Polymorphic mimicry - When Herpes Isn’t Just Herpes: Genital Herpes Mimicking Secondary Syphilis: A Case Report

Background: Herpes simplex virus type 2 (HSV-2) is a highly prevalent sexually transmitted infection (STI), affecting approximately 13% of the global population. While classic presentations involve painful vesicular clusters, HSV-2 can present atypically or trigger immune-mediated reactions like erythema multiforme (EM). These polymorphic presentations can mimic other STIs, particularly secondary syphilis, leading to diagnostic momentum and delayed appropriate therapy. Case presentation: A 47-year-old male with a history of recurrent genital ulcers presented to the emergency department with worsening penile lesions, anal pain, and a new onset rash on his palms and soles. He had been treated for presumed syphilis two months prior. Examination revealed vesiculopustular genital lesions, inguinal lymphadenopathy, perianal ulcers resembling fissures, and targetoid lesions on the extremities. The clinical triad of genital ulcers, anal pathology, and a palmoplantar rash strongly suggested secondary syphilis. However, syphilis serology returned negative. Polymerase chain reaction (PCR) testing confirmed HSV-2. The acral rash was diagnosed as EM secondary to HSV. Diagnosis and Outcome: The patient was diagnosed with HSV-2 proctitis and HSV-associated erythema multiforme. He was treated with high-dose valacyclovir. At the two-week follow-up, genital and anal lesions had healed, and the systemic rash had resolved. Conclusion: HSV-associated erythema multiforme can produce a clinical picture indistinguishable from secondary syphilis. Emergency clinicians must maintain a broad differential for genital ulcers with acral rashes. PCR testing is superior to syndromic diagnosis in complex presentations to prevent unnecessary antibiotic exposure and ensure timely antiviral management.