Skip to main content
SpringerLink
Log in

Hymenoptera Allergy and Mast Cell Activation Syndromes

  • Anaphylaxis and Drug Allergy (DA Khan and M Castells, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Mast cell activation syndrome (MCAS) can be diagnosed in patients with recurrent, severe symptoms from mast cell (MC)-derived mediators, which are transiently increased in serum and are attenuated by mediator-targeting drugs. When KIT-mutated, clonal MC are detected in these patients, a diagnosis of primary MCAS can be made. Severe systemic reactions to hymenoptera venom (HV) represent the most common form of anaphylaxis in patients with mastocytosis. Patients with primary MCAS and HV anaphylaxis are predominantly males and do not have skin lesions in the majority of cases, and anaphylaxis is characterized by hypotension and syncope in the absence of urticaria and angioedema. A normal value of tryptase (≤11.4 ng/ml) in these patients does not exclude a diagnosis of mastocytosis. Patients with primary MCAS and HV anaphylaxis have to undergo lifelong venom immunotherapy, in order to prevent further potentially fatal severe reactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157:215–25. Consensus paper from a group of experts defining criteria for diagnosis of mast cell disorders and proposing a global unifying classification of all mast cell disorders. These criteria help to diagnose mast cell activation syndromes.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Bilò BM, Bonifazi F. Epidemiology of insect-venom anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8:330–7.

    Article  PubMed  Google Scholar 

  3. Niedoszytko M, Bonadonna P, Oude Elberink JN, Golden DB. Epidemiology, diagnosis, and treatment of Hymenoptera venom allergy in mastocytosis patients. Immunol Allergy Clin North Am. 2014;34(2):365–81. Complete review about the management of patients with clonal mast cell disorders and Hymenoptera venom allergy, with particular attention of diagnosis and treatment of these patients.

    Article  PubMed  Google Scholar 

  4. Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol. 2011;128:147–52.

    Article  PubMed  Google Scholar 

  5. Valent P. Mast cell activation syndromes: definition and classification. Allergy. 2013;68:417–24.

    Article  CAS  PubMed  Google Scholar 

  6. Horny HP et al., editors. WHO classification of tumors of hematopoietic and lymphoid tissues. 4th ed. Lyon (France): IARC Press; 2008. p. 54–63.

    Google Scholar 

  7. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, Sanchez ML, Nunez R, Prados A, et al. A KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006;108(7):236672.

    Article  Google Scholar 

  8. Bonadonna P, Zanotti R, Caruso B, Castellani L, Perbellini O, et al. Allergen specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. J Allergy Clin Immunol. 2008;121:256–7.

    Article  CAS  PubMed  Google Scholar 

  9. Sonneck K, Florian S, Müllauer L, Wimazal F, Födinger M, Sperr WR, et al. Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: monoclonal mast cell activation syndrome. Int Arch Allergy Immunol. 2006;142:158–64.

    Article  PubMed  Google Scholar 

  10. Alvarez-Twose I, Gonzalez de Olano D, Sánchez-Muñoz L, Matito A, Esteban-López MI, Vega A, et al. Clinical, biological and molecular characteristics of systemic mast cell disorders presenting with severe mediator-related symptoms. J Allergy Clin Immunol. 2010;125:1269–78.

    Article  CAS  PubMed  Google Scholar 

  11. Alvarez-Twose I, Zanotti R, González-de-Olano D, Bonadonna P, Vega A, Matito A, et al. Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM. J Allergy Clin Immunol. 2014;133:520–8.

    Article  PubMed  Google Scholar 

  12. Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D, 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.

    Article  CAS  PubMed  Google Scholar 

  13. Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, et al. Demonstration of an aberrant mast cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood. 2007;110:2331–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Pardanani A, Chen D, Abdelrahman RA, Reichard KK, Zblewski D, Wood AJ, et al. Clonal mast cell disease not meeting WHO criteria for diagnosis of mastocytosis: clinicopathologic features and comparison with indolent mastocytosis. Leukemia. 2013;27:2091–4.

