Search

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4-RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype.

Background: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. Case presentation: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. Conclusions: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis is characterized by infiltration of the pancreas parenchyma by immunoglobulin G4 (IgG4)-positive plasma cells, chronic inflammation, and fibrosis. It can affect the entire body depending on the subtype. Distinguishing mass-forming type autoimmune pancreatitis from pancreatic cancer can often be challenging. A 60-year-old male presented to our outpatient clinic with abdominal discomfort. Computed tomography revealed a 4.8 cm mass in the pancreatic head obstructing the common bile duct. Endoscopic ultrasound-guided fine needle biopsy and endoscopic retrograde cholangiopancreatography with biliary drainage were performed. Pathological examination revealed no malignant cells, but more than 20 IgG4-positive cells were observed. Following two weeks of steroid treatment, the patient's symptoms improved, and follow-up imaging showed a reduction in the size of the pancreatic head mass. Herein, we report a case of mass-forming autoimmune pancreatitis initially misdiagnosed as pancreatic cancer. [ABSTRACT FROM AUTHOR]

Myocarditis is a potentially life-threatening inflammatory disease of the myocardium, often resulting from infectious and immune-mediated responses. Clinical presentation in severe cases often results in a devastating illness requiring extracorporeal membrane oxygenation support as a result of cardiogenic shock. Although endomyocardial biopsy is still considered the gold standard for diagnosis, it often reveals nonspecific lymphocytic infiltration. Because the precise cause is usually unknown, the initial treatment typically involves immunosuppression and frequent assessment of myocardial contractility. This report presents 3 rare cases of autoimmune diseases (polymyositis, immunoglobulin G4–related disease, and systemic lupus erythematosus) that require extracorporeal membrane oxygenation support as a result of fulminant myocarditis, including their follow-up periods.

Abstract Background To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. Case presentation A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. Conclusions This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.

Background Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. Methods This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. Results Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. Conclusion This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Abstract Background Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 105 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain. Case presentation This report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments. Conclusions The main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.

Abstract Background Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported. Case presentation A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications. Conclusion The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.

Abstract Immunoglobulin G4-related disease is a systemic immune-mediated disease with insidious evolution characterized by fibroinflammatory lesions over virtually any organ system. Despite the remarkable progression of knowledge, its etiology remains undefined. Due to its relapse-remitting pattern, it could accumulate irreversible damage, increasing comorbidities and mortality. This paper emphasizes key concepts for diagnosing and treating patients with this condition.

Objectives: Patients diagnosed with primary sclerosing cholangitis (PSC) but with characteristics of immunoglobulin G4 (IgG4)‐associated cholangitis (IAC) have been described. IAC often presents with biliary IgG4‐positive plasma cell (IgG4+ PC) infiltration and responds to corticosteroids. In PSC, the frequencies or implications of biliary IgG4+ PC are unknown. We aimed to characterize the phenomenon of biliary IgG4+ PC in patients with an established PSC diagnosis. Methods: Bile duct biopsies from 191 surveillance or therapeutic endoscopic retrograde cholangiography of 58 PSC patients were retrospectively analyzed for IgG4+ PC infiltration. Patients with ≥10 IgG4+ PC per high‐power field (HPF) were identified and characterized by clinical parameters, including serum IgG4 and cholangiographic presentations. Results: Altogether 39.7% of the PSC patients showed ≥10 IgG4+ PC/HPF in bile duct biopsies. Patients with biliary IgG4+ PC infiltration were significantly younger at diagnosis of PSC (P = 0.023). There was no association between biliary IgG4+ PC infiltration and transplant‐free survival (P = 0.618). Patients with IgG4+ PC infiltration in bile duct biopsies showed significantly higher baseline (P = 0.002) and maximum (P = 0.001) serum IgG4 compared to those without. Biliary IgG4+ PC infiltration was associated with high‐grade bile duct strictures (P = 0.05). IgG4‐positive plasma cell infiltrations were found multifocally in 72.7% of this subgroup of PSC patients. Conclusions: IgG4+ PC ≥10/HPF can be found abundantly in bile duct biopsies in PSC. Histological findings correlated with serum IgG4, age, and high‐grade bile duct strictures. IgG4+ PC was located multifocally, hinting at a systemic biliary phenotype. [ABSTRACT FROM AUTHOR]

