Symposium on the Definition and Management of Anaphylaxis: Summary report

Abstract

The phenomenon of anaphylaxis was first described in the scientific literature about 100 years ago by Portier and Richet,1Portier P. Richet C. De l'action anaphylactique de certains venins.C R Soc Biol (Paris). 1902; 54: 170-172Google Scholar who reported that their attempts to immunize dogs against the sting of jellyfish with Actinia extract instead brought about an acute anaphylactic episode.1Portier P. Richet C. De l'action anaphylactique de certains venins.C R Soc Biol (Paris). 1902; 54: 170-172Google Scholar, 2Dworetzky M. Cohen S.G. Portier, Richet, and the discovery of anaphylaxis: a centennial.J Allergy Clin Immunol. 2002; 110: 331-336PubMed Google Scholar In the extreme or classic form, anaphylaxis typically involves the cutaneous, respiratory, cardiovascular, and gastrointestinal systems, target organs all heavily populated with mast cells. Although medical practitioners can readily recognize such typical forms of anaphylaxis, its presentation is often more enigmatic, with variable target organ involvement and expression of symptoms. A perusal of various textbooks and reviews on the topic indicates that there is no consensus on exactly how to define anaphylaxis, and consequently, there is considerable disagreement about its prevalence, diagnosis, and management. In April 2004, the National Institute of Allergy and Infectious Diseases (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN) cosponsored a multidisciplinary Symposium on the Definition and Management of Anaphylaxis to bring together experts from various disciplines that deal with anaphylaxis. The goal was to review current knowledge and to discuss a definition, treatment strategies, and research objectives. This 2-day meeting brought together experts and representatives of 12 other professional, governmental, and lay organizations. Organizations represented at the NIAID/FAAN Symposium included the American Academy of Allergy, Asthma and Immunology; the American Academy of Family Physicians; the American Academy of Pediatrics; the American College of Allergy, Asthma and Immunology; the American College of Emergency Physicians; the American Society of Anesthesiologists; the Centers for Disease Control and Prevention; the Food Allergy Initiative; the International Life Sciences Institute; the National Association of EMS Physicians; the Society for Academic Emergency Medicine; and the US Food and Drug Administration (FDA). The meeting provided an opportunity for attendees to exchange information, gain a better perspective of how anaphylaxis is recognized and treated, find commonalities between the various specialities' approaches, and identify future research needs. The information presented in this article serves as a basis for future development of a clinical definition of anaphylaxis and a management strategy, and for expansion of a research agenda. In 1998, a Joint Task Force on Practice Parameters3Joint Task Force of Practice Parameters The diagnosis and management of anaphylaxis.J Allergy Clin Immunol. 1998; 101: S465-S528PubMed Google Scholar defined anaphylaxis as an “immediate systemic reaction caused by rapid, IgE-mediated immune release of potent mediators from tissue mast cells and peripheral basophils.” The most common etiologies of anaphylactic reactions include allergic responses to food, medications, Hymenoptera stings, and latex. Mechanistically, anaphylactic reactions are distinguished from anaphylactoid reactions, which “mimic signs and symptoms of anaphylaxis, but are caused by non-IgE-mediated release of potent mediators from mast cells and basophils.” Although they provide a mechanistic concept of anaphylaxis, these definitions are of marginal utility to the physician, emergency personnel, and other health care personnel faced with the diagnosis and treatment of a patient presenting with any of a variable constellation of signs and symptoms of this disorder. One of the major challenges in the study of anaphylaxis is the lack of a widely accepted standard working definition.4Brown A.F. McKinnon D. Chu K. Emergency department anaphylaxis: a review of 142 patients in a single year.J Allergy Clin Immunol. 