结节性多动脉炎的诊治进展

结节性多动脉炎（PAN）在早期是指代大多数的血管炎.随着对血管炎研究的深入,越来越多的特异性血管炎被划分出来.以前的“PAN合并类风湿关节炎”现在被命名为“类风湿关节炎血管炎”;而大多数“累及肺部的结节性多动脉炎”则改称为“嗜酸性肉芽肿性多血管炎”（EGPA,既往称为churg-strauss综合征）;随着抗中性粒细胞胞浆抗体（ANCA）检查在临床中的普及以及对ANCA在血管炎中的致病作用研究,显微镜下多血管炎（MPA）也从PAN中被区分出来[1].     

结节性多动脉炎及微型多发性血管炎的比较

系统性血管炎的分类标准至今未能确定。几十年来，人们习惯将结节性多动脉炎（dyarterltlsnodosa，PAN）与微型多发性血管炎（mlcrosconlcnolvangiitis，MPA）等同考虑，甚至美国风湿病协会制定的PAN诊断标准亦未将PAN与MPA相区分。但近年研究表明，PAN与MPA是两种不同类型的血管炎，现将这两种血管炎的临床及组织学特点介绍如下：三微型多发性血管炎（MPA）Dovson，Bull及Putt首先描述了微型结节性多动脉炎的病理改变。他们发现，在PAN患者所见到的节段坏死性肾小管肾炎实际上是一种微血管型PAN，它与Maier及Kussmaul等描述…     

结节性多动脉炎

结节性多动脉炎 (PAN) 186 6年由 Kaussmaul和 Maier首次提出。此后多年 PAN曾被用于小血管炎的通用名词 ,包涵了多种目前已独立出来的系统性血管炎 ,如 Wegener肉芽肿、巨细胞动脉炎等。近 10年来随着对血管炎认识的不断深入 ,特别是 1993年 Chapel- Hill会议新的分类标准出台 ,后显微镜下多血管炎 (MPA)也从 PAN中鉴别出来 ,PAN的概念更为明确。目前 PAN基本概念包括三个方面 :1中等或肌性小动脉受累 ,即不累及微小动脉、毛细血管或静脉系统 ;2PAN为非肉芽肿性的坏死性血管炎 ;3抗中性粒细胞胞浆抗体 (ANCA)阴性。1　诊断由于…     

结节性多动脉炎的诊断和治疗进展

结节性多动脉炎（PAN）是最早被阐述的系统性血管炎，是累及中等大小动脉或小动脉的一种坏死性血管炎，常有多系统受累。临床表现复杂且缺乏特异性，往往没有肾小球肾炎、肺损害及抗中性粒细胞胞浆抗体（ANCA）。PAN的诊断依赖于临床表现、实验室检查以及病理检查，找出其重要线索如：周围神经病变、胃肠道损害、高血压、HBsAg阳性等才能作出正确诊断。PAN的治疗主要是肾上腺糖皮质激素，对有重要脏器损害的患者使用细胞毒药物和血浆置换也是必要的。     

以腹痛为主要表现的结节性多动脉炎一例

结肯性多动脉炎（polyarteritis nodosa，PAN）是系统性血管炎的一种，主要累及中、小动脉，产生节段性坏死性病变。临床上属少见疾病。因累及部位小同，临床表现呈多样性，早期不易明确诊断我院发现以腹痛为主要表现的PAN 1例，报告如下。     

结节性多动脉炎并重症急性胰腺炎一例

结节性多动脉炎（polyarteritisnodosa，PAN）是以中小肌性动脉节段性炎症与坏死为特征的一种非肉芽肿性血管炎。PAN是一少见疾病，合并重症胰腺炎更为罕见。我院近遇1例伴有肾梗死、脾梗死及重症胰腺炎的PAN患者，经抢救治疗痊愈出院，结合文献复习报告如下。     

