Alopecia Areata Shares Inflammatory Link With Asthma

Alopecia areata and asthma are strongly linked, particularly through the inflammatory protein interleukin-33, suggesting a shared biological pathway and potential for targeted treatments like dupilumab. | Image Credit: onephoto - stock.adobe.com

Alopecia areata is associated with asthma based on the mediating role of IL-33 in both conditions, according to study findings published in Skin Research and Technology.¹

Patients with subtypes of alopecia are known to have an increased risk of comorbidities, especially with inflammatory factors.² Various autoimmune conditions—that include rheumatoid arthritis, inflammatory bowel disease, and psoriasis—have demonstrated associations with alopecia areata. Increased risks of vitiligo, lupus erythematosus, and thyroid disease are also present among patients with alopecia areata. Common conditions linked to alopecia include asthma, allergic rhinitis, atopic dermatitis, thyroid disease, type 1 diabetes, celiac disease, rheumatoid arthritis, and vitiligo.³ In addition, the National Alopecia Areata Foundation reports atopy and allergies attribute to alopecia.

Asthma was considered a related condition to alopecia areata in the present analysis because both conditions are associated with similar inflammatory proteins, such as IL-5 and IL-13.¹ Interleukins are a diverse group of proteins involved in immune and inflammatory responses, each classified based on their genetic sequence, receptor chain similarities, and their specific functions.⁴

“To overcome these challenges and offer clearer insights into potential causal pathways,” wrote the study authors “this study employs two-sample Mendelian randomization analysis to investigate interactions between asthma, circulating inflammatory proteins, and [alopecia areata].”¹

The Mendelian randomization study examined relationships between asthma and alopecia areata with genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and alopecia areata extracted from large-scale genome-wide association study (GWAS) data.

Results show an identifiable relationship between asthma and an increased risk of alopecia areata based on the inverse variance method (OR, 14.070; 95% CI, 1.410-140.435; P = .024). Certain single nucleotide polymorphisms linked to asthma were positively associated with alopecia areata, as well.

The study also found that higher levels of certain inflammatory cytokines, such as IL-2 receptor subunit beta, IL-33, and IL-18 receptor 1, were associated with an increased risk of alopecia areata. Among these, IL-33 was uniquely linked to alopecia areata and played a significant role in the shared risk between asthma and alopecia areata, contributing to 13.1% of the increased risk.

To better understand the relationship between asthma and alopecia areata, future research should consider the potential role of dupilumab. This FDA-approved drug has shown efficacy in promoting hair regrowth in pediatric patients with moderate to severe alopecia and coexisting atopic dermatitis.⁵ Moreover, it has been proven to alleviate asthma symptoms and enhance lung function.⁶ Dupilumab could be a valuable therapeutic option for patients afflicted by both asthma and alopecia areata or other hair loss disorders.

Generalizability may be limited within the study due to its primary reliance on individuals of European ancestry, and unmeasured variables could still be influencing our results, maintaining the observational nature.

The study represents a monumental movement toward a greater understanding of the relationship between asthma and alopecia, the authors underscored. Further research should aim to include more diverse cohorts and expand on collective observations while utilizing models to reveal the role of IL-33 in the pathogenesis of both conditions.

“Ultimately, elucidating the mechanisms underlying the association between asthma and [alopecia areata] holds promise for the development of targeted interventions aimed at improving the management of both conditions,” concluded the study authors.

References

1. Wu P, Tian K, Gao S, et al. Interleukin-33 links asthma to alopecia areata: Mendelian randomization and mediation analysis. Skin Res Technol. 2024;30(8):e13864. doi:10.1111/srt.13864

2. Santoro C. Alopecia areata linked to autoimmune, psychiatric risks. AJMC®. August 23, 2024. Accessed October 25, 2024. https://www.ajmc.com/view/alopecia-areata-linked-to-autoimmune-psychiatric-risks

3. Santoro C. Alopecia areata risk associated with atopy, allergies. AJMC®. May 13, 2024. Accessed October 25, 2024. https://www.ajmc.com/view/alopecia-areata-risk-associated-with-atopy-allergies

4. Akdis M, Aab A, Altunbulakli C, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138(4):984-1010. doi:10.1016/j.jaci.2016.06.033

5. Santoro C. Exploring comorbidities, dupilumab treatment in pediatric alopecia areata. AJMC®. July 24, 2024. Accessed October 28, 2024. https://www.ajmc.com/view/exploring-comorbidities-dupilumab-treatment-in-pediatric-alopecia-areata

6. Pavord ID, Casale TB, Corren J, et al. Dupliumab reduces exacerbations independent of changes in biomarkers in moderate-to-severe asthma. J Allergy Clin Immunol Pract. 2024;12(7):1763-1772. doi:10.1016/j.jaip.2024.03.031