Anaphylaxis¶
Chapter 364 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Anaphylaxis is a life-threatening systemic allergic reaction involving one or more organ systems, typically occurring within seconds to minutes of exposure to triggers like drugs, foods, or Hymenoptera stings.
- Key mediators include histamine, cysteinyl leukotrienes, prostaglandins, and anaphylatoxins (C3a, C5a) from mast cells, basophils, and eosinophils.
- Diagnosis relies on clinical history, with tryptase levels (peaking 60–90 min post-onset) and differential diagnosis including mastocytosis, hereditary angioedema, and scombroid poisoning.
- Treatment prioritizes epinephrine (0.3–0.5 mL 1:1000 IM), IV fluids, and vasopressors; avoid beta-blockers in anaphylaxis.
- Non-IgE-mediated anaphylaxis (e.g., from radiocontrast, paclitaxel, or heparin) requires distinct management and diagnostic approaches.
1. DEFINITION & OVERVIEW¶
Anaphylaxis is a potentially life-threatening systemic allergic reaction involving one or more organ systems, typically occurring within seconds to minutes of exposure to triggers such as drugs, foods, or Hymenoptera stings. It is characterized by rapid release of mediators from mast cells, basophils, and eosinophils, leading to widespread physiological effects.
1.1 Historical Context¶
The term 'anaphylaxis' was first described in 1902 by Richet and Portier, who observed fatal reactions in dogs immunized against sea anemone toxin. This phenomenon, termed 'ana (anti)-phylaxis,' led to the Nobel Prize in Physiology or Medicine in 1913.
1.2 Clinical Spectrum¶
Anaphylactic reactions are typically biphasic (10–20% of cases), with symptoms recurring 1 hour or more after initial resolution. Severe cases may present with cardiovascular collapse, respiratory failure, or airway obstruction.
2. EPIDEMIOLOGY¶
Anaphylaxis is a common emergency, with incidence rates varying by region and population. Drug reactions (e.g., antibiotics, NSAIDs) and food allergies (e.g., peanuts, shellfish) are leading triggers. Severe reactions are more common in patients with underlying asthma, cardiovascular disease, or mast cell disorders.
2.1 Risk Factors¶
Preexisting asthma, cardiovascular disease, and mast cell disorders (e.g., systemic mastocytosis) increase severity. Atopy is not a major risk factor for drug-induced anaphylaxis but is associated with radiocontrast sensitivity and food allergies.
2.2 Demographics¶
Anaphylaxis occurs across all age groups, but severe reactions are more common in adults. Patients with mast cell disorders (e.g., mastocytosis) are at higher risk for severe, biphasic reactions.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Anaphylaxis is mediated by IgE-dependent and non-IgE mechanisms. IgE cross-linking of Fc ε RI receptors on mast cells initiates degranulation, releasing histamine, leukotrienes, and anaphylatoxins. Non-IgE pathways involve direct mast cell activation by drugs (e.g., NSAIDs, heparin) or haptens.
3.1 Mediators¶
Histamine causes vasodilation, bronchoconstriction, and hypotension. Cysteinyl leukotrienes and prostaglandins contribute to bronchoconstriction and vascular permeability. Anaphylatoxins (C3a, C5a) activate complement and coagulation pathways, exacerbating inflammation.
3.2 Non-IgE Mechanisms¶
Drugs like NSAIDs, heparin, and neuromuscular blocking agents can trigger non-IgE-mediated anaphylaxis via direct mast cell degranulation or bradykinin pathways. Hapten-induced IgE formation (e.g., cetuximab, radiocontrast) is also implicated.
4. CLINICAL FEATURES¶
Clinical manifestations vary by organ system but often include cutaneous (urticaria, flushing), respiratory (airway obstruction, bronchospasm), cardiovascular (hypotension, shock), and gastrointestinal (nausea, vomiting) symptoms. Severe cases may present with laryngeal edema or angioedema.
4.1 Cutaneous Symptoms¶
Urticaria, flushing, and angioedema are common. Urticarial plaques may coalesce but typically resolve within 48 hours.
4.2 Respiratory and Cardiovascular Symptoms¶
Airway obstruction (stridor, hoarseness) and bronchospasm (wheezing, chest tightness) are critical. Hypotension and tachycardia may progress to cardiovascular collapse.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnoses include mastocytosis, hereditary angioedema, scombroid poisoning, and drug-induced reactions. Table 364-1 outlines key differentiating features.
