Study Finds Patients With Vitiligo at Higher Risk for Rheumatoid Arthritis, Systemic Lupus Erythematosus

Patients with vitiligo have a higher risk of developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), according to a study published in Skin Research and Technology.¹

The researchers explained that the exact pathogenesis of vitiligo, a disease where the selective loss of melanocytes results in white, depigmented spots appearing on the skin, remains unclear and complicated.² However, past research suggests genetics, autoimmunity, and oxidative stress are involved.¹ Autoimmunity is considered the primary contributing factor since vitiligo is often accompanied by various autoimmune diseases, like psoriasis and alopecia areata.

Similarly, many rheumatic diseases, which affect the skeletal system, joints, surrounding soft tissues, and other associated organs and structures, are closely linked to autoimmune reactions. Past observational studies found that patients with vitiligo have an elevated risk of developing rheumatic diseases. However, it remains uncertain whether vitiligo and rheumatic diseases are causally related.

Since observational studies cannot establish causality, the researchers conducted a 2-sample Mendelian randomization (MR) analysis to explore the causal connection between vitiligo and common rheumatic diseases, namely RA, SLE, ankylosing spondylitis (AS), and Sjögren’s syndrome (SS).

Patients with vitiligo have a higher genetic risk of developing rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). | Image Credit: shurkin_son - stock.adobe.com

For the outcome database, the researchers obtained the genetic instrumental variables (IVs) for each trait from available genome-wide association studies (GWAS). More specifically, they received the genetic IVs for RA and SLE from the IEU OpenGWAS database, and they extracted the genetic IVs for SS and AS from the Finn Gen Biobank. As for the exposure database, the researchers extracted genetic IVs for vitiligo from the largest GWAS meta-analyses.

Therefore, the researchers analyzed 14,361 cases of RA and 43,923 controls, along with 5201 cases of SLE and 9066 controls. Also, they studied 2495 cases of SS and 365,533 controls, as well as 2860 cases of AS and 270,964 controls. Additionally, they examined 4680 cases of vitiligo and 39,586 controls; all cases and controls were of European ancestry.

Predominantly, the researchers used the random-effects inverse variance weighted (IVW) method to conduct their analysis. To confirm the main analysis’s robustness, the researchers used several sensitivity analyses, including heterogeneity, outliers, and “leave-one-out” analyses.

The researchers found a positive genetic causal connection between vitiligo and RA with the IVW model (OR, 1.47; 95% CI, 1.29-1.68; P < .001); the sensitivity analyses indicated that patients with vitiligo had a 1.47-fold increased RA risk compared to those without vitiligo.

Similarly, the researchers discovered an association between genetically predicted vitiligo and an increased SLE risk (OR, 1.22; 95% CI, 0.90-1.66; P = .19). More specifically, the sensitivity analyses indicated that patients with vitiligo had a 1.22-fold higher risk of developing SLE than those without vitiligo.

Conversely, the researchers did not find significant genetic causal relationships between vitiligo and either SS (OR, 1.13; 95% CI, 0.96-1.32; P = .14) or AS (OR, 0.97; 95% CI, 0.87-1.09; P = .60). When using both the IVW model and the sensitivity analyses, the researchers noted that there was insufficient proof to establish a genetic causal connection between vitiligo and either SS or AS.

Overall, the researchers noted that their findings demonstrated the need for patients with vitiligo to be aware of their heightened risk for developing SLE and RA, urging them to remain vigilant. Based on their findings, they suggested areas for further research.

“Further validation of our findings in larger samples is warranted, and further in-depth studies are required to investigate the potential mechanisms of the cause-and-effect relationships described above,” the authors concluded.

References

1. Zhao M, Zhang Y, Sun G. Identifying the genetic association between common rheumatic diseases and vitiligo. Skin Res Technol. 2024;30(7):e13846. doi:10.1111/srt.13846
2. Bergqvist C, Ezzedine K. Vitiligo: A focus on pathogenesis and its therapeutic implications. J Dermatol. 2021;48(3):252-270. doi:10.1111/1346-8138.15743