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Montelukast and Churg-Strauss Syndrome

2001; Elsevier BV; Volume: 119; Issue: 2 Linguagem: Inglês

10.1378/chest.119.2.668

1931-3543

James F. Donohue,

Eosinophilic Disorders and Syndromes

To the Editor: In their recent review (March 2000), Wechsler andcoauthors1Wechsler ME Finn D Gunawardena D et al.Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma.Chest. 2000; 117: 708-713Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar stated that the relationship betweenmontelukast and Churg-Strauss syndrome (CSS) is not a direct drugeffect, but rather it arises from unmasking a previously existingcondition via corticosteroid withdrawal. However, since the truebackground incidence of CSS in asthmatics remains unknown, thepossibility that leukotriene modifiers have a causative role in CSS, perhaps due to an allergic response, remains equally plausible. First, there seems to be a high total number of cases of CSS associatedwith leukotriene-modifying agents. Wechsler and Drazen2Wechsler ME Drazen JM Leukotriene modifiers and Churg-Strauss syndrome: an update [abstract].Am J Respir Crit Care Med. 2000; 161: A195Google Scholarreported that, as of July 1999, there had been at least 52 suspectedcases of CSS associated with zafirlukast, 42 of which were confirmed by, Zeneca (Wilmington, DE); and at least 52 suspected cases of CSSassociated with montelukast, 36 of which were confirmed by Merck(Whitehouse Station, NJ). A recent presentation indicated that > 100cases of CSS have been reported to the US Food and Drug Administration, in association with the use of leukotriene modifiers.3Meyer RJ. Current new/update FDA Division pulmonary and allergy drug products. Presented at: 36th annual meeting of the American Academy of Allergy, Asthma and Immunology; March 5, 2000; San Diego, CAGoogle Scholar Historically, there was no similar increase in the number of CSScases when cromolyn was introduced for the treatment of perennialasthma in 1973. There was a report of a few cases that appeared tomatch the description of CSS.4Sheffer AL Rocklin RE Goetzl EJ Immunologic components of hypersensitivity reactions to cromolyn sodium.N Engl J Med. 1975; 293: 1220-1224Crossref PubMed Scopus (57) Google Scholar Unfortunately, no data werereported on the incidence of CSS for the years following theintroduction of beclomethasone dipropionate and triamcinolone in thiscountry. These drugs also were widely used as oral steroid-sparingagents. Perhaps their manufacturers could provide additional data onthe occurrence of CSS with these agents. Data from the United Kingdom, from the Medicines Control Agency Committee on Safety of Medicines, reported 63 cases of CSS through the, Yellow Card Scheme since 1963.5Medicines Control Agency/Committee on Safety of Medicines Leukotriene receptor antagonists: update on adverse reaction profiles.Curr Probl Pharmacovigil. 1999; 25: 13-20Google Scholar Of these, 59 caseswere documented during the 2-year period from 1998 to 1999, and 90% ofthe cases were associated with drugs used to treat asthma, particularlyleukotriene receptor antagonists. Indeed, in many cases there wasdocumented evidence of reduction or withdrawal of oral corticosteroidtherapy prior to the onset of the reaction. Although the reliability ofreporting cases of CSS by general practitioners is questionable, it isimportant to note that other steroid-sparing agents introduced in the, United Kingdom during that period, such as beclomethasone, budesonide, and salmeterol, were not accompanied by a similar rise in CSS, althoughoccasional case reports were noted. In addition, cases of CSS have been observed in steroid-naïveindividuals.6Katz RS Papernick M Zafirlukast and Churg-Strauss syndrome [letter].JAMA. 1998; 279: 1949Crossref PubMed Scopus (87) Google Scholar This possibility is also mentioned by themanufacturer in the package insert. In light of the above, the concluding statement by Wechsler et al, that"montelukast does not appear to directly cause the syndrome (CSS) inthese patients," would seem to be somewhat premature. Clearly, further study is imperative.