Insect Allergy: A Review of Diagnosis and Treatment

  • James M. TracyEmail author
  • Jeffrey G. Demain
Living reference work entry


Insect allergy is the third most common cause of the life-threatening condition anaphylaxis, following food and medications. Insect allergy anaphylaxis poses risk of considerable morbidity and mortality. Avoidance of the offending agent is the cornerstone to the management anaphylaxis regardless of the cause. However, unlike food and medication allergy, insect allergy has been effectively treated, using well-established protocols for many years. Hymenoptera are the insects most associated with allergy and anaphylaxis with at least 40 deaths per year attributed to insect stings in the United States. It is critical that healthcare professionals and the public understand the proper diagnosis as well as the long-term treatment of this potentially life-threatening allergy. Insect allergy from Hymenoptera, managed prospectively using venom immunotherapy, conveys up to 98% protection of anaphylaxis with future stings. Insects of the order Hymenoptera include bees, wasps, hornets, yellow jackets, and stinging ants. Stinging ant allergy will not be reviewed in this chapter. An understanding of the biology and habitat of the various Hymenoptera species is helpful in recommending insect avoidance strategies. The diagnosis of insect allergy relies on a history of a systemic allergic reaction followed by appropriate testing for venom-specific IgE. If the history of a generalized anaphylactic reaction to an insect sting and the presence of venom-specific IgE are confirmed, venom immunotherapy is indicated. It is venom immunotherapy, a disease modifying therapy, that provides the most effective protection against future sting reactions. Ultimately, recognition and lifesaving management is critical. Subsequently, evaluation and potentially long-term management of insect allergy include appropriate referral to an allergist familiar with insect allergy and, if indicated, venom immunotherapy.