Background: Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. Methods: This cross-sectional study included 426 adult patients with PTC (=1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm² were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. Results: Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm² was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. Conclusion: This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies. [ABSTRACT FROM AUTHOR]

A 68-year-old man was diagnosed with pericarditis associated with immunoglobulin G4-related disease and was administered prednisolone 2 years prior to presentation. During the process of tapering off from prednisolone 1 year later, edema of the lower legs and pleural effusion worsened. He gradually developed dyspnea on exertion, and laboratory examinations revealed elevated liver enzyme levels. Diuretics were administered; however, the symptoms did not resolve. Transthoracic echocardiography and cardiac catheterization revealed findings consistent with those of constrictive pericarditis. Pericardiectomy was considered and the perioperative risks due to possible recovery from liver dysfunction were discussed. Combinational elastography was subsequently performed. The results indicated the absence of liver fibrosis, suggesting that liver dysfunction was attributable to liver congestion; thus, the liver dysfunction was considered reversible. Subsequently, pericardiectomy was performed. Given that constrictive pericarditis can lead to liver dysfunction due to congestion, the perioperative risk is often controversial when considering surgical interventions. Combinational elastography may be useful in the preoperative evaluation of patients with cardiac diseases complicated by liver dysfunction to distinguish liver fibrosis, understand the pathogenesis of liver dysfunction, and determine subsequent treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported. Case presentation: A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications. Conclusion: The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection. [ABSTRACT FROM AUTHOR]

Objectives: Few studies have examined factors affecting steroid-free remission (SFR) in patients with immunoglobulin G4–related disease (IgG4-RD). The aim of this study was to investigate clinical factors affecting SFR in IgG4-RD. Methods: The medical records of 68 patients who met the 2020 revised comprehensive diagnostic criteria for IgG4-RD were reviewed retrospectively. SFR was defined as remission maintained for at least 6 months without corticosteroids. Cox regression analysis was performed to examine the associations between SFR and various clinical factors. The relapse rate after SFR was examined using the log-rank test. Results: After a median follow-up of 36 months, 30.9% (21/68) of patients with IgG4-RD achieved SFR. Multivariate Cox regression analysis revealed that IgG4-RD diagnosed by complete resection rather than by common diagnostic procedures was the only factor positively associated with SFR (hazard ratio, 7.41; 95% confidence interval, 2.23–24.60; P = .001). Furthermore, relapse after attainment of SFR was significantly less common in the group that underwent complete resection than in the group that did not undergo complete resection (log-rank P = .006). Conclusions: Patients with IgG4-RD diagnosed by complete resection had a higher likelihood of achieving SFR and a lower rate of relapse after attaining SFR. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 (IgG4)-related disease is an immune-mediated disorder that commonly manifests in the salivary glands. As a recently described disorder, the description and classification of IgG4-related disease is an ongoing process. Diagnosis of IgG4-related disease requires integration of clinical history, histopathology, and radiographic findings, including ultrasonography and sialography. In this case report, we correlate parotid ultrasonographic and sialographic findings in a patient with proven IgG4-related disorder confirmed from analysis of previous submandibular gland resections. We aim to highlight the utility of multimodality imaging in the diagnosis of IgG4-related disease. [ABSTRACT FROM AUTHOR]

