The diagnosis and management of anaphylaxis: An updated practice parameter

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These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.

The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing “The diagnosis and management of anaphylaxis: an updated practice parameter.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients.

Section snippets

Contributors

The Joint Task Force has made a concerted effort to acknowledge all contributors to this parameter. If any contributors have been excluded inadvertently, the Task Force will ensure that appropriate recognition of such contributions is made subsequently.

Chief editors

Phillip Lieberman, MD

Departments of Medicine and Pediatrics

University of Tennessee

College of Medicine

Memphis, Tennessee

Stephen F. Kemp, MD

Departments of Medicine and Pediatrics

University of Mississippi Medical Center

Jackson, Mississippi

John Oppenheimer, MD

Department of Internal Medicine

New Jersey Medical School

Pulmonary and Allergy Associates

Morristown, New Jersey

David M. Lang, MD

Allergy/Immunology Section

Division of Medicine

Director, Allergy and Immunology Fellowship Training Program

Cleveland

Workgroup contributors

John Anderson, MD

Aspen Medical Center

Fort Collins, Colorado

David I. Bernstein, MD

Department of Clinical Medicine

Division of Immunology

University of Cincinnati College of Medicine

Cincinnati, Ohio

Jonathan A. Bernstein, MD

University of Cincinnati College of Medicine

Department of Internal Medicine

Division of Immunology/Allergy Section

Cincinnati, Ohio

Jordan N. Fink, MD

Allergy-Immunology

Departments of Pediatrics and Medicine

Medical College of Wisconsin

Milwaukee, Wisconsin

Paul A. Greenberger, MD

Task force reviewers

Joann Blessing-Moore, MD

Department of Immunology

Stanford University Medical Center

Palo Alto, California

David A. Khan, MD

Department of Internal Medicine

University of Texas Southwestern Medical Center

Dallas, Texas

Rufus E. Lee, MD

Private Practice

Dothan, Alabama

Jay M. Portnoy, MD

Section of Allergy, Asthma & Immunology

The Children's Mercy Hospital

Professor of Pediatrics

University of Missouri-Kansas City School of Medicine

Kansas City, Missouri

Diane E. Schuller, MD

Department of Pediatrics

Pennsylvania

Reviewers

Mary C. Tobin, MD, Oak Park, Illinois

Jeffrey A. Wald, MD, Overland Park, Kansas

Dana V. Wallace, MD, Fort Lauderdale, Florida

Stephen Wasserman, MD, La Jolla, California

Category of evidence

  • Ia

    Evidence from meta-analysis of randomized controlled trials

  • Ib

    Evidence from at least one randomized controlled trial

  • IIa

    Evidence from at least on controlled study without randomization

  • IIb

    Evidence from at least one other type of quasiexperimental study

  • III

    Evidence from nonexperimental descriptive studies, such as comparative studies

  • IV

    Evidence from expert committee reports or opinions or clinical experience of respected authorities or both

Strength of recommendation

  • A

    Directly based on category I evidence

  • B

    Directly based on category II

Preface

Anaphylaxis is defined for the purposes of this document as a condition caused by an IgE-mediated reaction. Anaphylactoid reactions are defined as those reactions that produce the same clinical picture as anaphylaxis but are not IgE mediated. Where both IgE-mediated and non–IgE-mediated mechanisms are a possible cause, the term “anaphylactic” has been used to describe the reaction.

Anaphylactic reactions are often life-threatening and almost always unanticipated. Even when there are mild

Annotation 1: Is the history consistent with a previous episode of anaphylaxis?

All individuals who have had a known or suspected anaphylactic episode require a careful and complete review of their clinical history. This history might elicit manifestations, such as urticaria, angioedema, flushing, pruritus, upper airway obstruction, gastrointestinal symptoms, syncope, hypotension, lower airway obstruction, and/or dizziness.

Of primary importance is the nature of the symptoms characterizing the event. Essential questions to be asked are as follows:

  • 1.

    Were there cutaneous

Annotation 1. Anaphylaxis preparedness

It is important to stress that management recommendations are subject to physician discretion and that variations in sequence and performance rely on physician judgment. Additionally, a determination of when a patient should be transferred to an emergency facility depends on the skill, experience, and clinical decision making of the individual physician. Preparedness, prompt recognition, and appropriate and aggressive treatment are integral to parts of successful management of anaphylaxis. A

Evaluation and management of the patient with a history of episodes of anaphylaxis

  • 1.

