Montelukast and Churg-Strauss syndrome

Abstract

In the past few months, there have been several reports about zafirlukast and Churg-Strauss syndrome [1±3]. Montelukast is a new leukotriene receptor antagonist. We report a case of Churg-Strauss syndrome while the patient was on montelukast treatment.A 25-yr-old female nonsmoker with a 6-yr history of asthma and rhinitis was admitted to the author's hospital in December 1998. She had had fever of up to 398C, malaise, headache and chest discomfort for a week. She had been treated with inhaled budesonide or fluticasone, formoterol and terbutaline for the last 5 yrs (1993±1998). In January 1998, she was on prednisone for a few weeks. Subsequently, she did not receive any systemic corticosteroids. As her respiratory symptoms continued, she was started on montelukast treatment, 10 mg once daily, in August 1998. On admission, she was febrile and had a rash over her extremities. A chest radiograph showed bilateral basilar reticulonodular infiltrates over the left hilar area, and bilateral pleural effusion. The blood eosinophil count was 6310 9 cells . L -1 , and liver enzyme levels were slightly increased. The subsequent urinalyses performed after beginning corticoid treatment demonstrated proteinuria, and the serum creatinine level was normal. Arterial blood gas levels while breathing room air were: pH 7.45; arterial oxygen tension 5.6 kPa (42 mmHg); and arterial carbon dioxide tension 4.7 kPa (35 mmHg). The immunoglobulin E level was 655 IU . L -1 , and the sedimentation rate 75 mm . h -1 . Tests for cellular and perinuclear antineutrophil cytoplasm antibody and human immunodeficiency virus were negative. The electrocardiogram and echocardiogram showed no abnormalities. Thoracentesis disclosed an eosinophilic serous fluid with: pH 7.45; total protein concentration 43 g . mL -1 ; lactate dehydrogenase activity 152 IU . L -1 ; glucose concentration 159 mg . dL -1 ; amylase activity 20 IU . L -1 ; cholesterol concentration 42 mg . dL -1 ; triglyceride concentration 19 mg . dL -1 ; and interferon gamma activity 1.7 IU . mL -1 . Montelukast was discontinued and methylprednisolone (1 g . day -1 i.v. for 3 days, and 1 mg . kg -1 thereafter) and antibiotic treatment commenced. Fibreoptic bronchoscopy was performed. The bronchial appearance was normal and staining and culture of the bronchoalveolar fluid (BALF) were negative for bacteria, mycobacteria, viruses, Pneumocystis carinii and fungi. The BALF cell differential showed 61% eosinophils, 7% neutrophils and 24% lymphocytes. Transbronchial biopsy showed some interstitial eosinophils. The urine test for Legionella antigen was negative. The paranasal sinus radiograph was normal. Thoracoscopic lung biopsy showed interstitial and alveolar eosinophils, extravascular necrotizing granulomas and small and medium vessel vasculitis. All lung biopsy cultures were negative. The antibiotics were withdrawn. After commencing steroid treatment, the patient improved rapidly, the respiratory failure disappeared within 2 days and she remained afebrile. The eosinophil count decreased to 2.53...

Churg-Strauss Syndrome and Leukotriene-Modifying Agents

“…Many cases of CSS have been reported during postmarketing surveillance of zafirlukast, 12,21-28 pranlukast, 20,29 -31 and montelukast, 9,20,28,[32][33][34][35][36][37][38][39][40][41] but only 1 such case has been mentioned after zileuton therapy, 9 but has not yet been published as a case report. Communications have indicated that more than 100 cases of CSS associated with LTRA have been reported to the US Food and Drug administration, 42,43 while their manufacturers have independently added a warning to the drug labels and have even issued a letter to physicians.…”

Montelukast-Induced Adverse Drug Reactions: A Review of Case Reports in the Literature

“…Summarizing the case reports, the management of LTRA-induced CSS consisted of discontinuing the use of montelukast and the uptake of systemic corticosteroids, such as mometasone [20,32,34,37] and methylprednisolone [19,21,25,26,35]. Some authors managed CSS adding the immunosuppressive drugs cyclophosphamide and azathioprine to the steroids [21,26,32], while Villena et al [19] treated their patient with antibiotics and methylprednisolone.…”

“…Many patients were on salmeterol or salbutamol plus fluticasone propionate [19,21,24,26,27,32,38,39]. In some cases, the drugs taken by the patient included salbutamol, nedocromil, theophylline and beclomethasone [31].…”

“…In individuals suffering from asthma, LTRA-induced CSS commonly presents with a wide range of clinical signs, including fever, malaise, arthralgias, clinical jaundice, peripheral blood eosinophilia, eosinophilic hepatitis, scleritis and arthritis [19,20,21,22,23,24,25,26,27,28,29,30]. Pulmonary involvement can be prominent, and chest radiography can show mixed alveolar-interstitial eosinophilic (80%) infiltrates in the upper lobes [31].…”

The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study

“…Based on clinical observations, the most widely favoured hypothesis put forward so far to explain the potential link between LTRA and CSS stipulated that LTRA administration allows tapering of corticosteroids needed to treat the asthma, thereby coincidentally unmasking a latent form of CSS 6 8. However, that theory conflicted with reports of LTRA-associated CSS occurring in the absence of concomitant corticosteroid reduction,3 11 – 15 the overall modest corticosteroid-sparing effect of LTRA16 and the few similar observations made for drugs more potent at reducing oral corticosteroid doses such as inhaled corticosteroids 17 – 21. Most importantly, only rare observational studies sought to determine whether a real association exists between LTRA and CSS 22…”