Pulmonary vasculitic aneurysms occur most importantly in Behçet's disease and Hughes-Stovin syndrome (Table 2). There is an isolated case report on pulmonary artery aneurysms in a patient with giant cell arteritis [16].

Behçet's disease.—Behçet's disease is a chronic multisystemic vasculitis of unknown cause that may affect the lung in up to 8% of patients [17]. The natural history of Behçet's disease is characterized by chronic exacerbations. In a series of 2,179 patients with Behçet's disease, pulmonary arterial aneurysms were encountered in 1.1% [18]. Because aneurysms evolve rapidly, aneurysm size cannot be used to predict the risk of rupture. As a consequence, pulmonary aneurysm formation in untreated patients carries a high mortality rate of 30% within 2 years (mean patient survival, 10 months from onset of hemoptysis) [17, 18]. However, there is more recent evidence of complete resolution of up to 75% of aneurysms in patients receiving immunosuppressant treatment [6, 7]. Aneurysm regression was preceded by thrombus formation, which also disappeared after treatment.

Aneurysms in Behçet's disease are fusiform to saccular, are commonly multiple in number and bilateral, and are located in the lower lobe or main pulmonary arteries [7, 19]. Their size may range up to 7 cm. CT angiography is the method of choice for the detection of aneurysms and characterization of related disease- or therapy-induced changes, such as aneurysmal wall thickening, representing subadventitial hematoma formation; perianeurysmal air-space consolidation or ground-glass opacification, which is indicative of impending rupture [7, 20–22]; or formation of intraluminal thrombus under immunosuppressant therapy. Ancillary findings on CT include wedge-shaped consolidation, probably representing pulmonary hemorrhage or infarcts; peripheral mosaicism, resulting from focal air trapping; embolic small-vessel occlusion or mechanical vascular compression by aneurysms; and organizing or eosinophilic pneumonia [7, 23]. Cases of Behçet's disease with hemoptysis may be easily misdiagnosed as venous thromboembolism, particularly with frequent evidence of deep vein thrombosis, unless aneurysmal disease is recognized.

Hughes-Stovin syndrome.—Hughes-Stovin syndrome is a large-vessel vasculitis affecting pulmonary, and frequently bronchial, arteries and large systemic veins. It is widely accepted as a forme fruste of Behçet's disease because apart from vascular findings, clinical diagnostic criteria of the latter are absent [5, 24, 25]. It occurs predominantly in young adult men between their second and fourth decades. Pathologic features include systemic thrombi in the vena cava, cerebral sinuses, or limb veins; pulmonary artery occlusions due to emboli or thrombi; and one or more segmental pulmonary artery aneurysms, frequently associated with bronchial artery aneurysms. The radiologic features are similar to those of Behçet's disease, and CT angiography is essential for the diagnosis (Figs. 2A and 2B).

Takayasu's arteritis.—Takayasu's arteritis is a chronic progressive systemic arteritis of unknown cause that classically involves the aorta and its branches. Less known cardiopulmonary complications that may cause unexpected—even catastrophic—morbidity and mortality have been reported in almost 20% and may include isolated pulmonary arteritis in 10% of patients [26]. Pulmonary artery involvement does not appear to have any geographic or racial predilection. Literature data based on angiographic diagnosis suggest a mean incidence approaching 50%, and this figure is likely to be an underestimate [27].

When chronic relapsing nonspecific systemic disease becomes active arterial inflammation, CT will detect wall thickening with late enhancement (Fig. 1). A low-attenuation ring inside the vessel wall has been reported in the aorta, but not in the pulmonary arteries. Subsequent chronic arterial wall ischemia is characterized on CT angiography by central stenoocclusive disease with frequent occurrence of segmental mosaic perfusion [28–30] (Figs. 6A and 6B). Tunaci and coworkers [7] reported on periarterial air-space consolidation and air-space nodules in 54% of patients with parenchymal mosaicism, suggestive of peripheral arterial involvement with plexogenic arteriopathy. However, to date no studies have correlated the established histopathologic features with imaging findings of CT angiography, and it is unknown whether certain types of central lesions (constrictive wall thickening with thrombosis vs organized thrombosis with recanalization) can be differentiated on CT [31].

The aspect of large arterial constrictive wall thickening should allow differentiation of Takayasu's disease from chronic thromboembolic pulmonary hypertension, which does not feature arterial wall thickening, and from other rare entities without stenoocclusive changes such as extensive thrombosis in Eisenmenger's syndrome combined with gross pulmonary artery dilatation or enhancing expansile tumor thrombus in pulmonary artery sarcoma.

