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Anaphylaxis

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4 min read

Epidemiology & Risk Factors

  • Triggers:
    • Foods: Peanuts, tree nuts, shellfish, milk, eggs.
    • Meds: Beta-lactam Abx, NSAIDs, neuromuscular blocking agents, IV radiocontrast.
    • Venoms: Hymenoptera stings (bees, wasps, hornets, fire ants).
    • Others: Latex, allergen immunotherapy.
  • Pathophysiology:
    • IgE-Mediated (Type I Hypersensitivity): Cross-linking of FcεRI on mast cells and basophils → massive release of histamine, tryptase, leukotrienes, and prostaglandins.
    • Non-IgE-Mediated (Direct Mast Cell Activation): Radiocontrast agents, opioids, vancomycin (formerly “anaphylactoid”).
  • Risk Factors for Severe/Fatal Outcomes:
    • Pre-existing asthma or atopy.
    • Concurrent use of beta-blockers (blunts epinephrine response) or ACEi (impairs degradation of vasoactive kinins).
    • Delay in IM epinephrine administration.

Clinical Features

  • Onset: Rapid, acute presentation (seconds to hours post-exposure).
  • Dermatologic / Mucosal (>90%):
    • Pruritus, flushing, urticaria (hives).
    • Angioedema: Swelling of lips, tongue, uvula, and periorbital tissue.
  • Respiratory:
    • Upper airway: Stridor, hoarseness, dysphonia, sensation of throat tightness.
    • Lower airway: Wheezing, tachypnea, severe dyspnea, bronchospasm.
  • Cardiovascular:
    • Hypotension, reflex tachycardia (or bradycardia via Bezold-Jarisch reflex), syncope, lightheadedness, diaphoresis.
    • Distributive shock due to widespread vasodilation and increased vascular permeability (fluid extravasation into extravascular space).
  • Gastrointestinal:
    • Crampy abdominal pain, nausea, vomiting, severe diarrhea.

Diagnosis

  • Clinical Diagnosis (Must NOT be delayed for confirmatory testing):
    • Any 1 of the following 3 clinical criteria:
      1. Acute onset of skin/mucosal signs PLUS respiratory compromise OR hypotension/end-organ dysfunction.
      2. Rapid onset of ≥2 manifestations after exposure to a likely allergen (skin/mucosa, respiratory, hypotension, GI).
      3. Isolated hypotension (SBP < 90 mmHg or >30% drop from baseline) after exposure to a known allergen.
  • Key Labs (Retrospective Confirmatory):
    • Serum Tryptase: Elevated within 15–180 min of symptom onset; peaks at 1–2 hours. Useful to confirm diagnosis retrospectively in ambiguous cases.
    • Specific IgE (sIgE) / Skin prick testing: Outpatient follow-up (4–6 weeks post-event).
  • Imaging / Biopsy: None indicated acutely.

Differential Diagnostics

  • Vasovagal Syncope:
    • Diff by: Bradycardia, pallor, absence of urticaria/angioedema, absence of bronchospasm; prompt resolution in supine position.
  • Acute Asthma Exacerbation:
    • Diff by: Isolated lower airway signs (wheezing, dyspnea) without cutaneous manifestations, angioedema, or systemic hypotension.
  • Hereditary Angioedema (C1-Inhibitor Deficiency):
    • Diff by: Recurrent non-pruritic angioedema WITHOUT urticaria or pruritus; family history; low C4 level; triggered by minor trauma/stress.
  • Scombroid Fish Poisoning:
    • Diff by: Ingestion of improperly stored dark-meat fish (tuna, mahi-mahi); histamine intoxication affecting multiple individuals eating the same food; short latency (<1 hour); metallic/peppery taste.
  • Panic Attack / Vocal Cord Dysfunction:
    • Diff by: Inspiratory stridor/hyperventilation without true hypoxemia, absence of urticaria, angioedema, or hypotension; normal tryptase.
  • Systemic Mastocytosis:
    • Diff by: Chronic episodic flushing, abdominal pain, urticaria pigmentosa (Darier sign), persistently elevated baseline serum tryptase (>20 ng/mL), KIT D816V mutation.

Management

  1. First-Line / Emergency Stabilization (Priority 1):
    • Intramuscular (IM) Epinephrine (1:1000 / 1 mg/mL):
      • Adult dose: 0.3–0.5 mg IM into the mid-anterolateral thigh (vastus lateralis) immediately.
      • Peds dose: 0.01 mg/kg IM (max 0.3 mg) or auto-injector (0.15 mg for 7.5–30 kg).
      • Repeat every 5–15 minutes if symptoms persist or worsen. No absolute contraindications in anaphylaxis. c
    • Airway Management:
      • Administer high-flow 100% O2 via non-rebreather mask.
      • Low threshold for early endotracheal intubation before progressive laryngeal edema prevents visualization; prepare for cricothyrotomy if unable to intubate.
    • Circulatory Support & Positioning:
      • Place pt supine with legs elevated (Trendelenburg/flat) to preserve venous return; avoid sudden sitting or standing (can cause fatal empty-ventricle syndrome).
      • Establish large-bore IV access (16–18 gauge).
      • Aggressive IV Fluid Resuscitation: Rapid bolus of 1–2 L normal saline or lactated Ringer’s for hypotension.
  2. Second-Line / Adjunctive Therapy (Priority 2 - Never delay Epinephrine):
    • H1-Antihistamines (e.g., Diphenhydramine 25–50 mg IV/oral) + H2-Antihistamines (e.g., Famotidine 20 mg IV): Alleviates urticaria, pruritus, and flushing.
    • Inhaled Beta-2 Agonists (e.g., Albuterol nebulizer 2.5–5 mg): For refractory bronchospasm/wheezing unresponsive to initial epi.
    • Systemic Corticosteroids (e.g., Methylprednisolone 1–2 mg/kg IV or Prednisone 1 mg/kg PO): Used to prevent prolonged or biphasic reactions (delayed onset of action: 4–6 hours).
  3. Refractory Cases & Special Scenarios (Priority 3):
    • Refractory Shock: Continuous IV Epinephrine infusion (titrated to BP) if hypotension persists despite multiple IM epi doses and aggressive IVF.
    • Patients on Beta-Blockers:
      • Administer IV Glucagon (1–5 mg IV over 5 min, followed by infusion 5–15 mcg/min).
      • Mechanism: Activates adenylate cyclase directly, bypassing blocked beta-adrenergic receptors → ↑ inotropy and chronotropy.
  4. Monitoring & Disposition:
    • Observation: Monitor in ED for 4–8 hours (minimum) due to risk of biphasic anaphylaxis (recurrence of symptoms without re-exposure, occurring in up to 20% of pts within 1–72 hours).
    • Discharge:
      • Prescribe two Epinephrine auto-injectors (EpiPen 0.3 mg or EpiPen Jr 0.15 mg).
      • Provide hands-on self-administration training.
      • Provide action plan, medical alert bracelet recommendation, and outpatient allergy/immunology referral.

Complications

  • Fatal Airway Obstruction: Complete laryngeal/pharyngeal edema leading to asphyxiation.
  • Refractory Distributive/Hypovolemic Shock: Severe vasodilation and third-spacing leading to end-organ ischemia and cardiac arrest.
  • Biphasic Anaphylaxis: Second wave of symptoms occurring hours after resolution of the initial reaction without re-exposure. c
  • Kounis Syndrome: Allergic acute coronary syndrome caused by mast-cell mediator-induced coronary artery vasospasm ± plaque rupture.
  • Anoxic Encephalopathy: Secondary to prolonged hypoxemia or cardiovascular collapse.

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