Onset Of Churg-Strauss Syndrome Research Articles

Clinical features and prognosis of Churg-Strauss syndrome

We studied the clinical features and prognosis of 11 patients with Churg-Strauss syndrome (CSS). Subjects included 1 man and 10 women with a mean age of 56.3 years. All subjects had a history of bronchial asthma prior to the onset of CSS. It was noted that the age of onset of bronchial asthma was high, and most of the patients had suffered from frequent and severe asthmatic attacks during the periods preceding the vasculitis. Skin tests and IgE RAST revealed that less than half of the subjects were atopic. Therefore it is considered that asthmatics with late onset and severe symptoms have a high risk for CSS, and poor control of asthmatic symptoms may contribute to the onset of the vasculitis. Eleven of 12 cases including 1 patient with a relapse were treated with PSL alone (9 cases) or PSL plus cyclophosphamide (2 cases). Three patients died of heart failure or central nerve involvement. Vasculitis was ameliorated in the other cases (75%). Seven patients received maintenance therapy with low-dose of PSL (5 cases) or cyclophosphamide (2 case). None suffered from relapse of vasculitis during maintenance therapy. Discontinuation of therapy in five cases resulted in a relapse in only one case 62 months after the cessation of low-dose PSL. Although maintenance therapy appears to be useful in some CSS patients, the significance and indications for maintenance therapy should be further clarified.

Churg-Strauss syndrome presenting as myositis following unaccustomed exercise

A 68-year-old woman with a 4 year history of bronchial asthma developed marked myalgia in the extremities following exercise to which she was unaccustomed. Examination on admission, 11 days after onset, revealed myalgia, muscular weakness and cutaneous hemorrhagic bullae. Blood tests revealed eosinophilia (9160/mm 3) and elevation of creatinine kinase and C-reactive protein. Muscle biopsy in the quadriceps femoris showed small vessel vasculitis and eosinophilic infiltration. Skin biopsy revealed leukocytoclastic vasculitis with neutrophilic and eosinophilic infiltration and fibrinoid necrosis. We diagnosed her as having Churg-Strauss syndrome (CSS). Corticosteroid treatment relieved her symptoms and resulted in normalization of the laboratory test results. Myositis is rare as an initial manifestation of CSS. The previous studies on immunological changes after eccentric exercise suggest that unaccustomed exercise could induce an increase in the serum level of interleukin-6 and trigger the onset of CSS.

Involvement of Regulatory T Cells in the Pathogenesis of Churg-Strauss Syndrome

Background: Churg-Strauss syndrome (CSS) is a rare systemic necrotizing vasculitis that develops in some asthma patients. However, it remains unknown what types of asthma patients can develop this condition. In addition, CSS patients experience eosinophilic pneumonia (EP) before the onset, but some asthma patients do not develop CSS following EP. Few studies have addressed the immunological differences in both cases. Additionally, it is well known that abnormality or failure of immunological tolerance by regulatory T cells (Treg) directly triggers the onset of autoimmune diseases. To elucidate the involvement of Treg in the difference in the pathogenesis of patients with and without CSS, the frequency of naturally occurring Treg (nTreg) and Treg which dominantly produce IL-10 and TGF-β (Tr1) was measured in peripheral blood. Methods: Mononuclear leukocytes were obtained from patients with asthma, asthma accompanying EP and CSS. The cells were stimulated with PMA and ionomycin in the presence of brefeldin A to generate and accumulate cytokines. Cytokines in the cells were detected after fixation and permeabilization of these cells. Tr1 cells were evaluated as CD4+CD25+ T cells dominantly producing IL-10 and TGF-β, and nTreg were also evaluated as CD4+CD25+ T cells expressing FOXP3, a master transcriptional factor. Results: There was a significantly greater number of nTreg in the peripheral blood of EP patients in comparison to both patients with asthma and whole CSS. However, no significant difference was observed regarding the number of nTreg when patients with CSS were divided into inactive and active stage. In contrast, the detection frequency of Tr1 remarkably decreased in active CSS, especially at the time of onset of CSS, in comparison with asthma, EP and inactive CSS, while there was no difference between EP and inactive CSS. Additionally, the ability of CD4+CD25– T cells (responder T cells) to generate IL-2 when stimulated with PMA and ionomycin sharply decreased in active CSS. Conclusion: In the patient who does not develop CSS even after repeat EP, the frequency of Tr1 and the ability of responder T cells to generate IL-2 do not decrease, but show a remarkable decrease in the EP patient who develops CSS. These findings strongly suggest that Tr1 is responsible for maintaining immunological tolerance in peripheral blood, while also inhibiting the onset of CSS from EP.

