Epstein-Barr virus-associated infectious mononucleosis exhibits substantially higher non-treponemal test titers in biological false-positive reactions.

OBJECTIVES

Biological false-positive (BFP) reactions in rapid plasma reagin (RPR) tests can complicate syphilis screening interpretation. Although Epstein-Barr virus-associated infectious mononucleosis (EBV-IM) is a known cause of BFP reactions, the characteristics of RPR titers in such cases remain unclear. This study aimed to compare the RPR titers in BFP reactions between patients with EBV-IM and those with other underlying conditions.

METHODS

We retrospectively analyzed the RPR and Treponema pallidum hemagglutination assay (TPLA) results of all tests performed at a community hospital in Japan between April 2016 and March 2024. BFP reactions were defined as positive RPR and negative TPLA results. Clinical characteristics and RPR titers were compared between EBV-IM and other causes of BFP reactions.

RESULTS

Among 154 confirmed BFP cases, EBV-IM cases (n = 7) showed significantly higher RPR titers than other underlying conditions (n = 147) (median 28.5 relative units [RU], interquartile range [IQR]: 11.2-31.2 vs. 1.9 RU, IQR: 1.2-4.3, p < 0.001), despite a significantly younger age (median age 18 years, IQR: 17.4-25 vs. 72 years, IQR, 44.5-82, p < 0.001). Among all BFP cases, neoplasms were the most common underlying condition (22.1 %), followed by digestive diseases (8.4 %) and infectious diseases (7.8 %).

CONCLUSIONS

EBV-IM is associated with distinctively high RPR titers in BFP reactions, in contrast to the typically low titers observed under other conditions. Clinicians should be aware that high RPR titers can occur during BFP reactions, particularly in young patients with suspected EBV infection.