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

1. 1. 
      
2. Ulugbek B. Nurmatov^1,*, 
3. Edmund Rhatigan², 
4. F. Estelle R. Simons³ and
5. Aziz Sheikh^1,4

7. Allergy

   Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.) doi: 10.1111/all.12672

Abstract

Background

Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release.

Objectives

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five databases, three trial repositories and contacted an international panel of experts to identify published and unpublished trials, enrolling a total of 71 patients (63 adults).

Results

36 potentially relevant studies were identified. Of these, five crossover trials met the eligibility criteria. 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 RCTs were historic (reported from 1983-93), small (enrolling 8-15 patients), and used agents and/or dosing regimens that are now uncommonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found four 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 of 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.

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