Large vessel involvement by IgG4-related disease

Abstract

Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels.

Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall.

Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with rituximab, a majority responded positively.

Conclusions: IgG4-RD is a distinctive, unique, and treatable cause of large-vessel vasculitis. It can also involve blood vessels secondary to perivascular tumefactive lesions. The most common manifestation of IgG4-related vasculitis is aortitis with aneurysm formation. The most common secondary vascular manifestation is periaortitis with relative sparing of the aortic wall. Both primary vasculitis and secondary vascular involvement respond well to B cell depletion therapy.

Figure 1

Magnetic resonance angiography with moderate to severe stenosis of the right common carotid artery.

Figure 2

IgG4-related disease in a carotid artery atherosclerotic plaque. (A) Depicted is a low power (20× magnification) histologic image showing the carotid endarterectomy specimen from Case 2 with regions of dense inflammatory cell infiltration in the periphery (arrowheads). (B) At higher power (400× magnification) in these regions, there is a lymphoplasmacytic infiltrate with occasional eosinophils. By immunohistochemistry for IgG (C) and IgG4 (D), the majority of the IgG+ plasma cells expressed IgG4 (both 400× magnification).

Figure 3

CT scan of the abdomen showing diffuse, nonatherosclerotic arterial disease with aneurysmal dilatation of the abdominal aorta and common iliac arteries.

Figure 4

Right coronary artery and posterior descending artery with diffuse aneurysmal dilatation, circumferential mural thickening, and contrast enhancement as seen by 3D reconstruction (A), cross-sectional (B), and coronal (C) views.

Figure 5

(A) Cross-sectional CT chest with contrast displaying a soft tissue mass compressing the left pulmonary artery (red arrow) with resulting pulmonary arterial stenosis (green arrow head). Also seen is circumferential thickening and contrast enhancement of the ascending thoracic aorta (green arrow). (B) PET-CT showing FDG avidity of both the soft tissue mass around the pulmonary artery as well as the ascending thoracic aortic wall.

Figure 6

Post-rituximab PET imaging showing decreased FDG avidity of the ascending thoracic aortic wall and soft tissue mass encasing the left pulmonary artery (comparison: Fig. 5B).

Figure 7

(A) Cross-sectional CT angiography showing a dissection flap in the ascending aorta. (B) 3D reconstruction displaying the same ascending aortic dissection.

Figure 8

IgG4-related disease in the thoracic aorta. (A) Depicted is a low power (40× magnification) histologic image of the thoracic aorta from Case 12 showing dense inflammatory cell infiltration in adventitia and outer media. The dots indicate the media-adventitia border. (B) At higher power (400× magnification), there is a lymphoplasmacytic infiltrate associated with injury to medial smooth muscle cells. By immunohistochemistry for IgG (C) and IgG4 (D), the majority of the IgG+ plasma cells expressed IgG4 (both 400× magnification).

Figure 9

(A) CT pelvis showing a side wall soft tissue mass extending inferiorly and encasing the left iliac vessels and ureter. (B) Associated intense FDG avidity on concurrent PET imaging.

Figure 10

Pos-trituximab imaging revealing an unchanged soft tissue mass on CT (A) but substantially reduced FDG avidity on PET (Comparison Figure 9 A and B).

Figure 11

Medialization of the ureters in a patient with IgG4-related retroperitoneal fibrosis (green arrows) and periaortitis.