Anaphylaxis

Diagnosis

Indications for Testing

• Clinical history and examination consistent with anaphylaxis

Laboratory Testing

• Appropriate IgE testing
  • Testing is used to identify potential allergens to allow avoidance or desensitization
  • Single IgE level may be helpful based on history
  • Multiple allergen IgE testing (based on suspected allergens) may also be appropriate
  • No recommendations for routine determination of serum IgE level
    • In vitro IgE detection may not correlate with anaphylactic reaction
    • IgE levels do not correlate with antigen-specific IgE determinations
• Serum tryptase
  • Generally not used acutely except in cases where diagnosis is unclear
  • Levels peak 1 hour after onset of anaphylaxis; should be obtained within 3 hours of symptom onset
  • Elevation persists for 4-6 hours
  • Normal levels cannot be used to refute diagnosis of anaphylaxis
    • More common in food allergy anaphylaxis
  • Consider comparing to a baseline level taken after episode resolves
  • May be used postmortem (femoral vein sampling) to confirm anaphylaxis as cause of death (must be within ≤1 hour of death)
• Serum or plasma histamine
  • Levels peak 5 minutes after onset of anaphylaxis
  • Baseline levels return within 30-60 minutes
    • May be impractical because levels must be obtained at symptom onset
  • May be elevated in serum due to artifactual basophil activation during clotting
• Urine histamine
  • N-methylhistamine (a histamine metabolite) remains elevated in the urine for many hours after anaphylaxis
    • Best measured in 24-hour urine specimen
  • Reflects overall levels of released histamine
• Newer tests – CD63 and CD203 expression in basophils via flow cytometry

Differential Diagnosis 

• Cardiovascular symptoms
  • Vasovagal reaction
  • Panic attack
  • Other forms of shock
  • Pulmonary embolism
  • Hypoglycemia
  • Acute myocardial infarction
  • Thyrotoxicosis
  • Acute poisoning
  • Sepsis
• Respiratory symptoms
  • Asthma
  • Pulmonary embolism
  • Acute congestive heart failure
  • Foreign body in airway
  • Chronic obstructive pulmonary disease (COPD)
  • Vocal cord dysfunction syndrome
• Cutaneous symptoms
  • Flush syndrome
  • Hereditary or acquired angioedema
  • Systemic mastocytosis
  • Carcinoid tumor
  • Alcohol-induced flush
  • Urticarial vasculitis
  • Basophilic leukemia
• Neurologic symptoms
  • Seizure disorder
  • Acute poisoning
  • Stroke
  • Hypoglycemia
  • Anxiety disorder

Clinical Background

Anaphylaxis is an acute, potentially fatal hypersensitivity reaction that is most often IgE-mediated and can involve multiple organ systems.

Epidemiology

• Incidence
  • 75/100,000 lifetime incidence
    • 3-5/10,000 adults
    • 1/200 children
• Age – all ages
  • Most deaths from anaphylaxis occur in children <10 years
• Sex – M:F, equal

Risk Factors

• Previous history of anaphylaxis
• Hives or urticaria following allergen exposure
• One or more comorbidities
  • Asthma, atopic eczema, allergic rhinitis

Pathophysiology

• Involves activated mast cell release of multiple substances – cytokines, histamine, tryptase, prostaglandins
• Type 1 (IgE-immediate hypersensitivity)
  • Medications
  • Foods
    • Most frequent cause of anaphylaxis is reaction to foods (1/3 of cases)
  • Insect venoms
• IgE independent
  • Cold, heat
  • Drugs – opioids, muscle relaxants, NSAIDs, ACE inhibitors
  • Exercise
  • Radiocontrast media
• Interval to anaphylaxis depends on allergen
  • Food – 25-30 minutes after ingestion
  • Drugs – 10-20 minutes after administration
  • Insect stings – 10-15 minutes after sting
  • Blood or blood products in IgA-deficient (no detectable level) patients – 10-20 minutes after administration

Clinical Presentation

• Acute onset of illness
• Respiratory
  • Lower airway
    • Dyspnea 
    • Tachypnea 
    • Bronchospasm
    • Wheezing
  • Upper airway
    • Laryngeal wheezing
    • Tongue edema
    • Lip swelling
    • Stridor
• Cardiovascular 
  • Tachycardia 
  • Hypotension 
  • Cardiac arrhythmias 
  • Angina 
  • Cardiac arrest
  • Dizziness
  • Syncope
• Gastrointestinal 
  • Nausea 
  • Abdominal cramps 
  • Emesis 
  • Diarrhea
• Cutaneous/mucosal tissue
  • Erythema 
  • Generalized pruritus 
  • Urticaria
  • Angioedema
  • Rhinitis 
  • Conjunctivitis

Treatment

• Immediate
  • Epinephrine
  • Antihistamines
  • Corticosteroids
• Observation after initial treatment for a minimum of 4-6 hours
  • Recurrence of anaphylaxis is not uncommon 1-72 hours after initial event
• Fluid administration

Prevention

• Avoidance of known allergens
• Use of epinephrine pens when exposed to known allergen; epinephrine should be available at all times for possible repeat exposures
• Desensitization for insect stings

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory