In Canada, drug Allergy is managed by allergy & immunologists. Drug allergy is an immune-mediated hypersensitivity reaction to a medication that affects roughly 7% of the general adult population over their lifetime, with antibiotics, NSAIDs, and chemotherapy agents accounting for most cases. Reactions span minutes to weeks after exposure and range from mild rash to fatal anaphylaxis and severe cutaneous adverse reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis).
Drug allergy (ICD-10: T88.7 unspecified adverse effect of drug or medicament; specific subtypes coded under T78 and L51) is an immune-mediated hypersensitivity reaction to a medication or biological agent. It is distinct from non-immune adverse drug reactions, which account for roughly 80% of all adverse medication events and include pharmacologic side effects, drug interactions, idiosyncratic reactions, and intolerance. True drug allergy is classified by the Gell-Coombs framework into four immunopathologic types: Type I (IgE-mediated immediate reactions including urticaria, angioedema, bronchospasm, and anaphylaxis within minutes to two hours); Type II (cytotoxic antibody-mediated reactions such as drug-induced immune hemolytic anemia, thrombocytopenia, neutropenia); Type III (immune complex reactions including serum sickness, drug-induced vasculitis); and Type IV (T-cell-mediated delayed reactions ranging from morbilliform exanthema to severe cutaneous adverse reactions). Type IV is further subdivided into IVa (Th1 with macrophage activation), IVb (Th2 with eosinophil involvement, e.g.
The key symptoms of Drug Allergy are: Sudden itchy maculopapular rash, hives, or angioedema within minutes to two hours of exposure (IgE-mediated immediate reactions)., Wheezing, throat tightness, or stridor with hypotension developing minutes after drug exposure — anaphylaxis., Symmetric morbilliform (measles-like) rash on the trunk and extremities developing 5-14 days after starting a new drug (typical delayed reaction)., Painful, spreading erythema followed by blistering, mucosal involvement, and skin detachment in Stevens-Johnson syndrome or toxic epidermal necrolysis., Fever, facial edema, widespread rash, lymphadenopathy, and abnormal liver enzymes in DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) 2-8 weeks after starting an anticonvulsant or allopurinol., Rapidly spreading sterile pustules on a background of erythema, fever, and neutrophilia in acute generalized exanthematous pustulosis (AGEP)., Joint pain, urticaria, fever, and proteinuria 7-21 days after exposure — serum sickness or serum sickness-like reaction..
Diagnosis begins with a detailed history covering drug name and dose, indication, timing of reaction relative to first dose and last dose, character and distribution of symptoms, presence of systemic features (fever, mucosal involvement, organ dysfunction), prior exposures, and concomitant medications and infections. The history alone determines next steps: a mild morbilliform rash on day 7 of amoxicillin in a child is often safely confirmed with a graded oral challenge; a vesiculobullous eruption with mucosal involvement is SJS/TEN until proven otherwise and demands immediate drug withdrawal, supportive care, and never re-challenge. Skin testing is the gold standard for immediate Type I reactions to beta-lactams: skin prick test with major and minor determinants and amoxicillin, followed by intradermal testing if negative. Negative skin tests followed by a supervised graded oral challenge confirm safety with 95-99% accuracy for penicillin. Patch testing helps diagnose delayed reactions to many drugs at 48-96 hours. Specific IgE in vitro tests are useful adjuncts for some drugs (penicillin, neuromuscular blockers, chlorhexidine, omeprazole). Tryptase drawn 30 minutes to 4 hours after an anaphylactic episode confirms mast cell activation. For severe cutaneous reactions (SJS/TEN, DRESS, AGEP), skin biopsy and laboratory studies (complete blood count, liver function, renal function, eosinophil count) support diagnosis; the RegiSCAR criteria grade DRESS severity. Drug challenge is contraindicated in patients with history of severe cutaneous adverse reaction, anaphylaxis to high-risk agents, or unstable comorbidities. Penicillin allergy delabeling clinics are now widespread because incorrect labels drive worse antibiotic outcomes; structured assessment safely removes labels in approximately 90% of patients.
Outcomes vary widely by reaction type. Mild immediate and delayed drug allergic reactions resolve within days of discontinuing the drug, usually without long-term consequences. Anaphylactic reactions have a case-fatality under 1% when adrenaline is given promptly. Severe cutaneous adverse reactions have substantial mortality: TEN approximately 25-50% in mortality despite optimal care; SJS approximately 5-15%; DRESS approximately 5-10% (mostly from organ involvement). Long-term sequelae of SJS/TEN include ocular scarring (up to 50%), chronic skin pigmentary change, nail dystrophy, and psychological burden. DRESS survivors have a roughly 10% incidence of autoimmune disease (thyroiditis, type 1 diabetes, lupus) in the years following recovery and require long-term follow-up. Penicillin allergy labels that are correctly removed restore access to first-line antibiotics and are associated with shorter hospital stays, lower MRSA and C. difficile rates, and lower healthcare costs. Pharmacogenomic screening continues to expand and shift the prognosis of drug allergy toward primary prevention.
Allergy and immunology referral is appropriate after any anaphylactic reaction to a drug, suspected severe cutaneous adverse reaction (SJS/TEN, DRESS, AGEP), drug allergy that limits use of essential medications (penicillins, contrast media, chemotherapy), multiple drug allergies, and any patient labeled as drug-allergic who needs an excluded drug for a life-threatening indication. Specialists confirm or exclude allergy through validated testing and supervise desensitization if needed.
Find specialists →Immediate IgE-mediated reactions: symptoms resolve over hours to days; full recovery in 1-2 weeks. Mild delayed reactions: rash resolves over 1-3 weeks after drug withdrawal. DRESS: 4-12 weeks; relapses possible during steroid taper. SJS/TEN: skin recovery 3-6 weeks; eye and mucosal complications may persist for months. Drug desensitization induces temporary tolerance only — protective effect lost within hours of stopping the drug.
Light to moderate exercise is safe between reactions. Pause structured exercise during the acute phase of any moderate to severe reaction and resume gradually after symptoms resolve. Patients recovering from severe cutaneous adverse reactions need rehabilitation guided by the burn or specialty team, with skin care, scar management, and progressive activity reintroduction over months.
Look for a board-certified allergist/immunologist with documented experience in drug allergy testing, including penicillin skin testing, supervised oral challenge, and desensitization. Tertiary centers offering chemotherapy and antibiotic desensitization, severe cutaneous adverse reaction follow-up, and HLA testing provide the most complete care.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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