Pitfalls in the Serologic Diagnosis of Syphilis in Pregnancy: Is It Syphilis?

Background

Reverse syphilis screening for diagnosis of syphilis begins with a treponemal IgG/IgM screening test (e.g., multiplex flow immunoassay [MFI]; enzyme-linked immunoassay [ELISA]) that if reactive, is followed by a quantitative nontreponemal test (e.g., rapid plasma reagin [RPR]). Per CDC, reactive results on both tests confirm syphilis. Pregnancy, however, is associated with false-positive results on both treponemal screening and RPR tests. Confirmatory testing with the Treponema pallidum-Particle Agglutination (TP-PA) or fluorescent treponemal antibody absorption (FTA-ABS) test is needed to exclude false-positive TP IgG/IgM or RPR reactions but such testing is not routinely recommended.

Methods

Retrospective review of the electronic health records of 5 mothers who were tested for syphilis during pregnancy/delivery using the reverse sequence algorithm and their infants. Demographic, clinical, and laboratory data were recorded.

Results

All 5 mothers had a positive TP IgG/IgM test, reactive RPR test, but a nonreactive (NR) confirmatory test for syphilis (4, TP-PA; 1, FTA-ABS tests), indicative of false-positive screening tests.

Case 1: 20-yr Black woman who at 28 weeks, the TP IgG/IgM test was positive, but RPR and TP-PA tests were NR. At delivery, the TP-IgG/IgM test remained positive, and the RPR titer was 1:1. Repeat TP-PA test again was NR. The infant’s RPR test was NR, and the physical examination was normal.

Case 2: 29-yr white woman with Type 1 diabetes and polycystic ovarian syndrome. TP IgG/IgM test was positive with NR RPR and TP-PA tests. Repeat testing revealed a 1:1 RPR titer, but TP-PA NR. The infant was normal. The woman nor infant were treated for syphilis.

Case 3: 34-yr white woman with hypothyroidism. The TP IgG/IgM test was positive and RPR titer was 1:2, but both the FTA-ABS and TP-PA tests were NR at delivery (22 weeks). One infant died but neither were diagnosed with congenital syphilis.

Case 4: mother had a positive TP IgG/IgM test and RPR titer of 1:1 at delivery. She was diagnosed with syphilis and both mother and infant received benzathine penicillin, but on follow-up, both the mother and infant’s TP-PA tests were NR.

Case 5: 29-yr HIV-infected mother had a positive TP-IgG/IgM test and RPR titer of 1:2 at delivery. Mother’s TP-PA was NR.

Conclusion

Both false-positive TP IgG/IgM and RPR tests can occur during pregnancy, and performance of TP-PA testing is needed to confirm or refute a diagnosis of syphilis. These cases highlight current pitfalls in the serologic diagnosis of maternal and congenital syphilis.