Pulmonary Wegener's Granulomatosis Research Articles

Computed tomography findings in pulmonary involvement of Wegener's granulomatosis: pictorial review

Wegener's granulomatosis is a necrotising granulomatous vasculitis which has a variable manifestations in the chest that are best described on computed tomography. Imaging findings may include masses or nodules, which may cavitate; consolidations and ground-glass opacities. Wegener's granulomatosis can mimic pneumonia, malignancy, and noninfectious inflammatory diseases. The purpose of this pictorial essay is to demonstrate the characteristic computed tomography findings of pulmonary Wegener's granulomatosis.

Wegener's granulomatosis simulates pulmonary adenocarcinoma

Wegener's granulomatosis is a rare systemic granulomatous necrotizing vasculitis that characteristically involves the upper airways, lungs, and kidneys. Pulmonary Wegener's granulomatosis can present with multifocal lung involvement or solitary lung lesions. Diagnosing Wegener's granulomatosis on the basis of cytological material from sputum may be challenging for pathologists. A wrong diagnosis may lead to inappropriate treatment. We report a case of Wegener's granulomatosis in a patient who first presented with hemoptysis, poor appetite, and weight loss. Multifocal pulmonary nodules were seen on a chest radiograph and the features seen on sputum cytology were similar to those of lung adenocarcinoma. A lung biopsy sample proved granulomatous inflammation. Wegener's granulomatosis was diagnosed based on the biopsy sample and a positive cytoplasmic antineutrophil cytoplasmic antibody titer (1:1280). After treatment with prednisone and cyclophosphamide, the lung lesions resolved. We recommend measuring the cytoplasmic antineutrophil cytoplasmic antibody titer in patients with bilateral pulmonary lesions. A lung biopsy sample should always be obtained, even when the cytology findings suggest a malignancy.

Air trapping in Wegener’s granulomatosis: an additional finding on expiratory chest HRCT

This study was undertaken to assess the presence and extent of air trapping (AT) on high-resolution computed tomography (HRCT) in patients with Wegener's granulomatosis (WG) and to correlate the finding with the inspiratory pattern and bronchial/bronchiolar involvement. Twenty-one patients (7 M/14 F) with WG underwent inspiratory and expiratory HRCT. Images were evaluated for the presence and extent of AT and for airway involvement (bronchi/bronchioles); the predominant HRCT pattern was also documented. The attenuation difference was measured between the areas of AT on expiration and the same areas on inspiration in order to verify the finding of AT. The extent of AT was calculated by visual scoring and correlated with the predominant inspiratory patterns and bronchial/bronchiolar involvement. AT was found in seven patients (33.3%) and its extent ranged between 3% and 70% (mean 15.8±7). Two patients showed no lesions on inspiratory HRCT, and the only finding was AT on expiration. The attenuation difference between areas of AT on expiration and the same areas on inspiration ranged between 32 and 89 HU. Inspiratory HRCT was pathological in 19 patients (90.4%), and the principal lung patterns were nodular, cavitary or noncavitary (n=7, 38.9%); ground-glass opacities (n=5, 26.3%); masses (n=3, 15.8%); fibrotic (n=3, 15.8%); and consolidation with air bronchogram (n=1, 5.3%). Bronchial and bronchiolar involvement was found in 14 and five patients, respectively. No statistically significant correlation was found between AT extent and the findings on inspiration. In addition, there were no specific patterns that caused higher or lower scores of AT. Moreover, when bronchial or bronchiolar involvement was absent, the mean AT score was statistically significantly higher. Areas of AT represent a new and indirect HRCT finding--and in rare cases the only finding--of pulmonary WG. The nonsignificant correlation between AT extent and inspiratory findings may suggest AT as an additional HRCT finding in patients with WG.

