血管炎2017年ACR年会最新更新
2017年欧美anca相关性血管炎诊断标准抢先看
2017年欧美ANCA相关性血管炎诊断标准抢先看！
该标准适用于经风湿科医师判断，已确定患有中小血管炎的患者。
该标准首次提出使用“减分”来除外其他小血管的诊断，在标准中涵盖临床表现、影像学、病理学、血清学等多个特征，更符合风湿科临床医生的临床工作实践。
因此，该标准能更好地适用于临床工作，对临床实践有较好的指导作用，较1990年ACR诊断标准有突破性的进步，对MPA、GPA、EGPA三种AAV的诊断敏感性和特异性均明显提高。
该标准尚未被ACR/EULAR正式背书、仍有待进一步验证。
1 / 1。
最新EULAR 血管炎分类文献原文
EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitisNeil Basu1, Richard Watts2, Ingeborg Bajema3,Bo Baslund4, Thorsten Bley5, Maarten Boers6, Paul Brogan7, Len Calabrese8, Maria C. Cid9, Jan Willem Cohen-Tervaert10, Luis Felipe Flores-Suarez11, Shouichi Fujimoto12, Kirsten de Groot13, Loic Guillevin14, Gulen Hatemi15, Thomas Hauser16, David Jayne17, Charles Jennette18, Cees G. M. Kallenberg19, Shigeto Kobayashi20, Mark A. Little21, Alfred Mahr14, John McLaren22, Peter A. Merkel23,Seza Ozen24, Xavier Puechal25, Niels Rasmussen4, Alan Salama26, Carlo Salvarani27, Caroline Savage21, David G. I. Scott28, Mårten Segelmark29, Ulrich Specks30,Cord Sunderkotter31, Kazuo Suzuki32, Vladimir Tesar33, Allan Wiik34, Hasan Yazici15, Raashid Luqmani35Affiliations1. University of Aberdeen, Aberdeen, UK2. University of East Anglia, School of Medicine, Norwich, UK3. Leiden University Medical Center, Leiden, Netherlands4. Rigshospitalet, Copenhagen, Denmark5. University Hospital Freiburg, Freiburg, Germany6. VU University Medical Center, Amsterdam, Netherlands7. Institute of Child Health, London, UK8. Cleveland Clinic Foundation,Cleveland, USA9. Hospital Clinic, University of Barcelona.IDIBAPS Barcelona, Spain10. Maastricht UMC, Masstricht, Netherlands11. Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico12. Miyazaki University, Miyazaki, Japan13. Klinikum Offenbach, Offenbach, Germany14. University of Paris Descartes, Paris, France15. University of Istanbul, Istanbul, Turkey16. Immunologie-Zentrum Zürich, Zurich, Switzerland17. Addenbrooke’s Hospital, Cambridge, UK18. University of North Carolina, Chapel Hill, USA19. University Hospital Groningen, Groningen, Netherlands20. Juntendo Koshigaya Hospital, Saitama, Japan21. Renal Institute of Birmingham , University of Birmingham, Birmingham, UK22. Whytemans Brae Hospital, Kirkcaldy, UK23. Boston University School of Medicine, Boston, USA24. Hacettepe University, Ankara, Turkey25. Centre Hospitalier Le Mans, Le Mans, France26. Imperial College London, London, UK27. Arcispedale S Maria Nuova, Reggio Emilia, Italy28. Norfolk and Norwich University Hospital Trust, Norwich, UK29. Lund University, Lund, Sweden30. Mayo Clinc, Minnesota, USA31. Universitätsklinikum Münster, Münich, Germany32. Chiba University Graduate School of Medicine, Chiba, Japan33. Charles University, Prague, Czech Republic34. Statens Serum Institut, Copenhagen, Denmark35. University of Oxford, Oxford, UKKey words: Systemic vasculitis, Wegener's granulomatosis; Giant Cell Arteritis; VasculitisCorresponding authorRaashid Luqmani DM, FRCPConsultant Rheumatologist, Nuffield Orthopaedic CentreSenior Lecturer, University of OxfordWindmill Road, Oxford OX3 7LDUKTelephone: 00441865 738106Fax: 00441865 738058email: raashid.luqmani@The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd to permit this article (if accepted) to be published in ARD and any other BMJPGL products and sublicences such use and exploit all subsidiary rights, as set in our licence(/iflora/licence.pdf).AbbreviationsAAV Anti neutrophil cytoplasm antibody associated vasculitis ACR American College of RheumatologyANCA Anti neutrophil cytoplasm antibodyCHCC Chapel Hill Consensus ConferenceCRYO Cryoglobulinemic vasculitisCSS Churg-Strauss syndromeCT Computed TomographyEULAR European League Against RheumatismELISA Enzyme-linked immunosorbant assayGBM Glomerular basement membraneGCA– Giant cell arteritisHIV – Human immunodeficiency virusHSP Henoch Schönlein purpuraHV Hypersensitivity vasculitisIIF – Indirect immunofluorescenceKD Kawasaki diseaseLV Leucocytoclastic vasculitisMRA Magnetic Resonance AngiographyMRI Magnetic Resonance ImagingMPA Microscopic polyangiitisPAN– Polyarteritis nodosaPET - Positron Emission Tomography scanningTAK Takayasu diseaseWG Wegener’s granulomatosisAbstractObjectives: The systemic vasculitides are multi-organ diseases where early diagnosis and therapy can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis.Methods: The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce ‘points to consider’ in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used.Results: There was unanimous consensus for re-evaluating existing definitions and developing new criteria. 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of ANCA and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasizing its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered.Conclusions: Limitations in current classification criteria and definitions for vasculitis have been indentified and suggestions provided for improvement. Additionally it is proposed that,, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.IntroductionThe primary systemic vasculitides are a group of uncommon diseases (combined annual incidence >100 new cases per million),1 some of which are associated with an untreated 1-year mortality of >80%.2 Early diagnosis and treatment significantly improves outcome. Unfortunately, however, their relative rarity and heterogeneity frequently leads to diagnostic delay,3 which could be improved by better nomenclature.The terms ‘disease definition’, ‘classification’ and ‘diagnostic criteria’ are essential components of the nomenclature of any disease. However, they are frequently and incorrectly used interchangeably. For example the American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) are unhelpful in diagnosing early RA.4 In the vasculitides, each condition should be described (ie, disease definition), criteria listed to allow distinction from the general population and from similar, non-vasculitic ‘mimic’ conditions (ie, diagnostic criteria) and further criteria are required to distinguish one form of vasculitis from another (ie, classification