2001; 108: 861-866Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 5Brown A.F. Clinical features and severity grading of anaphylaxis.J Allergy Clin Immunol. 2004; 114: 371-376Abstract Full Text Full Text PDF PubMed Scopus (644) Google Scholar, 6Bohlke K. Davis R.L. DeStefano F. Marcy S.M. Braun M.M. Thospson R.S. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization.J Allergy Clin Immunol. 2004; 113: 536-542Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar In general, published studies use definitions that incorporate various signs and symptoms of anaphylaxis and specific intervals between allergen exposure and the clinical reaction, but specific elements of the definitions vary.6Bohlke K. Davis R.L. DeStefano F. Marcy S.M. Braun M.M. Thospson R.S. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization.J Allergy Clin Immunol. 2004; 113: 536-542Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 7Mueller H.L. Further experiences with severe allergic reactions to insect stings.N Engl J Med. 1959; 261: 374-377Crossref PubMed Scopus (53) Google Scholar, 8Klein J.S. Yocum M.W. Underreporting of anaphylaxis in a community emergency room.J Allergy Clin Immunol. 1995; 95: 637-638Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 9Kemp S.F. Lockey R.F. Wolf B.L. Lieberman P. Anaphylaxis: a review of 266 cases.Arch Intern Med. 1995; 155: 1749-1754Crossref PubMed Scopus (264) Google Scholar, 10Golden D.B. Kwiterovich K.A. Kagey-Sabotka A. Lichtenstein L.M. Discontinuing venom immunotherapy: extended observations.J Allergy Clin Immunol. 1998; 101: 298-305Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 11Novembre E. Cianferoni A. Bernardini R. Mugnaini L. Caffarelli C. Cavagni G. et al.Anaphylaxis in children: clinical and allergologic features.Pediatrics. 1998; 101: E8Crossref PubMed Scopus (223) Google Scholar, 12Yocum M.W. Butterfield J.H. Klein J.S. Volcheck G.W. Schroeder D.R. Silverstein M.D. Epidemiology of anaphylaxis in Olmsted County: a population-based study.J Allergy Clin Immunol. 1999; 104: 452-456Abstract Full Text Full Text PDF PubMed Scopus (419) Google Scholar One of the major consequences of this lack of standard definition is the failure to diagnose anaphylaxis consistently, as pointed out in several studies.6Bohlke K. Davis R.L. DeStefano F. Marcy S.M. Braun M.M. Thospson R.S. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization.J Allergy Clin Immunol. 2004; 113: 536-542Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 8Klein J.S. Yocum M.W. Underreporting of anaphylaxis in a community emergency room.J Allergy Clin Immunol. 1995; 95: 637-638Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, 13Sorensen H. Nielsen B. Nielsen J. Anaphylactic shock occurring outside hospitals.Allergy. 1989; 44: 288-290Crossref PubMed Scopus (80) Google Scholar In a review of 19,122 emergency department (ED) visits,8Klein J.S. Yocum M.W. Underreporting of anaphylaxis in a community emergency room.J Allergy Clin Immunol. 1995; 95: 637-638Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar 17 cases of anaphylaxis were identified, but only 4 had been appropriately diagnosed and coded. This lack of a consistent definition contributes to the wide variation in the management of anaphylaxis seen in North American EDs.14Clark S. Bock S.A. Gaeta T.J. Brenner B.E. Cydulka R.K. Camargo C.A. Multicenter study of emergency department visits for food allergies.J Allergy Clin Immunol. 2004; 113: 347-352Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar Study of the epidemiology of anaphylaxis has been hampered by lack of an agreed-on definition and a lack of required reporting of either fatal or serious events. A failure to agree on how severe a reaction must be to code it anaphylaxis as opposed to an allergic reaction and to appreciate the variable presentation of anaphylaxis contributes to the problem. Very few population-based studies have been attempted, so the actual incidence of anaphylaxis remains uncertain. Estimates of the incidence range from 10 to 20/100,000 population per year.6Bohlke K. Davis R.L. DeStefano F. Marcy S.M. Braun M.M. Thospson R.S. Epidemiology of anaphylaxis among children and adolescents enrolled in a health maintenance organization.J Allergy Clin Immunol. 