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Clinical characteristics and risk factors of antineutrophil cytoplasmic antibody-associated vasculitis complicated with infection
Jiang Chunhui, Wang Huifang, Guo Dandan, Fu Zixuan, Li Min, Liu Xuemei
PDF(29048 KB)
Clinical characteristics and risk factors of antineutrophil cytoplasmic antibody-associated vasculitis complicated with infection
Objective To investigate the characteristics and risk factors of infection in newly diagnosed patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods The clinical data of AAV patients (followed up for at least 6 months) in Affiliated Hospital of Qingdao University from September 2012 to September 2020 were retrospectively collected. According to whether infection occurred during follow-up, the patients were divided into infection group and non-infection group. The clinical characteristics and infection status of the two groups were analyzed, and the Cox regression analysis model was used to explore the influencing factors of infection. Results A total of 236 AAV patients were enrolled in this study, including 128 females (54.2%) and 108 males (45.8%), with a median age of 66.00 (59.76, 71.99) years. There were 202 patients (85.6%) with positive myeloperoxidase (MPO)-ANCA and 34 patients (14.4%) with positive protease 3 (PR3) -ANCA. There were 77 cases in the infection group and 159 cases in the non-infection group. A total of 121 infections occurred in 77 patients, and 54 infections (44.6%) occurred within 6 months after initial diagnosis. In the infection group the proportion of patients with hypertension history, pulmonary underlying diseases and patients who received hormone pulse therapy or plasma exchange, the incidence of lung, kidney, heart and gastrointestinal involvement, the level of serum creatinine and five factors score (FFS) at initial diagnosis were significantly higher than those in the non-infection group (all P<0.05), while the estimated glomerular filtration rate (eGFR) was significantly lower (P<0.05). Lung (73.6%) was the main infection organ of AAV patients. The most common pathogenic microorganisms were bacteria (64.0%), mainly Pseudomonas aeruginosa and Staphylococcus aureus, followed by fungi (33.7%, mainly Candida albicans). Multivariate Cox regression analysis showed that lung involvement (HR=1.682, 95%CI 1.034-2.734, P=0.036) and gastrointestinal involvement (HR=2.976, 95%CI 1.219-7.267, P=0.017) were the independent influencing factors for infection in AAV patients. Conclusions AAV patients have a higher incidence of infection within 6 months after initial diagnosis. The most common organ of infection in AAV patients is the lung, and the common pathogens are Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Lung involvement and gastrointestinal involvement are the independent risk factors for infection in AAV patients.
Antibodies, antineutrophil cytoplasmic / Vasculitis / Infection / Risk factors / Clinical characteristics {{custom_keyword}} /