系统性血管炎中抗内皮细胞抗体的检测及其临床意义分析

目的研究抗内皮细胞抗体（AECA）在系统性血管炎中阳性率,并分析其临床意义.方法固定的人脐静脉内皮细胞（HUVEC）为抗原,细胞酶联免疫吸附试验（ELISA）法检测129例系统性血管炎,57例系统性红斑狼疮（SLE）、25例类风湿关节炎（RA）等患者和85名正常对照者AECA阳性率并分析系统性血管炎组AECA与临床生化指标的相关性.结果系统性血管炎（58.9%）和SLE（46%）患者的AECA阳性率明显高于RA（4%）和正常人组（2.4%）（P＜0.01）.AECA在不同系统性血管炎中阳性率分别为：白塞病（BD）48%（28/59）、大动脉炎（TA）79%（22/28）、韦格纳肉芽肿病（WG）65%（13/20）、结节性多动脉炎（PAN）63%（5/8）、显微镜下多血管炎（MPA）44%（4/9）、变应性肉芽肿血管炎（CSS）80%（4/5）.AECA阳性的TA患者的血沉（ESR）平均水平明显高于AECA阴性组（P＜0.05）.PAN、WG、MPA、CSS患者中,AECA阳性者ESR水平（P＜0.05）和伯明翰系统性血管炎临床活动评分标准（BVAS）值（P＜0.01）明显高于AECA阴性者,BD患者中,AECA阳性病人具有皮肤针刺反应阳性率明显增多（P＜0.05）.随诊的11例系统性血管炎患者治疗前后AECA滴度和ESR的变化,差异有统计学意义（P＜0.05）.结论不同的系统性血管炎和SLE患者血清中均有较高的AECA阳性率,且此抗体与系统性血管炎的临床活动度明显相关,可作为观察病情活动的指标之一.     

结节性多动脉炎心血管病变特点

目的探讨结节性多动脉炎（polyarteritisnodosa,PAN）心血管病变特点,以便早期诊断及治疗,减轻患者缺血造成的永久性脏器损伤、改善预后。方法北京协和医院2002年1月至2012年8月PAN住院患者共64例,收集患者资料,对其临床特点及预后进行回顾性分析。结果64例PAN患者中,导致心血管病变者41例,PAN相关心血管受累发病率为64％。临床表现为缺血所致症状（腹痛、坏疽、胸闷,胸痛）,但多数患者并无相应临床表现。PAN累及心脏者11例（17．2％）,5例有胸闷、胸痛等心肌缺血症状表现,余6例无相应临床表现;7例冠状动脉受累,2例心包积液。41例PAN合并心血管病变者共197支动脉受累,每例患者平均受累动脉为（5±3）支。动脉病变以狭窄和闭塞最常见。多种表现可同时存在于1支动脉造成串珠样改变。对称性受累少见,非对称与对称性受累比例为57／46。内脏（25例）及下肢动脉（19例）受累最常见,其中以肾动脉（19例）、胫前（15例）和胫后动脉（12例）及肠系膜上动脉（9例）受累常见。41例PAN合并心血管病变者中,40例患者应用激素及免疫抑制剂,出现死亡或不可逆性脏器损害者5例（12．2％）。PAN合并心血管受累患者与未合并者在出现皮疹（46．3％vs．91．3％）、舒张压升高（68．3％vs．34．8％）、镜下血尿（4．9％vs26．1％）及激素治疗（冲击／大剂量／中小剂量）（13例／25例,3例vs．2例／19例／2例）上差异有统计学意义（均P〈0．05）。结论PAN合并心血管病变多见,数患者无相应临床表现。对有危险因素如舒张压升高者应积极予以筛查。PAN合并心血管病变易造成不可逆性脏器损害,早期发现、积极并综合治疗有助于改善预后。     

结节性多动脉炎16例临床分析

结节性多动脉炎(PAN)是坏死性血管炎的一种，其特征主要是累及中、小动脉的节段性坏死性病变。该病是一少见疾病，不易早期诊断，而早期治疗是影响预后的因素之。本文总结了北京协和医院1990—2001年住院病人确诊PAN共16例，旨在提高临床医生对本病的认识，尽早明确诊断，合理治疗，改善预后。     

