title: Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
authors.forename: Amaar
authors.initials: A
authors.lastname: Ghazale
authors.forename: Suresh T
authors.initials: ST
authors.lastname: Chari
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Levy
authors.forename: Mark D
authors.initials: MD
authors.lastname: Topazian
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Clain
authors.forename: Randall K
authors.initials: RK
authors.lastname: Pearson
authors.forename: Bret T
authors.initials: BT
authors.lastname: Petersen
authors.forename: Santhi Swaroop
authors.initials: SS
authors.lastname: Vege
authors.forename: Keith
authors.initials: K
authors.lastname: Lindor
authors.forename: Michael B
authors.initials: MB
authors.lastname: Farnell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001652:Bile Ducts / Q000187:drug effects / Q000276:immunology / Q000601:surgery; D001662:Biliary Tract Surgical Procedures; D002758:Cholangiography; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000627:therapeutic use*; D041781:Jaundice, Obstructive / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D012008:Recurrence; D013256:Steroids / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D007074:Immunoglobulin G; D007155:Immunologic Factors; D013256:Steroids