Secondary Syphilis Masquerading as Systemic Lupus Erythematosus: A Clinicopathologic Diagnostic Challenge

Secondary syphilis is known as the "Great Imitator" because of its diverse clinical manifestations, which may resemble infectious, inflammatory, and autoimmune diseases. Although it may mimic systemic lupus erythematosus (SLE), simultaneous clinical, serologic, and histopathologic features strongly suggestive of SLE are uncommon and can result in diagnostic error. We report the case of a 51-year-old man who presented with a three-month history of bilateral conjunctival injection, symmetrical polyarthralgia, diffuse alopecia, oral ulceration, and a generalized pruritic erythematous maculopapular eruption. Initial investigations revealed positive antinuclear antibodies (ANAs), hypocomplementemia, elevated inflammatory markers, and a skin biopsy favoring acute cutaneous lupus erythematosus (ACLE), leading to a provisional diagnosis of SLE. Despite treatment with hydroxychloroquine, methotrexate, and corticosteroids, his cutaneous disease persisted. Subsequent testing demonstrated strongly reactive rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA) results. Correlation of the clinical, serologic, and histopathologic findings established secondary syphilis as the underlying diagnosis. This case illustrates that secondary syphilis can closely mimic SLE across multiple diagnostic domains. Recognition of this uncommon presentation emphasizes the importance of maintaining a broad differential diagnosis and integrating clinical, serologic, and histopathologic findings to avoid misdiagnosis and unnecessary immunosuppressive therapy.