criteria). The primary purpose of diagnostic criteria is to diagnose the conditions of individual patients, but they can also be used to distinguish one type of vasculitis from another. Classification criteria are primarily intended to generate homogeneous (usually ‘classic’) sets of patients for research.5In the absence of validated diagnostic criteria for systemic vasculitis, the ACR classification criteria5 and the Chapel Hill Consensus Conference (CHCC)6 definitions are often used as substitutes.The ACR classification criteria for vasculitis have sensitivities of 71.0% to 95.3% and specificities between 78.7 and 99.7%.5 The most sensitive and specific criteria were for Churg–Strauss syndrome (CSS), giant cell arteritis (GCA) and Takayasu disease (TAK); hypersensitivity vasculitis (HV) was the least well defined condition (sensitivity 71.0%,specificity 83.9%).7 The ACR criteria have facilitated epidemiological and clinical studies. However, they have three main disadvantages:1.The failure to include microscopic polyangiitis (MPA), which was notcommonly used during the 1980s, despite its description in 1948.82.The lack of application of anti-neutrophil cytoplasm antibody (ANCA) as acriterion in the diagnosis of Wegener's granulomatosis (WG),9,–,11 MPA,10and CSS12 (and also in polyarteritis nodosa (PAN), because of itsabsence).13e of the initial diagnosis made by the participating doctor as the goldstandard.The ACR criteria were derived by determining which features distinguished one form of vasculitis from another. Unsurprisingly, the ACR criteria demonstrate poor reliability when applied as diagnostic criteria,14 as they were not designed for this purpose.The CHCC definitions for primary vasculitis,6 including MPA, describe features that should be present in a patient to warrant using a given term for either classification or diagnosis, but they do not specify what observations or criteria should be used to definitively determine that a given patients has a specific form of vasculitis. Attempts to validate CHCC definitions as diagnostic criteria (by including surrogate markers such as ANCA) have been unsuccessful.1516There is widespread controversy in relation to the use of ACR criteria and CHCC definitions. A recent survey of an international panel of experts reflects this (Table 1). The majority felt the ACR criteria for PAN, CSS, Henoch–Schönlein purpura (HSP) and HV and CHCC definitions for WG, MPA and PAN were no longer fit for purpose. Paediatricians have already developed a set of classification criteria addressing new developments based on their experience in childhood.17The European League Against Rheumatism (EULAR) convened an expert consensus group to consider re-evaluating definitions, classification and diagnostic criteria insystemic vasculitis, in order to highlight areas which require updating or are of concern and indicate what should be considered next.MethodsWorking groupA consensus group was formed comprising 39 experts in vasculitis. In order to encourage universal acceptance of the conclusions, we incorporated multiple disciplines and nationalities: rheumatology (15), nephrology (7), immunology (5), internal medicine (3), pathology (2), paediatrics (2), otolaryngology (1), pulmonology (1), dermatology (1), radiology (1) and clinical epidemiology (1) were represented from 10 European countries, USA, Mexico and Japan.The project conformed to the EULAR standing committees published standard procedures for the elaboration of recommendations.18 Since the groups' findings were based on a systematic literature review rather than a data-driven approach, it is appropriate to use the term ‘points to consider’ rather than ‘guidelines’ or‘recommendations’.Expert opinionWe used an iterative process to establish the major areas of concern/difficulties with the existing definitions/criteria. This involved a questionnaire to committee members who were asked to identify the key questions and issues relating to the current definitions, classification and diagnostic criteria, followed by a modified Delphi process. As a result, a set of questions was produced that provided the basis for a systematic literature search exploring studies on the diagnosis and classification of systemic vasculitis. These were used to fuel discussion and delineate points to consider as we develop and testnew/updated definitions and criteria in the future.Literature reviewWe used the PubMed Medical Subject Headings (MeSH) database and Cochrane library. Where MeSH terms were unavailable (eg, MPA), free text was used. Searches were not limited by time or language; reference lists were manually searched. We excluded studies without abstracts; those with cohorts of less than 10 patients; case reports; reviews and letters. We examined relevant studies of all forms of systemic vasculitis including paediatric and secondary forms. Antiglomerular basement membrane (anti-GBM) disease was also explored since it is closely related to the vasculitides. Search strings were derived by consensus, for example to examine the role of ANCA in diagnosis, the following string was employed: (‘vasculitis’ (MeSH) or ‘anti-GBM disease’ (MeSH) or ‘erythema induratum’ (MeSH) or ‘MPA’ or ‘cryo’ or ‘rheumatoid vasculitis’ or ‘nodular vasculitis’ or ‘infection associated vasculitis’ or ‘ANCA associated vasculitis’ or‘immune complex vasculitis’ or ‘renal vasculitis’ or ‘drug induced vasculitis’) and‘antibodies, antineutrophil cytoplasmic’ (MeSH) and ‘diagnosis’ (MeSH).We included all papers with an outcome identified in the Delphi exercise. Evidence was categorised according to the EULAR evidence hierarchy for diagnostic studies (Table 2).1920Results and discussionQuestions raised by Delphi exerciseA total of 10 questions were generated through the modified Delphi exercise (see Table3). Some questions could only be addressed by supplementing published evidence with consensus.Points for considerationThe results of the literature search were grouped into three main diagnostic topics (Table 