    Article  CAS  PubMed  Google Scholar 

  15. Picard M, Giavina-Bianchi P, Mezzano V, Castells M. Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clin Ther. 2013;35:548–62.

    Article  CAS  PubMed  Google Scholar 

  16. Gülen T, Hägglund H, Sander B, Dahlén B, Nilsson G. The presence of mast cell clonality in patients with unexplained anaphylaxis. Clin Exp Allergy. 2014;44:1179–87.

    Article  PubMed  Google Scholar 

  17. Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007;37:435–53.

    Article  CAS  PubMed  Google Scholar 

  18. Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014;69:1026–45.

    Article  CAS  PubMed  Google Scholar 

  19. Lieberman P, Camargo Jr CA, Bohlke K, Jick H, Miller RL, Sheikh A, et al. Epidemiology of anaphylaxis: findings of the American College of Allergy, Asthma and Immunology Epidemiology of Anaphylaxis Working Group. Ann Allergy Asthma Immunol. 2006;97:596–602.

    Article  PubMed  Google Scholar 

  20. Gonzalez de Olano D, Hoz de la Caballer B, Núñez López R, Sánchez Muñoz L, Cuevas Agustín M, Diéguez MC, et al. Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients with mastocytosis in Spain: a study of the Spanish Network on Mastocytosis (REMA). Clin Exp Allergy. 2007;37:1547–55.

    CAS  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. Gulen T, Hagglund H, Dahlen B, Nilsson G. High prevalence of anaphylaxis in patients with systemic mastocytosis: a single-centre experience. Clin Exp Allergy. 2014;44:121–9.

    Article  CAS  PubMed  Google Scholar 

  23. Ludolph-Hauser D, Ruëff F, Fries C, Schöpf P, Przybilla B. Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. Lancet. 2001;357(9253):361–2.

    Article  CAS  PubMed  Google Scholar 

  24. Oude Elberink JNK, de Moncky JGR, Kors JW, van Doormaal JJ, Dubois AE. Fatal anaphylaxis after a yellow jacket sting, despite venom immunotherapy, in two patients with mastocytosis. J Allergy Clin Immunol. 1997;99:153–4.

    Article  CAS  PubMed  Google Scholar 

  25. Rueff F, Placzek M, Przybilla B. Mastocytosis and Hymenoptera venom allergy. Curr Opin Allergy Clin Immunol. 2006;6:284–8.

    Article  PubMed  Google Scholar 

  26. Dubois AE. Mastocytosis and Hymenoptera allergy. Curr Opin Allergy Clin Immunol. 2004;4(4):291–5.

    Article  PubMed  Google Scholar 

  27. Gonzalez-de-Olano D, Alvarez-Twose I, Esteban-López MI, Sánchez-Muñoz L, de Durana MD, Vega A, et al. Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol. 2008;121:519–26.

    Article  PubMed  Google Scholar 

  28. Zanotti R, Bonadonna P, Bonifacio M, Artuso A, Schena D, Rossini, et al. Isolated bone marrow mastocytosis: an underestimated subvariant of indolent systemic mastocytosis. Haematologica. 2011;96:482–4.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Bonadonna P, Zanotti R, Müller U. Mastocytosis and insect venom allergy. Curr Opin Allergy Clin Immunol. 2010;10(4):347–53.

    Article  CAS  PubMed  Google Scholar 

  30. Alvarez-Twose I, Bonadonna P, Matito A, Zanotti R, González-de-Olano D, Sánchez-Muñoz L, et al. Systemic mastocytosis as a risk factor for severe Hymenoptera sting-induced anaphylaxis. J Allergy Clin Immunol. 2013;131(2):614–5.

