Rupioid Syphilis Beyond Immunosuppression: A Systematic Review of Cases in HIV-Negative Patients

Rupioid syphilis (malignant syphilis or lues maligna) is a severe ulcero-nodular manifestation of infection originating from Treponema pallidum. It is typically associated with immunosuppressed states, notably those derived from HIV co-infection. This systematic review aims to highlight the rare instances in which this multi-faceted disease affects those with HIV seronegative immune status. A review of cases was conducted using PubMed, Embase, and Web of Science databases with Boolean operators utilizing all variants of "malignant syphilis" or "lues maligna" or "rupioid syphilis" combined with "immunocompetent." Relevant studies included those from inception through August 2026. After removal of duplicates and screening, a total of 20 cases were selected based on inclusion criteria. The results revealed consistent clinical features, including systemic symptoms and ulcerative-necrotic lesions in 20 patients lacking underlying HIV immunosuppression. These findings underscore the importance of maintaining high clinical suspicion for syphilis in patients presenting with necrotic papuloulcerative lesions and systemic manifestations, regardless of HIV status, to ensure timely diagnosis and management.