Progression of IgG4-related coronary aneurysm without corticosteroid treatment after surgical resection: A case report

Abstract

Immunoglobulin G4-related disease (IgG4-RD) of the cardiovascular system is rare. Multiple approaches for the management of IgG4-RD have been reported, including surgical resection of affected tissues and treatment with systemic glucocorticoids being generally used. Therefore, the results of surgical resection alone are unknown. A 79-year-old male underwent total aortic arch replacement 5 years previously. Subsequently, a coronary aneurysm of the left circumflex artery (LCx) enlarged with pericardial effusion was removed 2 years after the first surgery. He was diagnosed with a confirmed IgG4-related coronary aneurysm. Serum IgG4 level was 331 mg/dL, and the aneurysm at the distal portion of the LCx was residual. However, he did not receive any corticosteroid treatment. Follow-up transthoracic echocardiography (TTE) revealed an abnormal echo-free cavity structure at 5 o'clock position of the short-axis view. This case describes the progression of residual IgG4-related coronary aneurysm, without corticosteroid therapy. A case with thoracic aortic disease combined with coronary aneurysm may be IgG4-RD. The possibility of progression is high in cases where serum IgG4 remains at a high level, especially without steroid treatment, and follow-up examinations, such as TTE and computed tomography, are more important. Therefore, we reaffirm that corticosteroid therapy may have been important.

Learning objective

Immunoglobulin G4-related disease (IgG4-RD) of the cardiovascular system is rare. Multiple approaches for the management of IgG4-RD have been reported, including surgical resection of affected tissues and treatment with systemic glucocorticoids being generally used. Therefore, the results of surgical resection alone, to avoid steroid-related complications, are unknown. Our case showed thoracic aortic disease combined with coronary aneurysm may be IgG4-RD. The importance of corticosteroid treatment was reaffirmed because the residual coronary aneurysm progressed without corticosteroid treatment.

Introduction

Immunoglobulin G4-related disease (IgG4-RD) is a generalized fibroinflammatory condition characterized by elevated serum IgG4 levels and a predominance of IgG4-positive plasma cells in the affected tissue. The 2020 revised comprehensive diagnostic criteria for IgG4-RD consisted of three major items: 1) clinical and radiological features; 2) serological diagnosis; and 3) pathological diagnosis [1]. Although IgG4-RD of the cardiovascular system is rare, IgG4-RD with cardiovascular involvement is characterized by aortitis, periaortitis, constrictive pericarditis, and coronary artery disease with aneurysm formation [2]. Few studies and case reports have reported IgG4-related thoracic aortitis concomitant with coronary aneurysm.

Some patients require urgent treatment because uncontrolled disease in certain organs can lead to irreversible damage. Urgent treatment may include a combination of glucocorticoids at moderate-to-high doses, as well as other mechanical interventions in specific organs. Multiple approaches for the management of IgG4-RD have been reported, including surgical resection of affected tissues and treatment with systemic glucocorticoids, immunosuppressive drugs, or biologic agents [3]. The short-term outcomes of most IgG4-RD patients treated with steroid therapy are good; however, the long-term outcomes are unknown because of several unknown factors, such as relapse, developed fibrosis, and associated malignancy [4]. Furthermore, the results of surgical resection alone, to avoid steroid-related complications, are unknown.

Herein, we report a case of residual IgG4-related coronary aneurysm progression after surgery for IgG4-related aortitis and coronary aneurysm without corticosteroid therapy.

