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
    • 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 

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
Test Name and Number Recommended Use Limitations Follow Up
Immunoglobulin E 0050345
Method: Quantitative ImmunoCAP® Fluorescent Enzyme Immunoassay

May be useful in evaluation of allergic disease

May also be elevated in AML, MDS, mastocytosis, hypereosinophilic syndrome

 
Tryptase 0099173
Method: Quantitative Fluorescent Enzyme Immunoassay

May be useful in confirming anaphylaxis; generally not used acutely except where diagnosis is unclear

Sample must be drawn near time of event (within 3 hrs of symptom onset)

Measures total tryptase; does not distinguish between alpha and beta protein types

 
Histamine, Whole Blood 0070037
Method: Quantitative Enzyme-Linked Immunosorbent Assay

May be useful in confirming anaphylaxis

Sample must be drawn near time of event

 
Histamine, Plasma 0070036
Method: Quantitative Enzyme-Linked Immunosorbent Assay

May be useful in confirming anaphylaxis

Sample must be drawn near time of event

 
Histamine, Urine 0070038
Method: Quantitative Enzyme Immunoassay

May be useful in confirming anaphylaxis

May be more useful than serum measures, but negative test does not rule out anaphylaxis