Perinuclear anti-neutrophil cytoplasmic antibody and refractory pouchitis

Refractory pouchitis (RP) is a debilitating complication of ileal pouch reservoirs that affects hypothesized that it reflects underlying Crohn's disease. Since perinuclear anti-neutrophil cytoplasmic antibody (pANCA) is found in approximately 70% of ulcerative colitis patients but only rarely in Crohn's disease patients, it may help distinguish Crohn's disease from ulcerative colitis. Therefore, to test whether RP reflects missed Crohn's disease, we determined the ANCA status of 26 patients with RP. The pANCA was positive in 42% of cases [50% of Kock pouch cases and 33% of ileoanal pull-through (IAPT) cases] and 57% of matched control subjects without pouchitis (N=42,P=NS). Moreover, 3/6 (50%) of IAPT RP subjects whose signs and symptoms most suggested Crohn's disease tested positive for pANCA. When compared to controls, IAPT cases exhibited significantly more preoperative extraintestinal manifestations (EIMs) of inflammatory bowel disease (P<0.05). The presence of preoperative EIMs was 100% predictive of postoperative EIMs (P<0.05). Review of pouch biopsies from cases of RP revealed no pathognomonic histologic features of Crohn's disease. These data confirm our previous suggestion that RP does not reflect underlying Crohn's disease but may be associated with the EIMs of inflammatory bowel disease.     

吗替麦考酚酯治疗寡免疫复合物型新月体肾炎的疗效观察

目的比较吗替麦考酚酯(MMF)与环磷酰胺(CTX)间断静脉冲击疗法治疗寡免疫复合物型新月体肾炎(PICGN)的临床疗效。方法将1999年6月至2005年9月在南京解放军肾脏病研究所住院经临床病理确诊的44例PICGN患者分为两组,甲基泼尼松龙静脉冲击后,分别接受MMF(MMF组22例)或CTX间断静脉冲击(CTX组22例)联合激素治疗。MMF剂量1.5 g/d或2.0 g/d;CTX剂量为0.5~0.75 g/m2,每月静脉滴注1次,6个月后改为每3个月1次。所有患者随访时间6个月或以上。比较两组治疗的临床疗效和副反应。结果治疗12个月时两组总显效率分别为90.9%和72.7%,差异无统计学意义,MMF组完全显效率(59.1%)显著高于CTX组(27.3%),MMF组13例抗中性粒细胞抗体(ANCA)阳性患者中有3例(23.1%)ANCA转阴,CTX组12例AN-CA阳性患者均未转阴。随访中,MMF组1例(4.5%)复发,复发率显著低于CTX组(5例,22.7%)。MMF组5例(22.7%)发生感染,其中3例为严重肺部感染,CTX组1例(4.5%)发生肺部感染。MMF组治疗初期接受替代治疗的5例(22.7%)患者中,随访12个月时4例摆脱替代治疗;CTX组治疗初期接受肾脏替代治疗的7例(31.8%)患者中,随访12个月时5例摆脱替代治疗。治疗初期未接受替代治疗的患者中,MMF组1例(4.5%)在随访7个月时进入终末期肾病(ESRD),CTX组有4例(23.5%)分别在随访第12~72个月时进入ESRD。MMF组2例患者死于巨细胞病毒肺炎,CTX组2例患者死亡,1例死于细菌性肺炎,1例死于意外。MMF组预测5年肾存活率(81.3%)高于CTX组预测5年肾存活率(51.3%),但差异无统计学意义。结论与传统CTX疗法比较,MMF治疗PICGN诱导显效率更高,改善肾功能作用明显,复发率低,肾存活时间长。     

Limited-form Wegener's granulomatosis without anti-neutrophil cytoplasmic antibody]

A 78-year-old woman was admitted because of dry cough and weight loss. A computed tomographic (CT) scan of the thorax showed multiple masses in both lungs with and without cavitation. No other organ lesions were detected. The patient was seronegative for antineutrophil cytoplasmic antibody (ANCA) and a routine sputum culture was normal. Because specimens from transbronchial and CT-guided transluminal lung biopsies disclosed non-specific granuloma with necrosis, an excisional biopsy of the mass by video-assisted thoracoscopic surgery was performed. The specimens contained geographic basophilic necrosis with palisading histiocytes, giant cells, and neutrophils. A limited form of Wegener's granulomatosis was diagnosed on the basis of the clinical and pathological features and effects of treatment.     

