Hypertrophic pachymeningitis with anti-neutrophil cytoplasmic antibody (p-ANCA), and diabetes insipidus

We treated a patient with idiopathic cranial hypertrophic pachymeningitis and elevated serum titer of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactive against myeloperoxidase. This 67-year-old man showed multiple cranial nerve-palsies, central diabetes insipidus (DI), and an intrasellar mass. DI and intrasellar mass had been present for 3 years, and DI had been well controlled by intranasal desmopressin. His nerve-palsies were most likely caused by thickened dura matter detected by the brain MRI. Granuloma may develop in the sella, and MRI findings in our patient are compatible to it. Corticosteroid and oral cyclophosphamide therapy improved his neurological symptoms and serum p-ANCA level with showing good correlation. DI improved temporally for 2 months. Few other cases of hypertrophic pachymeningitis with elevated p-ANCA have been reported, however the etiology is unknown. As p-ANCA antibodies have been detected in many of vasculitides, microvasculitis may be involved in some cases of idiopathic hypertrophic pachymeningitis.     

类固醇激素治疗溃疡性结肠炎近期疗效因素分析

目的 分析类固醇激素(简称激素)治疗溃疡性结肠炎疗效相关因素.方法 总结应用激素治疗住院病例123例的资料,在激素应用起第30天观察治疗反应,多因素分析影响疗效的因素.结果 完全有效、部分有效、无效病例分别为63例(51.2%)、25例(20.3%)、35例(28.5%).初治者有效率73.8%,复治者有效率67.4%,比较无显著性差异.有效组(完全有效及部分有效)与无效组比较,疗效仅与病变累及范围有关.病变范围超过脾曲者有效组20例(22.7%),无效组30例(85.7%),比较差异显著(P＜0.01).P-ANCA阳性率有效组为62.5%,无效组为40.0%,比较无显著性差异.两组间在性别、发病年龄、给药途径方面无显著性差异.结论 (1)对于复发病例激素仍可以作为溃疡性结肠炎急性期治疗的首选药物.(2)疗效与患者性别、发病年龄、给药途径及p-ANCA阳性与否无关.(3)病变范围广预示激素治疗失败可能性增加.     

Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory bowel diseases

Abstract: Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol-fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangitis     

Familial Churg-Strauss syndrome in two sisters

Churg-Strauss syndrome (CSS) is an uncommon systemic vasculitis with an increase in the number of eosinophils in the peripheral blood and tissues. Its pathogenesis is unknown, and there is no evidence that genetic factors influence susceptibility to this disease. We present a case of familial CSS in two sisters with atopic-type bronchial asthma and negative perinuclear anti-neutrophil cytoplasmic antibody results. We investigated the human leukocyte antigen typing of the sisters and their six living siblings but found no evidence for heritability of CSS. To our knowledge, this is the first report of familial CSS.     

Polymorphisms of the ICAM-1 Gene Are Associated with Inflammatory Bowel Disease, Regardless of the p-ANCA Status

The intercellular adhesion molecule-1 (ICAM-1) is of paramount importance for the initiation and propagation of various inflammatory conditions. An increased frequency of allele R241 of the ICAM-1 gene was previously described in p-ANCA-negative as compared to p-ANCA-positive ulcerative colitis and vice versa in Crohn's disease. One hundred sixteen healthy unrelated controls, 121 patients with ulcerative colitis, and 96 patients with Crohn's disease were genotyped for two polymorphisms of the ICAM-1 gene (R/G241, exon 4; and K/E469, exon 6), employing dot-blot hybridization and stratified according to their p-ANCA status. When compared with the control group the frequency of the allele R241 (P = 0.024) and the heterozygous genotype R/G241, P = 0.032) were significantly increased in ulcerative colitis, whereas the homozygous genotype G/G241 was found less frequently (P = 0.022). The heterozygous genotype K/E469 was observed less frequently (P = 0.001 and 0.037, resp.) than the homozygous genotype E/E469, which was more frequent in Crohn's disease and ulcerative colitis (P = 0.002 and 0.012, respectively). Further significant differences concerning the allele or genotype distribution were not observed. After stratification for the p-ANCA status significant differences concerning the frequencies of both the R241 and the E469 alleles were not detected when p-ANCA-positive inflammatory bowel disease and p-ANCA-negative inflammatory bowel disease were compared. Ulcerative colitis and Crohn's disease are associated with polymorphisms of the ICAM-1 gene, which might therefore represent a functional candidate gene. However, the observed associations are independent of the p-ANCA status.     

