Hypersensitivity reactions
Hypersensitivity reactions are the four Gell and Coombs mechanisms, IgE-mediated (I), cytotoxic antibody (II), immune complex (III), and delayed T-cell (IV), by which the immune system injures host tissue. Diagnosis matches the clinical phenotype to a type-specific test; the immediately life-threatening form, anaphylaxis, is treated first-line with intramuscular epinephrine.
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What this article covers
- Overview
Definition: hypersensitivity reactions are immune responses against a foreign or self antigen that injure the host; the Gell and Coombs scheme groups them into four mechanistically distinct types, I through IV.
- Epidemiology
Overall pattern: type I atopic disease is the most common hypersensitivity reaction; drug reactions drive most inpatient consultations for a new rash, while types II and III disease are individually rare.
- Risk factors
Atopy and prior sensitization: a personal or family history of asthma, allergic rhinitis, or eczema, and any prior reaction to the same allergen, predict a future type I reaction.
- Pathophysiology
Type I, IgE-mediated: allergen cross-links preformed, allergen-specific IgE on mast cells and basophils; an immediate phase (minutes) releases histamine and tryptase, and a late phase (hours) recruits eosinophils.
- Clinical features
Type I: urticaria, angioedema, flushing, bronchospasm, and gastrointestinal symptoms within minutes; about 90% of anaphylactic episodes include urticaria or angioedema.
- Differential diagnosis
Vasovagal syncope: mimics anaphylactic hypotension, but bradycardia, pallor, and diaphoresis replace the tachycardia and flushing of a type I reaction.
- Diagnosis
What establishes the diagnosis: there is no single unifying assay; the diagnosis is established by matching the clinical phenotype to a type-specific confirmatory test, allergen-specific IgE for type…
- Management
First-line, immediate for type I (anaphylaxis): epinephrine 0.3 to 0.5 mg (0.01 mg/kg) intramuscularly into the anterolateral thigh, repeated every 5 to 15 minutes; position supine with legs raised…
- Complications
Anaphylactic death: occurs within minutes from airway obstruction or refractory shock, particularly with cardiovascular disease or a drug trigger.
- Prognosis
Type I: most anaphylactic episodes resolve with prompt epinephrine; fatality is rare but rises with delayed treatment or cardiovascular disease.
- Prevention
Avoidance first, for every type: a documented trigger, drug, food, venom, or contact allergen, should be listed prominently in the record, with a written action plan.
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Related articles
- Anaphylaxis
Anaphylaxis is an acute, potentially fatal systemic hypersensitivity reaction from massive mast cell and basophil mediator release, presenting within minutes as skin, respiratory, cardiovascular, and gastrointestinal involvement after allergen exposure. It is a clinical, treat-first diagnosis, and intramuscular epinephrine is the immediate life-saving therapy.
- Serum sickness
Serum sickness is the prototypic type III (immune-complex) hypersensitivity, occurring about 1 to 2 weeks after exposure to a foreign protein or drug and presenting with fever, rash, and arthralgia. Diagnosis is clinical from the timing and triad with low complement and possible immune-complex markers, and treatment is stopping the trigger with antihistamines, NSAIDs, and corticosteroids for severe disease.
- Drug hypersensitivity reaction
Drug hypersensitivity reactions are immune-mediated adverse drug reactions classified by the Gell-Coombs system into immediate IgE-mediated (type I) and delayed T-cell-mediated (type IV) forms, ranging from urticaria and anaphylaxis to severe cutaneous reactions. Diagnosis rests on the reaction phenotype and timing, and management is stopping the culprit, treating by mechanism, and documenting the drug to prevent re-exposure.
- DRESS syndrome
DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is a severe delayed drug hypersensitivity presenting 2 to 6 weeks after the culprit drug with fever, a morbilliform rash with facial edema, lymphadenopathy, eosinophilia, and internal-organ involvement, especially hepatitis. Diagnosis uses the RegiSCAR criteria, and treatment is immediate drug withdrawal and systemic corticosteroids with a slow taper.
- Urticaria
Urticaria is transient, pruritic, edematous wheals from mast cell histamine release, classified by duration into acute (under 6 weeks) and chronic (6 weeks or longer, usually spontaneous/idiopathic). Diagnosis is clinical with minimal testing, and treatment is stepwise second-generation H1 antihistamines up-titrated as needed, adding omalizumab for refractory chronic disease.
- Angioedema
Angioedema is self-limited, non-pitting swelling of the deep dermis and submucosa that follows one of two mechanisms: mast cell (histamine) mediated, which occurs with urticaria and responds to epinephrine and antihistamines, or bradykinin mediated, which occurs without urticaria and does not. Distinguishing the two determines whether treatment is allergic therapy or bradykinin-targeted therapy, and airway involvement is the central danger.
- Graft-versus-host disease
Graft-versus-host disease is a complication of allogeneic hematopoietic stem cell transplantation in which donor T cells attack recipient tissues, classically the skin, liver, and gut in the acute form and multi-organ fibrosis in the chronic form. Diagnosis is clinical, supported by biopsy, and management is prophylaxis with a calcineurin inhibitor plus methotrexate and treatment with corticosteroids, escalating to agents such as ruxolitinib for steroid-refractory disease.