title: Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study.
abstract: OBJECTIVE
  The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms.
  
  
  METHODS
  Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured.
  
  
  RESULTS
  Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).
  
  
  CONCLUSIONS
  Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.
authors.affiliation: Department of Environmental Dermatology and Venereology, Medical University of Graz, Graz, Austria. peter.komericki@medunigraz.at
authors.forename: Peter
authors.initials: P
authors.lastname: Komericki
authors.forename: Georg
authors.initials: G
authors.lastname: Klein
authors.forename: Norbert
authors.initials: N
authors.lastname: Reider
authors.forename: Thomas
authors.initials: T
authors.lastname: Hawranek
authors.forename: Tanja
authors.initials: T
authors.lastname: Strimitzer
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Bettina
authors.initials: B
authors.lastname: Kranzelbinder
authors.forename: Werner
authors.initials: W
authors.lastname: Aberer
mesh_terms: D000284:Administration, Oral; D006631:Amine Oxidase (Copper-Containing) / Q000008:administration & dosage*; D001317:Austria; D018592:Cross-Over Studies; D003951:Diagnostic Errors / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005512:Food Hypersensitivity / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D015990:Placebo Effect; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D006632:Histamine; D006631:Amine Oxidase (Copper-Containing)