Trombose em artérias pulmonares pequenas e médias em granulomatose de Wegener: um estudo com microscopia confocal por varredura a laser

Wegener's granulomatosis (WG) can cause endothelial cell damage and thromboembolic events. Nevertheless, there have been few studies on the pulmonary microcirculation--small and medium-sized pulmonary arteries (SMSPA)--in patients with WG. The objective of this study was to quantify fibrin thrombi in the SMSPA of patients with WG. We analyzed 24 SMSPA samples collected from six patients with WG and 16 SMSPA samples collected from four patients without WG. In all samples, we used the endothelial cell marker CD34 and confocal laser scanning microscopy in order to detect intravascular fibrin thrombi. We calculated the total vessel area, the free lumen area, and the thrombotic area. The mean total vessel area was similar in the WG and control groups (32,604 µm² vs. 32,970 µm², p = 0.8793). Thrombi were present in 22 (91.67%) of the 24 WG group samples and in none of the control group samples (p < 0.0001; OR = 297; 95% CI: 13.34-6,612). The mean thrombotic area was greater in the WG group samples than in the control group samples (10,068 µm² vs. 0.000 µm²; p < 0.0001). In contrast, the mean free lumen area was smaller in the WG group samples than in the control group samples (6,116 µm² vs. 24,707 µm²; p < 0.0001). Confocal laser scanning microscopy revealed a significant association between pulmonary microvascular thrombosis and WG. This suggests a possible role of microvascular thrombosis in the pathophysiology of pulmonary WG, evoking the potential benefits of anticoagulation therapy in pulmonary WG. However, further studies are needed in order to confirm our findings, and randomized clinical trials should be conducted in order to test the role of anticoagulation therapy in the treatment of patients with pulmonary WG.

Active disease and residual damage in treated Wegener's granulomatosis: an observational study using pulmonary high-resolution computed tomography.

The purpose of this study was to determine to what extent high-resolution computed tomography (HRCT) of the lungs can distinguish active inflammatory disease from inactive cicatricial disease in patients treated for Wegener's granulomatosis (WG). Twenty-eight WG patients with active pulmonary disease underwent a first HRCT examination immediately before standard immunosuppressive treatment and a second examination after clinical remission had been achieved. Lesions remaining after treatment were categorized as residual damage and were compared with findings during active disease to see by what features active and cicatricial disease can be distinguished. During active disease 17 patients had nodules/masses, 12 had ground-glass opacities, 6 had septal lines and 6 had non-septal lines. After treatment, ground-glass opacities had resolved completely. Nodules/masses had resolved in 8 patients and had diminished in 7 patients. Residual nodules were distinguished from nodules/masses in active disease by lack of cavitation and a diameter of mostly <15 mm. In one-third of patients lines resolved, but in 8 instances new lines evolved during immunosuppression. During a follow-up period of a median 26.5 months (range 20.0-33.8), patients with residual nodules or lines had no more relapses than patients with completely cleared lungs. Treated pulmonary WG leaves substantial residual damage. High-resolution CT does assist in the distinction between active and inactive lesions. Ground-glass opacities, cavitating nodules/masses and masses measuring more than 3 cm represent active disease ordinarily. Non-cavitary small nodules and septal or non-septal lines can be either active or cicatricial lesions. The nature of these lesions needs to be clarified by longitudinal observation.

Pulmonary Wegener's Granulomatosis: Correlation Between High-Resolution CT Findings and Clinical Scoring of Disease Activity

To evaluate the usefulness of high-resolution CT (HRCT) for monitoring pulmonary disease activity in Wegener's granulomatosis (WG). Prospective study of CT and clinical data. Main referral hospital for rheumatic diseases and department of diagnostic radiology of collaborating university hospital. Seventy-three patients with WG underwent 98 staging examinations using HRCT. The status of pulmonary disease activity at the time of examination was scored according to clinical, bronchoscopic, BAL, and radiographic findings as follows: activity (n=25, group 1), past activity (n=45, group 2) and lack of any pulmonary disease (n=28, group 3). HRCT findings were correlated with the clinical scoring of pulmonary disease activity. Of 98 staging examinations 78 (79.6%) revealed abnormal CT scans showing the following main abnormalities: (a) nodules or masses (group 1: 16 [60.4%], group 2: 9 [20%]); (b) parenchymal bands (group 1: 12 [48%], group 2: 27 [60%], group 3: 6 [21.5%]); (c) septal thickening (group 1: 8 [32%], group 2: 6 [13.3%]); (d) parenchymal opacification (group 1: 7 [28%], group 2: 4 [8.9%]); and (e) pleural irregularity (group 1: 14 [56%], group 2: 22 [49%], group 3: 9 [32%]). Nodules/masses and areas of parenchymal opacification were significantly associated with florid disease activity of the lungs. Parenchymal bands and septal thickening were observed in both groups with pulmonary involvement, but statistical analysis revealed no significant difference. Pleural irregularities were nonspecific. HRCT may be a useful adjunct to clinical scoring of pulmonary disease activity in patients with WG and suspected lung involvement.

