Seronegative Rheumatoid Arthritis Increases Gout Risk: Study

A new study published in the journal of Arthritis Research & Therapy suggests that rheumatoid arthritis (RA) and gout may overlap more than previously recognized. Data indicate that seronegative RA has a causal role in increasing the risk of gout, pointing toward possible shared epidemiological links, genetic causality, or overlapping molecular mechanisms between the two conditions.

RA is a chronic autoimmune disorder that primarily attacks joints, while gout is typically caused by the buildup of uric acid crystals. Because their mechanisms differ, the coexistence of the diseases has historically been considered rare or coincidental. However, studies now argue that this overlap may be underestimated.

This research analyzed health data from nearly 20,000 participants which was collected through the National Health and Nutrition Examination Survey from 2007 to 2018. Among participants diagnosed with RA, 10.3% also had gout, when compared to 4.8% in matched individuals without RA. Statistical analysis indicated that RA patients were more than twice as likely to develop gout, which suggested RA is an independent risk factor.

The study also found that gout prevalence among RA patients has increased over time. This study suggest this trend may reflect improved survival among RA patients, better diagnosis of gout, or shared disease mechanisms that are only now being recognized.

While higher urate levels were associated with gout risk among RA patients, the relationship was nonlinear and did not fully explain the connection. Genetic analyses further supported this by showing that RA appears to increase the incidence of gout without necessarily raising urate levels directly.

Using genome-wide genetic data, this research found the strongest evidence for a causal relationship in seronegative RA, where no clear causal link was observed for seropositive RA, which highlighted the potential differences in disease biology.

To explore shared mechanisms, this study analyzed gene-expression data from the Gene Expression Omnibus and integrated the results with disease-associated gene databases which included Online Mendelian Inheritance in Man and GeneCards. This analysis identified more than 200 genes common to both conditions.

Many of these genes were involved in interferon signalling and antiviral responses. 5 genes in particular appeared central to this shared network, suggesting that immune-driven inflammation rather than urate metabolism alone may link the two diseases. Overall, this study suggest that RA and gout may overlap more often than clinicians expect and may share immune-related molecular pathways. 

Source:

Li, S., Zhao, Q., Cai, X., He, X., Li, S., Chen, Z., Wei, S., Mao, W., Chen, X., Yu, Y., Wu, T., Song, L., Wu, M., Zhang, J., Guo, X., & Yang, L. (2026). Rheumatoid arthritis and gout: a rare combination or overlooked coexistence? Arthritis Research & Therapy, 28(1), 48. https://doi.org/10.1186/s13075-026-03746-5