Review Question - QID 107202

This patient’s presentation is consistent with secondary syphilis, given the maculopapular rash on his palms, the white mucous patch on his tongue, and the visualization of spirochetes on dark-field microscopy. The negative RPR/VDRL test is a result of the prozone phenomenon, which is caused by excess antibodies leading to an imbalance of the antibody to antigen ratio.

The RPR/VDRL test is the initial screening test for syphilis infection. These tests detect anti-cardiolipin antibodies produced by an infected patient. With an appropriate ratio of antibody and antigen, a precipitation reaction called flocculation occurs, which demonstrates a positive test for syphilis infection. In HIV positive patients, there is hyperactivity of B-cell behavior that leads to excess production of anti-cardiolipin antibodies. The resulting excess antibody, or prozone phenomenon, leads to a failure to detect flocculation and a false negative RPR/VDRL test.

Birnbaum et al. review the presentation, diagnosis, and management of syphilis infection. The clinical manifestations and incubation times are reviewed in Illustration A. Patients suspected of having syphilis infection should initially be screened with the RPR/VDRL test. Within 3 weeks of the initial syphilis infection, there is a possibility for a false negative RPR/VDRL result, but the sensitivity is very high for cases of secondary syphilis. A more common problem with RPR/VDRL tests are false positives, which can be seen with an acute febrile illness, hepatitis, HIV, tuberculosis, lupus and other connective tissue disorders, malignancy, and IV drug use.

Sidana et al. review the prozone phenomenon in secondary syphilis. The prozone phenomenon occurs in about 1-2% of cases, with an increased incidence in HIV positive patients. Most hospital laboratories do not account for the prozone phenomenon when performing RPR/VDRL testing. When a RPR/VDRL screen returns negative in a patient with a high clinical suspicion for syphilis, the laboratory should be asked to dilute the patient’s serum to at least 1/16 to rule out the prozone phenomenon.

Figure A demonstrates a maculopapular rash on the bilateral palms and forearms. Figure B demonstrates a white mucous patch with erosion on the dorsal tongue. Figure C demonstrates the Treponema pallidum spirochete on dark-field microscopy. Illustration A reviews the incubation period and clinical manifestations of the different stages of syphilis.

Incorrect Answers:
Answer 1: A maculopapular rash and leukoplakia can be seen in HIV patients, but this patient’s symptoms and findings of spirochetes on dark-field microscopy are diagnostic for secondary syphilis.
Answer 3: This patient has secondary syphilis, not primary infection.
Answer 4-5: Alcohol and HIV infection are not known to directly affect the sensitivity of RPR/VDRL testing.