表1 抗中性粒细胞胞质抗体相关性血管炎患者的临床资料 |
| 项目 | 总数(n=236) | 感染组(n=77) | 非感染组(n=159) | 统计量(t/ Z/ χ2) | P值 |
|---|---|---|---|---|---|
| 年龄(岁) | 66.00(59.76，71.99) | 66.82(61.77，70.83) | 65.00(57.00，72.00) | 1.077 | 0.281 |
| 女性[例(%)] | 128(54.2) | 43(55.8) | 85(53.5) | 0.119 | 0.730 |
| 随访时间(月) | 32.38(15.67，56.58) | 35.10(12.00，58.19) | 30.67(16.06，51.75) | 0.078 | 0.938 |
| 吸烟[例(%)] | 85(36.0) | 27(35.1) | 58(36.5) | 0.045 | 0.832 |
| 糖尿病史[例(%)] | 27(11.4) | 12(15.6) | 15(9.4) | 1.937 | 0.164 |
| 高血压史[例(%)] | 103(43.6) | 44(57.1) | 59(37.1) | 8.467 | 0.004 |
| 肺部基础疾病[例(%)] | 55(23.3) | 27(35.1) | 28(17.6) | 8.843 | 0.003 |
| MPO-ANCA阳性[例(%)] | 202(85.6) | 67(87.0) | 135(84.9) | 0.187 | 0.666 |
| 受累部位 | |||||
| 肺部[例(%)] | 126(53.4) | 50(64.9) | 76(47.8) | 6.122 | 0.013 |
| 肾脏[例(%)] | 152(64.4) | 60(77.9) | 92(57.9) | 9.107 | 0.003 |
| 耳鼻喉[例(%)] | 43(18.2) | 19(24.7) | 24(15.1) | 3.196 | 0.074 |
| 心脏[例(%)] | 54(22.9) | 24(31.2) | 30(18.9) | 4.448 | 0.035 |
| 胃肠道[例(%)] | 12(5.1) | 9(11.7) | 3(1.9) | 8.396 | 0.004 |
| 神经系统[例(%)] | 18(7.6) | 9(11.7) | 9(5.7) | 2.676 | 0.102 |
| 实验室检查 | |||||
| 白细胞计数(×109/L) | 9.49(7.44，11.88) | 9.23(7.44，11.85) | 9.70(7.41，11.89) | 0.298 | 0.766 |
| 中性粒细胞计数(×109/L) | 6.97(5.10，9.23) | 6.67(5.16，8.87) | 6.99(4.89，9.49) | 0.265 | 0.791 |
| 淋巴细胞计数(×109/L) | 1.42(1.06，1.91) | 1.35(0.99，1.82) | 1.44(1.12，1.94) | 1.206 | 0.228 |
| 血小板计数(×109/L) | 297.13±111.18 | 288.62±122.59 | 301.25±105.28 | 0.818 | 0.414 |
| 血红蛋白(g/L) | 102.73±22.07 | 99.06±22.49 | 104.51±21.71 | 1.785 | 0.076 |
| C反应蛋白(mg/L) | 44.45(10.58，76.01) | 42.16(13.30，70.69) | 49.30(8.89，81.37) | 0.096 | 0.924 |
| 红细胞沉降率(ml/h) | 70.73±36.45 | 73.81±37.02 | 69.24±36.19 | 0.903 | 0.368 |
| 补体C3(g/L) | 1.06±0.26 | 1.02±0.25 | 1.07±0.25 | 1.681 | 0.094 |
| 补体C4(g/L) | 0.27(0.22，0.32) | 0.26(0.22，0.31) | 0.27(0.22，0.33) | 1.252 | 0.211 |
| IgG(g/L) | 13.90(11.10，16.30) | 13.30(10.30，16.35) | 14.20(11.43，16.02) | 0.959 | 0.338 |
| IgM(g/L) | 0.96(0.71，1.19) | 0.90(0.62，1.22) | 0.97(0.76，1.18) | 0.844 | 0.399 |
| IgE(IU/ml) | 143.05(49.68，363.69) | 112.00(31.28，379.55) | 174.69(53.99，344.98) | 0.625 | 0.532 |
| IgA(g/L) | 2.45(1.91，3.00) | 2.37(1.79，3.07) | 2.47(1.96，2.93) | 0.794 | 0.427 |
| 白蛋白(g/L) | 30.76±5.84 | 29.81±4.93 | 31.22±6.19 | 1.897 | 0.059 |
| 血肌酐(μmol/L) | 118.50(78.25，244.00) | 154.00(84.00，402.00) | 101.00(77.00，199.00) | 3.056 | 0.002 |
| eGFR | 52.72(18.89，78.23) | 31.16(11.38，75.83) | 58.89(24.56，78.54) | 2.929 | 0.003 |
| FFS(分) | 2.01±1.05 | 2.27±1.17 | 1.86±0.97 | 2.511 | 0.013 |
| 治疗方案 | |||||
| 激素冲击[例(%)] | 60(25.4) | 26(33.8) | 34(21.4) | 4.195 | 0.041 |
| 血浆置换[例(%)] | 30(12.7) | 16(20.8) | 14(8.8) | 6.704 | 0.010 |
| 单用激素[例(%)] | 81(34.3) | 27(35.1) | 54(34.0) | 0.028 | 0.867 |
| 激素+CTX[例(%)] | 124(52.5) | 39(50.6) | 85(53.5) | 0.164 | 0.685 |
| 激素+其他免疫抑制剂[例(%)] | 31(13.1) | 11(14.3) | 20(12.6) | 0.132 | 0.716 |
| 注：MPO-ANCA：髓过氧化物酶-中性粒细胞胞质抗体；eGFR：估算肾小球滤过率，单位为ml·min-1·(1.73 m2)-1；FFS：五因子评分；CTX：环磷酰胺；其他免疫抑制剂：霉酚酸酯、环孢素、硫唑嘌呤、他克莫司、利妥昔单抗等；正态分布的计量资料采用 |
表2 抗中性粒细胞胞质抗体相关性血管炎患者的感染特征 |
