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Stinging insect hypersensitivity: A practice parameter update

2004; Elsevier BV; Volume: 114; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2004.07.046

1097-6825

John E. Moffitt, David B.K. Golden, Robert E. Reisman, Rufus Lee, Richard A. Nicklas, Theodore M. Freeman, Richard D. deShazo, James M. Tracy, Jonathan A. Bernstein, Joann Blessing-Moore, David A. Khan, David M. Lang, Jay M. Portnoy, Diane E. Schuller, Sheldon L. Spector, Steven A. Tilles,

Entomological Studies and Ecology

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 “Stinging insect hypersensitivity: A Practice Parameter Update.” 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 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 “Stinging insect hypersensitivity: A Practice Parameter Update.” 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. Published practice parameters of the Joint Task Force on Practice Parameters for Allergy and Immunology include the following:1.Practice parameters for the diagnosis and treatment of asthma. J Allergy Clin Immunol 1995;96(suppl):S707-S870.2.Practice parameters for allergy diagnostic testing. Ann Allergy 1995;75:543-625.3.Practice parameters for the diagnosis and management of immunodeficiency. Ann Allergy 1996;76:282-94.4.Practice parameters for allergen immunotherapy. J Allergy Clin Immunol 1996;98:1001-11.5.Disease management of atopic dermatitis: a practice parameter. Ann Allergy 1997;79:197-211.6.The diagnosis and management of anaphylaxis. J Allergy Clin Immunol 1998;101(suppl):S465-S528.7.Algorithm for the diagnosis and management of asthma: a practice parameter update. Ann Allergy 1998;81:415-20.8.Diagnosis and management of rhinitis: parameter documents of the Joint Task Force on Practice parameters in Allergy, Asthma and Immunology. Ann Allergy 1998;81(suppl):S463-S518.9.Parameters for the diagnosis and management of sinusitis. J Allergy Clin Immunol 1998;102(suppl):S107-S144.10.Stinging insect hypersensitivity: a practice parameter. J Allergy Clin Immunol 1999;103:963-80.11.Disease management of drug hypersensitivity: a practice parameter. Ann Allergy 1999;83(suppl):S665–S700.12.Diagnosis and management of urticaria: a practice parameter. Ann Allergy 2000;85(suppl):S521-S544.13.Allergen immunotherapy: a practice parameter. Ann Allergy 2003;90(suppl):S1-S54.14.Symptom severity assessment of allergic rhinitis: part I. Ann Allergy 2003;91:105-14.These parameters are also available on the Internet at: http://www.jcaai.orgContributorsThe 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.EditorsJohn E. Moffitt, MDAssociate Vice Chancellor for Health AffairsExecutive Associate Dean School of MedicineProfessor of PediatricsUniversity of Mississippi Medical CenterJackson, MissDavid B. K. Golden, MDAssociate Professor of MedicineJohns Hopkins UniversityBaltimore, MdRobert E. Reisman, MDClinical Professor of Medicine and PediatricsState University of NY at Buffalo School of MedicineBuffalo, NYRufus E. Lee, MDPrivate PracticeDothan, AlaRichard A. Nicklas, MDClinical Professor of MedicineGeorge Washington Medical CenterWashington, DCAssociate editorsTheodore M. Freeman, MDSan Antonio, TexRichard D. deShazo, MDBilly Guyton Distinguished ProfessorChair, Department of MedicineUniversity of Mississippi Medical CenterJackson, MissJames M. Tracy, DOUniversity of NebraskaOmaha, NebI. Leonard Bernstein, MDClinical Professor of Medicine and Environmental HealthUniversity of Cincinnati College of MedicineCincinnati, OhioJoann Blessing-Moore, MDAssociate Clinical Professor of Medicine and PediatricsStanford University Medical CenterPalo Alto, CalifDavid Kahn, MDAssociate Professor of Internal MedicineDivision of Allergy and ImmunologyUniversity of Texas Southwestern Medical CenterDallas, TexDavid Lang, MDHead, Allergy/Immunology SectionDivision of MedicineDirector, Allergy/Immunology Fellowship Training ProgramCleveland Clinic FoundationCleveland, OhioDiane E. Schuller, MDProfessor of PediatricsPennsylvania State UniversityMilton S. Hershey Medical CollegeHershey, PaSheldon L. Spector, MDClinical Professor of MedicineUniversity of California–Los AngelesLos Angeles, CalifSteven A. Tilles, MDClinical Assistant Professor of MedicineUniversity of Washington School of MedicineSeattle, WashReviewersDavid F. Graft, MD, Minneapolis, MinnMichael R. Nelson, MD, PHD, Washington, DCRobert E. Reisman, MD, Williamsville, NYDana V. Wallace, MD, Ft Lauderdale, FlaAnne B. Yates, MD, Jackson, MissStinging insect hypersensitivity: A practice parameter updateTable of ContentsI.PrefaceII.Executive SummaryIII.AlgorithmIV.AnnotationsV.Summary StatementsVI.IntroductionVII.Stinging Insect IdentificationVIII.Stinging Insect ReactionsA.Management of Insect Sting Reactions1.local reactions2.systemic reactionsIX.Indications for referral to an allergist-immunologistX.Preventive ManagementXI.Immediate TreatmentXII.Immediate Hypersensitivity TestingA.Skin testing for honeybee, wasps, hornets, and yellow jacketsB.Skin testing for fire ant hypersensitivityC.In vitro testingXIII.ImmunotherapyA.Venom immunotherapy for bees, wasps, yellow jackets, and hornetsB.Criteria for immunotherapyC.Challenge stingsD.Large local reactionsE.Selection of venoms for immunotherapyF.Immunotherapy for fire ant venom hypersensitivityG.Dosage schedule for VITH.Duration of VITXIV.ReferencesPrefaceThe objective of “Stinging insect hypersensitivity: A practice parameter update” is to improve the care for patients with stinging insect hypersensitivity. This parameter is intended to refine guidelines for the use and interpretation of diagnostic methods and for the institution and implementation of measures to manage stinging insect hypersensitivity, with particular emphasis on the appropriate use of immunotherapy.“Stinging insect hypersensitivity: A practice parameter update” was developed by the Joint Task Force on Practice Parameters. The 3 major allergy and immunology societies (the American College of Allergy, Asthma and Immunology [ACAAI]; the American Academy of Allergy, Asthma and Immunology [AAAAI]; and the Joint Council of Allergy, Asthma and Immunology) charged the Task Force with the development of practice guidelines for stinging insect hypersensitivity. The document “Stinging insect hypersensitivity: a practice parameter update” builds on “Stinging insect hypersensitivity: a practice parameter” (Portnoy JM, Moffitt JE, Golden DBK, Bernstein IL, et al. J Allergy Clin Immunol 1999:103;963-80), which was previously published by the Joint Task Force. It follows the same format as that document, with some substantive changes reflecting advancements in scientific knowledge and their effect on management of insect sting allergy. “Stinging insect hypersensitivity: a practice parameter update” was written and reviewed by subspecialists in allergy and immunology. The project was exclusively funded by the 3 allergy and immunology societies noted above.A work group chaired by Dr John Moffitt prepared the initial draft, which was subsequently reviewed by the Joint Task Force. A comprehensive search of the medical literature was conducted with various search engines, including PubMed, and “immunotherapy,” “stinging insect allergy,” “anaphylaxis,” “venom,” and related search terms were used. Published clinical studies were rated by category of evidence and used to establish the strength of a clinical recommendation (Table I).Table IClassification of evidence and recommendations∗Printed with permission of the British Medical Journal from Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. BMJ 1999;318:593-6.Category of evidence IaEvidence from meta-analysis of randomized controlled trials IbEvidence from at least 1 randomized controlled trial IIaEvidence from at least 1 controlled study without randomization IIbEvidence from at least 1 other type of quasiexperimental study IIIEvidence from nonexperimental descriptive studies, such as comparative studies, correlation studies, and case-controlled studies IVEvidence from expert committee reports, opinions or clinical experience of respected authorities, or both LBEvidence from laboratory-based studies†Added by current authors.Strength of recommendation ADirectly based on category I evidence BDirectly based on category II evidence or extrapolated from category I evidence CDirectly based on category III evidence or extrapolated from category I or II evidence DDirectly based on category IV evidence or extrapolated from category I, II or III evidence EDirectly based on category LB evidence†Added by current authors. FBased on consensus of the Joint Task Force on Practice Parameters†Added by current authors.∗ Printed with permission of the British Medical Journal from Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. BMJ 1999;318:593-6.† Added by current authors. Open table in a new tab The working draft of “Stinging insect hypersensitivity: a practice parameter update” was reviewed by a large number of experts in allergy and immunology. These experts included reviewers appointed by the ACAAI and AAAAI. Copies of the working draft were distributed at the ACAAI annual meeting in the fall of 2002 and the AAAAI annual meeting in the spring of 2003. The authors carefully reviewed and considered additional comments from these reviewers. The revised final document presented here was approved by the sponsoring organizations and represents an evidence-based, broadly accepted consensus parameter.An annotated algorithm in this document summarizes the key decision points for the appropriate use of allergen immunotherapy (Fig 1). Specific recommendations guide the physician in selecting those patients for whom allergen immunotherapy for insect sting allergy is appropriate. Immunotherapy is recommended for patients with a history of a systemic reaction to Hymenoptera who demonstrate specific IgE antibodies to Hymenoptera venom, as described in the parameter.Allergen