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anaphylaxis

- Life-threatening systemic hypersensitivity reaction to contact with an allergen. - It may occur within minutes of exposure to the offending agent. Etiology: 1) almost any allergen may incite an anaphylactic reaction 2) pharmacologic causes: (14%)* [2,6,20] a) antibiotics - cephalosporins (common) - ceftriaxone* - penicillins (common) - amoxicillin, amoxicillin-clavulanate* - moxifloxacin b) insulin (common) c) dextran d) iodinated drugs - iopamidol*, iopromide* e) lidocaine* f) procaine g) NSAIDs [12] - ibuprofen, diclofenac* g) aspirin & contrast agents elicit anaphylactoid response (not true anaphylaxis) h) monoclonal antibodies [20] - infliximab, omalizumab (Xolair) i) intraoperative agents - propofol*, rocuronium* j) chemotherapeutic agents - paclitaxel* k) fluorescein* 3) antisera 4) pollen extracts 5) Hymenoptera venom (19%) [6] 6) foods (33%) [6] a) nuts, especially peanuts - peanut antigen may contaminate foods such as pastries, candies, yogurt, cookies, egg rolls, chilis b) shellfish c) eggs d) milk e) spices f) food additives 7) exercise-induced a) food allergy may condition anaphylactic response b) exercise induces the response c) neither food nor exercise alone elicits response 8) latex allergy a) gloves, condoms (during surgery, coitus) b) important cause of intraoperative anaphylaxis 9) IgA deficiency - transfusion reaction (anti-IgA, IgG or IgE) 10) seminal fluid 11) cold urticaria 12) idiopathic (25-40%), some may be psychogenic * most common cause of anaphylaxis-related deaths [10,20] * anaphylaxis-related deaths most common in elderly [10] Epidemiology: - 50 cases/100,000 patient years is high estimate [6] - mean age = 29 - peak incidence in children - case fatality highest in hostpitalized elderly [10] Pathology: 1) IgE-mediated antigen response to an antigen (anaphylactic reaction) 2) non-antibody antigen mechanism (anaphylactoid reaction) 3) mast cell degranulation a) release of histamine & other preformed mediators of anaphylaxis cause immediate effects b) leukotriene synthesis causes some of the delayed effects c) other mediator of anaphylaxis - prostaglandin D2 (major) - tumor necrosis factor-alpha (TNF-alpha) - interleukin-1 (IL-1) 4) anaphylactic shock results from severe hypovolemia due to fluid shifts resulting from increased vascular permeability & vasodilation [4] 4) treatment with beta-blockers is a risk factor for prolonged & severe reactions Clinical manifestations: 1) skin or mucous membrane manifestations (85%) often 1st signs/symptoms [19] a) pruritus, conjunctival pruritus b) urticaria - circumscribed, erythematous, pruritic papules & plaques - individual lesions resolve within 24 hours c) angioedema - diffuse swelling in deeper layers of the dermis - often occurs in face or extremities d) mucous membrane swelling - airway edema 2) pulmonary/respiratory tract manifestations (70%) a) respiratory distress b) hoarseness, stridor, laryngeal edema c) wheezing, bronchospasm, bronchorrhea 3) gastrointestinal manifestations (45%) a) nausea/vomiting b) diarrhea c) abdominal pain & distension 4) cardiovascular manifestations (45%) a) tachycardia, occasionally bradycardia [4] b) vasodilation, flushing, hypotension, distributive shock, vascular collapse c) arrhythmias 5) neurologic (15%) a) sense of impending doom b) headache c) encephalopathy [4] 6) 3 patterns of anaphylaxis a) acute reactions developing within 5 minutes (50%) b) biphasic reactions (25%) - early abdominal, intestinal or oral angioedema - respiratory symptoms & hypotension begin 1-2 hours later c) prolonged hypotension & respiratory failure, especially in patients taking beta-blockers Laboratory: - serum tryptase (released from mast cells) a) elevation occurs within 2 hours & is useful for confirming diagnosis b) less likely to be elevated after food-induced anaphylaxis c) baseline serum tryptase can identify patients at high risk for anaphylaxis - multiple allergen IgE testing - histamine in serum/plasma - levels peak 5 minutes after onset of anaphylaxis - baseline levels return within 30-60 minutes - N-methylhistamine in urine - see ARUP consult [8] Complications: - anaphylactic shock - biphasic reactions, recurrent symptoms after a symptom-free period following anaphylaxis - rare [15]; uo to 20% or patients within 72 hours [18] - severity of initial presentation predicts biphasic reaction [18] - asthma is a risk factor for poor outcome [19] Management: 1) epinephrine is 1st line [4] even in older patients [14] a) early, even prophylactic administration indicated [4] - even if hypotensive &/or tachycardia & in the emergency room [21] b) emergency administration IM given into thigh muscle 1/2 way between hip & knee; may be admnistered through clothing [21] c) 0.2-0.5 mL of a 1:1000 solution IM every 20 min PRN - IM rather than SC injection [4] - provides most consistent absorption & duration [21] d) IV infusion of a 1:10,000 solution for hypotension e) patients receiving beta blockers 1] may not respond to epinephrine 2] treatment with glucagon may be life-saving 2) IV access: normal saline vs balanced crystaloid for hypotension 3) glucagon is 2nd line [4] - 1-5 mg IV over 2-5 minutes - Emergency Department or ICU setting [5] - may reverse refractory hypotension & bronchospasm - especially useful in patients on beta-blockers - reversal of beta-blocker effects [4] 4) antihistamines (both H1 receptor antagonists & H2 receptor antagonists) a) for cutaneous symptoms only (not for lip swelling) [4,17] b) diphenhydramine 50-80 mg IV or IM c) cimetidine or ranitidine 5) intravenous glucocorticoids a) not useful for acute manifestations [17] b) not useful for preventing biphasic reactions [18] c) may help control persistent hypotension or bronchospasm 6) treat bronchospasm as asthma a) aminophylline 0.25-0.5 g IV for bronchospasm b) oxygen c) glucocorticoids d) albuterol & atrovent nebulizers 7) hospitalize for severe reactions a) supportive treatment for shock b) intubation for laryngeal edema c) risk of relapse in 12-24 hours d) monitor in intensive care unit for at least 12 hours [4] 8) prognosis a) may progress over 3-5 hours thus requires observation for life-threatening respiratory complications b) with timely supportive care, rarely fatal [4] c) biphasic (late) response is rare - prolonged monitoring after resolution of symptoms is not routinely indicated [11] 9) skin testing & desensitization 10) avoid offending agent 11) discharge with epinephrine autoinjector