2004; 113: 536-542Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 12Yocum M.W. Butterfield J.H. Klein J.S. Volcheck G.W. Schroeder D.R. Silverstein M.D. Epidemiology of anaphylaxis in Olmsted County: a population-based study.J Allergy Clin Immunol. 1999; 104: 452-456Abstract Full Text Full Text PDF PubMed Scopus (419) Google Scholar, 15Mullins R.J. Anaphylaxis: risk factors for recurrence.Clin Exp Allergy. 2003; 33: 1033-1040Crossref PubMed Scopus (200) Google Scholar In 2003, the new codes of the International Classification of Diseases, Tenth Revision, were put in place to describe fatal anaphylactic reactions, such as “anaphylactic shock due to adverse food reaction” (T78.0) and “anaphylactic shock, unspecified” (T78.2). However, data presented at the symposium indicated that these codes are underused. Until there are universally accepted diagnostic criteria, standardized coding, and reporting of anaphylaxis, the true incidence and lifetime prevalence of anaphylaxis will remain unknown. Aggregation of FcεRI by allergen-driven cross-linking of receptor-bound IgE activates mast cells and basophils to release mediators that induce the pathophysiologic features of the anaphylactic response.16Galli S.J. Kalesnikoff J. Grimbaldeston M.A. Piliponsky A.M. Williams C.M.M. Tsai M. Mast cells as “tunable” effector and immunoregulatory cells: recent advances.Ann Rev Immunol. 2005; 23: 749-786Crossref PubMed Scopus (1052) Google Scholar Initial sensitization occurs through a highly coordinated series of steps involving a variety of cell types and mediators,17Geha R.S. Jabara H.H. Brodeur S.R. The regulation of immunoglobulin E class-switch recombination.Nat Rev Immunol. 2003; 3: 721-732Crossref PubMed Scopus (337) Google Scholar which is affected by environmental exposure and complex genetic factors. Consequently, even identical twins raised together may lack complete clinical concordance (eg, peanut allergy: monozygotic twins, 64%, compared with dizygotic twins, 7%),18Sicherer S.H. Furlong T.J. Maes H.H. Desnick R.J. Sampson H.A. Gelb B.D. Genetics of peanut allergy: a twin study.J Allergy Clin Immunol. 2000; 106: 53-56Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar thereby highlighting the inaccuracy of making genetic predictions for any one individual, but recognizing the significant genetic component to allergic disease. An important immunologic feature of allergy is the fact that not all sensitized subjects exhibit clinical reactivity. Although the quantity of circulating IgE antibodies to both food and airborne allergens appears to correlate directly with the probability of clinical reactivity,19Sampson H. Ho D. Relationship between food-specific IgE concentration and the risk of positive food challenges in children and adolescents.J Allergy Clin Immunol. 1997; 100: 444-451Abstract Full Text Full Text PDF PubMed Scopus (997) Google Scholar, 20Pastorello E.A. Incorvaia C. Ortolani C. Bonini S. Canonica G.W. Romagnani S. et al.Studies on the relationship between the level of specific IgE antibodies and the clinical expression of allergy: definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens.J Allergy Clin Immunol. 1995; 96: 580-587Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 21Wood R.A. Phipatanakul W. Hamilton R.G. Eggleston P.A. A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy.J Allergy Clin Immunol. 1999; 103: 773-779Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar the exact series of events that occur between contact with an allergen by a sensitized individual, and sufficient activation of mast cells, basophils, and possibly other cells to induce an anaphylactic reaction, remains to be elucidated. When mast cells/basophils are activated, several well-characterized mediators are released (eg, histamine and tryptase). Unfortunately, tryptase is not found to be elevated consistently in the blood of patients presenting with anaphylaxis,22Lin R.Y. Schwartz L.B. Curry A. Pesola G.R. Knight R.J. Lee H.S. et al.Histamine and tryptase levels in patients with acute allergic reactions: an emergency department-based study.J Allergy Clin Immunol. 