Stinging insect hypersensitivity: A practice parameter update 2011

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology.The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Stinging insect hypersensitivity: a practice parameter update II.” 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 the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. 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. These parameters are not designed for use by pharmaceutical companies in drug promotion. The Joint Task Force understands that the cost of diagnostic tests and therapeutic agents is an important concern that may appropriately influence the work-up and treatment chosen for a given patient. The Joint Task Force recognizes that the emphasis of our primary recommendations regarding a medication may vary, for example, depending on third party payer issues and product patent expiration dates. However, since a given test or agent's cost is so widely variable, and there is a paucity of pharmacoeconomic data, the Joint Task Force generally does not consider cost when formulating Practice Parameter recommendations. In extraordinary circumstances, when the cost benefit of an intervention is prohibitive as supported by pharmacoeconomic data, commentary may be provided. These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Stinging insect hypersensitivity: a practice parameter update II.” 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 the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. 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. These parameters are not designed for use by pharmaceutical companies in drug promotion. The Joint Task Force understands that the cost of diagnostic tests and therapeutic agents is an important concern that may appropriately influence the work-up and treatment chosen for a given patient. The Joint Task Force recognizes that the emphasis of our primary recommendations regarding a medication may vary, for example, depending on third party payer issues and product patent expiration dates. However, since a given test or agent's cost is so widely variable, and there is a paucity of pharmacoeconomic data, the Joint Task Force generally does not consider cost when formulating Practice Parameter recommendations. In extraordinary circumstances, when the cost benefit of an intervention is prohibitive as supported by pharmacoeconomic data, commentary may be provided. To read the Practice Parameter in its entirety, please download the online version of this article from www.jacionline.org. The full document follows the Executive Summary. Please note that all references cited in the Executive Summary can be found in the online document. Most insect stings produce a transient local reaction that can last up to several days and generally resolves without treatment. Marked local swelling extending from the sting site is usually an IgE-mediated late-phase reaction.1Graft D.F. Schuberth K.C. Kagey-Sobotka A. Kwiterovich K.A. Niv Y. Lichtenstein L.M. et al.A Prospective study of the natural history of large local reactions following Hymenoptera stings in children.J Pediatr. 1984; 104 (IIb): 664-668Abstract Full Text PDF PubMed Google Scholar, 2Green A. Reisman R. Arbesman C. Clinical and immunologic studies of patients with large local reactions following insect stings.J Allergy Clin Immunol. 1980; 66 (IIb): 186-189Abstract Full Text PDF PubMed Google Scholar, 3Mauriello P.M. Barde S.H. Georgitis J.W. Reisman R.E. Natural history of large local reactions from stinging insects.J Allergy Clin Immunol. 1984; 74 (IIb): 494-498Abstract Full Text PDF PubMed Google Scholar, 4Nguyen S.A. Napoli D.C. Natural history of large local and generalized cutaneous reactions to imported fire ant stings in children.Ann Allergy Asthma Immunol. 2005; 94 (III): 387-390Abstract Full Text PDF PubMed Google Scholar The risk of a systemic reaction in patients who experience large local reactions is no more than 5% to 10%.1Graft D.F. Schuberth K.C. Kagey-Sobotka A. Kwiterovich K.A. Niv Y. Lichtenstein L.M. et al.A Prospective study of the natural history of large local reactions following Hymenoptera stings in children.J Pediatr. 