eMedicine Specialties > Radiology > Chest

Wegener Granulomatosis, Thoracic

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
Coauthor(s): Abid Irshad, MD, Assistant Professor, Department of Radiology, Medical University of South Carolina
Contributor Information and Disclosures

Updated: Oct 21, 2008

Introduction

Background

First 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}

There have been discussions about renaming the disease because of Wegener's association with the Nazi party in the 1930s. Wegener, a German pathologist, joined the so-called brownshirts, of the early Nazi party, and he was a member of the National Socialist Party. Working in the city of Lodz, where a closed ghetto for Jews was established, Wegener was said to have performed autopsies on some victims, and he may have reviewed a manuscript that was based on Nazi experiments. Although not implicated directly in war crimes, Wegener's involvement in Nazi Germany is considered by some to be a reason to desist from using his name eponymously as the name of this disease. An award in his honor was subsequently abandoned.^8,9,10

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Pathophysiology

The 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.

Frequency

United States

Wegener 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

• In the past, Wegener granulomatosis was considered to be almost uniformly fatal; the mean survival from the time of diagnosis was 5 months. Currently, the mainstay of treatment is a regimen of corticosteroids and cyclophosphamide. Although this regimen often results in complete remission initially, relapses are common, and cyclophosphamide toxicity limits long-term usage.
• Methotrexate and azathioprine may be used for remission maintenance.
• Initial remission rate exceeds 95%. Older age and an absence of ear, nose, and throat involvement are independent risk factors for mortality.
• The prognosis is poor for untreated individuals.

Race

Wegener 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

Sex

Men are affected with Wegener granulomatosis more often than women.

Age

At the time diagnosis, the mean age of patients with Wegener granulomatosis is approximately 45 years.

Anatomy

Nodules 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.

Presentation

The 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 Examination

Because 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 Techniques

The 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.

Differential Diagnoses

Other Problems to Be Considered

Various 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.

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