Anaphylaxis

Anaphylaxis is a rapid, severe, multisystem allergic reaction that can be fatal within minutes if untreated. It is mediated by the sudden, massive release of inflammatory mediators - primarily histamine and tryptase - from mast cells and basophils. The reaction may be IgE-mediated (classic allergic anaphylaxis triggered by reintroduction of a sensitizing antigen) or non-IgE-mediated (direct mast cell activation by certain medicines, contrast media, or physical triggers).

Clinical features evolve quickly, typically within minutes of exposure. Cutaneous signs (flushing, urticaria, angioedema) appear in 80-90% of cases. Respiratory symptoms include throat tightness, hoarseness, stridor, wheezing, and severe shortness of breath. Cardiovascular collapse manifests as hypotension, tachycardia, and shock. Gastrointestinal involvement may produce cramping, vomiting, and diarrhea. Diagnosis is clinical: any acute reaction involving two or more organ systems, or any reaction with hypotension after a known allergen, qualifies as anaphylaxis.

Common medicine triggers include penicillins (especially parenteral), cephalosporins, NSAIDs, contrast media, monoclonal antibodies, and biologic infusions. Foods (peanuts, tree nuts, shellfish, milk, eggs), insect stings (bees, wasps), and latex are other prominent causes. A growing concern is alpha-gal syndrome, a delayed anaphylaxis to red meat triggered by tick bites.

The single most important treatment is immediate intramuscular epinephrine (0.3-0.5 mg in the lateral thigh for adults; 0.15 mg for children under 30 kg). Epinephrine reverses bronchospasm, restores vascular tone, and blocks further mediator release. Delays in epinephrine administration are the strongest predictor of fatal outcome. Secondary therapies - antihistamines, corticosteroids, IV fluids, bronchodilators - are supportive, not substitutes. Patients require observation for biphasic reactions (recurrence hours after initial improvement) and discharge with two epinephrine auto-injectors plus an action plan.

A dangerous misconception is that antihistamines or steroids alone can treat anaphylaxis. They cannot - only epinephrine reverses the cardiovascular and airway collapse quickly enough. Another misconception is that mild reactions on first exposure mean future reactions will also be mild. Anaphylaxis severity is unpredictable; any prior allergic reaction to a substance warrants caution.

Prescribers should document allergies clearly, screen for cross-reactivity (e.g., between penicillins and cephalosporins), and ensure patients with prior anaphylaxis carry epinephrine auto-injectors at all times.

Long-term management involves identification of the trigger (often through allergy testing), strict avoidance, and immunotherapy where appropriate. Medicine desensitization protocols can allow medically essential medications to be given despite a history of anaphylaxis - for example, penicillin desensitization in pregnant patients with syphilis, or aspirin desensitization in aspirin-exacerbated respiratory disease. Beta blockers and ACE inhibitors complicate anaphylaxis treatment: beta blockers can blunt the response to epinephrine, and ACE inhibitors may worsen angioedema. Clinicians should review these medications in patients with known severe allergies. Mast cell activation syndromes and hereditary alpha-tryptasemia are emerging diagnoses in patients with unexplained or recurrent anaphylactoid reactions.