Leukotriene antagonists: Bystanders or causes of Churg-Strauss syndrome? * **

IN 1951, CHURG and Strauss (1) reported 13 cases of severe asthma with hypereosinophilia and pathologic evidence of necrotizing and granulomatous vasculitis, which was referred to as allergic granulomatosis and angiitis. The illnesses predated corticosteroid (CS) therapy for this disease, and all but 2 patients died. The major histologic features described were 1) tissue infiltration by eosinophils, 2) extravascular eosinophil granulomas, and 3) necrotizing vasculitis. The characteristic generalized granulomatous lesions suggested that these cases differed from periarteritis nodosa (as it was then called) and Wegener’s granulomatosis (1,2). Later, other allergic syndromes were proposed as more benign forms of allergic granulomatosis, while angiitis was regarded as the most malignant expression (2). In 1984, Lanham et al (3) emphasized that the then-designated Churg-Strauss syndrome (CSS) was best considered a clinicopathologic rather than a histopathologic diagnosis. They proposed 3 criteria: 1) asthma, 2) peak peripheral blood eosinophil count in excess of 1.5 10/L (1,500/mm), and 3) systemic vasculitis involving 2 or more extrapulmonary organs. They also proposed that CSS evolves in a phasic, developmental pattern, ie, from an initial allergic diathesis (usually allergic rhinitis), progressing into asthma, followed by peripheral blood eosinophilia, later eosinophilic tissue infiltrates, and, finally, reaching a terminal vasculitic stage. Pathologically, the allergic diathesis was believed to progress to CSS in 2 stages, the first characterized by eosinophilic infiltration in various organs and the second by actual necrotizing vasculitis and granuloma formation (4). Distinction between the earlier phase of eosinophilic infiltration and the later vasculitis stage is important both diagnostically and therapeutically (4-6). In 1995, the Churgs and colleagues (5) reaffirmed the concept of a phasic evolution of CSS. They reported 4 cases of asthma and eosinophilia with varying degrees of eosinophilic tissue infiltration, which either suggested or confirmed vasculitis (5). Corticosteroid therapy for asthma was believed to have partially or totally suppressed some of the manifestations in these cases. The incompletely evolved illnesses were labeled formes frustes CSS (5). Caution was raised about tapering of CS in steroid-dependent patients, thereby allowing the incomplete disease to fully develop. Incomplete CSS usually responds well to moderate dosages of CS, while the complete form requires larger dosages and, often, cytotoxic agents, and may be difficult to treat (5,6). Recently, Guillevin et al (6) reviewed clinical manifestations, prognostic factors, and long-term outcome of 96 CSS patients evaluated between 1963 and 1995. Among 80 patients who provided a detailed clinical history, 51 (64%) had evidence of allergy or atopy. At presentation, 94 (98%) of the 96 cases had asthma. The mean time lapse from onset of asthma to overt CSS was 8.9 10.9 years (range, 0-61 years). The 2 remaining patients developed asthma 6 and 12 months after onset of CSS. Various antigenic exposures or desensitization therapy for severe asthma presumably triggered the vasculitis in 22 (28%) of the 80 patients providing such data. In 8 (10%) cases, rapid discontinuation of oral CS preceded the onset of vasculitis within a few weeks or months. Of 60 survivors in long-term remission of CSS with asthma, 53 (88%) required permanent low-dosage oral CS (mean, 8.9 5.8 mg prednisone daily), and 7 (12%) were controlled with inhaled CS (6).