vaccine is the recommended term for the therapeutic agent used in allergen immunotherapy. This term is used in the document when the therapeutic use of the preparation is clear. The terms allergen extract or extract (vaccine) are used in the text where the nontherapeutic aspects of the allergen preparation are important.The Joint Task Force on Practice Parameters would like to thank members of the workgroup and Task Force, as listed elsewhere in this document.Executive summaryMost insect stings produce a transient local reaction that might last up to several days and generally resolves without treatment. Marked local swelling extending from the sting site might be an IgE-mediated late-phase reaction. The risk of a systemic reaction in patients who experience large local reactions is no more than 5% to 10%. More serious anaphylactic sting reactions account for at least 40 deaths each year in the United States. 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.Systemic reactions might be characterized by urticaria and angioedema, bronchospasm, edema of the large airway, hypotension, and other clinical manifestations. 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 is the most common cause 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, (3) undergo testing for specific IgE antibodies to stinging insects, (4) be considered for venom immunotherapy (VIT) if test results for specific IgE antibodies are positive, and (5) consider obtaining medical identification of 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. 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 is 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 sack in the skin after they sting. The 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 a sterile pseudopustule that has a distinctive appearance. 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.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 insect venom. Extracts of honeybee, yellow jacket, white-faced hornet, yellow hornet, and wasp venom are available for skin testing and 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. It is generally accepted that a positive 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. Skin testing with fire ant whole-body extract is considered indicative of specific IgE antibodies if a positive response occurs at a concentration of 1:500 wt/vol or less.For those patients who have 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 if the patient has negative skin test responses before concluding that VIT is not indicated. Negative skin test responses within the first few weeks after a reaction to an insect sting might require cautious interpretation. Rarely, patients can have an anaphylactic reaction with a subsequent sting despite negative skin and in vitro test responses, possibly because of a non–IgE-mediated mechanism.Because patients who have experienced an allergic reaction to an insect sting, as defined by history and a positive skin or in vitro test response for specific IgE antibodies to insect venom, are at risk for subsequent life-threatening reactions if re-stung, VIT should be considered in such patients. Approximately 30% to 60% of patients with a history of anaphylaxis from an insect sting and venom-specific IgE antibodies detectable by means of skin or in vitro testing will experience a systemic reaction when re-stung. As a result, it has been recommended that patients can be better selected for VIT on the basis of the results of an intentional sting challenge. Sting challenges, however, are not consistently reproducible and are associated with considerable risk. The standard management of insect sting hypersensitivity in the United States does not include a sting challenge.VIT is generally not necessary in children 16 years of age and younger who have experienced isolated cutaneous reactions without systemic manifestations after an insect sting from a wasp, hornet, yellow jacket, or wasp. VIT in adults who have experienced only cutaneous manifestations 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 those who experience reactions have milder reactions. VIT is generally not necessary for patients who have had only a large local reaction because the risk of a systemic reaction with 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.Once initiated, VIT should usually be continued for at least 3 to 5 years. 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. 