First published online May 25, 2006
British Journal of Radiology (2007) 80, 757-765
© 2007 British Institute of Radiology
doi: 10.1259/bjr/34705892
Imaging of Wegener's granulomatosis
S D Allen, MB BS, MRCS, FRCR
and
C J Harvey, MB BS, MRCP, FRCR
Department of Imaging, Imaging Sciences Department, Hammersmith Hospital, Imperial College Faculty of Medicine, Du Cane Road, London W12 ONN, UK
Correspondence: Steven Allen, Department of Imaging, Royal Marsden Hospital, Fulham Road, London SW3 6JJ. E-mail: stevendallen{at}hotmail.co.uk
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Abstract
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Wegener's granulomatosis is an uncommon multisystemic disorder of unknown aetiology. It is characterized histopathologically by necrotizing granulomatous vasculitis. Most commonly this involves the upper and lower respiratory tract, with pulmonary involvement occurring at some stage of the disease in almost all patients. However, many other organ systems can also be affected including the kidneys, orbits and central nervous system. For this pictorial review, we have assessed the imaging of 155 patients over a 10-year period in order to illustrate characteristic and some of the more unusual imaging features of Wegener's granulomatosis.
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Introduction
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First described over 70 years ago, Wegener's granulomatosis (WG) is an uncommon multisystemic vasculitis, affecting a wide age range, although most commonly presenting in the 5th decade. Males are affected slightly more commonly than females. Upper respiratory tract features are typical at presentation, such as sinusitis, nasal obstruction, rhinorrhoea and ulceration. More than 90% of patients with WG will have pulmonary involvement at some stage in their illness. This is manifest as cough, pleurisy, dyspnoea and haemoptysis. Chest infections are responsible for a large number of relapses in patients with established disease. Long term a 2.4 times risk of pulmonary malignancy is present [1].
Renal involvement occurs in approximately 83% of cases, and if untreated, death from renal failure within 5 months is usual, though steroids and cyclophosphamide, induce a complete remission in up to 75% [2, 3].
The American College of Rheumatology has classified WG according to specific criteria. The presence of two or more of abnormal urinary sediment (red cell casts), oral ulcers or nasal discharge, haemoptysis or granulomatous inflammation on pulmonary biopsy, are considered as features to distinguish WG from other vasculitides [4].
Pathologically, WG is characterized by necrotizing granulomatous inflammation of small vessel walls, resulting in areas of necrosis surrounded by haemorrhage, small microabscesses and granulomata within the lungs.
A normocytic anaemia, leucocytosis, elevated erythrocyte sedimentation rate (ESR), positive rheumatoid factor and antineutrophil cytoplasmic antibody (specifically PR3-ANCA) are often shown on serology. PR3-ANCA is positive in 85% of patients with active multiorgan WG, but this reduces to 30–40% in remission [1, 5].
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Imaging findings
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Chest
The most common imaging findings are discrete focal opacities that vary in size and appearance from diffuse consolidation to nodular masses. The latter may measure up to 10 cm in diameter, but are usually 2–4 cm (Figure 1
). They show no zonal predilection, are usually multiple, are rounded or oval in shape, and when >2 cm, cavitate in at least 25% [6] (Figures 2 and 3). Cavity walls vary in thickness considerably, but tend to become thinner with time. They may contain air–fluid levels if secondarily infected [7] (Figure 4). Nodules often occur concurrently with consolidation, and commonly resolve spontaneously, with or without scarring. On high resolution CT, ground-glass shadowing may surround the nodules, which may be due to haemorrhage. Relapse is frequently seen in areas of previous disease.
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Figure 1. 63-year-old man with pulmonary Wegener's granulomatosis. A chest radiograph shows multiple pulmonary masses, some of which are cavitating (arrows).
