Review of primary sclerosing cholangitis with increased IgG4 levels

Primary sclerosing cholangitis(PSC) is a chronic progressive liver disease. Subtypes of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype,disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed Pub Med,MEDLINE and Embase with the search terms "primary sclerosing cholangitis","IgG4", and "IgG4-related sclerosing cholangitis(IgG4-SC)". Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSCnormal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features,organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes(B*07, DRB1*15), T-helper2 and T-regulatory cytokines(IL4, IL10,IL13) and chemokines(CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC,although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.

IgG4-related sclerosing cholangitis and chronic sclerosing sialadenitis mimicking cholangiocarcinoma and neck malignancy

To the Editor:IgG4-related sclerosing cholangitis（IgG4-SC）has re cently been recognized as a biliary manifestation of IgG4-related disease（IgG4-RD）.Type 3 IgG4-SC pre sented biliary strictures in both the porta hepatis and the distal common bile duct（CBD）.;Its manifestation especially in the absence of autoimmune pancreatitis,is extremely rare and very similar to that of cholangiocarci noma（CC）.

Cholangitis:Diagnosis,Treatment and Prognosis

Cholangitis is a serious life-threatening situation affecting the hepatobiliary system.This review provides an update regarding the clinical and pathological features of various forms of cholangitis.A comprehensive search was performed in the PubMed,Scopus,and Web of Knowledge databases.It was found that the etiology and pathogenesis of cholangitis are heterogeneous.Cholangitis can be categorized as primary sclerosing(PSC),secondary(acute)cholangitis,and a recently characterized form,known as IgG4-associated cholangitis(IAC).Roles of genetic and acquired factors have been noted in development of various forms of cholangitis.PSC commonly follows a chronic and progressive course that may terminate in hepatobiliary neoplasms.In particular,PSC commonly has been associated with inflammatory bowel disease.Bacterial infections are known as the most common cause for AC.On the other hand,IAC has been commonly encountered along with pancreatitis.Imaging evaluation of the hepatobiliary system has emerged as a crucial tool in the management of cholangitis.Endoscopic retrograde cholangiography,magnetic resonance cholangiopancreatography and endoscopic ultrasonography comprise three of the modalities that are frequently exploited as both diagnostic and therapeutic tools.Biliary drainage procedures using these methods is necessary for controlling the progression of cholangitis.Promising results have been reported for the role of antibiotic treatment in management of AC and PSC;however,immunosuppressive drugs have also rendered clinical responses in IAC.With respect to the high rate of complications,surgical interventions in patients with cholangitis are generally restricted to those patients in whom other therapeutic approaches have failed.