Abstract Objectives To evaluate the performance of radiology-related inclusion criteria of the 2019 ACR-EULAR classification system in the diagnosis of IgG4-related disease (IgG4-RD). Methods This retrospective single-institution study included patients who received a diagnosis of IgG4-RD between January 2010 and December 2020. Two abdominal radiologists independently reviewed baseline imaging studies and scored radiology findings according to the 2019 ACR-EULAR classification criteria. Additional scores were assigned based on serological, histopathological, and immunostaining features. Results Seventy-four patients (58 males and 16 females) with a mean age of 59.3 ± 13.9 years diagnosed with IgG4-RD were included. 51/74 (68.9%) were classified as having IgG4-RD according to the 2019 ACR-EULAR classification criteria. To reach a score ≥ 20 in these 51 patients, the radiology domain was sufficient in 20/51 (39.2%) and adding the serology domain was required for another 20/51 (39.2%). The remaining 11/51 patients (21.6%) required the histopathology and immunostaining domains. Radiological involvement of two or more organs at presentation was significantly associated with a score of ≥ 20 and seen in 43/51 (84.3%) compared to 5/23 (21.7%) of the non-classified group (p

Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications.

Objective To analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of immunoglobulin G4 (IgG4)-related autoimmune pancreatitis (AIP), to improve the understanding of the imaging features of this disease, and to reduce imaging misdiagnosis. Methods A retrospective analysis was performed on the clinical data of 47 patients with IgG4-related AIP, among whom 33 underwent plain CT scan and contrast-enhanced CT scan, 24 underwent plain MRI scan, contrast-enhanced MRI scan, and magnetic resonance cholangiopancreatography (MRCP) examination, and 10 underwent combined CT and MRI examination to observe the morphology, changes in density/signal, contrast enhancement characteristics of the diseased pancreas, the peripancreatic and pancreatic duct changes, and the manifestations out of the pancreas. Results The CT and MRI scans showed that among the 47 patients, 27 had a “sausage-like”, diffusely enlarged pancreas and 20 had a focally enlarged pancreas. The plain CT scan showed a uniform and slightly low density; the contrast-enhanced CT scan of the lesion showed an inhomogeneous patchy enhancement in arterial phase, and a uniformly delayed progressive enhancement in portal vein phase and delayed phase. The MRI scan of the lesion showed inhomogeneous and slight hypointensity on T1WI-FS and slight hyperintensity on T2WI, the contrast-enhanced MRI scan showed an inhomogeneous mild enhancement in the early stage and a uniformly delayed progressive enhancement on delayed scan. The CT and MRI scans showed that 28 patients had capsule-like edges around the panc-reas, namely “capsule sign”, with a mild to moderate delayed enhancement on contrast-enhanced images. The MRCP showed that 10 patients had segmental stenosis of the main pancreatic duct and localized mild dilatation of the upstream pancreatic duct. The CT and MRI scans showed that 30 patients had changes in the bile duct system, with wall thickening, stenosis, and delayed enrichment of the pancreatic segment of common bile duct. The MRCP showed “beak-like” changes, and dilatation of upstream intrahepatic and extrahepatic bile ducts to varying degrees. Conclusion The CT and MRI findings of IgG4-related AIP have certain characteristics. The combination of imaging findings and relevant laboratory tests can help improve the diagnosis of this disease.

Abstract Background Immunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP. Case presentation Herein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient’s condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine. Conclusion The rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD.

Objectives: To evaluate the performance of radiology-related inclusion criteria of the 2019 ACR-EULAR classification system in the diagnosis of IgG4-related disease (IgG4-RD). Methods: This retrospective single-institution study included patients who received a diagnosis of IgG4-RD between January 2010 and December 2020. Two abdominal radiologists independently reviewed baseline imaging studies and scored radiology findings according to the 2019 ACR-EULAR classification criteria. Additional scores were assigned based on serological, histopathological, and immunostaining features. Results: Seventy-four patients (58 males and 16 females) with a mean age of 59.3 ± 13.9 years diagnosed with IgG4-RD were included. 51/74 (68.9%) were classified as having IgG4-RD according to the 2019 ACR-EULAR classification criteria. To reach a score ≥ 20 in these 51 patients, the radiology domain was sufficient in 20/51 (39.2%) and adding the serology domain was required for another 20/51 (39.2%). The remaining 11/51 patients (21.6%) required the histopathology and immunostaining domains. Radiological involvement of two or more organs at presentation was significantly associated with a score of ≥ 20 and seen in 43/51 (84.3%) compared to 5/23 (21.7%) of the non-classified group (p < 0.001). The group classified as having IgG4-RD showed a significantly higher proportion of elevated IgG4 levels (39/51, 76.5%) than the non-classified group (8/23, 34.8%) (< 0.001). Conclusion: The study findings support the effectiveness of the radiology-related inclusion criteria of the 2019 ACR-EULAR classification system in diagnosing IgG4-RD. Combining radiology and serology domains achieved the cut-off in 80% of IgG-RD patients, enabling non-invasive diagnosis. The classification of IgG4-RD was significantly associated with multi-organ involvement, particularly affecting the pancreas and biliary system. Critical relevance statement: This study is the first to evaluate the diagnostic performance of the radiology domain in the 2019 ACR-EULAR classification criteria. The study results confirm its utility and potential to enable non-invasive diagnosis when combined with serological testing in a significant proportion of patients. Key points: • A significant proportion of patients can be diagnosed with IgG4-RD using the radiology and serology domains exclusively. • Multi-organ involvement is significantly associated with classifying patients as IgG4-RD, with the pancreas and biliary system most frequently affected. • A high level of inter-reader agreement in the scoring of the radiology domain supports its reliability. [ABSTRACT FROM AUTHOR]

