Overview of allergic disease: Anaphylaxis - WAO White Book on Allergy 2026 - 2.11

Anaphylaxis is a rapid-onset, potentially fatal systemic hypersensitivity reaction marked by airway, breathing, or circulatory compromise, which may occur even without skin symptoms. It is driven primarily by mast-cell activation-usually through IgE-mediated pathways-leading to the release of mediators such as tryptase and histamine. Basophils can also contribute. Although traditionally considered rare, anaphylaxis has a lifetime prevalence of 0.3-5.1%, with incidence rising globally in both adults and children, likely due to increased allergic diseases. Fatalities remain relatively low. Common triggers vary by age and geography: foods such as milk, peanuts, and tree nuts dominate in children; medications-especially beta-lactam antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs)-are more common in adults; and insect venoms are major causes in some regions. Diagnosis is clinical, based on rapid multisystem involvement, despite sometimes isolated cardiovascular or non-inhaled respiratory symptoms may occur. First measures should be to remove the allergen if possible and position the patient appropriately. Immediate intramuscular epinephrine injected into the lateral thigh is the first-line treatment, with repeat dosing as needed. Intranasal epinephrine is emerging as a needle-free alternative. Adjunctive measures include oxygen, intravenous fluids, and bronchodilators for bronchospasm. Antihistamines and corticosteroids may alleviate some symptoms but do not reverse anaphylaxis and must not delay epinephrine administration. Long-term management focuses on identifying triggers through detailed history, IgE testing, skin testing, or challenge procedures; however, up to 10% of cases remain idiopathic. Patients require action plans and access to self-administered epinephrine, though availability is limited in many regions. Key unmet needs include global device access, harmonized definitions and severity scoring, improved education, digital health integration, and deeper investigation into mechanisms, biomarkers, genetics, and cofactors to optimize diagnosis, prevention, and care.