There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis, but is widely known to be insensitive. VDRL-CSF is often inappropriately ordered without prior confirmation of a positive serum treponemal test. We seek to describe the clinical characteristics and possible causes of biological false positives in patients with false positive VDRL-CSF.
We retrospectively identified cases of false positive VDRL-CSF across a 3-year period received by the Immunology and Serology Laboratory in the Department of Pathology, Singapore General Hospital. A false positive VDRL-CSF is defined as a reactive VDRL-CSF with a nonreactive Treponema pallidumparticle agglutination (TPPA)-CSF and/or Line Immuno Assay (LIA)-CSF IgG, whereas a true positive VDRL-CSF is a reactive VDRL-CSF with a concordant reactive TPPA-CSF and/or LIA-CSF IgG.
During the study period, a total of 1,926 patients received VDRL-CSF examination. Amongst these, 52 (2.70%) were true positive cases and 11 (0.57%) were false positive cases. One of these 11 patients was found to be misdiagnosed as neurosyphilis as per our laboratory definition. Amongst our eleven patients, one had advanced HIV disease and another one patient has known thyroid malignancy. Eventual diagnoses include 2 cases of meningoencephalitis, 2 cases of drug-induced psychosis, 3 cases of demyelinating disease and 4 cases of neurodegenerative diseases.
Biological false positive VDRL-CSF may be more common than we think. When investigating for neurosyphilis, a serological diagnosis of syphilis with a positive serum treponemal test should always preceed any CSF evaluation. CSF treponemal tests on VDRL-CSF reactive samples may also be necessary to confirm neurosyphilis in patients with a serological diagnosis of syphilis whose clinical presentation and/or progress with appropriate treatment is atypical.
S. Zheng, None