4). The following discussion combines the results of the literature search and expert opinion and attempts to cover the questions raised through the modified Delphi exercise. From the results, 17 ‘points to consider’ were extrapolated (Table 5).Diagnostic toolsBiopsyHistology is fundamental to the diagnosis of most forms of vasculitis and more importantly, perhaps, the exclusion of mimics. This is best highlighted by brain biopsy in central nervous system (CNS) vasculitis, where despite the potential for significant iatrogenic morbidity and variable yield (36% to 83%),2122 it remains the gold standard investigation due to its role in identifying alternative diagnoses such as infection. Significant variation exists in the utility of biopsy depending on the target organ. For example, the yield of kidney and temporal artery biopsies is high (80%2324 and 87%25 respectively). In contrast, ear, nose and throat (ENT) and transbronchial biopsies have a low reported sensitivity (0% to 42%).2326,–,30Clinically directed biopsies can improve yield as exemplified in the nerve,3132 lung23 and temporal artery.25 Further studies examining temporal artery sampling support the need for a prompt biopsy to reduce unnecessary corticosteroid exposure33,–,36;adequate sampling by length (0.5–2 cm)333738 with multiple sectioning39 and bilateral biopsies,25 in view of the problem of skip lesions. It would be difficult to justify the latter routinely.A more effective approach may be sequential sampling of cases where the first biopsy is negative, in patients with a high pretest probability of GCA.40Although previous proposed criteria and definitions have incorporated histology, there are no universally recognised histological criteria and little evidence to justify the inclusion of specific pathological features. Perhaps the exception is IgA as an essential criterion in the diagnosis of HSP. In a study of 182 cases of skin vasculitis, the presence of IgA was 98% sensitive for the clinical diagnosis of HSP; however, the specificity was very low (24%)41Laboratory testingThe discovery of specific autoantibodies characterised by immunofluorescence patterns, cytoplasmic ANCA (cANCA) and perinuclear ANCA (pANCA) and subsequently by the relevant target antigens, proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA),has been a major advance in the diagnosis of small vessel vasculitis,42 particularly WG and MPA. Sensitivity of ANCA varies significantly (34% to 92%)101143,–,47due to non-standardised assays,1148 different study designs,1444 differences in treatment, disease activity and disease type in the populations studied. MPO-pANCA predominates in MPA and PR3-cANCA in WG, however, this is not absolute. Geographical variation has been observed with the presence of MPO-pANCA in 60% of a cohort of Chinese patients with WG.49 In contrast, specificity is consistent between studies.104345 Most studies include disease controls, predominantly containing patients with inflammatory bowel disease, systemic lupus erythematosus (SLE) and RA, rather than healthy controls. However, the ideal control group should include vasculitis mimics.1042The combined use of indirect immunofluorescence and ELISA provides optimal performance.11105051 A meta-analysis of seven studies provided a weighted pooled sensitivity of 85.5% and specificity of 98.6% for MPO-pANCA and PR3-cANCA in the diagnosis of WG, MPA or renal limited vasculitis.43 PR3-ANCA and MPO-ANCA are the only ANCA specificities with proven diagnostic value for small vessel vasculitis. However, additional ANCA specificities may emerge as useful diagnostic markers in future.52The prevalence of ANCA in CSS is lower than in WG or MPA (38% to 73%). ANCA-positive CSS is associated with a higher frequency of glomerulonephritis.12In some vasculitides, the absence of ANCA can be of value. For example, in PAN, which, historically, has been difficult to differentiate from MPA.1353,–,55ANCA are only present in low titre or completely absent in all other vasculitides such as GCA56 and Kawasaki disease (KD).57 ANCA are not 100% specific for vasculitis; they are found in other autoimmune diseases and vasculitis mimics such as SLE,58 RA,59 HIV,60 tuberculosis,6162 inflammatory bowel disease,63 primary sclerosing cholangitis,64 drug reactions (eg, cocaine65 and propylthyourracil66), infective endocarditis and septic shock.67Thus ANCA analysis should not be abused for general screening purposes. Selectivity of test ordering improves positive predictive value51 and the use of ANCA requesting guidelines to avoid indiscriminate use may be justified.68Diagnostic radiologyRadiological diagnostics are of increasing use in the assessment of large vessel vasculitis. Traditionally, conventional contrast angiography has been an essential criterion in the diagnosis of TAK.6970 More recently, the less invasive applications of CT angiography and magnetic resonance angiography (MRA) have produced similar diagnostic performance (sensitivities of 95%71 and 100%72 respectively and specificity of 100%7172 for both, where contrast angiography is the reference standard). They provide the added advantage of visualising mural changes, although, overall the performance of angiographic techniques in early disease is poor. In contrast MRI and ultrasound (US) both detected mural inflammation,73,–,75 which may be useful in early diagnosis, but are inferior to angiography in late disease.737576 In future, early diagnosis of large vessel vasculitis may be facilitated by positron emission tomography scanning (PET) scanning. Retrospective studies suggesting sensitivities of 60% to 92% and specificities of 99% to 100% in the diagnosis of large vessel vasculitis, with greater sensitivity in detecting wall inflammation compared to MRI.77,–,79 There is, however, insufficient evidence at present to advocate PET as a standard in diagnostics, especially in view of its considerable radiation dose when combined with CT.US and MRI,80,–,82 but not PET83, may be a useful alternative to