1984; 104 (IIb): 664-668Abstract Full Text PDF PubMed Google Scholar, 3Mauriello P.M. Barde S.H. Georgitis J.W. Reisman R.E. Natural history of large local reactions from stinging insects.J Allergy Clin Immunol. 1984; 74 (IIb): 494-498Abstract Full Text PDF PubMed Google Scholar, 4Nguyen S.A. Napoli D.C. Natural history of large local and generalized cutaneous reactions to imported fire ant stings in children.Ann Allergy Asthma Immunol. 2005; 94 (III): 387-390Abstract Full Text PDF PubMed Google Scholar, 5Golden D.B.K. Kelly D. Hamilton R.G. Craig T.J. Venom immunotherapy reduces large local reactions to insect stings.J Allergy Clin Immunol. 2009; 123 (IIa): 1371-1375Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar More serious anaphylactic sting reactions account for at least 40 deaths each year in the United States.6Graft D.F. Insect sting allergy.Med Clin North Am. 2006; 90 (IV): 211-232Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar It is estimated that potentially life-threatening systemic reactions to insect stings occur in 0.4% to 0.8% of children and 3% of adults.7Bilo B.M. Bonifazi F. Epidemiology of insect-venom anaphylaxis.Curr Opin Allergy Clin Immunol. 2008; 8 (IV): 330-337Crossref PubMed Scopus (43) Google Scholar, 8Golden D.B.K. Marsh D.G. Kagey-Sobotka A. Addison B.I. Freidhoff L. Szklo M. et al.Epidemiology of insect venom sensitivity.JAMA. 1989; 262 (IIb): 240-244Crossref PubMed Google Scholar, 9Settipane G.A. Boyd G.R. Prevalence of bee sting allergy in 4992 Boy Scouts.Acta Allergol. 1970; 25 (III): 286-291Crossref PubMed Google Scholar, 10Settipane G.A. Newstead G.J. Boyd G.K. Frequency of Hymenoptera allergy in an atopic and normal population.J Allergy. 1972; 50 (IIb): 146-150Google Scholar Systemic reactions are characterized by symptoms and signs, including any combination of urticaria and angioedema, bronchospasm, edema of the large airway, hypotension, or other clinical manifestations of anaphylaxis.11Brown S.G. Clinical features and severity grading of anaphylaxis.J Allergy Clin Immunol. 2004; 114 (III): 371-376Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar The most serious anaphylactic reactions involve the cardiovascular and respiratory systems and are potentially life-threatening. The most common cardiovascular reaction is hypotension. Respiratory symptoms include symptoms of upper or lower airway obstruction. Laryngeal edema and circulatory failure are the most common causes of death from anaphylaxis. Patients who have a history of a systemic reaction to an insect sting should (1) be educated in avoidance of stinging insects, (2) carry epinephrine for emergency self-administration and be instructed in its appropriate indications and administration, (3) undergo testing for specific IgE antibodies to stinging insects, (4) be considered for immunotherapy (with insect venom or fire ant whole-body extract) if test results for specific IgE antibodies are positive, and (5) consider carrying medical identification for stinging insect hypersensitivity. Identification of the insect responsible for the sting reaction can be very useful in establishing the diagnosis, prescribing treatment, and educating patients in avoidance measures. Education regarding stinging insect avoidance can best be done by an allergist-immunologist who has training and experience in the diagnosis and management of stinging insect hypersensitivity. For example, yellow jackets generally build their nests in the ground and therefore can be encountered during yard work, farming, and gardening. Hornets are extremely aggressive and build large nests, usually in trees or shrubs, which, despite their size, often go undetected. Wasps build honeycomb nests often in shrubs and under eaves of houses or barns and, like yellow jackets and hornets, are