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

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.     

A case of sudden cardiac death due to isolated eosinophilic coronary arteritis

Spontaneous coronary artery dissection is a very rare event and occurs most often in young women following childbirth. It is also known as a rare focal complication in Churg-Strauss syndrome. Here, we present the case of a 43-year-old woman who died after spontaneous dissection of all three coronary arteries. The microscopic examination of coronary vessels showed severe eosinophilic infiltrations, whereas all extracardiac (medium-vessel and large-vessel) arteries were intact and free of inflammatory cells. Her history did not reveal allergy, asthma, or eosinophilia. To the best of our knowledge, this is the first case of spontaneous coronary dissection involving all coronary arteries without a history of Churg-Strauss syndrome or hypereosinophilic syndrome.     

Inhaled corticosteroids and Churg-Strauss syndrome: a report of five cases.

Churg-Strauss syndrome is an eosinophil-associated, small vessel granulomatous vasculitis, characterized by late onset asthma, upper airways disease, eosinophilia, and clinical manifestations of systemic vasculitis. Several cases of Churg-Strauss syndrome have been recognized in patients treated with cysteinyl leukotriene-receptor antagonists and weaned off systemic corticosteroids. These cases have led to a general warning on the possible development of Churg-Strauss syndrome after taking cysteinyl leukotriene-receptor antagonists. The authors report five cases of Churg-Strauss syndrome in severe steroid dependent asthmatics in whom inhaled corticosteroids allowed systemic corticosteroid withdrawal. It is concluded that physicians should monitor patients carefully when severe asthma is controlled with any substance allowing withdrawal from (or even avoidance) of systemic corticosteroids. Case-control studies should identify more precisely the risk factors of Churg-Strauss syndrome.     

Churg-Strauss syndrome: clinical and serological features of 19 patients from a single Italian centre

OBJECTIVE: Churg-Strauss syndrome is a rare multisystem vasculitis of unknown aetiology. Due to the rarity of the disease, few single-centre case series have been described. The aim of this study was to evaluate a small series from a single Italian centre in order to describe the clinical features of the disease, the treatment and long-term follow-up. METHODS: Nineteen Churg-Strauss syndrome patients were selected from the medical records of all vasculitis patients attending the Immunology Unit at the Department of Internal Medicine of the University of Pisa in the decade between 1989 and 2000. Data were obtained retrospectively. RESULTS: All the patients had asthma and hypereosinophilia. As in other case series, the lungs, skin and peripheral nervous system were the most commonly involved organs. The majority of our patient received i.v. pulses of methylprednisolone followed by i.v. pulses of cyclophosphamide. The outcome and long-term follow-up were good. There were no fatalities observed in this series during the follow-up period. CONCLUSIONS: Churg-Strauss syndrome is a systemic vasculitis occurring in patients with a history of asthma and allergic rhinitis. The positive results of the treatment protocol used in this preliminary study deserve to be tested in controlled multicentre studies.     

Churg-Strauss syndrome with myocarditis manifesting as acute myocardial infarction with cardiogenic shock: case report and review of the literature

A patient with a two-year history of worsening asthma presented with chest pain and shortness of breath. She developed cardiogenic shock. Analysis of blood chemistry detected increased troponin I concentration. Her electrocardiographic changes were consistent with a diagnosis of anteroseptal myocardial infarction. However, angiography showed normal coronary arteries. Left ventriculography showed severe mitral regurgitation and global hypokinesis. Peripheral eosinophilia was detected. Subsequent endomyocardial biopsy showed myocarditis with prominent eosinophil and plasma cell components. Churg-Strauss syndrome was diagnosed based on her history of asthma, evidence of peripheral eosinophilia and results of endomycardial biopsy. Treatment with a high dose of corticosteroids was initiated. As symptoms of heart failure improved - without recurrence of cardiac and respiratory symptoms - the dose of corticosteroids was gradually reduced. Eight months after her original presentation, she developed urticarial lesions on her abdomen and legs, with muscle soreness but no other associated symptoms. She was treated with a combination of prednisone and dapsone. After the diagnosis of Churg-Strauss syndrome, the patient remained symptom free with a normal ejection fraction for 15 months while taking prednisone.     

