Invited commentary

Abstract

Elevated serum immunoglobulin-G4 (IgG4) has been linked to several overlapping syndromes that are related to IgG4-producing plasma cells. These clinical syndromes include cholangitis, autoimmune hepatitis and pancreatitis, Sjögren's syndrome, nephritis, and retroperitoneal fibrosis, and the spectrum of this disease has been labeled “IgG4-related systemic disease.” Management of IgG4-related systemic disease generally includes immunosuppressive therapy; dramatic responses to medical therapy have obviated surgical management in many cases. Inflammatory aneurysms have long proved to be challenging for vascular surgeons, with chronic periaortitis, inflammation, and fibrosis increasing the difficulty of surgical repair, and, possibly paradoxically, reducing the risk of rupture. The authors have previously published their examination of a small series (n = 10) of inflammatory aneurysms, and showed that four of the 10 inflammatory aneurysms had abundant IgG4-positive plasma cells and histological changes typical of IgG4-related systemic disease. In this paper, the authors expand their examination to the 23 cases of inflammatory aneurysms that were treated over 12 years, 13 cases of which contained IgG4-positive plasma cells. These patients were associated with reduced risk of rupture, other allergic or autoimmune disorders, and positive serology for IgG4, IgE, and anti-nuclear antibody (ANA), compared with the 10 cases that did not contain IgG4-positive plasma cells. The implications of this report suggest that IgG4-related inflammatory aneurysms may be treated medically, rather than surgically; conversely, the high rate of rupture in IgG4-negative aneurysms suggests an aggressive therapeutic approach is warranted. Optimal medical and surveillance strategies need to be defined for IgG4-related aneurysms, and optimal surgical strategies, that minimize complication risk, need to be defined for IgG4-negative aneurysms. As the only other report of IgG4-related inflammatory aneurysm disease has come from another Japanese group,1Sakata N. Tashiro T. Uesugi N. Kawara T. Furuya K. Hirata Y. et al.IgG4-positive plasma cells in inflammatory abdominal aortic aneurysm: the possibility of an aortic manifestation of IgG4-related sclerosing disease.Am J Surg Pathol. 2008; 32: 553-559Crossref PubMed Scopus (83) Google Scholar the utility of these observations will be clarified as they are extended to other populations. There are implications for other vascular diseases as well. For example, Kawasaki disease is an acute inflammatory childhood vasculitis with intense secretion of cytokines that permanently damage the vascular endothelium and typically result in coronary aneurysms. This disease is usually treated with immune globulin and aspirin, with steroid therapy being controversial. Should Kawasaki disease prove to be IgG4-related, then additional insights into its management will be obtained. Ultimately, the increasing importance of the role of the immune system in the pathogenesis of atherosclerosis is being recognized. If IgG4-related systemic disease plays a causative role in the formation of atherosclerosis in even a small subset of patients, medical therapy for this important vascular disease may ultimately prove to be a reality. A new clinicopathological entity of IgG4-related inflammatory abdominal aortic aneurysmJournal of Vascular SurgeryVol. 49Issue 5PreviewRecently, the relationship between immunoglobulin (Ig)G4 and idiopathic sclerosing lesions has attracted much attention. IgG4-related disease was first described with regard to the pancreas (autoimmune pancreatitis), and has been expanded to various organ systems. We previously reported that inflammatory abdominal aortic aneurysm (IAAA) could be one of the manifestations of IgG4-related disease. In this study, we tried to elucidate the clinical characteristics of IgG4-related IAAA. Full-Text PDF Open Archive