Two cases of pulmonary disease with perinuclear anti-neutrophil cytoplasmic antibody]

We encountered two cases of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). The first was a case of idiopathic interstitial pneumonia diagnosed in a 73-year-old man since 1998. He was admitted to our hospital because of renal failure and anemia. The serum level of p-ANCA on admission was 264 EU, and specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis due to p-ANCA. He was treated with prednisolone pulse therapy and prednisolone (PSL), however interstitial pneumonia occurred during PSL tapering. We treated him for pulmonary fibrosis with plasmapheresis, methylprednisolone (mPSL) and cyclophosphamide (CPA), which suppressed the progress of the interstitial pneumonia. The second case was one of massive pulmonary hemorrhage in a 68-year-old man who was admitted to our hospital. Physical examination revealed anemia: the laboratory data, renal failure; and the serum level of p-ANCA was elevated to 611 EU. The specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis. The renal failure was not improved by PSL, but, together with the inflammation, responded to the combination of PSL and CPA. However, both patients died of serious infection. They were regarded as compromised patients because of the therapy mentioned above. No standard therapy has been established against p-ANCA positive pulmonary disease with renal failure. The treatment should control the progression of interstitial pneumonitis and pulmonary hemorrhage. It is important to consider the possibility of serious infection.     

血清抗中性粒细胞胞质抗体阳性肺间质病患者临床及预后分析

目的探究血清抗中性粒细胞胞质抗体(ANCA)阳性的间质性肺疾病患者的临床特点及预后。方法回顾性纳入2006年3月至2016年3月就诊于北京协和医院的间质性肺疾病患者274例,其中男81例,女193例,年龄(53±11)岁,根据诊断分为血清ANCA阳性肺间质病(ANCA-ILD)、结缔组织病相关性肺间质病和自身免疫特征的间质性肺炎(CTD-ILD/IPAF)及特发性间质性肺炎(IIP)组,分析3组患者在临床表现、血清学、肺功能、影像学、生存及复发方面的差异。结果274例患者中ANCA阳性38例(38/274,14%),发病年龄(59±10)岁,随访时间(52±31)个月,死亡7例(7/38,18%)。ANCA阳性患者发病年龄高于CTD-ILD/IPAF[(52±10)岁]和IIP[(53±11)岁,H=19.29,P<0.001],血红蛋白[(129±21)mg/L]低于CTD-ILD/IPAF[(138±15)mg/L]和IIP[(140±19)mg/L,H=8.17,P=0.017],ESR[(46±35)mm/1 h]高于CTD-ILD/IPAF[(26±24)mm/1 h]和IIP[(19±22)mm/1 h,H=19.73,P<0.001],治疗后肺功能FVC改善率(31%)低于CTD-ILD/IPAF(59%)和IIP(39%,χ^2=11.74,P=0.003),胸部CT病变吸收率(61%)低于CTD-ILD/IPAF(82%)和IIP(67%,χ^2=9.23,P=0.010),病死率(18%)高于CTD-ILD/IPAF(6%)和IIP(12%,χ^2=7.16,P=0.028)。结论ANCA阳性患者与其他类型肺间质病患者在临床特征方面存在差异,治疗效果不佳,预后较差。     

Poor renal outcomes in patients with anti-neutrophil cytoplasmic antibody-associated crescentic glomerulonephritis and normal renal function at diagnosis

Clinical Rheumatology - The aim of this study is to investigate the renal outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis in patients with normal...     

