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)
• 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

• Angioedema
• Urticaria
• Asthma
• Shock
• Epinephrine

References

• 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