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. For this reason, some experts recommend continuation of immunotherapy 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. The optimal duration of fire ant immunotherapy is less well defined. Most allergists consider stopping immunotherapy after a specified period (usually 4-5 years) either empirically or only when skin test responses become negative. Until further data are available, a definitive recommendation about the duration of immunotherapy for fire ant venom cannot be made.Less is known about the natural history of fire ant venom hypersensitivity and the effectiveness of immunotherapy than is known about other stinging insects. Fire ant whole-body extract has been shown to contain relevant venom allergens, and evidence continues to accumulate, despite the lack of any placebo-controlled study, to support the effectiveness of immunotherapy with fire ant whole-body extract.Patients who have experienced more than a local reaction to an insect sting should be prescribed injectable epinephrine (eg, EpiPen and EpiPenJr) and should be advised to carry it with them at all times. Because some patients who experience anaphylaxis might require more than one injection of epinephrine, prescription for more than one EpiPen or EpiPenJr should be considered. Patients and advocates who might be administering epinephrine should be taught how to administer this drug and under what circumstances this should be done. Although patients with coexisting conditions, such as hypertension or cardiac arrhythmias, or concomitant medications, such as β-adrenergic blocking agents, might require special attention, there is no contraindication to the use of epinephrine in a life-threatening situation, such as anaphylaxis. More than one dose of epinephrine might be required with persistence or recurrence of symptoms.Annotations to fig 1Box 1: patient presents with a history of insect sting reactionAlthough insects sting many persons each year, most individuals do not have significant reactions and do not need medical attention. Most who are stung have only local reactions and require only symptomatic, if any, treatment. Persons who have a history of insect stings causing systemic reactions require evaluation and usually treatment. Reactions can range from large local swelling to life-threatening systemic reactions. Delayed or toxic reactions might also occur. Taking a careful history can usually make the diagnosis of insect sting reaction.Box 2: history and physical examinationIdentification of the insect responsible might be helpful in diagnosis and treatment. Patients should be encouraged to bring the offending insect, if available, to the physician for identification.Factors that might be helpful in identification include the following:▪the patient's activity at the time of the sting (eg, cutting a hedge),▪the location of the person at the time of the sting (eg, close to an insect nest),▪the type of insect activity in the area where the patient was stung, and▪visual identification of the insect.Young children present special problems with identification of the culprit insect. The presence of a stinger, which is left primarily by honeybees, or the presence of a pustule as a result of a fire ant sting (up to 24 hours later) might help in insect identification.Box 3: was there a systemic reaction?Most insect stings result in local reactions. These include the following:▪redness,▪swelling, and▪itching and pain.Large local reactions usually include the following features:▪increase in size for 24 to 48 hours,▪swelling to more than 10 cm in diameter,▪possible involvement of more than one joint area, and▪5 to 10 days to resolve.Systemic reactions include a spectrum of manifestations ranging from mild to life-threatening. These include the following:▪cutaneous responses (eg, urticaria and angioedema),▪bronchospasm,▪large airway obstruction (tongue or throat swelling, laryngeal edema), and▪hypotension and shock.The key feature that distinguishes a systemic reaction from a large local reaction is the nature of the systemic symptoms and involvement of parts of the body not contiguous with the site of the sting.Box 4, A and B: provide symptomatic treatment if neededMost insect stings cause local reactions that are of little serious medical consequence, and no specific treatment is usually required. Some local reactions are manifested by extensive erythematous swelling surrounding the sting site that might persist for several days or more and can be accompanied by itching, pain, or both. Cold compresses might help to reduce local pain and swelling. Oral antihistamines and oral analgesics might also help to reduce the pain or itching associated with cutaneous reactions. Many physicians use oral corticosteroids for large local reactions; several reports support their effectiveness, although definitive proof of efficacy through controlled studies is lacking. Because the swelling is caused by mediator release and not by infection, antibiotics are not indicated unless there is evidence of secondary infection (a common misdiagnosis).Large local reactions can be IgE mediated but are almost always self-limited and rarely create serious health problems. Patients who have previously experienced large local reactions often have large local reactions to subsequent stings, and up to 10% might eventually have a systemic reaction. Some patients who have had large local reactions might seek guidance on insect avoidance measures. It is optional