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

Background:There has been some concern that leucotriene receptor antagonists might precipitate the onset of Churg-Strauss syndrome (CSS). A study was undertaken to investigate the relationship between the leucotriene receptor antagonist...

A retrospective study of bronchial hyperresponsiveness in patients with asthma before the onset of Churg–Strauss syndrome

Asthma is one of the most common clinical symptoms in Churg-Strauss syndrome (CSS). However, it is not known how lung function and bronchial hyperresponsiveness (BHR) prior to the development of CSS differs from asthmatics do not develop CSS. This retrospective cohort study was conducted to predict the onset of CSS and facilitate diagnosis in the early phase of the disease. We examined 24 pre-CSS asthmatic patients and 294 non-CSS asthmatic patients for clinical features, percent forced expiratory volume at 1 second (%FEV1), BHR to acetylcholine, and evaluated eosinophils (%) in the peripheral blood at their first hospital visit for asthma treatment. All of the 24 pre-CSS patients had adult-onset asthma. The asthma of 87.5% of pre-CSS patients at the first hospital visit before the onset of CSS was severe and was complicated by sinusitis. The eosinophils (%) in the peripheral blood was significantly higher than in non-CSS asthmatic patients. The %FEV1 in both the patients with severe asthma and the patients who developed CSS was lower than in patients with mild or moderate asthma. However, BHR in pre-CSS patients was significantly better than in non-CSS patients with severe asthma and was as mild as in patients with mild asthma. Patients who developed CSS had clinically severe asthma before the onset of CSS. The severity of their asthma was related to airflow limitation and eosinophilic inflammation in the peripheral blood, but not to BHR. These findings should prove useful in future early diagnosis and treatment of CSS.

Responsabilité des antileucotriènes dans la survenue d'un syndrome de Churg et Strauss

Churg-Strauss syndrome is a systemic necrotizing vasculitis involving small and medium-sized vessels. Classic features include asthma and hypereosinophilia. Antineutrophil cytoplasm antibodies (ANCA) are detected in about 40% of patients. Churg-Strauss syndrome has been reported in patients receiving leukotriene modifiers for asthma, in particular, leukotriene receptor antagonists (LTRA) (montelukast, zafirlukast or pranlukast). Clinical manifestations cases do not differ in these cases from those in Churg-Strauss syndrome without antileukotriene exposure. It is increasingly less likely that LTRA is the direct cause of this syndrome in those patients, although this hypothesis has not been completely ruled out. In many patients, LTRA treatment is prescribed because of worsening asthma, which is an early sign of Churg-Strauss syndrome. LTRA for asthma patients should be prescribed with great care, especially in cases of atypical or rapidly aggravated asthma. The onset of Churg-Strauss syndrome in patients treated with LTRA usually requires that they stop this treatment. Prescription of LTRA In patients with Churg-Strauss syndrome should be discussed with specialists.

Asthma drug use and the development of Churg–Strauss syndrome (CSS)

Case reports suggest that leukotriene modifier use may be associated with the onset of Churg-Strauss syndrome (CSS). Using pooled data from two nested case-control studies, we examined the association between asthma drug use and the development of CSS. The study was performed in three US managed care organizations and a US national health plan with chart access and complete electronic pharmacy data, with a covered population of 13.9 million. There were 47 cases of possible or definite CSS and 4700 asthma drug user controls identified between January 1, 1995 and December 31, 2002. We examined exposure to asthma drugs in cases and controls, including leukotriene modifiers (6 cases and 202 controls), in the two to 6 months prior to the onset of adjudicated CSS. While the crude association between use of leukotriene modifiers and CSS was strong (odds ratio (OR) 4.00, 95% confidence interval (CI): 1.49-10.60), in a multivariable analysis controlling for use of oral corticosteroids, inhaled corticosteroids, and number of categories of asthma drugs dispensed, there was no significant association (OR 1.32, 95% CI: 0.44-3.96). Use of inhaled and oral corticosteroids, evaluated as markers of asthma severity, were associated with CSS (OR 3.07, 95% CI: 1.34-7.03 and OR 5.36, 95% CI: 2.51-11.45, respectively). No association was found between CSS and leukotriene modifiers after controlling for asthma drug use However, it is not possible to rule out modest associations with asthma treatments given CSS is so rare and so highly correlated with asthma severity, suggesting further investigation is warranted.

