To evaluate the incidence of IgG4-related vascular disease (IgG4-VD) in aneurysm enlargement after endovascular aneurysm repair (EVAR).

Of 1482 EVAR cases in which patients underwent initial treatment at our hospital, 33 patients who underwent open surgery for an enlarged aneurysm were retrospectively identified. Histopathological examination of the aneurysm wall specimens was performed and the relationship of the histopathological findings with IgG4-VD was investigated.

The median aneurysm diameter at EVAR was 53 mm (interquartile range [IQR] 50-55), and the aneurysm diameter at open surgery was 79 mm (IQR 75-88). Six patients (18%) were histopathologically diagnosed with IgG4-VD. Relative to the non-IgG4-VD cases, the patients with IgG4-VD had a higher incidence of coronary artery disease (83% vs. 30%, p = 0.015) and greater aneurysm wall thickness at the time of open surgery (2.4 mm vs. 1.6 mm, p < 0.001). Serum IgG4 levels were significantly higher in patients with IgG4-VD than in those without IgG4-VD (218 mg/L vs. 46 mg/L, p = 0.002).

IgG4-VD was found in 18% cases with enlarged aneurysms after EVAR. If aneurysm enlargement is observed after EVAR, measurement of the aneurysm wall thickness using preoperative CT angiography and the evaluation of serum IgG4 levels could be useful for diagnosing occult IgG4-VD.

IgG4-related disease (IgG4-RD) is a systemic, immune-mediated, fibro-inflammatory condition with an uncertain etiology and pathophysiology that can affect multiple organs, presenting common clinical, radiological, and serological features. Although the disease is associated with IgG4, serum levels are not elevated in all patients and have also been described in other diseases. The aim of this study is to evaluate the clinical utility of elevated serum IgG4 as a screening marker in the suspicion of IgG4-related disease.

A retrospective single-center study was conducted, analysing serological IgG4 test requests from electronic medical records of patients ordered by various hospital departments from January 2010 to June 2023. Only those with elevated IgG4 levels were included in the analysis. Additionally, demographic data and final diagnoses, including those with IgG4-RD, were collected.

A total of 2288 test requests were reviewed, of which 247 showed elevated IgG4 levels (181 after excluding duplicates). Among the patients with elevated IgG4, only 11 met the criteria for IgG4-RD based on the 2011 Umehara-Okazaki classification and its 2020 update. However, only 6 patients (3.31%) met the more recent 2019 ACR/EULAR classification criteria for IgG4-RD. In the remaining patients with elevated IgG4, the most common diagnoses were respiratory diseases, such as COPD and asthma, followed by systemic autoimmune diseases, primarily SLE, RA, and EGPA. Elevated IgG4 levels were also observed in malignant neoplasms, predominantly lung and hematologic cancers.

Our study highlights that elevated IgG4 levels are not exclusive to IgG4-RD and can also be observed in various respiratory diseases (e.g., COPD), autoimmune diseases (e.g., SLE and RA), and neoplasms (e.g., lung cancer).

Tubulointerstitial nephritis (TIN) is an important disease involving a diverse set of factors that can cause both acute kidney injury and chronic kidney disease. The purpose of this cross-sectional study was to clarify the causative diseases and clinicopathological characteristics of TIN using the Japan Renal Biopsy Registry (J-RBR).

This cross-sectional study analyzed data from 22,049 cases registered in the J-RBR between 2018 and 2022. Clinicopathological findings at diagnosis were investigated.

Of the enrolled cases, 913 were diagnosed with TIN. "Drug-induced" was the most common (232 cases, 25.7%), followed by "IgG4-related kidney disease" (124 cases, 13.7%). Of "Drug-induced" TIN cases, "Chemotherapy-related" was the most common cause (63 cases, 27.2%), including 47 cases of "immune checkpoint inhibitor (ICI)-associated" TIN. IgM-positive plasma cell-rich TIN (IgMPC-TIN), which has been the focus of much attention in recent years, was also included, with 9 cases.

This is the first report of the clinicopathological findings of TIN patients in a large-scale, nationwide registry of renal biopsies. It was possible to identify recent trends in causative diseases, including an increase in chemotherapy-related TIN and IgMPC-TIN.

To investigate the clinical characteristics and treatment outcomes of IgG4-related ophthalmic disease (IgG4-ROD) in Korean patients.

A multicenter, retrospective case series study.

Three hundred and forty-one patients with IgG4-ROD from 24 hospitals in Korea.

The medical records of all patients with IgG4-ROD were reviewed, which were consistent with comprehensive diagnostic criteria. The demographic, clinical, histopathological, and laboratory data were also collected.

Frequencies of extra-lacrimal gland and extraorbital involvement, and treatment outcomes with potential predisposing factors.

Among the 341 patients with IgG4-ROD who were enrolled, 155 (45.5%) had definite IgG4-ROD. Extra-lacrimal gland involvement was observed in 53 patients (34.2%) and associated with older age, male sex, unilaterality, and higher serum IgG4 levels. Extraorbital involvement was observed in 52 of 77 (67.5%) patients with definite IgG4-ROD who underwent adequate systemic evaluation. Regarding treatment outcomes, 130 with definite IgG4-ROD who were followed up for more than 6 months were included for the analysis; 93 (71.5%) achieved remission, and 40 (30.8%) attained steroid-free remission. Surgical debulking was significantly associated with remission and steroid-free remission, whereas initial use of an immunomodulator with a steroid showed no significant association with the treatment outcome. The highest serum IgG4 tertile was negatively associated with steroid-free remission. Relapses occurred in 24 (28.6%) of 86 patients who experienced remission, and underlying diabetes was an associated risk factor.

