Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma

STUDY OBJECTIVES: We previously reported eight patients who developed Churg-Strauss syndrome in association with zafirlukast treatment for asthma and postulated that the syndrome resulted from unmasking of a previously existing condition due to corticosteroid withdrawal and not from a direct drug effect. The availability of montelukast, a new leukotriene receptor antagonist with a different molecular structure, permitted us to test this hypothesis. Our goals were to ascertain whether the Churg-Strauss syndrome developed in patients taking montelukast and other novel asthma medications, and to describe potential mechanisms for the syndrome. DESIGN: Case series. SETTING: Outpatient and hospital practices of pulmonologists in the United States and Belgium. PATIENTS: Four adults (one man, three women) who received montelukast as treatment for asthma; two women who received salmeterol/fluticasone therapy, but not montelukast. RESULTS: Churg-Strauss syndrome developed in the four asthmatic patients who received montelukast. In each case, there was a long history of difficult-to-control asthma characterized by multiple exacerbations that had required frequent courses of oral systemic corticosteroids or high doses of inhaled corticosteroids for control. Two other asthmatics who received fluticasone and salmeterol but not montelukast therapy developed the same syndrome with tapering doses of oral or high doses of inhaled corticosteroids. CONCLUSIONS: The occurrence of Churg-Strauss syndrome in asthmatic patients receiving leukotriene modifiers appears to be related to unmasking of an underlying vasculitic syndrome that is initially clinically recognized as moderate to severe asthma and treated with corticosteroids. Montelukast does not appear to directly cause the syndrome in these patients.     

Churg-Strauss syndrome associated with pregnancy

Churg-Strauss syndrome, an uncommon condition, occurs even more rarely in association with pregnancy. One month postpartum, a 25-year-old Japanese woman was hospitalized for dyspnea, fever, diarrhea, and complaints of dysesthesia in the right lower limb and right lumbar and abdominal region. Marked eosinophilia was present. Symptoms of bronchial asthma had developed early in the pregnancy, which concluded with delivery of a healthy baby at 39 weeks of gestation. Churg-Strauss syndrome was diagnosed and prednisolone was administered with a good response leading to remission. Three years after the first pregnancy, low-dose steroid therapy was continued through another pregnancy. The patient delivered another healthy baby at 39 weeks of gestation, this time with no exacerbation of symptoms.     

Churg-Strauss syndrome associated with omalizumab

Reports have suggested that the leukotriene receptor antagonists may cause Churg-Strauss syndrome following the tapering of oral corticosteroids or even in patients not treated with corticosteroids. We report a patient not treated with long-term corticosteroids and who developed Churg-Strauss syndrome with myocarditis and central nervous system involvement following the initiation of omalizumab. Given the possible role of omalizumab in the development of this vasculitis in our patient, we recommend careful monitoring of the appearance of Churg-Strauss symptoms and rising eosinophil count in patients treated with omalizumab.     

变应性肉芽肿性血管炎

变应性肉芽肿性血管炎 ,是系统性血管炎变 ,以哮喘、坏死性血管炎、血管外肉芽肿、外周血嗜酸粒细胞增多和多器官组织嗜酸粒细胞浸润为特征。临床少见 ,根据组织病理确诊的病例统计 ,发生率约 2 4 / 10 0万人口。因首先由Ｃｈｕｒｇ和Ｓｔｒａｕｓｓ两位病理学家描述 ,通常又称Ｃｈｕｒｇ Ｓｔｒａｕｓｓ综合征 (Ｃｈｕｒｇ Ｓｔｒａｕｓｓｓｙｎｄｒｏｍｅ ,ＣＳＳ)1　病因和发病机制　　多数ＣＳＳ病因不明。有个案报道吸入变应原 ,如放线菌 ,以及使用别嘌呤醇、抗惊厥制剂等药物可诱发ＣＳＳ ,但极少见。自 1996年扎鲁斯特上市应用以来 …     

Churg-Strauss syndrome

Churg-Strauss syndrome is a rare diffuse vasculitis that is almost invariably accompanied by severe asthma. Although overall prognosis is good, and treatment with prednisone alone or in combination with immunosuppressive drugs is usually successful, severe asthma typically persists. Diffuse organ involvement of Churg-Strauss syndrome, especially cardiovascular and rare involvement of the CNS and renal system, suggests a poorer prognosis than usual, and can be fatal. The cause of Churg-Strauss syndrome is unknown, but its characteristic histological findings and association with asthma distinguish it from other vasculitides. Controversy surrounds the use of asthma drugs-especially antileukotrienes--and development of the disorder. We review the epidemiological evidence for an association of drug treatment with Churg-Strauss syndrome, the diverse diagnostic and pathological criteria for this syndrome, and treatment options.     