2000; 106: 65-71Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar especially in food allergy,23Sampson H.A. Mendelson L.M. Rosen J.P. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.N Engl J Med. 1992; 327: 380-384Crossref PubMed Scopus (1477) Google Scholar and histamine is elevated only briefly at the outset of the reaction and is unstable to routine handling. Therefore, additional biomarkers need to be identified that are both present during most or all anaphylactic reactions and easily and rapidly measured. Allergic reactions begin when an allergen crosses an epithelial and/or endothelial barrier and then interacts with cell-bound IgE antibodies. The integrity of natural barriers such as the skin or the gastrointestinal tract must be breached, and these allergens must then gain access to the reactive, sensitized cells in tissues (mast cells) or blood (basophils). The release of cellular mediators then leads to end-organ responses in the skin, respiratory tract, cardiovascular system, and/or gastrointestinal tract and possibly the nervous system (Table I). The onset of severe symptoms is dependent on the causative factor. In one series, the median time to cardiac or respiratory arrest was 30 minutes for food, 15 minutes for insect venom, and 5 minutes for medications or contrast reagents.24Pumphrey R.S. Lessons for management of anaphylaxis from a study of fatal reactions.Clin Exp Allergy. 2000; 30: 1144-1150Crossref PubMed Scopus (882) Google Scholar Anaphylactic reactions are not necessarily uniphasic; additional patterns of reactions include delayed onset, protracted or persistent reactions, and biphasic reactions wherein the initial reaction is followed by a relatively symptom-free period and then the symptoms recur, often in severe form and more refractory to therapy.23Sampson H.A. Mendelson L.M. Rosen J.P. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.N Engl J Med. 1992; 327: 380-384Crossref PubMed Scopus (1477) Google Scholar, 25Starks B.J. Sullivan T.J. Biphasic and protracted anaphylaxis.J Allergy Clin Immunol. 1986; 78: 76-83Abstract Full Text PDF PubMed Scopus (311) Google Scholar The exact cells and mediators involved in each of these patterns have not been completely defined. Exercise, certain medications (eg, nonsteroidal anti-inflammatory drugs), anesthesia, and alcohol may affect the severity of the response to allergen. Furthermore, fatal reactions are more likely to occur in individuals with asthma,23Sampson H.A. Mendelson L.M. Rosen J.P. Fatal and near-fatal anaphylactic reactions to food in children and adolescents.N Engl J Med. 1992; 327: 380-384Crossref PubMed Scopus (1477) Google Scholar, 26Settipane G. Chafee R. Klein D.E. Boud G. Sturam J. Freye H. Anaphylactic reactions to Hymenoptera stings in asthmatic patients.Clin Allergy. 1980; 10: 659-665Crossref PubMed Scopus (22) Google Scholar, 27Bock S.A. Munoz-Furlong A. Sampson H.A. Fatalities due to anaphylactic reactions to foods.J Allergy Clin Immunol. 2001; 107: 191-193Abstract Full Text PDF PubMed Scopus (1354) Google Scholar possibly more so when the asthma is poorly controlled. An important physiologic consequence of anaphylaxis is the marked hypovolemia that may occur and the resulting empty ventricle syndrome in patients who remain in an upright position.28Pumphrey R.S.H. Fatal posture in anaphylactic shock.J Allergy Clin Immunol. 2003; 112: 451-452Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar A better understanding of the molecular interactions in the airway of individuals with asthma and of the cardiovascular physiology in anaphylactic reactions would aid in the treatment of subjects experiencing these events.Table IClinical signs and symptoms of anaphylaxisCutaneous/subcutaneous/mucosal tissue Flushing, pruritus, hives (urticaria), angioedema, morbilliform rash, pilor erection Pruritus of lips, tongue, and palate; edema of lips, tongue, and uvula Periorbital pruritus, erythema and edema, conjunctival erythema, tearingRespiratory Laryngeal: pruritus and tightness in the