scavengers, increasing the likelihood of their presence at outdoor events where food and drink are being served. Domestic honeybees are found in commercial hives, whereas wild honeybees might build their nests in tree hollows or old logs. Africanized honeybees are hybrids developed from interbreeding of domestic honeybees and African honeybees in South America and are much more aggressive than domestic honeybees, often attacking in swarms. Usually, honeybees and occasionally other stinging insects leave a barbed stinger and attached venom sac in the skin after they sting. The imported fire ant, which can be red or black, builds nests in mounds of fresh soil that can be 1 to 2 feet in diameter and elevated at least several inches. These ants are very aggressive, particularly if their nests are disturbed, and often sting multiple times in a circular pattern, producing sterile pseudopustules that have a distinctive appearance. Patients who have experienced a systemic reaction to an insect sting should be referred to an allergist-immunologist for skin testing or occasionally in vitro testing for specific IgE antibodies to insects. Extracts of honeybee, yellow jacket, white-faced hornet, yellow hornet, and wasp venom are available for skin testing and venom immunotherapy (VIT). Although there is no venom extract available for commercial use in patients with suspected fire ant hypersensitivity, whole-body extract is available and contains relevant venom allergens, the effectiveness of which is supported by accumulating evidence.12Butcher B. deShazo R. Ortiz A. Reed M. RAST-inhibition studies of the imported fire ant, Solenopsis invicta, with whole body extracts and venom preparations.J Allergy Clin Immunol. 1988; 81 (III): 1096-1100Abstract Full Text PDF PubMed Google Scholar, 13DeShazo R.D. Butcher B.T. Banks W.A. Reactions to the stings of the imported fire ant.N Engl J Med. 1990; 323 (IV): 462-466Crossref PubMed Google Scholar, 14Freeman T.M. Clinical practice. Hypersensitivity to Hymenoptera stings.N Engl J Med. 2004; 351 (IV): 1978-1984Crossref PubMed Scopus (38) Google Scholar, 15Freeman T.M. Hyghlander R. Ortiz A. Martin M.E. Imported fire ant immunotherapy: effectiveness of whole body extracts.J Allergy Clin Immunol. 1992; 90 (IIa): 210-215Abstract Full Text PDF PubMed Google Scholar, 16Hoffman D.R. Jacobson R.S. Schmidt M. Smith A.M. Allergens in Hymenoptera venoms. XXIII. Venom content of imported fire ant whole body extracts.Ann Allergy. 1991; 66 (III): 29-31PubMed Google Scholar, 17Rhoades R.B. Skin test reactivity to imported fire ant whole body extract—comparison of three commercial sources.J Allergy Clin Immunol. 1993; 91 ([abstract]) (IIb): 282Google Scholar, 18Strom G.B. Boswell M.D. Jacobs R.L. In vivo and in vitro comparison of fire ant venom and fire ant whole body extract.J Allergy Clin Immunol. 1983; 72 (IIb): 46-53Abstract Full Text PDF PubMed Google Scholar It is generally accepted that a positive intradermal skin test response to insect venom at a concentration of less than or equal to 1.0 μg/mL demonstrates the presence of specific IgE antibodies.19Hoffman D.R. Comparison of the radioallergosorbent test to intradermal skin testing in the diagnosis of stinging insect venom allergy.Ann Allergy. 1979; 43 (IIb): 211-213PubMed Google Scholar, 20Patrizzi R. Muller U. Yman L. Hoigne R. Comparison of skin tests and RAST for the diagnosis of bee sting allergy.Allergy. 1979; 34 (IIb): 249-256Crossref PubMed Google Scholar, 21Reisman R.E. Georgitis J.W. Frequency of positive venom skin tests in insect-allergic and non-allergic populations.J Allergy Clin Immunol. 1984; 73 (III): 187Abstract Full Text PDF Google Scholar, 22Schwartz H.J. Lockey R.F. Sheffer A.L. Parrino J. Busse W.W. Yunginger J.W. A multicenter study on skin test reactivity of human volunteers to venom as compared with whole body Hymenoptera antigens.J Allergy Clin Immunol. 