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Leukotriene receptor antagonist therapy and Churg–Strauss syndrome: culprit or innocent bystander?
  1. Richard Beasley1,
  2. Susan Bibby1,
  3. Mark Weatherall2
  1. 1
    Medical Research Institute of New Zealand, Wellington, New Zealand
  2. 2
    University of Otago Wellington, Wellington, New Zealand
  1. Professor Richard Beasley, Medical Research Institute of New Zealand, PO Box 10055, Wellington 6143, New Zealand; Richard.Beasley{at}

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Randomised controlled trials can provide strong evidence of the efficacy (or lack) of new drug treatments as well as the occurrence of common side effects.1 However, clinical safety issues can arise after new medications receive regulatory approval, particularly in relation to rare serious adverse events.2 Investigation of rare adverse events is often fraught with difficulty, leading to uncertainty, particularly when there is conflicting evidence from research utilising different methodologies. One recent example is the observed association between leukotriene receptor antagonist (LTRA) therapy, used in the treatment of asthma, and Churg–Strauss syndrome (CSS), a vasculitis of uncertain aetiology (also known as allergic granulomatous angiitis). CSS is certainly both rare and serious, with a background incidence of 3 per million per year in the general population, and a 1 year mortality rate of 7%.35

Soon after the introduction of LTRAs (zafirlukast, pranlukast and montelukast), numerous case reports and case series were published of patients who developed CSS after starting this therapy.613 The temporal relationship between the introduction of LTRA therapy and the development of CSS suggested a possible causal relationship. An underlying mechanism was proposed whereby LTRA therapy may lead to an imbalance in leukotriene receptor stimulation, resulting in unopposed activity of LTB4, a potent chemoattractant for eosinophils as well as neutrophils, which could potentially lead to eosinophilic tissue infiltration and the initiation of systemic vasculitis.14 15

A feature of a number of the case reports was that the introduction of the LTRA allowed significant oral steroid reduction, suggesting that this therapy may have unmasked previously existing CSS that had been suppressed by the steroids prescribed for asthma. Another observation was that some cases had severe or unstable asthma at the time LTRA therapy was introduced, which arguably may have represented …

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  • Competing interests: RB has received fees for consulting and speaking and reimbursement for attending symposia from Astra Zeneca, GlaxoSmithKline and Novartis. SB and MW have no conflict of interest to declare.

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