What is a type 1 hypersensitivity reaction?

Type 1 Hypersensitivity Reaction

Type 1 hypersensitivity is an acute IgE-mediated immune reaction where allergen exposure triggers cross-linking of IgE antibodies bound to mast cells and basophils, causing rapid degranulation and release of inflammatory mediators like histamine within minutes to hours (typically 1-6 hours) of exposure. 1

Immunologic Mechanism

• The reaction occurs when allergens cross-link IgE antibodies bound to FcεRI receptors on mast cells and basophils, triggering immediate degranulation. 1
• This represents a true allergic response—an immune-mediated hypersensitivity initiated by specific immunological mechanisms that occurs reproducibly upon exposure to defined allergens at doses normally tolerated by most people. 2, 1
• The IgE-mediated pathway is the classic type I hypersensitivity mechanism originally described in the Gell and Coombs classification system. 3, 4

Key Inflammatory Mediators Released

Histamine is the primary preformed mediator:

• Released within 5 minutes of mast cell activation 1
• Causes vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion 1
• Produces the prototypic short-lived urticarial response 5

Tryptase serves as a biochemical marker:

• Released from mast cells during degranulation 1
• Blood samples should be obtained 15 minutes to 3 hours after reaction onset for optimal measurement 1

Other mediators include prostaglandins, leukotrienes, cytokines, and chemokines that contribute to the variable clinical presentation and evolution of symptoms. 6, 5

Clinical Manifestations by Organ System

Cutaneous symptoms (most common):

• Urticaria (hives), pruritus, flushing, and angioedema affecting lips, tongue, or uvula 1, 7

Respiratory involvement:

• Upper airway: rhinorrhea, nasal congestion, sneezing, laryngeal edema, stridor 1
• Lower airway: bronchospasm, wheezing, dyspnea, reduced peak expiratory flow 1, 7

Cardiovascular manifestations:

• Hypotension, tachycardia, thready or unobtainable pulse, dizziness, syncope 1, 7
• In severe cases: cardiovascular collapse 1

Gastrointestinal symptoms:

• Nausea, vomiting, abdominal cramping, diarrhea 1, 7

Anaphylaxis represents the most severe form—a life-threatening systemic reaction involving multiple organ systems simultaneously. 2, 1, 7

Time Course and Onset

• Symptoms typically begin within minutes to 1-6 hours after allergen exposure, with most severe systemic reactions starting within 30 minutes. 2, 1
• In food-induced anaphylaxis, death can occur within 30-120 minutes of exposure. 1
• Approximately 70% of systemic reactions occur within the first 30 minutes. 1

Biphasic reactions warrant extended observation:

• Symptoms can resolve then recur in 1-23% of cases, typically within 24 hours 1
• This necessitates observation periods of 4-6 hours after treatment for food-induced anaphylaxis 1

Immediate Treatment Algorithm

First-line therapy for anaphylaxis:

• Epinephrine 0.01 mg/kg intramuscularly in the mid-outer thigh (maximum 0.5 mg adults, 0.3 mg children) is the cornerstone of treatment and must be administered immediately. 1, 7
• Delayed epinephrine administration increases morbidity and mortality. 1

Adjunctive therapies:

• H1-antihistamines for cutaneous symptoms (urticaria, pruritus) but never as substitute for epinephrine in anaphylaxis 1, 8
• Corticosteroids may prevent biphasic or protracted reactions but have delayed onset 1
• Bronchodilators for bronchospasm and wheezing 1

Critical Pitfalls to Avoid

Over-reliance on antihistamines alone for anaphylaxis is dangerous—epinephrine is mandatory for systemic reactions. 1, 8

Beta-adrenergic blockers and ACE inhibitors increase risk of severe reactions and may reduce epinephrine effectiveness. 1

Failure to distinguish true IgE-mediated reactions from non-allergic hypersensitivity reactions (anaphylactoid reactions, complement activation, bradykinin-mediated angioedema) can lead to inappropriate management. 1, 9

Inadequate observation periods after treatment miss biphasic reactions—patients should be monitored for at least 30 minutes after allergen immunotherapy and 4-6 hours after food-induced anaphylaxis. 1

Long-Term Management Strategy

• Allergen identification through clinical history and allergy testing is essential for prevention. 1
• Prescribe epinephrine auto-injectors for all patients with history of anaphylaxis. 1
• Provide comprehensive patient education on recognizing early symptoms and proper auto-injector technique. 1
• Refer to allergist-immunologist for skin testing, risk stratification, and consideration of desensitization protocols when first-line therapy cannot be avoided. 2, 1

Diagnostic Confirmation

Tryptase measurement can confirm mast cell involvement:

• Obtain sample during acute episode (15 minutes to 3 hours after onset) 1
• Compare to baseline tryptase level obtained after resolution 1

Skin testing with nonirritating concentrations of suspected allergens can identify IgE-mediated sensitization, particularly useful for drug hypersensitivity evaluation. 2