You are in: eMedicine Specialties > Radiology > CHEST Wegener Granulomatosis, ThoracicArticle Last Updated: Oct 21, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 13
  Author: James G Ravenel, MD, Associate Professor of Radiology, Vice Chair for Education, Chief of Thoracic Imaging, Department of Radiology, Medical University of South Carolina James G Ravenel is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of Program Directors in Radiology, Association of University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology Coauthor(s): Abid Irshad, MD, Assistant Professor, Department of Radiology, Medical University of South Carolina Editors: Jeffrey A Miller, MD, Associate Professor of Clinical Radiology, University of Medicine and Dentistry of New Jersey; Associate Chief of Service, Department of Radiology, Veterans Affairs of New Jersey Health Care System; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; John D Newell, Jr, MD, FACR, FCCP, FASER, Co-Director of Thoracic Imaging, UCDHSC; Director of Lung Imaging Center, Professor of Radiology and Professor of Medicine, Department of Radiology, University of Colorado Health Sciences Center, National Jewish Medical and Research Center; Univ. Colorado Hospital; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Clinical Assistant Professor of Radiology, University of Washington Medical School Author and Editor Disclosure Synonyms and related keywords: Wegener's granulomatosis, Wegener granulomatosis, necrotizing granulomatous vasculitis of the upper and lower respiratory tract, glomerulonephritis, small-vessel vasculitis, rhinogenic granulomatosis, classic Wegener granulomatosis, classic Wegener's granulomatosis, glomerulonephritis, lung disease, kidney disease INTRODUCTIONSection 2 of 13
  BackgroundFirst described in the 1930s by Friedrich Wegener as a rhinogenic granulomatosis, Wegener granulomatosis is a disease of unknown etiology that is characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tract, glomerulonephritis, and small-vessel vasculitis of variable degree (classic Wegener granulomatosis). A limited form has also been described in which the disease is primarily confined to the lung. In this form, involvement of the kidney, skin, and tracheobronchial tree is distinctly unusual.1, 2, 3, 4, 5, 6, 7 PathophysiologyThe etiology of Wegener granulomatosis has not been clearly elicited. Theories have focused on hypersensitivity reactions possibly related to microorganisms; however, to date, a causal relationship has not been established. More recently, a role for Staphylococcus aureus has been suggested on the basis of a higher than expected rate of detection of the organism in individuals with Wegener granulomatosis and a high relapse rate in chronic S aureus carriers. Regardless, the pathologic demonstration of a necrotizing granulomatous vasculitis without evidence of an infectious etiology is the hallmark of Wegener granulomatosis. Lung involvement occurs in more than 90% of cases, and examination of biopsy material from the lung generally leads to the diagnosis. Renal involvement occurs in as many as 75% of cases. However, evidence of vasculitis is rarely found in the kidneys, and the histologic diagnosis is usually that of nonspecific glomerulonephritis. The overall prevalence of tracheal involvement depends on the subset of patients studied; it ranges from 15-60%. Isolated laryngotracheal disease is rare. Other common sites of involvement include the paranasal sinuses, skin, and eye, although disease has been documented in virtually all organs and tissues. FrequencyUnited StatesWegener granulomatosis occurs with a frequency of approximately 1 case per 30,000 individuals. The diagnosis is presumably becoming more common because of enhanced recognition and testing for the disease (eg, cytoplasmic-antineutrophil cytoplasmic antibody [c-ANCA] testing). Mortality/Morbidity
RaceWegener granulomatosis is primarily a disease of whites. In a study of 85 patients, Leavitt et al found that 91% of affected individuals were white, whereas only 7% were African American.11 SexMen are affected with Wegener granulomatosis more often than women. AgeAt the time diagnosis, the mean age of patients with Wegener granulomatosis is approximately 45 years. AnatomyNodules in Wegener granulomatosis tend to be distributed in an arteriolocentric pattern, but otherwise, the distributions of central and peripheral lesions are equal. The presence of cavitation may be a manifestation of vasculitis with concomitant infarction and necrosis. Additionally, bronchiectasis, bronchial wall thickening, and interlobular septal thickening and fibrosis have all been described. In children, pulmonary hemorrhage and diffuse airspace abnormalities, rather than pulmonary nodules, are the predominant findings. Tracheal disease generally occurs in the setting of coexistent nasal or paranasal involvement; it may be evident only