Describe anaphylaxis with its mechanism, clinical features and management.

Definition and Mechanism

Prior sensitising exposure produces IgE, which binds mast cells and basophils — the person is sensitised but has NO symptoms → RE-exposure — antigen cross-links adjacent IgE molecules → Mast cell degranulation within seconds → Release of histamine, tryptase, leukotrienes, prostaglandins and platelet-activating factor → vasodilatation and massive capillary leak — up to a third of plasma volume can shift out of the circulation in minutes → bronchospasm, laryngeal oedema, urticaria, gut smooth muscle contraction → distributive shock, airway obstruction and death

• Anaphylactoid reactions result from direct mast cell degranulation or complement anaphylatoxins, without IgE — so they can occur on first exposure. Causes include radiocontrast media, vancomycin, opioids, NSAIDs and neuromuscular blockers. Management is identical

Causes and Clinical Features

• Common causes — drugs (penicillins and other beta-lactams, NSAIDs, anaesthetic agents, radiocontrast); foods (peanut, tree nuts, shellfish, egg, milk); insect stings; latex; heterologous serum (antivenom, antitoxin); vaccines rarely; and exercise-induced and idiopathic forms
• Biphasic reactions occur in up to 20%, recurring 1 to 72 hours after apparent recovery without further exposure — which is why observation after treatment is essential

Management

• Remove the trigger — stop the infusion, remove the sting
• Adrenaline 0.5 mg (0.5 mL of 1:1000) intramuscularly into the anterolateral thigh, repeated every 5 minutes as needed. The thigh is chosen because absorption is faster than from the deltoid or subcutaneous tissue. Do not wait for intravenous access
• Position — lie the patient flat with the legs raised; sitting or standing a hypotensive patient up has caused sudden death ("empty ventricle syndrome")
• Airway and high-flow oxygen; early intubation if the airway is threatened, since it becomes rapidly impossible
• Rapid intravenous fluids — large volumes of crystalloid, since the problem is distributive with massive capillary leak
• Second-line only — an antihistamine for the cutaneous symptoms, a corticosteroid to reduce the biphasic reaction, and a nebulised bronchodilator; none of these treats the acute event
• Refractory cases — adrenaline infusion; glucagon in patients on beta-blockers, who respond poorly to adrenaline, since it raises cardiac cAMP by a route that bypasses the blocked receptor
• Observe for 6 to 12 hours because of biphasic reactions

Prevention and Applied Aspects

• Take an allergy history before every prescription and injection, and ask what the previous reaction actually was
• Keep adrenaline immediately available wherever injections, antivenom, contrast or vaccines are given, and observe the patient for 20 to 30 minutes afterwards
• Every survivor needs an adrenaline auto-injector, training in its use, a written emergency plan, and referral for allergy assessment to identify the trigger
• Measure serum tryptase at presentation and again later; a rise confirms mast cell degranulation and supports the diagnosis retrospectively
• Never withhold antivenom from an envenomated patient for fear of a reaction — have adrenaline drawn up, treat the reaction if it occurs, and continue, because the alternative is death from envenomation
• Penicillin allergy labels are usually wrong and are carried for life; formal assessment and de-labelling restore access to the safest and cheapest antibiotics