Immunoglobulin G4–related multiple systemic aneurysms and splenic aneurysm rupture during steroid therapy

doi:10.1016/j.humpath.2013.07.035

Human Pathology

Volume 45, Issue 1, January 2014, Pages 175-179

https://doi.org/10.1016/j.humpath.2013.07.035 Get rights and content

Summary

Immunoglobulin G4 (IgG4)–related disorders in various organs have recently been described, but multiple systemic aneurysms have not yet been reported. Here, we present a 68-year-old Japanese man with multiple systemic aneurysms and tumor-forming pericoronary arteritis who was undergoing low-dose corticosteroid therapy. Elevated serum IgG4 (2390 mg/dL) and IgG4-positive plasmacyte infiltration in the salivary glands led to a diagnosis of IgG4-related disease. High-dose corticosteroid therapy was initiated, whereupon the inflammatory lesions shrank. However, the large, well-developed common hepatic aneurysm and splenic aneurysm did not change. Our patient died of splenic aneurysm rupture in the sixth month of treatment. The autopsy revealed IgG4-positive plasmacyte infiltration in the coronary wall and a thinned splenic aneurysm wall. This case suggests that early high-dose corticosteroid therapy may be necessary for the treatment of IgG4-related cardiovascular disorders. A minor salivary gland biopsy might facilitate the early diagnosis of IgG4-related disease even if ¹⁸F-fluorodeoxyglucose positron emission tomography provides no inflammatory findings.

Introduction

The mechanism of immunoglobulin G4 (IgG4)–related disease (an autoimmune disease) is gradually becoming clearer [1]. This disease causes inflammation in the pancreas, bile ducts, retroperitoneum, salivary glands, aorta, arteries, and various other organs [2]. Recently, we encountered an interesting case of IgG4-related cardiovascular disorder with significant therapeutic implications.

Section snippets

Case report

A 68-year-old Japanese man noticed a pulsatile mass on the right side of his neck and was admitted to our hospital. He had been undergoing low-dose corticosteroid therapy (7.5 mg/d of prednisolone) for polymyalgia rheumatica for 10 years. A physical examination and echography revealed aneurysms of the right internal carotid artery, bilateral subclavian arteries, left axillary artery, left brachial artery, coronary arteries, common hepatic artery, and splenic artery (Fig. 1A-C). He presented

Results

Because the patient was already under low-dose corticosteroid therapy, we started high-dose corticosteroid therapy (initially 60 mg/d of prednisolone) for IgG4-related disease. This treatment normalized the IgG, eosinophils, C-reactive protein, and erythrocyte sedimentation rate levels within 2 weeks, whereas the IgG4 and IgE levels did not return to normal until 12 weeks later. Physical examination detected shrinkage of the small aneurysms, such as those in the left axillary artery and left

Discussion

IgG4-related inflammatory aneurysms have been reported in large- to medium-sized arteries, such as the aortic arch [4], the thoracic aorta [5], the coronary artery [6], and others [7]. Solitary aneurysms are occasionally observed in IgG4-related disease, but multiple systemic aneurysms, such as in this case, have never been reported. Most cases of IgG4-related inflammatory aneurysm, including this one, exhibit IgG4-positive cell infiltration in the adventitia [4], but in some cases,

Acknowledgment

We received editorial assistance from Mr Christopher Holmes.

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Cited by (38)