Churg-Strauss syndrome

Churg-Strauss syndrome is a systemic ANCA-associated vasculitis arising almost exclusively in patients with a pre-existent asthma. Common clinical manifestations are marked blood eosinophilia, asthma, chronic sinusitis, cardiomyopathy, pulmonary infiltrates, gastrointestinal complaints and a multiplex neuropathy. The morphological substrate is an eosinophilic necrotizing vasculitis.Other eosinophilic disorders such as parasitic diseases, allergies and idiopathic hyper-eosinophilic syndrome have to be excluded. The mainstay of therapy is high-dose corticosteroids with the addition of cytotoxic drugs in patients with poor prognosis.     

Churg-Strauss syndrome

PURPOSE OF REVIEW: Churg-Strauss syndrome is a small-vessel necrotizing vasculitis typically characterized by asthma, lung infiltrates, extravascular necrotizing granulomas and hypereosinophilia. The most recent clinical studies on its pathogenesis and therapeutic management are reviewed here. RECENT FINDINGS: French and Italian clinical studies found that the clinical characteristics of patients with Churg-Strauss syndrome differed according to their antineutrophil cytoplasmic autoantibody status: cardiomyopathy predominated in antineutrophil cytoplasmic autoantibody-negative patients while necrotizing glomerulonephritis was more often observed in antineutrophil cytoplasmic autoantibody-positive patients. These histologically documented findings suggest the existence of different Churg-Strauss syndrome subtypes, characterized by the predominance of distinct pathogenetic mechanisms. To date, following the therapeutic recommendations for Churg-Strauss syndrome (i.e. corticosteroids and, when required, immunosuppressants), patient outcomes are good, with 5-year survival exceeding 90%, but often with the need to continue low-dose corticosteroids to control residual asthma. SUMMARY: The precise pathogenetic mechanisms of Churg-Strauss syndrome are only partly elucidated. Recent results suggest that antineutrophil cytoplasmic autoantibodies are probably more involved in the vasculitic manifestations of Churg-Strauss syndrome (e.g. glomerulonephritis) whereas eosinophil tissue infiltration and associated cytotoxicity would be responsible for cardiomyopathy. If confirmed, these results could support individual therapeutic stratification according to the clinical pattern. Furthermore, some patients may benefit from new biologic therapies under development, for example antiinterleukin-5 or antiimmunoglobulin E monoclonal antibodies.     

Churg-Strauss综合征

Churg-Strauss综合征(Churg-Strauss syndrome,CSS)是一种血管炎性疾病,表现为全身小至中等血管坏死性血管炎、血管内外肉芽肿形成、外周血嗜酸粒细胞增多以及组织及血管周围嗜酸粒细胞浸润。该病又称为变应性肉芽肿血管炎,但国内外文献多以CSS描述本病。CSS发病率为0.5/10万~6     

Churg-Strauss syndrome

Churg-Strauss syndrome is a vasculitis associated with asthma and eosinophilia. Respiratory involvement is marked by generally severe and often steroid-dependent late-onset asthma associated with allergic rhinitis and sometimes nasal polyposis and recurrent sinusitis. Asthma generally precedes the systemic vasculitis by a few years. General signs, eosinophilic gastroenteritis, peripheral multiplex neuropathy, cutaneous vasculitis, nephropathy, or arthromyalgia, predominate. Cardiac involvement is often silent but of severe prognosis. The chest X-ray usually shows irregularly delimited and sometimes labile infiltrates. Perinuclear antineutrophil cytoplasmic autoantibodies (ANCA) are found in two-thirds of the patients and strongly suggest the diagnosis. Clinically, the diagnosis is established by the presence of asthma, peripheral eosinophilia > 1.5 G/L, and systemic vasculitis involving at least two extra-pulmonary organs. Histological confirmation is usually necessary (nerve and muscle biopsy), showing small-vessel eosinophilic vasculitis, tissue infiltration with eosinophils, and eosinophilic granulomas. Treatment includes corticosteroids, which should be associated with immunosuppressive agents (cyclophosphamide) in severe cases.     

