Year: 2025
Type: review
Study design: Systematic Review
Abstract: Introduction Immunoglobulin G4-related disease (IgG4-RD) is a recently identified immune-mediated condition that is debilitating and often overlooked. While IgG4-RD has been reported in several organs, this study reviews cases where IgG4-RD caused pericarditis. Methods A systematic search was conducted from inception until March 1, 2025. All age groups and both sexes with confirmed pericarditis were included, along with the following inclusion criteria: 1) Patients with pericardial biopsy showing IgG4/IgG ratio of >40%. 2) Patients with pericardial biopsy revealing IgG4/HPF of >10. 3) Patients who had confirmed IgG4-RD from other organ biopsies through IgG4 staining, or diagnostic imaging suggestive of IgG4-RD, or pericardial biopsy with classic IgG4-RD histopathologic patterns, with elevated serum IgG4 levels, provided no other diagnosis was more likely. Results A total of 50 patients were included, with a mean age of 64.86±15.79 years. There were 36 (72%) males. The most common presenting symptom was dyspnea in 27 (54%) patients. Different pericardial involvements were reported, including pericardial thickening 37 (74%), constrictive pericarditis 28 (56%), pericardial effusion 23 (46%), pericardial calcification 6 (12%), and pericardial nodule 5 (10%). In 28 (56%) patients, only the pericardium was affected. In addition to the pericardium, eight (16%) patients had one other organ affected, and 11 (22%) patients had two additional organs affected. Two (4.5%) cases ended in demise. Conclusion Although rare, IgG4-RD can cause pericarditis, leading to pericardial thickening, effusion, constrictive pericarditis, or the formation of pericardial nodules. Treatment with corticosteroids or pericardiectomy has been associated with favorable outcomes. Introduction Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory condition that affects multiple organs in the body. It is a slowly progressing and often debilitating disease, with the potential to be fatal in some cases [1]. The condition was first suspected in the pancreas where a subset of autoimmune pancreatitis was associated with elevated levels of serum IgG4, now termed autoimmune pancreatitis type I [2]. The discovery that individuals with autoimmune pancreatitis also develop extra-pancreatic fibroinflammatory lesions containing abundant IgG4-bearing cells, in addition to histopathological features consistent with that in the pancreas, which include; dense lymphoplasmacytic infiltration, storiform fibrosis, and either obliterative or non-obliterative phlebitis, contributed to the establishment of the concept of IgG4-RD as a unique clinical entity in 2003 [1-3]. For decades, conditions such as Riedel thyroiditis, sclerosing cholangitis, Mikulicz’s syndrome, hypertrophic pachymeningitis, and retroperitoneal fibrosis were considered distinct entities. However, they are now classified within the spectrum of IgG4-RD, as they have been found to share similar histologic features and present concurrently in some patients [4]. The worldwide prevalence and incidence of IgG4-RD are mostly underreported. Still, studies from Japan have revealed that the incidence of autoimmune pancreatitis increased from 0.8 to 3.1 cases per 100,000 people between 2007 and 2016, suggesting a swift rise in recognition of IgG4-RD within just a decade [4]. There is a higher prevalence among males, with the average age at diagnosis typically ranging from the fifth to sixth decade of life. However, classic presentations have also been documented in pediatric patients [1]. Cigarette smoking is the only well-documented modifiable risk factor associated with the development of IgG4-RD [5]. A genome-wide association study revealed that the FC-γ receptor IIb and HLA-DRB1 regions were associated with an increased susceptibility to IgG4-RD, indicating a potential genetic predisposition to its pathogenesis [6]. The pathophysiology of IgG4-RD remains incompletely understood. However, several critical components have been identified, including the migration of activated B cells to the site of inflammation, where they facilitate the expansion and differentiation of T cells into CD4+ cytotoxic T lymphocytes (CTLs). These CD4+ CTLs subsequently induce apoptosis by releasing perforins and granzymes. In response, activated M2 macrophages clear the apoptotic cells while also contributing to the activation of fibroblasts. This activation is promoted through several mediators, including IFN-γ (interferon-gamma), TGF-β (transforming growth factor-beta), and IL-1 (interleukin-1) from CD4+ CTLs, along with PDGF (platelet-derived growth factor) from activated B cells, and various factors from macrophages. As fibroblasts become activated, they secrete extracellular matrix proteins, leading to tissue remodeling and fibrosis. Over time, the progressive expansion of the extracellular matrix and increased cell proliferation contribute to the development of tumor-like masses and the subsequent enlargement of affected organs, as observed in clinical settings [7]. While IgG4-RD has been reported in multiple organs, this study is the first to comprehensively review cases where it affects the pericardium, leading to pericarditis. Methods Study design The present systematic review was conducted per the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Literature search A thorough systematic search was conducted across Scopus, PubMed, Web of Science, and Google Scholar databases to retrieve studies published from inception until March 1, 2025. The search employed the following keywords: “IgG4 OR IgG4RD OR immunoglobulin AND pericarditis OR tamponade OR pericardial OR pericardium OR serositis OR serosal” Eligibility criteria The inclusion criteria were restricted to English-language publications involving only human subjects, specifically case-control studies, cohort studies, cross-sectional studies, or case reports. Additionally, due to the limited number of studies on this topic, conference papers containing adequate information were also included. All age groups, both sexes, with confirmed pericarditis through a combination of clinical examination, ECG (electrocardiography), diagnostic imaging (including echocardiography, magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET)), laboratory investigations, or histopathological examination of the pericardial tissue or fluid were included. Given the limited number of reports on this entity and a lack of standardized diagnostic criteria for IgG4-RD pericarditis, such as an established IgG4/IgG ratio or IgG4/high power field (HPF) in pericardial specimens or its necessity in the first place when other clues are suggestive of this disease, this review adopted an inclusive approach. With patients of either of the following criteria being included: 1) Patients with pericardial biopsy showing an IgG4/IgG ratio of >40% or reported as “increased”. 2) Patients with pericardial biopsy revealing IgG4/HPF of >10 or reported as “increased”. 3) Patients who had confirmed IgG4-RD from other organ biopsies through IgG4 staining, or diagnostic imaging suggestive of IgG4-RD, or pericardial biopsy with classic IgG4-RD histopathologic patterns, with elevated serum IgG4 levels, provided no other diagnosis was more likely. The exclusion criteria included studies with incomplete information about the patients or the method of diagnosis. Patients who were more likely to have pericarditis due to causes other than IgG4-RD. Studies from journals with inadequate peer review and questionable reliability were excluded [8]. Study selection The screening process commenced with two independent researchers who systematically reviewed the titles and abstracts of all identified studies. Following this initial assessment, a comprehensive full-text evaluation was conducted based on predefined inclusion and exclusion criteria. Studies that satisfied these eligibility criteria were subsequently selected for inclusion. In instances where disagreements emerged between the two researchers, a third author was consulted to mediate and resolve conflicts through discussion and consensus. Data items Data extraction was conducted using Microsoft Office Excel 2016. The following variables were collected for each study: first author’s name, year of publication, study design, country of origin, sample size, patient sex, age, past medical and surgical history, family history, presenting complaint, and duration of symptoms. Additionally, data regarding pericardial involvement were extracted, including the presence of pericardial thickening, constrictive physiology, pericardial calcification, and pericardial nodules. The presence or absence of pleural disease was also recorded. If available, findings from diagnostic imaging modalities such as chest radiography, echocardiography, CT, MRI, PET, and right heart catheterization were documented. Laboratory results, when reported, were extracted for C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum IgG4 levels, serum IgG4/IgG ratio, and any other notable laboratory parameters. Furthermore, the number of organs affected by IgG4-RD, and the histopathological findings were collected. Treatment modalities, including both successful and unsuccessful interventions, were documented, along with follow-up duration and clinical outcomes. Data analysis The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 26.0, which facilitated the quantitative synthesis of the information. Relevant variables were displayed in summary tables, with categorical data represented by frequency and percentage, and quantitative data summarized using the mean and standard deviation. Results Study selection The literature search yielded 87 studies from the databases.
Source: Barw Medical Journal
DOI: 10.58742/bmj.vi.204
Authors: Dilan Hikmat, Saman Al Barznji, Adolfo Martinez, Akhil Gaderaju, Mohammed Alaa Raslan, Mohammad Almasri, Karam Ghazal-Aswad, Ghasaq Saleh, Rohan Kumar, Maitri Shah
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4414525085