| 感染特征 | 数量(%) |
|---|---|
| 感染次数(次) | |
| 1 | 50(64.9) |
| 2 | 16(20.8) |
| ≥3 | 11(14.3) |
| 感染部位 | |
| 肺部 | 89(73.6) |
| 泌尿道 | 13(10.7) |
| 口腔 | 6(5.0) |
| 导管 | 5(4.1) |
| 腹膜 | 3(2.5) |
| 消化道 | 3(2.5) |
| 中枢神经系统 | 2(1.7) |
| 病原体类型 | |
| 细菌 | |
| 铜绿假单胞菌 | 10 |
| 金黄色葡萄球菌 | 8 |
| 大肠杆菌 | 6 |
| 阴沟肠杆菌 | 6 |
| 嗜麦芽窄食单胞菌 | 4 |
| 肠球菌 | 4 |
| 克雷伯菌 | 4 |
| 鲍曼不动杆菌 | 2 |
| 嗜血杆菌 | 2 |
| 肺炎球菌 | 2 |
| 产气杆菌 | 1 |
| 支气管炎伯特菌 | 1 |
| 其他革兰阴性杆菌 | 5 |
| 真菌 | |
| 白念珠菌 | 19 |
| 曲霉 | 9 |
| 青霉菌 | 1 |
| 病毒 | |
| EB病毒 | 1 |
| 未确定的病毒类型 | 1 |
| 注：其他革兰阴性杆菌：嗜水气单胞菌、弗氏柠檬酸杆菌、泛菌属 |
表3 抗中性粒细胞胞质抗体相关性血管炎患者发生感染的影响因素分析（Cox回归分析） |
| 影响因素 | 单因素分析 | 多因素分析 | ||
|---|---|---|---|---|
| HR(95%CI) | P值 | HR(95%CI) | P值 | |
| 年龄>65岁(是/否) | 1.500(0.950~2.368) | 0.082 | ||
| MPO-ANCA阳性(是/否) | 1.127(0.577~2.199) | 0.727 | ||
| 吸烟史(有/无) | 1.001(0.626~1.599) | 0.998 | ||
| 糖尿病史(有/无) | 1.499(0.808~2.779) | 0.199 | ||
| 高血压史(有/无) | 1.777(1.130~2.794) | 0.013 | 1.658(0.975~2.822) | 0.062 |
| 肺部基础疾病(有/无) | 1.527(0.950~2.455) | 0.080 | ||
| 肺部受累(有/无) | 1.741(1.090~2.782) | 0.002 | 1.682(1.034~2.734) | 0.036 |
| 肾脏受累(有/无) | 2.228(1.300~3.819) | 0.004 | 1.566(0.794~3.088) | 0.196 |
| 心脏受累(有/无) | 1.563(0.964~2.533) | 0.070 | ||
| 胃肠道受累(有/无) | 2.895(1.441~5.816) | 0.003 | 2.976(1.219~7.267) | 0.017 |
| 耳鼻喉受累(有/无) | 1.396(0.831~2.345) | 0.208 | ||
| 神经系统受累(有/无) | 2.206(0.838~5.804) | 0.109 | ||
| 血红蛋白<90 g/L(是/否) | 1.638(1.038~2.584) | 0.034 | 1.011(0.560~1.825) | 0.970 |
| 血清白蛋白<30 g/L(是/否) | 1.803(1.150~2.828) | 0.010 | 1.406(0.850~2.325) | 0.184 |
| 白细胞计数(每增加1×109/L) | 1.018(0.964~1.074) | 0.527 | ||
| 中性粒细胞计数(每增加1×109/L) | 1.031(0.983~1.081) | 0.213 | ||
| 淋巴细胞计数(每增加1×109/L) | 0.815(0.587~1.132) | 0.222 | ||
| 血小板计数(每增加1×109/L) | 1.000(0.998~1.002) | 0.839 | ||
| C反应蛋白(每增加1 mg/L) | 1.002(0.998~1.006) | 0.368 | ||
| 红细胞沉降率(每增加1 ml/h) | 1.004(0.998~1.010) | 0.182 | ||
| 补体C3(每增加1 g/L) | 0.505(0.229~1.117) | 0.092 | ||
| 补体C4(每增加1 g/L) | 1.042(0.127~8.550) | 0.970 | ||
| IgG(每增加1 g/L) | 0.994(0.953~1.036) | 0.765 | ||
| IgM(每增加1 g/L) | 0.962(0.692~1.336) | 0.816 | ||
| IgE(每增加1 IU/ml) | 1.000(1.000~1.001) | 0.262 | ||
| IgA(每增加1 g/L) | 0.885(0.706~1.109) | 0.289 | ||
| 血肌酐(每增加1 μmol/L) | 1.002(1.001~1.003) | <0.001 | 1.001(0.999~1.003) | 0.246 |
| eGFR[每增加1 ml·min-1·(1.73 m2)-1] | 0.987(0.980~0.995) | 0.001 | 1.005(0.990~1.020) | 0.514 |
| FFS(每增加1分) | 1.397(1.132~1.725) | 0.002 | 1.006(0.741~1.364) | 0.971 |
| 激素冲击(有/无) | 1.707(1.064~2.741) | 0.027 | 1.219(0.692~2.148) | 0.493 |
| 血浆置换(有/无) | 2.369(1.363~4.118) | 0.002 | 1.673(0.863~3.244) | 0.128 |
| 单用激素 | 参照 | 参照 | ||
| 激素+CTX | 0.851(0.544~1.332) | 0.481 | 0.931(0.524~1.653) | 0.806 |
| 激素+其他免疫抑制剂 | 1.107(0.584~2.100) | 0.755 | 0.908(0.420~1.966) | 0.807 |
| 注：MPO-ANCA：髓过氧化物酶-中性粒细胞胞质抗体；eGFR：估算肾小球滤过率；FFS：五因子评分；CTX：环磷酰胺；变量赋值：单用激素=0，激素+CTX=1，激素+其他免疫抑制剂=2 |
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To estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) and its subsets, granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), in a US‐based adult population.
