<< Allergy And Anaphylaxis: Principles Of Acute Emergency Management


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Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.

  1. Sampson HA, Munoz-Furlong A, Bock SA, et al. Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol. 2005;115(3):584-591. (Consensus statement)
  2. Lieberman P, Nicklas RA, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126(3):477-480. (Systematic review and expert consensus)
  3. Cohen SG, Zelaya-Quesada M. Portier, Richet, and the discovery of anaphylaxis: a centennial. J Allergy Clin Immunol. 2002;110(2):331-336. (Historial review)
  4. Clark S, Camargo CA Jr. Epidemiology of anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):145-163. (Epidemiologic review)
  5. Clark S, Espinola JA, Rudders SA, et al. Favorable trends in the frequency of US emergency department visits for food allergy, 2001-2009. Allergy Asthma Proc. 2013;34(5):439-445. (Multicenter retrospective cohort study)
  6. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Int Med. 2001;161(1):15-21. (Meta-analysis)
  7. Brown AFT, McKinnon D. Emergency department anaphylaxis: a review of 142 patients in a single year. J Allergy Clin Immunol. 2001;108(5):861-866. (Retrospective study; 142 cases)
  8. Wood RA, Camargo CA, Lieberman P, et al. Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. (Retrospective survey; 2059 patients)
  9. Decker WW, Campbell RL, Manivannan V, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: a report from the Rochester Epidemiology Project. J Allergy Clin Immunol. 2008;122(6):1161-1165. (Retrospective incidence study; 211 cases)
  10. Lin RY, Curry A, Pitsios VI, et al. Cardiovascular responses in patients with acute allergic reactions treated with parenteral epinephrine. Am J Emerg Med. 2005;23(3):266-272. (Descriptive randomized study; 63 patients)
  11. Harduar-Morano L, Simon MR, Watkins S, et al. A population-based epidemiologic study of emergency department visits for anaphylaxis in Florida. J Allergy Clin Immunol. 2011;128(3):594-U239. (Retrospective epidemiologic review; 2751 cases)
  12. Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107(1):191-193. (Retrospective epidemiologic case review; 32 cases)
  13. Bollinger ME, Dahlquist LM, Mudd K, et al. The impact of food allergy on the daily activities of children and their families. Ann Allergy Asthma Immunol. 2006;96(3):415-421. (Retrospective survey; 87 cases)
  14. Ross MP, Ferguson M, Street D, et al. Analysis of food-allergic and anaphylactic events in the national electronic injury surveillance system. J Allergy Clin Immunol. 2008;121(1):166- 171. (Retrospective case review; 141 cases)
  15. Techapornroong M, Akrawinthawong K, Cheungpasitporn W, et al. Anaphylaxis: a ten years inpatient retrospective study. Asian Pac J Allergy Immunol. 2010;28(4):262-269. (Retrospective review; 80 cases of anaphylaxis)
  16. Vetander M, Helander D, Flodstrom C, et al. Anaphylaxis and reactions to foods in children - a population-based case study of emergency department visits. Clin Exp Allergy. 2012;42(4):568-577. (Chart review; 383 cases)
  17. Sampson HA. Anaphylaxis and emergency treatment. Pediatrics. 2003;111(6 Pt 3):1601-1608. (Review)
  18. Castells MC, Horan RF, Sheffer AL. Exercise-induced anaphylaxis (EIA). Clin Rev Allergy Immunol. 1999;17(4):413-424. (Review)
  19. Beaudouin E, Renaudin JM, Morisset M, et al. Food-dependent exercise-induced anaphylaxis--update and current data. Eur Ann Allergy Clin Immunol. 2006;38(2):45-51. (Review)
  20. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105(4):259-273. e78. (Practice guideline)