Related

anaphylactoid reaction insect sting or anaphylaxis kit (Ana-Kit) shock

Specific

anaphylactic transfusion reaction

General

type 1 hypersensitivity; immediate hypersensitivity (allergy)

References

  1. Sampson HA et al. 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. J Allergy Clin Immunol 2006 Feb; 117:391 PMID: 16461139
  2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, page 145
  3. H. Quinny Cheng, USSF Fresno lecture, Oct 21, 1998
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Prescriber's Letter 12(7): 2005 Should Some Drugs Be Avoided in Patients at Risk of Anaphylaxis? Detail-Document#: 210714 (subscription needed) http://www.prescribersletter.com
  6. Decker WW et al, The etiology and incidence of anaphylaxis in Rochester, Minnnesota: A report from the Rochester Epidemiology Project. J Allergy Clin Immunol 2008, 122:1161 PMID: 18992928
  7. Prescriber's Letter 17(6): 2010 COMMENTARY: Self-injected Epinephrine in the Outpatient Treatment of Anaphylaxis GUIDELINES: American Academy of Allergy, Asthma and Immunology: The Diagnosis and Management of Anaphylaxis Detail-Document#: 260602 (subscription needed) http://www.prescribersletter.com
  8. ARUP Consult: Anaphylaxis The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/anaphylaxis
  9. Sheikh A, Shehata YA, Brown SG, Simons FE. Adrenaline for the treatment of anaphylaxis: cochrane systematic review. Allergy. 2009 Feb;64(2):204-12 PMID: 19178399
  10. Amrol DJ Anaphylaxis Incidence Is Increasing in the U.S. NEJM Journal Watch. April 22, 2014 Massachusetts Medical Society http://www.jwatch.org - Ma L et al. Case fatality and population mortality associated with anaphylaxis in the United States. J Allergy Clin Immunol 2014 Apr; 133:1075 PMID: 24332862 http://www.jacionline.org/article/S0091-6749%2813%2901642-4/abstract
  11. Grunau BE et al. Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis. Ann Emerg Med 2014 Jun; 63:736 PMID: 24239340
  12. Aun MV, Blanca M, Garro LS eta al Nonsteroidal anti-inflammatory drugs are major causes of drug- induced anaphylaxis. J Allergy Clin Immunol Pract. 2014 Jul-Aug;2(4):414-20 PMID: 25017529
  13. Simons FE, Sheikh A. Anaphylaxis: the acute episode and beyond. BMJ. 2013 Feb 12;346:f602 PMID: 23403828
  14. Kawano T et al. Epinephrine use in older patients with anaphylaxis: Clinical outcomes and cardiovascular complications. Resuscitation 2017 Jan 6; [e-pub]. PMID: 28069483 http://www.resuscitationjournal.com/article/S0300-9572(17)30001-1/abstract
  15. Hojlund S, Soe-Jensen P, Perner A et al. Low incidence of biphasic allergic reactions in patients admitted to intensive care after anaphylaxis. Anesthesiology 2019 Feb; 130:284-291 PMID: 30418213 https://insights.ovid.com/crossref?an=00000542-201902000-00020
  16. Commins SP. Outpatient Emergencies: Anaphylaxis. Med Clin North Am. 2017 May;101(3):521-536. Review. PMID: 28372711 Free PMC Article
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  18. Shaker MS, Wallace DV, Golden DBK et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol 2020 Apr; 145:1082 PMID: 32001253 https://www.jacionline.org/article/S0091-6749(20)30105-6/pdf
  19. NEJM Knowledge+ Question of the Week. Dec 8, 2020 https://knowledgeplus.nejm.org/question-of-week/1238/ - Bilo MB et al. Anaphylaxis. Eur Ann Allergy Clin Immunol 2020 Jun 19 PMID: 32550734 Free article
  20. Yu RJ, Krantz MS, Phillips EJ et al. Emerging causes of drug-induced anaphylaxis: A review of anaphylaxis-associated reports in the FDA Adverse Event Reporting System (FAERS). J Allergy Clin Immunol Pract 2021 Feb; 9:819. PMID: 32992044 PMCID: PMC7870524 (available on 2022-02-01) https://www.sciencedirect.com/science/article/abs/pii/S2213219820309995
  21. NEJM Knowledge+ Allergy/Immunology
  22. American Heart Association Basic Life Support Provider Manual eBook
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