Reversible Sensorineural Hearing Loss due to Pachymeningitis Associated with Elevated Serum MPO-ANCA

Hypertrophic pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. It is seldom reported to be related to sensorineural hearing loss, but it can cause sensorineural hearing loss which can be potentially reversed through treatment. Here, we report the case of a 54-year-old woman who had progressive, bilateral, worse in the left, sensorineural hearing loss and visual disturbance with an accompanying headache over several months. Brain MRI showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers. After empirical steroid and cyclophosphamide therapy, auditory impairment improved, especially in the high frequency region of the pure tone audiogram, and significant improvement in the word recognition test. Moreover, a follow-up MRI revealed much decreased enhancement of the dura mater, and the MPO-ANCA titer decreased to within the normal range. In the case of rapidly progressive sensorineural hearing loss or hearing impairment accompanying other cranial neuropathy, pachymeningitis should be taken into consideration, and brain MRI with gadolinium enhancement is the best method of detecting it. Also, to ensure proper treatment, a cautious evaluation including an ANCA work-up should be performed.     

Diagnostic role and clinical correlates of anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (p-ANCA) in Italian patients with inflammatory bowel diseases

Background. Anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) are serological markers associated, respectively, with Crohn’s disease and ulcerative colitis, whose clinical significance and possible diagnostic role are still poorly defined.

Aims. (a) To evaluate the sensitivity, specificity and predictive values of isolated and combined ASCA and p-ANCA assays in a large cohort of Italian patients with inflammatory bowel disease (IBD) and (b) to assess whether their presence is associated with particular clinical features of the disease.

Patients and methods. Hundred and forty-six IBD patients (93 with Crohn’s disease and 53 with ulcerative colitis) and 54 control patients were enrolled in the study. ASCA (IgA and IgG) and p-ANCA were determined by means of enzyme-linked immunosorbent assay and indirect immunofluorescence, respectively.

Results. The specificities were excellent for both tests (ASCA in Crohn’s disease, 98.1% both for IgA and IgG, and p-ANCA in ulcerative colitis, 92.5%); however, the sensitivities of both tests were low (59.1% for ASCA IgA, 44.1% for ASCA IgG, 39.6% for p-ANCA). ASCA specificity and positive predictive value reached 100% when positivity for both IgA and IgG was present. No significant association was found between the presence of a specific serological marker and patients’ clinical features.

Conclusions. This study confirms the low prevalence of p-ANCA observed in ulcerative colitis patients from the Mediterranean area. The low sensitivity of ASCA and p-ANCA, despite their rather high specificity, renders them of little value in the screening of the general population, where the prevalence of IBD is low. However, in our series, a double positivity for ASCA IgA and IgG identifies with certainty the presence of Crohn’s disease.     

Association of the HLA-DRB1＊0701 allele with perinuclear anti-neutrophil cytoplasmatic antibodies in Mexican patients with severe ulcerative colitis

AIM: To determine the association between the HLADRB1 alleles and perinuclear anti-neutrophil cytoplasmatic antibodies (p-ANCA) positive in Mexican patients with ulcerative colitis (DC). METHODS: Ninety Mexican mestizo patients (45 females) with DC, confirmed by biopsy, were studied. High resolution HLA typing was performed by PCR-SSO reverse dot blot and PCR-SSP. Molecular typing techniques were applied to define HLA-DRB1 alleles. Enzyme-linked immunosorbent assay and immunofluorescence techniques were used to detect p-ANCA. RESULTS: Forty-eight (53%) UC patients were positive for p-ANCA by ELISA and IF. We found that p-ANCA-positive UC patients had a significantly increased frequency of HLA-DR7 compared with p-ANCA-negative controls (22% vs 5.1%; pC = 0.02, OR = 5.2, CI 95%: 1.06-37.82). Disease activity was scored as severe in 20 patients, moderate in 8, mild in 14 and no activity in the remaining 38 patients according to the Truelove and Witts criteria. Subgroup analysis showed a significantly increased frequency of the HLA-DRB1*07 allele in 15 of 20 UC patients with severe activity of UC and p-ANCA positivity [100% vs 0%; pC = 0.0000001; OR = 35]. No significant differences were found between p-ANCA positive patients, HLA-DR alleles and other clinical features such as extraintestinal manifestations, proctocolectomy and extension. CONCLUSION: The HLA-DRB1*07 is associated with p-ANCA positive UC Mexican patients.     

Microscopic polyarteritis with renal and cerebral involvement

We report a 15-year-old girl who presented with renal failure requiring dialysis and a diagnosis of p-ANCA-associated vasculitis. She subsequently developed cerebral vasculitis during treatment with oral cyclophosphamide and prednisolone. Treatment with intravenous cyclophosphamide and plasma exchange produced a complete recovery. Received: 23 February 2000 / Revised: 31 May 2000 / Accepted: 5 June 2000