Acute Allergic Reaction and Anaphylaxis (> 6 months) - Curbside
Acute Allergic Reaction and Anaphylaxis (> 6 months)
Editors: Dan Imler, MD
Inclusion Criteria  (Any one criteria present)
  • Clinical concern for allergic or anaphylatic reaction
Exclusion Criteria
  • History of severe airway abnormality, surgery or tracheostomy
  • Pregnancy

Consider allergy consult

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Evidence
Total Notes: 13
Evidence

1 Pathophysiology

Allergic and anaphylactic reactions are the result of mast cell- and basophil-derived mediators being release by the body secondary to a triggering mechanism. These may be IgE-mediated or non IgE-mediated processes.



References:

2 Immediate intervention

In a case series of 164 anaphylaxis fatalities, the median time between onset of symptoms and respiratory / cardiac arrest:

  • Iatrogenic (5 min)
  • Insect venom-induced (15 min)
  • Food-induced (30 min)

Therefore, immediate assessment and resuscitation (including epinephrine if appropriate) should be employed in any patient with signs of allergy/anaphylaxis.



References:
  1. Lessons for management of anaphylaxis from a study of fatal reactions.
    Pumphrey RS
    Clin Exp Allergy. 2000;30(8):1144.

3 Anaphylaxis criteria

Identifying anaphylaxis is key to providing the life-saving treatment often required in this disease process. It also reduces the overreliance on adjunctive medications (antihistamines, steroids) which are not in favor of lifesaving medications (epinephrine). A multidisciplinary group of experts has created criteria to define the diagnosis of anaphylaxis. Using these criteria a retrospective cohort study found a sensitivity of 92 percent, specificity of 82 percent, positive-predictive value of 69 percent, and negative-predictive value of 98 percent.

Signs and symptoms common to anaphylaxis are:

  • Skin findings (90% of episodes)
    • Generalized hives, pruritus or flushing, swollen lips-tongue-uvula, itching, flushing, periorbital edema, conjunctival swelling/chemosis
  • Respiratory findings (70% of episodes)
    • Congestion, nasal discharge, change in voice, sensation of throat closure, stridor, difficulty breathing, cough, wheezing
  • Gastrointestinal findings (45% of episodes)
    • Abdominal pain, nausea, vomiting, diarrhea
  • Cardiovascular findings (45% of episodes)
    • dizziness, syncope, tachycardia, hypotension


References:
  1. Symposium on the definition and management of anaphylaxis: summary report.
    Sampson HA, Muñoz-Furlong A, Bock SA, Schmitt C, Bass R, Chowdhury BA, Decker WW, Furlong TJ, Galli SJ, Golden DB, Gruchalla RS, Harlor AD Jr, Hepner DL, Howarth M, Kaplan AP, Levy JH, Lewis LM, Lieberman PL, Metcalfe DD, Murphy R, Pollart SM, Pumphrey RS, Rosenwasser LJ, Simons FE, Wood JP, Camargo CA Jr
    J Allergy Clin Immunol. 2005;115(3):584.
  2. 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.
    Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW
    J Allergy Clin Immunol. 2006;117(2):391.
  3. Lessons for management of anaphylaxis from a study of fatal reactions.
    Pumphrey RS
    Clin Exp Allergy. 2000;30(8):1144.
  4. Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients.
    Campbell RL, Hagan JB, Manivannan V, Decker WW, Kanthala AR, Bellolio MF, Smith VD, Li JT
    J Allergy Clin Immunol. 2012 Mar;129(3):748-52.
  5. Anaphylaxis.
    Simons FE
    J Allergy Clin Immunol. 2010;125(2 Suppl 2):S161.
  6. Anaphylaxis: a review of causes and mechanisms.
    Kemp SF, Lockey RF
    J Allergy Clin Immunol. 2002;110(3):341.
  7. The diagnosis and management of anaphylaxis practice parameter: 2010 update.
    Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, Feldweg AM, Fink JN, Greenberger PA, Golden DB, James JM, Kemp SF, Ledford DK, Lieberman P, Sheffer AL, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D
    J Allergy Clin Immunol. 2010;126(3):477.
  8. Anaphylaxis: diagnosis and management.
    Brown SG, Mullins RJ, Gold MS
    Med J Aust. 2006;185(5):283.