Extraorbital involvement was detected in more than half of the patients with definite IgG4-ROD, emphasizing that broad systemic evaluation is warranted for these patients. Disease remission was achieved in 71.5% of patients, but relapse occurred in a significant number of patients. Steroid-free remission was positively associated with surgical debulking. These findings suggest that the surgical debulking of the lesions and patient tolerability to steroid therapy may affect treatment outcomes in IgG4-ROD.

To analyze the clinical characteristics of malignant lymphoma that closely resembles IgG4-related disease (IgG4-RD).

This study retrospectively analysis involving 31 patients who were lymphoma mimicking, IgG4-RD and 50 contemporaneous IgG4-RD patients serving as controls. Lymphoma mimicking IgG4-RD was defined as presenting with masses in the typical sites of IgG4-RD, with or without elevated serum IgG4 levels, and ultimately confirmed to be lymphoma. The clinical data, including the extent of lymph node involvement, maximum diameter of lymph nodes, systemic symptoms, and laboratory parameters were assessed. Student's t-test, the Mann-Whitney test, and the chi-squared test were used to compare the two groups.

Fever emerged as a distinctive feature in lymphoma patients. Compared to IgG4-RD, lymphoma patients exhibited a greater extent of lymph node involvement (p < 0.001), larger maximum diameters of lymph nodes (p = 0.007), and higher frequency of enlargement in supraclavicular (41.9% vs 10.0%; p = 0.001), armpit (45.2% vs 16.0%; p = 0.004), retroperitoneal (70.9% vs 10.0%; p < 0.001), and groin lymph nodes (41.9% vs 8.0%; p < 0.001). In contrast, IgG4-RD patients were more likely to show involvement of submandibular gland (58.0% vs 29.0%; p = 0.015) and pancreatic (44.0% vs 9.7%; p = 0.001). Additionally, lymphoma patients presented with higher levels of erythrocyte sedimentation rate (ESR) (p = 0.010), C-reactive protein (CRP) (p < 0.001), and lactate dehydrogenase (LDH) (p = 0.002), along with a higher prevalence of anemia (35.5% vs 4.0%; p < 0.001) and lower albumin levels (p = 0.039), while IgG4-RD patients had higher IgG4/IgG ratio (p < 0.001) and lower complement 3 (C3) (p = 0.009) levels than lymphoma patients.

Although patients with malignant lymphoma and IgG4-RD share some overlapping presentations, they differ significantly in some distinct features, including fever, pattern of lymph node and organ involvement distribution, and some laboratory parameters. Key Points • IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by elevated serum IgG4 levels, presenting lymphadenopathy and tumor-like sclerosing lesions in extranodal sites. • Lymphoma, a malignancy that originates from lymphocytes, can present with a variety of clinical manifestations, including painless swelling of lymph nodes and enlargement of different organs. • While patients with malignant lymphoma and IgG4-RD share certain overlapping clinical presentations, they exhibit significant differences in distinct features, including fever, patterns of lymph node and organ involvement, and various laboratory parameters.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder usually characterized by multi-organ involvement. Its pathogenesis is complex and involves genetic and environmental factors, while immune responses usually mediate organ damage and promote fibrosis, which is a key feature of the disease. IgG4 responses, however, are not exclusive to IgG4-RD and can be encountered in other diseases with phenotypes that partially overlap that of IgG4-RD. Although IgG4-RD has clinical and histological hallmarks, the lack of validated diagnostic criteria often makes the diagnosis challenging, requiring a multi-dimensional approach that integrates clinical, radiological and serological data. The present Review covers recent advances in the understanding of disease drivers and its clinical phenotypes, mainly focusing on the differential diagnosis with potential IgG4-RD mimickers, namely histiocytoses, lymphoproliferative disorders, systemic vasculitides and other immune-mediated conditions. The Review also provides a schematic approach to IgG4-RD treatment, including a brief overview of glucocorticoid-sparing agents and emerging therapies, from B cell-depleting monoclonal antibodies to cytokine-targeting drugs, the majority of which are currently under investigation in randomized clinical trials.

IgG4-related disease is a systemic autoimmune disorder characterized by multiorgan involvement, often presenting with pancreatic, renal, biliary, and salivary gland abnormalities. Diagnosis relies on clinical, serological, imaging, and occasionally histological findings. This report describes a 65-year-old male presenting with acute pancreatitis, bilateral renal lesions, and biliary strictures. Elevated serum IgG4 levels (3.76 g/L) confirmed the diagnosis using the 2019 ACR/EULAR and 2020 Comprehensive Diagnostic Criteria despite the lack of histological confirmation. Corticosteroid therapy led to rapid clinical and biochemical improvement, underscoring the importance of integrating multiple diagnostic modalities in managing IgG4-related disease and demonstrating the effectiveness of early intervention.

The tumor microenvironment has shown abilities to influence the progression and prognosis of intrahepatic cholangiocarcinoma (iCCA). However, little is known about the effect of IgG4+ plasma cells in iCCA.

We stained IgG4+plasma cells by immunohistochemistry and performed Kaplan-Meier survival analysis to detect the prognostic value. We also stained CD3, CD4, CD8 and Foxp3 positive T cells to explore its associations with IgG4+plasma cells.

We found that tumor infiltrated IgG4+plasma cells were associated with poor prognosis of iCCA, rather than IgG4+plasma cells in adjacent liver tissue. The number of IgG4+plasma cells was associated with CD8+ T cells. We divided the iCCA patients into 3 groups by IgG4+plasma cells to CD8+ T cells ratio. The group I (IgG4-/CD8+) had the best prognosis. The group II (IgG4-/CD8- or IgG4+/CD8+) and group III (IgG4+/CD8-) were independent risk factors of recurrence-free survival (HR = 1.69, group II; HR = 2.11, group III) and overall survival (HR = 1.76, group II; HR = 2.38, group III) compared with group I.

