Wechsler M E, Garpestad E, Flier S R, Kocher O, Weiland D A, Polito A J, Klinek M M, Bigby T D, Wong G A, Helmers R A, Drazen J M
Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
JAMA. 1998 Feb 11;279(6):455-7. doi: 10.1001/jama.279.6.455.
Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use of this drug increases, adverse events that occur at low frequency or in populations not studied in premarketing clinical trials may become evident.
To describe a clinical syndrome associated with zafirlukast therapy.
Case series.
Eight adults (7 women and 1 man) with steroid-dependent asthma who received zafirlukast.
Development of a clinical syndrome characterized by pulmonary infiltrates, cardiomyopathy, and eosinophilia following the withdrawal of corticosteroid treatment.
The clinical syndrome developed while patients were receiving zafirlukast from 3 days to 4 months and from 3 days to 3 months after corticosteroid withdrawal. All 8 patients developed leukocytosis (range, 14.5-27.6 x 10(9)/L) with eosinophilia (range, 0.19-0.71). Six patients had fever (temperature >38.5 degrees C), 7 had muscle pain, 6 had sinusitis, and 6 had biopsy evidence of eosinophilic tissue infiltration. The clinical syndrome improved with discontinuation of zafirlukast treatment and reinitiation of corticosteroid treatment or addition of cyclophosphamide treatment.
Development of pulmonary infiltrates, cardiomyopathy, and eosinophilia may have occurred independent of zafirlukast use or may have resulted from an allergic response to this medication. We suspect that these patients may have had a primary eosinophilic infiltrative disorder that had been clinically recognized as asthma, was quelled by steroid treatment, and was unmasked following corticosteroid withdrawal facilitated by zafirlukast.
扎鲁司特是一种强效白三烯拮抗剂，最近被批准用于治疗哮喘。随着该药物使用的增加，在上市前临床试验中未研究的低频率或特定人群中发生的不良事件可能会显现出来。
描述与扎鲁司特治疗相关的一种临床综合征。
病例系列。
8名患有激素依赖型哮喘的成年人（7名女性和1名男性），他们接受了扎鲁司特治疗。
在停用皮质类固醇治疗后，出现以肺部浸润、心肌病和嗜酸性粒细胞增多为特征的临床综合征。
该临床综合征在患者接受扎鲁司特治疗期间出现，时间为3天至4个月，以及在停用皮质类固醇治疗后的3天至3个月。所有8名患者均出现白细胞增多（范围为14.5 - 27.6×10⁹/L）并伴有嗜酸性粒细胞增多（范围为0.19 - 0.71）。6名患者发热（体温>38.5℃），7名患者有肌肉疼痛，6名患者有鼻窦炎，6名患者经活检有嗜酸性粒细胞组织浸润的证据。停用扎鲁司特治疗并重新开始皮质类固醇治疗或加用环磷酰胺治疗后，临床综合征有所改善。
肺部浸润、心肌病和嗜酸性粒细胞增多的发生可能与扎鲁司特使用无关，也可能是对该药物的过敏反应所致。我们怀疑这些患者可能患有原发性嗜酸性粒细胞浸润性疾病，临床上被诊断为哮喘，经类固醇治疗得到控制，在扎鲁司特促使停用皮质类固醇后病情显现。