Pulmonary Wegener's granulomatosis: changes at follow-up CT.

The objective of this study was to assess the reversibility of pulmonary lesions in Wegener's granulomatosis using serial CT. We reviewed the follow-up CT scans of ten treated patients with confirmed Wegener's granulomatosis. The delay between the first evaluation before treatment and the second, on patients in clinical and biological remission, ranged from 6 to 54 months (mean 20.5 months). Follow-up CT showed a decrease in the extent of disease in all cases. Lesions disappeared completely, without scarring, in 4 of 4 ground-glass opacities, 25 of 36 nodules, and 4 of 9 pulmonary consolidations; they disappeared with residual scarring in 8 of 8 masses, 3 of 9 pulmonary consolidations, and 2 of 36 nodules. The majority of lesions disappear without scarring. Residual fibrosis may follow the occurence of masses and pulmonary consolidation. Computed tomography permits assessment of cicatricial lesions.

Treated Wegener's granulomatosis: Distinctive pathological findings in the lungs of 20 patients and what they tell us about the natural history of the disease

Patients with an established diagnosis of Wegener's granulomatosis (WG) sometimes undergo lung biopsy when the disease does not behave in the expected manner. Treatment affects the tissue reaction. The microscopic recognition of partially treated disease is important, as the absence of expected lesions may lead to nonspecific diagnoses and inappropriate management. The appearance of treated disease over time may offer insight into its histogenesis and natural history. We correlated clinical features and pulmonary histology in 20 patients with WG after they had been treated with corticosteroids or cyclophosphamide or both. All patients had inflammatory or fibrotic pulmonary disease resulting from WG, but only 4 (20%) had macronodular necrosis typical of WG. Serum antineutrophil cytoplasmic antibody (ANCA) was elevated in all patients in whom it was measured. We divided the pathological findings into (1) vasculitis, (2) extravascular necrosis, (3) bronchiolitis, and (4) other lesions, and further divided them into (a) diagnostic for active disease, (b) suspicious for active disease, (c) suspicious for healing disease, (d) suspicious for residual disease, and (e) possible disease. Diagnostic or suspicious vascular lesions occurred in 15 patients (75%) and included granulomatous vasculitis, capillaritis or suspicious capillaritis, and neutrophilic vasculitis. Diagnostic or suspicious extravascular lesions occurred in 12 patients (60%) and included palisading granuloma, microabscess, macronodular pathergic necrosis, giant cell nodules, and micronodular scars. The giant cell nodules and nodular scars were an unusual healing pattern of palisading granulomas. Diagnostic bronchiolar lesions occurred in 1 patient (6%) and suspicious lesions in 13 patients (65%), including three novel patterns of bronchiolitis fibrosa (BF): (1) BF with giant cells, (2) BF with hemosiderin, and (3) BF with micronodular scars. Other features related to WG included diffuse alveolar damage, peculiar alveolar fibrin, interstitial fibrosis, pneumonitis resembling usual interstitial pneumonitis, and lipoid pneumonia. Classic necrotic nodules and vasculitis of WG should not be anticipated after therapy, but the diagnosis of pulmonary WG after treatment may be made if the effects of treatment on histology are considered. Changes in anticipated histology are found after therapy as short as 6 days. The histology typically has muted features. BF develops in most patients and may reflect a salutary effect of therapy. Palisading granuloma may convert to giant cell nodule or micronodular scar. Interstitial fibrosis is common, and pneumonitis resembling usual interstitial pneumonitis can develop. If only healing or residual disease is encountered, one should search further clinically and pathologically for active disease. Dampened inflammatory lesions represent smoldering disease that presumably needs additional therapy. Scarring presumably represents successfully treated but permanent disease.

