Eosinophilic lung diseases are a diverse group of pulmonary disorders associated with peripheral or tissue eosinophilia. They are classified as eosinophilic lung diseases of unknown cause (simple pulmonary eosinophilia [SPE], acute eosinophilic pneumonia [AEP], chronic eosinophilic pneumonia [CEP], idiopathic hypereosinophilic syndrome [IHS]), eosinophilic lung diseases of known cause (allergic bronchopulmonary aspergillosis [ABPA], bronchocentric granulomatosis [BG], parasitic infections, drug reactions), and eosinophilic vasculitis (allergic angiitis, granulomatosis [Churg-Strauss syndrome]). The percentages of eosinophils in peripheral blood and bronchoalveolar lavage fluid are essential parts of the evaluation. Chest computed tomography (CT) demonstrates a more characteristic pattern and distribution of parenchymal opacities than does conventional chest radiography. At CT, SPE and IHS are characterized by single or multiple nodules with a surrounding ground-glass-opacity halo, AEP mimics radiologically hydrostatic pulmonary edema, and CEP is characterized by nonsegmental airspace consolidations with peripheral predominance. ABPA manifests with bilateral central bronchiectasis with or without mucoid impaction. The CT manifestations of BG are nonspecific and consist of a focal mass or lobar consolidation with atelectasis. The most common CT findings in Churg-Strauss syndrome include sub-pleural consolidation with lobular distribution, centrilobular nodules, bronchial wall thickening, and interlobular septal thickening. The integration of clinical, radiologic, and pathologic findings facilitates the initial and differential diagnoses of various eosinophilic lung diseases.

Corynebacterium ulcerans infection of the lung mimicking the histology of Churg-Strauss syndrome. Chest. 2007 Apr;131(4):1237-9.

We report the first case of pulmonary Corynebacterium ulcerans infection mimicking Churg-Strauss syndrome (CSS). Productive cough, fever, general fatigue, and weight loss developed in a 50-year-old man. Laboratory data revealed prominent eosinophilia and elevated serum IgE. On chest images, multiple nodules and cavities were predominantly detected in the right lung. Histopathologic examination showed necrotizing granulomas and vasculitis with massive eosinophilic infiltration identical to the findings seen in CSS; however, clusters of Gram-positive, coryneform rods were observed in the alveolar spaces. A toxigenic strain of C ulcerans was isolated from lung tissue. The patient was treated with antibiotics, and a favorable clinical course ensued.

Churg-Strauss syndrome. Presse Med. 2007 May;36(5P2):875-889. Epub 2007 Apr 3.

Churg-Strauss syndrome is a systemic and pulmonary vasculitis, defined by its association with severe asthma and with hypereosinophilia of the blood and tissues. The systemic vasculitis is a small-vessel vasculitis frequently associated with purpura, mononeuritis multiplex, and, more rarely, with rapidly progressive glomerulonephritis or diffuse alveolar hemorrhage. Its prevalence of 7 to 13 per million population makes it one of the rarest of the systemic vasculitides. Anti-MPO (antimyeloperoxidase) pANCA (ANCA with a perinuclear fluorescence pattern) is present in 35-40% of cases and appears to determine a subgroup of patients with a higher frequency of renal damage, alveolar hemorrhage, and central nervous system damage. Cardiac involvement is an important cause of morbidity and the leading cause of mortality in Churg-Strauss syndrome. Treatment is based on corticosteroid therapy and immunosuppressive drugs (cyclophosphamide and azathioprine) and is determined according to validated prognostic criteria (Five-Factor Score). Complete remission occurs in almost 90% of cases, and the 10-year survival rate has reached 79.4%. Relapses are frequent (25% of cases) and even after recovery from vasculitis, most patients (90%) still have asthma requiring corticosteroid treatment.

Churg-Strauss syndrome.Semin Respir Crit Care Med. 2006 Apr;27(2):148-57.

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: update on clinical, laboratory and therapeutic aspects.Sarcoidosis Vasc Diffuse Lung Dis. 2006 Mar;23(1):3-12.

