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OBJECTIVE: To explore the association between HLA alleles and Churg-Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease. METHODS: Low-resolution genotyping of HLA-A, HLA-B, and HLA-DR loci and genotyping of TNFA -238A/G and TNFA -308A/G single-nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls. RESULTS: The frequency of the HLA-DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; chi(2) = 12.64, P = 0.0003, corrected P [P(corr)] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47-3.99). The HLA-DRB4 gene, present in subjects carrying either HLA-DRB1*04, HLA-DRB1*07, or HLA-DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; chi(2) = 16.46, P = 0.000058, P(corr) = 0.000232, OR 2.49, 95% CI 1.58-3.09). Conversely, the frequency of the HLA-DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; chi(2) = 7.62, P = 0.0057, P(corr) = 0.0228, OR 0.54, 95% CI 0.35-0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)-positive, with features of small-vessel vasculitis, and ANCA-negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA-DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001). CONCLUSION: These findings indicate that HLA-DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease.

We describe four patients with Churg-Strauss syndrome admitted to the hospital in 1988. Some clinical and histological features of particular relief are present in these cases. All patients had been treated with corticosteroids and they are now in remission. Our work suggests that Churg-Strauss syndrome is not a rare disease and that an early diagnosis and appropriate therapy may influence favourably at least long term survival.

Churg-Strauss angiitis or syndrome (CSA) is defined as an eosinophil-rich and granulomatous inflammation involving the respiratory tract, and necrotising vasculitis affecting small- to medium-sized vessels, and is associated with asthma and eosinophilia. It is usually classified among the so-called anti-neutrophil antibody (ANCA)-associated systemic vasculitides (AASVs) because of its clinical and pathological features that overlap with those of the other AASVs. However, two recent studies on large cohorts of patients have found that ANCAs, usually P-ANCAs/MPO-ANCAs, were present in only 38% of patients. Moreover, the ANCA status was shown to segregate with clinical phenotype. ANCA-positive patients were significantly more likely to have disease manifestations associated with small-vessel vasculitis, including necrotising glomerulonephritis, mononeuritis and purpura, whereas ANCA-negative cases were significantly more likely to have cardiac and lung involvement. Vasculitis was documented less frequently in histological specimens from ANCA-negative patients in comparison with ANCA-positive ones. These findings have led to postulate the predominance of distinct pathogenetic mechanisms in the two subsets of patients: an ANCA-mediated process in ANCA-positive patients and tissue infiltration by eosinophils with subsequent release of toxic product in ANCA-negative cases. Preliminary results suggest that ANCA-positive and ANCA-negative patients also might have a different genetic background. Corticosteroids remain the cornerstone of the initial treatment of CSA. The addition of cyclophosphamide is indicated in treatment of patients with poor-prognosis factors or in patients without poor-prognosis factors but those that are prone to relapses. The length of the maintenance therapy remains to be established. However, the vast majority of patients require long-term corticosteroids treatment to control asthma. © 2009 Elsevier Ltd. All rights reserved

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare disorder characterized by asthma, eosinophilia, and systemic vasculitis. Renal involvement is not regarded as a prominent feature, and its prevalence and severity vary widely in published reports that usually refer to small series of selected patients. METHODS: We examined the prevalence, clinicopathologic features, and prognosis of renal disease in 116 patients with CSS. RESULTS: There were 48 men and 68 women with a mean age of 51.9 years (range, 18 to 86 years). Signs of renal abnormalities were present in 31 patients (26.7%). Rapidly progressive renal insufficiency was documented in 16 patients (13.8%); urinary abnormalities, 14 patients (12.1%); and chronic renal impairment, 1 patient. There were 3 additional cases of obstructive uropathy. Sixteen patients underwent renal biopsy, which showed necrotizing crescentic glomerulonephritis in 11 patients. Other diagnoses were eosinophilic interstitial nephritis, mesangial glomerulonephritis, and focal sclerosis. Antineutrophil cytoplasmic antibody (ANCA) was positive in 21 of 28 patients (75.0%) with nephropathy versus 19 of 74 patients without (25.7%; P < 0.001). In particular, all patients with necrotizing crescentic glomerulonephritis were ANCA positive. After a median follow-up of 4.5 years, 10 patients died (5 patients with nephropathy) and 7 patients developed mild chronic renal insufficiency. Five-year mortality rates were 11.7% (95% confidence interval, 3.9 to 33.3) in patients with nephropathy and 2.7% (95% confidence interval, 0.7 to 10.7) in those without (P = 0.10). CONCLUSION: Renal abnormalities are present in about one quarter of patients with CSS. The prevailing picture is ANCA-associated necrotizing crescentic glomerulonephritis; however, other forms of nephropathy also may occur. Outcome and long-term follow-up usually are good.

Background: The asthmatic-prodromal phase of Churg–Strauss syndrome (CSS) is usually considered allergic, but data about the involved allergens are scarce. The aim of our work was to examine the prevalence of allergy in a group of CSS patients and in two control groups of persistent asthmatic subjects selected for eosinophilia >10% [first control group patients (CGP1)] and eosinophils