    Article  PubMed  Google Scholar 

  31. Zanotti R, Lombardo C, Passalacqua G, Caimmi C, Bonifacio M, De Matteis G, et al. Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels. J Allergy Clin Immunol. 2015;136(1):135–9. Paper that shows that the absence of urticaria or angioedema in severe reactions to hymenoptera stings with hypotension may represent the most relevant factor in identifying patients with mastocytosis regardless of their serum tryptase.

    Article  CAS  PubMed  Google Scholar 

  32. van Anrooij B, van der Veer E, de Monchy JG, van der Heide S, Kluin-Nelemans JC, van Voorst Vader PC, et al. Higher mast cell load decreases the risk of Hymenoptera venom-induced anaphylaxis in patients with mastocytosis. J Allergy Clin Immunol. 2013;132(1):125–30.

    Article  PubMed  Google Scholar 

  33. Wimazal F, Geisser O, Shnawa P, Sperr WR, Valent P. Severe life-threatening or disabling anaphylaxis in patients with systemic mastocytosis: a single-center experience. Int Arch Allergy Immunol. 2011;157:399–405.

    Article  PubMed  Google Scholar 

  34. Castells MC, Hornick JL, Akin C. Anaphylaxis after hymenoptera sting: is it venom allergy, a clonal disorder, or both? J Allergy Clin Immunol Pract. 2015;3(3):350–5.

    Article  PubMed  Google Scholar 

  35. Mueller H. Diagnosis and treatment of insect sensitivity. J Asthma Resp. 1966;3:331.

    Article  CAS  Google Scholar 

  36. Bilò BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN, Birnbaum J, et al. Diagnosis of Hymenoptera venom allergy. Allergy. 2005;60:1339–49.

    Article  PubMed  Google Scholar 

  37. Bonifazi F, Jutel M, Biló BM, Birnbaum J, Muller U. EAACI Interest Group on insect venom hypersensitivity. Prevention and treatment of hymenoptera venom allergy: guidelines for clinical practice. Allergy. 2005;60:1459–70.

    Article  CAS  PubMed  Google Scholar 

  38. Schafer T, Przybilla B. IgE antibodies to Hymenoptera venoms in the serum are common in the general population and are related to indications of atopy. Allergy. 1996;51:372–7.

    Article  CAS  PubMed  Google Scholar 

  39. Sturm GJ, Schuster C, Kranzelbinder B, Wiednig M, Groselj-Strele A, Aberer W. Asymptomatic sensitization to Hymenoptera venom is related to total immunoglobulin E levels. Int Arch Allergy Immunol. 2008;148:261–4.

    Article  PubMed  Google Scholar 

  40. Sturm GJ, Jin C, Kranzelbinder B, Hemmer W, Sturm EM, Griesbacher A, et al. Inconsistent results of diagnostic tools hamper the differentiation between bee and vespid venom allergy. PLoS One. 2011;6:e 20842.

    Article  CAS  Google Scholar 

  41. Hemmer W, Focke M, Kolarich D, Wilson IB, Altmann F, Wohrl S, et al. Antibody binding to venom carbohydrates is a frequent cause for double positivity to honeybee and yellow jacket venom in patients with stinging-insect allergy. J Allergy Clin Immunol. 2001;108:1045–52.

    Article  CAS  PubMed  Google Scholar 

  42. Sturm GJ, Kranzelbinder B, Schuster C, Sturm EM, Bokanovic D, Vollmann J, et al. Sensitization to Hymenoptera venoms is common, but systemic sting reactions are rare. J Allergy Clin Immunol. 2014;133:1635–43.

    Article  CAS  PubMed  Google Scholar 

  43. Przybilla B, Rueff F. Insect stings: clinical features and management. Dtsch Arztebl Int. 2012;109:238–48.

    PubMed Central  PubMed  Google Scholar 

  44. Severino M, Campi P, Macchia D, Manfredi M, Turillazzi S, Spadolini I, et al. European Polistes venom allergy. Allergy. 2006;61:860–3.