CD146在血管炎患者外周血白细胞表达的意义初探

目的探讨血管炎患者外周血白细胞CD146表达与临床活动性间的关系。方法流式细胞术检测39例活动期系统性血管炎患者[显微镜下多血管炎（MPA）13例,韦格纳肉芽肿（WG）9例,变应性肉芽肿性血管炎（CSS）2例,大动脉炎（TA）9例,白塞病（BD）4例,结节性多动脉炎（PAN）2例]及24例系统性红斑狼疮（SLE）患者外周血白细胞CD146表达,其中18例（MPA5例,WG4例,CSS2例,SLE4例,PAN2例,TA1例）患者经糖皮质激素和环磷酰胺治疗后于病情好转时再次检测。结果（1）与健康者相比,血管炎患者活动期中性粒细胞、淋巴细胞CD146表达增多,尤以中性粒细胞最多,差异均有统计学意义（P〈0．05）。（2）中性粒细胞CD146表达与淋巴细胞、单核细胞CD146表达相关（r值分别为0．66、0．853,P=0．000）,与病程、年龄、血沉、C反应蛋白、抗中性粒细胞胞浆抗体（ANCA）、PR3-ANCA、MPO-ANCA、血肌酐、伯明翰血管炎活动指数（BVAS）、系统性红斑狼疮疾病活动指数（SLEDAI）等无明显相关（r值分别为-0．108、-0．059、-0．073、-0．103、0．012、-0．5、-0．232、0．001、-0．08、0．089,P〉0．5）。（3）18例患者经治疗后好转期中性粒细胞、淋巴细胞CD146表达多数呈逐渐减少的趋势（P〈0．05）。结论CD 146在血管炎患者活动期外周血白细胞尤其是中性粒细胞中表达明显升高,随着糖皮质激素和免疫抑制剂治疗病情好转后呈下降或转阴趋势,其在血管炎发病机制中的意义有待深入研究。     

Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies

BACKGROUND: The classification of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) for epidemiology studies is confusing. The existing schemes such as American College of Rheumatology (ACR) criteria, Chapel Hill Consensus Conference (CHCC) definitions and Lanham criteria produce overlapping and conflicting classifications, making it difficult to compare incidence figures. Aim: To develop a consensus method of using these criteria and definitions for epidemiological studies to permit comparison without confounding by classification. METHODS: A stepwise algorithm was developed by consensus between a group of doctors interested in the epidemiology of vasculitis. The aim was to categorise patients with Wegener's granulomatosis, microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and PAN into single clinically relevant categories. The ACR and Lanham criteria for CSS, and ACR criteria for Wegener's granulomatosis were applied first, as these were considered to be the most specific. Surrogate markers for Wegener's granulomatosis were included to distinguish Wegener's granulomatosis from MPA. MPA was classified using the CHCC definition and surrogate markers for renal vasculitis. Finally, PAN was classified using the CHCC definition. The algorithm was validated by application to 20 cases from each centre and 99 from a single centre, followed by a paper case exercise. RESULTS: A four-step algorithm was devised. It successfully categorises patients into a single classification. There was good correlation between observers in the paper case exercise (91.5%; unweighted kappa = 0.886). CONCLUSION: The algorithm achieves its aim of reliably classifying patients into a single category. The use of the algorithm in epidemiology studies should permit comparison between geographical areas.     

Evaluation of the Sørensen diagnostic criteria in the classification of systemic vasculitis

OBJECTIVES: To evaluate the use of the diagnostic criteria for Wegener's granulomatosis (WG) and microscopic polyangiitis (mPA) proposed by S?rensen et al. in the classification of primary systemic vasculitis (PSV). METHODS: We applied to our cohort of PSV patients the American College of Rheumatology (ACR) criteria for WG, Churg-Strauss syndrome (CSS) and polyarteritis nodosa (PAN), the Chapel Hill Consensus Conference (CHCC) definitions for WG, mPA and CSS, the Hammersmith criteria for CSS and the S?rensen criteria for WG and mPA. RESULTS: Ninety-nine PSV cases were identified. Fifty-six fulfilled criteria for WG (ACR), 60 for PAN (ACR) and 15 for CSS (ACR). Four fulfilled the Hammersmith criteria for CSS. Thirty-nine were defined as mPA (CHCC). Fifty-three patients fulfilled the S?rensen criteria for WG and three for mPA. Five of six patients classified as WG (ACR) who did not meet the S?rensen criteria were excluded by eosinophilia. Six patients who did not fulfil WG (ACR) met the S?rensen criteria for WG. CONCLUSION: The classification of systemic vasculitis is complicated and many cases fulfil more than one set of criteria. The S?rensen criteria for WG is limited by its exclusion of eosinophilia despite reports of an association. We recommend that tissue eosinophilia or peripheral eosinophilia of <1.5x10(9)/l should not exclude a diagnosis of WG. With this modification, the S?rensen criteria for WG may be a useful method of classification, especially in confirming the classification of WG in patients who fulfil both WG (ACR) and mPA (CHCC). Few patients fulfilled the S?rensen criteria for mPA which suggests that they are not of value in classification.     

