Association of autoantibodies to myeloperoxidase with different forms of vasculitis

Antineutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase (MPO) were found in 53 patient sera that were routinely submitted for antineutrophil cytoplasmic antibody determination. Based on clinical and histologic criteria, 15 of these 53 patients were classified as having systemic necrotizing vasculitis of the polyarteritis group, 11 patients were classified as having Wegener's granulomatosis (WG), and 14 were classified as having idiopathic crescentic glomerulonephritis. The remaining 13 patients did not fulfill the diagnostic criteria for these disorders, although most of these patients had clinical symptoms compatible with these disorders. While all patients with WG had renal involvement, only 4 of the 15 patients with systemic necrotizing vasculitis of the polyarteritis group had glomerulonephritis. The sensitivity of autoantibodies to MPO for either systemic necrotizing vasculitis of the polyarteritis group, WG, or idiopathic crescentic glomerulonephritis was further tested in all our patients with these disorders (n = 104). Twenty-seven of 104 patients had autoantibodies to MPO. Furthermore, 69 of the remaining 77 patients had autoantibodies specific for the 29-kd serine protease, which has been reported to be specifically associated with WG. Sera from 8 patients were negative for either of these antibodies (92% sensitivity of autoantibodies to MPO and/or the 29-kd serine protease). The specificity of autoantibodies to MPO for either systemic necrotizing vasculitis of the polyarteritis group, WG, or idiopathic crescentic glomerulonephritis was also tested in selected groups of patients who had closely related diseases. Two of 144 patients had autoantibodies to MPO (specificity 99%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal arteritis associated with systemic necrotizing vasculitis

OBJECTIVE: To evaluate the clinical and laboratory characteristics of patients with systemic vasculitis associated with temporal artery involvement. METHODS: From a cohort of 120 patients fulfilling American College of Rheumatology criteria for temporal arteritis, we retrospectively identified 7 patients with systemic necrotizing vasculitis associated with histological temporal arteritis. RESULTS: Among the 7 patients, 2 had classic polyarteritis nodosa, one had unclassified systemic vasculitis, one had Wegener's granulomatosis (WG), and 3 had microscopic polyangiitis. The mean age of the patients was 70.2 years, and cranial symptoms revealed the disease in all but one patient. Temporal arteritis was generally associated with extracephalic manifestations suggestive of systemic vasculitis. Antineutrophilic cytoplasmic antibodies were positive in 3 of the 4 patients with small vessel vasculitis. Pathologically, the main temporal artery was involved in all but one patient, with inflammatory infiltrate of vasa vasorum and adventitia associated in 5 with small tributary involvement. Fibrinoid necrosis was rare, observed in 2 specimens; 2 patients with unclassified systemic vasculitis and WG had a classic giant cell arteritis (GCA) histologic pattern. Only one patient had exclusive involvement of small vessels, surrounding the spared main temporal artery. Muscle biopsies showed histopathological evidence of vasculitis in 2 patients, skin biopsy in one, and vein biopsy in the other. CONCLUSION: Temporal artery involvement in systemic necrotizing vasculitis was generally associated with extracranial clinical features suggestive of systemic vasculitis. Temporal artery biopsy is a simple tool for diagnosis of vasculitis, but the histopathological findings do not always discriminate between necrotizing vasculitis and classic GCA.     

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.     

Systemic necrotizing vasculitides in Turkey: a comparative analysis of 40 consecutive patients

Objective: The aim of this study was to analyze and compare the demographic and clinical features and prognosis of patients with different systemic necrotizing vasculitides (SNV) in Turkey. Patients and methods: Twenty-three patients with Wegeners granulomatosis (WG), 15 with polyarteritis nodosa (PAN), and two with Churg-Strauss syndrome were included in the study. The clinical and laboratory features of patients with WG and PAN were compared, and survival analysis was performed for the WG patients. Results: Twenty-one patients with WG had systemic disease involving kidneys, and two had localized disease. Fifteen patients were placed in the PAN group, 12 of whom were classified as having classic PAN and three with microscopic polyangiitis. Median follow-up time was 37 months (range 1–81) for WG patients and 41 months (range 5–132) for the PAN group. Upper respiratory tract, pulmonary, and renal involvement were significantly more frequent in the WG group than in PAN. Peripheral nervous system involvement was more frequent in the PAN group. In WG, survival was calculated as 59% at 35 months. High initial vasculitis damage index scores were found to be predictive for mortality. Conclusion: This study revealed that the most frequent type of SNV was WG in a tertiary rheumatology setting in Turkey. There was initial organ damage in most of the patients, frequently caused by severe renal involvement. In contrast to other published series, overt cardiovascular and gastrointestinal involvement were not observed in our patients with SNV.     

