Clinical meaning
Anaphylaxis is a severe, potentially fatal systemic hypersensitivity reaction (Type I) mediated by immunoglobulin E (IgE). During initial sensitization, the immune system produces allergen-specific IgE antibodies that bind to high-affinity FcepsilonRI receptors on mast cells and basophils throughout the body (skin, respiratory tract, GI tract, vasculature). Upon re-exposure, the allergen cross-links two IgE molecules on the mast cell surface, triggering immediate degranulation within seconds to minutes. The massive release of preformed mediators (histamine, tryptase, heparin) and newly synthesized mediators (leukotrienes C4/D4/E4, prostaglandin D2, platelet-activating factor) produces the hallmark effects: (1) Massive vasodilation and increased vascular permeability causing hypotension and angioedema; (2) Bronchospasm from smooth muscle contraction in lower airways causing wheezing and respiratory distress; (3) Upper airway edema (laryngeal, pharyngeal, tongue) causing stridor and potential complete airway obstruction; (4) Urticaria and flushing from cutaneous mast cell degranulation; (5) GI smooth muscle contraction causing nausea, vomiting, diarrhea, abdominal cramping. Biphasic anaphylaxis occurs in 5-20% of cases where symptoms recur 4-12 hours after initial resolution without re-exposure to the allergen, likely from late-phase inflammatory mediators. This necessitates observation periods of 4-6 hours after initial treatment. Epinephrine is the ONLY first-line treatment because it addresses ALL pathophysiological mechanisms: alpha-1 vasoconstriction reverses vasodilation, beta-1 increases cardiac output, and beta-2 causes bronchodilation and inhibits further mast cell degranulation.