    The history is the most important tool to determine whether a patient has had anaphylaxis and the cause of the episode. C

  • 2.

    A thorough differential diagnosis should be considered, and other conditions should be ruled out. C

  • 3.

    Laboratory tests can be helpful to confirm a diagnosis of anaphylaxis or rule out other causes. Proper timing of studies (eg, serum tryptase) is essential. B

  • 4.

    In the management of a patient with a previous episode, education is necessary. Emphasis on early treatment, specifically

Summary statements

  • 1.

    The history is the most important tool to determine whether a patient has had anaphylaxis and the cause of the episode. C

  • 2.

    A thorough differential diagnosis should be considered, and other conditions should be ruled out. C

  • 3.

    Laboratory tests can be helpful to confirm a diagnosis of anaphylaxis or rule out other causes. Proper timing of studies (eg, serum tryptase is essential). B

  • 4.

    In the management of a patient with a previous episode, education is necessary. Emphasis on early treatment, specifically

Summary statements

  • 6.

    Medical facilities should have an established protocol to deal with anaphylaxis and the appropriate equipment to treat the episode. In addition, telephone numbers for paramedical rescue squads and ambulance services might be helpful to have on hand. B

  • 7.

    Anaphylaxis is an acute life-threatening systemic reaction with varied mechanisms, clinical presentations, and severity that results from the sudden systemic release of mediators from mast cells and basophils. B

  • 8.

    Anaphylactic (IgE-dependent) and

Summary statements

  • 14.

    Severe food reactions have been reported to involve the gastrointestinal, cutaneous, respiratory, and cardiovascular systems. D

  • 15.

    The greatest number of anaphylactic episodes in children has involved peanuts, tree nuts (ie, walnuts, pecans, and others), fish, shellfish, milk, and eggs (C). The greatest number of anaphylactic episodes in adults is due to shellfish (C). Clinical cross-reactivity with other foods in the same group is unpredictable (B). Additives can also cause anaphylaxis (C).

  • 16.

Summary statements

  • 21.

    Latex (rubber) hypersensitivity is a significant medical problem, and 3 groups are at higher risk of reaction: health care workers, children with spina bifida and genitourinary abnormalities, and workers with occupational exposure to latex. B

  • 22.

    Skin prick tests with latex extracts should be considered for patients who are members of high-risk groups or who have a clinical history of possible latex allergy to identify IgE-mediated sensitivity. Although a standardized commercial skin test reagent

Summary statements

  • 26.

    The incidence of anaphylaxis during anesthesia has been reported to range from 1 in 4000 to 1 in 25,000. Anaphylaxis during anesthesia can present as cardiovascular collapse, airway obstruction, flushing, and/or edema of the skin. C

  • 27.

    It might be difficult to differentiate between immune and nonimmune mast cell–mediated reactions and pharmacologic effects from the variety of medications administered during general anesthesia. B

  • 28.

    Thiopental allergy has been documented with skin tests. B

  • 29.

    Neuromuscular

Summary statements

  • 38.

    Anaphylaxis caused by human seminal fluid has been shown to be due to IgE-mediated sensitization by proteins of varying molecular weight. B

  • 39.

    Localized seminal plasma hypersensitivity has been well described and is likely IgE mediated on the basis of successful response to rapid seminal plasma desensitization. C

  • 40.

    History of atopic disease is the most consistent risk factor. However, anecdotal case reports have been associated with gynecologic surgery, injection of anti-RH immunoglobulin, and the

Summary statements

  • 45.

    Exercise-induced anaphylaxis is a form of physical allergy. Premonitory symptoms can include diffuse warmth, itching, and erythema. Urticaria generally ensues, with progression to confluence and often angioedema. Episodes can progress to include gastrointestinal symptoms, laryngeal edema, and/or vascular collapse. B

  • 46.

    Factors that have been associated with exercise-induced anaphylaxis include medications (eg, aspirin or other nonsteroidal anti-inflammatory drugs) or food ingestion before and after

Summary statements

  • 51.

    The symptoms of idiopathic anaphylaxis are identical to those of episodes related to known causes. C

  • 52.

    Patients with idiopathic anaphylaxis should receive an intensive evaluation, including a meticulous history to rule out a definite cause of the events. C

  • 53.

    There might be a need for specific laboratory studies to exclude systemic disorders, such as systemic mastocytosis. This might include a serum tryptase measurement when the patient is asymptomatic, measurement of the ratio of β-tryptase to total

Summary statements

  • 54.