Insect Hymenoptera Anaphylaxis Epinephrine 


  1. Álvarez-Twose I, González de Olano D, et al. Clinical, biological and molecular characteristics of clonal mast cell disorders presenting with mast cell activation symptoms. J Allergy Clin Immunol. 2010;125:1269–78.CrossRefGoogle Scholar
  2. Bilò BM, Bonifazi F. Epidemiology of insect venom anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8:330–7.CrossRefGoogle Scholar
  3. Bonadonna P, Perbellini O, Passalacqua G, et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol. 2009;123:680–6.CrossRefGoogle Scholar
  4. Bonadonna P, Zanotti R, Müller U. Mastocytosis and insect venom allergy. Curr Opin Allergy Clin Immunol. 2010;10:347–53.CrossRefGoogle Scholar
  5. Bonifazi F, Jutel M, Bilo BM, Birnbaum J, Muller U, EAACI. Prevention and treatment of Hymenoptea venom allergy: guidelines for clinical practice. Allergy. 2005;60:1459–70.CrossRefGoogle Scholar
  6. Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;63:226–32.CrossRefGoogle Scholar
  7. De Root H. Allergy to Bumblebee. Curr Opin Allergy Clin Immunol. 2006;6:294–7.CrossRefGoogle Scholar
  8. Demain JG. Papular urticaria and things that bite in the night. Curr Allergy Asthma Rep. 2003;3(4):291.CrossRefGoogle Scholar
  9. Demain JG, Minaei AA, Tracy JM. Anaphylaxis and insect allergy. Curr Opin Allergy Clin Immunol. 2010;10:318–22.CrossRefGoogle Scholar
  10. Forester JP, Johnson TL, Arora R, Quinn JM. 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;28:485–8.CrossRefGoogle Scholar
  11. Franken HH, Dubois AE, Minkema HJ, et al. 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;93:431.CrossRefGoogle Scholar
  12. Freeman TM. Clinical practice. Hypersensitivity to hymenoptera stings. N Engl J Med. 2004;351:1978.CrossRefGoogle Scholar
  13. Galera C, Soohun N, Zankar N, et al. Severe anaphylaxis to bee venom immunotherapy: efficacy of pretreatment and concurrent treatment with omalizumab. J Investig Allergol Clin Immunol. 2009;19:225–9.PubMedGoogle Scholar
  14. Georgitis JW, Reisman RE. Venom skin tests in insect-allergic and insect-nonallergic populations. J Allergy Clin Immunol. 1985;76:803.CrossRefGoogle Scholar
  15. Goddard J. Physician’s guide to arthropods of medical importance. 4th ed. Boca Raton: CRC Press; 2003. p. 4.Google Scholar
  16. Goldberg A, Confino-Cohen R. Timing of venom skin tests and IgE determinations after insect sting anaphylaxis. J Allergy Clin Immunol. 1997;100:182.CrossRefGoogle Scholar
  17. Golden DBK, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Dose dependence of Hymenoptera venom immunotherapy. J Allergy Clin Immunol. 1981;67:370–4.CrossRefGoogle Scholar
  18. Golden DB, Marsh DG, Kagey-Sobotka A, et al. Epidemiology of insect venom sensitivity. JAMA. 1989;262:240.CrossRefGoogle Scholar
  19. Golden DBK, Kwiterovich KA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM. Discontinuing venom immunotherapy: outcome after five years. J Allergy Clin Immunol. 1996;97:579–87.CrossRefGoogle Scholar
  20. Golden DB, Marsh DG, Freidhoff LR, et al. Natural history of Hymenoptera venom sensitivity in adults. J Allergy Clin Immunol. 1997;100:760.CrossRefGoogle Scholar
  21. Golden DBK, Kwiterovich KA, Addison BA, Kagey-Sobotka A, Lichtenstein LM. Discontinuing venom immunotherapy: extended observations. J Allergy Clin Immunol. 1998;101:298–305.CrossRefGoogle Scholar
  22. Golden DBK, Kagey-Sobotka A, Lichtenstein LM. Survey of patients after discontinuing venom immunotherapy. J Allergy Clin Immunol. 2000;105:385–90.CrossRefGoogle Scholar
  23. Golden DB, Kagey-Sobotka A, Norman PS, et al. Insect sting allergy with negative venom skin test responses. J Allergy Clin Immunol. 2001;107:897.CrossRefGoogle Scholar
  24. Golden DB, Tracy JM, Freeman TM, et al. Negative venom skin test results in patients with histories of systemic reaction to a sting. J Allergy Clin Immunol. 2003;112:495.CrossRefGoogle Scholar
  25. Golden DB, Breisch NL, Hamilton RG, et al. Clinical and entomological factors influence the outcome of sting challenge studies. J Allergy Clin Immunol. 2006;117:670.CrossRefGoogle Scholar
  26. Golden DB, Moffitt JE, Nicklas RA, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J Allergy Clin Immunol. 2011;127:852–4.CrossRefGoogle Scholar