Churg-Strauss Syndrome Associated with Montelukast Therapy

Churg-Strauss syndrome is a rare form of eosinophilic vasculitis associated with asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have recently been reported in asthmatic patients being treated with antileukotriene receptor antagonists. However, whether these drugs have a direct pathogenic role remains controversial. We describe two patients who developed Churg-Strauss syndrome after starting treatment with montelukast.     

Cholestatic hepatitis: an uncommon presentation of Churg-Strauss syndrome

Churg-Strauss syndrome is a rare form of severe vasculitis characterized by severe asthma and hypereosinophilia. Liver involvement is rare. We report a case of a woman with serious cholestatic hepatitis and vasculitis, without severe asthma. Marked hypereosinophilia and liver biopsy confirmed diagnosis. Churg-Strauss syndrome must be recognized because digestive involvement is very serious and affect the prognosis of this disease.     

白三烯拮抗剂与变应性肉芽肿性血管炎的关系

随着白三烯拮抗剂应用于哮喘治疗以来,国内外越来越多的文献报道了使用白三烯拮抗剂后出现变应性肉芽肿性血管炎的病例.本文就变应性肉芽肿性血管炎、白三烯拮抗剂及两者间关系的研究进展做了相应综述介绍.     

Left ventricular dysfunction in Churg-Strauss syndrome

Churg-Strauss syndrome is a rare disorder characterized by hypereosinophilia and a systemic vasculitis occurring inpatients with asthma and allergic rhinitis. Vasculitis commonly affects the lungs, the heart, the skin, and the peripheral nervous system. Cardiac involvement is characterized by acute and constrictive pericarditis, myocarditis and endocarditis, as well as ischemic cardiomyopathy. Endomyocardial fibrosis similar to Loeffler's syndrome has been rarely described. In the presented case, a 43 year old man with a history of allergy and asthma suffered from increasing dyspnea, fever, pulmonary infiltates and cardiomyopathy. Laboratory studies were notable for marked hypereosinophilia. In a bronchoscopic lavage and transbronchial biopsy eosinophilic infiltrates accompanied by vasculitis were found, Churg-Strauss syndrome was diagnosed. Echocardiogram showed endomyocardial deposits in the apex of the right ventricle, right ventricular function was normal particular in the basal segments. The left ventricle was slightly enlarged and left ventricular function was impaired. The diastolic mitral in-flow showed a restrictive pattern. Additionally, a pericardial effusion was observed without signs of tamponade. The patient received corticosteroids, cyclophosphamide and cardiomyopathy-specific therapy and showed a marked improvement after 4 months.     

A case of Churg-Strauss syndrome in which positive rheumatoid factor and MPO-ANCA preceded the development of clinical symptoms of vasculitis]

A 52-year-old man in whom bronchial asthma had been diagnosed in 1995 was admitted for the treatment of Churg-Strauss syndrome in June 1997. Positive tests MPO-ANCA and rheumatoid factor preceded the symptoms of vasculitis for several months. A skin biopsy revealed infiltration of eosinophils in the vessel walls, and the diagnosis of Churg-Strauss syndrome was confirmed. After systemic administration of corticosteroids, the symptoms other than mononeuritis improved markedly, and his MPO-ANCA and rheumatoid factor became negative. Rheumatoid factor and MPO-ANCA may be useful for the early diagnosis of Churg-Strauss syndrome in patients with bronchial asthma in which a well-controlled disease develops into an intractable condition.     

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.     

Pleural effusion in Churg-Strauss syndrome

A 33-year-old man with a two-year history of asthma and sinusitis presented with wheezing, pleuritis, bilateral pleural effusions, and patchy basilar infiltrates on chest roentgenogram. Laboratory studies revealed peripheral blood eosinophilia, and pulmonary function studies showed an obstructive pattern which was bronchodilator responsive. Thoracocentesis yielded an acidotic exudative effusion with low glucose, low C3, eosinophilia, and a markedly increased rheumatoid factor. Open lung biopsy revealed extensive eosinophilic interstitial pneumonitis with necrotizing eosinophilic vasculitis. Although pleural effusions are present in 29 percent of Churg-Strauss patients, these effusions have not been well described. This report describes the pleural fluid findings in a case of Churg-Strauss syndrome.     