    There is a small risk of near-fatal and fatal anaphylactic reactions to allergen immunotherapy injections. C

    The rate of fatal anaphylaxis to allergen immunotherapy injections is approximately 1 in 2.5 million injections.66, 189, 190, 191 The rate of systemic reactions to allergen immunotherapy injections is approximately 0.5%.192 Thus although severe systemic reactions to allergen immunotherapy are uncommon, physicians and patients should be prepared for possible systemic reactions after

Summary statements

  • 57.

    In most cases low-molecular-weight medications induce an IgE-mediated reaction only after combining with a carrier protein to produce a complete multivalent antigen. B A few drugs might elicit IgE-mediated reactions without first combining with a carrier protein.

  • 58.

    Penicillin is the most common cause of drug-induced anaphylaxis. C

  • 59.

    Penicillin spontaneously degrades to major and minor antigenic determinants, and skin testing with reagents on the basis of these determinants yields negative results in

Summary statements

  • 70.

    Major risk factors related to anaphylaxis include, but are not limited to, prior history of such reactions, β-adrenergic blocker exposure, or atopic background. Atopic background might be a risk factor for venom- and latex-induced anaphylaxis and possibly anaphylactoid reactions to radiographic contrast material but not for anaphylactic reactions to medications.

  • 71.

    Avoidance measures are successful if future exposure to drugs, foods, additives, or occupational allergens can be prevented. Avoidance

References (232)

  • D.M. Douglas et al.

    Biphasic systemic anaphylaxis: an inpatient and outpatient study

    J Allergy Clin Immunol

    (1994)
  • B.J. Stark et al.

    Biphasic and protracted anaphylaxis

    J Allergy Clin Immunol

    (1986)
  • R. Cydulka et al.

    The use of epinephrine in the treatment of older adult asthmatics

    Ann Emerg Med

    (1988)
  • F.E.R. Simons et al.

    Epinephrine absorption in children with a history of anaphylaxis

    J Allergy Clin Immunol

    (1998)
  • F.E.R. Simons et al.

    Epinephrine absorption in adults: intramuscular versus subcutaneous injection

    J Allergy Clin Immunol

    (2001)
  • J.W. Runge et al.

    Histamine antagonists in the treatment of acute allergic reactions

    Ann Emerg Med

    (1992)
  • R.Y. Lin et al.

    Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists

    Ann Emerg Med

    (2000)
  • R.L. Jacobs et al.

    Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade

    J Allergy Clin Immunol

    (1981)
  • M.C. Laxenaire et al.

    Choc anaphylactoide mortel chez un malade traite par beta bloquants

    Ann Fr Anesth Reanim

    (1984)
  • R.F. Lockey et al.

    Fatalities from immunotherapy and skin testing

    J Allergy Clin Immunol

    (1987)
  • R.H. Shereff et al.

    Effect of beta-adrenergic stimulation and blockade on immediate hypersensitivity skin test reactions

    J Allergy Clin Immunol

    (1973)
  • Y. Matsumura et al.

    Hypersensitivity to histamine and systemic anaphylaxis in mice with pharmacologic beta adrenergic blockade: protection by nucleotides

    J Allergy Clin Immunol

    (1976)
  • C.V. Pollack

    Utility of glucagon in the emergency department

    J Emerg Med

    (1993)
  • M.S. Sherman et al.

    A bronchodilator action of glucagon

    J Allergy Clin Immunol

    (1988)
  • K.H. Lindner et al.

    Randomized comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation

    Lancet

    (1997)
  • I.G. Stiell et al.

    Vasopressin versus epinephrine for inhospital cardiac arrest: a randomized controlled trial

    Lancet

    (2001)
  • S.F. Kemp et al.

    Anaphylaxis: a review of 266 cases

    Arch Intern Med

    (1995)
  • C. Perez et al.

    Anaphylaxis: a descriptive study of 182 patients

    J Allergy Clin Immunol

    (1995)
  • M. Coghlan-Johnston et al.

    Demographic and clinical characteristics of anaphylaxis

    J Allergy Clin Immunol

    (2001)
  • J.M. Lee et al.

    Biphasic anaphylactic reactions in pediatrics

    Pediatrics

    (2000)
  • J.P. Wade et al.

    Exercise-induced anaphylaxis: epidemiological observations

    Prog Clin Biol Restriction

    (1989)
  • C.A. Wiggins

    Characteristics and etiology of 30 patients with anaphylaxis

    Immun Allergy Pract

    (1991)
  • C. Perez et al.