Case report

A 79-year-old male had a distal aortic arch aneurysm that had progressed without symptoms, and was treated with total aortic arch replacement. In addition, coronary aneurysms were detected in the proximal and distal portions of the left circumflex artery (LCx), which size was about 30 mm and 7 mm, respectively. Histopathological examination of the aortic wall specimen confirmed the pathological diagnosis criteria for IgG4-RD: 1) plasma-cell-based inflammatory cell aggregation and fibrosis. 2) Furthermore, many IgG4+ cells infiltrated, and the IgG4/IgG rate was over 40 % in immunostaining for IgG4 [1]. Therefore, he was diagnosed with IgG4-related aortitis and suspected IgG4-related coronary aneurysms. For reasons unknown, he was not treated with corticosteroid and was followed up. Subsequently, a coronary aneurysm proximal to the LCx expanded, and pericardial effusion was detected on contrast computed tomography (CT) and transthoracic echocardiography (TTE) (Fig. 1a-c). Therefore, the coronary aneurysm was removed, and coronary artery bypass grafting (saphenous vein graft - LCx) was carried out 2 years after the first surgery. Although the adhesion around the coronary aneurysm was mild, the distal portion of the LCx could not be identified. Histopathological examination of the aneurysm at the proximal portion of the LCx showed the same findings as those of the aortic aneurysm (Fig. 2). He was diagnosed with a confirmed IgG4-related coronary aneurysm; his serum IgG4 level was 331 mg/dL (the serological diagnosis criteria for IgG4-RD; >135 mg/dL [1]), and the aneurysm at the distal portion of the LCx was residual (Fig. 1d). However, the patient refused corticosteroid treatment and was treated only with aspirin 100 mg/day, carvedilol 10 mg/day, candesartan 8 mg/day, esomeprazole 20 mg/day, and atorvastatin 10 mg/day.

Fig. 1.

(a) Transthoracic echocardiography showed abnormal cavity structure in left atrioventricular groove before surgery. (b) and (c) Contrast computed tomography before surgery showed pericardial effusion and giant coronary artery aneurysm in the proximal portion of the left circumflex artery (LCx). (d) Contrast computed tomography after surgery. Coronary aneurysm was removed, and coronary artery bypass grafting (saphenous vein graft - LCx) showed coronary artery aneurysm in the distal portion of the LCx. Yellow arrows in (c) and (d) show the residual coronary artery aneurysm in the distal region of the LCx.

Fig. 2.

Histopathological examination of the surgical specimen. (a) and (b) Photomicrograph with hematoxylin and eosin staining showed plasma cell-based inflammatory cell aggregation and the presence of fibrosis. Photomicrograph with immunostaining for immunoglobulin (Ig) G (c) and IgG4 (d) showed many IgG4+ cell infiltrates, and the IgG4/IgG rate was over 40 %.

Laboratory data 1 year after the second surgery showed slightly elevated C-reactive protein levels (1.37 mg/dL), decreased renal function (serum creatinine levels, 1.15 mg/dL), and elevated serum IgG4 levels (428 mg/dL). Follow-up TTE 1 year after the second surgery for coronary aneurysm revealed an abnormal cavity structure, which was 17 mm large and echo-free on the lateral side of the left atrium at the 5 o'clock position of the parasternal short-axis view (Fig. 3). The left ventricular wall motion and ejection fraction were normal. Furthermore, 3 years after the second surgery, the abnormal cavity structure expanded to 21 mm in the short-axis view, and the echogenicity of the inner wall increased partly (Fig. 3). A planar CT scan showed a tumor-like shadow near the site of the residual aneurysm. As with TTE, the aneurysm had expanded on CT, and the serum IgG4 level was elevated (577 mg/dL). We suspected progression of the coronary aneurysm; however, the patient had no symptoms and refused contrast CT, positron emission tomography-CT, and corticosteroid treatment. The patient dropped out of the follow-up at our hospital, however, his clinical course is uneventful at other hospital follow-up.

Fig. 3.

Transthoracic echocardiography (parasternal short-axis view) and computed tomography (axial plane) at early postoperative period (a) and (d), 1-year follow-up (b) and (e), and 3-year follow-up (c) and (f) showed gradually progressing masses (yellow arrow) surrounding the left circumflex artery.

Discussion

This is a rare case of IgG4-related thoracic aortitis concomitant with coronary aneurysm. In addition, the residual IgG4-related coronary aneurysm progressed without corticosteroid therapy after surgery for IgG4-related aortitis and coronary aneurysm. The progression of a coronary aneurysm in the LCx as an abnormal cavity structure was first detected using TTE and was useful as a follow-up.