CEPHALIC PYODERMA GANGRENOSUM (PG)‐LIKE LESIONS AS A PRESENTING SIGN OF WEGENER'S GRANULOMATOSIS

Pyoderma gangrenosum (PG)-like lesions can be associated with Wegener's granulomatosis (WG); in rare instances, they could be the presenting sign of WG. The purpose of this study was to elucidate the relationship between these two disorders. The clinical and histologic data from a case of WG with primary ulcerative lesions of the face were compared with five other cases previously reported in the literature. A predominance among young men was noted. In three patients the histology of the skin ulcerations was suggestive of WG, in the remaining three, including the case described, it was nonspecific. Two cases developed pulmonary WG after the skin lesions cleared, showing that the extent and severity of skin lesions do not necessarily correlate with the systemic disease. When the histology of the skin is nonspecific, the diagnosis of PG or PG-like lesions of the head and neck should not be considered definitive and the patients should be carefully monitored to rule out the possible presence of WG.

Localized Wegener's Granulomatosis Relapsing as Diffuse Massive Intra-alveolar Hemorrhage

In a 75-year-old patient presenting with a solitary pulmonary mass, a localized form of Wegener's granulomatosis was diagnosed after lobectomy. In the absence of extrapulmonary manifestations and after a benign postoperative course, the patients was discharged without medical treatment. Three months later, diffuse alveolar hemorrhage developed abruptly, necessitating mechanical ventilation, and was followed by cardiac complications and a fatal outcome. This case and another previously reported strongly suggest the need for medical treatment in patients with a localized form of pulmonary Wegener's granulomatosis, even when complete remission after surgical resection of the lung lesion seems to have been achieved.

Imaging of thoracic Wegener's granulomatosis: The computed tomographic appearance

purpose: Computed tomography (CT) can play a major role in the examination of patients with diffuse infiltrative disorders of the lung. CT patterns of thoracic Wegener's granulomatosis were retrospectively evaluated in this study. The CT appearance was compared with imaging obtained by conventional plain roentgenograms.patients and methods: Fourteen patients with Wegener's granulomatosis seen during the last 5 years are described. Conventional chest roentgenograms and CT scans from these patients are reviewed.results: The most frequent manifestation found in the lungs of patients with Wegener's granulomatosis was that of rounded opacities with or without cavitation. This was observed in 7 of 14 patients. Relatively unexpected was the frequent occurrence of bronchovascular bundle cuffing with a quite constant and characteristic bronchocentric distribution. This finding was observed in 5 of 14 patients. Vasculitis sign was demonstrated in 2 of 14 patients. Widespread acinar infiltrates, usually confluent, were common and were seen in 5 of 14 of our patients; in 2 of the patients, these infiltrates were due to diffuse pulmonary hemorrhage. Tracheal stenosis was the cause of sudden acute respiratory failure that was observed in one patient. Pleural disease was present in 3 of 14 patients. Hilar and mediastinal lymphadenopathy was observed in one patient. An interstitial pattern was observed in 3 of 14 patients.conclusions: We conclude that an extremely wide spectrum of radiologic findings may be observed in this disease. In 14 patients we found 11 different roentgenographic manifestations; moreover, in 8 patients it was possible to describe more than 1 radiologic manifestation at the same time or during the course of the disease. This observation is not surprising, if we consider the wide variability and broad spectrum of pathologic features in pulmonary Wegener's granulomatosis. Because conventional roentgenograms failed in a great number of cases to visualize the exact pattern and the extent of thoracic involvement, we believe that CT is particularly helpful for the assessment of pulmonary involvement in Wegener's granulomatosis.