Table 364-1 Differential Diagnoses for IgE-Mediated Anaphylaxis¶
| CONDITION | DISTINGUISHED BY |
|---|---|
| Mastocytosis | Elevated baseline tryptase, spindle-shaped mast cells (MCs) on bone marrow |
| CONDITION | DISTINGUISHED BY |
|---|---|
| Pheochromocytoma | Elevated urine metanephrines |
| Carcinoid syndrome | Elevated urine 5-hydroxyindoleacetic acid |
| Hereditary angioedema | Decreased C4 during attacks |
| Acquired angioedema | Decreased C1q |
| Systemic capillary leak syndrome | Severe hypotension on presentation, lack of response to first-line hypersensitivity medications |
| Scombroid poisoning | Tryptase not elevated; negative skin test and oral challenge to fish |
| Drugs (opiates, neuromuscular blocking agents, vancomycin) | Direct MC degranulation triggered through MRGPRX2 receptor or other mechanism |
| Computed tomography radiocontrast | As-yet-undetermined mechanism |
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis relies on clinical history and laboratory biomarkers. Serum tryptase (peaking 60–90 min post-onset) and histamine levels are critical. Skin testing and specific IgE assays may confirm allergen triggers.
6.1 Biomarkers¶
Serum tryptase is the most reliable biomarker, with levels peaking 60–90 min post-onset and remaining measurable up to 5 h. Histamine levels are transient and less useful for retrospective diagnosis.
6.2 Diagnostic Criteria¶
The '20% + 2' rule: A tryptase level ≥ 20% above baseline + 2 ng/mL is diagnostic for acute mast cell activation. Baseline tryptase (BST) variability must be considered (e.g., 6% of Western populations have hereditary alpha-tryptasemia).
7. MANAGEMENT & TREATMENT¶
Immediate treatment includes intramuscular epinephrine (0.3–0.5 mL 1:1000), IV fluids, and vasopressors. Antihistamines, corticosteroids, and bronchodilators are adjuncts. Avoid beta-blockers in anaphylaxis.
7.1 First-Line Treatment¶
Epinephrine (0.3–0.5 mL 1:1000 IM) is the first-line intervention. Repeated doses may be required for severe reactions. Oxygen and airway management are critical for respiratory compromise.
7.2 Adjunctive Therapies¶
Antihistamines (e.g., diphenhydramine), corticosteroids (e.g., prednisone), and bronchodilators (e.g., albuterol) are used for symptom relief. IV fluids and vasopressors (e.g., norepinephrine) are indicated for refractory hypotension.
8. PROGNOSIS & COMPLICATIONS¶
Mortality is rare with prompt treatment but increases with delayed epinephrine use. Complications include cardiovascular collapse, respiratory failure, and biphasic reactions. Long-term risks include mast cell disorders (e.g., systemic mastocytosis).
8.1 Risk Factors for Poor Outcomes¶
Failure to administer epinephrine within 20 min of symptoms, underlying asthma, and cardiovascular disease are associated with higher mortality.
8.2 Long-Term Monitoring¶
Patients with recurrent anaphylaxis should undergo evaluation for mast cell disorders (e.g., tryptase testing) and avoid known triggers.
9. SPECIAL CONSIDERATIONS¶
Special populations include pregnant patients (no contraindications to epinephrine), pediatric patients (lower epinephrine dose), and elderly patients (higher risk of cardiovascular complications).
9.1 Drug-Induced Anaphylaxis¶
Non-IgE mechanisms (e.g., heparin, radiocontrast) require distinct management. Heparin-induced anaphylaxis is often due to oversulfated chondroitin sulfate contamination.
9.2 Food and Drug Allergies¶
Alpha-gal syndrome (AGS) causes delayed-onset anaphylaxis after mammalian meat consumption. Cetuximab-induced anaphylaxis is linked to alpha-gal IgE antibodies.
10. KEY POINTS & CLINICAL PEARLS¶
- Epinephrine is the first-line treatment for anaphylaxis. 2. Tryptase levels peak 60–90 min post-onset and are useful for retrospective diagnosis. 3. Non-IgE mechanisms (e.g., heparin, NSAIDs) require distinct management. 4. Delayed epinephrine use is a major risk factor for poor outcomes. 5. Patients with mast cell disorders (e.g., mastocytosis) are at higher risk for severe, biphasic reactions.