4 Serum tryptase

In some cases it may be difficult to tell if a patient is experiencing anaphylaxis or one of the many similar presenting disease processes (asthma, vasovagal syncope, sepsis, benign flushing, carcinoid syndrome, etc.). To further elucidate the diagnosis for long term follow up, serum markers collected soon after the onset of the episode may be beneficial.

Both mast cells and basophils produce tryptase, with mast cells releasing more than 500x that of basophils. When a mast cell is activated, they degranulate, releasing tryptase and histamine into the extracellular space. This tryptase is specific to the mast cells and can give a good indication of their activity. If warranted, serum tryptase should be measured between 15 min and 3 hours after a suspected anaphylaxis episode. A baseline level should also be drawn 24 hours after the event. Even if a tryptase is negative, it should not supplant the clinical diagnosis of anaphylaxis and treatment with epinephrine should not be avoided. In unclear cases, continuing with anaphylaxis treatment is often appropriate.

Tryptase levels are more likely to be elevated in insect stings, medication reactions and episodes involving hypotension.



References:
  1. Serum tryptase levels in atopic and nonatopic children.
    Komarow HD, Hu Z, Brittain E, Uzzaman A, Gaskins D, Metcalfe DD
    J Allergy Clin Immunol. 2009;124(4):845.
  2. Diagnostic value of tryptase in anaphylaxis and mastocytosis.
    Schwartz LB
    Immunol Allergy Clin North Am. 2006;26(3):451.
  3. Risk assessment in anaphylaxis: current and future approaches.
    Simons FE, Frew AJ, Ansotegui IJ, Bochner BS, Golden DB, Finkelman FD, Leung DY, Lotvall J, Marone G, Metcalfe DD, Müller U, Rosenwasser LJ, Sampson HA, Schwartz LB, van Hage M, Walls AF
    J Allergy Clin Immunol. 2007;120(1 Suppl):S2.
  4. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.
    Sampson HA, Mendelson L, Rosen JP
    N Engl J Med. 1992;327(6):380.
  5. Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients.
    Sala-Cunill A, Cardona V, Labrador-Horrillo M, Luengo O, Esteso O, Garriga T, Vicario M, Guilarte M
    Int Arch Allergy Immunol. 2013;160(2):192-9.
  6. Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis.
    Vadas P, Perelman B, Liss G
    J Allergy Clin Immunol. 2013 Jan;131(1):144-9.

5 Epinephrine

Except in extreme circumstances, all patients diagnosed with anaphylaxis should receive epinephrine. Epinephrine acts through alpha-1, beta-1 and beta-2 adrenergic agonist effects to increase vasoconstriction, inotropy, chronotropy bronchodilitation and decrease release of substances from mast cells and basophils. In addition to these effects, patients may also experience anxiety, dizziness, palpitations, tremor and other responses to the catecholamine surge.

Intramuscular injection in the lateral thigh is the preferred route of admiration as it consistently increases plasma and tissue concentrations in a rapid manner. This can be repeated every 5 to 15 minutes although it is rare that a patient will require more than one dose. Subcutaneous injection may provide suboptimal levels of epinephrine so care must be made in obese patients to penetrate the adipose layer into muscle. If a patient does not respond to epinephrine the provider should consider this a sign of poor perfusion to the muscular layers that requires a more aggressive fluid resuscitation. In addition, these patients may benefit from intravenous infusion of epinephrine.

Early administration of epinephrine has been shown to decrease mortality for anaphylaxis patients and decrease the likelihood of biphasic reactions. Therefore, immediate administration is key to the care of these patients and should not be delayed.



