IgG4-related sclerosing cholangitis: not always an obvious entity.
Ontology highlight
ABSTRACT:
SUBMITTER: Velegraki M
PROVIDER: S-EPMC8276355 | biostudies-literature | 2021 Jul-Aug
REPOSITORIES: biostudies-literature
Publications
IgG4-related sclerosing cholangitis: not always an obvious entity.
Velegraki Magdalini M Vardas Emmanouil E Dervenis Christos C Fragaki Maria M Nikolaou Pinelopi P Mpitouli Afroditi A Kazamias George G Sepsa Athanasia A Giannikaki Elpida E Paspatis Gregorios A GA
Annals of gastroenterology 20210226 4
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is a distinct type of cholangitis, currently recognized as a biliary manifestation of IgG4-related disease. We present a case of type 3 IgG4-SC in a patient with normal IgG4 serum levels, surgically treated for suspicion of cholangiocarcinoma. This case highlights that differentiating between isolated IgG4-SC and cholangiocarcinoma can present a challenging diagnostic dilemma. ...[more]
Similar Datasets
Project description:Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.
| S-EPMC8240333 | biostudies-literature
Project description:Background & aimsPrimary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) are chronic fibro-inflammatory immune-mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate non-invasive biomarkers for discriminating PSC and IgG4-SC are important to ensure a correct diagnosis, prompt therapy and adequate cancer surveillance.MethodsWe performed nuclear magnetic resonance (NMR)-based metabolomic profiling using serum samples collected prospectively from patients with PSC (n = 100), IgG4-SC (n = 23) and healthy controls (HC; n = 16).ResultsMultivariate analysis of the serum metabolome discriminated PSC from IgG4-SC with greater accuracy (AUC 0.95 [95%CI 0.90-0.98]) than IgG4 titre (AUC 0.87 [95%CI 0.79-0.94]). When inflammatory bowel disease (IBD) was excluded as a comorbid condition (IgG4-SC n = 20, PSC n = 22), the diagnostic AUC increased to 1.0, suggesting that the metabolome differences identified are not a result of the increased prevalence of IBD in PSC relative to IgG4-SC patients. Serum lactate (p < .0001), glucose (p < .01) and glutamine (p < .01) metabolites were increased in IgG4-related disease (IgG4-RD) and IgG4-SC individuals compared to PSC, whereas mobile choline (p < .05), 3-hydroxybutyric acid (p < .01) and -CH3 lipoprotein resonances (p < .01) were decreased.ConclusionsTaken together, serum metabolomic profiling has the potential to be incorporated as a diagnostic criterion, independent of IgG4 titre, to improve the diagnosis of IgG4-RD and help distinguish IgG4-SC from PSC.
| S-EPMC9546203 | biostudies-literature
Project description:BACKGROUND:We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). METHODS:To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. RESULTS:Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.7%) experienced spontaneous stent dislodgement after CS initiation, and seven (70%) of them developed stent dislodgement two weeks to two months after CS initiation. Among forty-one patients treated with CS alone without EBD, 10 patients had obstructive jaundice at the time of CS initiation and all of them achieved clinical improvement without biliary tract infection. During the follow-up, three patients (4.3%), all of whom had undergone EBD, developed bile-duct stones, while none of those treated with CS alone developed bile-duct stones (p = 0.032). Long-term biliary stenting was a risk factor for bile-duct stones. CONCLUSIONS:Biliary stent removal should be carried out within 2 weeks after CS initiation if biliary stricture improves to prevent stent dislodgement. Obstructive jaundice can be treated safely with CS alone in patients without infection. Clinicians should be aware of the possibility of bile-duct stones in patients treated with EBD.