Otologic immunoglobulin G4–related disease (IgG4-RD) is a rare and a relatively newer pathology. COVID-19, IgG4-RD, and type 2 diabetes, all have independent capabilities to considerably affect the immune system. The immunological effects of COVID are a global conundrum; consequently, the association of this trio (otologic IgG4-RD, COVID-19, and type 2 diabetes), the only reported case in literature, paves the way for a fascinating interplay to explore the knowledge of which would help optimize treatment and improve disease outcomes. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP. Case presentation: Herein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient's condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine. Conclusion: The rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD. [ABSTRACT FROM AUTHOR]

Patient: Female, 63-year-old Final Diagnosis: Ruptured right-sided iliac artery aneurysm • IgG4-RD Symptoms: Mentally compromised • acute shock with pale complexion • recurrent fevers, suggestive of pelvic infection Clinical Procedure: Pelvic drainage procedures anti-infection treatment low-dose glucocorticoids Specialty: Immunology • Infectious Diseases • Surgery Objective: Rare disease Background: Managing IgG4-related disease (IgG4-RD) in the context of vascular complications, such as aneurysms, poses significant challenges, particularly when considering surgical intervention options. The risk of rupture and infection in patients on long-term glucocorticoid therapy complicates treatment decisions. Case Report: A 63-year-old woman with a history of IgG4-RD presented with a ruptured right iliac artery aneurysm. She was on long-term oral glucocorticoid therapy. Initial emergency endovascular stent graft implantation was followed by embolization for suspected arterial bleeding and subsequent Salmonella bacteremia. Repeated hospitalizations involved stent graft removal and surgical repair due to persistent infection. Over 2 years, the patient required multiple pelvic drainages and long-term antibiotic and prednisolone therapy, yet her quality of life remained compromised. Conclusions: Our case highlights the unique challenges and considerations in the treatment of IgG4-related aneurysms. Patients with IgG4-RD who are on long-term oral glucocorticoids have an inherent risk of aneurysm rupture. We believe regular follow-ups to monitor the progression of the aorta and iliac arteries into aneurysms are essential. For patients who have developed aneurysms, it is advisable to reduce the dosage of glucocorticoids or even consider surgical treatment as soon as possible. As for the choice of surgical method, there is no consensus yet. While endovascular treatment is less invasive and quicker, it can increase the risk of rupture and bleeding. Open surgery might be a better option. More data are needed to make a definitive judgment. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease (IgG4-RD) is a novel fibroinflammatory disorder characterized by enlargement of the involved organs, elevated IgG4 levels, and abundant infiltration of IgG4-positive plasma cells. Indeed, primary colon cancers arising from IgG4-RD are rare. This case report describes a rare occurrence of simultaneous colorectal cancer and IgG4-RD in the same lesion in a 62-year-old male patient. The patient underwent a right hemicolectomy under the suspicion of primary colon cancer. The mass was grossly well-defined and yellowish tan, and the background colon was fibrotic. Microscopically, the tumor cells showed glandular differentiation characteristic of adenocarcinoma in a background of dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis in the pericolic fat tissue. IgG4 immunohistochemical staining showed diffuse positivity in infiltrating plasma cells. The patient