Penicillin Allergy

Penicillin allergy is a hypersensitivity reaction to penicillin antibiotics. About 10% of people carry the label, but fewer than 10% of them are truly allergic, so many labels can be safely removed.

Pathophysiology. Immediate IgE-mediated reactions occur within an hour of a dose (urticaria, angio oedema, bronchospasm, anaphylaxis), against the penicillin core or side chain. Delayed reactions are T cell mediated and range from benign maculopapular rash to severe cutaneous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP), organ injury and serum sickness like illness.

IgE sensitisation fades over time, and 80% of patients with a past IgE reaction lose sensitivity after 10 years.

Penicillin labels increase use of broad spectrum antibiotics, resistant infection, longer stay and cost.

• Immediate reactions: urticaria, angio oedema, wheeze, stridor, hypotension within 1 hour
• Delayed benign rash: maculopapular exanthem days after the start of treatment
• Severe cutaneous reactions: blistering rash, mucosal ulceration, fever, organ involvement
• Drug induced haemolytic anaemia, interstitial nephritis, hepatitis
• Rash during infectious mononucleosis treated with amoxicillin, which is not true allergy
• Gastrointestinal upset or headache reported as allergy

• Detailed history: drug, date, time to onset, features, treatment needed, and repeat exposures. Records from the time are useful.
• Risk assessment (PEN-FAST): penicillin allergy within the last 5 years (2 points), anaphylaxis, angio oedema or severe cutaneous reaction (2 points), treatment needed for the reaction (1 point). A score under 3 means low risk (under 5% positive test).
• Low risk patients: direct oral challenge with amoxicillin 500 mg in adults (children 25 mg/kg, maximum 500 mg), observe for 1 hour, with resuscitation available.
• Higher risk patients: skin prick and intradermal tests with benzylpenicilloyl polylysine, minor determinant mixture, penicillin G and amoxicillin, with specific IgE where available, followed by an oral challenge if negative.
• Do not challenge after a severe cutaneous reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP), drug induced organ injury or haemolysis.
• Delayed benign rash: a longer oral challenge (3 to 5 days) is used in children and adults after a negative immediate test.

Differential diagnosis.

• Viral exanthem or infectious mononucleosis rash
• Non-allergic drug side effects (gastrointestinal upset, headache)
• Urticaria from the infection
• Serum sickness like reaction
• Non-penicillin drug allergy
• Chronic spontaneous urticaria

• Remove the label after a negative test or challenge, record the result in the notes, and inform the patient and general practitioner.
• Active allergy: avoid penicillins and use an alternative antibiotic chosen by infection and local resistance. Cephalosporins with dissimilar side chains (for example cefuroxime, ceftriaxone, ceftazidime, cefazolin) can be given to most patients, since cross-reactivity is under 2%.
• Anaphylaxis: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh, repeated after 5 minutes if no improvement, plus oxygen and intravenous fluids, and observation for at least 6 hours.
• Severe delayed reactions: stop the drug, give supportive care and specialist treatment, and avoid all penicillins permanently.
• Desensitisation when penicillin is essential (for example syphilis in pregnancy, neurosyphilis, enterococcal endocarditis) in a monitored setting, using a stepwise dose escalation regimen by the oral or intravenous route, repeated whenever therapy is interrupted for over 24 hours.
• Wristband or medical alert for confirmed allergy, and updating of electronic records after delabelling.

Special groups.

• Pregnancy: penicillin is used for syphilis and group B streptococcal prophylaxis, so testing before or during pregnancy is advised.
• Children: most reactions are benign rashes during viral illness, so oral challenge is usually safe.

Monitoring. Observation for 1 hour after challenge, and contact if delayed rash occurs. No routine monitoring after delabelling.

Referral and escalation. Refer to a drug allergy service for anaphylaxis, severe cutaneous reaction history, multiple drug allergy labels, or when penicillin is essential. Emergency for anaphylaxis.