To the Editor:
In their recent review (March 2000), Wechsler and coauthors stated that the relationship between montelukast and Churg-Strauss syndrome (CSS) is not a direct drug effect, but rather it arises from unmasking a previously existing condition via corticosteroid withdrawal. However, since the true background incidence of CSS in asthmatics remains unknown, the possibility 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 eases of CSS associated with leukotriene-modifying agents. Wechsler and Drazen reported that, as of July 1999, there had been at least 52 suspected eases of CSS associated with zafirlukast, 42 of which were confirmed by Zeneca (Wilmington, DE); and at least 52 suspected cases of CSS associated with montelukast, 36 of which were confirmed by Merck (Whitehouse Station, NJ). A recent presentation indicated that [is greater than] 100 eases of CSS have been reported to the US Food and Drug Administration, in association with the use of leukotriene modifiers.
Historically, there was no similar increase in the number of CSS cases when cromolyn was introduced for the treatment of perennial asthma in 1973. There was a report of a few eases that appeared to match the description of CSS. Unfortunately, no data were reported on the incidence of CSS for the years following the introduction of beclomethasone dipropionate and triamcinolone in this country. These drugs also were widely used as oral steroid-sparing agents. Perhaps their manufacturers could provide additional data on the 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. Of these, 59 cases were documented during the 2-year period from 1998 to 1999, and 90% of the cases were associated with drugs used to treat asthma, particularly leukotriene receptor antagonists. Indeed, in many cases there was documented evidence of reduction or withdrawal of oral corticosteroid therapy prior to the onset of the reaction. Although the reliability of reporting cases of CSS by general practitioners is questionable, it is important 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, although occasional case reports were noted.
In addition, cases of CSS have been observed in steroid-naive individuals. This possibility is also mentioned by the manufacturer 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) in these patients," would seem to be somewhat premature. Clearly, further study is imperative.
Correspondence to: James F. Donohue MD, FCCP Division of Pulmonary Medicine, CB #7020, University of North Carolina School of Medicine, Chapel Hill, NC 25514-9117
 Wechsler ME, Finn D, Gunawardena D, et al. Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma. Chest 2000; 117:708-713
 Wechsler ME, Drazen JM. Leukotriene modifiers and Churg-Strauss syndrome: an update [abstract]. Am J Respir Crit Care Med 2000; 161:A195
 Meyer 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, CA
 Sheffer AL, Rocklin RE, Goetzl EJ. Immunologic components of hypersensitivity reactions to cromolyn sodium. N Engl J Med 1975; 293:1220-1224
 Medicines Control Agency/Committee on Safety of Medicines. Leukotriene receptor antagonists: update on adverse reaction profiles. Curr Probl Pharmacovigil 1999; 25:13-20
 Katz RS, Papernick M. Zafirlukast and Churg-Strauss syndrome [letter]. JAMA 1998; 279:1949
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