prozone phenomenon

The prozone phenomenon refers to a false negative serological test result that occurs due to excessive antibody titers. The prozone effect occurs more frequently in secondary syphilis (SS) and is relatively common in syphilis with concomitant human immunodeficiency virus (HIV) infection and in pregnancy (Awake P et al.2022).

In patients with syphilis and HIV co-infection, there is excessive antibody production due to abnormal B cell behavior, which leads to an overreaction to antigen stimulation (Cebolla-Verdugo M et al. 2025). Homosexuals have a higher risk of undetected clinical syphilis and HIV due to the painless and transient nature of the primary chancre. They may have a higher incidence of prozone due to HIV-induced B-cell dysfunction, which in turn may increase the likelihood of syphilis going undiagnosed and thus untreated. The simultaneous presence of HIV infection influences the clinical appearance of previously clearly defined diseases and their natural course as well as the response to therapy.

The incidence of the prozone phenomenon is reported to be between 0.5 % and 2 % (Spangler AS et al. 1990). It is assumed to be higher in HIV co-infection. The incidence of prozone phenomenon is gaining clinical importance due to the increasing number of people at risk of sexually transmitted diseases, especially HIV-positive individuals (Awake P et al. 2022).

Case report (Awake P et al.2022): A 20-year-old man presented with an asymptomatic reddish-brown rash on the palms of his hands and the sole of his left foot that had been present for 25 days. He was treated by his GP with topical steroids. The symptoms hardly improved and the rash persisted. A thorough examination revealed erosion on the glans penis and a shallow mucosal ulceration on the hard palate. Therefore, clinically there was a strong suspicion of an early syphilitic infection. The patient denied any history of sexual contact. A further systemic physical examination was performed but revealed no abnormalities. The RPR test was non-reactive. In addition, his CBC, chest X-ray, electrocardiogram (ECG) and other routine tests were all within normal limits. When the RPR test was repeated at a higher dilution, reactivity was seen at a dilution of 1:320. A Treponema pallidum hemagglutination test (TPHA) was performed, which was also positive. An HIV test was found to be seropositive. Therapy: Intramuscular injection of 2.4 MU benzathine penicillin; initiation of antiretroviral therapy (ART).

To rule out a prozone phenomenon, the patient's serum is diluted to bring the antibody concentration into the equivalence range. Therefore, it is important to notify the laboratory in this regard if the clinical findings are strongly suggestive of syphilis and the results of the non-treponemal serologic tests are negative (Awake P et al.2022).

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