1981; 67 (IIb): 81-85Abstract Full Text PDF PubMed Google Scholar Skin testing with fire ant whole-body extract is considered indicative of specific IgE antibodies if a positive response occurs at a concentration of 1:100 wt/vol or less by using the skin prick method or 1:1000 wt/vol or less by using the intradermal method.13DeShazo R.D. Butcher B.T. Banks W.A. Reactions to the stings of the imported fire ant.N Engl J Med. 1990; 323 (IV): 462-466Crossref PubMed Google Scholar, 14Freeman T.M. Clinical practice. Hypersensitivity to Hymenoptera stings.N Engl J Med. 2004; 351 (IV): 1978-1984Crossref PubMed Scopus (38) Google Scholar, 17Rhoades R.B. Skin test reactivity to imported fire ant whole body extract—comparison of three commercial sources.J Allergy Clin Immunol. 1993; 91 ([abstract]) (IIb): 282Google Scholar For those patients who have negative skin test responses despite a convincing history of anaphylaxis after an insect sting, especially if they experienced serious symptoms, such as upper airway obstruction or hypotension, it is advisable to consider in vitro testing for IgE antibodies or repeat skin testing before concluding that immunotherapy is not indicated.23Golden D.B.K. Kagey-Sobotka A. Hamilton R.G. Norman P.S. Lichtenstein L.M. Insect allergy with negative venom skin tests.J Allergy Clin Immunol. 2001; 107 (IIb): 897-901Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 24Golden D.B.K. Tracy J.M. Freeman T.M. Hoffman D.R. AAAAI Insect CommitteeNegative venom skin test results in patients with histories of systemic reaction to a sting.J Allergy Clin Immunol. 2003; 112 (IV): 495-498Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 25Reisman R.E. Insect sting allergy: the dilemma of the negative skin test reactor.J Allergy Clin Immunol. 2001; 107 (IV): 781-782Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Either or both of the serum measurements of specific IgE for insect venom or fire ant whole-body extract and the skin test responses might be temporarily nonreactive within the first few weeks after a systemic reaction to an insect sting and might require retesting in 6 weeks.26Goldberg A. Confino-Cohen R. Timing of venom skin tests and IgE determinations after insect sting anaphylaxis.J Allergy Clin Immunol. 1997; 100 (IIb): 183-184Google Scholar Although one might want to wait for this period of time before initial testing, it might be important to skin test patients without waiting, especially if rapid initiation of VIT is required. Rarely (<1% of patients with a convincing history of systemic reaction to a sting), patients can have an anaphylactic reaction from a subsequent sting despite negative skin and in vitro test results.23Golden D.B.K. Kagey-Sobotka A. Hamilton R.G. Norman P.S. Lichtenstein L.M. Insect allergy with negative venom skin tests.J Allergy Clin Immunol. 2001; 107 (IIb): 897-901Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 27vanderLinden P.G. Hack C.E. Struyvenberg A. vanderZwan J.K. Insect-sting challenge in 324 subjects with a previous anaphylactic reaction: current criteria for insect-venom hypersensitivity do not predict the occurrence and the severity of anaphylaxis.J Allergy Clin Immunol. 1994; 94 (IIb): 151-159Abstract Full Text Full Text PDF PubMed Google Scholar Some of these patients might have underlying systemic mastocytosis. Because patients who have a history of an allergic reaction to an insect sting and have a positive skin or in vitro test result for specific IgE antibodies to insects might be at risk for subsequent life-threatening reactions if re-stung, immunotherapy should be considered in such patients. Approximately 30% to 60% of patients with a history of systemic allergic reactions from an insect sting who have specific IgE antibodies detectable by means of skin or in vitro testing will experience a systemic reaction when re-stung.27vanderLinden P.G. Hack C.E. Struyvenberg A. vanderZwan J.K. Insect-sting challenge in 324 subjects with a previous anaphylactic reaction: current criteria for insect-venom hypersensitivity do not predict the occurrence and the severity of anaphylaxis.J Allergy Clin Immunol. 