Originally described over fifty years ago as a disorder of asthma, eosinophilic inflammation and small vessel vasculitis, Churg-Strauss syndrome is now defined as one of the ANCA-associated vasculitides. The predilection of disease manifestations for the respiratory tract, preferred affliction of small vessels including capillaries, and the frequent occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) justify this grouping together with Wegener's granulomatosis and microscopic polyangiitis. However, the allergic background in which the vasculitis presents, typically characterized by asthma and prominent peripheral blood and tissue eosinophilia, render it unique among the primary systemic vasculitis syndromes. Despite recent interest in a potential link between leukotriene receptor antagonist use for asthma and the onset of Churg-Strauss syndrome, it remains a rare disease with poorly understood pathogenesis. This review provides an update on the clinical diagnosis of Churg-Strauss syndrome in light of changing disease definitions and classifications, and focuses on evolving therapeutic approaches for this challenging systemic disorder.

Churg-Strauss syndrome and pulmonary fibrosis: an unusual association. Presse Med. 2006 Sep;35(9 Pt 1):1259-62.

INTRODUCTION: Churg-Strauss syndrome (CSS) is characterized by asthma, hypereosinophilia, and vasculitis involving at least two extrapulmonary organs. CASE: We report a case of a patient with antineutrophilic cytoplasmic antibody-negative CSS who developed pulmonary interstitial fibrosis (PIF). DISCUSSION: The possible relations between CSS and PIF are discussed. Because this case report is the first to describe features of pulmonary fibrosis in a patient with CSS, we cannot know whether this association is causal or fortuitous.

Churg-Strauss syndrome in children: a clinical and pathologic review.Pediatrics. 2006 Sep;118(3):e914-20. Epub 2006 Aug 7.

Churg-Strauss syndrome is a vasculitis accompanied by asthma and eosinophilia. It is generally considered a disease of adults; occurrence in children has been reported infrequently. Here we report 2 pediatric patients with Churg-Strauss syndrome manifesting with prominent pulmonary involvement. One, a 16-year-old with a previous history of asthma, presented with pleuritic chest pain and a peripheral pulmonary nodule complicated by an eosinophilic pleural effusion. The other patient presented at age 6 with cough, weight loss, and radiographic infiltrates. Lung biopsies revealed elements characteristic of Churg-Strauss syndrome, including eosinophilic microabscesses and vasculitis. Three- and 5-year follow-up showed continued symptoms in both patients despite medical therapy. Both patients illustrate many of the typical features of Churg-Strauss syndrome. We report these cases to expand the scant knowledge about Churg-Strauss syndrome in pediatric patients and to heighten awareness that this serious disease may affect the pediatric population. The relevant literature on Churg-Strauss syndrome, with specific reference to childhood cases, is reviewed.

Multiple tracheobronchial mucosal lesions in two cases of Churg-Strauss syndrome.Respirology. 2006 Jan;11(1):109-12

Churg-Strauss syndrome (CSS) is characterized by hypereosinophilia and a systemic necrotizing vasculitis seen almost exclusively in patients with asthma. The most common pathological findings in the chest in CSS are eosinophilic pneumonia, necrotizing vasculitis and granulomatous inflammation (extravascular granuloma). However, tracheobronchial mucosal lesions have rarely been reported in CSS. The authors report two patients with CSS who had multiple tracheobronchial mucosal lesions that were found by fibreoptic bronchoscopy. They were tiny nodular lesions and necrotizing bronchial inflammation with many eosinophils was observed upon pathological examination. The authors concluded that tracheobronchial mucosal lesions may be one of the manifestations of vasculitis seen in CSS.

Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome.Arthritis Rheum. 2005 Sep;52(9):2926-35.

OBJECTIVE: Churg-Strauss syndrome (CSS) is classified among the so-called antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75-95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features. METHODS: Immunofluorescence and enzyme-linked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status. RESULTS: ANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti-MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P = 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P = 0.019) and heart disease (5.7% versus 22.4%; P = 0.042). CONCLUSION: ANCAs are present in approximately 40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA-positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis.

Churg-strauss syndrome.Semin Respir Crit Care Med. 2004 Oct;25(5):535-45.