References:
  1. Lessons for management of anaphylaxis from a study of fatal reactions.
    Pumphrey RS
    Clin Exp Allergy. 2000;30(8):1144.
  2. Epinephrine and its use in anaphylaxis: current issues.
    Simons KJ, Simons FE
    Curr Opin Allergy Clin Immunol. 2010;10(4):354.
  3. Adrenaline for the treatment of anaphylaxis: cochrane systematic review.
    Sheikh A, Shehata YA, Brown SG, Simons FE
    Allergy. 2009;64(2):204.
  4. Emergency treatment of anaphylaxis.
    Simons FE
    BMJ. 2008;336(7654):1141.
  5. Adrenaline in the treatment of anaphylaxis: what is the evidence?
    McLean-Tooke AP, Bethune CA, Fay AC, Spickett GP
    BMJ. 2003;327(7427):1332.
  6. Effect of epinephrine on platelet-activating factor-stimulated human vascular smooth muscle cells.
    Vadas P, Perelman B
    J Allergy Clin Immunol. 2012 May;129(5):1329-33.
  7. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization.
    Kemp SF, Lockey RF, Simons FE, World Allergy Organization ad hoc Committee on Epinephrine in Anaphylaxis
    Allergy. 2008;63(8):1061.
  8. Epinephrine absorption in adults: intramuscular versus subcutaneous injection.
    Simons FE, Gu X, Simons KJ
    J Allergy Clin Immunol. 2001;108(5):871.
  9. Epinephrine absorption in children with a history of anaphylaxis.
    Simons FE, Roberts JR, Gu X, Simons KJ
    J Allergy Clin Immunol. 1998;101(1 Pt 1):33.
  10. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers.
    Soar J, Pumphrey R, Cant A, Clarke S, Corbett A, Dawson P, Ewan P, Foëx B, Gabbott D, Griffiths M, Hall J, Harper N, Jewkes F, Maconochie I, Mitchell S, Nasser S, Nolan J, Rylance G, Sheikh A, Unsworth DJ, Warrell D, Working Group of the Resuscitation Council (UK)
    Resuscitation. 2008;77(2):157.
  11. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.
    Sampson HA, Mendelson L, Rosen JP
    N Engl J Med. 1992;327(6):380.

6 Maintaining perfusion

Anaphylaxis increases vascular permeability which may result in massive shifts of fluids from the intravascular to extravascular space (up to 35 percent within minutes). Placement of two large bore IVs (or other venous access) is necessary to deliver large volumes of fluid to maintain adequate perfusion.  Any patient with orthostasis, hypotension, or incomplete response to intramuscular epinephrine should be started on IV fluids (normal saline) immediately with titration to adequate perfusion. Volumes up to 100 ml/kg may be required.

If possible patients showing signs of poor perfusion should be placed in a Trendelenburg position (recumbent position with the lower extremities elevated) to maximize venous return to the heart.

If patients continue to show poor perfusion despite IM epinephrine and IV fluids, consideration should be given to start a SLOW IV infusion of epinephrine.



References:
  1. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation.
    Brown SG, Blackman KE, Stenlake V, Heddle RJ
    Emerg Med J. 2004;21(2):149.
  2. The diagnosis and management of anaphylaxis practice parameter: 2010 update.
    Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, Feldweg AM, Fink JN, Greenberger PA, Golden DB, James JM, Kemp SF, Ledford DK, Lieberman P, Sheffer AL, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D
    J Allergy Clin Immunol. 2010;126(3):477.
  3. World Allergy Organization anaphylaxis guidelines: summary.
    Simons FE, Ardusso LR, BilòMB, El-Gamal YM, Ledford DK, Ring J, Sanchez-Borges M, Senna GE, Sheikh A, Thong BY, World Allergy Organization
    J Allergy Clin Immunol. 2011;127(3):587.
  4. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers.
    Soar J, Pumphrey R, Cant A, Clarke S, Corbett A, Dawson P, Ewan P, Foëx B, Gabbott D, Griffiths M, Hall J, Harper N, Jewkes F, Maconochie I, Mitchell S, Nasser S, Nolan J, Rylance G, Sheikh A, Unsworth DJ, Warrell D, Working Group of the Resuscitation Council (UK)
    Resuscitation. 2008;77(2):157.
  5. Anaphylaxis: diagnosis and management.
    Brown SG, Mullins RJ, Gold MS
    Med J Aust. 2006;185(5):283.
  6. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology.
    Muraro A, Roberts G, Clark A, Eigenmann PA, Halken S, Lack G, Moneret-Vautrin A, Niggemann B, RancéF, EAACI Task Force on Anaphylaxis in Children
    Allergy. 2007;62(8):857.
  7. Fatal posture in anaphylactic shock.
    Pumphrey RS
    J Allergy Clin Immunol. 2003;112(2):451.