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Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening autoimmune diseases. The epidemiological data on AAV in China are limited. The aim of the present study is to investigate the frequency, geographical distribution, and ethnic distribution of AAV in hospitalized patients in China, and its association with environmental pollution.We investigated the hospitalized patients in a national inpatient database covering 54.1% tertiary hospitals in China from 2010 to 2015. Diagnosis of AAV was extracted according to the definition of International Classification of Diseases (ICD)-10 codes and free text. Variables from the front page of inpatient records were collected and analyzed, including frequency, geographic distribution, demographic characteristics and seasonal variations of AAV. The association between various environmental pollutants and frequency of AAV was further analyzed.Among 43.7 million inpatients included in the study period, 0.25‰ (10,943) were diagnosed as having AAV. The frequency of AAV was relatively stable during the study period (from 0.34‰ in 2010 to 0.27‰ in 2015). The proportion of AAV increased with latitude (0.44‰ in Northern China and 0.27‰ in Southern China in 2015). Hospitalizations were mostly observed in winter (30.2%). The Dong population, an ethnic minority of the Chinese population, had the highest frequency of patients with AAV (0.67‰). We also found a positive association between the exposure to carbon monoxide and the frequency of AAV (R = 0.172, p = 0.025). In Yunnan province, the frequency of AAV increased 1.37-fold after the Zhaotong earthquake, which took place in 2014.Our present investigation of hospitalized patients provided epidemiological information on AAV in China for the first time. A spatial and ethnic clustering trend and an association between pollution and the frequency of AAV were observed.
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To determine the magnitude of all-cause mortality risk in patients with antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) compared with the general population through a meta-analysis of observational studies.We searched Medline and Embase databases from their inception to April 2015. Observational studies that met the following criteria were assessed by two researchers: (1) clearly defined AAV identified by either the American College of Rheumatology 1990 classification criteria or the 2012 Chapel Hill Consensus Conference disease definitions, and (2) reported standardised mortality ratios (SMR) and 95% CI. We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for all-cause mortality using random-effects model, tested for publication bias and heterogeneity.Ten studies met the inclusion criteria, comprising 3338 patients with AAV enrolled from 1966 to 2009, and a total of 1091 observed deaths. Overall, we found a 2.7-fold increased risk of death in patients with AAV when compared with the general population (meta-SMR: 2.71 (95% CI 2.26 to 3.24)). Analysis on studies that included only granulomatosis with polyangiitis cases also indicated a similar mortality risk (meta-SMR: 2.63 (95% CI 2.02 to 3.43)). There was no significant publication bias or small-study effect. Subgroup analyses showed that mortality risks were higher in older cohorts, with a trend towards improvement over time (ie, those with their midpoint of enrolment periods that were between 1980-1993 and 1994-1999, vs 2000-2005).Published data indicate there is a 2.7-fold increase in mortality among patients with AAV compared with the general population.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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The objective of this study was to evaluate causes of death in a contemporary inception cohort of ANCA-associated vasculitis patients, stratifying the analysis according to ANCA type.We identified a consecutive inception cohort of patients newly diagnosed with ANCA-associated vasculitis from 2002 to 2017 in the Partners HealthCare System and determined vital status through the National Death Index. We determined cumulative mortality incidence and standardized mortality ratios (SMRs) compared with the general population. We compared MPO- and PR3-ANCA+ cases using Cox regression models.The cohort included 484 patients with a mean diagnosis age of 58 years; 40% were male, 65% were MPO-ANCA+, and 65% had renal involvement. During 3385 person-years (PY) of follow-up, 130 patients died, yielding a mortality rate of 38.4/1000 PY and a SMR of 2.3 (95% CI: 1.9, 2.8). The most common causes of death were cardiovascular disease (CVD; cumulative incidence 7.1%), malignancy (5.9%) and infection (4.1%). The SMR for infection was greatest for both MPO- and PR3-ANCA+ patients (16.4 and 6.5). MPO-ANCA+ patients had an elevated SMR for CVD (3.0), respiratory disease (2.4) and renal disease (4.5). PR3- and MPO-ANCA+ patients had an elevated SMR for malignancy (3.7 and 2.7). Compared with PR3-ANCA+ patients, MPO-ANCA+ patients had a higher risk of CVD death [hazard ratio 5.0 (95% CI: 1.2, 21.2]; P = 0.03].Premature ANCA-associated vasculitis mortality is explained by CVD, infection, malignancy, and renal death. CVD is the most common cause of death, but the largest excess mortality risk in PR3- and MPO-ANCA+ patients is associated with infection. MPO-ANCA+ patients are at higher risk of CVD death than PR3-ANCA+ patients.© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) have high mortality despite the introduction of immunosuppressive therapy. We investigated factors associated with mortality of patients with AAV in a single Chinese cohort.
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We estimated the cumulative patient survival rates, the causes of death and the initial predictors of death in Korean patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA).We reviewed the medical records of 153 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We collected clinical and laboratory data including ANCA, Birmingham vasculitis activity score (BVAS), five factor score (FFS) (2009), comorbidities, medications and prognosis (death and relapse). The hazard ratio (HR) of variables at diagnosis for death in the disease course was assessed by the Cox hazard model analysis.The mean age of 153 AAV patients (47 men and 106 women) was 55.2 years and the mean follow-up duration was 51.5 months. Fourteen of 153 patients (9.2%) died (7 MPA and 7 GPA patients) during the mean follow-up of 56.9 months. In all patients with AAV, 1 year-, 5 year- and 10 year-cumulative patient survival rates were 96.1%, 94.8% and 92.8%, respectively. The most common cause of death was infection of various causes. FFS (2009) ≥2 (HR 16.520, p=0.012) and diffuse alveolar haemorrhage (DAH) (HR 3.705, p=0.042) at diagnosis could predict death during the follow-up in AAV patients in multivariate COX regression analysis.The overall mortality rate was 9.2% and 10-year cumulative patient survival rate was 92.8%. At diagnosis, FFS (2009) ≥ 2 and DAH were independent predictors of death during the follow-up in Korean patients with MPA, GPA and EGPA.
