EBV Amoxicillin Rash — SCE Dermatology MCQ

Correct answer: B — Ampicillin/Amoxicillin administered during EBV infectious mononucleosis causes a characteristic widespread morbilliform eruption in up to 70-100% of patients — this is not true penicillin allergy

The correct answer is B: Ampicillin/Amoxicillin administered during EBV infectious mononucleosis causes a characteristic widespread morbilliform eruption in up to 70-100% of patients, and this is not true penicillin allergy. The temporal link (rash appearing on aminopenicillin exposure during acute EBV infection) plus a positive monospot test is the classic exam pairing pointing to this well-recognised phenomenon rather than IgE-mediated hypersensitivity. The mechanism relates to transient EBV-driven immune activation (polyclonal B-cell stimulation and immune complex deposition) rather than a specific drug-antibody reaction, so it does not predict reactions to penicillins given outside the context of acute EBV infection. UK guidance therefore advises avoiding aminopenicillins in suspected or confirmed glandular fever because of the high rate of this eruption, but the episode should not be coded as a genuine penicillin allergy. Why the other options are wrong: A, No connection: The association is well documented and reproducible, occurring in a very high proportion of patients given aminopenicillins during acute EBV infection, so dismissing it as coincidence ignores an established clinical entity. B, confirms penicillin allergy requiring lifelong avoidance: The rash is EBV-related and self-limiting; labelling the patient penicillin-allergic is inappropriate and denies future safe use of penicillins once the acute EBV illness has resolved. C, anaphylaxis: There are no features of a type I hypersensitivity reaction (no urticaria, angioedema, bronchospasm or hypotension described); this is a delayed morbilliform exanthem, not an IgE-mediated emergency. E, treatment failure: A rash does not indicate antibiotic failure against tonsillopharyngitis; amoxicillin is in fact contraindicated here because the sore throat is due to EBV, a virus unaffected by antibiotics. Key point: A widespread morbilliform rash after aminopenicillins in a patient with confirmed EBV infectious mononucleosis is a well-recognised non-allergic drug-virus interaction and must not be recorded as true penicillin allergy.

Reference: GPnotebook, 'Ampicillin (amoxicillin) and glandular fever', https://gpnotebook.com/en-GB/pages/ear-nose-and-throat/ampicillin-amoxicillin-and-glandular-fever