7 H1 antihistamines

H1 antihistamines, such as cetirizine or diphenhydramine are effective at reducing itching and urticaria, however, they have shown NO effect on upper or lower airway obstruction, hypotension or shock and do NOT improve outcomes in anaphylaxis. They should NOT be used instead of epinephrine as the primary treatment of anaphylaxis. In addition, these medications have onsets of action of 30 to 40 minutes which is likely too long for the acute interventions needed for anaphylaxis.

H1 antihistamines may be used for symptomatic relief of itching and urticarial reactions which may be present both with and without anaphylaxis.



References:
  1. H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review.
    Sheikh A, Ten Broek V, Brown SG, Simons FE
    Allergy. 2007;62(8):830.
  2. Multicenter study of emergency department visits for food allergies.
    Clark S, Bock SA, Gaeta TJ, Brenner BE, Cydulka RK, Camargo CA, Multicenter Airway Research Collaboration-8 Investigators
    J Allergy Clin Immunol. 2004;113(2):347.
  3. Multicenter study of emergency department visits for insect sting allergies.
    Clark S, Long AA, Gaeta TJ, Camargo CA Jr
    J Allergy Clin Immunol. 2005;116(3):643.
  4. National study of US emergency department visits for acute allergic reactions, 1993 to 2004.
    Gaeta TJ, Clark S, Pelletier AJ, Camargo CA
    Ann Allergy Asthma Immunol. 2007;98(4):360.
  5. Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: a literature review.
    Banerji A, Long AA, Camargo CA Jr
    Allergy Asthma Proc. 2007;28(4):418.
  6. Diagnostic value of the serum-specific IgE ratio ofω-5 gliadin to wheat in adult patients with wheat-induced anaphylaxis.
    Park HJ, Kim JH, Kim JE, Jin HJ, Choi GS, Ye YM, Park HS
    Int Arch Allergy Immunol. 2012;157(2):147.

8 Bronchodilators

Bronchodilators such as albuterol may be used as an adjunctive medication in addition to epinephrine if there are signs of bronchospasm. Bronchodilators should not replace epinephrine in the treatment of anaphylaxis as they do not affect upper airway swelling, mucosal edema or the vascular effects of the disease.



References:
  1. The diagnosis and management of anaphylaxis practice parameter: 2010 update.
    Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, Feldweg AM, Fink JN, Greenberger PA, Golden DB, James JM, Kemp SF, Ledford DK, Lieberman P, Sheffer AL, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D
    J Allergy Clin Immunol. 2010;126(3):477.
  2. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers.
    Soar J, Pumphrey R, Cant A, Clarke S, Corbett A, Dawson P, Ewan P, Foëx B, Gabbott D, Griffiths M, Hall J, Harper N, Jewkes F, Maconochie I, Mitchell S, Nasser S, Nolan J, Rylance G, Sheikh A, Unsworth DJ, Warrell D, Working Group of the Resuscitation Council (UK)
    Resuscitation. 2008;77(2):157.
  3. Anaphylaxis: diagnosis and management.
    Brown SG, Mullins RJ, Gold MS
    Med J Aust. 2006;185(5):283.
  4. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology.
    Muraro A, Roberts G, Clark A, Eigenmann PA, Halken S, Lack G, Moneret-Vautrin A, Niggemann B, RancéF, EAACI Task Force on Anaphylaxis in Children
    Allergy. 2007;62(8):857.

9 Biphasic reactions

1 to 23 percent of all anaphylactic reactions with have a biphasic phase (a uniphasic response, followed by and asymptomatic period (> 1 hr) and then return of symptoms without any further antigen exposure). Although rare, “clinically important events” and fatalities may occur in the second phase. Most studies have shown that the second phase is usually less severe than the initial phase and most commonly involves urticarial.

Biphasic reactions up to 72 hours have been reported although the average time of return of symptoms was 10 hours.

