Alopecia Areata Tied to Higher Risks of Autoimmune and Psychiatric Comorbidities

Patients with alopecia areata had a higher prevalence of autoimmune and psychiatric comorbidities at diagnosis and an increased risk of new onset of these comorbidities after their diagnosis, according to a retrospective cohort study.

At the time of alopecia areata diagnosis, 30.9% of patients had psychiatric comorbidities compared with 26.8% of unmatched controls without alopecia areata (P<0.001), while 16.1% versus 8.9%, respectively, had autoimmune comorbidities (P<0.0001), reported Arash Mostaghimi, MD, of Brigham and Women’s Hospital in Boston, and colleagues.

After matching for sex, age, and geographic region, the overall incidence of any psychiatric disease was 10.2% for patients with alopecia areata and 6.8% for the control group within the first year after diagnosis (P<0.001), while the overall incidence of any autoimmune or immune-mediated disease was 6.2% and 1.5%, respectively (P<0.001), they wrote in JAMA Dermatology.

Overall, patients with alopecia areata had a significantly higher risk of developing a psychiatric comorbidity compared with controls (adjusted HR 1.3, 95% CI 1.3-1.4), as well as an autoimmune comorbidity (aHR 2.7, 95% CI 2.5-2.8).

Mostaghimi and colleagues noted that new onset of these comorbidities after an alopecia areata diagnosis “could further exacerbate the disease burden and reduce quality of life of those affected. Routine monitoring of patients with AA [alopecia areata], especially those at risk of developing comorbidities, may permit earlier and more effective intervention.”

“Both genetic and environmental factors play a role in AA, with reports suggesting that an upregulation of inflammatory cytokines (e.g., interferon-γ and interleukin-15) that signal through Janus kinases and other pathways may be involved,” the authors wrote, adding that these inflammatory pathways play a role in several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis.

Previous research has shown that patients with alopecia areata had a significantly higher likelihood of several comorbidities, including systemic lupus erythematosus, metabolic syndrome, and Hashimoto thyroiditis, in addition to an increased likelihood of anxiety and depression.

The authors also cited a literature review that reported “consistently negative mental health outcomes in those with AA, including emotional distress, reduced social functioning, and increased stress.”

Because alopecia areata and many of these comorbidities share underlying signaling pathways, it is not unreasonable to think effective and tolerable treatments could address multiple disorders simultaneously, Mostaghimi and team suggested, pointing to the recent FDA approval of the Janus kinase inhibitor baricitinib (Olumiant) for the treatment of alopecia areata. The drug is also approved for rheumatoid arthritis.

“Additionally, there is some evidence of interplay between depressive and dermatologic disorders and that treating the latter with advanced therapies can likewise reduce the impact of the former,” the authors noted.

Cathryn Sibbald, MD, MSc, of the University of Toronto and the Hospital for Sick Children in Toronto, told MedPage Today that “this large study definitely adds to the literature, despite limitations, mostly in the reliance on coding for diagnosis of alopecia areata and comorbidities.”

“I do think that it’s important to acknowledge the possibility that some of the comorbidities were present before alopecia areata diagnosis but were not diagnosed until after,” she said. “Regardless, the data provide a nice reminder that a review of systems and good physical exam in patients may help uncover and diagnose some of these comorbidities.”

“In my experience, anxiety is the most common psychiatric comorbidity, and although treating the alopecia may be helpful, patients frequently disclose a persistent fear of waking up with a new flare even if they have regrown and are on treatment,” Sibbald added. “I also have patients who benefit from both nonpharmacologic (e.g., therapists) and pharmacologic treatments for their psychiatric comorbidities. Support groups can also be very helpful.”

For this study, Mostaghimi and colleagues used data collected from January 2007 through April 2023 from the Merative MarketScan Research Database, which contains medical and drug claims data for more than 46 million patients in the U.S. At baseline, 63,384 patients with alopecia areata and 3,309,107 without the condition were identified. After matching, there were 16,512 and 66,048 patients in the alopecia areata and control groups, respectively.

The mean age of matched patients was 36.9 years, and 50.6% were women. The mean Charlson Comorbidity Index score was 0.1 for the alopecia areata group and 0.07 for the control group. Patients with diagnoses of other immune-mediated inflammatory skin disorders, autoimmune diseases, and psychiatric diseases during the baseline period were not included.

After matching, psychiatric diseases with the highest incidence for patients with alopecia areata compared with the control group were anxiety (4.0% vs 2.6%), sleep disturbance (2.6% vs 1.7%), and depression (1.9% vs 1.2%; all P<0.001), while autoimmune and immune-mediated disorders with the highest incidence were atopic dermatitis (2.2% vs 0.3%), vitiligo (1.0% vs 0.1%), and psoriasis (0.9% vs 0.2%; all P<0.001).

Psychiatric disorders with the highest risk included:

• Adjustment disorder (aHR 1.5, 95% CI 1.3-1.6, P<0.001)
• Panic disorder (aHR 1.4, 95% CI 1.2-1.7, P<0.001)
• Sexual dysfunction (aHR 1.4, 95% CI 1.1-1.8, P=0.003)

Autoimmune and immune-mediated disorders with the highest risk included:

• Systemic lupus erythematosus (aHR 5.7, 95% CI 4.6-7.2, P<0.001)
• Atopic dermatitis (aHR 4.3, 95% CI 3.9-4.8, P<0.001)
• Vitiligo (aHR 3.8, 95% CI 3.2-4.4, P<0.001)

The authors acknowledged that not accounting for levels of disease severity could have led to potential underestimation of disease burden and associated risk of comorbidities.

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