IgG4-related inflammatory aneurysms are reported in other large to medium-sized arteries and IgG4-related thoracic aortic lesions have been involved in 4 % of all thoracic aortic lesions [5]. However, few studies and case reports have reported IgG4-related thoracic aortitis concomitant with coronary aneurysm. The 2020 revised comprehensive diagnostic criteria for IgG4-RD consisted of three major items: 1) clinical and radiological features organs: diffuse or localized swelling or mass or nodule, 2) serological diagnosis: elevated serum IgG4 concentrations >135 mg/dL, and 3) pathological diagnosis: (i) Dense lymphocyte and plasma cell infiltration with fibrosis, (ii) Ratio of IgG4-positive plasma cells/IgG-positive cells >40 % and the number of IgG4-positive plasma cells >10 per high powered field, (iii) Typical tissue fibrosis, particularly storiform fibrosis, or obliterative phlebitis [1]. Our case meets all the criteria mentioned above: 1) aortitis and coronary aneurysm; 2) serum IgG4 of 331 mg/dL; 3) Ratio of IgG4-positive plasma cells/IgG-positive cells >40 % and the number of IgG4-positive plasma cells >10 per high powered field in both the aortic wall and coronary aneurysm specimens. Therefore, our case was rare because of IgG4-related thoracic aortitis concomitant with coronary aneurysm.

The first-line therapy for IgG4-RD is glucocorticoids, and almost all patients require maintenance treatment and experience disease recurrence without corticosteroid therapy [3]. Although the clinical course after corticosteroid therapy in IgG4-related aortitis, periaortitis, and periarteritis was effective in preventing new aneurysm formation, and a minority of patients developed luminal dilatation despite corticosteroid therapy in a retrospective multicenter study [6], no large-scale prospective and retrospective studies have evaluated the clinical course after corticosteroid therapy in IgG4-related coronary artery disease. The relevance of immunosuppressive therapy in IgG4-related coronary artery disease remains unclear. Recently, Ito et al. [7] reported that patients with isolated IgG4-related coronary periarteritis showed relatively low serum IgG4 levels and high responsiveness to glucocorticoids. Recurrence during follow-up examination occurs in approximately 10 % of cases in which the serum IgG4 level normalizes and in approximately 30 % of cases in which the serum IgG4 level remains high [8]. In this case, the serum IgG4 levels remained slightly elevated, and no corticosteroid treatment was administered, which might have caused the progression of the coronary aneurysm in the LCx. Appropriate treatment is important, and this patient should have received corticosteroid treatment, particularly at the time of surgery for the first distal aortic arch aneurysm.

Imaging is an important part of the diagnostic workup and follow-up of IgG4-related coronary disease. Coronary angiography is the gold standard tool for the diagnosis of coronary aneurysms because it provides information about the shape, size, location, and number of aneurysms [9]. Among noninvasive modalities, electrocardiogram-gated contrast CT can be suggested as the technique of choice for the follow-up of patients with coronary artery aneurysms because of improvements in terms of radiation dose with the current protocols [9]. TTE is also used to detect coronary aneurysms. Although the specificity of TTE when compared with conventional angiography for the detection of coronary aneurysms is good for in children, its diagnostic capability is limited in adults owing to any circumstances precluding the securing of optimal echocardiographic windows, including chronic obstructive lung disease, previous thoracic or cardiovascular surgery, morbid obesity, or other conditions. In this case, the patient was followed up with TTE and plain CT because of renal dysfunction and refusal to use contrast CT. Fortunately, progression of the aneurysm at the distal portion of LCx could be detected, and TTE was useful for follow-up. Fluorodeoxyglucose positron emission tomography-CT (PET-CT) can provide important information about the extent of the disease and the presence of active inflammation. Therefore, PET-CT is important for accurate diagnosis and evaluation of therapeutic response during follow-up in patients with IgG4-related coronary artery disease [10]. Even in our case, we should have performed PET-CT and discussed whether to treat the patient with steroids.

We encountered a case of IgG4-RD in which the residual coronary aneurysm distally of the LCx expanded after surgery for IgG4-related aortitis and coronary aneurysm. Thoracic aortic disease combined with coronary aneurysm may be IgG4-RD. The possibility of progression is high in cases where serum IgG4 remains at a high level, especially without steroid treatment, and follow-up examinations, such as TTE and CT, are more important. Therefore, we reaffirm that corticosteroid therapy may have been important.

Declaration of competing interest

The authors declare that they have no conflict of interest.