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Figure 2. 42-year-old man with pulmonary Wegener's granulomatosis. A coronal CT reformatted image of the chest shows a peripheral pulmonary mass, with early cavitation (arrow). There is a background mosaic pattern of lung attenuation, thought to be due to a mosaic perfusion abnormality caused by a primary vascular abnormality rather than ground-glass attenuation caused by air trapping.
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Figure 3. 48-year-old woman with pulmonary Wegener's granulomatosis. An axial CT image shows multiple pulmonary lesions (arrows). The largest of these has clearly cavitated. As in Figure 2 , there is a background mosaic pattern of lung attenuation, thought to be due to a mosaic perfusion abnormality caused by vasculitis.
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Figure 4. 52-year-old man with pulmonary Wegener's granulomatosis. An axial CT image showing a right-sided cavitating lesion (arrow). This has an air–fluid level within it, suggesting possible superadded infection. Haemorrhage into the cavity can also cause this appearance.
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Patchy or diffuse consolidation occurs usually secondary to pulmonary haemorrhage, and may also cavitate (5%) (Figures 5–7). Subpleural and wedge-shaped, focal parenchymal or peribronchoarterial consolidation may reflect granulomatous changes and pneumonia [7].
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Figure 5. 33-year-old woman with pulmonary Wegener's granulomatosis. An axial CT image shows a large pulmonary mass (arrow), with surrounding ground-glass change, suggesting haemorrhage.
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Figure 6. 56-year-old man with pulmonary Wegener's granulomatosis presenting with haemoptysis. A chest radiograph shows extensive, patchy bilateral consolidation. This patient had diffuse pulmonary haemorrhage.
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Figure 7. 28-year-old woman with pulmonary Wegener's granulomatosis presenting with haemoptysis. An axial CT image shows marked ground-glass change bilaterally. This is an appearance of diffuse pulmonary haemorrhage.
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Subglottic tracheal and bronchial wall thickening and subsequent narrowing may cause secondary lobar collapse, and is often refractory to systemic treatment [8] (Figure 8). Pleural thickening and small effusions may occur variably depending on the series quoted [6, 8].
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Figure 8. 54-year-old man with tracheal Wegener's granulomatosis. A coronal CT reformatted image shows bilateral stenoses of the main bronchi. The right bronchus intermedius is stented, with marked intraluminal soft tissue thickening (arrow).
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Nasal cavity and paranasal sinuses
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Non-specific mucosal thickening or antral opacification are typical early features, followed by nasal septal thinning and granulomatous ulcerated change. Bony destruction is also frequently demonstrated on CT (Figures 9 and 10) including a necrosed nasal septum (saddle nose deformity), though the sinuses may atrophy and the maxillary bone progressively ossify [9]. On MRI, granulomatous tissue varies in signal with the stage of inflammation. In the early phase of inflammation non-specific T2 weighted signal hyperintensity is present, but as granulomatous transformation progresses, granulomata appear hypointense [10].
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Figure 9. 40-year-old man with sinonasal Wegener's granulomatosis. An axial CT image of the sinuses shows marked ethmoidal mucosal disease, with bony thinning and destruction of the medial orbital wall and nasal septum (arrows).
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Figure 10. 46-year-old man with sinonasal Wegener's granulomatosis. A coronal CT reformatted image of the sinuses shows marked maxillary sinus disease bilaterally.
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Kidneys
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Limited forms of WG sparing the kidney are rare. Usually severe progressive necrotizing glomerulonephritis occurs resulting in rapid deterioration of renal function. Large echogenic kidneys on ultrasound without specific Doppler abnormalities are typical early findings (Figure 11). However, this may rapidly progress to scarred shrunken kidneys with chronic renal failure. More rarely, a pseudotumour may also be present as a non-specific infiltrative lesion indistinguishable from many other renal masses, isointense on T1 weighted and mixed signal on T2 weighted MRI [11].
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Figure 11. 62-year-old woman with renal Wegener's granulomatosis. A longitudinal ultrasound image shows an echogenic right kidney. Although this is a non-specific finding, it is the most common sign of early glomerulonephritis, implying involvement of the kidney by Wegener's granulomatosis.
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Orbits
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Orbital granulomata occur by contiguous spread from the nasal cavity and paranasal sinuses or as discrete entities, and classically induce a proptosis. Appearances on CT are of an ill-defined soft tissue mass completely obscuring the optic nerve and extraocular muscles, with associated local bony destruction. On MRI, low to intermediate signal granulomata on T1 weighted and T2 weighted imaging may be distinguished from surrounding fat and ocular muscles (Figures 12–14). Following contrast, varying degrees of enhancement may be observed, though a number of other neoplastic, infectious and inflammatory pathologies may appear similar [10].
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Figure 12. 43-year-old woman with orbital Wegener's granulomatosis. (a) An axial CT image showing a large right-sided orbital soft tissue mass. This had occurred due to granulomatous orbital invasion from adjacent ethmoidal disease (arrow). (b) An axial T2 weighted image showing inflammatory ethmoidal disease as signal hyperintensity. Granulomatous right orbital disease is shown as signal hypointensity (arrow).
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Figure 13. 31-year-old woman with orbital Wegener's granulomatosis. (a) A coronal T1 weighted image of the face, showing a large right-sided isointense orbital mass (black arrow). This had occurred due to granulomatous orbital invasion from significant nasal and maxillary and ethmoidal sinus disease (white arrows). (b) A coronal T1 weighted post-contrast, fat-saturated image of the face, showing the large right-sided orbital mass (black arrow). Signal enhancement has been subtle, though this can be quite variable. The inflammatory sinonasal disease has enhanced significantly (white arrows).
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Figure 14. 60-year-old man with orbital Wegener's granulomatosis. An axial CT image shows sinonasal and orbital disease. The orbital granulomata have calcified bilaterally which is an uncommon phenomenon in longstanding disease.
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Middle ear and skull base
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Typical infiltrative skull base lesions are variable signal intensity but more or less isointense to muscle on T1 weighted and T2 weighted imaging, and enhance moderately on both MRI and CT [12] (Figures 15–18). Otitis media secondary to inflammation of the orifice of the Eustachian tube is the most common feature of middle ear involvement, though local granulomatous disease can occur, with similar radiological appearances as the skull base. Rarely major salivary gland involvement appears as heterogeneous enlargement suggestive of a diffuse inflammatory process [13].
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Figure 15. 44-year-old man with skull base Wegener's granulomatosis. A coronal CT reformatted image of the left mastoid shows soft tissue opacification though no bony destruction of the mastoid air cells.
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Figure 16. 49-year-old woman with skull base Wegener's granulomatosis. A coronal CT reformatted image of the right petrous temporal bone shows soft tissue opacification of the middle ear cavity, with bony erosion of the incus (arrow).
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Figure 17. 65-year-old man with skull base Wegener's granulomatosis. (a) An axial T1 weighted image of the skull base shows significant sphenoid sinus disease, with direct extension into the petrous apices bilaterally (black arrows). This patient had multiple cranial nerve neuropathies, which is typical for this disease extent. Bilateral low signal granulomatous orbital disease is also shown (white arrows). (b) An axial T1 weighted image following intravenous gadolinium enhancement shows marked enhancement of inflammatory tissue in the petrous apices and sphenoid sinus (arrows), but to a lesser extent in the orbits, confirming granulomatous rather than active inflammatory tissue in this area.
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Figure 18. 62-year-old woman with Wegener's granulomatosis. (a) An axial CT image of the skull base shows sinonasal and maxillary sinus disease (black arrows). This has extended into the parapharyngeal space (white arrow), where it has identical appearances to a parapharyngeal abscess. Note is made of a nasal airway. (b) A contiguous CT image inferiorly in the same patient showing the parapharyngeal disease, which actually extended into the soft tissues of the posterior left neck (arrow).