We examined the distribution of IgG4+ plasma cells in iCCA and discovered its prognostic utility when combined with CD8+ T cell distribution in iCCA.

The perinephric myxoid pseudotumor of fat (PMPF) is an uncommon benign neoplasm characterized by a favorable prognosis. To date, 21 cases of PMPFs have been reported worldwide, and their detailed characteristics have not been fully elucidated. We report the 22nd case of PMPF, which is the first case in China and happened in a 54-year-old male with a 5.6 cm mass located in the lower inner aspect of the right kidney. The patient underwent a minimally invasive robot-assisted laparoscopic resection of the renal mass. Postoperative histopathological, immunohistochemical, and genetic testing results confirmed the diagnosis of PMPF. No evidence of recurrence was found during a follow-up period of 6 months postoperatively based on clinical and imaging data. This is a report of an unusual case of PMPF with an up-to-date review. According to the latest systematic review and clinical confirmation, PMPF is strongly associated with chronic kidney disease, which is further confirmed by our case. For PMPF, combining imaging methods and immunohistochemical staining is suggested, which may prove beneficial in clinical practice.

IgG4-related cholangitis (IRC) is a chronic cholestatic liver disease that often occurs concomitantly with autoimmune pancreatitis type 1. Both conditions are manifestations of IgG4-related disease, a systemic autoimmune-mediated fibroinflammatory disorder. Patients often present with jaundice and weight loss, mimicking hepatobiliary malignancies, such as cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer. Accurate diagnosis is challenging due to the absence of pathognomonic findings but can be achieved using the HISORt criteria (histology, imaging, serology, other organ involvement, and response to immunosuppressive therapy). Early diagnosis is critical to avoid unnecessary surgery and prevent progression to liver fibrosis or cirrhosis. IRC responds well to corticosteroid therapy, though relapses are common, necessitating long-term immunosuppressive treatment in many cases. Steroid-sparing agents for remission induction and maintenance therapy comprise immunomodulators, such as azathioprine, as well as B-cell depletion therapies, such as rituximab. This review provides a structured clinical overview of the diagnosis, differential diagnosis, and therapy, including novel therapeutic options, such as inebilizumab, for this rare yet severe condition. A key focus is on long-term surveillance strategies, which include laboratory tests, imaging (contrast-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography, ultrasound, endosonography), and, particularly in patients with fibrotic bile duct strictures, endoscopy (endoscopic retrograde cholangiopancreatography, cholangioscopy).

Immunoglobulin G4-related disease (IgG4-RD) is a distinct immunoinflammatory disorder of unknown aetiology that may involve one or more organs, either synchronously or metachronously. Nonetheless, the pathophysiological mechanism is complex and poorly understood. The hepatobiliary manifestations of IgG4-RD [IgG4-hepatobiliary (IgG4-HB)], per se, have been sporadically reported in the literature. We describe the clinicoradiological, histomorphological, serological, and therapeutic data of 16 cases of IgG4-HB diagnosed on needle core liver biopsies applying 2021 Japanese guidelines. These included 11 cases of IgG4-sclerosing cholangitis (IgG4-SC), two with IgG4-sinusoidal dilatation and congestion (IgG4-SDC) in the absence of increased IgG4+ plasma cells in tissue but raised in serum, and three cases of IgG4-autoimmune hepatitis (IgG4-AIH). There was a male preponderance (M/F=11/5), with a median age at diagnosis of 49.5 years (13-73). On imaging, mass lesions mimicking a pseudotumour (n=6) or even cholangiocarcinoma (n=3) and biliary stricture (n=9) were common in the IgG4-SC subgroup. There was a positive but insignificant correlation between serum and tissue IgG4 levels (Spearman r=0.24, p=0.37), although increasing serum IgG4 levels were associated with biliary stricture (p=0.653). There was a satisfactory response to steroid therapy among 12 of 14 cases (median duration of follow-up 16.5 months). To the best of our knowledge, this represents the largest histomorphological series of IgG4-HB on needle biopsy from a single tertiary care centre in India. A larger prospective study with longer follow-up data is needed to validate our observations.

We aimed to report the characteristics of paediatric IgG4-related disease (IgG4-RD) through a multicentre registry, to assess disease clusters, and to evaluate the performances of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria in this cohort.

Data of IgG4-RD patients in 13 paediatric rheumatology centres were recorded to a web-based registration system. The diagnosis of IgG4-RD was made according to the 2011 comprehensive diagnostic criteria.

Thirty-five children (19 females and 16 males) with IgG4-RD were enrolled. The median age at diagnosis was 13.3 (25p-75p; 9.9-15.2) years. The most common organ involvement was the eye (n = 21, 60%), followed by lymph nodes (n = 12, 34.3%), musculoskeletal system (n = 12, 34.3%), and neurological system (n = 9, 25.7%). We identified three clusters in our study cohort: those with eye involvement (n = 11, 31.4%), those with eye involvement and neurological findings (n = 15, 42.9%), and those with pancreato-hepatobiliary disease and lymph node involvement (n = 9, 25.7%). Serum IgG4 levels were high in 19 out of 28 patients (67.8%). All patients except one received corticosteroid treatment, and azathioprine was the most preferred drug as a steroid-sparing agent. The sensitivities of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were 5.7% and 88.5%, respectively.

IgG4-RD has a wide variety of clinical manifestations; however, in children, the most common presentation was orbital involvement. The 2020 RCD criteria had a better performance whereas the 2019 ACR/EULAR classification criteria performed poorly in paediatric patients.

