The linkage between Churg-Strauss syndrome and leukotriene receptor antagonists: fact or fiction?

Abstract

Epidemiologic evidence has shown that the worldwide prevalence of asthma is increasing. The leukotriene receptor antagonists (LTRAs) represent a new class of therapy for asthma. They have been developed in the last decade and play a pivotal steroid-sparing role in treating the inflammatory component of asthma. Consequently, reports of Churg-Strauss syndrome (CSS), a rare form of systemic vasculitis, have been recognized as a potential side effect in individuals with moderate to severe asthma on LTRA therapy. The serious nature of this disorder is worthy of prompt recognition by clinicians and aggressive therapy to avoid the subsequent longstanding effects of vasculitis. To validate the postulated linkage between the LTRAs and CSS, this review comprehensively evaluates reported cases in the literature and supports a pathophysiological relationship between the LTRAs and the development of CSS.

Figure 1

Biochemical pathways of the formation and action of the leukotrienes and sites of action of leukotriene modifying drugs. Source: Drazen JM, Israel E, O’Byrne PM. 1999. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med, 340:197–206. Reproduced with permission from the Massachusetts Medical Society. Copyright © 2005 Massachusetts Medical Society. All rights reserved.

Figure 2

Potential sites and effects of cysteinyl leukotrienes relevant to a pathophysiological role in asthma. Source: Hay DWP, Torphy TJ, Undem BJ. 1995. Cysteinyl leukotrienes in asthma: old mediators up to new tricks. Trends Pharmacol Sci, 16:304–9. Reproduced with permission from Elsevier. Copyright © 2005 Elsevier.

Figure 3

Categorization of cases based on the categories described by Masi and Hamilos (2002). Category A is when Churg-Strauss syndrome (CSS) manifestations began while on leukotriene receptor antagonists (LTRAs), but in the absence of glucocorticosteroid (GCS) therapy or without any basic change in the asthma management. Category B is when CSS manifested after receiving a LTRA in the setting of either tapering or discontinuing oral or inhaled GCS therapy. Category C is when LTRAs were started in the course of latent CSS, even without any concurrent GCS therapy or tapering/discontinuation of oral or inhaled GCS. Category D is when LTRAs were started in the course of latent CSS and GCS were being tapered or discontinued.