AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

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 a variable degree of small-vessel vasculitis (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.

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 based on the 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, finding evidence of vasculitis in the kidneys is rare, and the histologic diagnosis is usually nonspecific glomerulonephritis. The overall prevalence of tracheal involvement depends on the subset of patients studied and is 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 almost uniformly fatal, with mean survival of 5 months from the time of diagnosis. Currently, the mainstay of treatment is corticosteroids and cyclophosphamide. Although this regimen often results in initial complete remission, relapses are common, and cyclophosphamide toxicity limits long-term usage.
• Methotrexate and azathioprine can be used for remission maintenance.
• Initial remission rate exceeds 95%. Older age and absence of ear, nose, and throat involvement are independent risk factors for mortality.
• The prognosis is poor in 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.

Sex

Men are affected more often than women.

Age

The mean patient age at diagnosis 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 the 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, and it may be evident only at bronchoscopy. Findings include strictures, the most common manifestation, which usually involves the subglottic trachea, ulcerating tracheobronchitis, and tracheal nodules. Continual bronchial inflammation may lead to a cobblestone pattern.

Clinical Details

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, while 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. The nonspecific radiographic findings suggest a differential diagnosis that includes various infections and malignancies. These require further evaluation with biopsy or laboratory evaluation (c-ANCA testing) if the clinical findings are suggestive of Wegener granulomatosis.

Limitations of Techniques

The major limitation of radiographic techniques is the broad differential diagnosis of abnormalities in Wegener granulomatosis. Patients with Wegener granulomatosis may also have normal radiographic findings.

DIFFERENTIALS

Section 3 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Other Problems to be Considered

Various forms of vasculitis can 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 be usually be limited by evaluating the radiographic findings in the context of the clinical history.

RADIOGRAPH

Section 4 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Pulmonary nodules are the most common chest radiographic manifestation of Wegener granulomatosis and occur in 40-70% of the cases. Nodules may be solitary or multiple and can be 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.

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 can occasionally be visualized. Mediastinal adenopathy and pleural abnormalities are uncommon ( <10% of cases) and should prompt consideration of other diagnoses.

Degree of Confidence

Because Wegener granulomatosis is a rare disease, its appearance at the top of a differential diagnosis list 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/Negatives

Chest radiographs may show normal findings in as many as 20% of individuals with Wegener granulomatosis.

CT SCAN

Section 5 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

The major value of CT is in the further characterization of lesions found on chest radiograph, 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.

At CT, pulmonary nodules and masses range from 5 mm to 10 cm, and they are often cavitated. The lesions tend to be multiple and well defined, although the presence of more than 10 lesions is unusual.

Airspace disease may include the following: (1) bilateral and diffuse disease due to 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 may often be present in Wegener granulomatosis. They include interlobular septal thickening, parenchymal bands, and bronchial wall thickening. High-resolution CT can 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 also 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 can 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 the presence of nodules is more frequent in patients with active disease and although parenchymal bands are more often seen in quiescent disease, findings at various disease stages overlap considerably. Therefore, CT findings cannot be used to predict 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 findings of improvement.

MRI

Section 6 of 11  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

MRI does not have a role in defining disease in the thorax; however, it should be considered in cases of extrapulmonary disease that potentially involves the central nervous system.

NUCLEAR MEDICINE

Section 7 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Lesions in Wegener granulomatosis are gallium avid, as demonstrated in case reports. A negative gallium scan may be helpful in excluding active disease.

ANGIOGRAPHY

Section 8 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Findings

Although large pulmonary vessels may be attenuated at 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.

INTERVENTION

Section 9 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Tracheostomy may be required for tracheal strictures.

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

Media file 1:  Wegener granulomatosis, thoracic. Posteroanterior chest radiograph in a middle-aged man with Wegener granulomatosis shows heterogeneous airspace opacity, which occurs predominately in the lower lobes, and a focal ill-defined opacity in the right upper lobe. Findings are suggestive of pulmonary hemorrhage (see Images 2-3).
	View Full Size Image
Media type:  X-RAY

Media file 2:  Wegener granulomatosis, thoracic. Image obtained 4 months later in the same patient as in Image 1 shows nearly complete resolution of lower lobe airspace disease, with partial resolution of the right upper lobe opacity. A new cavity is present in the left upper lobe.
	View Full Size Image
Media type:  X-RAY