Giant cell arteritis.—Giant cell arteritis, an idiopathic vasculitis involving large arteries, predominantly the extracranial carotid branches and the aorta, may rarely involve central pulmonary arteries. The incidence of pulmonary involvement is unknown. Giant cell arteritis is characterized by a more aggressive clinical course than Takayasu's disease. However, the principal CT appearance of giant cell arteritis is similar to that of Takayasu's arteritis, with evidence of arterial wall thickening, stenosis, and thrombosis (Figs. 7A, 7B, 7C, 7D, and 7E). Ancillary findings in patients with giant cell arteritis include chronic basal reticulation and bulla formation and may differ from those in Takayasu's arteritis, which may show mosaic perfusion more frequently. However, the two disorders cannot be differentiated on the basis of imaging findings alone. From sporadic case reports, pulmonary hypertension appears to be less common in giant cell arteritis than in Takayasu's disease (Figs. 1, 7A, 7B, and 7C).

Acute arterial hemorrhage is a well-recognized complication of vasculitis affecting large pulmonary arteries. In Behçet's disease, rupture of a pulmonary artery into a bronchial lumen or into the parenchyma occurs in up to 50% of patients with pulmonary artery aneurysms, which has been reported as the major cause of death [7, 19]. Life-threatening arterial hemorrhage may also occur in patients with advanced Takayasu's arteritis complicated by pulmonary hypertension and rupture of systemic-to-pulmonary artery collaterals and rarely by rupture of vasculitic microaneurysms. Similarly, massive pulmonary hemorrhage has been described in giant cell arteritis as a complication of aneurysmal disease [32]. CT angiography is the noninvasive method of choice to show underlying arterial disease and indicate conservative management or surgery. However, Takayasu's arteritis and Behçet's disease may rarely be complicated by diffuse alveolar hemorrhage as a result of concomitant pulmonary capillaritis [18, 33, 34].

Diffuse alveolar hemorrhage is a common symptom of pulmonary capillaritis, although capillaritis—a term describing a histopathologic finding rather than a unique clinicopathologic syndrome—is, of course, not unanimously present in diffuse alveolar hemorrhage [35–37] (Tables 2 and 3). Patients typically present with hemoptysis, dyspnea, anemia, and bilateral air-space opacification with apical sparing on chest radiographs (Figs. 8A, 8B, and 8C). However, each of these features is nonspecific and, including hemoptysis, may be absent. Therefore, chest radiographs are usually not helpful in the differential diagnosis [37–40]. Although CT is valuable for the assessment of patients with hemoptysis and suspicion of a focal pulmonary parenchymal or vascular abnormality [41, 42], it is of limited use for the evaluation of patients with diffuse alveolar hemorrhage [43].

Regardless of the underlying disease, the high-resolution CT findings of diffuse alveolar hemorrhage are essentially similar: In the phase of acute hemorrhage, lobular or lobar areas of ground-glass opacity to consolidation predominate (Figs. 9, 10A, and 10B). In these patients, ground-glass opacity is generated by subtotal alveolar filling with blood and is accompanied by apparent prominence of segmental and subsegmental bronchi [43], which has been referred to as the “dark bronchus” sign. Within 2–3 days, intralobular lines and smooth interlobular septal thickening superimpose on areas of ground-glass opacity (Figs. 3A, 3B, and 3C) and may give rise to a crazy-paving pattern [44]. In the course of hemorrhage resorption, these patterns may resolve or with severe repeated hemorrhage may progress to interstitial fibrosis, which is readily depictable on high-resolution CT. During intervals between chronic recurrent bleeding episodes, ill-defined centrilobular nodules may be present (Figs. 11A and 11B), reflecting intraalveolar accumulation of pulmonary macrophages [43, 45]. Nodules have been reported to be uniform in size (1–3 mm) and are diffusely distributed with no zonal predominance [43].

Among the collagen vascular diseases, systemic lupus erythematosus is the most common cause of diffuse alveolar hemorrhage [46] with intensity varying from mildly chronic to highly acute [47, 48]. In the study of Zamora and coworkers [47], diffuse alveolar hemorrhage occurred in 3.7% of hospitalized patients with systemic lupus erythematosus, representing 22% of pulmonary complications.

Diffuse alveolar hemorrhage is chiefly caused by an acute necrotizing capillaritis that coincides to varying degrees with acute lupus pneumonitis in life-threatening diffuse alveolar damage [46, 49]. Typically, patients with diffuse alveolar hemorrhage present with rapid-onset tachypnea, cough, fever, hypoxia, and hemoptysis while displaying symptoms of generalized systemic lupus erythematosus vasculitis such as renal failure, arthritis, or rash [46]. However, because of the presence of more advanced concurrent systemic lupus erythematosus morbidity, diffuse alveolar hemorrhage is frequently missed at the time of its manifestation. Conversely, diffuse alveolar hemorrhage may also be the presenting feature of systemic lupus erythematosus [36, 37].