  21. Renaudin JM, Beaudouin E, Ponvert C, et al. Severe drug-induced anaphylaxis: analysis of 333 cases recorded by the Allergy Vigilance Network from 2002 to 2010. Allergy. 2013;68(7):929-937. (Retrospective case study; 333 cases)
  22. Golden DBK. Insect sting anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):261. (Review)
  23. Pollyea DA, George TI, Corless C, et al. When yellow jackets attack: recurrent and severe anaphylactic reactions to insect bites and stings. Am J Hematol. 2009;84(12):843-846. (Case report; 1 patient)
  24. Chiu AM, Kelly KJ. Anaphylaxis: drug allergy, insect stings, and latex. Immunol Allergy Clin North Am. 2005;25(2):389-405. (Review)
  25. Boxer MB, Greenberger PA, Patterson R. The impact of prednisone in life-threatening idiopathic anaphylaxis: reduction in acute episodes and medical costs. Ann Allergy. 1989;62(3):201-204. (Case studies; 2 cases)
  26. Alonso MAT, Dominguez JS, Sanchez-Hernandez JJ, et al. Clinical and functional differences among patients with idiopathic anaphylaxis. J Investig Allergol Clin Immunol. 2004;14(3):177-186. (Systematic review)
  27. Stoloff R, Adams SL, Orfan N, et al. Emergency medical recognition and management of idiopathic anaphylaxis. J Emerg Med. 1992;10(6):693-698. (Retrospective review; 225 patients)
  28. Wong S, Dykewicz MS, Patterson R. Idiopathic anaphylaxis. A clinical summary of 175 patients. Arch Int Med. 1990;150(6):1323-1328. (Retrospective review 175 patients)
  29. Brown SGA, Blackman KE, Stenlake V, et al. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emerg Med J. 2004;21(2):149-154. (Prospective study; 21 patients)
  30. Simons FER, Simons KJ. Epinephrine (Adrenaline) in Anaphylaxis. In: Ring J, ed. Anaphylaxis. Vol 95. Basel, Switzerland: Karger; 2010:211-222. (Textbook chapter)
  31. Gelincik A, Demirturk M, Yilmaz E, et al. Anaphylaxis in a tertiary adult allergy clinic: a retrospective review of 516 patients. Ann Allergy Asthma Immunol. 2013;110(2):96-100. (Retrospective review; 516 anaphylaxis cases)
  32. Simons FER. Anaphylaxis. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S161-S181. (Review)
  33. Brockow K, Jofer C, Behrendt H, et al. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;63(2):226-232. (Retrospective survey; 120 patients)
  34. Brown SGA, Blackman KE, Stenlake V, et al. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emerg Med J. 2004;21(2):149-154. (Prospective study; 21 patients)
  35. Brown SG. The pathophysiology of shock in anaphylaxis. Immunol Allergy Clin North Am. 2007;27(2):165-175. (Review)
  36. Fisher MM. Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse. Anaesth Intensive Care. 1986;14(1):17. (Observational study; 205 patients)
  37. Hara A, Fukahori S, Nakata H, et al. [A case of anaphlaxis caused by mite-contaminated Okonomi-yaki]. Arerugi = [Allergy]. 2006;55(5):574-577. (Case Report; 1 case)
  38. Williams AN, Woessner KM. Monosodium glutamate ‘allergy’: menace or myth? Clin Exp Allergy. 2009;39(5):640-646. (Review)
  39. Gadban H, Gilbey P, Talmon Y, et al. Acute edema of the tongue: a life-threatening condition. Annals Otol Rhinol Laryngol. 2003;112(7):651-653. (Case reports; 3 cases)
  40. Dyer PD. Late-onset angioedema after interruption of angiotensin converting enzyme inhibitor therapy. J Allergy Clin Immunol. 1994;93(5):947-948. (Case report; 1 case)
  41. Bezalel S, Mahlab-Guri K, Asher I, et al. Angiotensin-converting enzyme inhibitor-induced angioedema. Am J Med. 2015;128(2):120-125. (Review)
  42. Kostis JB, Kim HJ, Rusnak J, et al. Incidence and characteristics of angioedema associated with enalapril. Arch Int Med. 2005;165(14):1637-1642. (Double-blind randomized controlled OCTAVE trial; 12,557 patients)