Relapses in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective study

Clinical Rheumatology - To investigate the activity of relapsing events (RE) and their mode of presentation in patients with anti-neutrophil cytoplasmic (ANCA)-associated vasculitis (AAV). Patients...     

肾脏受累为主的抗中性粒细胞胞质抗体相关性血管炎患者的预后及其相关危险因素分析

目的 探讨肾脏受累为主的抗中性粒细胞胞质抗体(ANCA)相关性血管炎患者的预后及其影响因素.方法 对2006-2008年我院诊断的64例肾脏受累为主的ANCA相关性血管炎患者进行回顾性分析,并对其进行前瞻性随访,使用Logistic回归、Cox回归等分析与患者肾脏预后有关的危险因素.结果 ①共入选64例患者,其中男性40例,女性24例,平均年龄(59.9±2.0)岁.随访21～55个月,平均(38±16)个月,期间34例(53％)患者出现死亡或进入长期肾脏替代治疗.②预后不同的2组患者起病时血肌酐[分别为(624±246)、(245±127) μmol/L,t=7.17,P=0.005]、红细胞沉降率(ESR)[分别为(112±24)、(76±48) mm/l h,t＝3.74,P＜0.01]、血浆白蛋白[分别为(294±31)、(316±42) g/L,t=-2.27,P=0.01]、血红蛋白[分别为(79±13)、(99±33) g/L,t=-3.23,P＜0.01 ]差异均有统计学意义.Logistic回归及Cox回归分析证实起病时血肌酐[β=1.004,95％可信区间(CI) 1.002～1.006,P＜0.01]及ESR[β=1.018,95％CI1.000～1.037,P=0.046]是预测患者预后的独立危险因素.③ROC曲线结果显示起病时血肌酐和ESR曲线下面积分别为0.95,0.80;敏感性均为94％,特异性分别为93％和70％.结论 以肾脏受累为主的ANCA相关性血管炎患者预后差,起病时血肌酐水平和ESR可能是判断患者预后的重要影响因素.     

寡免疫复合物型新月体肾炎的临床病理分析

为提高对寡免疫复合物型新月体肾炎（ＰＩＣＧＮ）的诊断率，报告１８例ＰＩＣＧＮ患者，占所有肾活检病例的０．３１％，新月体肾炎的２３．１０％。血管炎包括微型多动脉炎和结节性多动脉炎为常见继发病因，抗中性粒细胞胞浆抗体（ＡＮＣＡ）阳性率为４７．１％。临床上多表现为急进性肾功能减退（８３．３％），肉眼血尿发生率高（６１．１％），除贫血外，肾外表现较少。病理上血管襻坏死（６１．１％），单核及中性粒细胞浸润（４４．４％）及小血管炎等为常见的急性病变；然而，肾小球硬化（４４．４％），肾小管萎缩（８３．３％），肾间质纤维化（７２．２％）等慢性化病变也较严重。所有患者行免疫抑制治疗，１２例随访８～７２个月，无１例死亡，仅３例进入终末期肾功能衰竭。     

Analysis of clinical features and prognosis of anti-glomerular basement membrane antibody positive patients with anti-neutrophil cytoplasmic antibodies

正Objective To investigate the characteristics and outcome of glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody.Methods The sera of 23 antiGBM glomerulonephritis patients were collected and were tested for ANCA respectively.Characteristics and outcome of patients with coexisting anti-GBM antibody and     

Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab

OBJECTIVES: Rituximab (RIT) is a monoclonal anti-CD20 antibody, which depletes B-lymphocytes but not plasma cells. RIT is used for treatment of B-cell lymphomas, but has also shown beneficial effects in autoimmune diseases. In this case series RIT was used in anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. DESIGN: Case series with a structured follow-up of treated patients. SETTING: Departments of Nephrology and Rheumatology of a university hospital. SUBJECTS: Two women with myeloperoxidase-ANCA-positive microscopic polyangiitis and seven patients (five men and two women) with proteinase 3-ANCA-positive Wegener's granulomatosis. All patients were resistant to conventional therapy or had relapsed repeatedly after cessation of cyclophosphamide (Cyc). INTERVENTIONS: The cases were treated with intravenous infusions of RIT once a week two times (three cases) or four times (six cases). To prevent formation of antibodies to RIT, mycophenolate mofetil (five patients), azathioprine (one patient), or a short course of Cyc (two patients) were added or allowed to continue. MAIN OUTCOME MEASURES: Remission at 6 months assessed with Birmingham vasculitis activity score. The cases were followed 6-24 months and relapse rate was also noted. RESULTS: Eight of nine patients responded completely and one case responded partially. Pulmonary X-ray improved (four cases), progress of lower extremity gangrene stopped (one case), remission of neuropathy was stable (one patient), renal vasculitis went into remission (two cases), and severe musculoskeletal pain improved (one case). Minor relapse in the nose occurred in two cases. No adverse events or major infections were noted. CONCLUSION: RIT seems promising and safe in ANCA-positive vasculitis, and controlled studies should be conducted.     

Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody

A subset of patients with crescentic glomerulonephritis (CGN) is characterized serologically by the presence of antineutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane antibody (anti-GBM) called “double positive” disease. The clinical significance of the occurrence of both antibodies is not clear. This study aims to describe the clinical and histologic characteristics and outcomes of CGN in a US cohort of double positive (DP) patients and compare them to patients with anti-GBM disease only or ANCA only (ANCA-associated vasculitis (AAV)). Renal biopsies with a diagnosis of CGN with either pauci-immune or linear immunofluorescence were selected and classified as AAV, anti-GBM disease, or DP based on serologic testing at the time of biopsy. Data on demographics, clinical presentation, treatment, and outcome were obtained by chart review. Six patients with anti-GBM disease, 9 with DP disease, and 18 AAV patients matched for year of diagnosis with DP were identified. Extrarenal disease manifestations were more prominent in the DP patients. The DP patients had severe renal dysfunction at presentation with eight of nine patients requiring dialysis at presentation. Renal biopsy findings of DP patients were similar to anti-GBM disease with majority of glomeruli showing cellular crescents. Eighty-nine percent of patients were treated with immunosuppressive therapy and 78 % with plasmapheresis. At 1 year, all nine DP patients reached end-stage renal disease. We conclude that the DP patients share extrarenal manifestations similar to AAV patients while the renal manifestations resemble anti-GBM patients clinically and histologically. The renal prognosis of DP patients remains poor despite treatment.     

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies in patients with inflammatory bowel disease

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies (x-, c- and pANCA, respectively) are associated with a variety of inflammatory diseases, including inflammatory bowel disease (IBD). Anti-neutrophil cytoplasmic antibodies are more common in patients with ulcerative colitis (UC) than in patients with Crohn's disease (CD). Most publications only refer to p- and cANCA in relation to IBD. We have prospectively evaluated the reactivity of sera from 58 patients with IBD and 10 healthy controls against human neutrophils with emphasis on the distinction of the ANCA types. The sera were incubated with ethanol- and formaldehyde-fixed granulocytes to differentiate between c-, p- and xANCA. The results showed that 10 of 24 patients with UC were positive for ANCA, whereas only one of 34 patients with CD was ANCA positive. These results correspond to a sensitivity of 42%, a specificity of 97%, a negative predictive value of 91% and a positive predictive value of 75% in UC. Of the 11 ANCA-positive sera, two showed a cytoplasmic staining pattern, three showed a perinuclear and six an atypical staining pattern. The disease activity was not correlated to either the ANCA titre or to the presence of ANCA in the serum. In conclusion, ANCA are of limited value in differentiating between UC and CD. Because the majority of ANCA in patients with IBD are xANCA, these ANCA should be explored by not only incubating on ethanol-fixed granulocytes, but also on formaldehyde-fixed granulocytes.