temporal artery biopsy for the diagnosis of GCA. In a meta-analysis of 23 studies (2036 patients), the diagnostic value of US in GCA, using the ‘halo’ sign, a dark area around the temporal artery vessel, provided a weighted sensitivity and specificity of 69% and 82% respectively, compared to biopsy and 55% and 94% compared to ACR criteria. Abnormal findings appear to increase the likelihood of disease, thereby justifying a biopsy, while negative results decrease the post-test probability and reduce the need for a biopsy.84 The presence of bilateral halos may obviate the need of biopsy.80 Alternatively, 3T MRI of cranial arteries provides high diagnostic sensitivity (89% to 94%) and specificity (92% to 100%) indetecting vessel wall inflammation, although studies are based on small numbers performed at a limited number of centres.8182The available evidence to support other radiological strategies is not convincing.Abdominal angiographic abnormalities, particularly microaneurysms, are regarded as synonymous with PAN. However, studies assessing angiography in PAN have included a significant number of patients with MPA.85,–,87 Reported sensitivities are variable (58% to 89%) and one study described a specificity of 89% in populations with suspected medium vessel vasculitis. In practice, despite the absence of evidence, the risks of formal angiography encourage increased use of digital subtraction angiography and MRA as alternatives.In terms of granulomatous antibody-associated vasculitides, CT and MRI can be useful in diagnosing ENT disease.Compared to CT, sinus visualisation with MRI is sensitive (92%) in detecting inflammatory changes in WG.88 In contrast, MRI is poor in delineation of destruction (5% of cases) compared to CT (40% of cases).89 Although not diagnostic, they are necessary for guided biopsies that may lead to a diagnosis.The use of radiology in CNS vasculitis is controversial. The lack of a gold standard has caused difficulties in assessing its diagnostic performance in this rare and heterogeneous condition. Conventional angiography has low specificity (14% to 60%)2190 and variable sensitivity (15% to 92%).91 Angiography alone is not pathognomonic and must be interpreted in the clinical context. Distinguishing reversible vasospasm is a particular problem. MRI, CT and MRA have a role, but no investigation provides diagnostic certainty.Surrogate markersIt is clear that currently available diagnostic tools are imperfect, thus future criteria, at least in the short term, will rely heavily on clinical surrogate markers.The ACR classification criteria is dominated by clinical characteristics.5 Supplementing CHCC definitions with clinical features and biomarkers to form diagnostic criteria has not been effective in WG and MPA, however, alteration of the criteria improves their performance16 as classification criteria in WG (specifically by not excluding cases with hypereosinophilia) but not in MPA. The development of novel biomarkers may ultimately prove superior to biopsy, which provides suboptimal yield in practice.Classification treeWe recommend the development of updated criteria and re-evaluation of current disease definitions.A preliminary nomenclature scheme based upon a classification tree was agreed as work in progress and provides a basis for future validated classification and diagnostic criteria.The proposed scheme will accommodate the following features:1.The group raised concerns that ‘inflammation of blood vessels’, the truepathological definition, captured many diseases not considered to beclinical forms of vasculitis. Future criteria should focus only on clinicallyrelevant vasculitis defined as a disease where pathological evidence ofblood vessel inflammation is considered to be an important part of thedisease. Thus, all forms of vascular disease will be defined as either‘vasculitis’ or ‘predominantly non-inflammatory vasculopathy’. The latterwould include atherosclerosis, haemolytic uraemic syndrome andfibromuscular dysplasia.2.The use of eponyms should be reviewed. There is evidence linking Dr FWegener with the Nazi regime, but how substantial this link is remainsundetermined.92 Similar concerns have led to the removal of the term‘Reiter’s syndrome' in favour of reactive arthritis.93 The committee hasdiscussed this further with EULAR and ACR and have prepared adocument raising the relevant issues which is currently being reviewed bythe German society of rheumatology. We recognise that an alternative to the term for WG could be ANCA-associated vasculitis with granulomatosis (Wegener's granulomatosis).In general, it was agreed that wide-scale abandonment of historicallyestablished terms would cause confusion and therefore any change would need to be introduced gradually, with initial retention of the old names in addition to the new, more appropriate names.3.The name for any disease should, where possible, reflect itspathophysiological basis. Our understanding of specific aetiologies invasculitis is limited, but expanding. A significant proportion of patients with PAN and cryoglobulinaemic vasculitis (cryo) carry hepatitis B94 and C95 infections, respectively and there is evidence to suggest that theseviruses induce direct vessel damage via immune complex formation. This should be reflected in their definitions and names.4.Age is worthy of inclusion in the definitions of some forms of vasculitis,but not all.The spectrum of large vessel vasculitis has traditionally been set according to age5 with a cut-off of 50 years between GCA and TAK. The concept of ‘age at disease onset’ should be considered (as per the ACR criteria)5 since many patients with TAK present several years after their true disease onset with symptoms such as claudication. Age is currently used to define HSP, but at least 10% of cases occur in adulthood.50 Adults with HSP oftenfollow a distinct clinical course from children, in particular, with worse renal outcomes.96 In contrast, KD is mainly a paediatric disease. Adultcases are rare and benign.975.Vasculitis