throat, dysphagia, dysphonia and hoarseness, dry staccato cough, stridor, sensation of pruritus in the external auditory canals Lung: shortness of breath, dyspnea, chest tightness, deep cough and wheezing/bronchospasm (decreased peak expiratory flow) Nose: pruritus, congestion, rhinorrhea, sneezingCardiovascular Hypotension Feeling of faintness (near-syncope), syncope, altered mental status Chest pain, dysrhythmiaGastrointestinal Nausea, crampy abdominal pain, vomiting (stringy mucus), diarrheaOther Uterine contractions in women, and aura of doom Open table in a new tab Although the immunobiology and pathophysiology of anaphylaxis are basically the same regardless of the provoking factor, different allergens lead to subtle differences in the response. For the correct diagnosis of drug-induced anaphylaxis, accurate historical information is needed, such as when the inciting agent was given, the interval to reaction, medications the patient had received previously (to determine previous sensitization), and the patient's response to therapy. Objective data such as records from the ED or referring physician may help in making the correct diagnosis. If drug immunogens are known (eg, penicillin or large-molecular-weight proteins such as insulin), both in vivo and in vitro tests may be useful in identifying relevant allergens. Unfortunately, validated tests for IgE-mediated reactions are unavailable for most drugs and biologics. The identification of relevant immunogenic determinants and the development of valid diagnostic agents are urgently needed. Patients who have had drug-induced anaphylactic reactions should be instructed to discuss their reactions with their doctor, and a causative agent/trigger should be identified by skin testing when possible.29Gruchalla R.S. Drug allergy.J Allergy Clin Immunol. 2003; 111: S548-S559Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar Likewise, physicians should take a careful history of patients to evaluate the likelihood of potential drug-induced anaphylaxis before prescribing or administering medications. Anaphylaxis to anesthesia is a rare, serious adverse reaction. The incidence of anesthetic-induced anaphylaxis varies between 1:3500 and 1:20,000, and the mortality rate is reported to be approximately 4%, with an additional 2% surviving with severe brain damage.30Mertes P.M. Laxenaire M.C. Alla F. Groupe d'Etudes des Reactions Anaphylactoides Peranesthesiques. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000.Anesthesiology. 2003; 99: 536-545Crossref PubMed Scopus (473) Google Scholar, 31Hepner D.L. Castells M.C. Anaphylaxis during the perioperative period.Anesth Analg. 2003; 97: 1381-1395Crossref PubMed Scopus (310) Google Scholar, 32Moss J. Allergic to anesthetics.Anesthesiology. 2003; 99: 521-523Crossref PubMed Scopus (20) Google Scholar The early signs are often unrecognized, and cardiovascular collapse is often the sole presentation, occurring in about 50% of cases. Bronchospasm and hypotension also may be the sole presenting features, making the diagnosis quite difficult, because these clinical conditions are more common under anesthesia and may have many different causes. In addition, the diagnosis may be missed altogether, resulting in serious implications for future anesthetics. Neuromuscular blocking drugs have been reported as the most common trigger.31Hepner D.L. Castells M.C. Anaphylaxis during the perioperative period.Anesth Analg. 2003; 97: 1381-1395Crossref PubMed Scopus (310) Google Scholar, 33Mertes P. Laxenaire M.C. Allergic reactions occurring during anaesthesia.Eur J Anaesthesiol. 2002; 19: 240-262PubMed Google Scholar, 34Fisher M. Anaphylaxis to anaesthetic drugs.in: Anaphylaxis: Novartis Foundation Symposium 257. John Wiley & Sons, Ltd, London2004: 193-206Crossref Google Scholar Some reactions are caused by the direct activation of mast cells, whereas others appear to be IgE-mediated. Data regarding the utility of skin testing are controversial because of the possibility of false-positive results.35Levy J.H. Gottage M. Szlam F. Zaffer R. McCall C. Weal and flare responses to intradermal rocuronium and cisatracurium in humans.Br J Anaesth. 