was administered adjuvant chemotherapy and prednisolone therapy. The patient's serum IgG4 levels gradually decreased, and a follow-up positron emission tomography-computed tomography scan 1 year after surgery showed no evidence of local or distant recurrence of colorectal cancer. IgG4-RD occurring concurrently with primary colon adenocarcinoma has not been reported. Increased awareness of this rare coexistence can guide clinicians in navigating diagnostic complexities and selecting optimal therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: Distinguishing immunoglobulin G4 (IgG4)-related disease ocular involvement (IgG4-ROD) from other non-IgG4 pathologies in the orbit and eyeball is often complex. The objective was to compare clinical, analytical, imaging, and anatomopathological features of IgG4-ROD with other inflammatory and/or autoimmune ocular diseases (non-IgG4-ROD). Methods: An observational, descriptive, and retrospective study included 18 patients diagnosed with IgG4-ROD according to Umehara's 2011 and/or 2020 comprehensive criteria, from 3 centers. Additionally, 12 patients with non-IgG4-ROD between 2014 and 2022 were selected, forming 2 groups. Data collection involved visualizing medical records. Demographic profile, clinical manifestations, analytical, histopathological, and radiological findings were analyzed using SPSS Statistics 19. Categorical variables were presented as frequencies and percentages, and continuous variables as means with standard deviation or median with interquartile range. Proportions were compared using the chi-square test, and means and medians were compared using T-tests and nonparametric tests. A confidence level of a = .05 was selected. Results: Thirty patients were analyzed: 18 with IgG4-ROD and 12 with non-IgG4-ROD. Among the latter, diagnoses included Histiocytosis (n = 4), Amyloidosis (n = 3), malignant secondary malignancy (n = 2), and other conditions (n = 3). Female sex predominated in IgG4-ROD (78% vs. 50%, P = .12). Mean age was 44 years, with no group difference (P = .26). Bilateral involvement was more common in non-IgG4 (92% vs. 72%, P = .21). Predominant symptoms in IgG4-ROD were proptosis, ocular pain, xerophthalmia, palpebral edema, and diplopia, while palpebral edema and ocular motility disturbance were more usual in other pathologies. Proptosis, xerophthalmia, and diplopia were significantly more frequent in IgG4-ROD (P = .042, P = .021, P = .021, respectively). Parotid involvement showed significant association in IgG4-ROD at 33% (P = .031). Statistically significant differences were observed in elevated serum IgG4 levels (67%, P = .002), IgG (P = .037), and IgG2 levels = 5.3 g/L (56%, P = .023) in IgG4-ROD. There was also a significant difference between the association of eosinophilia and the non-IgG4 group (67% vs. 22%, P = .034), as did mean serum IgG value and the IgG4-ROD group (P = .037). Lacrimal gland involvement associated with IgG4-ROD (P = .032). Histopathologically, IgG4-ROD showed significant associations with lymphoplasmacytic infiltrate (100%, P = .004), storiform fibrosis (36%, P = .05), and presence of Eosinophils (64%, P = .003). Conclusion: Immunoglobulin G4-related ophthalmic disease showed significant associations with xerophthalmia, proptosis, diplopia, and parotid involvement. Elevated serum IgG4, IgG, and IgG2 levels were also linked to this condition. Imaging studies revealed lacrimal gland involvement. Furthermore, lymphoplasmacytic infiltrate, storiform fibrosis, and eosinophil presence were significant in histopathological findings. Conversely, serum eosinophilia, bilateral involvement, and palpebral edema in imaging studies were statistically related to the non-IgG4 group. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications. [ABSTRACT FROM AUTHOR]

