Anaphylaxis

Diagnosis

Indications for Testing

  • Clinical history and examination consistent with anaphylaxis

Laboratory Testing

  • IgE testing
    • Used to identify potential allergens to allow avoidance or desensitization
    • Multiple allergen IgE testing (based on suspected allergens) may 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 does not add information except in cases where diagnosis is unclear
    • Levels peak 1 hour after onset of anaphylaxis
      • Test should be obtained within 3 hours of symptom onset to be useful
    • Elevation persists for 4-6 hours
    • Consider comparing to a baseline level taken after episode resolves
    • Normal levels do not rule out anaphylaxis
      • More common to have normal levels in food allergy anaphylaxis
    • Postmortem femoral vein sampling may be useful 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
      • May be impractical because levels must be obtained at symptom onset
    • Baseline levels return within 30-60 minutes
    • Basophil activation during clotting may cause artifactual elevation
  • Urine histamine
    • Measures N-methylhistamine, a histamine metabolite
    • Remains elevated in the urine for many hours after anaphylaxis
      • Preferred specimen is 24-hour urine
    • 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
    • 50-2,000 episodes/100,000 (American College of Allergy, Asthma and Immunology, 2006)
  • Age – all
    • 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
    • Common triggers include food, drugs, insect stings, exercise, vaccines
  • Type 1 (IgE-immediate hypersensitivity)
    • Medications
    • Foods – most frequent cause of anaphylaxis
      • Most common foods – fish, shellfish, peanuts, tree nuts, soy, eggs, wheat, and milk
    • 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
  • Allergies may change with time

Clinical Presentation

  • Acute onset of illness
    • May have biphasic recurrence 6-8 hours after initial anaphylaxis
  • Cardiovascular 
    • Angina
    • Cardiac arrest
    • Cardiac arrhythmias 
    • Hypotension 
    • Tachycardia
  • Cutaneous/mucosal tissue – most common symptoms
    • Angioedema
    • Conjunctivitis
    • Erythema/flush
    • Generalized pruritus without rash
    • Rhinitis
    • Urticaria
  • Gastrointestinal 
    • Abdominal cramps
    • Diarrhea
    • Emesis
    • Nausea
  • Neurologic
    • Dizziness
    • Seizures
    • Syncope
  • Respiratory
    • Lower airway
      • Bronchospasm
      • Dyspnea 
      • Tachypnea 
      • Wheezing
    • Upper airway
      • Laryngeal wheezing
      • Lip swelling
      • Rhinitis
      • Stridor
      • Tongue edema

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

   
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