Treponemal and Lipoidal IgM Tests in the Diagnosis and Management of Syphilis Among Nonpregnant Adults: A Systematic Review

There are many commercially available tests that isolate immunoglobulin M (IgM) antibodies to either treponemal-specific or lipoidal (nontreponemal) antigens. These IgM tests for syphilis are distinct from standard serologies that are routinely used (e.g., T. pallidum particle agglutination, or TPPA), most of which detect a combination of IgM and IgG antibodies. There are several clinical scenarios where IgM tests for syphilis may be of clinical utility: in diagnosing early primary syphilis, in differentiating early from late latent syphilis, in detecting reinfections, and in identifying persons at increased risk for complications such as neurological syphilis. We performed a systematic review of IgM tests for syphilis among nonpregnant adults, focusing on these clinical scenarios. Thirteen studies were included. The current data suffer from limited sample sizes and significant heterogeneity in syphilis staging, IgM assays, and serological comparators. Whether IgM serologies offer additional clinical benefits beyond standard serologies is unclear. These tests should not be routinely used in the absence of higher quality data.