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Central nervous system
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WG most frequently affects the peripheral nervous system, with mononeuritis multiplex present in up to 22%. Involvement of the CNS occurs in only 8% of patients, with cranial neuropathy the most common manifestation. It may occur due to local vasculitis, direct spread from adjacent disease in the skull base, paranasal or orbital region, or spread from remote granulomatous lesions [14]. Enhancing diffuse or focal dural thickening and multiple non-specific white matter lesions with increased signal on T2 weighted and fluid attenuated inversion recovery (FLAIR) images are the most common imaging findings [15] (Figures 19 and 20). Intracerebral haemorrhage, subarachnoid haemorrhage and cerebral arterial and venous thrombosis can also occur due to weak vessel walls secondary to vasculitic inflammation. Infarcts may also result from renal failure induced hypertension, emboli from marantic endocarditis or vessel occlusion by a skull base granuloma [14]. Remote brain parenchymal granulomatous lesions are rare. Pituitary involvement is manifest as an enhancing inflammatory mass, mostly occurring from direct skull base spread. Brain atrophy also appears more common than in normal subjects, which may reflect cerebral vasculitis [15].
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Figure 19. 57-year-old woman with central nervous system Wegener's granulomatosis. An axial fluid attenuated inversion recovery (FLAIR) image of the brain shows multiple areas of white matter signal hyperintensity. Although a non-specific finding, these appearances are a common form of cerebral Wegener's granulomatosis, indicative of vasculitis.
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Figure 20. 41-year-old woman with central nervous system Wegener's granulomatosis. An axial T1 weighted image post intravenous gadolinium enhancement. Frontal sinus disease is shown (black arrow), and adjacent dural thickening is also present in the near and adjacent area (white arrow). Enhancing diffuse or focal dural thickening is the most common manifestation of cerebral Wegener's granulomatosis.
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Spleen
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Splenic involvement is rare in WG, but segmental splenic infarction may result from diffuse arteritis resulting in occlusion of distal parenchymal splenic arteries, which are end vessels without collateral flow. This may have the appearance of a peripheral wedge-shaped area of low attenuation on CT, but may be subcapsular or diffuse hypodensity in larger infarctions [16] (Figure 21). Histologically small foci of necrotizing granulomatous arteritis may occur even in the absence of symptomatology.
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Figure 21. 30-year-old woman with Wegener's granulomatosis. (a) An ultrasound image of the spleen shows peripheral low echogenicity (arrow). (b) A colour Doppler image of the spleen in the same patient showing a normal central perfusion. (c) Following administration of 2.4 ml intravenous Sonovue (Bracco, Italy) microbubble contrast imaging was performed in a low MI (mechanical index) contrast pulse sequence mode (CPS; Acuson-Siemens, USA). The left hand image shows microbubble-specific imaging demonstrating perfusion of the central portion of the spleen with sparing of the subcapsular region (arrow). The right hand image depicts the corresponding B mode, once again showing peripheral low echogenicity (arrow). Appearances are consistent with subcapsular infarction secondary to vasculitis.
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Cardiac
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Pericarditis, coronary vasculitis and valvular lesions are the most common presentations, with cardiac involvement occurring in approximately 28% [1]. Radiological features are non-specific though granulomatous infiltration may be visualized.
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Paediatric
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WG is relatively rare in childhood but from the largest series to date, paediatric WG is similar to the adult disease. The major differences include pulmonary haemorrhage at presentation, which is manifest as multifocal parenchymal infiltrates. Also, absence of endobronchial disease may be a significant differentiating feature [17].
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Conclusion
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WG is an uncommon multisystemic disorder, which although most commonly affecting the respiratory system, can also affect a large number of other organ systems and produce a broad spectrum of imaging findings. In this review we have illustrated the common and more unusual imaging appearances of this condition using multiple imaging modalities.
Received for publication November 24, 2005.
Revision received January 18, 2006.
Accepted for publication February 6, 2006.
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Abstract
Introduction