    Article  CAS  PubMed  Google Scholar 

  45. Bonadonna P, Caruso B, Labardi D, Dama A, Senna G, Passalacqua G. Treatment with American Polistes venom was ineffective in an Italian patient allergic to European Polistes. Allergy. 2007;62(8):966–7.

    Article  CAS  PubMed  Google Scholar 

  46. Bonadonna P, Zanotti R, Melioli G, Antonini F, Romano I, Lenzi L, et al. The role of basophil activation test in special populations with mastocytosis and reactions to hymenoptera sting. Allergy. 2012;67:962–5.

    Article  CAS  PubMed  Google Scholar 

  47. Bonadonna P, Gonzalez-de-Olano D, Zanotti R, Riccio A, De Ferrari L, Lombardo C, et al. Venom immunotherapy in patients with clonal mast cell disorders: efficacy, safety, and practical considerations. J Allergy Clin Immunol Pract. 2013;1:474–8.

    Article  PubMed  Google Scholar 

  48. Müller UR. Recombinant Hymenoptera venom allergens. Allergy. 2002;57:570–6.

    Article  PubMed  Google Scholar 

  49. Incorvaia C, Mauro M, Pravettoni V, Pucci S. Hypersensitivity to Hymenoptera venom: advances in diagnosis and implications for treatment. Recent Patents on Inflammation & Allergy Drug Discovery 2011, 5, 128–135 (A)

  50. Kosnik M, Korosec P. Importance of basophil activation testing in insect venom allergy. Allergy Asthma Clin Immunol. 2009;5(1):11.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Golden DB, Tracy JM, Freeman TM, Hoffman DR. Negative venom skin test results in patients with histories of systemic reaction to a sting. J Allergy Clin Immunol. 2003;112:495–8.

    Article  PubMed  Google Scholar 

  52. Kranke B, Sturm G, Aberer W. Negative venom skin test results and mastocytosis. J Allergy Clin Immunol. 2004;113:180–1.

    Article  PubMed  Google Scholar 

  53. Haeberli G, Bronnimann M, Hunziker T, Muller U. Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy. Clin Exp Allergy. 2003;33:1216–20.

    Article  CAS  PubMed  Google Scholar 

  54. Kors JW, van Doormaal JJ, de Monchy JG. Anaphylactoid shock following Hymenoptera sting as a presenting symptom of systemic mastocytosis. J Intern Med. 1993;233(3):255–8.

    Article  CAS  PubMed  Google Scholar 

  55. Gonzalez-de-Olano D, Alvarez-Twose I, Morgado JM, Lopez MI, Castro AV, Diaz D, et al. Evaluation of basophil activation in mastocytosis with Hymenoptera venom anaphylaxis. Cytometry B Clin Cytom. 2011;80:167–75.

    Article  CAS  PubMed  Google Scholar 

  56. Bidad K, Nawijn MC, van Oosterhout AJ, van der Heide S, Elberink JN. Basophil activation test in the diagnosis and monitoring of mastocytosis patients with wasp venom allergy on immunotherapy. Cytometry B Clin Cytom. 2014;86:183–90.

    Article  PubMed  Google Scholar 

  57. Kosnik M. Anaphylaxis to venom without IgE antibody. Allergy. 2000;55:676–7.

    Article  CAS  PubMed  Google Scholar 

  58. Mosbech H, Christensen J, Dirksen A, Soborg M. Insect allergy. Predictive value of diagnostic tests: a three-year follow-up study. Clin Allergy 1986;16:433–40.25 venom immunotherapy

  59. Simons FER, Ardusso LR, Bilo MB, Dimov V, Ebisawa M, El-Gamal YM, et al. 2012 update: World Allergy Organization Guidelines for the assessment and management of anaphylaxis. Curr Opin Allergy Clin Immunol. 2012;12:389–99.

    Article  PubMed  Google Scholar 

  60. Ridolo E, Montagni M, Bonzano L, Savi E, Peveri S, Costantino MT, et al. How far from correct is the use of adrenaline auto-injectors? A survey in Italian patients. Emerg Med. 2015

  61. Song TT, Worm M, Lieberman P. Anaphylaxis treatment: current barriers to adrenaline auto-injector use. Allergy. 2014;69(8):983–91.