Effect of classification on the incidence of polyarteritis nodosa and microscopic polyangiitis

Objective. Polyarteritis nodosa (PAN) has been used as a generic term for systemic vasculitis. The distinction between classic PAN and microscopic polyangiitis (MPA) has not always been made. The aims of this study were to compare the American College of Rheumatology (ACR) criteria for PAN with the Chapel Hill Consensus Conference (CHCC) definitions of classic PAN and MPA, and to estimate the annual incidence of PAN and MPA. Methods. The 1990 ACR criteria and CHCC definitions for systemic vasculitis were applied to an unselected cohort of 130 patients with systemic vasculitis attending a single district hospital in the UK between February 1, 1988 and January 31, 1994. Results. Eight patients who met the ACR criteria for PAN and who also met the CHCC definition of MPA but not classic PAN were identified. A further 5 patients met the CHCC definition of MPA but not the ACR criteria for any other type of systemic vasculitis. No patient who met the CHCC definition of classic PAN was identified. The annual incidence of MPA was calculated to be 3.6/million (95% confidence interval 1.7–6.9), and the annual incidence of PAN (ACR criteria) was 2.4/million (95% confidence interval 0.9–5.3). Conclusion. Classic PAN as defined by the CHCC is rare, because small vessel involvement is excluded from this definition.     

Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): a concomitant disease or a feature of FMF?

BACKGROUND: Familial Mediterranean Fever (FMF) is caused by mutations in the gene encoding pyrin and is characterized by self-limited, recurrent attacks of fever and serositis. Vasculitis has been increasingly reported in FMF. A study evaluating the prognosis in FMF and polyarteritis nodosa (PAN) patients has not been reported previously. OBJECTIVES: To determine the special characteristics and the prognosis of PAN in FMF patients. METHODS: A questionnaire was used for the present survey. The setting was 7 referral centers from Turkey and Israel. Seventeen patients who were diagnosed with FMF and who developed PAN were included. PAN was diagnosed in those who met the Chapel Hill consensus criteria for microscopic polyarteritis or classic PAN. The clinical features of these 17 patients and the outcomes of their vasculitis were analyzed. RESULTS: The age at diagnosis of PAN in these FMF patients ranged from 3.5 to 37 years. All patients had constitutional symptoms, elevated acute phase reactants, and myalgia at the time PAN was diagnosed. The diagnosis of PAN was confirmed by renal angiography in 8 patients, by renal biopsy in 6 patients, and by muscle and/or nodule biopsies in 6 patients. A number of patients had definite features of both classic PAN and microscopic polyarteritis. CONCLUSIONS: When compared with other PAN patients, those with FMF tended to have a younger age at PAN onset, more frequent perirenal hematomas, and an overall better prognosis. The cases with overlapping features of microscopic and classic PAN pose a problem for the current classification of vasculitis. We suggest that the clinical representation of PAN in FMF patients has certain characteristics and may be a feature of FMF per se.     

Studies on criteria for clinicopathological diagnosis of allergic granulomatous angiitis (AGA)]

Comparative studies in the evaluation of criteria for clinicopathological diagnosis of AGA which was proposed by Japanese Health and Welfare Ministry (JHWM) in 1988 and American College of Rheumatology (ACR) in 1990 were conducted. Twenty seven Japanese patients with AGA and 231 Japanese controlled patients with polyarteritis nodosa (PAN) and Wegener's granulomatosis (WG) were used as material patients who had been provided a second questionnaire in 1984 sponsored by the JHWM. As a result, the JHWM criteria was 85.2% in sensitivity and 96.5% in specificity, which was superior to the ACR criteria being 74.1% in sensitivity and 93.9% in specificity. These results were due to the low sensitivity and low accuracy in paranasal sinus abnormality and pulmonary infiltrates which were included in the ACR criteria. Furthermore, the JHWM criteria could be diagnosed as AGA using not only the histopathological findings but by the clinical symptoms alone. The controlled patients who were overdiagnosed as AGA using ACR criteria were thought to be included as patients with WG. On the other hand, the controlled patients who were overdiagnosed as AGA using JHWM criteria were thought to be included as patients with overlap syndrome of AGA and PAN. Accuracy of polyneuropathy, muscle weakness, melena and pretibial edema were over 60%, indicating that these clinical symptoms were available for vasculitis symptoms of the JHWM criteria.     

Microscopic polyangiitis (microscopic polyarteritis) with late emergence of generalised Wegener's granulomatosis.

