Description
- Acute, life-threatening, multi-system hypersensitivity reaction
- Two mechanisms, identical clinical picture
- IgE-mediated - food, venom, drug, latex
- Non-IgE / direct mast cell activation - opiates, vancomycin, radiocontrast, NSAIDs, neuromuscular blockers
- The old "anaphylactoid" label is obsolete - treatment is the same
- Biphasic reaction in ~5% - recurrence 1-72h (usually <8h) without re-exposure
- Protracted anaphylaxis - hours, refractory to initial treatment
Epidemiology
- Lifetime prevalence ~0.5-2%
- Triggers: food (children), drugs and venom (adults)
- Australian anaphylaxis admissions rising ~5-10%/yr
- Fatalities rare: food ~1-3/yr, drug and venom each contribute more adult deaths
- Adolescents and young adults with food allergy and asthma = highest fatality risk group
Aetiopathogenesis
- Allergen cross-links IgE on FcepsilonRI of mast cells and basophils
- -> preformed mediator release: histamine, tryptase, heparin
- -> newly synthesised: leukotrienes, PGD2, PAF
- Effects
- Vasodilatation + inc capillary permeability -> distributive shock, up to 35% of intravascular volume shifts in 10 min
- Bronchoconstriction, mucus, laryngeal oedema
- inc GI smooth muscle activity -> vomiting, cramping
- Non-IgE routes: direct MRGPRX2 activation (opiates, vancomycin, quinolones), complement anaphylatoxins, NSAID COX-1 inhibition
- Cofactors lower the threshold: exercise, NSAIDs, alcohol, infection, beta-blockade
- Underlying mastocytosis / raised baseline tryptase amplifies severity (esp. venom)
Diagnosis1 exam ›
Clinical diagnosis. Treat before confirming.
Definition - anaphylaxis is likely when
- A. Acute onset with skin and/or mucosal involvement, PLUS at least one of
- Respiratory compromise - dyspnoea, wheeze, stridor, hypoxaemia
- Hypotension or end-organ hypoperfusion - collapse, incontinence
- Severe GI symptoms - persistent vomiting, crampy abdominal pain
- B. OR acute hypotension/bronchospasm/laryngeal involvement after exposure to a known allergen, even without skin signs
- Skin involvement absent in 10-20% - its absence does not exclude anaphylaxis
- In children, persistent severe GI symptoms after a known food allergen count as anaphylaxis
Severity grading (ASCIA)
- Mild-moderate allergic reaction: urticaria, angioedema, tingling mouth, abdominal pain/vomiting (non-insect)
- Anaphylaxis: any airway, breathing or circulatory involvement, or persistent vomiting after insect sting
Serum tryptase
- Collect within 3h of onset (peak 1-2h), plus a baseline >24h later or at follow-up
- Rise supports mast cell degranulation but does not distinguish IgE from non-IgE mechanism
- Normal tryptase does not exclude anaphylaxis (often normal in food-triggered events)
- Persistently elevated baseline tryptase (>8 ng/mL) -> investigate for mastocytosis or hereditary alpha-tryptasaemia
After the event
- Allergist referral for SPT / specific IgE 4-6 weeks later (earlier testing risks false negatives during the refractory period)
Management2 exam ›
A. Immediate - in order
1. Remove the trigger (stop the infusion, remove the sting)
2. IM adrenaline into the anterolateral thigh
- Adult 0.5 mg (0.5 mL of 1:1000); child 0.01 mg/kg to max 0.5 mg
- Autoinjector: 150 mcg (7.5-20 kg), 300 mcg (>20 kg), 500 mcg option in adults
- Repeat every 5 minutes as required - no ceiling
- No absolute contraindication. Delay is the modifiable cause of death
3. Lie flat, legs elevated (sit only if breathing is difficult; stand never)
- Sudden upright posture can precipitate empty-ventricle cardiac arrest
4. High-flow oxygen, IV access
5. IV crystalloid 20 mL/kg bolus, repeat - the shock is profoundly volume-depleted
B. Refractory anaphylaxis (no response after 2 IM doses)
- Adrenaline infusion - specialist/monitored setting only
- IV bolus adrenaline is reserved for peri-arrest: dangerous arrhythmia and hypertensive stroke
- Glucagon 1-2 mg IV if on a beta-blocker - bypasses beta-blockade via direct adenylate cyclase activation
- Vasopressin or metaraminol for refractory vasoplegia
- Nebulised adrenaline for stridor (adjunct only, never instead of IM)
- Salbutamol for persistent bronchospasm
C. Adjuncts - not first-line, no mortality benefit
- Corticosteroids - for late/biphasic reaction and coexisting asthma; do not treat the acute event
- Antihistamines - symptomatic relief of urticaria/itch only
- Never delay adrenaline to give either
D. Observation and discharge
- Observe at least 4h after last adrenaline dose; longer (12h+) if severe, refractory, biphasic history, asthma, or remote from care
- Discharge with:
- Two adrenaline autoinjectors + training
- ASCIA Anaphylaxis Action Plan
- Written trigger avoidance advice
- MedicAlert
- Allergist referral
E. Longer-term
- Venom immunotherapy - 3-5 years, reduces recurrent sting anaphylaxis from ~50-70% to <5%
- Drug allergy delabelling, especially penicillin
- Review beta-blockers and ACE inhibitors where feasible
- Optimise asthma
Associations
- Asthma - determines severity and fatality
- Mastocytosis, hereditary alpha-tryptasaemia
- Atopic dermatitis, food allergy, allergic rhinitis
- Beta-blockers, ACE inhibitors - reduce response to adrenaline / potentiate reaction
- Alpha-gal syndrome - delayed 3-6h anaphylaxis to mammalian meat after tick bite
- Exercise- and NSAID-dependent food anaphylaxis (omega-5 gliadin)
- Perioperative: neuromuscular blockers, chlorhexidine, latex, antibiotics
Natural history & complications
- Most reactions resolve fully with prompt adrenaline
- Biphasic reactions ~5%, predicted by severe initial reaction and requirement for >1 adrenaline dose
- Recurrence risk depends entirely on trigger avoidability
- Venom without immunotherapy: 50-70% on re-sting
- Food: ~10%/yr accidental exposure
Death
- Rare, and usually from delayed adrenaline
- Food -> asphyxia from upper airway obstruction/bronchospasm
- Venom and drug -> cardiovascular collapse
- Median time to arrest: drug ~5 min, venom ~15 min, food ~30 min
Monitor
- Adrenaline autoinjector currency and technique at every review
- Asthma control
- Baseline tryptase if unexplained or severe reaction
7 of 7 sections written · drafted 2026-09-08