Churg-Strauss syndrome with pericardial and myocardial involvement]

We report the case of a 63-year-old female diagnosed with Churg-Strauss syndrome with both pericardial tamponade and myocardial involvement with congestive heart failure. Allergic granulomatosis and angiitis (Churg-Strauss syndrome) is classically characterized by hypereosinophilia and systemic necrotizing vasculitis of medium and small arteries in patients with previous allergic rhinitis or bronchial asthma. Subsequently the disease has been shown to be associated with cardiac involvement and is responsible for higher morbidity and mortality. The literature for Churg-Strauss syndrome of the heart is reviewed and recent advances in the clinical management of the disease according to appropriate therapeutic strategies are recommended.     

Isolated oculomotor nerve palsy in Churg-Strauss syndrome

A 30-year-old man with bronchial asthma complained of horizontal diplopia. Partial oculomotor nerve palsy with restrictions of elevation and adduction, and mydriasis was observed in the left eye. Cranial magnetic resonance imaging demonstrated an infarct lesion in the territory of the left superior median mesencephalic branch of the posterior cerebral artery. Based on bronchial asthma, hypereosinophilia, mononeuropathy multiplex, pulmonary eosinophilia and positive perinuclear antineutrophil cytoplasmic antibody in the serum, the patient was diagnosed as having Churg-Strauss syndrome. This is the first case of oculomotor nerve palsy due to midbrain infarction associated with Churg-Strauss syndrome.     

Churg–Strauss syndrome (CSS) in a patient receiving pranlukast

Pranlukast is a cysteinyl leukotriene receptor I antagonist (LTRAs) approved for treatment of asthma in Japan since 1995. Compared to other LTRAs, such as zafilukast and montelukast, only few cases with Churg-Strauss syndrome (CSS) have been reported in association with treatment with pranlukast. We describe a 17-year-old Japanese male patient who developed CSS with a 13 month history of mild asthma receiving pranlukast for 11 months without systemic and/or inhaled corticosteroid administration prior to development of CSS. From the aspect of temporal relationship between treatment with pranlukast and development of CSS, a direct induction of CSS by pranlukast is suggested in our case.Abbreviations ANCA Antineutrophil cytoplasmic antibodies - CSS Churg–Strauss syndrome - LTRA Leukotriene receptor I antagonist     

Churg-Strauss syndrome revealed by acute abdominal pain.

We describe a 10-year-old girl with Churg-Strauss syndrome, who presented with acute abdominal pain, bloody diarrhea, and pulmonary infiltrates. She had a 6-year history of severe asthma. Bronchoalveolar lavage showed marked eosinophilia. She responded well to high-dose intravenous corticosteroid pulse therapy for 3 consecutive days, followed by oral steroids without developing major side effects. This case should remind pediatricians of the rare existence of this vasculitis in children. Relapse is not uncommon, and long-term careful supervision is necessary.     

Churg–Strauss syndrome presenting with massive pericardial effusion

We describe a case of Churg-Strauss syndrome (CSS) presenting with a massive pericardial effusion without overt myocardial dysfunction. A 60-year-old man was referred to our hospital because of exertional dyspnea and fever. Initial chest multidetector-row computed tomography showed a massive pericardial effusion. The presence of eosinophilia, infiltrates of both lungs, pathological evidence of necrotizing vasculitis associated with eosinophilic infiltration, and history of asthma fulfilled the criteria of CSS. Massive pericardial effusion can be the first manifestation of cardiac involvement in CSS.     

A case of Churg-Strauss syndrome: tissue diagnosis established by sigmoidoscopic rectal biopsy.

A case is presented of Churg-Strauss syndrome in a young man in whom the definitive diagnostic procedure was a full thickness sigmoidoscopic rectal biopsy, with submucosal sampling. Gastrointestinal changes in Churg-Strauss syndrome, a rare systemic illness characterised by asthma, blood and tissue eosinophilia, vasculitis, and granulomatous inflammation are common but poorly reported. The endoscopic and histopathological features of a case are described and emphasise the potential value of a limited sigmoidoscopy in establishing the diagnosis, when lower gastrointestinal symptoms are present.     

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Clinical Rheumatology - Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma....