IgG4-related disease as a variable-vessel vasculitis: A case series of 13 patients with medium-sized coronary artery involvement

Abstract

Introduction: IgG4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease that can affect multiple organ systems. Although large-vessel vasculitis is a well-recognized manifestation of IgG4-RD, this condition is generally not regarded as a vasculitis. We aimed to describe coronary artery involvement (CAI), a vascular distribution about which little is known in IgG4-RD.

Material and methods: Patients with IgG4-related CAI were identified from a large, prospective IgG4-RD cohort. CAI was confirmed by imaging evidence of arterial or periarterial inflammation in any coronary artery. We extracted details regarding demographics, features of IgG4-RD, and manifestations of CAI.

Results: Of 361 cases in the cohort, 13 (4%) patients had IgG4-related CAI. All were male and all had highly-elevated serum IgG4 concentrations, with a median value of 955 mg/dL (interquartile range [IQR]: 510-1568 mg/dL; reference: 4-86 mg/dL). Median disease duration at the time of CAI diagnosis was 11 years (IQR: 8.23-15.5 years). Extensive disease in the coronary arteries was the rule: all three major coronary arteries were involved in 11 patients (85%). The coronary artery manifestations included wall thickening or periarterial soft tissue encasement (85%), stenosis (69%), calcification (69%), and aneurysms or ectasia (62%). Five patients (38%) had myocardial infarctions, 2 (15%) required coronary artery bypass grafting, and 2 (15%) developed ischemic cardiomyopathy.

Discussion: Coronary arteritis and periarteritis are important manifestations of IgG4-RD, which should be regarded as a variable-vessel vasculitis that is among the most diverse forms of vasculitis known. Potential complications of CAI include coronary artery aneurysms, myocardial infarction, and ischemic cardiomyopathy.

Keywords: Coronary arteritis; IgG4-related disease; Variable-vessel vasculitis; Vasculitis.

Figure 1.

Spectrum of coronary artery involvement in IgG4-related disease.

Figure 2.

Major patterns of coronary artery involvement in IgG4-related disease. Images include axial CT (A), left heart catheterization (B), 3D volume-gated reconstruction of CTA (C), and curved planar reformatting of coronary CTA (D-G). Findings include fusiform aneurysmal dilatation (A-C) with mural thrombi (A, arrows), ectasia (C) periarterial soft tissue (D, E; arrows), and stenosis (F, G; arrows). Panel C demonstrates ectasia of the entire coronary tree with focal fusiform aneurysmal dilatations (arrows).

Figure 3.

Left circumflex involvement in IgG4-related disease. A) Axial PET CT showing FDG avidity (arrow) centered around the left circumflex coronary during clinically active disease. B) Follow-up PET CT during clinical remission showing interval decrease in FDG uptake (arrow).

Figure 4.

Arteritis and periarteritis. A) Coronary computed tomography (CTA) in the short-axis view demonstrating the left anterior descending artery (LAD) aneurysm (arrow). B) Delayed contrast-enhanced CT showing enhancement of the aneurysmal LAD wall consistent with arteritis (arrow). C) LAD curved planar reformatted (CPR) and D) Pseudo colorized image of the LAD CPR image showing the soft tissue thickening around the LAD (arrows). E) Delayed phase image in short axis showing enhancement of the soft tissue thickening consistent with periarteritis (arrows).

Figure 5.

Evolution of IgG4-related coronary arteritis over time. A) Saccular right coronary artery (RCA) aneurysm with initial wall thickening which in follow-up is replaced by arterial wall calcification (arrows). B) Interval progression of focal RCA periarterial soft tissue during disease flare. C) New development of focal periarterial soft tissue surrounding the left anterior descending artery during disease flare.

Figure 6.

Histopathology. Carotid artery biopsy at A) 20x magnification and B) 400x magnification showing dense lymphoplasmacytic infiltrate with >200 IgG4+ cells/high-powered field. C) CD138 stain and D) IgG4 stain demonstrate that 56% of CD138+ cells are IgG4+.