Brief about anaphylactic
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Anaphylaxis - A Clinical Brief
Definition
Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction that arises when mast cells (and possibly basophils) are activated by multivalent allergens binding to IgE and high-affinity IgE receptors (FcεRI) on their surfaces. This triggers the release of potent mediators - histamine, tryptase, prostaglandin D2, and leukotriene C4 - causing widespread effects on the cardiovascular, cutaneous, respiratory, and gastrointestinal systems.
The term "anaphylactic" specifically describes reactions mediated by IgE, while "anaphylactoid" (now less used) refers to non-IgE-mediated but clinically identical reactions.
- Goldman-Cecil Medicine, p. 2693
Epidemiology
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Lifetime incidence: 2-8% in adults (higher in children due to food allergy)
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~1,500-2,000 deaths annually in the United States
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Foods and insect stings each account for ~100 deaths/year
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Occurs in roughly 2% of the worldwide population, up to 5% in the US
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~50% of reactions occur at home; ~15% at a medical facility
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Fatal anaphylaxis is rare, representing < 1% of cases
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Prevalence has been increasing over the past two decades
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ROSEN's Emergency Medicine, p. 2386
Common Triggers
| Category | Examples |
|---|---|
| Medications | Antibiotics (penicillin, cephalosporins), NSAIDs, chemotherapy, monoclonal antibodies, radiocontrast media, muscle relaxants |
| Foods | Peanuts, tree nuts, shellfish, fish, cow's milk, eggs, wheat, soy |
| Insect stings | Hymenoptera (bees, wasps, ants, sawflies), fire ants |
| Latex | Natural rubber latex (gloves, catheters, medical equipment) |
| Exercise | Exercise-induced anaphylaxis (especially when combined with food) |
| Idiopathic | No identifiable cause in some cases |
In hospitals, antibiotics and radiocontrast media are the most common triggers. In emergency departments, NSAIDs are a leading cause.
Pathophysiology
- Sensitization: On first allergen exposure, IgE antibodies are produced and bind to FcεRI receptors on mast cells and basophils.
- Re-exposure: The allergen cross-links surface-bound IgE, triggering mast cell degranulation.
- Mediator release:
- Histamine - vasodilation, increased vascular permeability, bronchoconstriction
- Tryptase - activates complement, marker for mast cell activation
- Prostaglandin D2 - bronchoconstriction, vasodilation
- Leukotrienes C4/D4 - prolonged bronchoconstriction, mucus secretion
- Systemic effects: Massive vasodilation, fluid shift into tissues, hypotension, airway compromise
Non-IgE mechanisms (direct mast cell activation) occur with radiocontrast media, opioids, and physical triggers (cold, exercise).
Risk Factors for Severe Anaphylaxis
- Advanced age, pregnancy, infancy
- Pre-existing asthma, cardiovascular disease
- Use of beta-blockers or ACE inhibitors (blunts compensatory response, worsens severity)
- History of mastocytosis
- Hereditary alpha-tryptasemia (affects up to 5% of the population)
- Upright posture at onset (promotes cardiovascular collapse)
- Delayed epinephrine administration
Clinical Features
Symptoms typically appear within minutes to 2 hours of exposure. The faster the onset, the more severe the reaction.
| System | Symptoms | Frequency |
|---|---|---|
| Skin/mucosal | Urticaria, flushing, pruritus, angioedema, pallor | 80-90% |
| Respiratory | Wheeze, stridor, dyspnea, throat tightness, cough, hypoxemia | 70-80% |
| Cardiovascular | Hypotension, tachycardia, dysrhythmia, syncope, shock | 30-50% |
| GI | Crampy abdominal pain, nausea, vomiting, diarrhea | 25-30% |
| CNS | Anxiety, confusion, dizziness, seizure (from hypoperfusion) | 20-30% |
Note: Hypotension/shock is rarely the presenting feature in infants and children - it is much more common in adults.
Biphasic Anaphylaxis
A second wave of symptoms can occur 1-72 hours after apparent resolution without re-exposure to the trigger (occurs in ~5-20% of cases).
Diagnostic Criteria (NIAID/FAAN / WAO)
Anaphylaxis is highly likely when ANY ONE of the following is met:
Criterion 1: Sudden onset (minutes to hours) of skin/mucosal involvement PLUS at least one of:
- Respiratory compromise
- Reduced BP or end-organ dysfunction (syncope, incontinence)
Criterion 2: Two or more of the following occurring rapidly after allergen exposure:
- Skin/mucosal involvement
- Respiratory compromise
- Reduced BP or end-organ dysfunction
- Sudden GI symptoms
Criterion 3: Reduced BP after known allergen exposure (systolic < 90 mmHg or > 30% drop from baseline)
Sensitivity 95-97%, Specificity 71-82%.
Management
Immediate (First-Line)
1. Epinephrine (ADRENALINE) - THE CORNERSTONE OF TREATMENT
- IM injection into the anterolateral thigh (vastus lateralis) - preferred route
- Dose: 0.3-0.5 mg (adults) of 1:1,000 concentration; 0.01 mg/kg in children
- Can be repeated every 5-15 minutes if needed
- No absolute contraindications in anaphylaxis
- Delay in epinephrine administration is associated with increased mortality
2. Call for help / activate emergency response
3. Position the patient: Supine with legs elevated (unless respiratory compromise - then sit up slightly). Avoid upright posture.
4. Oxygen: High-flow oxygen via non-rebreather mask
5. IV access + IV fluids: Aggressive crystalloid resuscitation for hypotension
Second-Line (Adjunctive - NOT substitutes for epinephrine)
| Drug | Dose | Purpose |
|---|---|---|
| H1 antihistamine (diphenhydramine) | 25-50 mg IV/IM | Relieves urticaria/pruritus |
| H2 antihistamine (famotidine/ranitidine) | 20-50 mg IV | Adjunct for urticaria |
| Corticosteroids (methylprednisolone) | 1-2 mg/kg IV | Prevent biphasic reaction |
| Salbutamol/albuterol (nebulised) | 2.5-5 mg | Refractory bronchospasm |
| Glucagon | 1-5 mg IV | For patients on beta-blockers (bypasses beta-receptor) |
Antihistamines and corticosteroids are adjuncts only - they do NOT reverse airway obstruction or shock. Epinephrine must come first.
Refractory Anaphylaxis
- IV epinephrine infusion (1-4 mcg/min)
- Norepinephrine or vasopressin for refractory hypotension
- Consider airway management (intubation/cricothyrotomy) for severe angioedema
Observation and Discharge
- Minimum 4-6 hours observation after symptom resolution (due to biphasic risk)
- Patients with severe/refractory reactions: observe for 12-24 hours
- Epinephrine auto-injector (EpiPen) prescribed on discharge for all confirmed cases
- Refer to allergy/immunology for trigger identification and long-term management
- Consider allergen immunotherapy for insect venom allergy
Prevention
- Allergen avoidance counseling
- Medical alert bracelet/ID
- Radiocontrast pre-medication protocol: Prednisone 50 mg PO at 13h, 7h, and 1h before procedure + diphenhydramine 50 mg 1h before
- Venom immunotherapy for Hymenoptera allergy (reduces risk of future anaphylaxis from ~60% to <5%)
Sources: Goldman-Cecil Medicine (International Edition), p. 2693-2696 | ROSEN's Emergency Medicine, p. 2386-2392
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