OBJECTIVES: Recent proposals for the nomenclature of systemic vasculitis have focused on a distinction between (classic) polyarteritis nodosa (PAN) and microscopic polyangiitis or polyarteritis (MPA). Thus, MPA may cause necrotising vasculitis of medium sized or small arteries but, unlike PAN, involvement of "microscopic" vessels must always be present in the former. This study aimed to show that the term "MPA" may represent a source of misinterpretation and to help illustrate difficulties of applying diagnostic criteria/definitions for conditions of unknown aetiology or variable clinical presentation and course. METHODS: Among 1250 consecutive patients screened for antineutrophil cytoplasmic antibodies (ANCA), 59 had been found to have idiopathic necrotising and crescentic glomerulonephritis plus ANCA while five had been found to have isolated pulmonary haemorrhage with biopsy verified necrotising alveolar capillaritis plus ANCA. None of these patients had clinical or histological evidence of Wegener's granulomatosis (WG) or evidence of biopsy verified vasculitis involving vessels other than glomerular or pulmonary capillaries at the time of presentation. RESULTS: Six of the 64 patients who met definition criteria for MPA at the time of initial diagnoses had entered into complete clinical remission upon appropriate corticosteroid and cyclophosphamide treatment between two weeks and three months, though subsequently (20 to 72 months; mean time: 42.3 months) developed characteristic clinical and histological features of overt WG. CONCLUSIONS: Microscopic polyangiitis/polyarteritis may be a dynamic condition with clinical and histopathological features evolving over time to other forms of small vessel vasculitis, mainly WG, thereby meaning that follow up would be necessary not only to control a given patient but also to make a final diagnosis. This follow up should be for a long time as there may be a long interval between initial presentation and subsequent development of WG lesions.     

Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa

A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa.     

Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of Rheumatology Subcommittee on Classification of Vasculitis

We describe the histopathologic criteria for the diagnosis of 7 selected vasculitis syndromes: polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Henoch-Sch?nlein purpura, giant cell (temporal) arteritis, and Takayasu arteritis. The criteria apply to the stereotypical cases in each category; they were formulated after a review of submitted biopsy material from 278 of the 1,000 patients entered into the American College of Rheumatology Vasculitis Study Registry, and from prior experience with the pathologic diagnosis of vasculitis in 1,079 nonregistry patients.     

Clinical features and outcomes in 348 patients with polyarteritis nodosa: A systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French vasculitis study group database

Objective

Previous studies of polyarteritis nodosa (PAN) included patients with microscopic polyangiitis, because these entities were not distinguished prior to the Chapel Hill Consensus Conference (CHCC). This study was undertaken to describe the main characteristics of and long‐term outcomes in patients with well‐characterized PAN diagnoses.

Methods

We conducted a systematic retrospective study of 348 patients who were diagnosed as having PAN between March 1963 and October 2005, were registered in the French Vasculitis Study Group database, and satisfied the American College of Rheumatology and CHCC criteria. Patient characteristics and outcomes were analyzed and compared according to hepatitis B virus (HBV) status.

Results

At diagnosis, the mean ± SD age was 51.2 ± 17.3 years. The most frequent findings were general symptoms (93.1%), neurologic manifestations (79%), skin involvement (49.7%), abdominal pain (35.6%), and hypertension (34.8%); 66.2% had renal artery microaneurysms; 70.1% had histologically proven PAN. Patients with HBV‐related PAN (n = 123) had more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and hypertension compared with patients with non–HBV‐related PAN (n = 225). During a mean ± SD followup of 68.3 ± 63.5 months, 76 patients (21.8%) relapsed (63 with non–HBV‐related PAN [28%] versus 13 with HBV‐related PAN [10.6%]; P < 0.001); 86 patients (24.7%) died (44 with non–HBV‐related PAN [19.6%] versus 42 with HBV‐related PAN [34.1%]; P = 0.003). Five‐year relapse‐free survival rates were 59.4% (95% confidence interval [95% CI] 52.6–67.0) versus 67.0% (95% CI 58.5–76.8) for non–HBV‐related PAN and HBV‐related PAN, respectively. Multivariate analysis retained age >65 years, hypertension, and gastrointestinal manifestations requiring surgery or at least consultation with a surgeon as independent predictors of death, whereas patients with cutaneous manifestations or non–HBV‐related PAN had a higher risk of relapse.

Conclusion

Our findings indicate that the rate of mortality from PAN remains high, especially for the elderly, and relapses do occur, particularly in patients with non–HBV‐related PAN with cutaneous manifestations.

     

Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa

Abstract

A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa.