Atypical Dermatological Manifestations of Syphilis in Advanced HIV: A Case-Based Narrative Review

Syphilis, a sexually transmitted infection caused by Treponema pallidum (T. pallidum), is re-emerging globally. Recent epidemiological data show a rising incidence, particularly among men who have sex with men (MSM). Known as 'the great mimic' for its broad clinical spectrum, secondary syphilis classically presents with a maculopapular rash involving the trunk and extremities. However, it can also present with atypical cutaneous manifestations, especially in immunocompromised patients. This aspect may contribute to delayed diagnosis and treatment. Starting from a clinical case, we will conduct a literature review on syphilis/HIV coinfection, with a particular focus on the broad spectrum of cutaneous manifestations and the key differential diagnoses involved. We report the case of a 60-year-old male living with HIV who presented with non-pruritic, polymorphic skin lesions sparing the palms and soles. The patient had a prior history of treated latent syphilis. Initial diagnostic workup excluded common differentials, including monkeypox and fungal infections. Serologic testing confirmed active syphilis with a reactive Rapid Plasma Reagin (RPR) titer of 1:32, skin biopsy showed dense plasma cell-rich infiltrate, and immunohistochemistry was positive for T. pallidum. Despite negative cerebrospinal fluid findings, neurological symptoms prompted treatment with intravenous penicillin G, and the symptoms resolved with treatment. This case underscores the importance of considering syphilis in the differential diagnosis of atypical dermatologic presentations, given its increasing prevalence and potential for severe systemic involvement.