Clinical meaning
Anaphylaxis is a severe, potentially fatal systemic hypersensitivity reaction that is rapid in onset and can cause death within minutes if not treated promptly. It is the most extreme form of a type I (IgE-mediated) immediate hypersensitivity reaction, though non-IgE-mediated mechanisms can also produce identical clinical presentations (anaphylactoid reactions).
In classic IgE-mediated anaphylaxis, prior sensitisation to an allergen is required. During initial exposure, the immune system produces allergen-specific IgE antibodies that bind to high-affinity Fc-epsilon receptors on mast cells and basophils. On subsequent re-exposure, the allergen cross-links these surface-bound IgE molecules, triggering massive mast cell and basophil degranulation. This releases a flood of preformed and newly synthesised mediators.
Histamine is the primary mediator, causing vasodilation, increased vascular permeability, smooth muscle contraction (bronchospasm, GI cramps), and mucus hypersecretion. Tryptase (a protease from mast cells) causes tissue damage and can be measured as a serum marker of mast cell activation. Prostaglandins (especially PGD2) and leukotrienes (LTC4, LTD4, LTE4) amplify and prolong the inflammatory response. Leukotrienes are 1000 times more potent than histamine at causing bronchospasm, explaining why antihistamines alone are insufficient to treat anaphylaxis.
Platelet-activating factor (PAF) promotes further vascular permeability, platelet aggregation, and hypotension. The severity of PAF levels correlates with the severity of anaphylaxis. Cytokines (TNF-alpha, IL-4, IL-13) are released in a secondary wave, contributing to the late-phase reaction.
The most common triggers are foods (peanuts, tree nuts, shellfish, milk, eggs), medications (penicillin and other beta-lactams, NSAIDs, neuromuscular blocking agents), insect stings (Hymenoptera - bees, wasps, hornets), and latex. In the healthcare setting, medications and latex are the most common triggers. In some cases, no trigger is identified (idiopathic anaphylaxis).