2000; 85: 844-849Crossref PubMed Scopus (81) Google Scholar Prevention of these reactions will require further studies as well as guidelines on the utility of skin testing. Onset of anaphylaxis to insect stings is generally rapid, and fatal insect stings tend to be more rapid in onset, with 96% of fatal reactions beginning within 30 minutes of the sting.36Barnard J. Studies of 400 Hymentoptera sting deaths in the United States.J Allergy Clin Immunol. 1973; 52: 259-264Abstract Full Text PDF PubMed Scopus (254) Google Scholar Consequently there is a need to emphasize rapid treatment with epinephrine (often self-administered) for these reactions in susceptible subjects rather than taking a wait-and-see approach, and to strongly encourage follow-up evaluation and expert counseling. This is the only form of anaphylaxis for which immunotherapy is currently available to prevent reactions to subsequent stings.37Golden D.B. Kagey-Sobotka A. Norman A.P. Hamilton R.G. Lichtenstein L.M. Outcomes of allergy to insect stings in children, with and without venom immunotherapy.N Engl J Med. 2004; 351: 668-674Crossref PubMed Scopus (225) Google Scholar It is important to recognize that cutaneous symptoms may be absent in as many as 20% of cases of anaphylaxis,38Lockey R.F. Turkeltaub P. Baird-Warren I.A. Olive C.A. Olive E.S. Peppe B.C. et al.The Hymenoptera venom study I, 1979-1982: demographics and history-sting data.J Allergy Clin Immunol. 1998; 82: 370-381Abstract Full Text PDF Scopus (107) Google Scholar with urticaria absent in more than 30% of cases. Currently, most fatal reactions cannot be prevented because they occur on the first sting reaction, and diagnostic skin tests are not useful for screening because they are positive in 25% of adults.39Golden D.B. Marsh D.G. Kagey-Sabotka A. Freidhoff L.R. Szklo M. Valentine M. et al.Epidemiology of insect venom sensitivity.JAMA. 1989; 262: 240-244Crossref PubMed Scopus (243) Google Scholar The lack of an anaphylactic response to a sting in individuals who are highly sensitized or even recently reactive requires future investigation to reveal the mechanism that prevents such individuals from reacting. Food-induced anaphylaxis is the most common single cause of anaphylaxis treated in EDs in the United States, especially in the younger population.40Sampson H.A. Anaphylaxis and emergency treatment.Pediatrics. 2004; 111: 1601-1608Google Scholar The majority of reactions are not fatal. There are no known laboratory parameters that predict the severity of food-induced reactions, although there may be a correlation between the number of IgE-binding sites (epitopes) recognized by a patient's IgE antibodies on a food protein (epitope diversity) and the likelihood of a severe reaction.41Shreffler W.G. Beyer K. Burks A.W. Sampson H.A. Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes.J Allergy Clin Immunol. 2004; 113: 776-782Abstract Full Text Full Text PDF PubMed Scopus (298) Google Scholar However, currently there is no way to identify who will have a severe reaction or to predict when it will occur. In general, reactions worsen with the development of asthma and as children get older. Early use of epinephrine is important and can prevent progression to severe reactions.42Gold M.S. Sainsbury R. First aid anaphylaxis management in children who were prescribed an epinephrine autoinjector device (EpiPen).J Allergy Clin Immunol. 2000; 106: 171-176Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Latex is the second leading cause of anaphylaxis during the perioperative period. Although the incidence of latex anaphylaxis has increased over the period of the last 20 years, it now appears to have reached a plateau largely because of increased awareness of the problem, a decreased use of latex products, and new labeling warnings about the presence of latex in medical products enforced by the FDA.43Hepner D.L. Castells M.C. Latex allergy: an update.Anesth Analg. 