Leukotriene modifiers and Churg-Strauss syndrome - Adverse effect or response to corticosteroid withdrawal?

Zafirlukast, montelukast and pranlukast are all cysteinyl leukotriene recep tor antagonists that have recently been approved for the treatment of asthm a. Within 6 months of zafirlukast being made available on the market, 8 pat ients who received the agent for moderate to severe asthma developed eosino philia, pulmonary infiltrates, cardiomyopathy and other signs of vasculitis ; the syndrome that these patients developed was characteristic of the Chur g-Strauss syndrome. All of the patients had discontinued systemic corticost eroid use within 3 months of presentation and all developed the syndrome wi thin 4 months of zafirlukast initiation. The syndrome dramatically improved in each patient upon reinitiation of corticosteroid therapy. Since the initial report, there have been multiple similar cases reported t o the relevant pharmaceutical companies and to federal drug regulatory agen cies in association with zafirlukast as well as with pranlukast, montelukas t, and with use of high doses of inhaled corticosteroids, thus leading to a n increased incidence rate of the Churg-Strauss syndrome. Many potential me chanisms for the association between these drugs and the Churg-Strauss synd rome have been postulated including: increased syndrome reporting due to bi as; potential for allergic drug reaction; and leukotriene imbalance resulti ng from leukotriene receptor blockade. However, careful analysis of all rep orted cases suggests that the Churg-Strauss syndrome develops primarily in those patients taking these asthma medications who had an underlying eosino philic disorder that was being masked by corticosteroid treatment and unmas ked by novel asthma medication-mediated corticosteroid withdrawal, similar to the forme fruste of the Churg-Strauss syndrome. It remains unclear what the exact mechanism for this syndrome is and whethe r this represents an absolute increase in cases of vasculitis, but it appea rs that none of the asthma medications implicated in leading to the develop ment of Churg-Strauss syndrome was directly causative of the syndrome. Thes e agents remain well tolerated and effective medications for the treatment of asthma, although physicians must be wary for the signs and symptoms of t he Churg-Strauss syndrome, particularly in patients with moderate to severe asthma in whom corticosteroids are tapered.