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中华医学会肾脏病学分会专家组. 抗中性粒细胞胞质抗体相关肾炎诊断和治疗中国指南[J]. 中华肾脏病杂志, 2021, 37(7): 603-620. DOI: 10.3760/cma.j.cn441217-20210107-00092.
抗中性粒细胞胞质抗体（anti-neutrophil cytoplasmic antibody，ANCA）相关肾炎（ANCA-associated glomerulonephritis，AAGN）是造成中老年肾脏病患者急性肾功能减退的主要原因，病情严重，人肾存活率低。我国AAGN患者的ANCA类型、临床特征及预后与欧美国家的AAGN存在差异。基于我国对AAGN的临床研究证据并借鉴国外相关指南，中华医学会肾脏病学分会组织专家制定了ANCA相关肾炎的诊断和治疗中国指南，在AAGN的诊断和评估、随访管理、诱导期和维持期治疗、顽固性和复发性AAGN的治疗及感染的预防等方面提出了推荐或建议，为规范临床实践和个体化治疗决策的制定提供了指导意见。
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An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.
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| [14] |
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| [15] |
Involvement of the gastrointestinal (GI) tract is a rare complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The aim was to describe frequency, diagnosis, treatment, and outcome of GI disease in a large series of patients in a single center.A database that includes all patients with GPA and MPA diagnosed since 1997 in a defined area of southeastern Sweden as well as prevalent older cases and tertiary referral patients was screened for patients with GI disease. Data were retrieved from the patient's medical records, and GI manifestations of vasculitis were defined as proposed by Pagnoux, in 2005.Fourteen (6.5%) of 216 consecutive patients with GPA/MPA had GI manifestations. Abdominal pain and GI bleeding were the most common symptoms. Radiology was important for detection of GI disease, while endoscopy failed to support the diagnosis in many patients. Because of perforation, 5 patients underwent hemicolectomy or small intestine resection. Primary anastomosis was created in 2/5 and enterostomy in 3/5 patients. One patient had a hemicolectomy because of lower GI bleeding. One sigmoid abscess was treated with drainage, and 1 intraabdominal bleeding condition with arterial coiling. Two patients died from GI disease. GPA and MPA patients with and without GI disease exhibited a similar overall survival.GI disease was found in 6.5% among 216 patients with GPA or MPA. Surgery was judged necessary only in cases with GI perforation or severe bleeding. Multidisciplinary engagement is strongly recommended.
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| [16] |
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| [17] |
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| [18] |
To provide a comprehensive review of the central nervous system (CNS) involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including the pathogenesis, clinical manifestations, ancillary investigations, differential diagnosis, and treatment. Particular emphasis is placed on the clinical spectrum and diagnostic testing of AAV. AAV is a pauci-immune small-vessel vasculitis characterized by neutrophil-mediated vasculitis and granulomatousis. Hypertrophic pachymeninges is the most frequent CNS presentation. Cerebrovascular events, hypophysitis, posterior reversible encephalopathy syndrome (PRES) or isolated mass lesions may occur as well. Spinal cord is rarely involved. In addition, ear, nose and throat (ENT), kidney and lung involvement often accompany or precede the CNS manifestations. Positive ANCA testing is highly suggestive of the diagnosis, with each ANCA serotype representing different groups of AAV patients. Pathological evidence is the gold standard but not necessary. Once diagnosed, prompt initiation of induction therapy, including steroid and other immunosuppressants, can greatly mitigate the disease progression. Early recognition of AAV as the underlying cause for various CNS disorders is important for neurologists. Ancillary investigations especially the ANCA testing can provide useful information for diagnosis. Future studies are needed to better delineate the clinical spectrum of CNS involvement in AAV and the utility of ANCA serotype to classify those patients. We searched Pubmed for relevant case reports, case series, original research and reviews in English published between Sep 1st, 2001 and Sep 1st, 2018. The following search terms were used alone or in various combinations: "ANCA," "proteinase 3/PR3-ANCA," "myeloperoxidase/MPO-ANCA," "ANCA-associated vasculitis," "Wegener's granulomatosis," "microscopic polyangiitis," "Central nervous system," "brain" and "spinal cord". All articles identified were full-text papers.