Antineutrophil cytoplasmic antibodies (ANCA) and systemic vasculitis: update of assays, immunopathogenesis, controversies, and report of a novel de novo ANCA-associated vasculitis after kidney transplantation

OBJECTIVES: To characterize antineutrophil cytoplasmic antibodies (ANCA), their major autoantigens, disease associations, and pathophysiology in systemic vasculitides. To describe a patient with a novel de novo ANCA-associated vasculitis after kidney transplantation. METHODS: We reviewed and compiled the literature on ANCA-related topics and systemic vasculitis. Laboratory and clinical data from a cadaveric kidney transplant patient who developed necrotizing vasculitis involving glomerular capillaries, with crescent formation associated with P-ANCA and myeloperoxidase, were analyzed. RESULTS: Large-scale multi-center testing of patient and normal sera by the European ANCA Assay Standardization Project using immunofluorescence assays and enzyme immunoassays indicate the assays have good sensitivity and specificity, and diagnostic utility for ANCA-associated vasculitis. A few investigations covering basic and clinical research with ANCA remain controversial: whether endothelial cells do or do not express a 29-kd neutral serine protease termed proteinase-3 (PR-3), the target of ANCA in most individuals with Wegener's granulomatosis, and whether anti-myeloperoxidase (MPO) ANCAs recognize a restricted number of epitopes on MPO. This issue has relevance for using monoclonal antibodies to treat patients with vasculitis who have adverse effects from immunosuppressive drugs. The two allelic forms of FcgammaRIIa (H131/R131) and the two of FcgammaRIIlb (NA1/NA2) are discussed as possible inheritable genetic elements for vasculitic disorders and for signaling responses. Stimulatory and costimulatory molecules, and cytokine profiles of T lymphocytes are characterized to show that these cells are actively involved in the ANCA-associated vasculitides. The patient described had a de novo ANCA associated small vessel vasculitis which developed after renal transplantation. CONCLUSIONS: There have been significant advances in the development of sensitive and specific ANCA assays. The immunopathogenetic mechanism of ANCA involves the constitutive FcgammaRs, ligands, and signaling responses to activate cytokine-primed neutrophils. This may lead to the generation of reactive oxygen intermediates, degranulation, and secretion of intracellular granule contents, and ultimately inflammation and vasculitis.     

Prevalence and specificity of antineutrophil cytoplasmic antibodies (ANCA) in connective tissue diseases

Antineutrophil cytoplasmic antibodies (ANCA) have specificity for constituents of neutrophil granules. There are two different types of ANCA identifiable by indirect immunofluorescence method. One type produces the cytoplasmic staining pattern (C-ANCA) and the second-perinuclear (P-ANCA). The aim of the study was to evaluate the frequency of ANCA in patients with connective tissue diseases (CTD). Serum samples were obtained from 394 patients suffering from CTD. The patients group consisted of 86 patients with lupus erythematosus systemic (LES) (including 30 with LES accompanied with glomerulonephritis), 136 cases with rheumatoid arthritis (RA) (including 18 patients with RA and vasculitis), 42 patients with systemic sclerosis (SSc), 76 cases of Sj?gren's syndrome (SS), 30 with Wegener's granulomatosis (WG), and 24 patients with polyarteritis nodosa (PAN). All patients fulfilled ARA criteria for the classification of CTD. The control group consisted of 42 healthy individuals. ANCA were detected by immunofluorescence method according to Wiik, and by an antigen-specific--enzyme-linked immunosorbent assay (ELISA). Proteinase 3 (PR-3), myeloperoxidase (MPO), elastase (ELA), lactoferrin (LC) and lysozyme (LZ), as well as cathepsin G were used as antigens in ELISA method. ANCA were detected in sera of 86 (21.8%) patients with CTD. C-ANCA pattern was observed in 28 (7.1%) cases, and p-ANCA in 58 (14.7%). C-ANCA were detected in sera of 28 (93%) patients with WG. P-ANCA were showed in 12 (13.9%) patients with LES, in 12 (50%) cases with PAN, in 20 (14.7%) with RA, in sera of 4 (9.5%) patients with SSc and in 10 (13.1%) with SS. No ANCAs were detected in healthy individuals. Ani-PR-3 antibodies were showed in sera of 26 patients, anti MPO in 30 cases, anti-ELA in sera of 12 patients, and anti-LC in 14 cases, but anti-LZ in 4 patients with CTD. The presence of ANCA in CTD patients may indicate the vascular inflammatory process during the course of the disease. It is a very important factor for the clinical course, and prognosis in the CTD patients.     

Temporal arteritis in young subjects. A trial of nosological classification apropos of 6 cases]

Six young-adult patients (19- to 32-years-old) are described: 3 men with temporally localized systemic vasculitis (thromboangiitis obliterans 2, Churg-Strauss angiitis 1) and 3 patients (2 men, 1 woman) with isolated temporal arteritis. Temporal arteritis in subjects under 40 years of age consists of either a temporal localization of systemic vasculitis (thromboangiitis obliterans or Buerger's disease, Churg-Strauss angiitis or polyarteritis nodosa) or a distinct entity of which only 12 biopsy-proven cases have been reported to date. The latter is differentiated from temporal (giant cell) arteritis of the older patient by a higher incidence in men, and the absence or rarity of general symptoms, ocular complications and an accelerated erythrocyte sedimentation rate. Two types of temporal arteritides in young adults seem to be distinguishable: an asymptomatic form with an isolated temporal nodule and a more symptomatic one. In some cases, temporal arteritis in young adults corresponds to a unique entity "juvenile temporal arteritis", which seems to be different from Takayasu's arteritis, localized forms of polyarteritis nodosa and Kimura's disease. Although its treatment remains difficult to define, therapy of the symptomatic form could include steroids, whereas the asymptomatic one seems to require only simple monitoring.     

Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produce a characteristic cytoplasmic staining pattern of neutrophils (c-ANCA) and are directed against proteinase 3 (Pr3), a serine protease from the azurophilic granules. c-ANCA, more or less equivalent to anti-Pr3, occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement, and in some 40% to 50% of patients with vasculitic overlap syndromes suggestive of WG such as microscopic polyarteritis. The presence of c-ANCA is highly specific for those diseases (greater than 98%). Changes of levels of c-ANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (p-ANCA) occur in a wide range of diseases. They are directed against different cytoplasmic constituents of neutrophils. Among those, antibodies to myeloperoxidase are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa with visceral involvement, and vasculitic overlap syndromes. Their specificity for this group of necrotizing vasculitides is high (94% to 99%), although they may occur in patients with hydralazine-induced glomerulonephritis, anti-glomerular basement membrane disease, and possibly in some patients with idiopathic systemic lupus erythematosus. Antibodies to leukocyte elastase are incidentally found in patients with vasculitic disorders, whereas lactoferrin antibodies are detected in patients with primary sclerosing cholangitis with or without ulcerative colitis and in rheumatoid arthritis. Their diagnostic significance awaits further studies. p-ANCA of undefined specificity may distinguish ulcerative colitis (sensitivity of 75%) from Crohn's disease (sensitivity of 20%). p-ANCA also occur in autoimmune liver diseases: in 75% of patients with chronic active hepatitis, in 60% to 85% of those with primary sclerosing cholangitis, and in about 30% of patients with primary biliary cirrhosis. Finally, p-ANCA are detected in chronic arthritides and in some 5% of healthy controls. Assessment of their diagnostic value has to await further characterization of the antigens involved, allowing the development of antigen-specific assays.     

Establishment of a pilot pediatric registry for chronic vasculitis is both essential and feasible: a Childhood Arthritis and Rheumatology Alliance (CARRA) survey

OBJECTIVE: To identify the need for, and feasibility of, establishing a web-based USA/Canadian registry of children with chronic systemic vasculitis--an otherwise insufficiently studied population. METHODS: Physician members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA; n = 126) were invited to complete 2 surveys exploring vasculitis-related experience, beliefs about childhood versus adult vasculitis, and commitment to contribute patients to a prospective registry. Diagnoses included Wegener's granulomatosis (WG), childhood polyarteritis nodosa, microscopic polyangiitis (MPA), Takayasu's arteritis, primary angiitis of the central nervous system (PACNS), vasculitis, and unclassified vasculitis. RESULTS: One or both surveys were completed by 102 (81%) physicians. Almost half of first-survey respondents had been in practice for > 15 years. Collective estimated lifetime experience was >1500 patients (WG and unclassified vasculitis were the most common diagnoses). Three hundred seventeen children with vasculitis were seen in the year preceding the survey, with most physicians seeing only 2-5 patients. The majority of respondents believed that childhood vasculitis differed from adult disease, particularly with respect to classification criteria and disease activity markers. Fifty-nine members committed to contribute 2 years' data (approximately 120 patients) to a pilot registry limited to time of diagnosis, focusing on WG, MPA, Churg-Strauss syndrome, PACNS, and unclassified vasculitis. CONCLUSION: We obtained overwhelming consensus from an experienced body of pediatric rheumatologists on the need to study childhood-onset vasculitis independently from adult disease, together with commitment from sufficient members to prospectively contribute 2 years' data to a limited pilot registry to answer some basic questions about presenting and diagnostic features and initial treatment practices at disease onset.     

Prevalence of rheumatic manifestations and antineutrophil cytoplasmic antibodies in haematological malignancies. A prospective study

OBJECTIVE: To evaluate the prevalence of antineutrophil cytoplasmic antibodies (ANCA) and rheumatic manifestations associated with chronic haematological malignancies. METHODS: Two groups of patients were prospectively studied (group I: 60 patients with myelodysplastic syndromes and group II: 140 patients with lymphoid malignancies) for clinical 'immune' manifestations and ANCA. RESULTS: In the myelodysplastic group, six patients had ANCA-negative systemic medium-size vasculitis, one had systemic vasculitis with cytoplasmic ANCA, one relapsing polychondritis, one giant cell arteritis, one polymyalgia rheumatica, one polyarthritis and two fasciitis. In group II, two patients had ANCA-negative systemic vasculitis, two had leucocytoclastic vasculitis associated with tuberculosis, two had polyarthritis, one polymyalgia rheumatica and one giant cell arteritis. Six sera were ANCA-positive with perinuclear pattern in four cases, atypical pattern in one and cytoplasmic pattern in one. Two sera had anti-myeloperoxidase (MPO) specificity, and others had no known specificity; none had anti-proteinase 3 (PR3) specificity. Global prevalence of ANCA in our cohort was 3%, similar to the French general population. CONCLUSION: Polyarteritis nodosa-type systemic vasculitis and polymyalgia rheumatica were the most frequent findings (18%) in myelodysplastic syndromes and particularly in chronic myelomonocytic leukaemia. ANCA were not helpful for the diagnosis of vasculitis. Vasculitis associated with infection, in particular tuberculosis, must be ruled out.     

A case of microscopic polyangiitis associated with aortic valve insufficiency

Microscopic polyangiitis (MPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by inflammation of small-sized vessels. Although there have been some reports of ANCA-associated vasculitis presenting as aortitis syndrome, MPA rarely involves large-sized vessels such as the aorta. We report an unusual case of MPA combined with severe acute aortic valve insufficiency in a 56-year-old man. He initially presented with prolonged fever, skin rash, and rapidly progressive glomerulonephritis. P-ANCA and anti-myeloperoxidase (MPO) antibodies were positive, but the c-ANCA and anti-proteinase-3 antibodies were negative. Skin biopsy of the lower leg showed necrotizing arteritis. Kidney biopsy was also performed, which revealed diffuse necrotizing and crescentic glomerulonephritis (GN) consistent with pauci-immune ANCA-associated GN. Serial echocardiographic evaluations revealed aortic valve changes and worsening acute aortic valve insufficiency over a two-month period. Despite intensive treatment, our patient developed sudden cardiac arrest and died. Our patient demonstrated typical clinical features and histopathologic findings for systemic vasculitis and had a positive anti-MPO antibody, all of which were consistent with the diagnosis of MPA. Thus, MPA may have been the cause of acute aortic valve insufficiency in this case.     

The lung in systemic vasculitis

Pulmonary vasculitis is usually caused by one of three disorders: (1) Wegener's granulomatosis (WG); (2) Churg-Strauss syndrome (CSS), or allergic angiitis and granulomatosis; or (3) a nonspecific small vessel systemic necrotizing vasculitis (SNV), or microscopic polyarteritis. WG, the most common cause of lung vasculitis, has features of a granulomatous vasculitis of the upper airway and lung and widespread small vessel vasculitis involving the kidneys and other organs. The features of pulmonary WG overlap with those of malignancy and infectious granulomatous lung disease; accurate diagnosis generally requires open lung biopsy. CSS is defined by the triad of asthma, eosinophilia, and systemic vasculitis. Easily accessible tissues should be biopsied, but the clinical features are so distinctive that tissue biopsy is not invariably required for diagnosis. CSS must be differentiated from other diseases that cause pulmonary infiltrates with eosinophilia, including infections. Nonspecific SNV causes diffuse alveolar hemorrhage due to pulmonary capillaritis. Concomitant segmental necrotizing glomerulonephritis is almost always present. Diagnosis is made by renal biopsy, compatible extrarenal features, exclusion of nonimmune causes of lung hemorrhage, and exclusion of WG to the extent possible.     

新分类标准对结节性多动脉炎诊断影响的研究初探

随着对抗中性粒细胞胞质抗体（ANCA）相关性血管炎的认识及乙型病毒性肝炎疫苗的广泛接种,结节性多动脉炎（PAN）的诊断发生了很大变化。本研究结合2012年Chapel Hill共识会议（CHCC）对PAN的定义和2007年欧洲药品管理局 （EMA）对中小血管炎分类法则,对2002年1月至2018年12月在北京协和医院住...     

Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic leukemia

OBJECTIVE: To determine the clinical aspects of systemic vasculitis associated with chronic myelomonocytic leukemia (CMML). METHODS: In this retrospective study, 8 patients suffering from systemic vasculitis associated with CMML are described. The French and English literature on systemic vasculitis associated with myelodysplasia was reviewed. RESULTS: All 8 patients had a systemic medium-sized vessel vasculitis which fulfilled the American College of Rheumatology criteria for polyarteritis nodosa in the setting of active CMML. Antineutrophil cytoplasmic antibodies (ANCA) were negative in 7 patients. One patient had cytoplasmic ANCA by indirect immunofluorescence without antiproteinase 3 or antimyeloperoxydase antibodies on the enzyme-linked immunosorbent assay. At presentation, 6 patients had fever of unknown origin, 5 had polymyalgia rheumatica, 3 had sensory hearing loss, and 4 had eosinophilia. None had viral infection or drug-associated vasculitis. Diagnostic procedures included renal or hepatic angiography in 6 patients which showed microaneurysms in 4, skin and temporal artery biopsy in 2 which showed vasculitis, and 1 postmortem examination which showed gastroduodenal arteritis. All patients were treated with corticosteroids, and 7 received immunosuppressive drugs. Death was attributable to vasculitis in 2 cases, infection in 3, and other vasculitis-related causes in 2. In a review of the French-English literature, we found 11 similar cases of ANCA-negative systemic vasculitis, generally associated with refractory anemia, with or without blast excess. CONCLUSIONS: Systemic ANCA-negative polyarteritis nodosa-type vasculitis seems closely associated to CMML. Clinical presentation is nonspecific, and systemic vasculitis should be suspected when a patient with myelodysplasia develops atypical manifestations. Renal, gastrointestinal, or hepatic angiography are useful diagnostic procedures when more invasive biopsies should be avoided because of low platelet count. The prognosis of CMML-associated systemic vasculitis is poor.     