We present a 50-year-old female with IgG4-related disease (IgG4-RD) of the urethra. She had been diagnosed with IgG4-RD involving the pancreas, lacrimal glands, salivary glands, kidneys, and right breast 5 years earlier, which had remitted after steroid treatment. In recent months, she had experienced urinary incontinence. Her local physician noted a urethral stricture. Magnetic resonance imaging (MRI) showed a lesion surrounding the urethra, with a slightly high signal intensity on T2-weighted and short-term inversion recovery images, and a mildly high signal intensity on diffusion-weighted images. Accordingly, IgG4-RD involving the urethra was suggested. Her serum IgG4 level was slightly elevated at 127 mg/dL, which is below the normal upper limit of 135 mg/dL. A transurethral biopsy revealed significant lymphocytic and IgG4-positive plasma cell infiltrates (50-80/high-power field), fibrosis, and obstructive phlebitis. Thus, IgG4-RD of the urethra was confirmed. A systematic search including CT and MRI did not reveal any new gross lesions. Steroid therapy improved her symptoms within a few days. Follow-up MRI revealed shrinking of the urethral lesion and lower signal intensity on T2-weighted images. IgG4-RD with urethral lesions is extremely rare. No cases of diagnosis of IgG4-RD urethral lesions based on MRI findings before biopsy have been reported to date. When a middle-aged woman presents with uniform circumferential urethral lesions, IgG4-RD should be considered in the differential diagnosis. Here, we report detailed imaging findings and radiological differential diagnoses, and discuss relevant literature.

IgG4-related diseases are fibroinflammatory disorders affecting multiple organs, with autoimmune pancreatitis (AIP) being a common manifestation. Steroid therapy is effective in inducing remission but has complex effects on glucose metabolism. Diabetes occurs in 40% to 80% of AIP patients, and steroids can worsen glucose tolerance, although some studies suggest they may improve pancreatic endocrine function. An 81-year-old man with elevated IgG4 levels and imaging findings consistent with AIP initially declined treatment. His condition worsened, leading to poor glycemic management and referral to our hospital. Imaging confirmed AIP and tests showed impaired insulin and glucagon secretion. He was diagnosed with pancreatic diabetes secondary to IgG4-related AIP. Initially, intensive insulin therapy was administered, but within 3 months, both insulin and glucagon secretion declined significantly in the arginine-stimulation test, necessitating steroid therapy with prednisolone (35 mg/day) for the AIP. The high dose of steroid treatment enhanced both insulin and glucagon secretion capacities but gradually declined with dose tapering. On the other hand, although steroid therapy poses a temporary risk of hyperglycemia, it likely prevented further deterioration of pancreatic endocrine function.

This case highlights the possibility that Immunoglobulin G4-related disease (IgG4-RD) lesions can also occur in the sternoclavicular joint. If a neoplastic lesion is found in the sternoclavicular joint, a biopsy should be attempted to diagnose IgG4-RD as a differential.

Acute pancreatitis stemming from IgG4-Related Disease (IgG4-RD) seldom coincides with Systemic Lupus Erythematosus (SLE), highlighting the importance of investigating autoimmune conditions in patients with IgG4-RD. We present the case of a 57-year-old male with a medical history notable for hypertension, photosensitivity, arthritis, and malar rash, who presented with 6 weeks of persistent epigastric pain. Computed Tomography (CT) of the abdomen revealed hallmark features such as fat stranding around the pancreatic tail and gallbladder wall thickening, confirming the diagnosis of acute pancreatitis and cholecystitis. Post-cholecystectomy, histopathological examination of the gallbladder displayed IgG4-positive staining in multiple vessels, accompanied by perivascular inflammation and fibrinoid necrosis infiltrated by lymphocytes and neutrophils, confirming the diagnosis of IgG4-RD. Subsequent evaluation prompted by systemic manifestations revealed an ANA titer of 1:5120 and a dsDNA titer of 1:80, leading to the diagnosis of SLE. The patient later developed mononeuropathy, which improved upon initiation of immunosuppressive therapy. This case underscores the intricate interplay between IgG4-RD and SLE, an association documented to a limited extent in literature, thereby emphasizing the imperative of considering alternative autoimmune diseases with manifestations akin to IgG4-RD.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory condition characterized by tumor-like lesions, dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells, and often elevated serum IgG4 levels. Ocular involvement is common, typically affecting the lacrimal glands and extraocular muscles. However, intraocular manifestations such as uveitis and scleritis are less frequent. We report the case of a 66-year-old Japanese man presenting with bilateral uveitis, posterior scleritis, serous retinal detachment, and choroidal thickening, initially mimicking intraocular lymphoma. His serum IgG4 and soluble interleukin-2 receptor levels were markedly elevated. Magnetic resonance imaging showed posterior eyeball wall thickening with restricted diffusion and diffuse thickening of the nasal mucosa and hard palate mucosa. Computed tomography revealed an asymptomatic retroperitoneal mass around the aorta. Salivary gland biopsy confirmed dense lymphoplasmacytic infiltration with increased IgG4-positive plasma cells (80/HPF) and an elevated IgG4/IgG ratio (~50%), consistent with IgG4-RD. The patient responded well to oral corticosteroid therapy with improvement in visual acuity. This case highlights the rare but important presentation of intraocular manifestations in IgG4-RD.

IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease.

In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission.

A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo.

Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).

Autoimmune pancreatitis (AIP), which is considered the pancreatic expression of a systemic immunoglobulin G4-related disease, is characterized by excessive infiltration of plasmacytes bearing immunoglobulin G4 and a unique form of fibrosis in multiple organs. This relatively new disease entity has garnered great attention from clinicians, but its pathophysiology remains poorly understood. Recent discoveries indicate that plasmacytoid dendritic cell activation followed by robust production of type I interferon and interleukin-33 plays a key role in driving chronic fibro-inflammatory responses in both murine and human AIP. Furthermore, the compositional alterations in the gut microbiota, known as intestinal dysbiosis, triggered plasmacytoid dendritic cell-driven pathogenic type I interferon responses. Intestinal dysbiosis is associated with a breakdown in intestinal barrier function; thus, we examined whether the latter condition affects the development of experimental AIP. Our recent research has revealed that intestinal barrier disruption worsens experimental AIP by facilitating the translocation of pathogenic bacteria, such as Staphylococcus sciuri, to the pancreas from the gut. These results indicate the "gut-pancreas axis" underlies the immunopathogenesis of AIP, and the maintenance of intestinal barrier integrity can prevent the worsening of AIP by inhibiting pancreatic colonization by harmful gut bacteria. In this mini review, the interactions between AIP development and gut microbiota are discussed with the aim of providing useful information not only for researchers but also for clinicians.

