title: H1-antihistamines for primary mast cell activation syndromes: a systematic review.
abstract: BACKGROUND
  Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release.
  
  
  OBJECTIVE
  To assess the effectiveness and safety of orally administered H1 -antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments.
  
  
  METHODS
  We systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials.
  
  
  RESULTS
  A total of 36 potentially relevant studies were identified. Of these, five crossover trials, enrolling a total of 71 patients (63 adults), met the eligibility criteria. All five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H1 -antihistamine with placebo, two compared two different H1 -antihistamines, and one study compared H1 - and H2 -antihistamines with oral cromolyn sodium. Four of the five randomized controlled trials were historic (reported from 1983-1993), small (enrolling 8-15 patients), and used agents and/or dosing regimens that are now less commonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine, and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found 4 weeks of treatment with the second-generation H1 -antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation to elicit Darier's sign.
  
  
  CONCLUSIONS
  There is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness, and safety of second-generation H1 -antihistamines in treatment of primary MCAS.
authors.affiliation: Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK.
authors.forename: U B
authors.initials: UB
authors.lastname: Nurmatov
authors.affiliation: Victoria Hospital Kirkcaldy, NHS Fife, Kirkcaldy, Fife, UK.
authors.forename: E
authors.initials: E
authors.lastname: Rhatigan
authors.affiliation: Departments of Pediatrics and Child Health, and Immunology, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: F E R
authors.initials: FE
authors.lastname: Simons
authors.affiliation: Allergy and Respiratory Research Group, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK.|Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sheikh
mesh_terms: D019468:Disease Management; D006634:Histamine H1 Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008415:Mastocytosis / Q000175:diagnosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013577:Syndrome; D016896:Treatment Outcome
chemical_list: D006634:Histamine H1 Antagonists
keywords: H1-antihistamines; mastocytosis; primary mast cell activation syndrome; systematic review