Anaphylaxis

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

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
  • Tryptase (serum)
    • Generally not informative 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
  • Histamine
    • Serum or plasma
      • 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
      • Measures histamine metabolite (N-methylhistamine)
      • Remains elevated in the urine for many hours after anaphylaxis
        • Preferred specimen is 24-hour urine
      • Reflects overall levels of released histamine
  • CD63 and CD203 expression by flow cytometry
    • Newer tests
    • Markers of basophil activation

Differential Diagnosis

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, elderly
  • 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
    • Mastocytosis

Pathophysiology

  • Involves activated mast cell release of multiple substances – cytokines, histamine, tryptase, prostaglandins
    • Common triggers include food, drugs, insect stings, exercise, vaccines
  • 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 that trigger anaphylaxis may change with time

Clinical Presentation

  • Acute onset of illness
    • May have biphasic recurrence 6-8 hours after initial episode
  • 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

 

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.

Immunoglobulin E 0050345
Method: Quantitative ImmunoCAP® Fluorescent Enzyme Immunoassay

Limitations

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

Tryptase 0099173
Method: Quantitative Fluorescent Enzyme Immunoassay

Limitations

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

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

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

Histamine, Urine 0070038
Method: Quantitative Enzyme Immunoassay

N-Methylhistamine, 24-Hour Urine 2011034
Method: Quantitative Liquid Chromatography/Tandem Mass Spectrometry/Colorimetry

Guidelines

Lieberman P, Camargo CA, Bohlke K, Jick H, Miller RL, Sheikh A, Simons ER. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol. 2006; 97(5): 596-602. PubMed

Muraro A, Roberts G, Simons ER. New visions for anaphylaxis: an iPAC summary and future trends. Pediatr Allergy Immunol. 2008; 19 Suppl 19: 40-50. PubMed

Muraro A, Roberts G, Worm M, Bilò MB, Brockow K, Rivas F, Santos AF, Zolkipli ZQ, Bellou A, Beyer K, Bindslev-Jensen C, Cardona V, Clark AT, Demoly P, Dubois AE J, DunnGalvin A, Eigenmann P, Halken S, Harada L, Lack G, Jutel M, Niggemann B, Ruëff F, Timmermans F, Vlieg-Boerstra BJ, Werfel T, Dhami S, Panesar S, Akdis CA, Sheikh A, EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014; 69(8): 1026-45. PubMed

Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson F, Bock A, Branum A, Brown SG A, Camargo CA, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons E, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med. 2006; 47(4): 373-80. PubMed

Simons ER, Ardusso LR F, Bilò B, Dimov V, Ebisawa M, El-Gamal YM, Ledford DK, Lockey RF, Ring J, Sanchez-Borges M, Senna GEnrico, Sheikh A, Thong BY, Worm M, World Allergy Organization. 2012 Update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunol. 2012; 12(4): 389-99. PubMed

General References

Arnold JJ, Williams PM. Anaphylaxis: recognition and management. Am Fam Physician. 2011; 84(10): 1111-8. PubMed

Atkins D, Bock A. Fatal anaphylaxis to foods: epidemiology, recognition, and prevention. Curr Allergy Asthma Rep. 2009; 9(3): 179-85. PubMed

Ben-Shoshan M, Clarke AE. Anaphylaxis: past, present and future. Allergy. 2011; 66(1): 1-14. PubMed

Da Broi U, Moreschi C. Post-mortem diagnosis of anaphylaxis: A difficult task in forensic medicine. Forensic Sci Int. 2011; 204(1-3): 1-5. PubMed

Liberman DB, Teach SJ. Management of anaphylaxis in children. Pediatr Emerg Care. 2008; 24(12): 861-6; quiz 867-9. PubMed

Sclar DA, Lieberman PL. Anaphylaxis: underdiagnosed, underreported, and undertreated. Am J Med. 2014; 127(1 Suppl): S1-5. PubMed

Simons ER, Sheikh A. Anaphylaxis: the acute episode and beyond. BMJ. 2013; 346: f602. PubMed

Medical Reviewers

Last Update: April 2016