largest studies to evaluate the association between anti-TNF use and alopecia used the French Pharmacovigilance Database. Béné, J. et al found exposure to anti-TNF to be more frequent in alopecia reports than in other adverse drug reaction reports, with a ROR of 3.0 (95% CI 2.3, 4.0)27. However, like other studies in this field, this study’s alopecia outcome included all subtypes of alopecia, not solely AA. Besides select case reports on AA 13,31, the majority of anti-TNF associated alopecia research has either examined hair loss in general, or primarily focused on psoriatic alopecia 19–21,24,27–32. Therefore, our study is one of the first to focus solely on the forms of AA in the setting of anti-TNF use for IBD. In addition, we were also able to describe in more detail the phenotype and severity of alopecia and response to interventions. Interestingly, many patients experienced improvement in their AA despite continuing anti-TNF treatment, similar to what has been observed for anti-TNF associated psoriasis. The mechanism of anti-TNF induced hair loss is unclear. Proposed mechanisms of psoriatic alopecia development include changes in cell trafficking through type 1 interferon and interleukin-23/T-helper 17 axis, especially in certain genetically predisposed individuals 10–12. A similar mechanism may mediate the development of anti-TNF-induced AA, though like all biologic-associated paradoxical immune-mediated skin reactions, the pathogenesis of these complications remains to be robustly defined. There may also be an underlying genetic predisposition as evidence by the younger age at diagnosis (often associated with greater genetic burden 31,32) and higher frequency of other immune-mediated diseases, as seen in our study.
There are several limitations to this study. First, the results of this study are limited to hair loss in the pattern of alopecia focalis, totalis, or universalis. Our findings may not apply to other causes of hair loss, such as psoriatic alopecia, male/female pattern baldness, and telogen effluvium. This may explain the discrepancy with prior studies that found general hair loss to improve with effective treatment of IBD including with anti-TNF 19. This study also has a moderate sample size and may have insufficient power for weaker associations. The retrospective design of the study limits us to the details found in routine clinical care, where the details for SALT score calculation is variable. We acknowledge the possibility of confounding by severity, such as AA being a marker of more severe underlying IBD rather than association with anti-TNF use. However, over two-thirds of patients had no or minimal disease activity at AA diagnosis, and there was no difference in disease phenotype, other biologic use (often used 2nd or 3rd line during the study period) or surgery suggesting this is unlikely to be the only explanation. In addition, although we looked at alopecia-specific treatments such as steroid injection and JAK inhibitors, we did not have sufficient power to systematically investigate if switching to a different IBD agent after discontinuation of the offending agent led to better control of alopecia.
In conclusion, we found that individuals with IBD who later develop AA were more likely to be using anti-TNF at time of alopecia onset when compared to controls who never had AA. The trend towards higher rates of IMD co-occurrence and earlier IBD diagnosis in the AA cohort may suggest that at baseline those who later develop AA may already be at a higher risk of immune mediated dysregulations. Longitudinal research with larger cohort sizes will be needed to define incidence of AA in anti-TNF users, and objectively define frequency of occurrence among those using anti-TNF treatment.