Epstein-Barr Virus (EBV) Masquerading as Exudative Tonsillitis and Rash in a Transgender Adolescent

A 19-year-old transgender adolescent on hormonal therapy with a history of recent hospitalization for exudative tonsillitis presented with worsening sore throat, dysphagia, fever, and a diffuse, generalized macular rash involving the back, face, abdomen, arms, and legs. Despite prior antibiotic treatment with amoxicillin, her symptoms recurred, prompting further evaluation. Laboratory findings revealed leukocytosis with lymphocytic and monocytic predominance, elevated inflammatory markers, and a positive Epstein-Barr virus (EBV) test, confirming infectious mononucleosis. Imaging demonstrated persistent tonsillitis without abscess formation, and additional testing identified concurrent herpes simplex virus (HSV)-1 oral ulcers. Given persistent fevers and systemic inflammation, hemophagocytic lymphohistiocytosis (HLH) was considered but not confirmed. Management included IV clindamycin for tonsillitis, corticosteroids for airway inflammation, and doxycycline for atypical pneumonia. Over the 10-day hospitalization, the patient showed gradual improvement, with resolution of the rash and all other symptoms. The rash was ultimately diagnosed as an amoxicillin-induced rash associated with EBV infection. This case highlights the importance of recognizing amoxicillin-induced rash in EBV infection and distinguishing it from allergic reactions and other common rashes, including but not limited to scarlet fever, viral exanthem, drug reactions, and HLH. Although various skin rashes are common in the transgender population, a literature review found no evidence linking amoxicillin-induced EBV rash to transgender patients. Accurate diagnosis aids in the appropriate selection of antimicrobial therapy and helps avoid unnecessary antibiotic restrictions due to misattributed allergic reactions.