  43. Zilberberg MD, Nathanson BH, Jacobsen T, et al. Descriptive epidemiology of hereditary angioedema emergency department visits in the United States, 2006. Allergy Asthma Proc. 2011;32(5):390-394. (Epidemiology study; 2705 patients)
  44. Weis M. Clinical review of hereditary angioedema: diagnosis and management. Postgrad Med. 2009;121(6):113-120. (Review)
  45. Hill BJ, Thomas SH, McCabe C. Fresh-frozen plasma for acute exacerbations of hereditary angioedema. Am J Emerg Med. 2004;22(7):633. (Case report)
  46. Pekdemir M, Ersel M, Aksay E, et al. Effective treatment of hereditary angioedema with fresh-frozen plasma in an emergency department. J Emerg Med. 2007;33(2):137-139. (Case series; 3 patients)
  47. Bains SN, Hsieh FH. Current approaches to the diagnosis and treatment of systemic mastocytosis. Ann Allergy Asthma Immunol. 2010;104(1):1-10. (Systematic review)
  48. Simons FER, Ardusso LR, Bilò MB, et al. International consensus on (ICON) anaphylaxis. World Allergy Organ J. 2014;7(1):9. (Consensus statement)
  49. Rudders SA, Banerji A. An update on self-injectable epinephrine. Curr Opin Allergy Clin Immunol. 2013;13(4):432-437. (Review)
  50. Segal N, Garty BZ, Hoffer V, et al. Effect of instruction on the ability to use a self-administered epinephrine injector. Isr Med Assoc J. 2012;14(1):14-17. (Cross-sectional convenience study; 141 patients)
  51. Capps JA, Sharma V, Arkwright PD. Prevalence, outcome and pre-hospital management of anaphylaxis by first aiders and paramedical ambulance staff in Manchester, UK. Resuscitation. 2010;81(6):653-657. (Retrospective review; 816 cases)
  52. Rea TD, Edwards C, Murray JA, et al. Epinephrine use by emergency medical technicians for presumed anaphylaxis. Prehosp Emerg Care. 2004;8(4):405-410. (Case control study; 66 cases)
  53. Ban KM, Bramwell K, Sakles JC, et al. Airway forum. Intern Emerg Med. 2006;1(2):151-154. (Case Review)
  54. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. part 10.6: Anaphylaxis. Circulation. 2005;112(24 suppl):IV143- IV145. (Consensus guidleines)
  55. Sheikh A, ten Broek VM, Brown SGA, et al. H1-antihistamines for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2007;1:CD006160. (Systematic review)
  56. National Institute for Health and Clinical Excellence (NICE). Anaphylaxis: assessment to confirm an anaphylactic episode and the decision to refer after emergency treatment for a suspected anaphylactic episode. London (UK): National Institute for Health and Clinical Excellence (NICE); 2011. 25 p. (Clinical guideline; no. 134). (Expert review and consensus guideline)
  57. Kemp SF, Lockey RF. Anaphylaxis: a review of causes and mechanisms. J Allergy Clin Immunol. 2002;110(3):341-348. (Review)
  58. Banerji A, Rudders SA, Corel B, et al. Repeat epinephrine treatments for food-related allergic reactions that present to the emergency department. Allergy Asthma Proc. 2010;31(4):308-316. (Retrospective chart review; 486 patients)
  59. Nakanishi T, Yasuda S, Kubota Y, et al. Allergic contact dermatitis presenting in the emergency department. Contact Dermatitis. 2005;52(1):52-53. (Case reports; 10 cases)
  60. Bork K, Staubach P, Eckardt AJ, et al. Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency. Am J Gastroenterol. 2006;101(3):619-627. (Study with retrospective and prospective arms; 153 and 23 patients, respectively)
  61. Vadas P, Perelman B, Liss G. Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis. J Allergy Clin Immunol. 2013;131(1):144-149. (Prospective cross-sectional study; 41 patients)
  62. Sicherer SH, Leung DYM. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2013. J Allergy Clin Immunol. 2014;133(2):324- 334. (Review)
  63. Finkelman FD, Rothenberg ME, Brandt EB, et al. Molecular mechanisms of anaphylaxis: lessons from studies with murine models. J Allergy Clin Immunol. 2005;115(3):449-457. (Systematic review)
