A 54–year–old AAM with HIV/AIDS and G6PD deficiency presented with severe weakness and a diffuse rash with alopecia that began 3 months ago. His weakness progressed gradually and he now required assistance to ambulate. He reported anorexia and depressed mood but denied fever, chills, cough or diarrhea. He lives with his HIV–positive wife and does not use illicit drugs, tobacco or alcohol. Physical examination showed oral thrush, patchy alopecia and a diffuse desquamating macular rash with erythrodermic and hypopigmented patches over his entire body including palms and soles (Fig. 1). Laboratory data revealed anemia of chronic disease, CD4 count 6/mL, HIV RNA Viral Load 99,000 copies/mL and a normal TSH. Rapid plasma reagin (RPR) was nonreactive even with dilution testing. Cerebrospinal fluid analysis was unremarkable with sterile cultures, a nonreactive Venereal Disease Research Laboratory (VDRL) and a negative cryptococcal antigen. A skin biopsy was performed and showed abundant Treponema pallidum (Fig. 2) yielding the diagnosis of secondary seronegative syphilis. He was treated with penicillin G benzathine according to CDC guidelines with good response.
We present a case of seronegative syphilis. Our patient had multiple negative serologies by his infectious disease physician prior to admission. Initially a prozone effect was thought responsible for the negative RPR but serum dilution to 1:124 failed to detect antibodies against T. pallidum. Treponemal serologic antibody studies including fluorescent treponemal antibody absorption (FTA–ABS), microhemagglutination test for antibodies to T. pallidum (MHA–TP), T. pallidum particle agglutination assay (TP–PA) and T. pallidum enzyme immunoassay (TP–EIA) have 84% sensitivity in primary syphilis and nearly 100% sensitivity in secondary and tertiary syphilis. The gold standard, however, remains direct observation of the spirochete by dark field or fluorescent microscopy. Seronegative syphilis occurs rarely in late HIV infection. In AIDS, an impaired humoral immune system diminishes the response to T. pallidum antigen, causing a negative serology result.
The diagnosis of syphilis remains challenging since it resembles many conditions. With a clinical suspicion for syphilis in the setting of negative serology, direct microscopic examination of lesions is indicated. Untreated syphilis can have devastating consequences which is unacceptable when affordable and effective treatment exists.
Figure 1T. pallidum detection in skin biopsy by IHC.
Figure 2Skin photo.