Wegener's granulomatosis: symptoms, diagnosis, and treatment

PURPOSE: To provide nurse practitioners with a basic understanding of the clinical presentation, diagnosis, diagnostic testing, pharmacological treatment, and prevalence of Wegener's granulomatosis (WG). DATA SOURCES: Published research and clinical articles, and a case report. CONCLUSIONS: WG is a systemic disease characterized by vasculitis, necrosis, and granulomas. The diagnosis of WG is difficult, particularly early in the disease process. In order to confirm the diagnosis, the patient should undergo specific tests such as antineutrophil cytoplasm antibodies, erythrocyte sedimentation rate, C-reactive protein, and biopsy of the tissue involved. IMPLICATIONS FOR PRACTICE: The diagnosis of WG is often delayed because of the vague symptoms on presentation. Initial symptoms, such as chronic fatigue, upper respiratory infection, sinusitis, and otitis media are common and may not be alarming. Recognizing symptoms, ordering diagnostic tests, and providing appropriate pharmacological therapy is key to diagnosing and treating WG.     

Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils

Anti-neutrophil cytoplasmic autoantibodies (ANCA) specifically associated with Wegener's granulomatosis were found to be directed against a saline-soluble glycoprotein triplet that migrates on SDS gels as distinct bands of Mr 29,000, 30,500, and 32,000 and is present in the azurophilic granules. This antigen was specifically recognized by all cytoplasmic-staining (C)-ANCA-positive sera from patients with Wegener's disease. C-ANCA antigen bound [3H]diisopropylfluorophosphate, which indicates that it is a serine protease, but it could clearly be distinguished from the serine proteases elastase and cathepsin G. Stimulation of cytochalasin B-treated neutrophils with FMLP induced release of C-ANCA antigen. This indicates that in vivo C-ANCA might interact with the C-ANCA antigen after its release upon inflammatory stimulation. We further demonstrate that in some perinuclear staining (P-ANCA) patients' sera autoantibodies against other myeloid lysosomal enzymes can be detected, such as antimyeloperoxidase and antielastase. C-ANCA and P-ANCA thus represent a novel class of autoantibodies directed against myeloid lysosomal enzymes. The originally described Wegener-specific C-ANCA show an apparently uniform specificity for the 29,000 serine protease. In contrast, P-ANCA may recognize myeloperoxidase as well as elastase and/or other antigens.     

Wegener's granulomatosis of the breast

Wegener's granulomatosis is a multisystem disorder characterized by necrotizing granulomatous inflammation and vasculitis of small vessels and can affect any organ system. The most common sites of involvement are upper and lower respiratory tracts, and kidneys. Breast involvement is unusual and very rare. We report a case of breast Wegener's granulomatosis in a 32-year-old woman who presented with pulmonary lesions and palpable masses in the left breast. Mammography showed multiple, sharply delineated nodules without microcalcifications. Ultrasonography revealed multiple hypoechoic solid lesions, some of them with anechoic areas of necrosis. Computed tomography showed multiple nodules. Histopathology of excision biopsy specimens of breast lesions revealed necrotizing granulomatous material consistent with Wegener's granulomatosis. Twenty reports of breast involvement in this rare disease were found in the literature; however, the respective ultrasonographic and computed tomography findings have not hitherto been described.     

Pulmonary lesions in Wegener's granulomatosis

Pulmonary lesions are the commonest and prognostically unfavourable visceral pathology in Wegener's granulomatosis. The author discusses clinically and reongenologically detectable lesions associated with this systemic vasculitis with special reference to its most severe forms (alveolar bleeding and infectious complications frequently caused by active immunosuppressive therapy). Diagnostic (including early) and modem therapeutic modalities of Wegener's granulomatosis are considered.     

捕获法ELISA检测抗蛋白酶3抗体对韦格纳肉芽肿的临床应用价值

目的探讨捕获法ELISA检测血液中抗蛋白酶3抗体对韦格纳肉芽肿(Wegener's granulomatosis,WG)的敏感性和特异性以及与间接免疫荧光法(indirec timmunofluorescence assay,IIF)的相关性。方法用捕获法ELISA、经典ELISA及IIF检测72例WG患者、206例健康献血员和24例其他自身免疫性疾病患者血清中的抗蛋白酶3(proteinase3,PR3)抗体和胞浆型抗中性粒细胞胞浆抗体(cytoplasmic anti-neutrophil cytoplasmic antibodies,cANCA)。结果PR3捕获法ELISA、经典ELISA测抗PR3对WG的敏感性分别为87.5%和73.6%,二者的特异性均为100%;单独用捕获法ELISA或IIF检测,对WG的检出率分别为87.5%和84.7%,而联合应用检出率可达到91.6%。结论捕获法ELISA检测抗PR3对WG的敏感性以及与IIF的相关性优于经典ELISA,对可疑WG患者,两法联合应用可提高WG的诊断率。     

Wegener's granulomatosis in the upper respiratory tract

Wegener's granulomatosis is a distinct clinico-pathological entity characterised by necrotising vasculitis of small arteries and veins in conjunction with the formation of granuloma in the upper and lower respiratory tracts, and glomerulonephritis. The vast majority of patients have antineutrophil cytoplasmic antibodies in the serum with a characteristic cytoplasmic pattern. However, in early phases of the disease only the upper respiratory tract may be affected, clinical and histological features may be nonspecific, and antineutrophil cytoplasmic antibodies not present. In this paper we present four patients with involvement of the upper respiratory tract suspicious for early Wegener's granulomatosis. We emphasise the significance of clinical, histological and serological parameters in the early detection of Wegener's granulomatosis.     

Infarction of the tongue in Wegener's granulomatosis.

Wegener's granulomatosis is a form of systemic vasculitis. Untreated, it has a 90% two year mortality, but complete remission can be obtained in 93% of patients following treatment with cyclophosphamide (usually in combination with steroids). There is early and major involvement of the respiratory tract. Renal involvement adversely affects prognosis.     

Serum chitotriosidase activity and Wegener's granulomatosis

Objective:We evaluated serum chitotriosidase activity in patients with Wegener's granulomatosis (WG) and compared the values to controls.Design and Methods:We used a standard fluorometric assay to measure chitotriosidase enzyme activity.Results:Serum chitotriosidase enzyme activity levels were higher in WG patients. We found no association between clinical disease activity and chitotriosidase enzyme activity.Conclusions:Serum chitotriosidase enzyme activity has limited utility as a biomarker in WG patients.     

韦格纳肉芽肿病肺部损害的CT分析

目的探讨韦格纳肉芽肿WG肺部CT表现,提高对该病的诊断水平。方法总结分析经病理和临床证实的WG11例的肺部表现,其中胸片11例,胸部CT平扫加增强扫描8例。结果 11例中,肺部有异常表现10例。异常表现中片状浸润病灶3例,多发结节影(直径小于3cm)4例,肿块(直径大于3cm)3例,空洞8例,条状阴影1例。4例多种病灶混合存在。结论 WG肺部表现呈多样性,以片状浸润、结节和空洞病变最常见,薄壁空洞和环形空洞具特征性。此病要与肺炎、肺脓肿、肺结核和肺癌等疾病相鉴别。