The diagnosis of syphilitic uveitis is supported by history and clinical presentation. It is confirmed by serologic testing. Primary syphilis may occasionally be diagnosed by direct visualization of spirochetes with dark-field microscopy and by direct fluorescent antibody tests of lesion exudates or tissue. Serodiagnosis is based on the results of both nontreponemal and treponemal antigen tests. Nontreponemal tests include the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) evaluations. Treponemal tests include the fluorescent treponemal antibody absorption (FTA-ABS) assay and the microhemagglutination assay for T pallidum antibodies (MHA-TP).
Nontreponemal and treponemal antigen tests
Nontreponemal antibody titers correlate with disease activity, generally increasing during primary or secondary syphilis and decreasing when the spirochetes are not active, such as during latent syphilis or after adequate antibiotic treatment. They are useful barometers for monitoring therapy for both systemic and ocular disease. Results of treponemal tests become positive during the secondary stage of syphilis and remain positive throughout the patient’s life; as such, they are not useful in assessing therapeutic response.
Testing for HIV infection should be performed in all patients with syphilis, given the high frequency of coinfection. As a result of passive transfer of immunoglobulin G (IgG) across the placenta, VDRL and FTA-ABS IgG test results are positive among infants born to mothers with syphilis. For this reason, serodiagnosis of congenital syphilis is made using the immunoglobulin M (IgM) FTA-ABS test, which indicates infection in the infant.
False-positive nontreponemal test results occur in a variety of medical conditions, including systemic lupus erythematosus (SLE), leprosy, advanced age, intravenous drug abuse, bacterial endocarditis, tuberculosis, vaccinations, infectious mononucleosis, HIV infection, atypical pneumonia, malaria, pregnancy, rickettsial infections, and other spirochetal infections (eg, Lyme disease). False-positive treponemal test results are rare (1%–2%) and may occur with other spirochetal infections (Lyme disease, leptospirosis), autoimmune disease (SLE, primary biliary cirrhosis, and rheumatoid arthritis), leprosy, malaria, and advanced age. Although nontreponemal tests are appropriate for screening large populations with a relatively lower risk for syphilis, specific treponemal tests, such as FTA-ABS, have a higher predictive value in patients with uveitis and should be used in conjunction with nontreponemal tests in diagnosing and treating ocular syphilis. Both the false-positive and false-negative rates of serologic testing may be greater in HIV-infected patients. A lumbar puncture with examination of cerebrospinal fluid (CSF) is warranted in every case of syphilitic uveitis. A positive CSF VDRL result and/or pleocytosis is diagnostic for neurosyphilis, as CSF VDRL may be nonreactive in some cases of active CNS involvement. Although less specific, the CSF FTA-ABS test is highly sensitive and may be useful in excluding neurosyphilis. Follow-up for patients with chorioretinitis and abnormal CSF findings requires spinal fluid examination every 6 months until the cell count, protein, and VDRL results return to normal.
Other tests such as specific enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR)–based DNA amplification techniques are being used with increasing frequency in the serodiagnosis of syphilis. Given their high sensitivity and specificity, these techniques, particularly PCR analysis of intraocular and/or cerebrospinal fluids, may be valuable in confirming the diagnosis in atypical cases.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.