A 22-year-old medical student develops fever to 39.5°C, severe sore throat, and cervical lymphadenopathy 3 days after starting ampicillin for presumed bacterial tonsillitis. On examination he has a maculopapular rash covering the trunk and limbs, mild splenomegaly, and exudative tonsillitis. Monospot test is positive. What is the mechanism of the rash in this patient?
- A Direct viral exanthem from Epstein-Barr virus
- B Immune complex-mediated hypersensitivity reaction to ampicillin in the setting of EBV infection ✓
- C IgE-mediated type I hypersensitivity (true penicillin allergy)
- D Drug reaction with eosinophilia and systemic symptoms (DRESS)
Explanation
The characteristic ampicillin/amoxicillin rash in infectious mononucleosis (EBV infection) occurs in > 90% of patients given aminopenicillins and is an immune-mediated phenomenon, not a true IgE-mediated allergy. EBV causes massive B-cell proliferation, generating antibodies including those that cross-react with aminopenicillin drug-hapten complexes, leading to immune complex and T-cell–mediated skin reactions. Importantly, this does not predict future penicillin allergy; the patient can usually tolerate penicillin after EBV has cleared. True type I hypersensitivity would produce urticaria/angioedema/anaphylaxis within minutes. DRESS is characterized by late-onset rash (> 2 weeks after drug start), internal organ involvement, and eosinophilia — distinct features from this presentation.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.