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.


  • 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


  • 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


  • 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


  • 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

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
N-Methylhistamine, 24-Hour Urine 2011034
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry/Colorimetry

May be useful in confirming anaphylaxis