Aortitis and periaortitis refer to the inflammation of the aortic wall and the surrounding tissues. Both conditions are associated with various diseases and express nonspecific manifestations. Early diagnosis and treatment are crucial to improve the prognosis of the disease. This study aimed to assess the causes and main clinical features of aortitis and periaortitis in patients from a single centre in Spain. Observational, retrospective study of patients diagnosed with aortitis or periaortitis at a Spanish referral center over the last decade. 134 patients (87 female; mean age of 55.1 ± 9.1 years) were recruited, 132 of which had aortitis and two periaortitis. Aortitis was associated with giant cell arteritis (n = 102), Takayasu's arteritis (n = 6), IgG4-related disease (n = 6), infectious diseases (n = 3), malignancy (n = 1), drugs (n = 1), isolated aortitis (n = 1), and other immune-mediated inflammatory diseases (IMIDs) (n = 12). IMIDs included were Sjögren's syndrome (n = 2), sarcoidosis (n = 2), rheumatoid arthritis (n = 2), axial spondyloarthritis (n = 2), inflammatory bowel disease (n = 1), primary biliary cirrhosis (n = 1), idiopathic pulmonary fibrosis (n = 1), and polyarteritis nodosa (n = 1). Periaortitis was due to idiopathic retroperitoneal fibrosis in both cases. Imaging techniques used for diagnosis included 18F-FDG PET/CT scan (n = 133), CT-angiography (n = 44), and/or MRI-angiography (n = 33). Polymyalgia rheumatica (52.2%) and asthenia (53.7%) were the most common manifestations, followed by limb claudication (23.9%) and inflammatory back pain (26.9%). Acute-phase reactants were typically increased. Aortitis is a common condition and may be associated with multiple non-infectious diseases. Its clinical presentation is often unspecific, requiring a high level of suspicion to get an early diagnosis and treatment.

Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disease with idiopathic and secondary causes. Idiopathic disease is more common and is believed to be immune mediated; associations with autoimmune diseases and/or inflammatory disorders such as IgG4 related disease are often present. Common complications include hydronephrosis and venous stenosis and/or thrombosis. Due to its nonspecific clinical presentation, imaging is vital for diagnosis; in addition, imaging may help distinguish idiopathic from secondary causes and can aid in distinguishing early/active disease from chronic/inactive disease. Magnetic resonance imaging is the preferred imaging modality to stage and monitor the disease, though CT and PET/CT imaging may also be of value. While the imaging findings can overlap with other diseases, there are some characteristic findings which can favor RPF. However, a biopsy is needed for a definitive diagnosis.The following article discusses the clinical features, imaging appearances across modalities, associated complications, potential diagnostic pitfalls, and treatment approaches for RPF. The role of advanced imaging techniques, such as diffuse weighted imaging and 18F-FDG PET/MRI, in the evaluation of RPF will also be included.

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells.1 We report the case of a 56-year-old man who presented with nasal obstruction for 5 years. Rhinoscopy revealed hypertrophy and sclerosis of the inferior turbinate, whereas computed tomography revealed inflammation of the anterior ethmoid sinus and frontal sinuses. An endoscopic inferior turbinectomy was performed, and IgG4-RD was definitively diagnosed based on the histopathological features of the turbinate tissue. Prednisolone was administered postoperatively. IgG4-RD presenting with hypertrophy and sclerosis of the inferior turbinate is rare. Awareness of IgG4-RD originating in the sinonasal cavity is essential to avoid delayed diagnosis.

Immunoglobulin G4-related disease (IgG4-RD), a rare immune-mediated disease affecting multiple organs, rarely involves the pleura. This study presents a case of pleural IgG4-RD and reviews the literature to elucidate the patient population, manifestations, and diagnostic and treatment characteristics of pleural IgG4-RD. This study aimed to expand the existing case database of pleural IgG4-RD and enhance the understanding and management of this rare disease.

We report a case of IgG4-RD involving the pleura in an 80-year-old woman with a weight of 62 kg and a body mass index (BMI) of 23.2 kg/m2. Additionally, we reviewed pleural biopsy-confirmed IgG4-RD cases in the PubMed, Scopus, Web of Science, Embase, and Science Direct databases.

Forty-one patients with IgG4-RD confirmed by pleural biopsy were included. The median age was 69 years, with male predominance (31, 75.6 %). The most common manifestations were pleural effusion (37, 90.2 %) and dyspnea (26, 63.4 %). Elevated serum IgG4 levels were observed in 38 patients (92.7 %), with a median value of 398.2 mg/dL. Twenty-six patients met two histological criteria for IgG4-RD. Thirty-seven patients received glucocorticoid therapy, 34 of whom achieved clinical improvement.