1994; 94 (IIb): 151-159Abstract Full Text Full Text PDF PubMed Google Scholar, 28Brown S.G. Wiese M.D. Blackman K.E. Heddle R.J. Ant venom immunotherapy: a double-blind placebo-controlled crossover trial.Lancet. 2003; 361 (Ib): 1001-1006Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 29Franken H.H. Dubois A.E.J. Minkema H.J. vanderHeide S. deMonchy J.G.R. Lack of reproducibility of a single negative sting challenge response in the assessment of anaphylactic risk in patients with suspected yellow jacket hypersensitivity.J Allergy Clin Immunol. 1994; 93 (IIb): 431-436Abstract Full Text PDF PubMed Google Scholar, 30Golden D.B.K. Langlois J. Valentine M.D. Treatment failures with whole body extract therapy of insect sting allergy.JAMA. 1981; 246 (III): 2460-2463Crossref PubMed Google Scholar, 31Hunt K.J. Valentine M.D. Sobotka A.K. Benton A.W. Amodio F.J. Lichtenstein L.M. A controlled trial of immunotherapy in insect hypersensitivity.N Engl J Med. 1978; 299 (Ib): 157-161Crossref PubMed Google Scholar, 32Muller U. Thurnheer U. Patrizzi R. Spiess J. Hoigne R. Immunotherapy in bee sting hypersensitivity: bee venom versus wholebody extract.Allergy. 1979; 34 (IIa): 369-378Crossref PubMed Google Scholar, 33Reisman R.E. Natural history of insect sting allergy: relationship of severity of symptoms of initial sting anaphylaxis to re-sting reactions.J Allergy Clin Immunol. 1992; 90 (IIb): 335-339Abstract Full Text PDF PubMed Google Scholar, 34Settipane G.A. Chafee F.H. Natural history of allergy to Hymenoptera.Clin Allergy. 1979; 9 (III): 385-391Crossref PubMed Google Scholar As a result, it has been suggested that patients can be better selected for immunotherapy on the basis of the results of an intentional sting challenge.27vanderLinden P.G. Hack C.E. Struyvenberg A. vanderZwan J.K. Insect-sting challenge in 324 subjects with a previous anaphylactic reaction: current criteria for insect-venom hypersensitivity do not predict the occurrence and the severity of anaphylaxis.J Allergy Clin Immunol. 1994; 94 (IIb): 151-159Abstract Full Text Full Text PDF PubMed Google Scholar, 35Blaauw P.J. Smithuis L.O.M.J. The evaluation of the common diagnostic methods of hypersensitivity for bee and yellow jacket venom by means of an in-hospital insect sting.J Allergy Clin Immunol. 1985; 75 (IIb): 556-562Abstract Full Text PDF PubMed Google Scholar Sting challenges, however, are not consistently reproducible and are associated with considerable risk.29Franken H.H. Dubois A.E.J. Minkema H.J. vanderHeide S. deMonchy J.G.R. Lack of reproducibility of a single negative sting challenge response in the assessment of anaphylactic risk in patients with suspected yellow jacket hypersensitivity.J Allergy Clin Immunol. 1994; 93 (IIb): 431-436Abstract Full Text PDF PubMed Google Scholar, 36Rueff F. Przybilla B. Muller U. Mosbech H. The sting challenge test in Hymenoptera venom allergy.Allergy. 1996; 51 (IV): 216-225PubMed Google Scholar The standard management of insect sting hypersensitivity in the United States does not include a sting challenge.37Valentine M.D. Insect sting anaphylaxis.Ann Intern Med. 1993; 118 (IV): 225-226Crossref PubMed Google Scholar A recent study of severe and recurrent anaphylaxis highlights that patients with severe insect sting reactions should also be evaluated for mast cell disorders. Work-up for mast cell disorders might include baseline serum tryptase measurement and bone marrow biopsy. Throughout this document, the use of the terms venom immunotherapy, VIT, venom testing, and venom refers to both venom and imported fire ant whole-body extracts unless otherwise stated. VIT is generally not necessary in children 16 years of age and younger who have experienced isolated cutaneous systemic reactions without other systemic manifestations after an insect sting.38Golden D.B.K. Kagey-Sobotka A. Norman P.S. 