title: Patients still reacting to a sting challenge while receiving conventional Hymenoptera venom immunotherapy are protected by increased venom doses.
abstract: BACKGROUND
  Up to 20% of patients allergic to Hymenoptera venom are not protected by conventional venom immunotherapy (VIT) with 100 microg of any single venom.
  
  
  OBJECTIVE
  We sought to evaluate the efficacy of an increased venom dose in patients allergic to Hymenoptera venom still reacting systemically to a sting challenge despite immunotherapy with 100 microg of venom every 4 weeks.
  
  
  METHODS
  In this retrospective study patients were included who still had reacted systemically to a sting challenge with a living bee or wasp despite VIT with a maintenance dose of 100 microg every 4 weeks. The maintenance dose was increased to 150 or 200 microg every 4 weeks, and a second sting challenge was performed. If a patient reacted again, the dose was further increased. Baseline mast-cell tryptase levels were assessed by using a fluoroenzyme immunoassay in stored patient sera.
  
  
  RESULTS
  While receiving a maintenance dose of 100 microg of venom every 4 weeks for 7 to 38 months, 18 patients reacted systemically to a bee sting and 22 reacted to a wasp sting. After an increase of the maintenance dose to 150 microg, 2 of 4 patients allergic to bee venom (BV) and 6 of 6 patients allergic to yellow jacket venom (YJV) no longer reacted systemically to the sting challenge. The respective rates of full protection were 13 of 14 and 15 of 16 in patients with an increase of the maintenance dose to 200 microg from the start. Of those 4 individuals not protected by the first dose increase, one patient allergic to BV (prior dose of 150 microg) and one patient allergic to YJV (prior dose of 200 microg) did not react systemically to a further sting challenge while receiving 200 microg of BV or 250 microg of YJV, respectively. One patient allergic to BV who had a systemic reaction to the sting challenge while receiving 150 microg was not protected after a dose increase to 200 microg; she later received a dose of 400 microg of BV, and no further sting challenge was performed. The patient allergic to BV who still reacted systemically after a first dose increase to 200 microg was a female patient with urticaria pigmentosa. She had repeated systemic adverse reactions to further BV immunotherapy, necessitating discontinuation of the treatment; however, she tolerated well VIT with 200 microg of YJV. In all other patients, no unusual adverse reactions to the increased venom doses were observed. Baseline serum tryptase levels were elevated above 13.5 microg/L (95th percentile in normal subjects) in 9 (28.1%) of 32 patients.
  
  
  CONCLUSIONS
  The majority of patients allergic to Hymenoptera venom who still reacted systemically to a sting challenge despite VIT with a dose of 100 microg every 4 weeks can be fully protected by an increased maintenance dose. This dose increase is well tolerated by most patients. The rather high proportion of patients with elevated baseline serum tryptase levels necessitates further investigation of a possible association between mastocytosis and treatment failure of conventionally dosed VIT.
authors.affiliation: Clinic and Policlinic for Dermatology and Allergology, University of Munich, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ruëff
authors.forename: A
authors.initials: A
authors.lastname: Wenderoth
authors.forename: B
authors.initials: B
authors.lastname: Przybilla
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001514:Bee Venoms / Q000276:immunology*; D001516:Bees; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007299:Insect Bites and Stings / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000097:blood; D053802:Tryptases; D014862:Wasp Venoms / Q000276:immunology*; D014863:Wasps
chemical_list: D001514:Bee Venoms; D014862:Wasp Venoms; D012697:Serine Endopeptidases; D053802:Tryptases