IgG4-RD with pleural involvement mainly manifests as pleural effusion and dyspnea, responding to glucocorticoid therapy. The possibility of this disease should be considered in patients with pleural effusion and enlargement of tissues or organs. Medical staff should attach importance to the application of the Comprehensive Geriatric Assessment (CGA) and the Geriatric Interdisciplinary Team (GIT) in the disease management of older patients.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease that is believed but not confirmed to have an autoimmune origin. Since its discovery nearly two decades ago, our understanding of its pathophysiology and clinical manifestations has grown substantially. Early diagnosis and treatment of this elusive disease can prevent substantial organ damage from end-stage fibrosis. This underscores the importance of prompt recognition, full characterization, and astute management. The American College of Rheumatology/European League Against Rheumatism Classification Criteria provide a framework for approaching the diagnosis of IgG4-RD even though they were not intended for diagnostic purposes. The approach to diagnosis involves recognizing the typical disease manifestations and incorporating clinical, radiological, serological, and histopathological information. The exclusion of disease mimickers, particularly malignancy and other inflammatory conditions, is essential. Both glucocorticoids and B cell depletion are effective at inducing remission in IgG4-RD in most patients. The optimal approach to the use of these agents is now being defined in clinical trials.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by IgG4-positive plasma cell infiltration that can affect multiple organs, including the cardiovascular system. The diagnosis of IgG4-RD relies on a combination of clinical, serological, radiological and pathological findings. However, due to the varied and insidious clinical presentations, normal IgG4 levels in a significant percentage of patients and frequent multi-organ involvement, imaging plays a crucial role in the diagnosis of IgG4-RD. The aim of this study is to comprehensively examine the imaging findings in IgG4-related cardiovascular disease for accurate diagnosis and appropriate treatment.

A systematic search was conducted across the electronic databases PubMed, Scopus, Embase and Web of Science, to 1 September 2023, following PRISMA guidelines, searching for studies reporting detailed cardiovascular imaging findings in IgG4-RD.

The search yielded 68 studies (60 case reports, 5 case series, 2 cross-sectional, 1 case-control) with 120 cases of cardiovascular IgG4-RD. Most of the cases were male, averaging 62.8 years. The common initial symptoms were dyspnoea and chest pain. The most common imaging finding was vasculopathy, including vessel wall thickening, periarteritits, periaortitis, aortitis, stenosis, ectasia, aneurysm formation, intramural haemorrhage, fistula formation and dissection, followed by pericardial involvement and mediastinal masses. Case series and cross-sectional studies also showed vasculopathy to be the most common finding on various imaging modalities, including angiography and PET/CT, highlighting the complex pathology of IgG4-RD.

This study evaluated current IgG4-RD articles, revealing a higher prevalence in men and vasculopathy as the most common cardiovascular complication.

This study aimed to investigate the expression condition of a proliferation-inducing ligand (APRIL) in lacrimal gland lesions of patients with IgG4-associated ophthalmic diseases (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma.

Fifteen patients with IgG4-ROD, 3 with MALT lymphoma, and 1 with elevated IgG4 with lacrimal gland lesions, treated in West China Hospital of Sichuan University from April 2022 to November 2023, were included. Immunofluorescence staining was used to detect the expression of APRIL in the specimen of lacrimal gland.

The average expression level of APRIL in patients with lacrimal gland lesions of IgG4-ROD and MALT lymphoma were 8471.12 pixels/HPF and 2950.78 pixels/HPF respectively. The positive rates of APRIL were 10.49% and 7.23% respectively. CD138 and APRIL were colocalized, and the positive rate of their colocalization was 8.83%, and the positive areas of colocalization coincidence was 946.84 pixels/HPF in patients with IgG4-ROD. CD20 and APRIL were colocalized, and the positive rate of their colocalization was 7.04%, and the positive areas of colocalization coincidence was 949.78 pixels/HPF in patients with MALT lymphoma. We also found that the expression level and the positive rate of APRIL were positively correlated with the level of serum IgG4 in IgG4-ROD patients (r=0.5820, P=0.029; r= 0.6261, P=0.017; respectively). In addition, the positive rate and the positive areas of CD138 and APRIL colocalization were also positively correlated with serum IgG4 level (r=0.6420, P=0.013; r= 0.5673, P=0.034; respectively).

APRIL is highly expressed in lacrimal gland lesions of patients with IgG4-ROD and MALT lymphoma. This overexpression may facilitate the enrichment of CD138+ plasma cells and is associated with elevated serum IgG4 levels in patients with IgG4-ROD. Additionally, it may promote the proliferation of CD20+ B lymphocytes in patients with MALT lymphoma.APRIL may play a certain role in the possible transformation of IgG4-ROD into MALT lymphoma.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterised by IgG4-positive plasma cell infiltration into different tissues and organs. Among the heterogeneous clinical features of IgG4-RD, serositis, including pleural and pericardial effusions, is a rare and poorly understood presentation. We described a woman in her late 70s who developed recurrent chylothorax and failed to respond to corticosteroids, immunosuppressives and intrapleural octreotide injection while being treated for newly diagnosed IgG4-RD with serositis as the only manifestation. Her chylothorax was thought to be due to fibroinflammatory damage of the lymphatic duct system from her IgG4-RD, as other differential diagnoses have been largely excluded. We demonstrate the difficulty in establishing the diagnosis of IgG4-RD when only serositis is present, the importance of meticulous workup ruling out other causes and clinical judgement in identifying disease complications versus evaluating alternative diagnoses.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition of unknown etiology characterized by lymphocytic infiltration, fibrosis, and infiltration of IgG4-positive plasma cells. It affects various organs, including the pancreas and salivary glands. Immunological abnormalities are suspected to play a role in its pathogenesis, and there is an epidemiological link to allergic conditions and type 2 inflammation. This study focused on the expression of thymus and activation-regulated chemokine (TARC)/CCL17, which is involved in the migration of T helper 2 and/or regulatory T cells, in salivary gland tissues of patients with IgG4-RD. We analyzed 60 salivary gland biopsy samples obtained from patients at Sapporo Medical University Hospital between 2015 and 2020. Immunohistochemical analysis revealed TARC/CCL17 positivity in 87.2% of histologically confirmed IgG4-RD cases and negativity in 84.6% of histologically unconfirmed but clinically suspected IgG4-RD cases. There was a significant correlation between histologically confirmed IgG4-RD and TARC/CCL17 expression, suggesting its potential diagnostic utility and possible involvement in the pathogenesis of IgG4-RD.

