Anaphylaxis

Background

  • Acute, life-threatening, systemic allergic reaction involving multiple organ systems
  • IgE-mediated (type I hypersensitivity) in most cases; can also be non-IgE mediated (anaphylactoid)
  • Biphasic reaction occurs in 5-20% of cases (recurrence 1-72 hours after initial reaction, usually within 8-10 hours)[1]
  • Epinephrine is the ONLY first-line treatment — delays in administration increase mortality

Common Triggers

  • Foods (most common overall): peanuts, tree nuts, shellfish, fish, milk, eggs, wheat, soy
  • Medications: antibiotics (penicillin, cephalosporins), NSAIDs, neuromuscular blocking agents
  • Insect stings: Hymenoptera (bees, wasps, hornets, fire ants)
  • Latex
  • Exercise-induced anaphylaxis (sometimes food-dependent)
  • Idiopathic (~20% — no identifiable trigger)

Clinical Features

  • Onset: minutes to hours after exposure (usually within 30 minutes)
  • Skin/mucosal (90%): urticaria, flushing, angioedema, pruritus
  • Respiratory (70%): laryngeal edema, stridor, bronchospasm, wheezing, dyspnea
  • Cardiovascular (45%): hypotension, tachycardia, distributive shock, syncope, cardiac arrest
  • GI (45%): nausea, vomiting, abdominal cramps, diarrhea
  • Neurologic: anxiety, dizziness, altered mental status
  • Anaphylaxis can occur WITHOUT skin findings (~10-20% of cases)

Diagnostic Criteria (Any ONE of Three)

  • Criterion 1: Acute onset with skin/mucosal involvement AND respiratory compromise OR hypotension
  • Criterion 2: Two or more systems involved rapidly after likely allergen: skin, respiratory, cardiovascular, GI
  • Criterion 3: Hypotension after exposure to known allergen (SBP <90 or >30% decrease from baseline)

Differential Diagnosis

  • Angioedema (hereditary or ACE-inhibitor — no urticaria)
  • Vasovagal syncope (bradycardia; no urticaria/wheezing)
  • Asthma exacerbation
  • Urticaria alone (without systemic involvement)
  • Carcinoid syndrome, mastocytosis, scombroid fish poisoning
  • Anxiety / panic attack
  • Vocal cord dysfunction

Evaluation

  • Anaphylaxis is a clinical diagnosis — do NOT delay treatment for labs
  • Serum tryptase: elevated supports diagnosis (draw within 1-3 hours of onset)
    • Normal tryptase does NOT exclude anaphylaxis
    • Useful for postmortem diagnosis and distinguishing from other causes
  • Monitor: continuous ECG, pulse oximetry, blood pressure
  • Consider: CBC, BMP, troponin (Kounis syndrome — allergic MI)

Management

Epinephrine (Cornerstone of Treatment)

  • Epinephrine 0.3-0.5 mg (1:1,000) IM in anterolateral thigh (vastus lateralis)
    • Pediatric: 0.01 mg/kg (max 0.3 mg) IM
    • Repeat every 5-15 minutes as needed
    • Do NOT delay — there are NO absolute contraindications to epinephrine in anaphylaxis
  • If refractory or in shock:
    • Epinephrine infusion: 0.1-0.5 mcg/kg/min IV (mix 1 mg in 250 mL NS = 4 mcg/mL)
    • IV epinephrine bolus (only for cardiac arrest or refractory shock): 0.1 mg of 1:10,000 IV
  • IM > SC (faster absorption; SC absorption unreliable in shock)

Adjunctive Therapies

  • IV fluids: aggressive NS bolus (1-2L in adults; 20 mL/kg in children) — distributive shock with massive third-spacing
  • Albuterol 2.5-5 mg nebulized for bronchospasm (does not replace epinephrine)
  • H1 antihistamine: diphenhydramine 25-50 mg IV (treats urticaria/pruritus; does NOT treat life-threatening features)
  • H2 antihistamine: famotidine 20 mg IV (adjunctive)
  • Corticosteroids: methylprednisolone 125 mg IV or prednisone 1 mg/kg PO
    • Theoretical benefit in preventing biphasic reaction (limited evidence)
    • Do NOT rely on steroids as primary treatment (slow onset: 4-6 hours)
  • Glucagon 1-5 mg IV for patients on beta-blockers (resistant to epinephrine)

Refractory Anaphylaxis

  • Epinephrine infusion + aggressive volume resuscitation
  • Vasopressin 1-2 units IV bolus for refractory hypotension
  • Glucagon for beta-blocker use
  • Consider methylene blue 1-2 mg/kg IV for refractory vasoplegia
  • Secure airway early if airway edema progressing (may require surgical airway)

Disposition

  • Observe minimum 4-6 hours after last dose of epinephrine (biphasic reaction monitoring)
  • Extended observation (8-24 hours) if:
    • Severe initial reaction (hypotension, intubation)
    • History of biphasic reactions
    • Delayed presentation
    • Poor access to medical care
  • Discharge with:
    • Epinephrine auto-injector prescription (EpiPen or equivalent) — prescribe 2 devices
    • Antihistamine (diphenhydramine or cetirizine) for 3 days
    • Prednisone 40-60 mg PO daily × 3-5 days
    • Allergist referral
    • Written anaphylaxis action plan
    • Strict avoidance of trigger
    • Return precautions: return immediately if symptoms recur

See Also

References

  1. ↑ Lee S, et al. Biphasic anaphylaxis: review of incidence, clinical predictors, and observation recommendations. Immunol Allergy Clin North Am. 2015;35(2):313-326. PMID 25841553
  • Lieberman P, et al. Anaphylaxis — a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015;115(5):341-384. PMID 26505932
  • Cardona V, et al. World Allergy Organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13(10):100472. PMID 33204386
  • Simons FER, et al. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4(2):13-37. PMID 23268454
  • Shaker MS, et al. Anaphylaxis — a 2020 practice parameter update. J Allergy Clin Immunol. 2020;145(4):1082-1123. PMID 32001253
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