No peripheral eosinophilia was noted on his blood smear. Blood cultures were negative for bacteria, mycobacteria, and fungi. Initial rapid plasma reagin (RPR) was nonreactive in an undiluted specimen and at 1:1024 dilution ruling out a prozone effect. Liver function tests were mildly elevated, and a hepatitis B viral DNA was 2 million copies/mL. A parvovirus polymerase chain reaction, serum cryptococcal antigen, and toxoplasma immunoglobulin G were all negative.
A punch biopsy was performed and revealed interface dermatitis associated with lymphoplasmacytic infiltrates, and spirochetes were noted on Steiner stain (Fig. 3). One month later, repeated RPR was positive with a 1:32 dilution and the fluorescent treponemal antibody absorbed (FTA-ABS) test was also positive.
Patient was treated with intramuscular injection of 2.4 million units of benzathine penicillin resulting in resolution of his symptoms.
The patient had secondary syphilis with initial negative serologic testing. The high clinical suspicion for secondary syphilis in our patient despite an initial negative RPR and the absence of prozone effect prompted a skin biopsy to confirm the diagnosis.
Early syphilis is on the rise in men having sex with men due to an increase in unsafe practices likely favoring the transmission of other sexually transmitted diseases.1
Early diagnosis of syphilis is therefore important in a patient presenting with rash but can be difficult due to a broad range of differential diagnosis making syphilis the "great imitator." Treponema pallidum is a fastidious organism that does not grow in routine laboratory cultures. Therefore, the diagnosis usually relies on serologic testing. The diagnosis is made more difficult with initial false-negative serologic tests or delay in positive reactions particularly in HIV patients. Although nontreponemal tests are believed to be virtually 100% sensitive in secondary syphilis, this may not be applicable in a HIV setting particularly in the advanced stage of the disease.2 Due to a dysregulation of the humoral immune system in AIDS patients, response to T. pallidum antigens can be decreased resulting in a negative result or a delayed positive result.
To our knowledge, 9 other cases of seronegative syphilis in HIV patients have been described in the literature.3-9 The median age was 33 (range, 26-45) years. Seven were male and 2 were female. Seronegative secondary syphilis occurred mostly in the setting of AIDS, with CD4 counts ranging from 69 to 340 cells/μL. Three patients had a previous history of syphilis.6,8,9 A chancre was present in addition to the generalized skin rash in only 1 of the patients.3 Initial negative serology resulted in delayed diagnosis in all patients. Repeated serology was available in 6 patients3-7 and remained negative in 2 of them.6 Diagnosis was made by skin biopsy in all patients except one where the patient had multiple episodes of syphilis in the past and was treated empirically for secondary syphilis despite a negative RPR.6
Treatment of secondary syphilis prevents late complications of the disease as well as sexually transmitted diseases transmission in a high-risk group such as HIV patients. The treatment of secondary syphilis in HIV-infected patients does not differ when compared to non-HIVpatients. When follow-up was available on the 9 patients reported in the literature, all patients had resolution of their symptoms. Two patients experienced a Jarisch-Herxheimer reaction.6,7 It has also been reported that an initial negative RPR will become positive after penicillin therapy likely due to destruction of a large number of treponemes enhancing the production of reaginic antibodies.10
Physicians need to be aware of a negative or a delayed positive serology in early syphilis especially in the setting of an immunocompromised state. A high index of suspicion is required and a skin biopsy is often needed to establish the diagnosis.
The authors thank Dr Jeannette Guarner from the Department of Pathology and Dr Steven T. Prior from the Department of Medicine for their help.
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10. Dutta RK, Malik AK. An unusual case of seronegative secondary syphilis (case report). Indian J Dermatol