Montelukast and Churg-Strauss syndrome

I read with interest the case report by Tuggey and Hosker where Churg-Strauss syndrome was associated with the use of montelukast in an asthmatic patient in whom there was no recent exposure to oral corticosteroid. However, it is worth noting that the patient was using a high dose of inhaled fluticasone propionate (1.5 mg/day) via a large volume spacer prior to the introduction of montelukast. In this respect, a large volume spacer has been shown to double the systemic bioavailability of fluticasone propionate compared with a metered dose inhaler, in terms of its propensity for adrenal suppression. In a dose ranging study in asthmatic patients a comparison was made between inhaled fluticasone propionate via a 750 ml large volume spacer (Volumatic) and oral prednisolone. Regression analysis showed significant (p<0.05) dose-response relationships with both drugs for suppression of peripheral blood eosinophils (fig 1), in keeping with their systemic bioavailability. At the highest doses studied for prednisolone (20 mg/day) and fluticasone propionate (2 mg/day nominal dose) there was a 1.5-fold (95% CI 0.8 to 2.7) greater suppression of blood eosinophils with prednisolone than with fluticasone although, as indicated by the confidence interval (which included unity), this did not represent a significant diVerence between the drugs. Our data are in keeping with those of Toogood et al who also showed dose related suppression of blood eosinophils with inhaled budesonide and oral prednisolone. It is therefore evident that a high dose of inhaled fluticasone via a spacer, as reported in the case of Tuggey and Hosker, might have been suppressing the eosinophil count and therefore masking previously undiagnosed Churg-Strauss syndrome prior to starting montelukast. Indeed, it has been shown in a previous meta-analysis of 13 studies that, in terms of relative systemic bioactivity for producing suppression of early morning plasma cortisol, 1 mg inhaled fluticasone is approximately equivalent to 10 mg oral prednisolone. The learning point here is that high doses of inhaled corticosteroid may exhibit suYcient systemic bioactivity as a class eVect to suppress previously undiagnosed Churg-Strauss syndrome in the same way as low doses of oral corticosteroids. Furthermore, the revised package insert for fluticasone propionate (as Flovent, GlaxoWellcome Inc, Research Triangle Park, North Carolina, USA) now has an insertion in the section on precautions and adverse reactions stating that “in rare cases patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with ChurgStrauss syndrome. These events usually but not always have been associated with the reduction and/or withdrawal of oral corticosteroids following the introduction of fluticasone propionate. A causal relationship between fluticasone propionate and these underlying conditions has not been established”. It is also diYcult to understand, in the case described by Tuggey and Hosker, how the introduction of montelukast may have precipitated Churg-Strauss syndrome and a peripheral eosinophilia, given that studies have shown montelukast actually to suppress the peripheral blood eosinophil count.