| S-EPMC7192452 | biostudies-literature
Project description:Background & aimsDistinction of immunoglobulin G4-associated cholangitis (IAC) from primary sclerosing cholangitis (PSC) or cholangiocarcinoma is challenging. We aimed to assess the performance characteristics of endoscopic retrograde cholangiography (ERC) for the diagnosis of IAC.MethodsSeventeen physicians from centers in the United States, Japan, and the United Kingdom, unaware of clinical data, reviewed 40 preselected ERCs of patients with IAC (n = 20), PSC (n = 10), and cholangiocarcinoma (n = 10). The performance characteristics of ERC for IAC diagnosis as well as the ? statistic for intraobserver and interobserver agreement were calculated.ResultsThe overall specificity, sensitivity, and interobserver agreement for the diagnosis of IAC were 88%, 45%, and 0.18, respectively. Reviewer origin, specialty, or years of experience had no statistically significant effect on reporting success. The overall intraobserver agreement was fair (0.74). The operating characteristics of different ERC features for the diagnosis of IAC were poor.ConclusionsDespite high specificity of ERC for diagnosing IAC, sensitivity is poor, suggesting that many patients with IAC may be misdiagnosed with PSC or cholangiocarcinoma. Additional diagnostic strategies are likely to be vital in distinguishing these diseases.
| S-EPMC3246637 | biostudies-literature
Project description:ObjectivesImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and autoimmune pancreatitis (AIP) are characterized by an abundance of circulating and tissue IgG4-positive plasma cells. T-follicular helper (Tfh) cells are necessary for B-cell differentiation into plasma cells. We aimed at elucidating the presence and phenotype of Tfh cells and their relationship with disease activity in IgG4-SC/AIP.MethodsCirculating Tfh-cell subsets were characterized by multiparametric flow cytometry in IgG4-SC/AIP (n = 18), disease controls with primary sclerosing cholangitis (n = 8), and healthy controls (HCs, n = 9). Tissue Tfh cells were characterized in IgG4-SC/AIP (n = 12) and disease control (n = 10) specimens. Activated PD1+ Tfh cells were cocultured with CD27+ memory B cells to assess their capacity to support B-cell differentiation. Disease activity was assessed using the IgG4-responder index and clinical parameters.ResultsActivated circulating PD-1+CXCR5+ Tfh cells were expanded in active vs inactive IgG4-SC/AIP, primary sclerosing cholangitis, and HC (P < 0.01), with enhanced PD-1 expression on all Tfh-cell subsets (Tfh1, P = 0.003; Tfh2, P = 0.0006; Th17, P = 0.003). Expansion of CD27+CD38+CD19lo plasmablasts in active disease vs HC (P = 0.01) correlated with the PD-1+ Tfh2 subset (r = 0.69, P = 0.03). Increased IL-4 and IL-21 cytokine production from stimulated cells of IgG4-SC/AIP, important in IgG4 class switch and proliferation, correlated with PD-1+ Tfh2 (r = 0.89, P = 0.02) and PD-1+ Tfh17 (r = 0.83, P = 0.03) subsets. Coculture of PD1+ Tfh with CD27+ B cells induced higher IgG4 expression than with PD1- Tfh (P = 0.008). PD-1+ Tfh2 cells were strongly associated with clinical markers of disease activity: sIgG4 (r = 0.70, P = 0.002), sIgE (r = 0.66, P = 0.006), and IgG4-responder index (r = 0.60, P = 0.006). Activated CXCR5+ Tfh cells homed to lymphoid follicles in IgG4-SC/AIP tissues.ConclusionsCirculating and tissue-activated Tfh cells are expanded in IgG4-SC/AIP, correlate with disease activity, and can drive class switch and proliferation of IgG4-committed B cells. PD1+ Tfh2 cells may be a biomarker of active disease and a potential target for immunotherapy.
| S-EPMC6602789 | biostudies-literature
Project description:Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum gamma-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, "IgG4-related sclerosing disease", and suggest that AIP is a pancreatic lesion reflecting this systemic disease.