Initial Cutaneous Manifestations Consistent With Mononeuropathy Multiplex in Churg-Strauss Syndrome

Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis, is a rare entity that is characterized by systemic vasculitis in patients with a history of asthma. Patients with CSS show a marked peripheral blood eosinophilia, but the pathogenesis remains unknown. A retrospective review was performed in 9 cases of CSS in whom cutaneous findings were present as an initial manifestation. All 9 patients had purpura and petechiae as well as severe pain and paresthesias of the lower extremities. Four patients (44%) used leukotriene receptor antagonists to treat their asthma, and 3 (75%) of them developed CSS within 3 months. Five patients (56%) were positive for perinuclear antineutrophil cytoplasmic antibodies before therapy, but in all 5 the levels of perinuclear antineutrophil cytoplasmic antibody normalized. Serum IgE levels were elevated in all patients before treatment but decreased after treatment. Histologically, all patients demonstrated leukocytoclastic vasculitis and eosinophilic infiltration. Eight biopsy specimens (73%) revealed marked eosinophilia around the nerve fibers in the dermis. Palisading granulomas in association with vessel-based changes were present in 4 (36%) of 11 biopsy specimens. These characteristic cutaneous clinical patterns that are consistent with the presence of mononeuropathy multiplexes in the lower extremities may help physicians establish an earlier diagnosis. Both eosinophils and IgE, as well as perinuclear antineutrophil cytoplasmic antibodies to some degree, likely participate in skin lesion development in CSS. Furthermore, there appears to be a correlation between treatment with leukotriene receptor antagonists and the onset of CSS in some cases.

Leukotriene antagonists and the Churg-Strauss syndrome

Background and Objectives: Leukotriene antagonists (LTAs), or antileukotrienes, are a new group of anti-inflammatory drugs used for the treatment of asthma. They might substitute for or allow tapering of corticosteroids in asthmatic patients. These drugs have been associated with the development of Churg-Strauss syndrome (CSS), a rare form of vasculitic angiitis. It is unclear whether the development of CSS is a direct drug effect or an unmasking of a preexisting condition on withdrawal of steroids for asthma. We present a case of CSS in a patient treated with montelukast and review the literature to analyze the association between LTAs and the development of CSS. Method: We reviewed the literature using MEDLINE from February 1966 to October 2000. To the cases identified, we present an additional case of a patient who underwent a diagnostic lung biopsy. Results: Twenty-two case reports of patients receiving LTAs who developed CSS were identified. The onset of CSS occurred 2 days to 10 months after starting treatment with LTAs. All patients had received inhaled or oral steroids for asthma. The interval between the last oral corticosteroid treatment and CSS onset ranged from 3 days to 8 months. Conclusions: To date, there is no compelling evidence that the development of CSS in asthmatic patients receiving LTAs results from a direct drug effect. Rather, it appears that tapering of corticosteroids in these patients unmasks the multiorgan manifestations of the disease. We believe that the use of LTAs should not be influenced by the apparent increase in the incidence of CSS and that these are still safe drugs for asthma. Semin Arthritis Rheum 31:218-227. Copyright 2002, Elsevier Science (USA). All rights reserved.

Churg-Strauss syndrome.

A syndrome comprising asthma, allergic rhinitis, pulmonary and systemic small-vessel vasculitis, and extravascular granulomas was described in 1951 by Churg & Strauss, mainly from autopsied cases (1). Clinical studies of patients with polyarteritis nodosa, associated asthma, pulmonary in®ltrates, and eosinophilia had been reported previously (2±5). Churg & Strauss described the pathologic lesions and distinguished this entity from polyarteritis nodosa. They described basic anatomic changes consisting of ``widespread vascular lesions of the type seen in polyarteritis nodosa, and of characteristic tissue alteration in the vessel wall and in the extravascular system. This tissue alteration . . . comprised necrosis of eosinophilic exudate, severe `®brinoid' collagen change, and granulomatous proliferation of epithelioid and giant cells.'' Churg & Strauss considered it to be a distinct histopathologic entity which they termed ``allergic granuloma''.