Vitiligo Leads to Heightened Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus, According to Mendelian Randomization

Patients with vitiligo should be made aware of the potential development of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as vitiligo is linked to a heightened risk of both rheumatic diseases, according to a study recently published in Skin Research and Technology.¹

Image Credit: © TripleP Studio - stock.adobe.com

Background and Methods

Rheumatic diseases affecting the musculoskeletal system, including joints, bones, muscles, and the surrounding soft tissues, are often associated with autoimmune reactions.

Research has also demonstrated that individuals with vitiligo experience a higher incidence of various autoimmune diseases, such as alopecia areata, psoriasis, thyroid diseases, inflammatory bowel disease, type 1 diabetes, RA, and SLE, with recent research suggestive of a genetic causal link between vitiligo and autoimmune thyroid diseases.² Some observational studies, such as one published in Dermatology, have led to the conclusion that individuals with vitiligo have a significantly elevated risk of developing rheumatic diseases.³

In order to address potential limitations of these observational studies, researchers Zhao et al conducted a 2-sample Mendelian randomization analysis, while simultaneously investigating the potential causal relationship between vitiligo and common rheumatic diseases, specifically RA, SLE, Sjögren's syndrome, and ankylosing spondylitis.

Genetic instrumental variables for vitiligo and the rheumatic diseases were obtained from large-scale genome-wide association studies. For vitiligo, the data came from the largest genome-wide association study meta-analysis, including 4680 cases and 39,586 controls of European ancestry. The outcome datasets for RA and SLE were sourced from the IEU OpenGWAS database, while the datasets for SS and AS were extracted from the FinnGen Biobank.

Findings

The analysis revealed a significant genetic connection between vitiligo and RA. Using the inverse variance weighted method, the odds ratio was 1.47, with a 95% confidence interval of 1.29 to 1.68, and a p-value of less than 0.001. This indicates that individuals with vitiligo have a 47% higher risk of developing RA compared to those without vitiligo. The weighted median method yielded similar results, further supporting this finding with an odds ratio of 1.28.

Sensitivity analyses further confirmed these results.

When examining the relationship between vitiligo and SLE, researchers found that the initial inverse variance weighted analysis did not show a significant association. However, sensitivity analyses revealed significant variability.

After removing these outliers and reanalyzing, researchers noted a significant genetic link between vitiligo and SLE, suggesting that individuals with vitiligo have a 22% higher risk of developing SLE.

The analysis did not find a significant genetic link between vitiligo and Sjögren's syndrome or ankylosing spondylitis.

Conclusions

"Our MR study provides evidence supporting the idea that vitiligo leads to a higher risk of RA and SLE," according to Zhao et al. "This finding emphasizes the need for patients with vitiligo to maintain a high level of vigilance and be aware of the possible risk of developing RA and SLE. Regular monitoring is essential to manage and address this potential complication."

These study findings are confirmed by previous studies, including a large-scale epidemiological study (Choi CW, Eun SH, Choi KH, Bae JM, 2017) and a systematic study (Lee JH, Ju HJ, Seo JM, et al, 2023).

Moving forward, researchers recommended further validation of these findings through larger studies and larger samples.

References

1. Zhao M, Zhang Y, Sun G. Identifying the genetic association between common rheumatic diseases and vitiligo. Skin Res Technol. Published online July 5, 2024. https://doi.org/10.1111/srt.13846
2. Chen Y, Zhang Y, Liu W, Huang X, Luo X, Wang H. The causal relationship between vitiligo and autoimmune thyroid diseases: a bidirectional two-sample Mendelian randomization analysis. Skin Res Technol. 2024; 30(6):e13742.
3. Sheth VM, Guo Y, Qureshi AA. Comorbidities associated with vitiligo: a ten-year retrospective study. Dermatol. 2013; 227(4): 311-315.