Palmoplantar Maculopapular Rash Mimicking Secondary Syphilis in Infectious Mononucleosis After Sequential Antibiotic Exposure: A Case Report

Infectious mononucleosis caused by Epstein-Barr virus (EBV) commonly presents with pharyngitis, lymphadenopathy, and fever. Cutaneous eruptions may occur, particularly following antibiotic exposure. We report a case of a man in his late 20s who developed a widespread maculopapular rash following sequential exposure to multiple antibiotics in the setting of acute EBV infection. The rash progressed to involve the palms and soles, raising concern for secondary syphilis and a possible drug hypersensitivity reaction. Investigations demonstrated marked lymphocytosis, elevated inflammatory markers and deranged liver enzymes. Throat culture was negative for beta-haemolytic streptococci and the antistreptolysin O titre did not suggest recent streptococcal infection. Treponema pallidum antibody testing and measles polymerase chain reaction (PCR) were negative. Subsequent EBV PCR and repeat serology supported acute EBV infection. The patient improved with conservative management, with resolution of the rash and normalization of the white cell count and liver enzymes at follow-up. Retrospective review also identified prior intravenous amoxicillin exposure during admission for appendicitis, adding further uncertainty regarding the cause of the eruption. This case highlights the diagnostic complexity of rash occurring during acute EBV infection following multiple antibiotic exposures and the importance of considering both EBV-associated exanthem and drug hypersensitivity in the differential diagnosis. Accurate assessment of suspected penicillin allergy is important to guide future antibiotic prescribing.