First described in 1951 as an allergic and granulomatous angiitis, Churg-Strauss syndrome (CSS) is a small-vessel vasculitis. Mean age at the time of diagnosis is approximately 50 years, with a sex ratio around 1. Asthma is the central feature of CSS and precedes the systemic manifestations in almost all cases, whereas 70% of the patients have maxillary sinusitis, allergic rhinitis, and/or sinus polyposis. General symptoms are frequent, and associated with pulmonary infiltrates in 38 to 77% of the patients; peripheral neuropathy, usually mononeuritis multiplex, in 64 to 75%; skin involvement in 40 to 70%; and gastrointestinal tract symptoms in 37 to 62%. Cardiac involvement is common, with pericarditis in 23% of the patients and myocarditis in 13%, and represents the primary cause of mortality. Hypereosinophilia is the main biological feature of CSS, whereas antineutrophil cytoplasm antibodies (ANCA), especially anti-myeloperoxidase (MPO), are found in one third to one half of the patients. Triggering factors, such as vaccination, desensitization, or exposure to leukotriene-receptor antagonists, have been suspected as contributing to the development of CSS, but its etiology has not yet been fully elucidated. T-helper type 2 (Th2) lymphocytes, by analogy with the pathogenesis of asthma, eosinophils infiltrating tissues, and anti-MPO ANCA are probably implicated in the pathogenesis of vasculitic lesions. CSS usually responds rapidly to corticosteroids. Adjunction of cyclophosphamide is indicated when at least one factor of poor prognosis is present. With treatment, remission is obtained in more than 80% of the patients, but it is often impossible to withdraw corticosteroids completely because of residual asthma. Relapses occur in 25% of the patients, half during the first year. The 10-year survival rate was 79% for our patients, with 73% of them requiring low-dose prednisone maintenance therapy for persistent asthma.

Churg-Strauss syndrome: high resolution CT and pathologic findings.J Thorac Imaging. 2005 May;20(2):74-80.

OBJECTIVES: The purpose of this study was to evaluate high-resolution CT findings in 7 patients with Churg-Strauss syndrome and to compare the CT with the histopathologic findings. MATERIALS AND METHODS: High-resolution CT scans of 7 asthmatic patients (4 women, 3 men, age range, 34-62 years, mean 49 years) with Churg-Strauss syndrome were reviewed by 2 observers. Histologic specimens of lung obtained at surgical (n = 3) or transbronchial (n = 3) biopsy or autopsy (n = 1) were reviewed by an expert lung pathologist. The diagnosis of Churg-Strauss was based on clinical, laboratory, and histologic findings. RESULTS: Parenchymal and airway abnormalities included ground-glass opacities (n = 5), areas of air-space consolidation (n = 4), centrilobular nodules (n = 5), nodules 1-3 cm in diameter (n = 3), interlobular septal thickening (n = 4), bronchial wall thickening (n = 4), and areas of atelectasis (n = 1). Surgical biopsy (n = 3) and autopsy (n = 1) specimens demonstrated airspace disease in 3 patients, interlobular septal thickening in 3 patients, and airway abnormalities in 2 patients. Histologically, the airspace disease included eosinophilic pneumonia (n = 2) and small foci of organizing pneumonia (n = 1). The septal thickening was due to edema combined with numerous (n = 2) or few (n = 1) eosinophils. The airway abnormalities (n = 2) included muscle hypertrophy and large airway wall necrosis (n = 1) and eosinophilic infiltration of the airway walls (n = 1). Transbronchial biopsy (n = 3) demonstrated increased eosinophils. CONCLUSION: The main high-resolution CT findings of Churg-Strauss syndrome consist of airspace consolidation or ground-glass opacities, septal lines, and bronchial wall thickening. These reflect the presence of eosinophilic infiltration of the airspaces, interstitium, and airways, and interstitial edema.

 

Allergic granulomatosis and angiitis in the absence of asthma and blood eosinophilia: a rare presentation of limited Churg-Strauss syndrome.Rheumatol Int. 2004 Sep;24(5):301-4. Epub 2003 Nov 20.

Allergic granulomatosis and angiitis, also known as Churg-Strauss syndrome (CSS), is an uncommon vasculitis of unknown etiology. We report a 21-year-old male patient with fatigue, dry cough, and progressive dyspnea. He had no history of asthma or eosinophilia. Thorax computed tomography showed bullous/cystic areas with thin walls in varying sizes (5-15 mm). Histopathological examination of the open lung biopsy revealed granulomatous infiltration with histiocytes and eosinophilic leukocytes. This extremely rare variant of CSS is discussed.

Churg-Strauss syndrome.Rev Pneumol Clin. 2003 Feb;59(1):17-24.

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.

Left ventricular dysfunction in Churg-Strauss syndrome.Z Kardiol. 2003 Aug;92(8):677-81.

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.

Diagnostic features and differential diagnosis of Churg-Strauss syndrome in the lung. A review.Am J Clin Pathol. 2000 Nov;114(5):767-72.