Risk factors for a biphasic reaction include:

  • Severe initial symptoms
  • Delayed administration of epinephrine
  • Slow resolution of initial symptoms
  • History of asthma (contradictory studies)
  • Ingestion of allergens (contradictory studies)

Post-anaphylactic observation periods are controversial and variable between guidelines. Patients with biphasic risk factors should be observed longer for which we suggest a minimum of 12 hours. Guidelines for low risk patients vary between 2 and 6 hours. We suggest a minimum of 2 hours. 



References:
  1. Biphasic anaphylactic reactions.
    Lieberman P
    Ann Allergy Asthma Immunol. 2005;95(3):217.
  2. Biphasic and protracted anaphylaxis.
    Stark BJ, Sullivan TJ
    J Allergy Clin Immunol. 1986;78(1 Pt 1):76.
  3. Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis.
    Grunau BE, Li J, Yi TW, Stenstrom R, Grafstein E, Wiens MO, Schellenberg RR, Scheuermeyer FX
    Ann Emerg Med. 2014;63(6):736.
  4. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients.
    Ellis AK, Day JH
    Ann Allergy Asthma Immunol. 2007;98(1):64.
  5. Multiphasic anaphylaxis: an uncommon event in the emergency department.
    Brady WJ Jr, Luber S, Carter CT, Guertler A, Lindbeck G
    Acad Emerg Med. 1997;4(3):193.
  6. Biphasic anaphylactic reactions in pediatrics.
    Lee JM, Greenes DS
    Pediatrics. 2000;106(4):762.
  7. Not so immediate hypersensitivity--the danger of biphasic anaphylactic reactions.
    Brazil E, MacNamara AF
    J Accid Emerg Med. 1998;15(4):252.
  8. Anaphylaxis presentations to an emergency department in Hong Kong: incidence and predictors of biphasic reactions.
    Smit DV, Cameron PA, Rainer TH
    J Emerg Med. 2005;28(4):381.
  9. Anaphylaxis and biphasic phase in Thailand: 4-year observation.
    Lertnawapan R, Maek-a-nantawat W
    Allergol Int. 2011 Sep;60(3):283-9.
  10. Biphasic systemic anaphylaxis: an inpatient and outpatient study.
    Douglas DM, Sukenick E, Andrade WP, Brown JS
    J Allergy Clin Immunol. 1994;93(6):977.
  11. Anaphylaxis: clinical patterns, mediator release, and severity.
    Brown SG, Stone SF, Fatovich DM, Burrows SA, Holdgate A, Celenza A, Coulson A, Hartnett L, Nagree Y, Cotterell C, Isbister GK
    J Allergy Clin Immunol. 2013 Nov;132(5):1141-1149.e5.
  12. The post-anaphylaxis dilemma: how long is long enough to observe a patient after resolution of symptoms?
    Kemp SF
    Curr Allergy Asthma Rep. 2008;8(1):45.
  13. The diagnosis and management of anaphylaxis: an updated practice parameter.
    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
    J Allergy Clin Immunol. 2005;115(3 Suppl 2):S483.
  14. American Academy of Allergy, Asthma&Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis.
    Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV, American Academy of Allergy, Asthma&Immunology, American College of Allergy, Asthma and Immunology
    J Allergy Clin Immunol. 2007;120(6):1373.

10 Glucagon

Patients with anaphylaxis, who are resistant to epinephrine or taking beta-blockers, may be treated with glucagon. Glucagon’s inotropic and chronotropic effects are not mediated through beta-receptors and therefore may provide cardiovascular support if epinephrine alone is not effective. Glucagon increases the likelihood of vomiting so patients receiving it should be also treated with an anti-emetic and monitored closely, especially if they have a suppressed mental status.

 



References:
  1. Best evidence topic report. Glucagon infusion in refractory anaphylactic shock in patients on beta-blockers.
    Thomas M, Crawford I
    Emerg Med J. 2005;22(4):272.
  2. Use of glucagon in intractable allergic reactions and as an alternative to epinephrine: an interesting case review.
    Compton J.
    J Emerg Nurs. 1997 Feb;23(1):45-7.

11 Post-discharge care

Patients with allergic reactions or anaphylaxis are at greater risk of anaphylaxis in the future. Up to 23 percent of patients with anaphylaxis may have a biphasic reaction. Because of this, home discharge care is vitally important for these patients. We suggest that all patients should receive:

  • An anaphylaxis emergency action plan
  • Counseling regarding use of medic alert tag
  • Counseling regarding allergen identification and avoidance
  • Prescription and counseling on use of an epinephrine auto-injector
  • Follow up with PMD or allergy specialist


References:
  1. Anaphylaxis, killer allergy: long-term management in the community.
    Simons FE
    J Allergy Clin Immunol. 2006;117(2):367.
  2. American Academy of Allergy, Asthma&Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis.
    Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV, American Academy of Allergy, Asthma&Immunology, American College of Allergy, Asthma and Immunology
    J Allergy Clin Immunol. 2007;120(6):1373.
  3. Anaphylaxis in the community: learning from the survivors.
    Simons FE, Clark S, Camargo CA Jr
    J Allergy Clin Immunol. 2009;124(2):301.
  4. SAFE: a multidisciplinary approach to anaphylaxis education in the emergency department.
    Lieberman P, Decker W, Camargo CA Jr, Oconnor R, Oppenheimer J, Simons FE
    Ann Allergy Asthma Immunol. 2007;98(6):519.
  5. Voluntarily reported unintentional injections from epinephrine auto-injectors.
    Simons FE, Edwards ES, Read EJ Jr, Clark S, Liebelt EL
    J Allergy Clin Immunol. 2010;125(2):419.
  6. World Allergy Organization anaphylaxis guidelines: summary.
    Simons FE, Ardusso LR, BilòMB, El-Gamal YM, Ledford DK, Ring J, Sanchez-Borges M, Senna GE, Sheikh A, Thong BY, World Allergy Organization
    J Allergy Clin Immunol. 2011;127(3):587.
  7. The diagnosis and management of anaphylaxis practice parameter: 2010 update.
    Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, Bernstein JA, Burks AW, Feldweg AM, Fink JN, Greenberger PA, Golden DB, James JM, Kemp SF, Ledford DK, Lieberman P, Sheffer AL, Bernstein DI, Blessing-Moore J, Cox L, Khan DA, Lang D, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph C, Schuller DE, Spector SL, Tilles S, Wallace D
    J Allergy Clin Immunol. 2010;126(3):477.

12 H2 antihistamines

There is no evidence (including a systematic review) that H2 antihistamines have any effect on anaphylaxis OR urticaria. They may provide some additional relief of itch along with H1 antihistamines. They do not impact upper or lower airway edema or hypotension and should not replace epinephrine as the primary treatment of anaphylaxis.



References:
  1. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists.
    Lin RY, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, Tenenbaum C, Westfal RE
    Ann Emerg Med. 2000;36(5):462.
  2. H2-antihistamines for the treatment of anaphylaxis with and without shock: a systematic review.
    Nurmatov UB, Rhatigan E, Simons FE, Sheikh A
    Ann Allergy Asthma Immunol. 2014 Feb;112(2):126-31.
  3. Histamine H2-receptor antagonists for urticaria.
    Fedorowicz Z, van Zuuren EJ, Hu N
    Cochrane Database Syst Rev. 2012;3:CD008596.

13 Glucocorticoids

Although commonly used, there is no evidence (including a Cochrane review) that steroids affect the initial signs and symptoms of anaphylaxis OR prevent biphasic reactions. Glucocorticoids onset of action is several hours which is too late to affect the initial symptoms of anaphylaxis. In addition, mast cells are relatively resistant to their pharmacologic effect. A single study of 103 patients showed a trend that those patients falling into the uniphasic reaction had more steroids (55% vs. 35%) and at higher doses (63 mg vs. 31 mg) than biphasic patients. However, this trend was not statistically significant AND other studies have found no evidence that steroids decrease the incidence of biphasic reactions.



References:
  1. Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients.
    Ellis AK, Day JH
    Ann Allergy Asthma Immunol. 2007;98(1):64.
  2. Biphasic and protracted anaphylaxis.
    Stark BJ, Sullivan TJ
    J Allergy Clin Immunol. 1986;78(1 Pt 1):76.
  3. Glucocorticoids for the treatment of anaphylaxis.
    Choo KJ, Simons FE, Sheikh A.
    Cochrane Database Syst Rev. 2012 Apr 18;4:CD007596.