Churg-Strauss syndrome

Churg-Strauss syndrome was originally called "allergic granulomatosis and angiitis," describing the combination of eosinophilic inflammation, extravascular granulomas, and necrotizing vasculitis occurring in patients with severe asthma. It is now classified as a small-vessel vasculitis and, together with Wegener's granulomatosis and microscopic polyangiitis, as one of the vasculitides associated with antineutrophil cytoplasmic autoantibodies (ANCA). Glucocorticoid-sparing agents used in the treatment of asthma, such as leukotriene receptor antagonists, may unmask this particular form of vasculitis as oral glucocorticoids are withdrawn. ANCA occur in 40-75% of patients with active disease and typically react with myeloperoxidase. Patients' symptoms are defined by various degrees of eosinophilic inflammation and necrotizing vasculitis, which may affect any organ. On presentation, Churg-Strauss syndrome needs to be differentiated from other eosinophilic pneumonias, idiopathic hypereosinophilic syndrome, and Wegener's granulomatosis and microscopic polyangiitis. Churg-Strauss syndrome remains a rare disease with a poorly understood pathogenesis. Treatment consists primarily of glucocorticoids. Patients who have ANCA at the time of presentation should be treated according to the treatment principles for ANCA-associated vasculitides. However, the exact role of glucocorticoid-sparing immunosuppressive agents and treatment options for refractory disease remain poorly studied.     

Churg-Strauss syndrome after reduction of inhaled corticosteroid in a patient treated with pranlukast for asthma

Recently, various forms of Churg-Strauss syndrome (CSS) have been reported in association with the use of leukotriene receptor antagonists. A 53-year-old woman with a 5-year history of asthma associated with chronic sinusitis presented mononeuropathy, hypereosinophilia, and positive P-ANCA in October 1999. She had been treated with pranlukast (450 mg/day) and beclomethasone dipropionate (BDP) at a dose of 1,200 microg/day which had gradually been tapered to 800 microg/day over the previous 17 months. She was found to have CSS, and 60 mg/day of prednisolone was administered instead of pranlukast, resulting in an improvement of her symptoms and eosinophilia. Later, we confirmed that serum P-ANCA had been positive before the pranlukast treatment, but CSS vasculitis had not appeared at that time. We speculated that an underlying incomplete form of CSS was being masked in this case and that the reduction of inhaled corticosteroid might have been responsible for the unmasking of CSS.     

Montelukast and Churg-Strauss syndrome

The association of leukotriene receptor antagonists and Churg-Strauss Syndrome (CSS) has been recognised for several years. However, whether these drugs have a direct pathogenic role remains controversial. The present case describes an asthmatic patient, who developed severe obstructive symptoms and progressive heart failure after two sequential exposures to montelukast. As the patient exhibited a markedly raised blood eosinophil count with diffuse infiltrates on chest x-ray and signs of myocarditis, CSS was suspected. The disease was confirmed by open lung biopsy. The symptoms improved rapidly after administration of high dose immunosuppression with methylprednisolone and cyclophosphamide. This case is noteworthy because the time course of events strongly suggests a direct aetiological role for montelukast in the development of CSS. The pathophysiological mechanism of the association remains unknown.     

Incidence of Churg-Strauss syndrome in asthma drug users: a population-based perspective

OBJECTIVE: To estimate the incidence of Churg-Strauss syndrome (CSS) among a large population of asthma drug users. METHODS: A retrospective study was conducted among patients who had been dispensed asthma drugs at 3 managed care organizations. Adults who received >or =3 dispensings of an asthma drug during any consecutive 12-month period between January 1, 1995 and June 30, 2000 were identified. Information on patient age, gender, enrollment status, asthma drugs dispensed, and inpatient and outpatient diagnoses and procedures was obtained from automated databases. Chart reviews were performed on persons identified by combinations of diagnostic and billing codes indicative of CSS. A rheumatologist reviewed abstracted information on all subjects; those who met >or =2 American College of Rheumatology criteria for CSS were reviewed by 2 clinical experts. Each clinical expert independently rated the cases; disagreements were resolved by consensus. Cases classified as having "probable/definite" CSS were included in these analyses. The incidence of CSS was estimated overall and according to patient gender, age, and calendar year. RESULTS: From a population of 184,667 asthma drug users contributing 606,184 person-years of exposure, 21 incident cases of CSS were identified (overall incidence of 34.6 per million person-years; 95% confidence interval 21.4 to 53.0). Incidence rates did not differ by gender and age group. The incidence rates for 1995, 1996, 1997, 1998, 1999, and the first 6 months of 2000 were 0, 22, 52, 75, 14, and 14 per million person-years respectively. CONCLUSIONS: Results from this population-based study suggest a somewhat lower incidence of CSS in asthma drug users than previously reported and provides important information as to the risk of developing CSS from a population-based perspective.     

Treatment of Wolff-Parkinson-White syndrome associated with asthma

We performed division of accessory pathways in five asthma patients associated with Wolff-Parkinson-White (WPW) syndrome, for whom the administration of a beta-blocker for the tachycardia is contraindicated, and the administration of bronchodilators for the asthma attack may cause premature ventricular contractions. As a result, the tachycardic attacks disappeared postoperatively, both at rest and following administration of bronchodilators. Radical treatment of WPW syndrome by division the accessory pathway is considered to be necessary for the safe treatment of asthma.