Wegener Granulomatosis

Chest CT from eight patients with pulmonary Wegener granulomatosis were reviewed. The CT features of parenchymal lung involvement included multiple nodules or masses (seven of eight; 88%), ranging in size from 0.3 to 5.0 cm. Lung nodules demonstrated distinct feeding vessels in seven of eight patients (88%); and lesions similar to pulmonary infarcts, i.e., peripheral wedge-shaped lesions abutting the pleura, were identified in seven cases (88%). Scarring, spiculation, and pleural tags emanating from pulmonary nodules were prominent features (seven of eight; 88%). Other findings included cavitation (four of eight; 50%), air bronchograms through nodules (two of eight; 25%), and pleural effusions (two of eight; 25%). One patient on immunosuppressant therapy also demonstrated scattered ground glass infiltrates due to complicating pneumocystis pneumonia. In comparison to corresponding conventional chest radiography, CT examinations revealed more parenchymal lesions in five of eight cases (63%) and bilateral disease instead of unilateral disease in one of eight cases (13%). Feeding vessels were only identified on CT. Wegener granulomatosis is a primary necrotizing granulomatous vasculitis, and when it affects the lung it demonstrates CT features that are similar to other vessel-related disorders of the lung such as septic emboli, pulmonary infarcts, and tumor emboli of hematogenous metastases. We believe that these CT features--nodules with feeding vessels and wedge-shaped lesions abutting the pleura--are related to the necrotizing angiitis that affects pulmonary arteries and veins in this disease.

The diagnosis of Wegener's granulomatosis from transbronchial biopsy specimens

It is widely believed that thoracotomy is necessary to obtain biopsy specimens adequate for the histopathologic demonstration of pulmonary Wegener's granulomatosis (WG). We report five patients with WG who were diagnosed by transbronchial biopsy (TBB). In three cases, a diagnosis of WG was made by TBB alone. In the other two patients, subsequent open lung biopsies confirmed the TBB findings but did not add essential diagnostic information. Our experience suggests TBB may be appropriate as the initial diagnostic procedure in selected cases of suspected WG. This approach requires an understanding of the diverse histologic features of WG and the correlation of clinical and pathologic data.

Pulmonary Wegener's Granulomatosis: A Clinical and Imaging Study of 77 Cases

We studied 77 patients with biopsy-proven WG and pulmonary manifestations, to characterize the nature and frequency of the clinical, imaging and endoscopic features of this condition. Pulmonary symptoms were cough, mild dyspnea, hemoptysis and chest pain. Five patients had no pulmonary symptoms. Imaging features consisted of nodules, infiltrates and pleural opacities. A CT scan proved useful by disclosing cavities in opacities or opacities which were not seen on an x-ray film. Fiberoptic bronchoscopy was performed in 74 patients, and it was macroscopically abnormal in 55 percent (showing bronchial inflammation or stenosis or both or isolated hemorrhage). Six patients presented with alveolar hemorrhagic syndrome. Four patients had a pleural exudate rich in polymorphonuclear leukocytes. The WG was limited to the lung in seven patients. Sixteen patients died because of active disease or iatrogenic complications (two). An improved knowledge of clinical and imaging features of WG could help the clinician reach an earlier diagnosis.

Wegener's granulomatosis of lung: diagnosis and treatment. Experience with 12 cases.

Twelve patients with pulmonary Wegener's granulomatosis are reported. In seven patients the disease appeared to be limited to the lungs; four patients had upper respiratory tract involvement, and one had cutaneous and subcutaneous lesions. A link between pulmonary and disseminated forms of this syndrome was provided by a patient who had a solitary pulmonary lesion for 4 years, after which involvement of the upper respiratory tract and the other lung developed. The course of the disease was extremely variable, rapid progression occurring in three patients, whereas one patient has had the disease for 12 years with little deterioration of health. Corticoid treatment resulted in transitory improvement in three patients and progression in four. Eight patients received cytotoxic therapy. One death occurred as the result of drug toxicity; at necropsy no evidence of Wegener's granulomatosis remained. Excellent responses have been obtained in three patients treated with chlorambucil and four treated with azathioprine. Surgical resection of pulmonary lesions was apparently curative in two cases but was unsuccessful in three. Recognition of this not uncommon disorder is important since cytotoxic therapy appears to be uniformly effective.