Secondary syphilis mimicking lepromatous leprosy: A diagnostic challenge

Secondary syphilis is well recognized for its diverse dermatological manifestations and has long been described as the “great imitator,” with clinical presentations that can mimic conditions such as psoriasis, drug eruptions, and leprosy, making recognition of atypical features essential for timely diagnosis and treatment. We report a 55-year-old male hotel worker with hypertension who presented with a three-week history of generalized, asymptomatic erythematous papulosquamous lesions involving the trunk, face, scalp, palms, and soles, associated with intermittent arthralgia. Examination revealed generalized erythematous scaly papules and plaques over the trunk, diffuse facial infiltration with nodular induration of the earlobes, scalp scaling without alopecia, and coppery-coloured scaly patches over the palms and soles, along with a large painless superficial ulcer on the scrotum. There was no peripheral nerve thickening or neurological deficit. Initial differential diagnoses included leprosy and secondary syphilis. 
Slit skin smears were negative for acid-fast bacilli, while histopathology demonstrated a dense upper dermal perivascular and periadnexal inflammatory infiltrate predominantly composed of plasma cells. Serological testing showed a highly reactive Venereal Disease Research Laboratory (VDRL) titre of 1:1024 and a positive Treponema pallidum particle agglutination assay (TPPA), confirming secondary syphilis. The patient was treated with a single intramuscular dose of benzathine penicillin G (2.4 million units), and at one-month follow-up, lesions had regressed with a decline in VDRL titre to 1:512 after treatment. This case highlights the importance of considering syphilis in the differential diagnosis of asymptomatic generalized cutaneous eruptions mimicking leprosy, emphasizing the role of careful clinical evaluation supported by appropriate serological and histopathological investigations for accurate diagnosis and management.