2003; 96: 1219-1229Crossref PubMed Scopus (97) Google Scholar A surveillance system is needed to track cases of latex-induced anaphylaxis and latex allergy. To determine how many people are affected with latex allergy, an FDA-approved reagent for skin testing is essential to reduce the wide variation in reported sensitization. Latex anaphylaxis is largely preventable by instituting latex-safe protocols, which include substituting latex-free gloves when latex is not essential, and substituting low-powder, low-protein gloves when latex is essential.44Liss T.M. Tarlo S.M. Natural rubber latex-related occupational asthma: association with interventions and glove changes over time.Am J Ind Med. 2001; 40: 347-353Crossref PubMed Scopus (69) Google Scholar Exercise can lead to typical anaphylaxis.45Castells M. Horan R. Sheffer A. Exercise-induced anaphylaxis (EIA).Clin Rev Allergy Immunol. 1999; 17: 413-424Crossref PubMed Scopus (51) Google Scholar A variety of activities can lead to exercise-induced anaphylaxis (EIA), including jogging, walking, tennis, and dancing. EIA is unpredictable and often difficult to diagnose. It has been suggested that as many as 50% of cases of EIA may be associated with the ingestion of a food, ie, food-associated EIA.46Horan R. Sheffer A. Food-dependent exercise-induced anaphylaxis.Immunol Allergy Clin North Am. 1991; 11: 757-766Google Scholar In such cases, delaying exercise for about 5 hours after eating will prevent reactions. The pathogenesis and true incidence of EIA remain unknown. The diagnosis of idiopathic anaphylaxis is a diagnosis of exclusion.47Ring J. Darsow U. Idiopathic anaphylaxis.Curr Allergy Asthma Rep. 2002; 2: 40-45Crossref PubMed Scopus (38) Google Scholar The exact incidence of idiopathic anaphylaxis is unknown, but several studies estimate that nearly 20% of cases of anaphylaxis are idiopathic. There are no clinically distinguishing features (although 33% of cases are nocturnal), and it may be fatal. Management often consists of prophylactic corticosteroid and antihistamine therapy.48Lencher K. Grammar L.C. A current review of idiopathic anaphylaxis.Curr Opin Allergy Clin Immunol. 2003; 3: 305-311Crossref PubMed Scopus (35) Google Scholar As demonstrated by the diverse organizations that participated in the NIAID/FAAN symposium, anaphylaxis is seen by different types of clinicians in a variety of clinical settings. This presents a formidable challenge to the creation of a disease definition that will fit all settings. Regardless of setting, however, epinephrine is the medication of choice for treating anaphylaxis. Anaphylaxis is a rare condition in the prehospital setting, accounting for about 0.5% of ambulance runs, and about 10% of these cases receive epinephrine.49Kane K.E. Cone D.C. Anaphylaxis in the prehospital setting.J Emerg Med. 2004; 27: 371-377Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar There are significant variations in emergency medical services protocols regarding the definition and treatment of anaphylaxis.49Kane K.E. Cone D.C. Anaphylaxis in the prehospital setting.J Emerg Med. 2004; 27: 371-377Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar The inconsistencies in case definitions, documentation, and diagnostic and treatment protocols limit the utility of the data in this area. Currently it is within the scope of practice for paramedics to use epinephrine to treat anaphylaxis. There are insufficient data to support or refute the benefits and/or safety of basic emergency medical services responders using self-injectable epinephrine for the treatment of anaphylaxis. More research is needed to determine whether the use of self-injectable epinephrine by Basic Life Support personnel for treating anaphylaxis is warranted. Anaphylaxis is a relatively infrequent diagnosis in the ED compared with allergic reactions, eg, 1 in 439 encounters in one series.50Brown A.F. McKinnon D. Chu K. Emergency department anaphylaxis: a review of 142 patients in a single year.J Allergy Clin Immunol. 2001; 108: 861-866Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar Anaphylaxis is typically defined as an allergic reaction with multiorgan involvement, respiratory insufficiency, and hemodynamic compromise. The ED treatment guidelines for anaphylaxis are similar to those recommended in the allergy and immunology literature, which includes ensuring a patent airway, establishing intraveno