H1-antihistamines for primary mast cell activation syndromes: a systematic review

BackgroundPrimary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release. ObjectivesTo assess the effectiveness and safety of orally administered H-1-antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments. MethodsWe systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials. ResultsA 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 H-1-antihistamine with placebo, two compared two different H-1-antihistamines, and one study compared H-1- and H-2-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 4weeks of treatment with the second-generation H-1-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. ConclusionsThere is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness, and safety of second-generation H-1-antihistamines in treatment of primary MCAS.