| S-EPMC2780632 | biostudies-other
Project description:BackgroundPrimary sclerosing cholangitis (PSC) is a chronic liver disease leading to inflammation with scaring and strictures of bile ducts, which can lead to liver cirrhosis. A subtype of PSC characterized by high serum IgG4 (sIgG4) levels has been reported to be associated with poor outcomes, but the exact role and the longitudinal development of sIgG4 levels in PSC progression remains to be clarified. The aim of this study was to investigate if subsequent analysis of sIgG4 levels allows the identification of the PSC phenotype with high sIgG4.MethodssIgG4 values were repeatedly analysed in a well-characterized European PSC cohort of 110 individuals. Biochemical parameters, clinical endpoints, death and liver transplantation were compared between PSC subgroups.Results12.7% (n = 14) of PSC patients showed increased sIgG4 levels (PSC-IgG4). The values normalized in 57.1% (n = 8; PSC-IgG4norm) during follow-up measurements, whereas the values remained permanently elevated in 42.9% (n = 6; PSC-IgG4const). Serum values of AP and γGT were significantly higher in PSC-IgG4const compared to PSC-IgG4norm at final blood sampling. Furthermore, mean age at PSC diagnosis was markedly lower in PSC-IgG4const compared to PSC-IgG4norm.ConclusionsThis is the first study analyzing longitudinal development of sIgG4 in PSC. Our data indicate that only sequential determination of sIgG4 levels allow to accurately distinguish between the PSC phenotype with high sIgG4 and PSC with low sIgG4.
| S-EPMC11301849 | biostudies-literature
Project description:BackgroundEven though IgG4-related disease has gained increased attention worldwide, the diagnosis remains challenging. IgG4-related sclerosing cholangitis (IgG4-SC) is not well described in the western hemisphere and may mimic cholangiocarcinoma (CC), especially when occurring without other symptoms such as, e.g. concurrent pancreatitis or retroperitoneal fibrosis. We present a case to add further information to the diagnosis and treatment of this challenging disease.Case reportA 60-year-old male patient presented with painless jaundice. Prior medical history showed diabetes mellitus type I, high blood pressure, and deep vein thrombosis. Diagnostic investigations were strongly suspicious of a Klatskin tumor, although biopsies were inconclusive. The tumor marker Carbohydrate Antigen 19-9 (CA 19-9) was elevated. Prior to the recommended surgery, the patient had two second opinions in two different university hospitals, both arguing for surgery as well. The patient received hilar resection with right hemihepatectomy. During the postoperative course, some major complications occurred, i.e. recurrent pleural effusion, abscess in the liver resection area, sepsis, ileus, and restricted liver metabolism. Treatment with prednisolone did not show any improvement. Approximately 3 months after surgery, the patient died in consequence of acute respiratory failure. Histology showed no signs of CC, but IgG4-SC could be diagnosed.ConclusionIn the case of preoperative signs of CC, differential diagnosis of IgG4-SC needs to be considered, in particular, in cases with missing histologic proof of malignant disease.
| S-EPMC6604574 | biostudies-literature
Project description:Increased serum levels of IgG4 have been reported in 9%-15% of patients with primary sclerosing cholangitis (PSC); it is not clear whether this increase contributes to pathogenesis. We performed genetic analyses of the HLA complex in patients with PSC from Norway, Sweden, and from the United States. We found an association between levels of IgG4 above the upper reference limit and specific HLA haplotypes. These patients had a significantly lower frequency of the strongest PSC risk factor, HLA-B*08, than patients without increased IgG4, and significantly higher frequencies of HLA-B*07 and HLA-DRB1*15. HLA genotype therefore might affect the serum concentration of IgG4, and increased IgG4 might be a marker of a distinct phenotype of PSC.
| S-EPMC4409500 | biostudies-literature
Project description:Dense tissue infiltrates of IgG4(+) plasma cells >50/high-powered field (HPF) are purportedly highly specific for IgG4-related disease. However, the frequency and significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing cholangitis (PSC) applying these cut-offs has not been determined. We sought to determine the incidence of intrahepatic IgG4-positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be mild (10-29 IgG4(+) cells/HPF) in 23.0%, moderate (30-50/HPF) in 9.0% and marked (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4(+) staining (P < 0.001). No patient had marked peripheral IgG4(+) staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post-transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4(+) staining, whereas mild staining was seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4(+) lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4(+) , this does not seemingly associate with clinical disease course.
| S-EPMC4351857 | biostudies-literature