at bronchoscopy. Strictures are the most common manifestation; they usually involve the subglottic trachea. Other findings include ulcerating tracheobronchitis and tracheal nodules. Continual bronchial inflammation may lead to a cobblestone pattern. Clinical DetailsThe presentation is usually a result of nonspecific signs and symptoms. Systemic complaints such fever, malaise, arthralgias, and weight loss are common. Patients may also complain of upper respiratory tract symptoms such as persistent sinus pain and/or drainage, mucosal ulcerations, epistaxis, otalgia, and otitis media. Lower respiratory tract complaints of cough, dyspnea, and hemoptysis may also be present. Hoarseness and stridor are often present when the trachea is involved. Overall, upper or lower respiratory tract symptoms are present in more than 85% of affected individuals. Laboratory assessment often reveals an elevation in nonspecific inflammatory markers, with elevations in the erythrocyte sedimentation rate and C-reactive protein level. The c-ANCA result has been shown to be positive in more than 88% of patients with the disease. Renal parameters often show evidence of kidney involvement; urine analysis frequently shows active sediment. Pathologic confirmation requires the presence of a necrotizing granulomatous vasculitis in the absence of an infectious etiology; samples are best obtained from the lung. Although the use of the c-ANCA result has largely replaced clinical findings as the means for diagnosing Wegener granulomatosis, clinical criteria were used in the past. The presence of nasal or oral inflammation, abnormal chest radiographic findings, urinary sediment, and suggestive biopsy results are all elements in the clinical diagnosis. The presence of 2 of 4 criteria is 88% sensitive and 92% specific for the diagnosis. Preferred ExaminationBecause most patients have respiratory symptoms, chest radiographs are usually obtained first. These may be followed by CT scans of the chest for better delineation of the abnormalities. Radiographic findings are nonspecific. The differential diagnosis includes various infections and malignancies. If the clinical findings are suggestive of Wegener granulomatosis, further evaluation with biopsy or laboratory studies (eg, c-ANCA testing) is required.12, 13, 14 Limitations of TechniquesThe major limitation of radiographic techniques is the broad differential diagnosis of abnormalities in Wegener granulomatosis. Radiographic findings in patients with Wegener granulomatosis may be normal. DIFFERENTIALSSection 3 of 13
[Lung, Drug-induced Disease] Aspergillosis, Thoracic Aspiration Pneumonia Bacterial Blastomycosis, Thoracic Bronchiolitis Obliterans Organizing Pneumonia Coccidioidomycosis, Thoracic Lung Cancer, Non-Small Cell Lung, Metastases Pneumonia, Atypical Bacterial Pneumonia, Typical Bacterial Pneumonia, Viral Pulmonary Edema, Noncardiogenic Sarcoidosis, Thoracic Trachea, Stenosis Other Problems To Be ConsideredVarious forms of vasculitis may lead to pulmonary hemorrhage, similar to Wegener granulomatosis. Pulmonary infarcts, septic pulmonary emboli, metastatic squamous cell carcinoma, fungal infection, and rheumatoid nodules should be considered when the presentation includes multiple solid and cavitary nodules. The differential diagnosis of tracheal stenosis includes post-intubation stricture or trauma, relapsing polychondritis, sarcoidosis, inflammatory bowel disease, and amyloidosis. Although the list of differential diagnoses and other problems is exceedingly broad and varied, the differential diagnosis can usually be limited by evaluating the radiographic findings in the context of the clinical history. RADIOGRAPHSection 4 of 13
FindingsPulmonary nodules are the most common chest radiographic manifestation of Wegener granulomatosis; they occur in 40-70% of the cases. Nodules may be solitary or multiple; they are cavitated in as many as 50% of patients with nodules. Both thick- and thin-walled cavities may be present. Their size varies, ranging from 1.5-10 cm, and the nodules may wax and wane over time. Pneumothorax in association with cavitary nodules and subpleural blebs has been reported (see Images 1-6).15, 16, 17 Airspace opacities are a second manifestation of Wegener granulomatosis. Usually, these findings involve a localized region of consolidation that may occasionally show central necrosis that mimics a lung abscess. Most frequently, this finding is the result of pulmonary hemorrhage, although pulmonary edema secondary to renal involvement may also occur. In one study of children, the airspace pattern was slightly more common. Over time, several of these opacities evolved into thin-walled cavitary lesions. Other less common pulmonary manifestations include atelectasis and reticular interstitial opacities. Tracheal-bronchial abnormalities are rarely noted on chest radiographs, although tracheal stenosis may occasionally be visualized. Mediastinal adenopathy and pleural abnormalities are uncommon (<10% of cases) and should prompt consideration of other diagnoses. Degree of ConfidenceBecause Wegener granulomatosis is a rare disease, its appearance at the top of a differential diagnosis is unusual. Exceptions involve patients with sinusitis or renal disease and cavitary nodules or those with any of the mentioned radiographic findings and the appropriate clinical and laboratory findings. Most often, radiographs are helpful in confirming the diagnosis and in assessing the extent of pulmonary involvement. False Positives/NegativesChest radiographs may be normal in as many as 20% of individuals with Wegener granulomatosis. CT SCANSection 5 of 13