With mortality rates of 50–60%, the prognosis of patients with diffuse alveolar hemorrhage is very poor and acute diffuse alveolar hemorrhage may recur in survivors [46]. CT displays typical nonspecific features of diffuse alveolar hemorrhage with the spectrum of findings ranging from ground-glass opacification to consolidation, coinciding with similar changes of acute systemic lupus erythematosus pneumonitis [44] (Fig. 12). Therefore, in the absence of hemoptysis, lung biopsy, which may reveal immune complexes on immunofluorescence, has been recommended by some authors [39, 50].

Diffuse alveolar hemorrhage has also been reported in a small number of patients with mixed connective tissue disease, and it occurred predominantly in association with glomerulonephritis [51–53]. However, Schwarz and coworkers [54] reported a patient with isolated pulmonary capillaritis and diffuse alveolar hemorrhage. Similarly, diffuse alveolar hemorrhage has been reported in a small number of cases of rheumatoid arthritis [55, 56], either in association with glomerulonephritis and antineutrophil cytoplasmic autoantibody (ANCA) positivity [52, 55, 57] or as an isolated pulmonary capillaritis without evidence of extrapulmonary vasculitic disease [54]. Otherwise, chronic pulmonary vasculitis in rheumatoid arthritis involves small and medium-sized muscular pulmonary arteries with sparing of pulmonary capillaries and may induce pulmonary arterial hypertension [58, 59] (Figs. 5A, 5B, 5C, and 5D).

Pulmonary–renal syndrome.—Up to 70% of patients presenting with the pulmonary–renal syndrome, the combination of diffuse alveolar hemorrhage and glomerulonephritis, have positive findings for ANCA [60], with frequent occurrences of different ANCA subtypes in patients with Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, or idiopathic pulmonary–renal syndrome [56, 61–63]. However, irrespective of the underlying condition, patients with ANCA positivity and diffuse alveolar hemorrhage present common histologic features of a pauciimmune hemorrhagic alveolar capillaritis [61].

Wegener's granulomatosis.—Wegener's granulomatosis is an idiopathic inflammatory systemic disease that is characterized by a necrotizing granulomatous vasculitis of the upper and lower respiratory tract, the lungs being involved in approximately 90%; focal necrotizing glomerulonephritis; and small-vessel vasculitis affecting arteries, capillaries, and veins [64]. The mean age of onset is the fifth decade [65–67]. Pulmonary symptoms include hemoptysis, cough, chest pain, and dyspnea [66]. Confinement to the lungs is well recognized and usually precedes systemic manifestations [68].

On lung biopsy in patients with diffuse alveolar hemorrhage, neutrophilic capillaritis similar to that seen in patients with systemic lupus erythematosus can be found and is commonly associated with histologic features specific for Wegener's granulomatosis, such as granulomatous inflammation and necrotizing vasculitis of larger vessels [39]. In a series of 77 patients, diffuse alveolar hemorrhage occurred in six cases (8%) [69]. These patients presented with classic clinical and radiologic signs. In all cases, renal and upper respiratory tract disease was present, and five patients showed involvement of other organs.

Interestingly, the clinical and CT features of some patients with diffuse alveolar hemorrhage seem to differ from those of patients with nonhemorrhagic Wegener's disease because most of these patients present with acute renal failure and diffuse alveolar hemorrhage may precede the occurrence of other high-resolution CT findings [52, 70–77] (Fig. 9). Papiris and coworkers [78] described diffuse air-space consolidation as a predominant CT feature in two patients with Wegener's granulomatosis–associated diffuse alveolar hemorrhage. They also found peribronchovascular nodules in these patients (Figs. 3A, 3B, 3C, 8A, 8B, and 8C).

The prognosis of patients with Wegener's granulomatosis with diffuse alveolar hemorrhage is relatively favorable if the CT diagnosis is confirmed rapidly, prompting the administration of immunosuppressant agents [37, 39, 69, 79]. Nonhemorrhagic pulmonary abnormalities of Wegener's disease include a bronchocentric variant manifesting as chronic bronchiolitis [80], bronchocentric granulomatosis [80, 81], organizing pneumonia [82], and lipoid pneumonia [80]. Typical CT features include multiple nodules with a size-related tendency to cavitate [61, 83–85] (Figs. 13A, 13B, and 13C); peribronchovascular interstitial thickening with mild bronchiectasis in up to 40% [83]; and, less frequently, pleural thickening, pleural effusion, or wedge-shaped pleural-based areas of consolidation [40].

