Distinguishing early rheumatoid arthritis from self-limited viral arthritis remains a persistent diagnostic challenge for rheumatologists. A large real-world laboratory analysis now quantifies just how often acute rubella and parvovirus B19 infections intersect with rheumatoid arthritis suspicion, and where misclassification risk is highest.
In a retrospective analysis published in BMJ Open, investigators from Labcorp, led by Min Kyung Lee, PhD, examined 211,917 IgM tests for rubella and 644,473 IgM tests for parvovirus B19 (B19V) conducted through Labcorp between 2014 and 2023. They used linked diagnostic codes and longitudinal laboratory data to evaluate arthritis-related clinical suspicion and rheumatoid arthritis (RA)-associated biomarker testing in adults with serologic evidence of recent viral infection.
Among adults tested, 2.1% were rubella IgM–positive. Although rubella has been eliminated domestically, these patients were more likely than IgM-negative adults to have arthritis-related ICD-10 codes submitted at the time of testing (1.4% vs 0.5%, P<0.001) and to undergo same-day RA biomarker testing (1.3% vs 0.5%, P<0.001).
When RA-associated testing was performed, rubella IgM–positive adults had a higher rate of biomarker positivity than IgM-negative adults (26.4% vs 11.1%, P=0.003), suggesting that some patients already met serologic criteria for inflammatory arthritis at presentation. However, longitudinal follow-up of 1,867 patients with rubella IgM testing showed no statistically significant association between rubella IgM positivity and subsequent suspected RA diagnosis after adjustment for age and sex (adjusted HR 1.31; 95% CI 0.63–2.69).
The authors interpret this pattern as a reminder that acute rubella (true infection, vaccine-related serology, or IgM cross-reactivity) can prompt RA evaluation without clearly predicting RA development.
The parvovirus B19 results had clearer clinical significance. Among adults, 2.1% tested positive for B19V IgM. These patients were substantially more likely to carry arthritis-related diagnostic codes than IgM-negative adults, including arthritis (12.6% vs 8.1%), joint disorders (25.5% vs 11.2%), and soft tissue disorders (7.0% vs 5.0%; P<0.001 for all).
More than one in five B19V IgM–positive adults (21.3%) underwent RA-associated diagnostic testing, compared with 14.3% of IgM-negative adults (P<0.001). Despite this heightened suspicion, RA biomarker positivity was lower in the B19V IgM–positive group (12.8% vs 15.5%, P<0.001), reinforcing the concept of parvovirus B19 as a clinical RA mimic rather than concurrent disease.
In longitudinal analysis of 22,683 adults with B19V IgM testing and follow-up data, B19V IgM positivity was associated with a 33% increased risk of a future suspected RA diagnosis (adjusted HR 1.33; 95% CI 1.10–1.61). The authors emphasize that this likely reflects persistent joint symptoms driving reevaluation, not biologic progression to RA.
“Differentiating B19V arthritis from RA may be difficult,” the authors wrote. “Fortunately, patients with B19V arthritis symptoms prolonged over many years do not develop joint erosion, a typical finding in RA progression. The difficulty in differential diagnosis is based on the need to identify B19V IgM during the acute illness. B19V viraemia typically resolves by the onset of arthritis, and an isolated B19V IgG may represent remote past infection as B19V IgG may persist lifelong.”
All authors are employed by Labcorp and reported having no disclosures.
Source: BMJ Open