FindingsThe major value of CT is in the further characterization of lesions found on chest radiography, as well as in the depiction of unsuspected or radiographically occult abnormalities. Occasionally, CT findings are normal. Like the chest radiographic findings, the predominant CT manifestations of Wegener granulomatosis include pulmonary nodules with or without cavitation and airspace consolidation (see Images 7-9).18, 19 Airspace disease may include the following: (1) bilateral and diffuse disease caused by pulmonary hemorrhage, (2) scattered parenchymal disease with eventual coalescence of lesion, or (3) localized disease with ill-defined margins and air bronchograms or central cavitation. In the last case, the lesions may be surrounded by a halo of ground-glass opacity, which presumably occurs secondary to hemorrhage. Interstitial abnormalities are often present in Wegener granulomatosis. They include interlobular septal thickening, parenchymal bands, and bronchial wall thickening. High-resolution CT may be helpful in better defining these lesions. Pleural thickening, pleural effusion, and adenopathy may be present, but they are not usually associated with Wegener granulomatosis. Tracheobronchial abnormalities are better evaluated with CT than with other modalities. Although as many as 60% of patients with Wegener granulomatosis have tracheobronchial abnormalities, to the authors' knowledge, no good data about the sensitivity and specificity of CT are available. In cases of suspected tracheobronchial involvement, thin, overlapping, axial sections with 2-dimensional and 3-dimensional reformations may provide better delineation of the length and degree of stenosis. These are particularly helpful when a tight stricture precludes the passage of a bronchoscope. Although nodules occur more frequently in patients with active disease and although parenchymal bands are more often seen in patients with quiescent disease, findings at various disease stages overlap considerably. Therefore, CT findings cannot be used to determine disease activity. CT has greater utility in determining the response to corticosteroid and cytotoxic drug therapy. An increase in the size or number of parenchymal abnormalities suggests relapse, whereas decreasing nodule size, thickening of cavity walls, and increasing spiculation of lesions have all been described as indicating of improvement. MRISection 6 of 13
FindingsMRI may be useful in documenting myocardial lesions. Lesions may be diffuse or focal, involving the midventricular wall; they are not typical of patterns associated with myocardial ischemia. Cardiac MRI findings overlap with those of other nonischemic myocardial diseases such as sarcoidosis and amyloidosis. MRI of the brain and/or spine should be considered in cases of extrapulmonary disease that potentially involves the central nervous system. ULTRASOUNDSection 7 of 13
FindingsIn a highly selected population, a high prevalence of echocardiographic abnormalities thought to be directly related to Wegener granulomatosis was found. These abnormalities included regional wall motion abnormalities; left ventricular systolic dysfunction with decreased ejection fraction; and pericardial effusion. In this population, mortality was increased among patients who had cardiac involvement.20 NUCLEAR MEDICINESection 8 of 13
FindingsLesions in Wegener granulomatosis are gallium avid, as demonstrated in case reports. A negative gallium scan may be helpful in excluding active disease.21 ANGIOGRAPHYSection 9 of 13
FindingsAlthough large pulmonary vessels may be attenuated on pulmonary angiography, catheter angiography has no role in the diagnosis or management of Wegener granulomatosis. Rare cases of overlap involving Takayasu arteritis and Wegener have been described. INTERVENTIONSection 10 of 13
Tracheostomy may be required for tracheal strictures.22 FURTHER READINGSection 11 of 13
Wegener's Granulomatosis. Vasculitis Foundation. Kansas City, MO. http://www.vasculitisfoundation.org/. Accessed October 21, 2008.
MULTIMEDIASection 12 of 13
REFERENCESSection 13 of 13
Wegener Granulomatosis, Thoracic excerpt Article Last Updated: Oct 21, 2008 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