Background: Nervous system involvement in immunoglobulin G4-related disease (IgG4-RD) has been rarely reported. Case Description: We describe an unusual case of IgG4-RD manifested as paresthesia in the right lower extremity. A 51-year-old male presented with paresthesia in the right S1-S3 regions. A neurological examination revealed peripheral neuropathy. Blood examination results were normal, barring slightly elevated IgG levels. Initial magnetic resonance imaging of the swollen right S1 and S2 nerve roots revealed lymphoma, schwannoma, and sarcoidosis. However, following the biopsy, the pathological findings were not typical of these diseases. Abdominal computed tomography revealed perirenal lesions, and IgG4-RD was suspected. The patient had a serum IgG4 level of 724 mg/dL. Additional pathological evaluations of the swollen S1 nerve revealed findings that corresponded to the diagnostic criteria for IgG4-RD. Oral steroid therapy was initiated, which improved paresthesia, and the swollen S1 nerve root gradually shrank. Conclusion: This report highlights a rare case of IgG4-RD involving nerve roots that neurosurgeons should consider. [ABSTRACT FROM AUTHOR]

Background and Objectives: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated, systemic condition of unknown etiology, associated with fibroinflammatory lesions. Diagnosis is set in the presence of IgG4-positive plasma cell infiltration of the involved tissue and elevated serum IgG4 levels. However, approximately 30% of patients have normal serum IgG4 levels. IgG4-RD may affect several organs, including the pancreas, bile ducts, mesentery, retroperitoneum, and salivary glands, but the involvement of the gastrointestinal tract is uncommon. Materials and Methods: The case series of 4 patients with IgG4-RD involving the intestinal tract was observed in the period of 2017–2022. Colorectal and ileal biopsy specimens were stained with hematoxylin and eosin and immunohistochemical techniques using monoclonal antihuman IgG4 primary antibody. Diagnosis of IgG4-RD was based on the presence of >50 cells/ HPF and IgG4/IgG ratio >40 confirmed by two pathologists. Results: IgG4-RD was set in patients previously diagnosed as affected by Crohn's disease. Conclusions: Systematic IgG4 immunohistochemical staining should be considered in the diagnostic workup of patients with gastrointestinal strictures, mimicking Crohn's disease. The exact prevalence of the condition is likely more frequent than reported and should be defined by a large series of consecutive patients. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 (IgG4)-related disease has the potential to impact any part of the body, including the walls of large- and medium-sized blood vessels and the ureters. While histopathologic examination is currently the standard method for identifying organ involvement and diagnosing IgG4-related disease (IgG4-RD), obtaining biopsy or surgical samples from vessel or ureteral walls is challenging. Given that patients may display only mild symptoms, non-invasive imaging plays a vital role in both diagnosing and managing IgG4-related diseases. Multidetector CT scans are valuable in establishing the primary diagnosis, identifying anatomical landmarks and assessing their relationships. Involvement of the genitourinary organs, such as the ureter, bladder, urethra, and male and female reproductive organs in IgG4-RD, is infrequent when compared to kidney involvement. The imaging findings may include the presence of a localised mass within or surrounding the affected organ or a generalised enlargement of the organ. This report includes cross-sectional images of five cases of IgG4-RD involving large- and medium-sized blood vessels (the aorta and superior mesenteric artery) and the ureters. Contribution: This case series provides insight into the various imaging appearances of IgG4-related retroperitoneal organ involvement and helps differentiate it radiologically from retroperitoneal fibrosis.

Immunoglobulin G4-related diseases(IgG4-RD)are chronic, systemic diseases that have received much attention in recent years. IgG4-RD can affect almost all tissues of the body, mainly manifested by swelling and space-occupying changes in the involved sites. It is called IgG4-related ophthalmic disease(IgG4-ROD)when the lesions invade the ocular area. The disease mainly invades the lacrimal glands, orbital fat, infraorbital nerve, extraocular muscles, and eyelids. At present, the main treatment modalities for IgG4-ROD include medication, surgery, and radiation therapy, etc. With the enhanced understanding of the disease and the increasing cure rate in recent years, this article reviews the latest progress in the epidemiological characteristics, clinical manifestations, imaging features, diagnosis and treatment of IgG4-ROD.