    Anaphylaxis: a descriptive study of 182 patients

    J Allergy Clin Immunol

    (1995)
  • P. Lieberman

    Unique clinical presentations of anaphylaxis

    Immunol Allergy Clin North Am

    (2001)
  • A. Cianferoni et al.

    Clinical features of severe acute anaphylaxis in patients admitted to a university hospital: an 11 year retrospective review

    J Allergy Clin Immunol

    (2001)
  • S.D. Dibs et al.

    Anaphylaxis in children: a 5 year experience

    Pediatrics

    (1997)
  • M.A.T. Alonso et al.

    Idiopathic anaphylaxis: a descriptive study of 81 patients in Spain

    Ann Allergy Asthma Immunol

    (2001)
  • E. Soreide et al.

    Severe anaphylactic reactions outside hospital: etiology, symptoms and treatment

    Acta Anaesthesiol Scand

    (1988)
  • J. Valabhji et al.

    Unexplained loss of consciousness: systemic mastocytosis

    J R Soc Med

    (2000)
  • S.G.A. Brown et al.

    Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation

    Emerg Med J

    (2004)
  • L. LeHane

    Update on histamine fish poisoning

    Med J Aust

    (2000)
  • L.B. Schwartz et al.

    The time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis

    J Clin Invest

    (1989)
  • D. LaRoche et al.

    Biochemical markers of anaphylactoid reactions to drugs. Comparison of plasma histamine and tryptase

    Anesthesiology

    (1991)
  • M. Kaliner et al.

    Increased urine histamine and in contrast media reactions

    Invest Radiol

    (1984)
  • J.W. Yunginger et al.

    Laboratory investigation of deaths due to anaphylaxis

    J Forensic Sci

    (1991)
  • D. Randall et al.

    Elevated postmortem tryptase in the absence of anaphylaxis

    J Forensic Sci

    (1995)
  • E. Edston et al.

    Increased mast cell tryptase in sudden infant death syndrome: anaphylaxis, hypoxia, or artifact?

    Clin Exp Allergy

    (1999)
  • Project Team of the Resuscitation Council (UK)

    Emergency medical treatment of anaphylactic reactions

    J Accid Emerg Med

    (1999)
  • J.P. Wade et al.

    Exercise-induced anaphylaxis: epidemiologic observations

    Proc Clin Biol Res

    (1989)
  • E. Brazil et al.

    Not so immediate hypersensitivity—the danger of biphasic allergic reactions

    J Accid Emerg Med

    (1998)
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    Disclosure of potential conflict of interest: P. Lieberman—none disclosed. S. F. Kemp has consultant arrangements with MedPointe Pharmaceuticals. J. Oppenheimer—none disclosed. D. M. Lang—none disclosed. I. L. Bernstein—none disclosed. R. A. Nicklas—none disclosed. J. A. Anderson—none disclosed. D. I. Bernstein—none disclosed. J. Bernstein is on the Speakers' Bureau for Merck, GlaxoSmithKline, AstraZeneca, Aventis, Medpointe, Pfizer, Schering-Plough, and IVAX. J. N. Fink—none disclosed. P. A. Greenberger—none disclosed. D. K. Ledford—none disclosed. J. Li—none disclosed. A. L. Sheffer—none disclosed. R. Solensky—none disclosed. B. L. Wolf—none disclosed. J. Blessing-Moore—none disclosed. D. A. Khan has consultant arrangements with Pfizer; receives grants/research support from AstraZeneca; and is on the Speakers' Bureau for Pfizer, Merck, Aventis, and GlaxoSmithKline. R. E. Lee—none disclosed. J. M. Portnoy—none disclosed. D. E. Schuller is on the Speakers' Bureau for Boehringer-Ingelheim. S.L. Spector has had consultant arrangements with, has received grants/research support from, and has been on the Speakers' Bureau for Abbott, Allen & Hanburys, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Fisons, Forest, ICN, Key, Eli-Lilly, 3M, Miles, Muro, Pfizer, Purdue Frederick, Schering-Plough, Wallace, and Witby. S. A. Tilles—none disclosed.

    Reprint requests: Joint Council of Allergy, Asthma & Immunology, 50 N Brockway St, #3-3, Palatine, IL 60067.

    This parameter was edited by Dr Nicklas in his private capacity and not in his capacity as a medical officer with the Food and Drug Administration. No official support or endorsement by the Food and Drug Administration is intended or should be inferred.

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