Microscopic polyangiitis.—a nongranulomatous necrotizing systemic vasculitis that affects arterioles, capillaries, and venules and, rarely, medium-sized vessels [86]—is differentiated from Wegener's granulomatosis on clinical grounds and by means of histology from renal or skin biopsy specimens. Glomerulonephritis is almost unanimously (97%) present. Relapsing diffuse alveolar hemorrhage is a key feature of microscopic polyangiitis, occurring in approximately 40% of patients and in almost 30% at presentation. The largest proportion of the 30% mortality rate for patients with microscopic polyangiitis is related to pulmonary vasculitis. The occurrence of diffuse alveolar hemorrhage is of additional value in the differentiation from other vasculitic entities such as polyarteritis nodosa, in which diffuse alveolar hemorrhage is exceedingly rare [87–93] (Figs. 13A, 13B, 13C, 14A, and 14B).

Chest symptoms of microscopic polyangiitis include hemoptysis, dry cough, chest pain, and shortness of breath progressing to irreversible air-flow obstruction [86, 94]. The high-resolution CT appearances of diffuse alveolar hemorrhage in microscopic polyangiitis are similar to those in other vasculitic disorders, including signs of ensuing pulmonary fibrosis. However, evidence of interstitial fibrosis may precede the onset of clinical vasculitis by several years and is generally associated with the presence of serum perinuclear ANCA [95]. In stationary clinical phases, high-resolution CT may show normal findings or may display centrilobular ground-glass nodules representing alveolar macrophages, perivascular inflammatory infiltrate, or diffuse interstitial fibrosis (Figs. 4A and 4B).

Churg-Strauss syndrome.—Churg-Strauss syndrome is an ANCA-associated systemic vasculitis affecting small arteries and veins. Clinical features include neuropathy; peripheral blood eosinophilia (> 10%); and, in most cases, increasingly severe asthma [96]. Paranasal sinus abnormality may be present. Renal involvement rarely causes severe symptoms and in most cases consists of segmental glomerulonephritis similar to Wegener's granulomatosis [96]. Before systemic vasculitic involvement occurs, patients usually progress to a stage characterized by transient, nonfixed pulmonary infiltrates on chest radiography due to extravascular eosinophilic pulmonary infiltration.

On CT, multifocal peripheral air-space opacifications that may be consolidative or ground-glass are located predominantly at the lung bases (Figs. 4A and 4B). Furthermore, high-resolution CT features include centrilobular nodules, which are more frequently observed within areas of ground-glass opacification, areas of ground-glass opacity in the periphery of larger nodules, or lobular consolidations; these CT findings have been referred to as the halo sign [97]. Inconsistently, high-resolution CT may display cavitating nodules, smooth interlobular septal thickening, and evidence of airway disease attributable to asthma [98]. Diffuse alveolar hemorrhage is a rare complication of Churg-Strauss syndrome and has been shown to cause large symmetric air-space consolidations on chest radiographs or peripheral areas of ground-glass opacity on CT scans [51, 99] (Figs. 10A and 10B).

Pulmonary hypertension occurs in patients with central vasculitic stenoocclusive disease, with a reported incidence in pulmonary Takayasu's disease of up to approximately 50% (Fig. 1). Only a few case reports have described pulmonary hypertension complicating giant cell arteritis or Behçet's disease. Pulmonary hypertension is being reported with increasing incidence in rheumatic diseases, including mixed connective tissue disease and systemic lupus erythematosus (up to 45% and 43%, respectively), and is being reported less frequently in rheumatoid arthritis [40].

Patients with small-vessel pulmonary vasculitis and pulmonary hypertension are generally expected to have a poor prognosis, a 2-year mortality rate of approximately 25–50%, in those with systemic lupus erythematosus and comparable figures in patients with mixed connective tissue disease, sarcoidosis, and probably rheumatoid arthritis. However, there are no routine echocardiographic screening algorithms for pulmonary hypertension in these three entities; therefore, the role of MDCT in diagnosing pulmonary hypertension in individuals who undergo chest CT for search of interstitial lung disease is probably underestimated (Figs. 5A, 5B, 5C, and 5D). In adult patients, a main pulmonary artery diameter exceeding the ascending aortic width or a diameter of 28 mm on CT angiography has a positive predictive value of more than 90% for the presence of pulmonary hypertension.

Currently, there are no known radiologic features that can serve as predictors for the development of pulmonary hypertension in any underlying pulmonary vasculitis. The combined occurrence of pulmonary hypertension and diffuse alveolar hemorrhage should always give rise to the suspicion of underlying pulmonary collagen vascular disease. Conversely, the isolated occurrence of pulmonary hypertension as a presenting clinical feature does not exclude the presence of any of these disorders.