Gastroenterology

Gastroenterology

Volume 134, Issue 3, March 2008, Pages 706-715
Gastroenterology

Clinical–Liver, Pancreas, and Biliary Tract
Immunoglobulin G4–Associated Cholangitis: Clinical Profile and Response to Therapy

https://doi.org/10.1053/j.gastro.2007.12.009Get rights and content

Background & Aims: Immunoglobulin (Ig)G4-associated cholangitis (IAC) is the biliary manifestation of a steroid-responsive multisystem fibroinflammatory disorder in which affected organs have a characteristic lymphoplasmacytic infiltrate rich in IgG4-positive cells. We describe clinical features, treatment response, and predictors of relapse in IAC and compare relapse rates in IAC with intrapancreatic vs proximal bile duct strictures. Methods: We reviewed clinical, serologic, and imaging characteristics and treatment response in 53 IAC patients. Results: IAC patients generally were older (mean age, 62 y) men (85%), presenting with obstructive jaundice (77%) associated with autoimmune pancreatitis (92%), increased serum IgG4 levels (74%), and abundant IgG4-positive cells in bile duct biopsy specimens (88%). At presentation, biliary strictures were confined to the intrapancreatic bile duct in 51%; the proximal extrahepatic/intrahepatic ducts were involved in 49%. Initial presentation was treated with steroids (n = 30; median follow-up period, 29.5 months), surgical resection (n = 18; median follow-up period, 58 months), or was conservative (n = 5; median follow-up period, 35 months). Relapses occurred in 53% after steroid withdrawal; 44% relapsed after surgery and were treated with steroids. The presence of proximal extrahepatic/intrahepatic strictures was predictive of relapse. Steroid therapy normalized liver enzyme levels in 61%; biliary stents could be removed in 17 of 18 patients. Fifteen patients treated with steroids for relapse after steroid withdrawal responded; 7 patients on additional immunomodulatory drugs remain in steroid-free remission (median follow-up period, 6 months). Conclusions: IAC should be suspected in unexplained biliary strictures associated with increased serum IgG4 and unexplained pancreatic disease. Relapses are common after steroid withdrawal, especially with proximal strictures. The role of immunomodulatory drugs for relapses needs further study.

Section snippets

Materials and Methods

The protocol was approved by the Mayo Clinic institutional review board. From a database of patients with AIP, prospectively maintained by one of the authors (S.T.C.), we identified 49 patients with biliary strictures and proven AIP; 14 of these patients had undergone a pancreaticoduodenectomy for suspected pancreatic cancer owing to presentation with obstructive jaundice and a pancreatic head mass. AIP was diagnosed by the recently published HISORt criteria (Histology, Imaging, Serology, Other

Demographics and Presenting Clinical Features

The mean patient age was 62 ± 2 years (range, 14–85 y) and 83% were older than age 50. The majority of patients were men (85%). Clinical features on presentation included obstructive jaundice in 41 (77%), weight loss in 27 (51%), steatorrhea in 8 (15%), new-onset diabetes mellitus in 4 (8%), and abdominal pain in 14 of the 53 patients (26%). Abdominal pain did not require narcotics in any patient.

Histology and IgG4 Immunostaining

Four patients had resection (surgical) specimens that revealed a lymphoplasmacytic infiltrate in

Discussion

AIP now is viewed as the pancreatic manifestation of a systemic disease referred to as ISD.6 Several small case series have described biliary strictures in association with AIP13, 14, 15, 16, 17, 18, 19, 20, 21, 22 (Table 3) that characterize the biliary manifestation of ISD. We have proposed the term IAC to describe this entity.12 Similar to AIP, IAC patients have a striking male preponderance and typically present in the sixth and seventh decades of life with obstructive jaundice, weight

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