Risk of autoimmune thyroid diseases in individuals with alopecia areata: A nationwide case‐control study

Dear Editors, Alopecia areata (AA) is one of the most common organ-specific autoimmune conditions, characterized by non-scarring, patchy hair loss due to autoimmune activity targeting the skin. It is a chronic disorder that primarily affects children and young adults and involves both genetic and environmental factors.1 AA may be associated with other inflammatory or autoimmune diseases, such as systemic lupus erythematosus, vitiligo, and thyroid-related disorders (AITD), particularly autoimmune forms such as Hashimoto's thyroiditis and Graves' disease.2, 3 Several studies have investigated the association between AA and AITD, revealing a significant, though variably reported, link.2, 4-7 Therefore, acquiring new, large-scale data from diverse populations worldwide is essential for a more comprehensive understanding. This study sought to explore the association between AA and autoimmune AITD through a population-based case-control design. We conducted a population-based retrospective case-control cohort study that included all patients diagnosed with AA between 2005 and 2019, as recorded in Maccabi Healthcare Services (MHS), the second-largest state-mandated health fund in Israel, which covers approximately 26% of the national population. The MHS database includes demographic information, AA diagnoses (established by board-certified dermatologists using clinical diagnosis codes), comorbid diseases, and treatment data. Diagnoses of Graves' disease and Hashimoto's disease were made by general physicians and identified using the ICD-10 coding system. All patients with a diagnosis code of AA – regardless of age, severity, or treatment – were included in the study and matched with healthy controls at a 1:2 ratio based on sex for comparison. The primary outcome was the assessment of the prevalence of autoimmune AITD among individuals with AA compared to the control group. Logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between AA and AITD. Data were analyzed using SPSS version 29. p values < 0.05 were considered statistically significant. A total of 33,401 patients with AA were included in the study, representing 1.3% of the MHS population during the study period. These patients were matched to 66,802 controls. In both groups, 56.5% were male. The mean age at AA onset was 29.9 ± 16.9 years. Out of the total cohort, 5,843 individuals (5.83%) were diagnosed with AITD, among whom 5,165 with Hashimoto's disease (5.15%) and 678 with Graves' disease (0.68%). Hashimoto's disease was identified in 2,316 individuals with AA (6.93%) and in 2,849 healthy controls (4.26%), demonstrating a significant association with AA (OR = 1.67, 95% CI 1.58–1.77; p < 0.01). Similarly, Graves' disease was diagnosed in 309 individuals with AA (0.93%) and in 369 controls (0.55%), also indicating a significant association (OR = 1.68, 95% CI 1.44–1.96; p < 0.01) (Figure 1). Hashimoto's disease preceded AA diagnosis in 55% of the total cohort, while Graves' was diagnosed before AA in 75% of the individuals. The diagnosis was simultaneous (during a 3-month period) with AA diagnosis in 3.5% of both AITD. AA was diagnosed before Hashimoto's and Graves' disease in 41.5% and 24.5% of the total cohort, respectively. Xin et al., in their meta-analysis of 17 articles involving 2,850 cases of AA and 4,667 controls, found that the overall prevalence of AITD in patients with AA was significantly increased compared to controls (OR = 3.66; 95% CI 2.90–4.61).5 Ly et al., in a systematic review of 102 studies comprising 680,823 patients with AA and 72,011,041 healthy controls, reported an even stronger association with Hashimoto's thyroiditis, with an OR of 4.31 (95% CI 2.51–7.40).2 Additionally, a Korean nationwide, population-based, cross-sectional study found a significant association between AA and both Graves' disease (OR = 1.42; 95% CI 1.32–1.52) and Hashimoto's thyroiditis (OR = 1.16; 95% CI 1.08–1.24), that was comparable to our findings.6 Notably, these associations were significantly stronger in patients with severe AA. Furthermore, a study by Kinoshita-Ise et al. reported that AA is significantly associated with the presence of thyroid antibodies – specifically TPO-Ab (thyroid peroxidase antibodies) and TG-Ab (thyroglobulin antibodies) – rather than with overt clinical or laboratory-defined thyroid dysfunction.7 A shared genetic susceptibility between AA and AITD has been suggested by Noso et al., who identified the HLA-DQB103 allele and the DRB115:01–DQB1*06:02 haplotype as significantly more frequent in TR-Ab-positive patients with AA compared to controls.8 In conclusion, although our study has several limitations related to its retrospective design and the limitation to assess all potential confounding factors, it confirms the significant association between AA and autoimmune AITD. Yet further research is needed to evaluate the clinical usefulness of routine thyroid screening in individuals with AA. Open access funding enabled and organized by Projekt DEAL. None.