We reported the case of a male patient with Churg-Strauss syndrome (CSS) heralding as symptoms typical of polymiositis. During high-dose cortisone therapy (1.5 mg/kg/day), he developed a severe multiplex mononeuritis, poorly responsive to immunoglobulins and methotrexate administration. After 6 months he developed a partial deficiency of the right sciatic popliteus and the radial nerves. Sural nerve biopsy showed a characteristic necrotizing vasculitis of the epineural vessels with granulocyte and eosinophil infiltrates. In the course of CSS, peripheral nervous system involvement is frequent and can lead to disability. For this reason, it must be promptly recognized and properly treated.

We assessed the clinicopathological features of 28 patients with peripheral neuropathy associated with Churg-Strauss syndrome. Initial symptoms attributable to neuropathy were acute painful dysaesthesiae and oedema in the dysaesthetic portion of the distal limbs. Sensory and motor involvement mostly showed a pattern of mononeuritis multiplex in the initial phase, progressing into asymmetrical polyneuropathy, restricted to the limbs. Parallel loss of myelinated and unmyelinated fibres due to axonal degeneration was evident as decreased or absent amplitudes of sensory nerve action potentials and compound muscle action potentials, indicating acute massive axonal loss. Epineurial necrotizing vasculitis was seen in 54% of cases; infiltrates consisted mainly of CD8-positive suppressor/cytotoxic and CD4-positive helper T lymphocytes. Eosinophils were present in infiltrates, but in smaller numbers than lymphocytes. CD20-positive B lymphocytes were seen only occasionally. Deposits of IgG, C3d, IgE and major basic protein were scarce. The mean follow-up period was 4.2 years, with a range of 8 months to 10 years. Fatal outcome was seen only in a single patient, indicating a good survival rate. The patients who responded well to the initial corticosteroid therapy within 4 weeks regained self-controlled functional status in longterm follow-up (modified Rankin score was < or = 2), while those not responding well to the initial corticosteroid therapy led a dependent existence (P < 0.01). In addition the patients with poor functional outcomes had significantly more systemic organ damage caused by vasculitis (P < 0.05). Necrotizing vasculitis mediated by cytotoxic T cells, leading to ischaemic changes, appears to be a major cause of Churg-Strauss syndrome-associated neuropathy. The initial clinical course and the extent of systemic vasculitic lesions may influence the long-term functional prognosis.

OBJECTIVE: To determine the frequency and the types of neurologic involvement in a series of patients with Churg-Strauss syndrome (CSS). DESIGN: We reviewed the medical records of 47 consecutive patients with CSS who were examined at the Mayo Clinic between January 1974 and June 1992. MATERIAL AND METHODS: The study patients were classified into two groups:(1) those with a histopathologically confirmed diagnosis of CSS who had evidence of either vasculitis or Churg-Strauss granuloma, the presence of asthma, and peripheral eosinophilia (more than 10% eosinophils) on at least one differential leukocyte count (N = 33) and (2) those with a clinical diagnosis of CSS who had evidence of vasculitis based on either multiple mononeuropathy or necrotizing cutaneous lesions, the presence of asthma, and peripheral eosinophilia (more than 10% eosinophils) on at least one differential leukocyte count (N = 14). RESULTS: Of the 47 patients, 29 (62%) had neurologic involvement. Peripheral neuropathy was detected in 25 patients: 17 had multiple mononeuropathy, 7 had distal symmetric polyneuropathy, and 1 had an asymmetric polyneuropathy. Three patients had cerebral infarctions. Less commonly identified problems included radiculopathies, ischemic optic neuropathy, and bilateral trigeminal neuropathy. Asthma preceded the onset of neurologic involvement in all cases (mean duration, 6.7 years. Follow-up data, when available, showed that corticosteroid therapy usually yielded improvement or stabilization. CONCLUSION: Neurologic involvement is common in CSS, usually manifesting as peripheral neuropathy. In this series of patients, asthma preceded the neurologic manifestations.