  64. Simons FER, Frew AJ, Ansotegui IJ, et al. Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol. 2007;120(1 Suppl):S2-S24. (Expert review and consensus)
  65. Rodrigo G, Pollack C, Rodrigo C, et al. Heliox for non-intubated acute asthma patients. Cochrane Database Syst Rev. 2006;18(4):CD002884. (Cochrane Systematic Review)
  66. Gavalas M, Sadana A, Metcalf S. Guidelines for the management of anaphylaxis in the emergency department. J Accid Emerg Med. 1998;15(2):96-98. (Expert guidelines)
  67. Waugh J, Gardner D, Vines D. Effect of heliox on end-tidal CO2 measurement in healthy adults. Respir Care. 2013;58(11):1945-8. (Prospective observational study; 20 patients)
  68. Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers. Resuscitation. 2008;77(2):157-169. (Expert guideline)
  69. Alrasbi M, Sheikh A. Comparison of international guidelines for the emergency medical management of anaphylaxis. Allergy. 2007;62(8):838-841. (Systematic review)
  70. Kemp SF, Lockey RF, World Allergy Organization ad hoc Committee on Epinephrine in Anaphylaxis. Epinephrine: the drug of choice for anaphylaxis-a statement of the world allergy organization. World Allergy Organ J. 2008;1(7 Suppl):S18-S26. (Consensus statement)
  71. Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108(5):871-873. (Prospective randomized trial; 13 patients)
  72. Simons FE, Roberts JR, Gu X, et al. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol. 1998;101(1 Pt 1):33-37. (Prospective randomized trial; 17 patients)
  73. Sheikh A, Shehata YA, Brown SG, et al. Adrenaline (epinephrine) for the treatment of anaphylaxis with and without shock. Cochrane Database Syst Rev. 2008;4:CD006312. (Systematic review)
  74. Sheikh A, Simons FER, Barbour V, et al. Adrenaline auto-injectors for the treatment of anaphylaxis with and without cardiovascular collapse in the community. Cochrane Database Syst Rev. 2012;8:CD008935. (Systematic review)
  75. Simons FER. First-aid treatment of anaphylaxis to food: focus on epinephrine. J Allergy Clin Immunol. 2004;113(5):837- 844. (Review)
  76. Lin RY, Curry A, Pesola GR, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med. 2000;36(5):462-468. (Prospective randomized trial ; 91 patients)
  77. Choo KJ, Simons FE, Sheikh A. Glucocorticoids for the treatment of anaphylaxis. Cochrane Database Syst Rev. 2012;4:CD007596. (Systematic review)
  78. Lieberman P. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol. 2005;95(3):217-226. (Systematic review)
  79. Nuchprayoon I, Garner P. Interventions for preventing reactions to snake antivenom. Cochrane Database Syst Rev. 2000;2:CD002153. (Systematic review)
  80. Buck ML, Wiggins BS, Sesler JM. Intraosseous drug administration in children and adults during cardiopulmonary resuscitation. Ann Pharmacother. 2007;41(10):1679-1686. (Systematic review)
  81. Von Hoff DD, Kuhn JG, Burris HA 3rd, et al. Does intraosseous equal intravenous? A pharmacokinetic study. Am J Emerg Med. 2008;26(1):31-38. (Prospective randomized crossover study)
  82. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clinical Exp Allergy. 2000;30(8):1144-1150. (Retrospective study; 164 patients)
  83. Javeed N, Javeed H, Javeed S, et al. Refractory anaphylactoid shock potentiated by beta-blockers. Cathet Cardiovasc Diagn. 1996;39(4):383-384. (Case report; 1 patient)
  84. Zaloga GP, DeLacey W, Holmboe E, et al. Glucagon reversal of hypotension in a case of anaphylactoid shock. Ann Int Med. 1986;105(1):65-66. (Case report; 1 patient)
  85. Benitah E, Nataf P, Herman D. [Anaphylactic complications in patients treated with beta-blockers. Apropos of 14 cases]. Therapie. 1986;41(2):139-142. (Case studies; 14 cases)
