Reviews and feature article
Anaphylaxis: Recent advances in assessment and treatment

https://doi.org/10.1016/j.jaci.2009.08.025Get rights and content

The incidence rate of anaphylaxis is increasing, particularly during the first 2 decades of life. Common triggers include foods, medications, and insect stings. Clinical diagnosis is based on a meticulous history of an exposure or event preceding characteristic symptoms and signs, sometimes but not always supported by a laboratory test such as an elevated serum total tryptase level. Physician-initiated investigation of patients with anaphylaxis whose symptoms and signs are atypical sometimes leads to important insights into previously unrecognized triggers and mechanisms. In idiopathic anaphylaxis, in which no trigger can be confirmed by means of skin testing or measurement of specific IgE, the possibility of mastocytosis or a clonal mast cell disorder must be considered in addition to the possibility of a previously unrecognized trigger. Long-term risk reduction in patients with anaphylaxis focuses on optimal management of relevant comorbidities such as asthma and other respiratory diseases, cardiovascular disease, and mastocytosis or a clonal mast cell disorder; avoidance of the relevant confirmed allergen trigger; and relevant immunomodulation such as medication desensitization, venom immunotherapy, and possibly in the future, immunotherapy with food. Emergency preparedness for recurrence of anaphylaxis in community settings includes having epinephrine (adrenaline) autoinjectors available, knowing when and how to use them, and having a written, personalized anaphylaxis emergency action plan and up-to-date medical identification. Randomized controlled trials of the pharmacologic interventions used in an acute anaphylaxis episode are needed.

Section snippets

Epidemiology

The true rate of occurrence of anaphylaxis from all triggers in the general population is unknown.3, 4 Community-based population estimates are difficult to evaluate because of under-diagnosis and under-reporting, as well as miscoding and the use of a variety of case definitions and measures of occurrence.4, 5, 6 Despite this, it is clear that anaphylaxis is not rare and that the rate of occurrence is increasing, especially in the first 2 decades of life.7, 8, 9 In a retrospective,

Pathogenesis

An understanding of potential triggers, mechanisms, and patient-specific risk factors in anaphylaxis is the key to performing an appropriate risk assessment in someone who has previously experienced an acute anaphylaxis episode (Fig 1).1, 3, 15, 16

Risk assessment: Diagnosis of anaphylaxis

Anaphylaxis is unpredictable and can occur in anyone, anywhere, at any time. It is underrecognized by patients and underdiagnosed by health care professionals.6

Risk assessment: Confirmation of the anaphylaxis trigger

In each patient with a history of anaphylaxis, it is important to identify and confirm the trigger and the effector mechanism, because most long-term preventive measures are trigger-and mechanism-specific.

Long-term risk reduction: Preventive measures

Long-term preventive measures to reduce the risk of fatality in patients with anaphylaxis include optimal management of relevant comorbidities such as asthma, cardiovascular disease, and mastocytosis, and awareness of other concomitant factors as described in the “Patient-specific risk factors” section, as well as trigger avoidance and immunomodulation (Fig 2).1, 3, 15

Long-term risk reduction: Emergency preparedness

Anaphylaxis sometimes recurs despite relevant avoidance measures and immunomodulation. When this happens, it is impossible to predict whether the patient will die within minutes, respond to treatment, or recover spontaneously because of endogenous compensatory mechanisms such as secretion of epinephrine, angiotensin II, and endothelin I.16 Therefore, those at risk, and their caregivers and friends should be prepared to recognize and treat unanticipated recurrences of anaphylaxis in the

Summary

This clinical review has highlighted important recent advances leading to a better understanding of anaphylaxis epidemiology, pathogenesis, risk assessment, and long-term risk reduction in the community. These advances are summarized in the text box “What do we know?” Despite the excellent progress made in the past few years, many crucial questions remain to be answered, as summarized in the text box “What is still needed?”

What do we know?

  1. The incidence rate of anaphylaxis is increasing, especially in young

References (100)

  • W.K. Liew et al.

    Anaphylaxis fatalities and admissions in Australia

    J Allergy Clin Immunol

    (2009)
  • F.E.R. Simons

    Anaphylaxis. 2008 Mini-primer on allergic and immunologic diseases

    J Allergy Clin Immunol

    (2008)
  • F.E.R. Simons et al.

    Risk assessment in anaphylaxis: current and future approaches

    J Allergy Clin Immunol

    (2007)
  • A. Kuehn et al.

    Anaphylaxis provoked by ingestion of marshmallows containing fish gelatin

    J Allergy Clin Immunol

    (2009)
  • L.M. Moore et al.

    Seal and whale meat: two newly recognized food allergies

    Ann Allergy Asthma Immunol

    (2007)
  • A. Cheifetz et al.

    The incidence and management of infusion reactions to infliximab: a large center experience

    Am J Gastroenterol

    (2003)
  • S.L. Limb et al.

    Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma

    J Allergy Clin Immunol

    (2007)
  • M. Rezvani et al.

    Anaphylactic reactions during immunotherapy

    Immunol Allergy Clin North Am

    (2007)
  • Z. Peng et al.

    Immune responses to mosquito saliva in 14 individuals with acute systemic allergic reactions to mosquito bites

    J Allergy Clin Immunol

    (2004)
  • M. Basagana et al.

    Allergy to human seminal fluid: cross-reactivity with dog dander

    J Allergy Clin Immunol

    (2008)
  • S.L. Fernando

    Cold-induced anaphylaxis

    J Pediatr

    (2009)
  • F.D. Finkelman

    Anaphylaxis: lessons from mouse models

    J Allergy Clin Immunol

    (2007)
  • G. Zanoni et al.

    Dextran-specific IgG response in hypersensitivity reactions to measles-mumps-rubella vaccine

    J Allergy Clin Immunol

    (2008)
  • L.B. Schwartz

    Diagnostic value of tryptase in anaphylaxis and mastocytosis

    Immunol Allergy Clin North Am

    (2006)
  • F.E.R. Simons

    Anaphylaxis in infants: can recognition and management be improved?

    J Allergy Clin Immunol

    (2007)
  • M.J. Greenhawt et al.

    Food allergy and food allergy attitudes among college students

    J Allergy Clin Immunol

    (2009)
  • K. Chaudhuri et al.

    Anaphylactic shock in pregnancy: a case study and review of the literature

    Int J Obstet Anesth

    (2008)
  • P. Bonadonna et al.

    Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels

    J Allergy Clin Immunol

    (2009)
  • J. Wang et al.

    Correlation of serum allergy (IgE) tests performed by different assay systems

    J Allergy Clin Immunol

    (2008)
  • B. Pereira et al.

    Prevalence of sensitization to food allergens, reported adverse reaction to foods, food avoidance, and food hypersensitivity among teenagers

    J Allergy Clin Immunol

    (2005)
  • D.B. Golden et al.

    Natural history of Hymenoptera venom sensitivity in adults

    J Allergy Clin Immunol

    (1997)
  • A. Nowak-Wegrzyn et al.

    Work group report: oral food challenge testing

    J Allergy Clin Immunol

    (2009)
  • D.C. de Graaf et al.

    Bee, wasp and ant venomics pave the way for a component-resolved diagnosis of sting allergy

    J Proteonomics

    (2009)
  • I. Cerecedo et al.

    Mapping of the IgE and IgG4 sequential epitopes of milk allergens with a peptide microarray-based immunoassay

    J Allergy Clin Immunol

    (2008)
  • T. Boyano-Martinez et al.

    Accidental allergic reactions in children allergic to cow's milk proteins

    J Allergy Clin Immunol

    (2009)
  • A.W. Burks et al.

    Oral tolerance, food allergy, and immunotherapy: implications for future treatment

    J Allergy Clin Immunol

    (2008)
  • J.M. Skripak et al.

    A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy

    J Allergy Clin Immunol

    (2008)
  • G. Longo et al.

    Specific oral tolerance induction in children with very severe cow's milk-induced reactions

    J Allergy Clin Immunol

    (2008)
  • K.D. Srivastava et al.

    Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-gamma-producing CD8+ T cells

    J Allergy Clin Immunol

    (2009)
  • M.C. Castells et al.

    Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases

    J Allergy Clin Immunol

    (2008)
  • D.B.K. Golden

    Insect sting allergy and venom immunotherapy: a model and a mystery

    J Allergy Clin Immunol

    (2005)
  • P.A. Greenberger

    Idiopathic anaphylaxis

    Immunol Allergy Clin North Am

    (2007)
  • M.C. Carter et al.

    Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis

    J Allergy Clin Immunol

    (2007)
  • F.E.R. Simons

    Anaphylaxis: evidence-based long-term risk reduction in the community

    Immunol Allergy Clin North Am

    (2007)
  • J. Soar et al.

    Emergency treatment of anaphylactic reactions—guidelines for healthcare providers

    Resuscitation

    (2008)
  • F.E.R. Simons

    First-aid treatment of anaphylaxis to food: focus on epinephrine

    J Allergy Clin Immunol

    (2004)
  • P. Lieberman

    Biphasic anaphylactic reactions

    Ann Allergy Asthma Immunol

    (2005)
  • T.T. Song et al.

    Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues

    Ann Allergy Asthma Immunol

    (2005)
  • F.E.R. Simons et al.

    Hazards of unintentional injection of epinephrine from auto-injectors: a systematic review

    Ann Allergy Asthma Immunol

    (2009)
  • F.E.R. Simons et al.

    Anaphylaxis in the community: learning from the survivors

    J Allergy Clin Immunol

    (2009)
  • Cited by (0)

    Series editors: Donald Y.M Leung, MD, PhD, and Dennis K. Ledford, MD

    View full text