Media file 3:  Wegener granulomatosis, thoracic. Image obtained 1 year after Image 2 shows that the left upper lobe cavity has enlarged, without a change in wall thickness. Multiple new cavitary and noncavitary nodules are present in the right lung.
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Media type:  X-RAY

Media file 4:  Wegener granulomatosis, thoracic. Thick-walled right upper lobe cavity in Wegener granulomatosis.
	View Full Size Image
Media type:  X-RAY

Media file 5:  Wegener granulomatosis, thoracic. Cut surface of a gross pathologic specimen that corresponds to Image 4 shows a thick-walled cavity with internal hemorrhage and necrosis. Courtesy of Russell Harley, MD.
	View Full Size Image
Media type:  Photo

Media file 6:  Wegener granulomatosis, thoracic. Wegener granulomatosis is present as a single pulmonary mass. Chest radiograph shows a single right lower-lobe mass.
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Media type:  X-RAY

Media file 7:  Wegener granulomatosis, thoracic. CT scan of the patient in Image 5 shows a well-circumscribed right lower-lobe mass. Biopsy revealed necrotizing granulomatous vasculitis, which is consistent with Wegener granulomatosis.
	View Full Size Image
Media type:  CT

Media file 8:  Wegener granulomatosis, thoracic. CT image obtained with lung window settings show a typical appearance of nodules in Wegener granulomatosis. Multiple ill-defined peripheral nodules have a halo with a ground-glass appearance. The halo is thought to represent adjacent pulmonary hemorrhage.
	View Full Size Image
Media type:  CT

Media file 9:  Wegener granulomatosis, thoracic. Three-dimensional shaded-surface display of the trachea shows eccentric narrowing of the subglottic trachea in this patient with airway involvement due to Wegener granulomatosis.
	View Full Size Image
Media type:  CT

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Nuclear Medicine
• Angiography
• Intervention
• Multimedia
• References

• Aberle DR, Gamsu G, Lynch D. Thoracic manifestations of Wegener granulomatosis: diagnosis and course. Radiology. Mar 1990;174(3 Pt 1):703-9. [Medline].
• Allen NB. Wegener's granulomatosis. In: Goldman L Bennett JC, eds. Cecil Textbook of Medicine. 21st ed. 2000: 1529-32.
• Cordier JF, Valeyre D, Guillevin L, et al. Pulmonary Wegener''s granulomatosis. A clinical and imaging study of 77 cases. Chest. Apr 1990;97(4):906-12. [Medline].
• Daum TE, Specks U, Colby TV, et al. Tracheobronchial involvement in Wegener''s granulomatosis. Am J Respir Crit Care Med. Feb 1995;151(2 Pt 1):522-6. [Medline].
• Frazier AA, Rosado-de-Christenson ML, Galvin JR, Fleming MV. Pulmonary angiitis and granulomatosis: radiologic-pathologic correlation. Radiographics. May-Jun 1998;18(3):687-710; quiz 727. [Medline].
• Langford CA. Wegener''s granulomatosis: current and upcoming therapies. Arthritis Res Ther. 2003;5(4):180-91. [Medline].
• Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener''s granulomatosis. Arthritis Rheum. Aug 1990;33(8):1101-7. [Medline].
• Maskell GF, Lockwood CM, Flower CD. Computed tomography of the lung in Wegener''s granulomatosis. Clin Radiol. Dec 1993;48(6):377-80. [Medline].
• McDonald TJ, Neel HB 3rd, DeRemee RA. Wegener''s granulomatosis of the subglottis and the upper portion of the trachea. Ann Otol Rhinol Laryngol. Nov-Dec 1982;91(6 Pt 1):588-92. [Medline].
• Popa ER, Tervaert JW. The relation between Staphylococcus aureus and Wegener''s granulomatosis: current knowledge and future directions. Intern Med. Sep 2003;42(9):771-80. [Medline].
• Reuter M, Schnabel A, Wesner F, et al. Pulmonary Wegener''s granulomatosis: correlation between high-resolution CT findings and clinical scoring of disease activity. Chest. Aug 1998;114(2):500-6. [Medline].
• Slart RH, Jager PL, Poot L. Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener''s granulomatosis. Ann Rheum Dis. Jul 2003;62(7):659-62. [Medline].
• Wadsworth DT, Siegel MJ, Day DL. Wegener''s granulomatosis in children: chest radiographic manifestations. AJR Am J Roentgenol. Oct 1994;163(4):901-4. [Medline].

Article Last Updated: Nov 17, 2004