Background: IgG4-related disease is a rare, chronic inflammatory disorder characterized by lymphoplasmacytic infiltration, 'storiform' fibrosis, and elevated IgG4 levels in affected tissues. This disease has a broad and heterogeneous clinical spectrum that includes four main phenotypes: pancreatic-hepatobiliary disease, retroperitoneal/aortic fibrosis, head and neck disease, and Mikulicz syndrome. Case Description: An 85-year-old male patient with a clinical presentation, which is unusual outside Asia, of IgG4-related disease phenotype Mikulicz syndrome, characterized by bilateral dacryoadenitis, orbital pseudotumor, and no evidence of significant systemic participation. Despite extensive involvement in the orbital and glandular region, the patient did not develop serious organ complications, a behavior rarely documented in the literature. Despite the serum IgG4 levels being normal (<135 mg/dL), the clinical and radiological picture suggested IgG4-RD, emphasizing the need for a biopsy for a definitive diagnosis. Histopathological examination revealed a dense lymphoplasmacytic infiltrate, storiform fibrosis, and more than 40% IgG4-positive cells, confirming the diagnosis. Results: Treatment with prednisone was initiated alongside azathioprine for long-term control. Calcium and vitamin D3 supplementation were added to prevent glucocorticoid-induced osteoporosis. Remarkable clinical improvement was observed within 24 h, with progressive orbital and glandular symptoms resolution. Over a year, the patient exhibited complete resolution of the orbital tumors, total recovery of vision, and no relapses. The only sequelae observed were dry eye. Conclusions: This case highlights the need to consider IgG4-RD with normal serum IgG4 levels, the importance of histopathology for diagnosis, and the efficacy of steroids as first-line treatment. A multidisciplinary approach is essential for timely treatment.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic, progressive inflammatory disease with fibrosis that affects multiple organs, while symptomatic peripheral nerve invasion is very rare. Here we present a Chinese male aged 77 years with peripheral neuropathy, membranous nephropathy, and interstitial lung disease diagnosed with IgG4-RD. The patient exhibited elevated levels of IgG4 and IgG4/IgG ratios in the blood. A chest computed tomography (CT) showed interstitial pneumonia in both lungs and multiple mediastinal lymphadenopathy. Additionally, electromyography shows neurogenic lesions in both lower extremities and axonal lesions involving motor nerves. Biopsies of the kidney showed membranous nephropathy with numerous IgG4-positive plasma cells. Patients treated with cyclophosphamide and high-dose methylprednisolone showed improvement in neuropathy, proteinuria, and interpulmonary severity. This case demonstrates the unusual presentation of IgG4-RD where peripheral neuropathy is the main feature with multisystem involvement but without mass lesions. It underscores the varied clinical manifestations of this disease.

Retroperitoneal fibrosis (RPF) is a rare condition marked by inflammation and fibrosis affecting the peritoneal and retroperitoneal soft tissues. In recent years, the identification of IgG4-related diseases has brought to light a significant association with fibrous disorders, including RPF, which were once considered independent. In this comprehensive cohort study, we performed a comparative analysis of the demographic, clinical, laboratory, histopathological, and therapeutic characteristics between patients with IgG4-related RPF and those with idiopathic retroperitoneal fibrosis (iRPF).

We performed a retrospective analysis of 117 patients diagnosed with RPF at the First Affiliated Hospital of Naval Medical University between July 2007 and July 2023.

Demographic, clinical, laboratory, histopathological, and therapeutic characteristics of 70 iRPF patients and 47 IgG4-related patients were systematically compared. The IgG4-related group exhibited an older age of onset, with a predominant occurrence among adult males. Significantly elevated levels of eosinophilia and IgE were observed in the IgG4-related group. Most patients across both groups displayed elevated CRP and ESR levels. Furthermore, at the time of diagnosis, the IgG4-related group had higher serum creatinine and lower levels of complement. The most prevalent clinical manifestation in both groups was flank pain. The proportion of lymphoplasmic infiltration and storiform fibrosis in IgG4-related RPF group was significantly higher. The IgG4-related RPF group had significantly higher IgG4-positive plasma cell count, IgG4/total IgG ratio, and eosinophils count than that in iRPF group.

We conducted a comparative analysis of demographic, clinical, laboratory, histopathological, and therapeutic differences between the iRPF patients and the IgG4-related patients. Clarifying the distinctive characteristics of these two groups will contribute to a better understanding of the condition and facilitate the development of specific treatment strategies tailored to each group. Key Points • Identification of distinct clinical features and outcomes between IgG4-related and iRPF patients in a large retrospective study.

It is often challenging to differentiate between IgG4-related disease (IgG4-RD) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) due to their similar clinical presentations. Recently, growing evidence has suggested a strong connection between AAV and IgG4-RD.

A 60-year-old woman was transferred to our hospital with fever and kidney dysfunction. Abdominal computed tomography revealed widespread infiltrative lesions in both kidneys.

Laboratory tests and subsequent renal biopsy confirmed both antineutrophil cytoplasmic antibody-associated vasculitis and IgG4-related disease.

We initiated plasmapheresis, oral cyclophosphamide, and high-dose glucocorticoids for treatment. Despite this, the patient's condition worsened, requiring emergency hemodialysis.

After 3 months of continued immunosuppressive treatment, renal function improved and hemodialysis was discontinued.

Our case showed an overlap of AAV and IgG4-RD, which might support the hypothesis of an overlap syndrome of AAV and IgG4-RD. Clinicians should have a high index of suspicion when diagnosing fever of unknown origin, with the possibility of overlapping AAV and IgG4-RD.