is divided into primary and secondary forms. Primary entitiesmay move into the secondary category if aetiologies are discovered.Secondary vasculitis includes vasculitis due to infection, drugs, malignancyand connective tissue diseases.6.The use of predominant vessel size and type will remain a majordiscriminator. In addition to ‘small’, ‘medium’ and ‘large’, a ‘nopredominant vessel size’ category would be incorporated. This allows theinclusion of syndromes such as Behçets disease, CNS vasculitis, Cogan'ssyndrome and relapsing polychondritis.ConclusionsThere is currently no gold standard test for the diagnosis of vasculitis. We have critically appraised the value of biopsy, serology and radiology for diagnosing vasculitis to define an evidence base from which to modernise current definitions and criteria. We have identified areas of potential improvement in current definitions and criteria. The available evidence is insufficient to make definitive recommendations for diagnostic criteria. However, the points represent position statements to allow the development of future definitions and validated diagnostic/classification criteria. There is clear consensus among the international community to embrace this challenge. This work provides the foundation for a proposed large multicentre study to develop new criteria from prospective cohorts that would take current diagnostic testing into consideration.Footnotes•Funding EULAR Executive Secretariat, Ministerio de Cienciae Innovación, SAF 08/04328 (MCC), and the American College of Rheumatology.•Provenance and peer review Not commissioned; externally peer reviewed. •Competing interest None.TablesTable 1 Percentage of committee dissatisfied with disease criteria/definition* Disease ACR (%) CHCC (%)GCA 38 27TAK 45 27PAN 76 59KD n/a 14WG 43 68MPA n/a 59CSS 76 36HSP 86 14HV 75 n/aLV n/a 41Cryo n/a 36GCA – Giant cell arteritis; TAK – Takayasu disease; PAN – Polyarteritis nodosa; KD – Kawasaki disease; WG – Wegener’s granulomatosis; MPA – Microscopic polyangiitis; CSS – Churg-Strauss syndrome; HSP – Henoch Sconlein purpura; HV – Hypersensitivity vasculitis; LV – Leucocytoclastic vasculitis; Cryo – Cryoglobulinemic vasculitis* 22 participantsTable 2: The EULAR evidence hierarchy for diagnosis based on study designGrade EvidenceIa Meta-analysis of cohort studiesIb Meta-analysis of case control studiesIIa Cohort studiesIIb Case control/cross sectional comparative studiesIII Non-comparative descriptive studiesIV Expert opinion。
风湿病最新诊断标准解读
至少1项临床标准 + 1 项实验室标准
诊断APS
2002年干燥综合征国际分类标准
I.口腔症状：3项中有1项或1项以上 1、每日感口干持续3个月以上； 2、成年后腮腺反复或持续肿大； 3、吞咽干性食物时需用水帮助。 II.眼部症状：3项中有1项或1项以上 1、每日感到不能忍受的眼干持续3个月以上 2、有反复的砂子进眼或砂磨感觉； 3、每日需用人工泪液3次或3次以上。 III.眼部体征：下述检查任1项或1项以上阳性 1、Schirmer I 试验（＋）（5mm/5分）； 2、角膜染色（＋）（4 van Bijsterveld计分法）。 IV.组织学检查：下唇腺病理示淋巴细胞灶1（指4mm2组 织内至少有50个淋巴细胞聚集于唇腺间质者为一 灶）。 V.唾液腺受损：下述检查任1项或1项以上阳性；
心脏和神经系统病变等）或典型脊柱关节病的临床表现（如炎性下腰痛、交 替性臀区疼痛、肌腱端炎或虹膜炎等）不是反应性关节炎确诊的必须具备的 条件。 Reiter综合征：关节炎（主要在下肢）+非淋菌性尿道炎+结膜炎 +排除强直性脊柱炎、银屑病关节炎或其他风湿病。
反应性关节炎诊断及治疗指 南
骨关节炎分类标准(1995ACR)
骨关节炎诊断及治疗指南 中华风湿病学杂志2010年6月第
骨关节炎分类标准(1995ACR)
系统性硬化症
系统性硬化症 极早期系统性硬化病 CREST综合征
1980年美国风湿病学会制订的系统硬化病诊断标准
（一）主要指标 近端硬皮：对称性手指及掌指或跖趾近端皮肤增厚、紧硬，不易提起。
（二）次要指标 （1）硬皮指：上述皮肤改变仅限于手指； （2）指端下凹性结疤或指垫变薄：由于缺血指端有下陷区，指垫组织丧失； （3）下肺纤维化：无原发性肺疾病而双下肺出现网状条索、结节、密度增 加，亦可呈弥漫斑点状或蜂窝状。
抗中性粒细胞胞浆抗体相关性小血管炎等ANCA相关性血管炎诊断标准、复发和感染、治疗进展、治疗共识总结
抗中性粒细胞胞浆抗体相关性小血管炎等ANCA相关性血管炎诊断标准、复发和感染、治疗进展、治疗共识不同总结诊断标准抗中性粒细胞胞浆抗体相关性小血管炎（AAV）是一组自身免疫性疾病，主要累及小血管，病理以血管壁坏死性炎症为特征，少见免疫复合物沉积。
主要包括肉芽肿性血管炎（GPA）、显微镜下多血管炎（MPA）、嗜酸性肉芽肿性血管炎（EGPA）。
表1：2022年ACR/EULAR关于GPA分类标准确诊为小或中血管炎，并且排除其他诊断：以上得分≥5分者可以分类诊断为GPA，敏感性92％，特异性94％表2：2022年ACR/EULAR关于EGPA分类标准确诊为小或中血管炎，并且排除其他诊断：以上得分≥6分的患者可以分类诊断为EGPA，敏感性85％，特异性99％表3：2022年ACR/EULAR关于MPA分类标准确诊为小或中血管炎，并且排除其他诊断以上得分≥5分的患者可以分类诊断为MPA，该标准敏感性91%、特异性94%。
AAV复发和感染ANCA检测对诊断及分类、病理活检的重要性（如肾或肺组织活检），血管炎的病情评估包括疾病活动度、严重程度、损伤，并结合分期来判断病情是否严重。
此外，AAV最大的临床特点是极易复发，约25%~33%的患者会出现复发，平均复发时间为24个月。
复发时临床表现各不相同，以皮肤和关节表现最多见，而肺、肾表现较少，也可出现以往末受累器官受累。
另外治疗免疫抑制使用不足会导致AAV复发，而免疫抑制过度则会发生感染。
随着长期应用糖皮质激素和细胞毒药物或免疫抑制剂治疗，临床医生还需要密切重视其副作用尤其是感染。
AAV治疗进展AAV的治疗分为诱导缓解与维持缓解阶段，戴冽教授指出在诱导缓解治疗期间应尽快使疾病达到缓解，以防止造成器官的不可逆损害。
维持阶段的治疗是使疾病持续处于缓解状态，减少疾病复发。
1、诱导缓解的治疗药物是糖皮质激素联合免疫抑制剂。
糖皮质激素是AAV诱导缓解的一线治疗药物。
最常用于诱导缓解治疗的免疫制剂为环磷酰胺（CTX）、以B细胞为靶向的单克隆抗体利妥昔单抗。
1990年acr大动脉炎分类标准
文章主题：1990年ACR大动脉炎分类标准探析1. 背景介绍在医学领域，大动脉炎是一种严重的血管疾病，可导致动脉壁的炎症和损伤，进而影响血液循环和供血功能。
1990年，美国风湿病学会（ACR）发布了一套大动脉炎分类标准，对该疾病进行了系统性的分类和定义，为诊断和治疗提供了重要的依据。
2. ACR大动脉炎分类标准内容概述根据ACR的分类标准，大动脉炎可分为多种类型，包括巨细胞动脉炎、临床缺乏病症的动脉炎和其他相关的血管炎性疾病。
该标准不仅考虑了病理学特征，还结合了临床表现和影像学检查结果，为医生提供了准确诊断和治疗的依据。
3. 评估ACR大动脉炎分类标准的深度和广度在评估ACR大动脉炎分类标准的深度和广度时，首先需要深入了解其中所涉及到的各种类型和相关因素。
对于每一种类型，都需要探讨其病因、临床表现、诊断方法和治疗原则，并将其与其他类型进行比较和对照。
还需要考虑到该标准在临床实践中的应用性和实用性，以及对未来研究和发展的指导意义。
4. 文章正文根据ACR的大动脉炎分类标准，巨细胞动脉炎是一种主要侵袭中大型动脉的血管炎症性疾病，最常见的累及动脉为颌面动脉、紫檀动脉和锁骨下动脉等。
患者主要表现为头痛、颈椎压痛、发热和全身倦怠等症状。
临床医生可通过检查血沉率、C反应蛋白和影像学检查来确诊该疾病。
治疗原则主要包括糖皮质激素和免疫抑制剂，有些病例还需要手术干预。
除了巨细胞动脉炎外，ACR的分类标准还明确了一类临床缺乏病症的动脉炎，此类患者早期临床表现轻微，但通过影像学检查可明显发现动脉壁炎症的改变。
这种类型的动脉炎常见于年轻女性，临床治疗主要以激素和免疫抑制剂为主，控制炎症的还需注意其长期的并发症和预后。
ACR的大动脉炎分类标准还涉及到其他相关的血管炎性疾病，如桡骨动脉炎、多血管炎和血管粥样硬化等，这些疾病虽然在临床表现和发病机制上有所不同，但都具有一定的共性和相关性。
了解这些相关疾病对于全面了解大动脉炎的分类和诊断意义重大。
最新：中国儿童抗中性粒细胞胞质抗体相关性肾炎诊断与治疗临床实践指南(2023)
最新：中国儿童抗中性粒细胞胞质抗体相关性肾炎诊断与治疗临床实践指南（2023）摘要抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）是一类发病原因不明，以小血管炎症和纤维素样坏死为主要病理改变、累及全身的自身免疫性疾病。
AAV患儿肾脏受累导致ANCA相关性肾炎（AAGN）,引起肾功能持续性恶化，是儿童终末期肾病的重要原发疾病。
为规范儿童AAGN的诊断与治疗，改善AAGN预后,中华医学会儿科学分会肾脏学组、中华儿科杂志编辑委员会联合发起制订〃中国儿童抗中性粒细胞胞质抗体相关性肾炎诊断与治疗临床实践指南（2023）〃，为临床医务工作者对儿童AAGN的诊断、治疗等重要问题提供规范的指导。
抗中性粒细胞胞质抗体（anti-neutrophi1cytop1asmicantibody z ANCA）相关性血管炎（ANCAassociatedvascu1itis,AAV）是以侵犯小动脉、小静脉及毛细血管为主的系统性疾病，主要病理特征为小血管炎症和纤维素样坏死。
临床类型包括显微镜下多血管炎（microscopicpo1yangiitis,MPA\肉芽肿性多血管炎（granu1omatosiswithpo1yangiitis z GPA∖嗜酸性肉芽肿性多血管炎（eosinophi1icGPA,EGPA X AAV的病因及发病机制尚未完全清楚，可能与遗传、环境、感染及药物等因素导致机体对中性粒细胞蛋白酶3（proteinase3,PR3）或髓过氧化物酶(mye1operoxidase,MPO)抗原的免疫耐受性丧失相关。
AAV病情凶险，可引起多脏器功能障碍。
肾脏是常受累的器官之一，ANCA相关性肾炎(ANCAassociatedg1omeru1onephritis,AAGN)严重威胁患者生命。
与成人相比，儿童AAV肾脏受累更为常见且严重，29%~32%的患儿最终进展至终末期肾病(endstagekidneydisease,ESKD);部分患儿起病隐匿，可仅有肾脏受累，就诊时已进入ESKD o现有的多个AAV 相关诊治指南均未特别关注AAGN且未纳入儿童相关证据，儿童AAGN的治疗策略多源于成人证据的推荐。