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 (IIb): 668-674Crossref PubMed Scopus (138) Google Scholar, 39Valentine M.D. Schuberth K.C. Kagey-Sobotka A. Graft D.F. Kwiterovich K.A. Szklo M. et al.The value of immunotherapy with venom in children with allergy to insect stings.N Engl J Med. 1990; 323 (Ib): 1601-1603Crossref PubMed Google Scholar VIT in adults who have experienced only cutaneous manifestations of a systemic reaction is controversial but usually recommended. VIT is extremely effective in reducing the risk of a subsequent systemic reaction from an insect sting to less than 5%, and sting reactions that occur during VIT are usually milder than those experienced before VIT.28Brown S.G. Wiese M.D. Blackman K.E. Heddle R.J. Ant venom immunotherapy: a double-blind placebo-controlled crossover trial.Lancet. 2003; 361 (Ib): 1001-1006Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 31Hunt K.J. Valentine M.D. Sobotka A.K. Benton A.W. Amodio F.J. Lichtenstein L.M. A controlled trial of immunotherapy in insect hypersensitivity.N Engl J Med. 1978; 299 (Ib): 157-161Crossref PubMed Google Scholar, 32Muller U. Thurnheer U. Patrizzi R. Spiess J. Hoigne R. Immunotherapy in bee sting hypersensitivity: bee venom versus wholebody extract.Allergy. 1979; 34 (IIa): 369-378Crossref PubMed Google Scholar VIT is generally not necessary for patients who have had only a large local reaction because the risk of a systemic reaction to a subsequent sting is relatively low. In fact, the vast majority of patients who have had a large local reaction do not need to be tested for specific IgE antibodies to insect venom. There is growing evidence that VIT significantly reduces the size and duration of large local reactions and thus might be useful in subjects who have unavoidable, frequent, or both large local reactions.5Golden D.B.K. Kelly D. Hamilton R.G. Craig T.J. Venom immunotherapy reduces large local reactions to insect stings.J Allergy Clin Immunol. 2009; 123 (IIa): 1371-1375Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 40Walker R. Jacobs J. Tankersly M. Hagan L. Freeman T. Rush immunotherapy for the prevention of large local reactions secondary to imported fire ant stings.J Allergy Clin Immunol. 1999; 103 (IIb): S180Google Scholar, 41Severino M.G. Cortellini G. Bonadonna P. Francescato E. Panzini I. Macchia D. et al.Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind placebo-controlled trial.J Allergy Clin Immunol. 2008; 122 (Ib): 44-48Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar Once initiated, VIT should usually be continued for at least 3 to 5 years.42Bonifazi F. Jutel M. Bilo B.M. Birnbaum J. Muller U. EAACI Prevention and treatment of Hymenoptera venom allergy: guidelines for clinical practice.Allergy. 2005; 60 (IV): 1459-1470Crossref PubMed Scopus (196) Google Scholar, 43Graft D.F. Golden D. Reisman R. Valentine M. Yunginger J. The discontinuation of Hymenoptera venom immunotherapy. Report from the Committee on Insects.J Allergy Clin Immunol. 1998; 101 (IV): 573-575Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar An increasing body of evidence suggests that despite the persistence of a positive skin test response, 80% to 90% of patients will not have a systemic reaction to an insect sting if VIT is stopped after 3 to 5 years.44Forester J.P. Johnson T.L. Arora R. Quinn J.M. Systemic reaction rates to field stings among imported fire ant sensitive patients receiving >3 years of immunotherapy versus <3 years of immunotherapy.Allergy Asthma Proc. 2007; 28 (IIb): 485-488Crossref PubMed Scopus (9) Google Scholar, 45Golden D.B.K. Kwiterovich K.A. Kagey-Sobotka A. Valentine M.D. Lichtenstein L.M. Discontinuing venom immunotherapy: outcome after five years.J Allergy Clin Immunol. 1996; 97 (IIb): 579-587Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar, 46Golden D.B.K. Kwiterovich K.A. Addison B.A. Kagey-Sobotka A. Lichtenstein L.M. Discontinuing venom immunotherapy: extended observations.J Allergy Clin Immunol. 1998; 101 (III): 298-305Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 47Golden D.B.K. Kagey-Sobotka A. Lichtenstein L.M. Survey of patients after discontinuing venom immunotherapy.J Allergy Clin Immunol. 2000; 105 (III): 385-390Abstract Full Text Full Text PDF PubMed Google Scholar, 48Hafner T. Dubuske L. Kosnik M. Long-term efficacy of venom immunotherapy.Ann Allergy Asthma Immunol. 2008; 100 (III): 162-165Abstract Full Text Full Text PDF PubMed Google Scholar, 49Haugaard L. Norregaard O.F.H. Dahl R. In-hospital sting challenge in insect venom-allergic patients after stopping venom immunotherapy.J Allergy Clin Immunol. 1991; 87 (IIb): 699-702Abstract Full Text PDF PubMed Google Scholar, 50Lerch E. Muller U. Long-term protection after stopping venom immunotherapy.J Allergy Clin Immunol. 1998; 101 (IIb): 606-612Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 51Muller U. Berchtold E. Helbling A. Honeybee venom allergy: results of a sting challenge 1 year after stopping venom immunotherapy in 86 patients.J Allergy Clin Immunol. 1991; 87 (IIb): 702-709Abstract Full Text PDF PubMed Google Scholar, 52Reisman R.E. Duration of venom immunotherapy: relationship to the severity of symptoms of initial insect sting anaphylaxis.J Allergy Clin Immunol. 1993; 92 (IIa): 831-836Abstract Full Text PDF PubMed Scopus (47) Google Scholar There are no specific tests to distinguish which patients will relapse after stopping VIT, but there is a higher risk in some patients than others. Relapse is less likely with 5 years than with 3 years of VIT.50Lerch E. Muller U. Long-term protection after stopping venom immunotherapy.J Allergy Clin Immunol. 1998; 101 (IIb): 606-612Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 53Keating M.U. Kagey-Sobotka A. Hamilton R.G. Yunginger J.W. Clinical and immunologic follow-up of patients who stop venom immunotherapy.J Allergy Clin Immunol. 1991; 88 (IIb): 339-348Abstract Full Text PDF PubMed Google Scholar Although most patients can safely discontinue immunotherapy after this period of time, some patients with a history of severe anaphylaxis with shock or loss of consciousness still might be at continued risk for a systemic reaction if VIT is stopped, even after 5 years of immunotherapy.46Golden D.B.K. Kwiterovich K.A. Addison B.A. Kagey-Sobotka A. Lichtenstein L.M. Discontinuing venom immunotherapy: extended observations.J Allergy Clin Immunol. 1998; 101 (III): 298-305Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 47Golden D.B.K. Kagey-Sobotka A. Lichtenstein L.M. Survey of patients after discontinuing venom immunotherapy.J Allergy Clin Immunol. 2000; 105 (III): 385-390Abstract Full Text Full Text PDF PubMed Google Scholar, 52Reisman R.E. Duration of venom immunotherapy: relationship to the severity of symptoms of initial insect sting anaphylaxis.J Allergy Clin Immunol. 1993; 92 (IIa): 831-836Abstract Full Text PDF PubMed Scopus (47) Google Scholar For this reason, some experts recommend an extended duration of immunotherapy, possibly indefinitely, in such patients. Other criteria suggested for stopping VIT include a decrease in serum venom-specific IgE to insignificant levels or conversion to a negative skin test response.54Reisman R.E. Venom immunotherapy: When is it reasonable to stop.J Allergy Clin Immunol. 1991; 87 (IV): 618-620Abstract Full Text PDF PubMed Google Scholar Some patients have relapsed despite negative venom skin test responses. Repeat skin (or venom-specific IgE serum) testing is not required for consideration of discontinuing VIT. Measurements of venom-specific IgG antibodies have no predictive value when discontinuing VIT. The decision on stopping VIT requires a context-sensitive flexibility based on the available evidence. The optimal duration of fire ant immunotherapy is less well defined. Most allergists consider stopping fire ant immunotherapy after a specified period (usually 3-5 years) either empirically or only when skin test or in vitro test results become negative.55Moffitt J.E. Barker J.R. Stafford C.T. Management of imported fire ant allergy: results of a survey.Ann Allergy Asthma Immunol. 1997; 79 (IV):