The present study attempted to define the clinical, radiological, immunological and pathological characteristics of microscopic polyangiitis (MPA), and to separate them from classic PAN (c-PAN) and Churg-Strauss syndrome (CSS). In most cases, patients presenting microaneurysms and/or multiple vessel stenoses, which reflect medium-sized vessel involvement, did not have antineutrophil cytoplasmic antibodies (ANCA)(6.6%). Conversely, patients with glomerulonephritis almost never had abnormal angiograms. Furthermore, the clinical characteristics of ANCA-positive patients also indicate small-sized vessel involvement. Skin involvement (73.1 vs 26.7%, P < or = 0.05), glomerulonephritis (38.5 vs 0%, P < or = 0.001) and the presence of ANCA (34.6 vs 6.7%, P < or = 0.05) were significantly more frequent in patients with normal than abnormal angiograms, respectively. Conversely, hypertension (66.7 vs 23.1%, P < or = 0.02), renal vasculitis (46.7 vs 0%, P < or = 0.001) and hepatitis B antigenaemia (60 vs 11.5%, P < or = 0.01) were significantly more common in patients with abnormal angiograms. Stratification of patients according to vessel size showed that, except for skin involvement (P < or = 0.05) and glomerulonephritis (P < or = 0.01), which are direct manifestations of small-sized vessel diseases, clinical symptoms of PAN or CSS, angiographic findings and ANCA were not correlated to arteriole size. Although at present it is not possible to separate definitively MPA from c-PAN, our results show that ANCA should be considered diagnostic for MPA and, in most cases, should be an exclusion criterion for c-PAN. Conversely, small-sized vessel involvement can be observed in patients presenting characteristics of c-PAN, MPA or CSS and, therefore, is not a sufficient criterion for assigning diagnosis.

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.

The Churg-Strauss syndrome (CSS) is an unusual disease that presents as a systemic vasculitis and peripheral eosinophilia in a patient with chronic atopic disease. Although often not prominent on initial presentation, cardiac involvement is a major cause of morbidity and mortality in patients with CSS. We report a case of a young woman with CSS who had a myocardial infarction. Coronary arteriography was performed for recurrent chest pain and demonstrated diffuse vasculopathy consistent with vasculitis in CSS. We have also included a review of the literature on cardiac involvement in CSS.

OBJECTIVE: To examine the safety and efficacy of methotrexate (MTX) plus low-dose prednisolone for induction of remission in non life- or organ-threatening courses and for remission maintenance in Churg-Strauss syndrome (CSS). METHODS: In an open-label study 11 patients were treated with MTXfor induction of remission at initial diagnosis and relapse. Twenty-five patients received MTX for maintenance of remission. Primary endpoints were the achievement of remission and the incidence of relapses, respectively. Doses of concomitant prednisolone (PRD) and side effects were secondary endpoints. RESULTS: Induction of remission was achieved in 8/11 patients with MTX/PRD. Median time to remission was 5 months (range 2-9). Remission was maintained in 12 of 23 with available long-term follow-up (median 48 months). Eleven patients experienced 8 major and 3 minor relapses with a median time from remission to first relapse of 9 months. With MTX, the median cumulative PRD dose during the induction phase was 6.2 g. In the maintenance phase PRD could be reduced by 53% in responders. Apart from one case of MTX-induced pneumonitis, adverse events were confined to mild/moderate episodes of infection and leucopenia. No opportunistic infections occurred, neither did steroid-specific adverse events. CONCLUSIONS: MTX is safe and effective for the induction of remission in non-life-threatening CSS. It allows a considerable reduction of PRD and thus avoidance of PRD-related adverse events. However, the ability of MTX to prevent relapses in CSS appears limited. The identification of an optimal maintenance regimen and prognostic factors for treatment response requires trials with larger patient numbers.

