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

Background: Herpes simplex virus (HSV) infections can present atypically, mimicking a variety of other dermatologic and sexually transmitted diseases. This clinical variability can lead to misdiagnosis and delayed treatment. Case Presentation: We present the case of a 47-year-old male with a history of recurrent genital sores who presented with uncomplicated genital and anal ulcers along with a new targetoid rash on his palms and soles. The clinical picture, particularly the acral rash, strongly suggested secondary syphilis, for which he was empirically treated. Diagnosis and Outcome: Subsequent laboratory testing was negative for syphilis but polymerase chain reaction (PCR) testing of the lesions returned positive for HSV type 2. The acral rash was clinically diagnosed as erythema multiforme (EM) secondary to the HSV infection. The patient’s symptoms and lesions resolved completely following treatment with high-dose valacyclovir. Conclusion: This case highlights that HSV-triggered erythema multiforme can create a clinical presentation that strongly mimics secondary syphilis. Clinicians should maintain a high index of suspicion for HSV and its polymorphic manifestations in the differential diagnosis of patients presenting with genital ulcers and associated acral rashes.