    Article  CAS  PubMed  Google Scholar 

  62. Niedoszykto M, DeMonchy J, vanDoormal JJ, Jassem E, Oude Elberink JNG. Mastocytosis and insect venom allergy: diagnosis, safety and efficacy of venom immunotherapy. Allergy. 2009;64:1237–45.

    Article  Google Scholar 

  63. Incorvaia C, Frati F, Dell’Albani I, Robino A, Cattaneo E, Mauro M, et al. Safety of hymenoptera venom immunotherapy: a systematic review. Expert Opin Pharmacother. 2011;12:2527–32.

    Article  CAS  PubMed  Google Scholar 

  64. Simioni L, Vianello A, Bonadonna P, Marcer G, Severino M, Pagani M, et al. Efficacy of venom immunotherapy given every 3 or 4 months: a prospective comparison with the conventional regimen. Ann Allergy Asthma Immunol. 2013;110:51–4.

    Article  CAS  PubMed  Google Scholar 

  65. Cifuentes L, Vosseler S, Blank S, Seismann H, Pennino D, et al. Identification of Hymenoptera venom-allergic patients with negative specific IgE to venom extract by using recombinant allergens. J Allergy Clin Immunol. 2014;133(3):909–10.

    Article  CAS  PubMed  Google Scholar 

  66. Bilò BM, Bonifazi F. Hymenoptera venom immunotherapy. Immunotherapy. 2011;3(2):229–46.

    Article  PubMed  Google Scholar 

  67. Engler RJ, Davis WS. Rush Hymenoptera venom immunotherapy: successful treatment in a patient with systemic mast cell disease. J Allergy Clin Immunol. 1994;94:556–9.

    Article  CAS  PubMed  Google Scholar 

  68. Galera C, Soohun N, Zankar N, Caimmi S, Gallen C, Demoly P. Severe anaphylaxis to bee venom immunotherapy: efficacy of pretreatment and concurrent treatment with omalizumab. J Investig Allergol Clin Immunol. 2009;19:225–9.

    CAS  PubMed  Google Scholar 

  69. Kontou-Fili K. High omalizumab dose controls recurrent reactions to venom immunotherapy in indolent systemic mastocytosis. Allergy. 2008;63:376–8.

    Article  CAS  PubMed  Google Scholar 

  70. Reimers A, Müller U. Fatal outcome of a vespula sting in a patient with mastocytosis after specific immunotherapy with honey bee venom. Allergy Clin Immunol Int J WAO Org. 2005;17:68–70.1.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy Unit, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale Stefani 1, 37126, Verona, Italy

    Patrizia Bonadonna & Carla Lombardo

  2. Section of Hematology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata di Verona, Piazzale L.A. Scuro, 10-37134, Verona, Italy

    Massimiliano Bonifacio & Roberta Zanotti

  3. Multidisciplinary Outpatients clinics for Mastocytosis (GISM), Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

    Patrizia Bonadonna, Massimiliano Bonifacio, Carla Lombardo & Roberta Zanotti

Authors
  1. Patrizia Bonadonna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Massimiliano Bonifacio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carla Lombardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberta Zanotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrizia Bonadonna.

Ethics declarations

Conflict of Interest

Dr. Bonifacio reports grants from Novartis Farma and personal fees from Ariad Pharmaceuticals and Amgen. Drs. Bonadonna, Bonifacio, Lombardo, and Zanotti declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Anaphylaxis and Drug Allergy

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bonadonna, P., Bonifacio, M., Lombardo, C. et al. Hymenoptera Allergy and Mast Cell Activation Syndromes. Curr Allergy Asthma Rep 16, 5 (2016). https://doi.org/10.1007/s11882-015-0582-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-015-0582-5

Keywords

Search

Navigation