# False-positive treponemal syphilis serology linked to EBV-related heterophile antibodies: Insights from a multi-platform diagnostic

## TL;DR

A rare case shows that EBV-related antibodies can cause false-positive syphilis tests, highlighting the need for careful diagnosis.

## Contribution

This case highlights a rare cause of false-positive syphilis serology due to EBV-induced heterophile antibodies.

## Key findings

- EBV-induced heterophile antibodies caused false-positive treponemal tests in a patient with no syphilis.
- Blocking heterophilic antibodies resolved the false-positive results in TPPA and TP-Ab.
- The case underscores the importance of combining clinical history with molecular testing for accurate diagnosis.

## Abstract

Syphilis serological false positives associated with interference from heterophile antibodies induced by Epstein–Barr virus (EBV) remain rarely reported. This report aims to document a rare case of syphilis serology discordance ultimately attributed to EBV infection, imitating syphilis serology.

A 34-year-old woman presented with facial skin lesions and underwent syphilis screening. Initial testing revealed reactive Treponema pallidum (T. pallidum) antibody (TP-Ab), positive T. pallidum particle agglutination assay (TPPA), and negative toluidine red unheated serum test (TRUST). Subsequent testing, including chemiluminescent platforms, immunofluorescence (FTA-ABS), Western blot, and colloidal gold methods, was non-reactive. Comprehensive workup for autoimmune and endocrine disorders was unremarkable. Further investigation revealed elevated antiphospholipid antibodies and positive EBV serologies. EBV DNA was detected. After heterophilic antibody blocking, TPPA and TP-Ab returned to negative, confirming false-positive results.

This case illustrates that heterophile antibody interference can simultaneously affect both particle agglutination and chemiluminescence-based treponemal assays, leading to false-positive results. It emphasizes the necessity of interpreting serological findings in conjunction with clinical history and, when appropriate, confirmatory molecular testing, in order to prevent misdiagnosis and unnecessary treatment.