Churg-Strauss Syndrome and Leukotriene-Modifying Agents

Abstract

In Brief Churg-Strauss syndrome (CSS) is a primary systemic necrotizing vasculitis of unknown origin, which is typically characterized by the association of asthma and blood eosinophilia. Leukotriene-modifying agents include zileuton, a 5-lipoxygenase inhibitor, and 3 selective leukotriene type 1 receptor antagonists (LTRA: zafirlukast, montelukast, and pranlukast) that have all been approved for the treatment of persistent asthma. Since 1996, when the first LTRA became available, more than 100 cases of CSS possibly related to LTRA use have been recorded by the US Food and Drug administration, and more than 50 cases have been described in the literature. These CSS developed 2 days to 15 months after LTRA introduction. Their clinical and biologic manifestations were similar to those of CSS occurring independently of LTRA use; however, the former may develop more often cardiomyopathy, but neuropathy and anticytoplasmic autoantibodie positivity less frequently than in the latter form of CSS. Notably, outcome after LTRA discontinuation and under systemic steroid therapy was usually good. These cases of CSS may result from the unmasking of an underlying incipient “forme fruste” of the vasculitis, during the steroid withdrawal or tapering made possible by LTRA therapy, or from a direct causal role of LTRA. Pertinently, these hypotheses are not exclusive and, until further studies clarify this point, the wisest strategy seems to be to discontinue or avoid their use in CSS patients, to carefully monitor asthmatic patients taking these drugs and to remember that CSS onset may resemble a worsening of persistent mild or severe asthma. Leukotriene-modifying agents, mainly leukotriene type 1 receptor antagonists (montelukast, zafirlukast, and pranlukast), have become part of the standard armamentarium in antiasthma therapy. Although premarketing studies have shown their safety, some concern about the risk of Churg-Strauss syndrome being triggered by these agents has progressively emerged, in light of the increasing frequency of cases being reported. We have critically reviewed the literature and explain why this potential, but controversial, risk has incited manufacturers to add a warning to the drug labels.