IgG4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. While primarily affecting the pancreas, bile ducts, and salivary glands, IgG4-RD can also involve the gastrointestinal tract, raising questions about its relationship with inflammatory bowel disease (IBD). Recent studies suggest that patients with IBD may exhibit histological and serological features consistent with IgG4-RD, such as a dense lymphoplasmacytic infiltration, a storiform-type of fibrosis and a prominent IgG4 immune response. This overlap represents a diagnostic challenge, as differentiating between primary IBD and IgG4-RD involving the gut is crucial for appropriate treatment. Further research is essential to delineate the prevalence of tissue and serum IgG4 expression in patients with IBD. This approach could classify subtypes of IBD, enabling advancements in non-invasive diagnosis and monitoring as well as personalized therapies. The purpose of this review is to summarize the available evidence regarding intestinal involvement in IgG4-RD and the role of both serum and tissue IgG4 in inflammatory bowel diseases IBD.

Graves' ophthalmopathy (GO) with elevated IgG4 levels has different characteristics from patients with GO who do not have elevated IgG4 levels, but the study findings are contradictory. The goal of this study was first to investigate the relationship between IgG4/IgG and IgG4 levels and the occurrence of GO and then to investigate the clinical and laboratory characteristics of patients with GO who had elevated IgG4 levels. This study control group consisted of 57 Graves' disease(GD)patients with no complicated ocular disease and a median followup of 54.41 months, while the experimental group included 171 GO patients. The clinical and laboratory characteristics of the GD and GO groups were compared. Using an IgG4/IgG cut-off value of 8%, the GO patients were divided into two groups: high IgG4/IgG and low IgG4/IgG, and the differences in clinical and laboratory characteristics between these two groups, as well as between the GO patients before and after 3 months of treatment, were analyzed. The study results show that serum IgG4/IgG levels were independently correlated with the occurrence of GO, but not significantly correlated with GO activity. Patients with high IgG4/IgG levels of GO exhibit distinct characteristics, which may be associated with an unstable balance of lymphocyte subsets.

Immunoglobulin G4-related disease (IgG4-RD) share clinical features with primary Sjögren's syndrome (pSS). This study aimed to identify altered serological parameters and potential biomarkers of IgG4-RD and pSS.

Forty IgG4-RD patients, 40 pSS patients, and 40 healthy controls (HC) were enrolled in this study. Routine serological parameters and clinical manifestations were assessed. IgG subclasses (IgGSc) were detected using a Siemens BN P, and lymphocyte subsets were analyzed using flow cytometry. Cytokines assays were performed using cytometric bead array.

Compared to pSS, IgG4-RD patients had higher IgG4 (p <0.001) and lower IgG1 (p =0.014). The natural killer (NK) cells (p = 0.004), CD4+ T cells (p = 0.028), and TBNK cells (p = 0.040) were increased in IgG4-RD compared to pSS. IgG4 used to differentiate IgG4-RD from pSS produced an area under the curve (AUC) of up to 0.952. In addition, we compared serum parameters, immune cells, and cytokines of IgG4-RDwith mouth dryness or eye dryness with those of pSS with the same symptoms, and similar serological changes were observed. IgG4-RD patients with mouth dryness had higher IgG4 (p <0.001) and Th cells (p = 0.016) but lower IgG1 (p = 0.009) compared to pSS with dry mouth. IgG4-RD patients with eye dryness had higher levels of IgG4 (p <0.001), Treg cells (p = 0.037), and NK cells (p = 0.017) than pSS patients with eye dryness. Moreover, IgG4-RD patients with mouth and eye dryness had higher levels of B (p = 0.006), Th (p = 0.026), Th2 (p = 0.007), and Treg cells (p = 0.028) than IgG4-RD patients without mouth and eye dryness.

Immune system disorder is an outstanding feature of IgG4-RD, and its feature differ from pSS. Assessment of immune status is important in the diagnosis and differential diagnosis of IgG4-RD.

A 70-year-old man underwent nephrectomy for renal cell carcinoma followed by 3 cycles of pembrolizumab as adjuvant chemotherapy. Three months later, he complained of appetite loss. He was diagnosed with secondary adrenal insufficiency and pancreatic tumor. Amylase and immunoglobulin G (IgG) 4 levels were normal. The differential diagnosis poses challenges in distinguishing pancreatic cancer, renal cell carcinoma metastasis, and autoimmune pancreatitis, necessitating tumor resection surgery. A histological examination revealed IgG4-related sclerosing pancreatitis. Postoperatively, there was no recurrence of pancreatitis. It is essential to consider the potential development of IgG4-related diseases after the administration of immune checkpoint inhibitors.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems. Retroperitoneal fibrosis (RPF) is a rare condition characterized by the development of fibrous tissue in the retroperitoneal space. The coexistence of SLE and RPF is extremely uncommon, and this report aims to enhance understanding of this complex relationship.

A 32-year-old woman presented with sudden-onset syncope. Her medical history revealed a 5-year history of SLE, and imaging studies identified a retroperitoneal mass.

A comprehensive diagnostic workup, including magnetic resonance imaging (MRI) and biopsy, confirmed retroperitoneal fibrosis secondary to SLE.

The patient was treated with high-dose corticosteroids, immunosuppressive therapy, and the biologic agent rituximab.

The patient's symptoms markedly improved, and follow-up MRI demonstrated significant regression of the retroperitoneal lesion.

RPF associated with SLE is exceptionally rare. This case underscores the importance of early diagnosis and a coordinated multidisciplinary approach in managing such complex conditions. Glucocorticoid therapy remains the cornerstone of treatment, augmented by immunosuppressants and biologic agents when necessary.