Immunoglobulin G4-related hepatic artery aneurysm
2024, Journal of Vascular Surgery Cases, Innovations and Techniques
A 49-year-old man who was a current smoker with a history of hypertension, dyslipidemia, and coronary artery disease after coronary stent placement presented because of abdominal and back pain. Contrast-enhanced computed tomography showed a 30-mm, large hepatic artery aneurysm. Resection of the aneurysm and autogenous vein bypass grafting was performed, which resulted in a successful outcome without any complications. Pathologic examination of the aneurysm confirmed that it was related to immunoglobulin G4 (IgG4). The patient's serum IgG4 level was within the normal range, and no other signs of IgG4-related organ lesions were observed.
Coronary Periarteritis and Pericardial Thickening Could Be Predictors for Coronary Artery Events Complicated by IgG4-Related Disease
2023, CJC Open
IgG4-related disease (IgG4-RD) is a systemic disease characterized by serum IgG4 upregulation, massive infiltration of IgG4-positive plasma cells, and storiform fibrosis, which results in nodules or thickening of the involved organs. Cardiologists have recently recognized that IgG4-RD can be complicated by coronary artery events (CAEs); however, the mechanisms and clinical characteristics of this phenomenon are unknown. We evaluated the clinical signs of patients with coronary periarteritis (CP), aortic periarteritis (AP), and pericardial thickening, which are complications of IgG4-RD, to determine the contributing factors.
We retrospectively examined 19 patients with IgG4-RD who attended or consulted a cardiologist in our department at the University of Tokyo Hospital between January 1, 2004, and December 31, 2021.
The frequency of CAEs was significantly higher in the CP group than in the non-CP group. Furthermore, the CP group had significantly lower event-free survival than the non-CP group (log-rank test, P = 0.008). However, the frequency of incidents and event-free survival for CAEs after IgG4-RD diagnosis did not differ significantly between the AP and non-AP groups. Although no statistically significant difference was present between the frequency of CAEs for those with vs without pericardial thickening, the group with pericardial thickening had significantly worse event-free survival than the group without pericardial thickening (log-rank test, P = 0.017).
The incidence and clinical course of CAEs complicated by IgG4-RD could be predicted by identifying CP and pericardial thickening in IgG4-RD but not AP.
La maladie liée aux immunoglobulines de type G4 (ML-IgG4) est une maladie généralisée caractérisée par une augmentation du taux sérique d’IgG4, par une infiltration massive de plasmocytes exprimant les IgG4 et par une fibrose storiforme, qui produit des nodules ou un épaississement des organes touchés. Les cardiologues ont récemment reconnu que la ML-IgG4 peut être compliquée par des événements coronariens; les mécanismes et caractéristiques cliniques de ce phénomène demeurent cependant inconnus. Nous avons évalué les signes cliniques chez des patients atteints de périartérite coronarienne (PC), de périaortite (PA) et d’épaississement du péricarde, des complications de la ML-IgG4, pour tenter d’établir les facteurs contributifs.
Nous avons examiné de manière rétrospective les dossiers de 19 patients atteints de ML-IgG4 qui ont été admis à notre service de l’Hôpital de l’Université de Tokyo ou qui ont consulté un cardiologue du service entre le 1^er janvier 2004 et le 31 décembre 2021.
La fréquence des événements coronariens était significativement plus élevée dans le groupe PC que dans les autres groupes. Par ailleurs, le groupe PC avait une survie sans événement significativement plus courte que les autres groupes (test logarithmique par rangs; p = 0,008). En outre, la fréquence des événements coronariens et la survie sans événement coronarien après un diagnostic de ML-IgG4 ne variaient pas de manière significative entre le groupe PA et les autres groupes. Bien qu’aucune différence statistiquement significative n’ait été constatée quant à la fréquence des événements coronariens entre les patients présentant un épaississement du péricarde et les autres patients, le premier groupe affichait une survie sans événement significativement plus courte que l’autre (test logarithmique par rangs; p = 0,017).
L’incidence et le déroulement clinique des événements coronariens compliqués par la ML-IgG4 pouvaient être anticipés dans les cas de ML-IgG4 en présence de PC et d’un épaississement du péricarde, mais pas de PA.
Arterial-bronchial fistula from ruptured immunoglobulin G4-related subclavian artery aneurysm
2020, Journal of Vascular Surgery Cases and Innovative Techniques
Citation Excerpt :
The incidence of vasculitis as a cause of SAA is unknown. Although rare, IgG4-related SAA has been described only in a case with multiple IgG4-related aneurysms reported by Tajima et al.7 Commonly, surgery is indicated for subclavian aneurysms to prevent rupture and thromboembolism. Although no clear surgical indications exist in terms of aneurysm size, the rupture of such aneurysms can be fatal.
Immunoglobulin G4 (IgG4)-related disease is a systemic chronic inflammatory disease caused by infiltration of IgG4-positive plasma cells into the systemic organs. IgG4-related arterial disease is relatively rare not only in the aorta but also in the small to medium-sized arteries. If IgG4-related vasculitis is suspected on the basis of the preoperative medical history and radiologic and serologic examination findings, a definitive diagnosis can be obtained by open repair and pathologic examination to determine the prognosis and need for additional treatment. Here, we report the successful treatment of arterial-bronchial fistula caused by a ruptured IgG4-related subclavian artery aneurysm.