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| [19] |
Comprehensive multisystem clinical assessment using the Birmingham Vasculitis Activity score (BVAS) is widely used in therapeutic studies of systemic vasculitis. Extensive use suggested a need to revise the instrument. The previous version of BVAS has been revised, according to usage and reviewed by an expert committee.To modify and validate version 3 of the BVAS in patients with systemic vasculitis.The new version of BVAS was tested in a prospective cross-sectional study of patients with vasculitis.The number of items was reduced from 66 to 56. The subscores for new/worse disease and persistent disease were unified. In 313 patients with systemic vasculitis, BVAS(v.3) correlated with treatment decision (Spearman's r(s) = 0.66, 95% CI 0.59 to 0.72), BVAS1 of version 2 (r(s) = 0.94, 95% CI 0.92 to 0.96), BVAS2 of version 2 in patients with persistent disease (r(s) = 0.60, 95% CI 0.21 to 0.83), C-reactive protein levels (r(s) = 0.43, 95% CI 0.31 to 0.54), physician's global assessment (r(s) = 0.91, 95% CI 0.89 to 0.93) and vasculitis activity index (r(s) = 0.88, 95% CI 0.86 to 0.91). The intraclass correlation coefficients for reproducibility and repeatability were 0.96 (95% CI 0.95 to 0.97) and 0.96 (95% CI 0.92 to 0.97), respectively. In 39 patients assessed at diagnosis and again at 3 months, the BVAS(v.3) fell by 17 (95% CI 15 to 19) units (p<0.001, paired t test).BVAS(v.3) demonstrates convergence with BVAS(v.2), treatment decision, physician global assessment of disease activity, vasculitis activity index and C-reactive protein. It is repeatable, reproducible and sensitive to change. The new version of BVAS is validated for assessment of systemic vasculitis.
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| [20] |
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| [21] |
Researchers have developed several equations to predict glomerular filtration rate (GFR) in patients with chronic kidney diseases (CKD). However, there are scarcely any studies performed to discern the best equation to estimate GFR in patients with pure obstructive nephropathy. In present study, we assessed the suitability of six prediction equations and compared their performance in eGFR evaluation for Chinese patients with obstructive nephropathy.A total of 245 adult patients with obstructive nephropathy were enrolled. We evaluated the performance of the 3 Modification of Diet in Renal Disease equations (MDRD) (the original MDRD7, 7MDRD; the abbreviated MDRD, aMDRD; and re-expressed abbreviated MDRD, re-aMDRD) and 3 Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI) (CKD-EPI equation based on creatinine alone, CKD-EPIcr; CKD-EPI equation based on cystatin C alone, CKD-EPIcys; CKD-EPI equation based on combined creatinine-cystatin, CKD-EPIcr-cys). The measured GFR (mGFR) by mTc-DTPA renal dynamic imaging method was used as the reference GFR.The mean age of the study population was 51.61 ± 14.17 and 131 were male (53.47 %). The mean measured GFR was 66.54 ± 23.99 ml/min/1.73 m. Overall, the CKD-EPIcr-cys equation gave the best performance with the best correlation (R = 0.72) and agreement (-34.87, 40.83). CKD-EPIcr-cys equation also exhibited the highest accuracy (69.39 %, P < 0.01) and diagnostic efficacy (ROC = 0.874) with the smallest bias (2.98, P < 0.01). In the subgroup of the lowest GFR, CKD-EPIcys equation exhibited the highest accuracy (52.69 %) and the smallest bias (0.27). In the youngest age subgroup, CKD-EPIcys equation had the highest accuracy (71.64 %) and the smallest bias (-1.24). In other subgroups stratified by GFR, age and gender, CKD-EPIcr-cys equation remained the best performance.The 3 CKD-EPI equations performed better than the 3 MDRD equations in estimating GFR in Chinese obstructive nephropathy patients; while the CKD-EPI equation based on combined creatinine-cystatin C provided the best estimation of GFR.
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| [22] |
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| [23] |
Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV.We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)].AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.
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| [24] |
To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome.A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated.Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96-228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause.Our results confirm that major infections are the main cause of death in patients with AAV.
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| [25] |
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| [26] |
Antineutrophil cytoplasmic antibodies (ANCAs) are autoantibodies specific for antigens located in the cytoplasmic granules of neutrophils and lysosomes of monocytes. ANCAs are associated with a spectrum of necrotizing vasculitis that includes granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Pulmonary vasculitis and related extravascular inflammation and fibrosis are frequent components of ANCA vasculitis. In this review, we detail the factors that have been associated with the origin of the ANCA autoimmune response and summarize the most relevant clinical observations, in vitro evidence, and animal studies strongly indicating the pathogenic potential of ANCA. In addition, we describe the putative sequence of pathogenic mechanisms driven by ANCA-induced activation of neutrophils that result in small vessel necrotizing vasculitis and extravascular granulomatous necrotizing inflammation.Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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| [27] |
胡剑, 高春林, 张沛, 等. 抗中性粒细胞胞质抗体相关性血管炎发病机制及治疗的研究进展[J]. 中华肾脏病杂志, 2020, 36(5): 412-416. DOI: 10.3760/cma.j.cn441217-20190920-00078.
抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）主要以小血管壁的炎性反应和纤维素样坏死为病理表现，伴随血清ANCA 阳性，累及全身多系统的自身免疫性疾病。主要临床表现包括：显微镜下多血管炎（MPA），肉芽肿性多血管炎（GPA），嗜酸性肉芽肿性多血管炎（EGPA）等。最常见累及器官包括呼吸道及肾脏，病情凶险，死亡率高。本文旨在综述AAV发病机制及治疗方法的最新研究进展。
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| [28] |
We investigated the association of airway comorbidities with the clinical phenotypes and outcomes of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA)-positive ANCA-associated vasculitis (AAV).An AAV patient multicenter cohort trial was established in 13 hospitals in western Japan between 2012 and 2018. We examined 143 of the new-onset MPO-ANCA-positive AAV patients. Their clinical characteristics and comorbidities at disease onset were compared based on clinical phenotypes. Multivariate analysis was performed to identify factors predictive of remission and death.Twenty-seven cases with granulomatosis with polyangiitis (GPA), 10 with eosinophilic GPA (EGPA), 81 with microscopic polyangiitis (MPA), and 25 with unclassified AAV were identified. The average age of MPO-ANCA-positive patients was 71.4 years. Comorbidity (87.4%) and airway comorbidity (70.6%) were frequently observed in these patients. Examination of the clinical phenotypes revealed that the cases of GPA were frequently accompanied by infectious airway comorbidity (upper airway disease, bronchiectasis, pulmonary infections), and most of the cases of MPA and unclassified AAV were accompanied by fibrotic interstitial lung disease (fILD) or emphysema. Among MPO-ANCA-positive patients, infectious airway comorbidity was predictive of both remission (HR 1.58, = 0.03) and mortality (HR 2.64, = 0.04), and fILD was predictive of mortality (HR 7.55, = 0.008). The combination of infectious airway comorbidities and fILD caused the worst survival outcomes in patients.MPO-ANCA-positive AAV was frequently accompanied by airway comorbidities. In addition to fILD, infectious airway comorbidities were closely associated with those clinical phenotypes and outcomes.Copyright © 2021 by the Journal of Rheumatology.
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| [29] |
Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.
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| [30] |
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| [31] |
Involvement of the gastrointestinal (GI) tract is a rare complication of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The aim was to describe frequency, diagnosis, treatment, and outcome of GI disease in a large series of patients in a single center.A database that includes all patients with GPA and MPA diagnosed since 1997 in a defined area of southeastern Sweden as well as prevalent older cases and tertiary referral patients was screened for patients with GI disease. Data were retrieved from the patient's medical records, and GI manifestations of vasculitis were defined as proposed by Pagnoux, in 2005.Fourteen (6.5%) of 216 consecutive patients with GPA/MPA had GI manifestations. Abdominal pain and GI bleeding were the most common symptoms. Radiology was important for detection of GI disease, while endoscopy failed to support the diagnosis in many patients. Because of perforation, 5 patients underwent hemicolectomy or small intestine resection. Primary anastomosis was created in 2/5 and enterostomy in 3/5 patients. One patient had a hemicolectomy because of lower GI bleeding. One sigmoid abscess was treated with drainage, and 1 intraabdominal bleeding condition with arterial coiling. Two patients died from GI disease. GPA and MPA patients with and without GI disease exhibited a similar overall survival.GI disease was found in 6.5% among 216 patients with GPA or MPA. Surgery was judged necessary only in cases with GI perforation or severe bleeding. Multidisciplinary engagement is strongly recommended.
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| [32] |
Although the gastrointestinal (GI) tract including its related organs is not generally regarded as one of the primary organ systems of primary and secondary vasculitic disorders, there are numerous mechanisms of these diseases operative in or around the different structures and compartments of the GI tract.A majority of the respective clinical symptoms and problems are linked to an alteration of (peri)vascular homeostasis. Alteration of perivascular matrix metabolism can also affect the functional integrity and motility of the GI tract. Apart from the specific GI phenomena of the individual diseases as outlined in detail in this review, the epidemiology of GI involvement follows in general the characteristics of the respective underlying systemic disease. In addition, gender and age do neither influence the occurrence nor the severity of the GI manifestations significantly. With respect to clinical symptoms, vasculitides may result in abdominal pain, bleeding, ileus, intestinal necrosis and hematochezia because of reduced blood flow and hyper-acute occlusion in the antiphospholipid syndrome. Small-bowel involvement in vasculitic entities can cause pseudoobstruction, obstruction, malabsorption and bacterial overgrowth. Laboratory parameters can point to specific diseases but are frequently nonspecific. Thus, if biopsy fails or in unclear endoscopic situations, a variety of imaging techniques including Doppler ultrasound, abdominal CT, MRI and angiography are used and required for identification and localization of the underlying disease. Therapeutic strategies in vasculitides usually include corticosteroids and immunosuppressants, for example, cyclophosphamide in granulomatosis with polyangiitis and in panarteriitis nodosa but also biologics such as rituximab in ANCA-associated vasculitides. Virostatic drugs including interferon-α and ribavirin can be used in hepatitis B- and C-triggered vasculitides such as panarteriitis nodosa and hepatitis C-associated cryoglobulinemia.Immediate diagnostic and therapeutic steps of action need to be performed if vasculitis of the GI tract is suspected in order to avoid irreversible damage to organs and to improve the well-being and life of the affected patient.© 2016 S. Karger AG, Basel.
