Primary Sclerosing Cholangitis Associated with Elevated ImmunoglobulinG4: Clinical Characteristics and Response to Therapy

Abstract

Steroid responsive biliary strictures in patients fulfilling criteria for primary sclerosing cholangitis (PSC) have been reported. The clinical course and response to therapy in patients with PSC with elevated immunoglobulin G4 (IgG4) levels has not been investigated previously. Patients with PSC were screened for IgG4-related biliary disease during 2006 to 2008 and data were collected prospectively. A total of 33 out of 285 (12%) patients with PSC (18 males) had elevated IgG4 (>140mg/dL) with a median age of 46 years (interquartile range 29-60); 24 could be evaluated. All patients had both intrahepatic and extrahepatic biliary strictures. Pancreatic disorders were found in 4 (17%), and 11 of 24 (46%) presented with jaundice; 8 of 24 (33%) received biliary stenting for a median time of 4 months (0-6). Liver cirrhosis was diagnosed in 12 of the 24 (50%). Overall, 18 patients were treated with corticosteroids and 6 patients managed conservatively. Nine of 10 patients with elevated bilirubin had improvement. Alkaline phosphatase decreased significantly at 2 months and at last follow-up. IgG4 levels at baseline were 242 (216-357) mg/dL and decreased to 109 (80-236) at 2 months (P < 0.05) and 174 (115-269) at last follow-up (P < 0.05). A total of 39% had adverse effects of steroids, mostly hyperglycemia. Relapses occurred in 7 of the 14 (50%), but biliary stents could be removed in all. Elevated IgG4 levels were observed in 12% of typical patients with PSC. Prevalence of cirrhosis was high, suggesting a severe liver disease course. Most patients had a good biochemical response to steroids, but adverse effects were common. Future work should be directed at finding therapy that is more effective, better tolerated, and of more lasting benefit.

Update on primary sclerosing cholangitis

“…Importantly, slight elevations (up to 5 g/L) of serum IgG4 of uncertain relevance occur also among PSC patients not fulfilling criteria for IgG4 associated cholangitis. Among these patients, a more aggressive disease course is often seen [75], but the pathogenetic significance of the detected serum IgG4 elevation and management of these patients have not been defined.…”

Prevalence of IgG-4-associated cholangiopathy based on serum IgG-4 levels in patients with primary sclerosing cholangitis and its relationship with inflammatory bowel disease

“…The positive predictive value in relation to IAC in patients who had serum IgG-4 levels between 1 and 2 times higher than the normal levels was 28%. A study by Björnsson et al (20) conducted on 285 patients with PSC found that 12% of patients had higher than normal serum IgG-4 levels and of these, 4 patients (17%) had pancreatic involvement. The use of serum IgG-4 in the diagnosis of IAC from PSC is helpful, but should not be used as the sole factor for the diagnosis of IAC (1,11).…”

IgG4 Sclerosing Cholangitis and Post Infantile Giant Cell Hepatitis: A Case Report of an Extraordinary Co-presentation

“…IgG4 associated sclerosing cholangitis (IgG4-SC) -as a variant of PSC -had been correctly reclassified as IgG4-RD-SC) [4]. Being characterized by a favorable response to glucocorticoids and immunosuppressive agents makes the distinction between IgG4-SC and PBC mandatory [5]. The diagnostic value of IgG4 serum levels is questioned as about 40% of IgG4-RD patients have normal serum levels [4,5].…”

“…Being characterized by a favorable response to glucocorticoids and immunosuppressive agents makes the distinction between IgG4-SC and PBC mandatory [5]. The diagnostic value of IgG4 serum levels is questioned as about 40% of IgG4-RD patients have normal serum levels [4,5]. Interplay between IgG4 positive tissue immunostaining, along with both clinical and cholangiographic features of cholangiopathy, is required for proper diagnosis [5].…”

“…The diagnostic value of IgG4 serum levels is questioned as about 40% of IgG4-RD patients have normal serum levels [4,5]. Interplay between IgG4 positive tissue immunostaining, along with both clinical and cholangiographic features of cholangiopathy, is required for proper diagnosis [5]. Histopathological discrimination between IgG4-SC and cholangiocarcinoma is essential; however, this is not usually easy with the difficulty in the endoscopic transpapillary bile duct biopsy [6].…”