Alopecia Areata and Systemic Lupus Erythematosus: Insights From a Nationwide Case–Control Study

Hair loss is a common feature in systemic lupus erythematosus (SLE), caused by telogen effluvium, scarring alopecia, as well as alopecia areata (AA) [1]. Studies have demonstrated that AA patients have an increased risk of developing other autoimmune or inflammatory conditions, including SLE [2]. The magnitude of this increased risk varies significantly across studies. It is crucial to obtain additional large-scale data from diverse populations worldwide. The present study aimed to investigate the prevalence of SLE in patients with alopecia areata (AA) using a nationwide case–control study design. We accessed the computerized database of Maccabi Healthcare Services (MHS), which covers 2,354,000 individuals, and conducted a retrospective analysis. The study protocol was approved by the MHS Institutional Review Board. AA diagnoses were based on standardized codes entered by board-certified dermatologists. All AA cases from 2005 to 2019 were included and matched in a 1:2 ratio with healthy controls based on age and gender. SLE diagnoses were identified through ICD-10 (International Statistical Classification of Diseases and Related Health Problems, 10th Revision) codes entered by hospital rheumatologists, adhering to the EULAR/ACR (European Alliance of Associations for Rheumatology/American College of Rheumatology) criteria. The proportion of SLE was calculated in both groups, and odds ratios (OR) with 95% confidence intervals (CI) were determined using a regression model in SPSS version 28.0 (IBM, Armonk, NY, USA). The literature estimates the prevalence of SLE in the general population between 0.038% and 0.27% [3]. We chose a prevalence of 0.25% (the calculated prevalence of SLE in our study's control group), a 50% margin of error, and 95% confidence to calculate our sample size using an accepted formula. Other variables such as ethnicity, family history, and comorbid autoimmune disorders were not available for inclusion. A subgroup analysis by age (children < 18 years, adults 18–40 years, and adults > 40 years) was also conducted. Data from 33,401 patients with AA and 66,802 matched controls were included, of which 56.5% and 43.5% were males and females, respectively. The mean age at onset of AA was 29.9 ± 16.9 years. Among the total cohort, 82,873 individuals (82.7%) were born in Israel, while 17,330 (17.3%) were immigrants from various continents. Israeli-born individuals were more prevalent among AA patients (29,044; 87%) compared to controls (53,829; 80.6%) (p < 0.001). Of the total cohort, 460 individuals (0.5%) were diagnosed with SLE, of which 296 (0.9%) were AA patients and 164 (0.25%) were controls, indicating a significant association between AA and SLE (OR = 3.63, 95% CI [3.00–4.40], p < 0.01). AA was significantly associated with SLE across all categories when stratified by age subgroups. The strongest association was observed among children (OR = 4.00, 95% CI [1.88–8.56], p < 0.01) (Table 1). Although a rare disease, with a prevalence of 0.9% among subjects with AA in our study, SLE is significantly associated with AA. These results align with the literature, where the odds ratios ranged from 2.1 to 5.53 [2, 4]. The strengths of this study include the large and representative population involved and the precise diagnoses provided by MHS. However, it is limited by the lack of subgroup analyses, particularly regarding AA severity (patch AA versus alopecia totalis/alopecia universalis) or SLE versus cutaneous LE. This strong association, confirmed across diverse populations and all age groups in our study, has considerable significance. It underscores the need for screening and further monitoring of AA patients, since biomarkers are not routinely monitored. In addition, AA, like other inflammatory autoimmune diseases, is increasingly being treated with Janus kinase (JAK) inhibitors, which are currently under investigation for SLE with promising effective results [5]. Considering our findings regarding the prevalence of SLE among AA, we suggest screening and possibly initiating early personalized targeted treatment. The authors declare no conflicts of interest.