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| [33] |
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| [34] |
To compare the accuracy of the Birmingham Vasculitis Activity Score (BVAS), version 3, and the Five Factor Score (FFS), version 1996 and version 2009, to assess survival in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).A total of 550 patients with AAV (41.1% with granulomatosis with polyangiitis, 37.3% with microscopic polyangiitis, and 21.6% with eosinophilic granulomatosis with polyangiitis), diagnosed between 1990 and 2016, were analyzed. Receiver operating characteristic (ROC) curves and multivariable Cox analysis were used to assess the relationships between the outcome and the different scores.Overall mortality was 33.1%. The mean ± SD BVAS at diagnosis was 17.96 ± 7.82 and was significantly higher in nonsurvivors than in survivors (mean ± SD 20.0 ± 8.14 versus 16.95 ± 7.47, respectively; P < 0.001). The mean ± SD 1996 FFS and 2009 FFS were 0.81 ± 0.94 and 1.47 ± 1.16, respectively, and were significantly higher in nonsurvivors than in survivors (mean ± SD 1996 FFS 1.17 ± 1.07 versus 0.63 ± 0.81 [P < 0.001] and 2009 FFS 2.13 ± 1.09 versus 1.15 ± 1.05 [P < 0.001], respectively). Mortality rates increased according to the different 1996 FFS and 2009 FFS categories. In multivariate analysis, BVAS, 1996 FFS, and 2009 FFS were significantly related to death (P = 0.007, P = 0.020, P < 0.001, respectively), but the stronger predictor was the 2009 FFS (hazard ratio 2.9 [95% confidence interval 2.4-3.6]). When the accuracy of BVAS, 1996 FFS, and 2009 FFS to predict survival was compared in the global cohort, ROC analysis yielded area under the curve values of 0.60, 0.65, and 0.74, respectively, indicating that 2009 FFS had the best performance. Similar results were obtained when comparing these scores in patients diagnosed before and after 2001 and when assessing the 1-year, 5-year, and long-term mortality. Correlation among BVAS and 1996 FFS was modest (r = 0.49; P < 0.001) but higher than between BVAS and the 2009 FFS (r = 0.28; P < 0.001).BVAS and FFS are useful to predict survival in AAV, but the 2009 FFS has the best prognostic accuracy at any point of the disease course.© 2019, American College of Rheumatology.
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| [35] |
To determine the incidence rate, predictors and outcome of severe infections in a population-based cohort of ANCA-associated vasculitis (AAV).The study included 325 cases of AAV (152 female) diagnosed from 1997 through 2016 from a defined geographic area in Sweden. All severe infection events (requiring hospitalization and treatment with intravenous antimicrobials) were identified. The Birmingham vasculitis activity score (BVAS) was used to evaluate disease activity, and organ damage was assessed using the vasculitis damage index (VDI). Patients were followed from time of AAV diagnosis to death or December 2017.A total of 129 (40%) patients suffered at least one severe infection. In 2307 person-years (PY) of follow-up, 210 severe infections were diagnosed. The incidence rate of severe infections was 9.1/100 PY and was highest during the first year following AAV diagnosis at 22.1/100 PY (P < 0.001). Pneumonia, sepsis and urinary tract infection were the most common infections. Opportunistic infections constituted only 6% of all severe infections. In Cox regression analysis age and BVAS at diagnosis were the only factors independently predicting severe infection [hazard ratio: 1.54 (P < 0.001) and 1.27 (P = 0.001), respectively]. Severe infection was associated with poorer prognosis with respect to median VDI score 12 months post-AAV diagnosis, renal survival and mortality. Severe infections were the cause of death in 32 patients (22% of all deaths).. Severe infection is a common problem in AAV, with the most important prognostic factors being older age and high disease activity at diagnosis. Severe infections are associated with permanent organ damage and high mortality.© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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| [36] |
We investigated the development rate and time, risk factors, predictors, and aetiologies of hospitalised infection in Korean patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We retrospectively reviewed the medical records of 154 patients with AAV. Hospitalised infection was considered only when patients were admitted for serious infection related to AAV or AAV treatment. The gap-time was defined as the period from diagnosis to the first hospitalised infection or to the last visit for uninfected patients. We calculated Birmingham vasculitis activity score (BVAS) or BVAS for granulomatosis with polyangiitis (GPA) and five factor score (FFS (2009)) and reviewed medications administered. We set the optimal cut-offs of BVAS and that of FFS (2009) at diagnosis at 20.5 and 1.5. Forty-four patients (28.6%) were admitted for serious infection. One-, 5- and 10-year hospitalised infection free survival rates were 85.1, 77.9 and 72.7%, respectively. In multivariable logistic regression analysis of significant variables in comparison analysis, only chest manifestation at diagnosis (OR 2.692) was remarkably associated with hospitalised infection. In multivariable Cox hazard model analysis of significant variables in Kaplan-Meier analysis, BVAS at diagnosis ≥ 20.5 (HR 2.375) and chest manifestation at diagnosis (HR 2.422) were independent predictors of hospitalised infection during the gap-time. Bacterial pneumonia was the most common infectious aetiology (N = 29), followed by fungal infection including aspergillosis (N = 6). BVAS and chest manifestation at diagnosis can predict hospitalised infection during the gap-time.
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姜春晖：查阅文献、研究设计、数据汇总分析、文章撰写；王惠芳：帮助设计、统计分析、文章修改；郭丹丹、 付子萱、李敏：数据收集、查阅文献；刘雪梅：研究设计指导、文章修改、研究经费支持
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