Churg-Strauss syndrome is a rare systemic vasculitis occurring in patients with asthma and blood eosinophilia. Lungs, skin, and nervous system are the most common sites of involvement, although many other organs are affected frequently. The diagnosis often is established from clinical findings or biopsy of extrapulmonary sites, and lung biopsy is performed infrequently. The classic pathologic findings in the lung include a combination of eosinophilic pneumonia, granulomatous inflammation, and vasculitis. All 3 features may not be present in every case, however, and diagnosis often requires careful correlation of the clinical and pathologic findings. The differential diagnosis in the lung includes diseases that are associated with eosinophil infiltrates or a combination of eosinophil infiltrates and granulomatous inflammation. Distinguishing these various diseases from Churg-Strauss syndrome is especially important, since many are more common than Churg-Strauss syndrome, and treatment is usually different.

Churg-Strauss syndrome.Klin Monatsbl Augenheilkd. 1999 Mar;214(3):171-4.

BACKGROUND: The Churg-Strauss syndrome, also known as allergic granulomatosis with angiitis, is a rare necrotizing vasculitis with unknown pathogenesis. The necrotizing granulomatous vasculitis involves small and medium-sized arteries, capillaries and veins, leading to the characteristic changes of intra- and extravascular, eosiniphilic granulomas, accompanied by clinically symptoms: bronchial asthma, hypereosinophilia and fever. Ocular manifestations are rarely reported. CASE REPORT: A 53-year-old woman suffered from bronchial asthma, relapsing lung infiltrates and sinusites since 1994. In August 1997 she suddenly disclosed vasculitic skin manifestations on both legs and a mononeuritis of the left peroneus nerve. At the same time visual acuity of the right eye decreased, before she had shown some attacks of amaurosis fugax. The funduscopy showed a central retinal artery occlusion. Laboratory findings: blood eosinophilia of 20%, elevated IgE value to 396 kU/l (normal value < 120 kU/l), and negative parameters for antineutrophil cytoplasmatic antibodies (p- and c-ANCA). CONCLUSION: The clinical and laboratory findings are characteristic signs for the Churg-Strauss syndrome. Without such typical manifestations the histologic examination leads to the diagnosis and helps to differentiate this disease from other necrotizing vasculitides, e.g. panarteriitis nodosa or Wegener's granulomatosis.

Churg-Strauss syndrome.Rev Med Suisse Romande. 1995 Feb;115(2):147-51.

Allergic granulomatosis and angiitis (Churg-Strauss syndrome) is characterized by a systemic vasculitis in the context of bronchial asthma and eosinophilia. Pathologically, there is a necrotizing vasculitis of small arteries and veins with extravascular granulomas, infiltration of vessels and perivascular tissue with eosinophilia. Pulmonary, peripheral nervous system, cardiovascular and cutaneous manifestations are most frequently encountered. Renal failure and high blood pressure are more rare. These features, within the setting of bronchial asthma and eosinophilia, differentiate Churg-Strauss syndrome from polyarteritis nodosa. Steroid associated to cyclophosphamide have considerably improved the prognosis and risk of relapse.

Allergic angiitis with granulomatosis: the Churg and Strauss syndrome.
Rev Med Interne. 1994;15 Suppl 2:226s-233s.

Churg-Strauss Syndrome is a disorder characterized by pulmonary and systemic necrotizing vasculitis, extravascular granulomas, and eosinophilia occurring almost exclusively in patients with asthma or a history of allergy. The clinical manifestations most commonly associated with asthma are mononeuritis multiplex, gastrointestinal, cutaneous, cardiac and renal involvement. ANCA are found in 2/3 of the patients with Churg-Strauss Syndrome and are usually p-ANCA. The treatment of Churg-Strauss Syndrome relies on corticosteroids and cyclophosphamide.

The status of Churg-Strauss syndrome among other hypereosinophilic, granulomatous and vasculitic diseases.Z Rheumatol. 1988 Nov-Dec;47(6):388-96.

The Churg-Strauss syndrome is a disorder characterized by hypereosinophilia and systemic vasculitis occurring in patients with asthma and allergic rhinitis. Only few patients are identified as having this syndrome. The three histological criteria are necrotizing vasculitis, tissue infiltration by eosinophils, and extravascular granulomas; they often do not coexist in one patient. To find a clinical approach to diagnosis, it is necessary to exclude other disorders with hypereosinophilia, granulomas, and vasculitis. In regard to this clinical viewpoint it seems that the syndrome is not as rare as may be assumed according to the relevant autopsy findings. Two cases are reported in which the Churg-Strauss syndrome developed together with rheumatoid arthritis; in one case it was likely triggered by treatment with D-penicillamin.