Characteristics and prognosis of IgG4-related periaortitis/periarteritis: A systematic literature review
2019, Autoimmunity Reviews
Citation Excerpt :
Long-term prognosis remained unclear. We identified 27 articles that described 27 patients with IgG4-related coronary arteritis [20,25,27,32–55] (Table 4). The mean age was 66 years and 81% were men.
Immunoglobulin G4 (IgG4)-related disease is a systemic chronic fibroinflammatory disease that can affect almost every organ of the body. IgG4-related periaortitis/periarteritis is a newly recognized subset of IgG4-related disease, and its characteristics and prognosis remain unclear. We investigated the clinical characteristics and prognosis of IgG4-related periaortitis/periarteritis.
We performed a systematic literature review of IgG4-related periaortitis/periarteritis. Additionally, we have summarized the characteristics and prognosis of IgG4-related coronary arteritis.
We investigated 248 patients with IgG4-related periaortitis/periarteritis. All studies reported the condition in elderly patients, and male predominance was observed. The infra-renal abdominal aorta and iliac arteries were the most commonly affected sites. Most reports showed the serum C-reactive protein elevation in this disease entity, in contrast to non-vascular IgG4-related disease. Based on radiological findings observed in 27 patients with IgG4-related coronary arteritis, vasculitic lesions were classified into 3 types: stenotic (67% of patients), aneurysmal (42%), and diffuse wall thickening type (92%). Serum IgG4 level, but not C-reactive protein level, was associated with the number of affected organs in IgG4-related coronary arteritis. Corticosteroid treatment with or without cardiac surgery or percutaneous coronary intervention was effective in most patients with IgG4-related coronary arteritis; however, 33% of patients showed an unfavorable clinical course including disease progression, relapse, or death. Pre-treatment stenosis and/or aneurysms were associated with progression of stenosis or aneurysm after corticosteroid treatment.
Most clinical characteristics were similar between the IgG4-related periaortitis/periarteritis and the non-vascular IgG4-related disease groups; however, serum C-reactive protein level elevation was observed only in the former. Although corticosteroid treatment was effective, this disease can be life-threatening secondary to myocardial infarction, aortic dissection, and aneurysmal rupture. Pre-treatment evaluation of stenosis or aneurysms is important for predicting progression of stenosis or aneurysm after corticosteroid treatment.
IgG4-Related Disease: A New Etiology Underlying Diffuse Intracranial Dilating Vasculopathy
2017, World Neurosurgery
Citation Excerpt :
In one previous case involving vertebrobasilar dolichoectasia, postmortem histologic analysis revealed marked infiltration of IgG4-containing plasma cells in the adventitia and media of affected vessels,19 and increased levels of proinflammatory cytokines have been observed in patients harboring intracranial aneurysms, particularly in ruptured aneurysms.20 Peripheral vascular and cardiovascular disease also has been attributed to IgG4-RD with cases of inflammatory aortic aneurysms,3-6 peripheral artery aneurysms,21 coronary vessel disease,8 and valvular disease.7 The vascular pathophysiology observed in association with IgG4-RD is thought to be similar to HIV vasculopathy.
Diffuse intracranial aneurysmal vasculopathy is a rare condition, previously described in patients with human immunodeficiency virus infection. IgG4-related disease (IgG4-RD) is a recognized inflammatory disease of systemic organs, leading to fibrosis of connective tissues. It also has been linked to inflammatory dilating aortic aneurysms, coronary vascular disease, hypophysitis, orbital pseudotumor, and pachymeningitis. It has not yet been described as a cause of diffuse intracranial dilating vasculopathy. Histologically, this disease is characterized by IgG4-plasma cell infiltration, fibrosis, and phlebitis.
A 40-year-old woman presented with acute heart failure, valvular insufficiency, and mycotic coronary aneurysms, concerning for endocarditis. Infectious workup was negative. Concurrent neurovascular workup revealed intracranial aneurysms, appearing mycotic in origin. Despite aggressive treatment for more than 5 years, she suffered multiple episodes of subarachnoid hemorrhage from a progressive dilating intracranial vasculopathy. Serum IgG levels and aneurysm wall pathology were consistent with IgG4-RD.
This is the first reported case of a diffuse intracranial dilating vasculopathy secondary to IgG4-RD. Recognition of similar pathologic findings in clinical presentation and radiologic workup should prompt further rheumatologic workup and possible immunosuppressive therapies.
Solitary recurrence of IgG4-related giant coronary aneurysm: Case report and review of the literature focusing on treatment strategies and complications
2024, Modern Rheumatology Case Reports

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Case studyImmunoglobulin G4–related multiple systemic aneurysms and splenic aneurysm rupture during steroid therapy

Summary

Introduction

Section snippets

Case report

Results

Discussion

Acknowledgment

Mod Pathol

J Vasc Surg

Hum Pathol

J Cardiol

IgG4-related disease

N Engl J Med

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

Mod Rheumatol

IgG4-related inflammatory aneurysm of the aortic arch

Pathol Int

Case study
Immunoglobulin G4–related multiple systemic aneurysms and splenic aneurysm rupture during steroid therapy