ANCA相关性血管炎诊疗进展教学课件
anca相关性血管炎诊疗进展教学课件pptxx年xx月xx日contents •介绍•临床特征及诊断•病因及发病机制•治疗及预后•最新研究进展•讨论与总结目录01介绍anca相关性血管炎(ANCA相关性血管炎)是一种少见的自身免疫性疾病，主要累及小血管和中等血管。
患者可表现为全身性血管炎，同时可伴有肺、肾、皮肤等多器官和组织受累。
定义与概述1anca相关性血管炎的基本特点23anca相关性血管炎多见于中老年女性，且多数患者有吸烟史。
患者可出现发热、乏力、肌肉疼痛等非特异性症状，也可出现肾脏、呼吸系统受累表现。
anca相关性血管炎的病理学特征为血管壁纤维素样坏死、炎症细胞浸润和中性粒细胞胞质抗体沉积。
诊疗现状及发展历程01anca相关性血管炎的诊断标准为存在活动性小血管炎、血清ANCA阳性及组织病理学符合血管炎表现。
02目前治疗以糖皮质激素和免疫抑制剂为主，早期治疗可有效控制病情进展，延长患者生存期。
03近年来，随着对ANCA相关性血管炎发病机制的深入研究，生物制剂等新型治疗手段逐渐应用于临床，为患者带来新的治疗选择。
02临床特征及诊断临床表现血管炎病变引起的症状包括疼痛、麻木、感觉异常等全身症状发热、乏力、肌肉疼痛等受累器官的症状根据不同的器官受累，出现相应的症状，如肺部受累可引起咳嗽、咳痰、呼吸困难等目前较为公认的诊断标准为美国风湿病学会（ACR）1994年提出的分类标准，包括主要标准和次要标准，其中主要标准为ANCA阳性；次要标准包括：蛋白尿＞0.5g/d，肾功能不全血沉＞30mm/h，有神经系统表现，有血管炎表现等诊断流程对于可疑患者，首先进行ANCA筛查，若ANCA阳性，则进行进一步检查，如病理学检查、影像学检查等，以明确诊断诊断标准诊断标准与流程VS03与其他自身免疫性疾病的鉴别ANCA相关性血管炎还需与其他自身免疫性疾病进行鉴别，如系统性红斑狼疮等鉴别诊断与其他相关性血管炎的异同点01与其他血管炎的鉴别ANCA相关性血管炎需与其他类型的血管炎进行鉴别，如结节性多动脉炎、韦格纳肉芽肿等02与其他相关性疾病的鉴别ANCA相关性血管炎还需与其他相关性疾病进行鉴别，如感染、肿瘤等03病因及发病机制HLA-DRB1基因与ANCA相关性血管炎发病相关遗传因素如感染、职业暴露等环境因素抗GBM抗体、抗PR3抗体等自身抗体在血管炎发病中起作用自身免疫异常ANCA与自身抗体结合形成免疫复合物，沉积于血管壁免疫复合物沉积中性粒细胞、淋巴细胞等炎症细胞浸润血管壁，引起血管炎炎症细胞浸润炎症细胞释放的细胞因子和炎症介质对血管壁造成损伤和破坏血管损伤和破坏与其他自身免疫性疾病的关系ANCA相关性血管炎常与其他自身免疫性疾病同时存在与肿瘤的关系部分ANCA相关性血管炎患者可能并发肿瘤，如多发性骨髓瘤等与其他因素的关系04治疗及预后免疫抑制剂联合糖皮质激素使用，可提高疗效、减少复发。
2022大血管炎的治疗进展与指南建议
2022大血管炎的治疗进展与指南建议（全文）大血管炎（LVV ）包括大动脉炎（TAK ）和巨细胞动脉炎（GCA ）, 主要引起大血管肉芽肿性血管炎症, 是成年人最常见的原发性脉管炎。
其发病机制涉及血管炎症和损伤, 促进内膜增生、外膜增厚和壁内血管化, 从而损害血管完整性和组织灌注, 并导致组织缺血。
血管炎症可能引起许多临床特征, 包括视力障碍、中风、缺血和主动脉瘤。
诊断LVV的最佳方法是结合病史、体格检查、各种实验室检查和影像学检查。
其治疗包括糖皮质激素（GC）、常规免疫抑制剂和生物制剂。
本文旨在总结LVV的治疗药物、最新进展和指南建议。
LVV的一般治疗LVV的药物治疗包括诱导缓解（抑制初始血管炎症）和维持缓解。
GC无疑是治疗的核心, 高剂量GC是活动性疾病诱导缓解的金标准。
然而, 其使用受限于两个问题。
其一, GC在抑制长期血管并发症方面不那么有效。
其二, GC 有众所周知的不良反应。
近47%接受GC单药治疗的患者在减量过程中复发, 导致长期治疗和GC累积暴露量较高。
基于这些原因, 已提出将免疫抑制剂和生物制剂作为附加治疗。
1.GCA的治疗药物甲氨蝶吟（MTX ）是治疗GCA最常用的免疫抑制剂。
对3项随机安慰剂对照MTX试验的荟萃分析表明, 经MTX治疗后, 患者复发率较低, 相对 GC累积剂量较低, 无GC复发率较高。
尽管MTX通常是一种疗效良好且安全的药物, 但应考虑其对老年人的潜在毒性, 尤其是在肾功能受损的情况下。
目前, 硫唑嘌吟、环磷酰胺和来氟米特的数据有限, 由于这些药物未能显示出显著的风险/效益比, 因此不建议将MTX以外的常规免疫抑制剂用于治疗GCA。
TNF抑制剂治疗GCA的临床试验仍然显示无效。
托珠单抗（TCZ ）是一种抗白细胞介素6 （IL-6）受体抑制剂, 是目前应用最广泛、最有效的用于GCA 的生物制剂。
TCZ治疗新诊断和难治性/复发性GCA的有效性和安全性已在2项随机、双盲、安慰剂对照试验中得到证明, 其可以减少复发和GC的累积剂量, 而不会增加严重的不良反应。
2017 ACR：不容错过的干燥综合征研究热点
2017 ACR：不容错过的干燥综合征研究热点北京大学人民医院风湿免疫科何菁2017年11月4日～8日，美国风湿病年会（ACR）在美丽的圣地亚哥举行。
来自世界各地的17,000多与会者都相约来到这里。
会议囊括了干燥综合征（SS）基础与临床的前沿研究，下面简述这些研究热点，希望能够为国内同仁注入新的知识。
一、干燥综合征治疗新观点美国宾夕法尼亚大学干燥中心负责人的Frederick B. Vivino教授在会议上总结了美国近3年干燥专家共识的总观点，认为干燥综合征给美国社会带来了很多压力，在该病的诊断和治疗方面学术界也面临很多挑战。
目前的治疗还仅仅是缓解症状和对症，但是在评估免疫相关药物的利弊后，阻止干燥综合征并发症的发生和发展已经提上日程。
以下是新形成的几个治疗推荐。
针对疲劳的治疗推荐如下：1.教育患者学会自我评估和锻炼以减轻疲劳（强）；2.应用羟氯喹（弱）；3.不推荐应用DHEA类（雄激素）药物（强）；4.不推荐TNF-a抑制剂（强）。
（备注，其中强中弱为推荐等级）针对骨骼肌肉疼痛或炎性肌病的推荐如下：1.一线治疗是羟氯喹（中）；2.若效果不佳换用甲氨蝶呤或者羟氯喹联合甲氨蝶呤治疗（中）；3.症状重者可短期应用小剂量激素，即15mg每日起用，1个月内减停（强）；4.长期应用激素缓解后尽快减量（中）；5.来氟米特（弱）；6.柳氮磺胺吡啶（弱）；7a.硫唑嘌呤（弱）；7b.如果合并脏器受累，硫唑嘌呤强于来氟米特和柳氮磺胺吡啶。
口腔治疗建议是：1.所有口干患者均给予含氟的局部治疗（强）；2.含矿化物的漱口水（中）；3.双氯苯双胍己烷漱口（弱）；4.刺激唾液分泌（弱）。
眼科治疗时患者需先由眼科大夫进行诊断鉴别，区别是泪液缺失引起还是睑板腺炎症引起。
如果是单纯的泪液缺失，则治疗上由轻到重分别是：1.教育和改善环境因素，泪液替代等；2.抗炎性眼药水，Omega 3补充，泪道栓子，促分泌素，湿镜；3.血清制品眼药，绷带镜，泪点灼烧术；4. 系统抗炎治疗，眼睑手术。
系统性血管炎最新分类盘点
系统性⾎管炎最新分类盘点系统性⾎管炎⼀般指以⾎管壁炎症与坏死为主要病理特征的⼀组炎性⾃⾝免疫性疾病，分为原发性和继发性。
⾎管炎可引起⾎流减少或⾎管阻塞，导致组织缺⾎、坏死，⾎管本⾝也可因炎症受损，导致永久性狭窄、形成动脉瘤或者破裂。
1分类⼏⼗年来，⾎管炎的分类是⼀个具有挑战性的问题。
1990年，美国风湿病学会（ACR）提出的⾎管炎分类标准可以帮助诊断，但是缺乏⾜够的敏感性和特异性。
1994 年的Chapel Hill 共识会议（CHCC）提出了⾎管炎的疾病定义，但是并未体现疾病的组织病理学特点。
欧洲药品管理局（EMA）对抗中性粒细胞胞浆抗体（ANCA）相关⾎管炎以及结节性多动脉炎进⾏分类，以进⾏流⾏病学研究，但也有其局限性。
随着对疾病发病机制的认识，系统性⾎管炎的命名及定义在持续更新。
2012年CHCC根据主要受累⾎管的⼤⼩对⾎管炎进⾏了命名和分类，⽬前应⽤最为⼴泛（表1）。
根据病变⾎管的⼤⼩，系统性⾎管炎⼤致可分为⼤⾎管炎（LVV）、中⾎管炎（MVV）和⼩⾎管炎（SVV），但是有些疾病累及的⾎管⼤⼩可能会有重叠，另外，有的系统性⾎管炎累及⾎管⼤⼩可变。
在定义⾎管⼤⼩时，“⼤⾎管”是指主动脉及其主要分⽀，“中⾎管”是指主要的内脏动静脉及其初始分⽀，“⼩⾎管”是指⼩动脉、⽑细⾎管及⼩静脉。
1.1 ⼤⾎管炎1.1.1 ⼤动脉炎（TAK）⼤动脉炎指主要累及主动脉及其⼀级分⽀的慢性⾁芽肿性动脉炎。
通常在50岁之前发病，⼥性多见。
炎症和损伤往往局限于受累⾎管的⼀部分，但是也可出现⼴泛受累，例如全主动脉炎（pan-aortitis）。
1.1.2 巨细胞动脉炎（GCA）⼜称为颞动脉炎，常为⾁芽肿性动脉炎。
主要累及主动脉及其主要分⽀，包括颈动脉分⽀，尤其是颞动脉。
通常在50岁之后发病，其中70~90岁个体的发病率显著增加，常伴发风湿性多肌痛。
还有其他类型的⼤⾎管炎，有的尚⽆特定名称，如特发性孤⽴性主动脉炎；有的是其他类型⾎管炎或全⾝炎症性疾病的⼀部分，如科根综合征或复发性多软⾻炎。
ANCA相关血管炎
1. 显微镜下多血管炎（MPA）
MPA是一种坏死性血管炎，主要累及毛细血管、微静脉或微动脉，最常表现为坏死性肾小球肾炎和/ 或肺毛细血管炎。
1
c-ANCA或PR3-ANCA抗体阳性
-1
嗜酸细胞计数≥1×10^9/L
-4
总分在6分或以上者可以诊断为MPA
ANCA相关血管炎的诊断 ——嗜酸性肉芽肿性多血管炎
1990年美国风湿病学会（ACR）关于EGPA分类标准 ①哮喘 ②外周血嗜酸性粒细胞增多，＞10％ ③单发或多发性神经病变 ④游走性或一过性肺浸润 ⑤鼻窦病变 ⑥血管外嗜酸性粒细胞浸润。
ANCA相关血管炎的诊断 ——显微镜下多血管炎
2017年ACR/EULAR联合制定的MPA分类标准
Байду номын сангаас
条目
定义
得分
临床标准 鼻腔血性分泌物、溃疡、鼻痂或鼻窦-鼻腔充血/不通畅、鼻中隔缺损或穿孔
-3
实验室标准 p-ANCA或MPO-ANCA抗体阳性
6
胸部影像检查提示肺纤维化或肺间质性病变
5
极少或没有免疫复合物沉积的肾小球肾炎
2. 肉芽肿性多血管炎（GPA）
GPA是一种坏死性血管炎，主要累及小型至中型血管，如毛细血管、微静脉、微动脉、动脉和静脉。
3. 嗜酸性肉芽肿性多血管炎（EGPA）
EGPA是一种富含嗜酸性粒细胞的坏死性血管炎，主要累及小型至中型血管。
肉芽肿性多血管炎和显微镜下多血管炎的流行病学
指南速递2019ACREULARIgG4相关性疾病分类标准
指南速递2019ACREULARIgG4相关性疾病分类标准在2018年美国风湿病学会（ACR）年会上，ACR宣布，全球首部IgG4相关性疾病的分类标准已经起草完成。
就在近日，该标准的定稿在Arthritis and Rheumatology杂志在线提前发表，并将于2020年1月刊正式与大家见面。
主要内容先睹为快。
IgG4相关性疾病（IgG4-RD）几乎可在所有器官中引起纤维性炎性病变。
IgG4-RD可以治疗，但由于常常表现为肿块、纤维化等，易被误诊为肿瘤如胰腺癌或者其他自身免疫病如干燥综合征等，其诊断需要联系临床、血清学、影像学和病理学资料。
2019 ACR/EULAR分类标准的提出，是IgG4-RD领域的重要里程碑。
总体而言，该分类标准将IgG4-RD的诊断分成了三个步骤：第一步，入选！必须证明该可能的IgG4‐RD病例至少有1个器官（11个之一）受累，受累表现与IgG4‐RD一致。
第二步，除外！患者不可符合包括了总计32项临床、血清学、影像学和病理学指标的排除标准。
符合上述任意一个标准，都不考虑进一步的IgG4-RD分类。
第三步，评分！应用8项加权纳入标准分别评估临床、血清学、放射学和病理学结果。
详细步骤如下：步骤1. 入选标准是†或否典型器官（如胰腺、唾液腺、胆管、眼眶、肾、肺、主动脉、腹膜后、硬脊膜或甲状腺）出现特征性的临床或放射学表现*，或上述器官之一出现炎症伴有不明病因的淋巴浆细胞浸润的病理证据。
* 指受累器官增大或出现肿瘤样肿块，不包括：①胆管，倾向于发生狭窄；②主动脉，典型表现是动脉壁增厚或动脉瘤扩张；③肺，支气管血管束增厚多见。
† 如果不符合入选标准，则不能进一步考虑将患者归为IgG4-RD。
步骤2. 排除标准：项目和指标‡是或否§临床发热对糖皮质激素无客观应答血清学原因不明的淋巴细胞减少或血小板减少外周嗜酸性粒细胞增多抗中性粒细胞细胞质抗体（特别是抗蛋白酶3或髓过氧化物酶）阳性SSA/Ro或SSB/La抗体阳性双链DNA、RNP或Sm抗体阳性出现其他疾病特异性自身抗体冷球蛋白血症影像学已知的可疑恶性肿瘤或感染的放射学检查结果，未充分探查快速的放射学进展符合Erdheim-Chester病表现的长骨异常脾大病理学提示恶性肿瘤的细胞浸润，未充分评估与炎性肌纤维母细胞瘤一致的标志物明显的中性粒细胞性炎症坏死性血管炎明显的坏死以肉芽肿性炎症为主巨噬细胞/组织细胞疾病的病理学特征以下情况的已知诊断多中心Castleman病克罗恩病或溃疡性结肠炎（如果只有胰胆管病变）桥本甲状腺炎（如果仅有甲状腺受累）‡ 应根据患者的临床情况对是否符合排除标准进行个体化评估。
AAV诊治策略专题知识
ANCA有关性血管炎（AAV）
AAV旳基本病理特征
GPA和EGPA血管周围有肉芽肿形成。
肉芽肿：中央坏死、边沿类上皮细胞和多核巨细胞、外周淋巴细胞
急性期：中性或嗜酸粒浸润/中性粒细胞碎裂，慢 性期：小血管纤维化，官腔狭窄。
肾脏最易受累，92%肾小球可见新月体形成， 64.3%患者新月体百分比>50%，半数以上伴肾小 球毛细血管袢节段坏死。绝大多数存在严重旳肾 小管间质病变。
肾脏：肾性高血压、蛋白尿、异常尿沉渣、坏死性 肾小球肾炎
消化系统：腹泻、腹痛、消化道出血、肝酶升高。
化验异常：血Cr及BUN升高、贫血、WBC升高、血小 板降低、低补体血症、高γ球蛋白、血沉增快、 CRP增高
ANCA阳性、抗内皮细胞抗体阳性 影像学体现
By January 2023, a total of 658 patients had been recruited by 33 sites from 18 countries.
声门下狭窄
肺部结节
多系统受累旳皮肤血管炎
多发性单神经炎
眶内球后肿物
AAV以外ANCA（+）旳疾病
CTD (SLE, SSc, RA…..) 非AAV旳血管炎 胃肠道疾病（UC,CD,PSC） 感染性疾病 恶性肿瘤（淋巴瘤……）
抗内皮细胞抗体 （Antiendothelial cell antibodies，AECA）
中档血管炎：结节性多动脉炎、川崎病
小血管炎：韦格纳肉芽肿、显微镜下多血管炎、 Churg-Strauss综合征、过敏性紫癜、皮肤白细胞 破碎性血管炎、冷球蛋白血症性血管炎
大中小动脉、静脉均可受累：贝赫切特综合征 （白塞病）
不足
还有一部分血管炎未被纳入该分类：如血栓 闭塞性脉管炎，某些不常见旳血管炎(肺出血 肾炎综合征，Cogan综合症，低补体性血管炎) 以及继发性血管炎；
血管炎分类标准(chcc标准)
血管炎分类标准(chcc标准)
血管炎是一组以血管炎性病变为主要特征的疾病，其分类标准
采用的是临床和病理学特征。
目前，临床上常用的分类标准是
Chapel Hill Consensus Conference (CHCC)关于血管炎的分类标准。
CHCC标准将血管炎分为大血管炎和小血管炎两大类。
大血管炎
主要包括巨细胞动脉炎、临床和病理特征相似的大动脉炎、中等血
管炎和其他少见的大血管炎。
小血管炎则包括抗中性粒细胞胞浆抗
体相关的小血管炎、免疫复合物相关的小血管炎、其他少见的小血
管炎以及无特异性小血管炎。
具体而言，CHCC标准将大血管炎和小血管炎分为六大类，包括，巨细胞动脉炎、巨细胞动脉炎相关的其他血管炎、大动脉炎、中等
血管炎、抗中性粒细胞胞浆抗体相关的小血管炎和免疫复合物相关
的小血管炎。
这种分类标准有助于医生在临床实践中更好地识别和
诊断血管炎，为患者提供更精准的治疗方案。
总的来说，CHCC标准是目前临床上广泛采用的血管炎分类标准，它将血管炎分为大血管炎和小血管炎两大类，并进一步细分为六大
类，有助于医生更好地理解和诊断血管炎，为患者提供更科学的治疗方案。
原发性胆汁性胆管炎伴嗜酸性肉芽肿性血管炎一例
601综合病例研究新医学2023年8月第54卷第8期原发性胆汁性胆管炎伴嗜酸性肉芽肿性血管炎一例肖巧 肖华 王容 赵川 【摘要】 原发性胆汁性胆管炎（PBC ）病因尚不清楚，可能与基因、遗传、环境等因素有关，熊去氧胆酸是该病的一线治疗药物。
嗜酸性肉芽肿性血管炎（EGPA ）是一种系统性血管炎性疾病，以坏死性血管炎、组织器官嗜酸性粒细胞浸润和血管外肉芽肿形成为主要特征。
该文报道1例65岁男性患者以反复四肢皮疹为主要表现，反复肝功能异常，同时存在哮喘样喘息，镜下血尿，肾功能异常及嗜酸性粒细胞增多，最后诊断为PBC 合并EGPA 。
该例提示不明原因嗜酸性粒细胞增多，同时合并皮肤、肺、肝、肾、免疫等多器官损害时，需考虑是否为风湿免疫系统疾病。
【关键词】 原发性胆汁性胆管炎；肝硬化；嗜酸性肉芽肿性血管炎；嗜酸性粒细胞增多症；多器官损害Primary biliary cholangitis complicated with eosinophilic granulomatous with polyangiitis: a case report Xiao Qiao ， Xiao Hua ， Wang Rong ， Zhao Chuan. Department of Infectious Diseases ， Suining Central Hospital ， Suining 629000， China Corresponding author ， Xiao Qiao ， E -mail:****************【Abstract 】 The etiology of primary biliary cholangitis （PBC ） is unclear ， which may be associated with genetic ， hereditary andenvironmental factors ， etc . Ursodeoxycholic acid （UDCA ） is the fi rst -line drug for the treatment of PBC. Eosinophilic granulomatouswith polyangiitis （EGPA ） is a systemic vascular inflammatory disease characterized by necrotizing vasculitis ， in fi ltration of eosinophilsin tissues and organs ， and formation of extravascular granulomas. In this report ， a 65-year -old male patient presented with recurrent rashes on four limbs ， recurrent abnormal liver function ， asthma -like wheezing ， microscopic hematuria ， abnormal renal function ， and eosinophilia. He was fi nally diagnosed with PBC complicated with EGPA. This case suggests that the possibility of rheumatic immune system disease should be considered for patients with unexplained eosinophilia complicated with multiple organ damage ， such as skin ， lung ， liver ， kidney ， and immune system.【Key words 】 Primary biliary cholangitis ； Cirrhosis of liver ； Eosinophilic granulomatous with polyangiitis ； Eosinophilia ；Multiple organ damage原发性胆汁性胆管炎（PBC ）是一种慢性自身免疫性肝内胆汁淤积性非化脓性破坏性小胆管炎，血生物化学指标特点是血清碱性磷酸酶（ALP ）、γ-谷氨酰转移酶（GGT ）升高，免疫学特点是抗线粒体抗体（AMA ）阳性、血清IgM 升高，组织学上有非化脓性破坏性胆管炎和小胆管破坏的证据［1］。
2009年美国ACR对SLE的分类修订标准
2009年美国ACR对SLE的分类修订标准临床标准: ⑴急性或亚急性皮肤狼疮表现; ⑵慢性皮肤狼疮表现; ⑶口腔或鼻咽部溃疡; ⑷非瘢痕性秃发; ⑸炎性滑膜炎,可观察到2个或更多的外周关节有肿胀或压痛,伴晨僵; ⑹浆膜炎;⑺肾脏病变: 尿蛋白>0.5g/d或出现红细胞管型; ⑻神经病变:癫痫发作或精神病, 多发性单神经炎, 脊髓炎, 外周或颅神经病变, 脑炎; ⑼溶血性贫血; ⑽白细胞减少(至少1次细胞计数< 4.0×109/L)或淋巴细胞减少(至少1次细胞计数< 1.0×109/L) ; •血小板减少症(至少1次细胞计数<100×109 /L)。
免疫学标准: ⑴ANA滴度高于实验室参考标准；⑵抗dsDNA抗体滴度高于实验室参考标准(ELISA法测需有2次高于该参考标准) ；⑶抗Sm抗体阳性；⑷抗磷脂抗体：狼疮抗凝物阳性/梅毒血清学试验假阳性/抗心磷脂抗体是正常水平2倍以上或抗β2GPI中滴度以上升高；⑸补体减低：C3、C4、CH50；⑹无溶血性贫血但Coombs试验阳性。
确诊条件：⑴肾脏病理证实为狼疮肾炎并伴ANA或抗dsDNA 阳性；⑵以上临床及免疫指标中有4条以上符合（至少包含1项临床指标和1项免疫学指标）。
该标准敏感性94%，特异性92%。
表1. 美国风湿病学院1997年修订的SLE分类标准1. 颊部红斑固定红斑，扁平或高起，在两颧突出部位2. 盘状红斑片状高起于皮肤的红斑，粘附有角质脱屑和毛囊栓；陈旧病变可发生萎缩性瘢痕3. 光过敏对日光有明显的反应，引起皮疹，从病史中得知或医生观察到4. 口腔溃疡经医生观察到的口腔或鼻咽部溃疡，一般为无痛性5. 关节炎非侵蚀性关节炎，累及2个或更多的外周关节，有压痛，肿胀或积液6. 浆膜炎胸膜炎或心包炎7. 肾脏病变尿蛋白>0.5g/24小时或+++，或管型（红细胞、血红蛋白、颗粒或混合管型）8. 神经病变癫痫发作或精神病，除外药物或已知的代谢紊乱9. 血液学疾病溶血性贫血，或白细胞减少，或淋巴细胞减少，或血小板减少10. 免疫学异常抗ds-DNA抗体阳性，或抗Sm抗体阳性，或抗磷脂抗体阳性（后者包括抗心磷脂抗体、或狼疮抗凝物阳性、或至少持续6个月的梅毒血清试验假阳性三者之一）11. 抗核抗体在任何时候和未用药物诱发“药物性狼疮”的情况下，抗核抗体滴度异常SLE好发于生育年龄女性，多见于15~45岁年龄段，女∶男比例为7 ~ 9∶1。
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高冠民 郑州大学第一附属医院风湿免疫科
系统性血管炎（Systemic Vasculitis）
• • • • 以血管的炎症与坏死为主要病理改变 常累及全身多个系统，也可局限于某一脏器 常累及的部位为皮肤、肾脏、肺、神经系统 临床表现复杂多样，变化多端
历史