Vasculitis and the gastrointestinal tract

Vasculitis, defined as a non-infectious inflammatory disorder of blood vessels, can affect vessels of any type in any organ. The gastrointestinal (GI) tract may thus also be involved. In systemic disorders as mixed connective tissue disease (MCTD) and systemic lupus erythematodes (SLE), patients may present with symptoms of gastrointestinal disfunction such as motility disorders, caused by alterations in the connective tissue. True vasculitis however also occurs in the GI tract. Severe, occlusive damage often leads to ischemia that may result in ulceration and perforation. Non-occlusive vascular disease may lead to vascular leakage resulting in oedema and haemorrhage. Those patients often present with diarrhoea or symptoms of bleeding. GI involvement is frequent in Henoch-Sch?nlein purpura and also often noted in polyarteritis nodosa (PAN), microscopic polyangiitis, Wegener's syndrome and Churg-Strauss syndrome. Furthermore, GI vasculitis has also been described in giant cell arteritis, Takayasu's disease, Buerger's disease and leucocytoclastic vasculitides as essential mixed cryoglubulinemia, lupus vasculitis, rheumatoid disease, MCTD, drug-induced vasculitis and Beh?et's disease. The diagnosis and classification of vasculitis relies upon a combination of clinical, serological, haematological, radiological and histological findings. Establishing a precise diagnosis can be difficult but is important because treatment and prognosis can be highly variable.     

Prevalence of antineutrophil cytoplasmic antibodies in patients with various pulmonary diseases or multiorgan dysfunction

OBJECTIVE: To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with diseases that may mimic systemic vasculitides, such as severe multiorgan dysfunction (MOD) and parenchymal pulmonary disorders. METHODS: We conducted a prospective study of patients with MOD admitted to the medical intensive care unit and patients with various lung diseases seen at the outpatient pulmonary clinic of a tertiary care hospital. Patients with a documented diagnosis of Wegener's granulomatosis (WG) served as positive controls. ANCA were determined in serum samples from each patient by a combination of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) for antibodies to proteinase-3 and myeloperoxidase (anti-MPO). RESULTS: Ninety-nine patients with MOD, 29 outpatients with various lung disorders, and 18 patients with WG were included in the study. ANCA were detected by IIF alone in 16% (15/96) of patients with nonvasculitic MOD and 17% (5/29) of outpatients with various pulmonary disorders. The majority of the positive IIF specimens from each group displayed an atypical IIF pattern (73% and 80%, respectively). Only 1 specimen from patients with nonvasculitic disorders was positive for anti-MPO. ANCA by both IIF and ELISA were detected in 78% (12/14) of control patients with WG. CONCLUSION: Detection of ANCA by the combination of IIF and antigen-specific assays for proteinase 3 and myeloperoxidase in diseases that mimic systemic vasculitides is highly specific for WG, microscopic polyangiitis, and Churg-Strauss syndrome.     

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.     

Maladie de Wegener à c-ANCA de type anti-MPO révélée par une uvéite

Wegener's granulomatosis (WG) is a rare systemic necrotizing granulomatous vasculitis affecting small- to medium-sized vessels, associated with antineutrophil cytoplasm antibodies (ANCA), mainly anti-proteinase 3. Rarely, ANCA may be directed against myeloperoxidase. We report a 58-year-old woman who developed an uveitis as the presenting manifestation of Wegener's granulomatosis who highlight the usefulness of internist and ophthalmologist collaboration.     

Anti-neutrophil cytoplasmic antibodies tests: which tests should be used in practice?

Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) has become an important tool for supporting a diagnosis of systemic necrotizing small vessel vasculitis: Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and oligo-symptomatic forms of these. These so-called ANCA-associated vasculitides most often necessitate the institution of therapies with cytotoxic as well as anti-inflammatory agents, and hence, a firmly established diagnosis is mandatory to avoid unnecessary and risky treatment. In the laboratory of today the most appropriate way to detect the presence of vasculitis-associated ANCA is by using both indirect immunofluorescence and direct enzyme immuno-assay for antibodies to proteinase 3 and myeloperoxidase. The diagnostic specificity of these latter assays towards systemic vasculitis can only be secured by setting a suitably high cut-off value, chosen in collaboration with clinicians after testing carefully selected disease control sera. When classical cytoplasmic ANCA as well as a significant level of proteinase 3-ANCA are found in a given serum this combined result strongly indicates vasculitis. Similarly, the combination of perinuclear ANCA and a significant level of myeloperoxidase-ANCA is close to 100% specific for vasculitis.