A case of syphilis associated with immune reconstitution inflammatory syndrome and review of the literature

Background: Immune reconstitution inflammatory syndrome (IRIS) associated with syphilis has rarely been described in HIV-infected patients. Diagnosis can be challenging because it is not always possible to discern it from a recent infection or a worsening of an undiagnosed one. Case presentation: An HIV-positive 42-year-old man with a poor compliance history of antiretroviral therapy presented at our unit and complained of ocular symptoms. Ocular syphilis diagnosis was posed after initial misdiagnosing with cytomegalovirus infection, and antiretroviral therapy compliance improved after switching to a bictegravir-based regimen. Despite intravenous (IV) penicillin, we observed an initial worsening with the appearance of new skin lesions, and IRIS syphilis was suspected. In the literature, 14 cases of IRIS syphilis are described, all regarding male patients. Seven were HIV naïve to therapy, and 7 HIV-experienced with poor therapy compliance. Basal syphilis serology was negative in ten, with subsequent seroconversion after the development of IRIS. IRIS-syphilis development was observed after a median time of 28 days from ART initiation; 10 cases were considered "unmasking-IRIS" and 4 "paradoxical-IRIS". Skin and ocular involvement were the most often reported. In most cases, it was not necessary to use a systemic steroid. A good outcome was reported in 12. Conclusions: Syphilis should be considered in differential diagnosis with other diseases associated with IRIS. A negative syphilis serology before beginning antiretroviral therapy could convey the impression that syphilis has been ruled out. Whereas a high index of suspicion should be maintained when symptoms suggestive of syphilis, such as ocular and skin manifestations, are noticed after therapy has begun.