  27. Golden DB, Demain J, Freeman T, Graft D, Tankersley M, Tracy J, et al. Stinging insect hypersensitivity: a practice parameter update 2016. Ann Allergy Asthma Immunol. 2017;118(1):28–54.CrossRefGoogle Scholar
  28. González de Olano D, Alvarez-Twose I, Esteban-López MI, et al. Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol. 2008;121:519.CrossRefGoogle Scholar
  29. Graft DF. Insect sting allergy. Med Clin N Am. 2006;90:211–32.CrossRefGoogle Scholar
  30. Graft DF, Schuberth KC, Kagey-Sobotka A, et al. A prospective study of the natural history of large local reactions after Hymenoptera stings in children. J Pediatr. 1984;104:664.CrossRefGoogle Scholar
  31. Graft DF, 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;101:573–5.CrossRefGoogle Scholar
  32. Gurlanick MW, Benton AW. Entomological aspects of insect sting allergy. In: Levine MI, Lockey RF, editors. Monograph on insect allergy. 4th ed. Pittsburgh: Dave Lambert Associates; 2003. p. 11.Google Scholar
  33. Hamilton RG. Responsibility for quality IgE antibody results rests ultimately with the referring physician. Ann Allergy Asthma Immunol. 2001;86:353.CrossRefGoogle Scholar
  34. Hamilton RG. Diagnostic methods for insect sting allergy. Curr Opin Allergy Clin Immunol. 2004;4:297.CrossRefGoogle Scholar
  35. Hoffman DR. Allergens in Hymenoptera venom. XXV. The amino acid sequence of Antigen 5 molecules. The structural basis of antigenic crossreactivity. J Allergy Clin Immunol. 1993;92:707–16. (III)CrossRefGoogle Scholar
  36. Hoffman DR, Jacobson RS. Allergens in Hymenoptera venom. XII. How much protein in a sting? Ann Allergy. 1984;52:276–8.PubMedGoogle Scholar
  37. Hoffman DR, El-Choufani SE, Smith MM, et al. Occupational allergy to bumblebee: allergens of Bombusterrestris. J Allergy Clin Immunol. 2001;108:855–60.CrossRefGoogle Scholar
  38. Hunt KJ, Valentine MD, Sobotka AK, Benton AW, Amodio FJ, Lichtenstein LM. A controlled trial of immunotherapy in insect hypersensitivity. N Engl J Med. 1978;299:157–61.CrossRefGoogle Scholar
  39. King TP, Joslyn A, Kochoumian L. Antigenic cross-reactivity of venom proteins from hornets, wasps and yellow jackets. J Allergy Clin Immunol. 1985;75:621–8. (III)CrossRefGoogle Scholar
  40. Kontou-Fill K, Fillis CI, Voulgari C, Panayiotidis PG. Omalizumab monotherapy for bee sting and unprovoked ‘anaphylaxis’ in a patient with systemic mastocytosis and undetectable specific IgE. Ann All Asthma Immunol. 2010;104:537–9.CrossRefGoogle Scholar
  41. Kosnik M, Korosec P. Importance of basophil activation testing in insect venom allergy. Allergy Asthma Clin Immunol. 2011;5:11.CrossRefGoogle Scholar
  42. Kruse P, Erzen R, Silar M, et al. Basophil responsiveness in patients with insect sting allergies and negative venom-specific immunoglobulin E and skin prick test results. Clinical Exp Allergy. 2009;39:1730–7.CrossRefGoogle Scholar
  43. Lerch E, Muller U. Long-term protection after stopping venom immunotherapy. J Allergy Clin Immunol. 1998;101:606–12.CrossRefGoogle Scholar
  44. Light WC, Reisman RE, Shimizu M, Arbesman CE. Unusual reactions following insect stings. Clinical features and immunologic analysis. J Allergy Clin Immunol. 1977;59:391.CrossRefGoogle Scholar
  45. Manivannan V, Campbell RL, Bellolio MF, et al. Factors associated with repeated use of epinephrine for the treatment of anaphylaxis. Ann Allergy Asthma Immunol. 2009;103:395–400.CrossRefGoogle Scholar
  46. Mauriello PM, Barde SH, Georgitis JW, Reisman RE. Natural history of large local reactions from stinging insects. J Allergy Clin Immunol. 1984;74:494.CrossRefGoogle Scholar
  47. Moffitt JE. Allergic reactions to insect stings and bites. South Med J. 2003;96:1073–9.CrossRefGoogle Scholar
  48. More D, Nugent J, Hagen L, et al. Identification of allergens in the venom of the common stripped scorpion. Ann Allergy Asthma Immunol. 2004;93:493–8.CrossRefGoogle Scholar
  49. Muller 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;87:702–9.CrossRefGoogle Scholar
  50. Muller U, Helbling A, Berchtold E. Immunotherapy with honeybee venom and yellow jacket venom is different regarding efficacy and safety. J Allergy Clin Immunol. 1992;89:529–35.CrossRefGoogle Scholar