1866年 临床医师Küssmaul和病理医师Maier描述了一例 具有 发热、厌食、感觉异常、肌无力、肌痛、腹痛以及少 尿的患者，血管病理显示为全身中到小动脉的结节性 炎性损害，称之为结节性动脉周围炎 (periarteritis nodosa)。 1903年 Ferrari称之为结节性多动脉炎 (polyarteritis nodosa)， 后来被称为“经典的结节性多动脉炎”。
系统性血管炎的分类
不同血管受累可能出现的临床表现
ANCA 间接免疫荧光
pANCA-MPO
cANCA—PR3
•
• • • • • • •
蛋白水解酶3（Proteinase-3, PR3）
ANCA的靶抗原
髓过氧化物酶（Myeloperoxidase，MPO） 弹性蛋白酶（Elastase） 乳铁蛋白（Lactoferria，LF） 组织蛋白酶G（Cathepsin G） 溶酶体（Lysozyme）、 α-烯醇化酶（α-enolase） β-葡萄糖醛酸酶(β-glucuronidase) 增加痛透性杀菌蛋白（ Baxtericidal/permeabilityincreasing protein,BPI） • 人溶酶体相关膜蛋白2（Human lysosomal-asocited membrane protein2，HLAMP2） • 防御素（Defensin）、天青杀素（Azurocidin）
1952年 Zeek首次对血管炎进行了分类，首次提出了坏死性血 管炎 (necrotizing angiitis)用以区分5类系统性血管 炎，即超敏性血管炎、变应性肉芽肿性血管炎、风 湿性动脉炎、结节性动脉周围炎和颞动脉炎，此分 类中未包括韦格纳肉芽肿以及大动脉炎 (Takayasu arteritis)。 1964年 Alarcón-Segovia分类标准 1975年 de shazo分类标准 1978年Fauci分类和 1988年Scott分类标准等。
ANCA相关疾病
• ANCA经常出现于炎症性肠病（IBD）,溃疡 性结肠炎比克隆病常见。抗原靶点是非－ PR3和非－MPO的，一些抗原已经报道， 如组织蛋白酶G、乳铁蛋白、弹性溶菌酶和 BPI，但大部分还不明确。 • 其它消化系统疾病（GI）如硬化性胆管炎 和自身免疫性肝炎，有报道ANCA阳性 （多种非－PR3-ANCA,非－MPOANCA）。
2017年 ACR报道
ANCA相关疾病
• 结缔组织病的病人如RA、SLE和肌炎，偶可表现 出ANCA阳性，但大多是非MPO-ANCA, 和非 PR3－ANCA。 • 胆囊纤维化、心内膜炎感染、HIV感染，偶尔会 出现ANCA阳性。 这有特殊的临床意义，因为感 染可以出现酷似血管炎的症状。 • CTD出现的ANCA阳性和大多感染性疾病的 ANCA阳性都是非－PR3-ANCA和非－MPOANCA。
Churg-Stauss
Churg-Strauss
Microscopic Polyangiitis
Microscopic Polyangiitis
伯明翰系统性血管炎活动评分 (Birmingham vasculitis activity score, BVAS)
伯明翰系统性血管炎活动评分(BVAS)
系统性表现
(最高总分3分)
1. 2. 3. 4. 5. 6. 7. 8. 无 不适 肌痛 关节痛/关节炎 发热(<38.5℃) 发热(>38.5℃) 过去1月内体重下降(1~2Kg) 体重下降( > 2Kg) 0 1 1 1 1 2 2 3
皮肤表现
(最高总分6分) 1. 2. 3. 4. 5. 6. 7. 无 梗死 紫癜 其他皮肤血管炎 溃疡 坏疽 多发肢端坏疽 0 2 2 2 2 4 6
ANCA相关性血管炎的特点比较
肉芽肿性血管炎 ANCA阳性率 ANCA抗原 肾脏受累 肺部受累 上呼吸道症状 眼部受累 神经系统受累 心血管受累 胃肠道受累 皮肤黏膜 80%-90% PR3＞MPO 80% 90% 90% 眼眶假性肿瘤 50% 少见 50% 显微镜下多血管 炎 70% MPO＞PR3 90% 50% 35% 少见 30% 少见 50% 嗜酸细胞性肉芽肿性 多血管炎 50% MPO＞PR3 45% 70% 50% 少见 70% 常见（ANCA阴性） 50%
历史
1994年
Lie就Chapel Hill会议的阐述了不同意见， 如川崎病可以累及冠状动脉的分支小动脉，并 以Zeek的分类标准为基础提出了自己的分类标 准，本分类提出血管炎有原发性和继发性之分， 使血管炎的概念更为广泛，且更符合临床实际。 白塞病可累及大、中、小血管的血管炎，其中小静 脉最常受累，但上述血管炎分类中皆未将其收入。 2012年 更新
历史
1993年Chapel Hill会议 （Chapel Hill Consensus Conference, CHCC）
主要根据受累血管的大小对系统性血管炎进行了命名 和定义。此次会议首次提及并建议使用显微镜下多血 管炎这一命名，而非显微镜下多动脉炎 (microscopic polyarteritis)，因为显微镜下多血管炎主要累及微动 脉、静脉和毛细血管，可无动脉受累。
以下各项为前4周内，由血管炎所致的新近表现或病情加重 – – – – – – – – – 系统性表现 皮肤表现 粘膜/眼 耳鼻喉 胸部 心血管 腹部 肾脏 神经系统 3(最高总分) 6(最高总分) 6(最高总分) 6(最高总分) 6(最高总分) 6(最高总分) 9(最高总分) 12(最高总分) 9(最高总分)
说明： 1．各系统评分皆有最高限，评分总分最高63分 2．15分以上为活动 3 ．本表引自 Loqmani R A, Bacon P A, moots R J, et al. Birmingham vasculitis activity score (BVAS) in systemic necrotizing vasculitis. Q J Med, 1994, 87:671-8.
粘膜/眼
(最高总分6分)
• • • • • • •
无 口腔溃疡 生殖器溃疡 结膜 葡萄膜炎 视网膜渗出 视网膜出血
0 1 1 2 4 6 6
耳鼻喉
(最高总分6分) • • • • • • • • • • 无 流涕/鼻塞 鼻窦炎 鼻衄 结痂 外耳道渗出 中耳炎 新近耳聋 声嘶/喉炎 声门以下受累 0 2 2 4 4 4 4 6 2 6
皮肤，肌肉和外周神经受累
肾损害
• 血尿、蛋白尿、RPGN
– 可隐袭起病 – 多为非少尿性 – 易误诊为CRF
• 免疫病理和电镜
– Pauci-immune?
• 光镜
– 襻坏死 – 新月体形成 – 病变不平行
肺受累的表现
• 90%肺受累 – 50%肺出血 – 咳嗽、咯血、呼吸困难 • 胸片 – 阴影、结节和空洞 • 易误诊为感染、肿瘤 和结核 – 弥漫性肺泡毛细血管炎 • 易误诊为感染、肺水 肿
1936年 描述了韦格纳肉芽肿 (Wegener‘s granulomatosis, WG) 1948年 就被提及的“显微镜下的动脉周围炎 (microscopic form of polyarteritis nodosa) 1951年 描述了变应性肉芽肿性血管炎 (Churg-Strauss syndrome)。
• • • • •
显微镜下型多血管炎占70-80% 肾受累：100% 肺受累：391/478（82%） 绝大多数误漏诊 病情危重，BVAS积分高
我国ANCA相关小血管炎的特点 赵明辉
辛岗等。中华风湿病杂志 2003;7(1):30-33 于峰等。中华儿科杂志 2003;41(11):831-834 Xin et al. Clin Diagn Lab Immunol. 2004;11(3):559-62 Wang et al. Experimental Gerontology 2004，In press
ANCA检测的指征
1、肾小球肾炎，尤其是急进性肾小球肾炎 2、肺出血，尤其是肺肾综合征 3、具有系统性特征的皮肤血管炎 4、多发肺结节 5、上呼吸道慢性破坏性疾病 6、长期鼻窦炎和中耳炎 7、声门下气管狭窄 8、多发性神经炎和外周神经病变 9、眼眶后肿物 （1999年 ANCA和血管炎的澳大利亚国际会议）
伯明翰系统性血管炎活动评分(BVAS)
1．各系统评分皆有最高限， 评分总分最高 63分 2．15分以上为活动 3．本表引自Loqmani R A, Bacon P A, moots R J, et al. Birmingham vasculitis activity score (BVAS) in systemic necrotizing vasculitis. Q J Med, 1994, 87:671-8.
Clin Kidney J. 2015 Jun;8(3):343-50
非常常见，紫癜、皮下结节、瘀斑、瘀点、溃疡等
39例ANCA相关性血管炎患者的临床表现
项目 发热、乏力 肺脏累及 肾脏累及 关节疼痛 皮疹 周围神经病变 鼻塞、鼻衄 腹痛 耳鸣、耳痛 结膜炎 阳性例数 28 27 23 20 11 9 6 3 3 2 百分率（%） 71.7 69.2 58.9 51.3 28.2 23.0 15.3 7.6 7.6 5.1
腹部
(最高总分9分)
• • • • • •
无 腹痛 血性腹泻 胆囊穿孔 肠梗死 胰腺炎
0 3 6 9 9 9
肾脏
(最高总分12分)
1. 2. 3. 4. 5. 无 高血压(收缩压>90mmHg) 蛋白尿(> +或> 0.2g/24h) 血尿(> + 或> 10RBC/ml) 肌酐 125-249umol/L 250-499umol/L >500umol/L 肌酐上升率>10% 0 4 4 8 8 10 12 12