Treatment of cardiac dysfunction associated with Churg-Strauss syndrome (CSS) is empiric since the histologic findings provided by endomyocardial biopsy are rare and often nondiagnostic. Myocardial necrotizing vasculitis presenting as restrictive cardiomyopathy has not been reported before. A case of CSS, presenting with fever and progressive heart failure due to pericarditis, eosinophilic endomyocarditis, and myocardial necrotizing vasculitis, is reported. Cardiac involvement assessed by noninvasive (cardiac two-dimensional echocardiogram and nuclear magnetic resonance [NMR] imaging) and invasive (cardiac catheterization, angiography, and biopsy) studies showed a moderate degree of pericardial effusion and left ventricular (LV) dysfunction (ejection fraction 0.40), severe diastolic dysfunction (increased right and LV filling pressure with a dip and plateau pattern) and a severe reduction of cardiac index (1.6 L/min/m2). Histologic characteristics showed marked eosinophilic infiltration of the endocardium and myocardium with myocitolysis and fibrinoid necrosis of arterioles, venules, and capillaries. Combination therapy of steroids and cyclophosphamide resulted in both a clinical (regression of pericardial effusion, normalization of systolic and diastolic dysfunction, and increase of cardiac index to 2.8 L/min/m2) and histologic (sequential endomyocardial biopsies at 1, 3, and 6 months of follow-up) resolution of cardiac involvement. No recurrences were registered at 12-month follow-up with the patient receiving a maintenance drug regimen.

A 61-year-old man developed mononeuritis multiplex accompanied by eosinophilia in 1993. Approximately 3 years later, acute renal dysfunction, a subendocardial tumor, and a high peripheral anti-neutrophil cytoplasmic antibody titer were also detected. Renal biopsy revealed glomerular crescents and interstitial infiltration of eosinophils, so allergic granulomatosis and angiitis was diagnosed. These clinical abnormalities regressed with steroid therapy. He had no history of asthma. This was therefore considered to be an atypical form of Churg-Strauss syndrome with rapidly progressive glomerulonephritis.

A 76-year-old woman hospitalized for treatment of an inferior vena cava thrombus was noted to have eosinophilia as well as asthma, peripheral neuropathy, jaw claudication and visual loss. Pathological review of a temporal artery biopsy revealed vasculitis with eosinophils but no giant cells. Treatment with high dose corticosteroids resulted in improvement of visual acuity from hand motion to 20/60. Whereas at least 6 cases of temporal artery involvement with Churg-Strauss syndrome have been reported, visual loss has occurred in only 3 patients. In each of these cases, visual loss was permanent.

Haemosiderin-laden alveolar macrophages are a common finding in patients with alveolar bleeding. Iron-positive macrophages, suggestive of subclinical alveolar bleeding, were found to be fairly common in bronchoalveolar lavage (BAL) fluid in primary systemic vasculitis but uncommon in collagen vascular diseases (CVDs) and rheumatoid arthritis (RA). To substantiate the impression that subclinical alveolar bleeding may be a feature distinguishing between these disorders, fibreoptic bronchoscopy and BAL were performed in 49 patients with active Wegener's granulomatosis or Churg-Strauss syndrome and 44 patients with CVDs or RA, all of them without clinically manifest alveolar bleeding. The percentage of iron-positive cells was compared with clinical and radiological findings. Only a minority of the CVD and RA patients had iron-positive alveolar macrophages; the 95th percentile of the median number of such cells was 5%. Fifty-three per cent of the patients in the vasculitis group had >5% iron-positive cells, with individual counts ranging up to 95%. Patients with iron-positive macrophages had more extensive disease, more frequent microhaematuria, a higher antineutrophil cytoplasmic antibody titre, a higher myeloperoxidase concentration in the BAL fluid and somewhat more frequent low-attenuation opacities in pulmonary high-resolution computed tomography than the patients with a low iron-positive cell count. In conclusion, subclinical alveolar bleeding was, indeed, a common finding in antineutrophil cytoplasmic antibody-associated vasculitis, which distinguished these disorders from lung disease due to collagen vascular diseases or rheumatoid arthritis. Its association with indices of disease activity, although weak in this cross-sectional study, merits a longitudinal study of its value for the long-term monitoring of vasculitis patients.