but usually not necessary to prescribe an injectable epinephrine kit for use if the patient experiences a systemic reaction in the future. The vast majority of patients with large local reactions need only symptomatic care and are not candidates for testing for venom-specific IgE or VIT. Immunotherapy has, however, been shown to reduce the severity of large local reactions with future stings in a patient with a history of severe local reactions and venom-specific IgE, but a previous report found immunotherapy to be ineffective in preventing reoccurrence of large local reactions.Box 5: prescribe epinephrine for self-administration/refer to an allergist-immunologist/recommend insect avoidancePreventive management includes measures to prevent subsequent stings and to prevent subsequent systemic reactions if the patient is stung. Injectable epinephrine should be provided, and the patient should be instructed on its proper administration and use. Patients should also consider obtaining a medical identification bracelet or necklace. A patient with a history of severe reaction should have injectable epinephrine prescribed because even if the test result for venom-specific IgE is negative, there is a small risk of a systemic reaction. For those patients with very mild or questionable systemic reactions and negative test results for venom-specific IgE, there is no consensus regarding prescription of injectable epinephrine because many physicians believe it is not warranted, whereas others prefer to prescribe it in this situation. Referral to an allergist is appropriate for any patient who has had an allergic reaction and is indicated for any patient who is a potential candidate for immunotherapy, as outlined in Box 6.Box 6, A, B, and C: is the patient a child whose reaction was limited to the cutaneous system?The usual criteria for immunotherapy include a systemic reaction to an insect sting and demonstration of venom-specific IgE by either skin or in vitro testing. However, immunotherapy is usually not prescribed for patients 16 years of age and younger who have experienced only cutaneous systemic reactions after an insect sting. They only have about a 10% chance of having a systemic reaction if re-stung, and if a subsequent systemic reaction does occur in these children, it is very unlikely to be worse than the initial isolated cutaneous reaction. Therefore VIT is generally not necessary for patients 16 years of age and younger who have experienced only cutaneous systemic reactions. VIT is still an acceptable option if there are special circumstances, such as lifestyle considerations, that place the child at risk for frequent or multiple stings or if the parents or guardians request venom immunotherapy. Although there is still some controversy in regard to adults who have experienced only cutaneous systemic reactions, there is insufficient evidence to justify withholding VIT for that group of individuals at this time. Although most physicians generally apply the same criteria in selecting patients to receive immunotherapy for fire ant allergy, it is not established that children with only systemic cutaneous reactions are not at risk for serious systemic reactions to subsequent stings. Because the natural history of fire ant hypersensitivity in children who have only cutaneous manifestations has not been well elucidated and there is increased risk of fire ant stings in children who live in areas in which fire ants are prevalent, immunotherapy can be considered for such children.Box 7: perform skin testingSkin tests should be performed on patients for whom venom immunotherapy might be indicated. Skin prick tests with a concentration in the range of 1.0 μg/mL are often performed before intracutaneous tests but are not used by all allergists.Intracutaneous tests usually start with a concentration in the range of 0.001 to 0.01 μg/mL. If intracutaneous test results at this concentration are negative, the concentration is increased by 10-fold increments until a positive skin test response occurs or a maximum concentration of 1.0 μg/mL is reached. Increasing concentrations of fire ant extract are also used (see text section on fire ants). Positive and negative controls should be placed during skin testing.Because the insect that caused the sting reaction often cannot be identified, testing is usually done with all of the commercially available venom extracts. However, fire ant is only included under special circumstances (see text). Venoms might contain shared antigenic components. Cross-sensitization and extensive immunologic cross-reactivity have been demonstrated between hornet and yellow jacket venoms (vespids); cross-reactivity is also fairly common, although less extensive, between wasp and other venoms and is uncommon between honeybee and vespid venoms. Fire ant venom has very limited cross-reactivity with other stinging insect venoms.Box 8: positive skin test response?Venom immunotherapy is recommended for patients