  51. Niedoszytko M, de Monchy J, van Doormaal JJ, et al. Mastocytosis and insect venom allergy: diagnosis, safety and efficacy of venom immunotherapy. Allergy. 2009;64:1237–45.CrossRefGoogle Scholar
  52. Oude Elberink JNK, deMonchy JGR, Kors JW, et al. Fatal anaphylaxis after a yellow jacket sting, despite venom immunotherapy, in two patients with mastocytosis. J Allergy Clin Immunol. 1997;100:11–5.CrossRefGoogle Scholar
  53. Parker JL, Santrach PJ, Dahlberg MJ, Yunginger JW. Evaluation of Hymenoptera-sting sensitivity with deliberate sting challenges: inadequacy of present diagnostic methods. J Allergy Clin Immunol. 1982;69:200.CrossRefGoogle Scholar
  54. Peternelj A, Silar M, Bajrovic N, et al. Diagnostic value of the basophil activation test in evaluating Hymenoptera venom sensitization. Wien Klin Wochenschr. 2009;121:344–8.CrossRefGoogle Scholar
  55. Regularly updated maps of the fire ant range and agriculture quarantine areas within the United States. Accessed 14 Mar 2018.
  56. Reisman RE. Insect sting allergy: the dilemma of the negative skin test reactor. J Allergy Clin Immunol. 2001;107:781.CrossRefGoogle Scholar
  57. Reisman RE. Unusual reactions to insect stings. Curr Opin Allergy Clin Immunol. 2005;5:355.CrossRefGoogle Scholar
  58. Reisman RE, Livingston A. Venom immunotherapy: 10 years of experience with administration of single venoms and 50 micrograms maintenance doses. J Allergy Clin Immunol. 1992;89:1189–95.CrossRefGoogle Scholar
  59. Reisman RE, Mueller U, Wypych J, Eliott W, Arbesman CE. Comparison of the allergenicity and antigenicity of yellow jacket and hornet venoms. J Allergy Clin Immunol. 1982;69:268–74. (III)CrossRefGoogle Scholar
  60. Rueff F, Przybilla B, Bilo MB, Muller U, Scheipl F, Aberer W, et al. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase – a study of the EAACI Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol. 2009;124:1047–54.CrossRefGoogle Scholar
  61. Rueff F, Przybilla B, Bilo MB, Muller U, et al. Predictors of side effects during build-up phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase. J Allergy Clin Immunol. 2010;126:105–11.CrossRefGoogle Scholar
  62. Sampson HA, Mendclson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380–4.CrossRefGoogle Scholar
  63. Schumacher MJ, Tveten MS, Egan NB. Rate and quantity of venom from honeybee stings. J Allergy Clin Immunol. 1994a;93:832–5.CrossRefGoogle Scholar
  64. Schumacher MJ, Tveten MS, Egen NB. Rate and quantity of delivery of venom from honeybee stings. J Allergy Clin Immunol. 1994b;93:831–5.CrossRefGoogle Scholar
  65. Schwartz HJ, Yunginger JW, Schwartz LB. Is unrecognized anaphylaxis a cause of sudden unexpected death? Clin Exp Allergy. 1995;25:866–70.CrossRefGoogle Scholar
  66. Severino MG, Campi P, Macchia D, Manfredi M, et al. European Polistes venom allergy. Allergy. 2006;61:860–3.CrossRefGoogle Scholar
  67. Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2008;121(2 Suppl):S402–7.CrossRefGoogle Scholar
  68. Simons PER, Sampson HA. Anaphylaxis epidemic: fact or fiction? J Allergy Clin Immunol. 2008;122:1166–8.CrossRefGoogle Scholar
  69. Simons FER, Frew AJ, Ansotegui IL, Bochner BS, Finkelman F, Golden DBK, et al. Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol. 2007;l20:S2–24.CrossRefGoogle Scholar
  70. Valentine M. Insect venom allergy: diagnosis and treatment. J Allergy Clin Immunol. 1984;73:299–304.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Allergy, Asthma and Immunology Associates, P.COmahaUSA
  2. 2.Division of Allergy and ImmunologyCreighton University College of MedicineOmahaUSA
  3. 3.Creighton UniversityOmahaUSA
  4. 4.Department of Pediatrics/Allergy Asthma & Immunology Center of AlaskaUniversity of WashingtonAnchorageUSA
  5. 5.WWAMI School of Medical EducationUniversity of AlaskaAnchorageUSA

Section editors and affiliations

  • Dennis K. Ledford
    • 1
  1. 1.Division of Allergy & Immunology, Dept. of Internal MedicineUniversity of South Florida Morsani College of Medicine, James A Haley Veterans' Hospital, Asthma and Immunology Associates of Tampa BayTampaUSA

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