Drug allergies and mechanisms - allergies

Scope

Clinical assessment and management of the suspected drug-allergic patient, penicillin being the paradigm case
Distinct problem from the underlying immunology (see companion mechanisms note): most labelled allergies are not confirmed, and unnecessary avoidance causes measurable harm

Penicillin allergy labelled in ~10% of the population; confirmed true allergy in <5% once formally assessed
Labelled patients receive more broad-spectrum antibiotics -> inc rates of resistant organisms, C. difficile, surgical site infection, treatment failure, and cost

See mechanisms note - Type I (IgE) for immediate reactions, Type IV for delayed/SCAR reactions
Cross-reactivity: penicillin/cephalosporin cross-reactivity is far lower than historically taught (~1-2%, driven by shared side-chain structure, not the beta-lactam ring itself) - most cephalosporins are safe in penicillin-allergic patients
Carbapenems - very low cross-reactivity with penicillin, generally safe even in confirmed penicillin allergy

Risk	Features	Approach
Low risk	Isolated rash (non-blistering, no mucosal involvement), remote reaction, GI upset only, unknown/unclear reaction, family history alone	Direct oral challenge without prior skin testing
Moderate risk	Urticaria, delayed mild reaction with uncertain features	Skin testing +/- graded challenge
High risk	Anaphylaxis, recent severe reaction, recurrent reactions to multiple beta-lactams	Specialist allergy assessment, skin testing before any challenge
SCAR history	SJS/TEN, DRESS, AGEP	Never challenge - lifelong avoidance of culprit and structurally related drugs

Direct oral challenge in low-risk patients is now supported without preceding skin testing - a major shift enabling non-allergist-led delabelling programs
Serum tryptase if reaction was severe/anaphylactic, timed appropriately

Low-risk penicillin allergy -> direct oral amoxicillin challenge, observed ~30-60 min, safe and effective, increasingly delivered by non-allergist clinicians (pharmacist- or nurse-led protocols)
Update the medical record immediately on a negative challenge - removes the label, not just "tolerates challenge"

Anaphylaxis - IM adrenaline first-line, call for help, remove/stop the drug, supportive management (airway, fluids)
Urticaria/angioedema without anaphylaxis - antihistamine +/- corticosteroid, stop the drug
SCAR (SJS/TEN, DRESS, AGEP) - stop the drug immediately, supportive/burns-unit care for extensive TEN, dermatology/immunology involvement

Choose an alternative agent with low cross-reactivity (most cephalosporins safe despite penicillin allergy, except those sharing an identical side chain - e.g. avoid cefaclor/cephalexin if reaction was to amoxicillin)
Desensitisation if the allergic drug is the only effective option (e.g. penicillin for neurosyphilis in pregnancy, or specific antibiotic-resistant infections) - specialist-supervised, temporary tolerance only
Document clearly: culprit drug, reaction phenotype, date, and safe alternatives trialled

Over-labelled allergy -> broad-spectrum antibiotic use -> antimicrobial resistance, C. difficile infection
Multiple drug allergy syndrome - reported reactions to several unrelated drug classes, often reflects non-immune sensitivity rather than true multi-drug allergy
Anxiety/avoidance behaviour disproportionate to actual risk once a label is applied

IgE-mediated penicillin allergy wanes over time - ~50% lose sensitivity by 5 years, ~80% by 10 years - supports periodic re-assessment rather than a permanent, unquestioned label
SCAR-related avoidance is lifelong
Successful de-labelling has a durable, measurable benefit on subsequent antibiotic choice and outcomes

8 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.