  86. Greenhawt MJ, Singer AM, Baptist AP. Food allergy and food allergy attitudes among college students. J Allergy Clin Immunol. 2009;124(2):323-327. (Prospective survey; 513 respondents)
  87. Choo KJL, Nurmatov U, Sheikh A. Emergency action plans for people at risk of anaphylaxis (major allergy) (protocol). Cochrane Database Syst Rev. 2012;4: CD009773. (Systematic review)
  88. Simons FER. Lack of worldwide availability of epinephrine autoinjectors for outpatients at risk of anaphylaxis. Ann Allergy Asthma Immunol. 2005;94(5):534-538. (Cross-sectional survey)
  89. DeMuth KA, Fitzpatrick AM. Epinephrine autoinjector availability among children with food allergy. Allergy Asthma Proc. 2011;32(4):295-300. (Cross-sectional study; 63 patients)
  90. Lieberman P, Nicklas RA, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126(3):477-80. (Expert review and consensus guideline)
  91. Mackway-Jones K. Best evidence topic report. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Emerg Med J. 2005;22(12):887. (Review)
  92. Edwards ES, Gunn R, Simons ER, et al. Bioavailability ofepinephrine from Auvi-Q compared with EpiPen. Ann Allergy Asthma Immunol. 2013;111(2):132-137. (Randomized single-blind 2-treatment, 3-period, 3-sequence cross-over study; 71 patients)
  93. Edwards ES, Edwards ET, Gunn R, et al. Design validation and labeling comprehension study for a new epinephrine autoinjector. Ann Allergy Asthma Immunol. 2013;110(3):189. (Prospective observational study; 40 subjects)
  94. Lewis LM, Graffeo C, Crosley P, et al. Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. Ann Emerg Med. 2015;65(2):204-213. (Multicenter randomized controlled trial; 76 patients)
  95. Bas M, Greve J, Stelter K, et al. Therapeutic efficacy of icatibant in angioedema induced by angiotensin-con-verting enzyme inhibitors: a case series. Ann Emerg Med. 2010;56(3):278-282. (Case series; 8 patients)
  96. Oliveira N, Duarte N, Vincente W, et al. Methylene blue: an effective treatment for contrast medium-induced anaphylaxis. Med Sci Monit. 2003;9(11):CS102-CS106. (Case report; 3 patients)
  97. Zheng F, Barthel G, Collange O, et al. Methylene blue and epinephrine: a synergetic association for anaphylactic shock treatment. Crit Care Med. 2013;41(1):195-204. (Prospective animal study; 60 rats)
  98. Ishoo E, Shah U, Grillone G, et al. Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999;121(3):263-268. (Retrospective chart review; 80 patients)
  99. Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions—guidelines for healthcare providers. Resuscitation. 2008;77(2):157-169. (Clinical guidelines)
  100. Lieberman P. Biphasic anaphylactic reactions. Annals Allergy Asthma Immunol. 2005;95(3):217-226. (Literature review)
  101. Ellis A, Day J. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients. Annals Allergy Asthma Immunol. 2007;98(1):64-69. (Prospective study; 103 patients)
  102. Rohacek M, Edenhofer H, Bircher A, et al. Biphasic anaphylactic reactions occurrence and mortality. Allergy. 2014;69(6):791-797. (Retrospective chart review; 532 patients with anaphylaxis)
  103. Grunau BE, Li J, Yi TW, et al. Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis. Ann Emerg Med. 2014;63(6):736-744. (Retrospective chart review; 2819 emergency department patient encounters)
  104. Alrasbi M, Sheikh A. Comparison of international guidelines for the emergency medical management of anaphylaxis. Allergy. 2007;62(8):838-841. (Review)
Publication Information

Elizabeth Singer, MD, MPH, FACEP; David Zodda, MD;

Publication Date

August 1, 2015

CME Expiration Date

August 31, 2018

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