Guideline sources The following summarized guidelines for the evaluation and management of igG4-related sclerosing cholangitis are prepared by our editorial team based on guidelines from the European Association for the Study of the Liver (EASL 2022), the British Society of Gastroenterology (BSG 2019), and the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS 2019). 1 2 3 CalculatorClinical diagnostic criteria of IgG Guidelines 1. Screening and diagnosis Clinical presentation: recognize that 90% of patients with IgG4-related sclerosing cholangitis have autoimmune pancreatitis. Recognize that IgG4-related sclerosing cholangitis is also associated with dacryoadenitis, sialadenitis, retroperitoneal fibrosis, kidney lesions, pulmonary https://web.pathway.md/diseases/recH8y0BYPZWlc2XV 1/5 6/24/23, 2:28 PM IgG4-related sclerosing cholangitis Pathway lesions, lymph node lesions, and vascular lesions (aorta and coronary arteries). Take into consideration these IgG4-related lesions. B Diagnostic criteria: Diagnose IgG4-related sclerosing cholangitis according to the recommendations of the international consensus guidelines. B Diagnose IgG4-related sclerosing cholangitis based on the following four criteria: characteristic biliary imaging findings elevation of serum IgG4 levels coexistence of IgG4-related diseases, except involving the biliary tract characteristic histopathologic features. B Evaluate the effectiveness of corticosteroid therapy as an optional extra diagnostic criterion, performed in a specialized facility with the opportunity of detailed examinations such as endoscopic biliary biopsy and EUS-guided fine-needle aspiration, to confirm the diagnosis of IgG4-related sclerosing cholangitis after negative work up for malignancy. B Differential diagnosis (cholangiocarcinoma): Obtain the following work-up for differential diagnosis from cholangiocarcinoma: Situation Guidance Clinical course, concomitant diseases Medical history Serum IgG4 levels Laboratory tests Cholangiography, contrast-enhanced CT or intraductal ultrasound for bile duct wall findings Imaging Peroral cholangioscopy for mucosal findings Endoscopy Biopsy or brush cytology for pathologic findings. B Pathology Consider obtaining any of the following for differential diagnosis from cholangiocarcinoma: serum IgG4 levels contrast-enhanced CT and MRI/MRCP EUS intraductal ultrasound peroral cholangioscopy bile duct biopsy. C Differential diagnosis, primary sclerosing cholangitis: As per BSG 2019 guidelines: https://web.pathway.md/diseases/recH8y0BYPZWlc2XV 2/5 6/24/23, 2:28 PM IgG4-related sclerosing cholangitis Pathway Do not rely solely on elevated IgG4 levels for definite diagnosis of IgG4-related sclerosing cholangitis or distinguishing IgG4-related sclerosing cholangitis from PSC, although it supports the diagnosis of clinically suspected IgG4-related disease. D Recognize that other organ involvement, particularly pancreatic manifestations of IgG4-related disease, may provide important information to distinguish IgG4-related sclerosing cholangitis from PSC. B As per JSHBPS 2019 guidelines: Obtain the following work-up for differential diagnosis from PSC: Situation Guidance Age of onset, clinical course, coexisting diseases Medical history Serum IgG4 levels Laboratory tests Image findings of biliary trees Imaging Liver histology Pathology Effectiveness of corticosteroid therapy. B Treatment response Consider obtaining any of the following for differential diagnosis from PSC: serum IgG4 levels contrast-enhanced CT and MRI/MRCP endoscopic retrograde cholangiography intraductal ultrasound peroral cholangioscopy bile duct biopsy. C 2. Diagnostic investigations Immunoglobulin G4: obtain serum IgG4 levels for the diagnosis of IgG4-related sclerosing cholangitis. B Diagnostic imaging: Consider obtaining ultrasound for the diagnosis of IgG4-related sclerosing cholangitis. C Obtain contrast-enhanced CT and MRI/MRCP to detect dilation or stenosis of bile ducts and to have a complete image of the biliary system. B Corticosteroid trial: Consider administering corticosteroid trials by experts familiar with autoimmune pancreatitis and IgG4-related sclerosing cholangitis or in patients with diagnostically challenging cases of IgG4- https://web.pathway.md/diseases/recH8y0BYPZWlc2XV 3/5 6/24/23, 2:28 PM IgG4-related sclerosing cholangitis Pathway related sclerosing cholangitis without autoimmune pancreatitis or other organ involvement only after exclusion of cholangiocarcinoma. C Obtain ERCP/MRCP after 1 or 2 weeks of steroid administration at a dose of 0.4-0.6 mg/kg for the assessment of effectiveness of the trial, by confirming resolution of findings on bile duct images, for the diagnosis of IgG4-related sclerosing cholangitis. Consider obtaining reevaluation, including resection of cases suspicious for cancer, in the absence of amelioration. B 3. Diagnostic procedures Endoscopic retrograde cholangiography: consider performing endoscopic retrograde cholangiography to detect diffuse or segmental stricture of the intrahepatic and/or extrahepatic bile ducts in patients with IgG4-related sclerosing cholangitis. C Bile duct biopsy: As per BSG 2019 guidelines, attempt obtaining confirmatory histological diagnosis in patients with suspected IgG4-related sclerosing cholangitis. B As per JSHBPS 2019 guidelines, consider performing bile duct biopsy for the diagnosis of IgG4- related sclerosing cholangitis. C Show 2 more 4. Medical management Corticosteroids: As per EASL 2022 guidelines, initiate prednisone/prednisolone (0.5-0.6 mg/kg/day) as first-line therapy for untreated active IgG4-related cholangitis. Evaluate treatment response after 2-4 weeks before prednisone/prednisolone tapering by clinical, biochemical and/or radiological criteria. B As per BSG 2019 guidelines, initiate corticosteroid as first-line therapy in patients with active IgG4-related sclerosing cholangitis. B As per JSHBPS 2019 guidelines, initiate corticosteroids in almost all patients with IgG4-related sclerosing cholangitis. Consider administering immediate corticosteroids in patients with IgG4- related sclerosing cholangitis and obstructive jaundice, acute cholangitis, or symptomatic extrabiliary IgG4-related diseases. B Show 5 more Immunosuppressants: As per EASL 2022 guidelines: Consider initiating corticosteroid-sparing immunosuppressants for up to 3 years (such as azathioprine, 6-mercaptopurine, mycophenolate mofetil), and potentially beyond, starting during prednisone/prednisolone tapering as maintenance treatment of IgG4-related cholangitis to reduce the risk of IgG4-related cholangitis relapse. C https://web.pathway.md/diseases/recH8y0BYPZWlc2XV 4/5 6/24/23, 2:28 PM IgG4-related sclerosing cholangitis Pathway Consider initiating rituximab alternatively when relapse has occurred. C As per BSG 2019 guidelines, consider initiating continued immunosuppressive therapy in all patients with IgG4-related sclerosing cholangitis, including patients with multiorgan involvement in IgG4-related disease. B 5. Therapeutic procedures Biliary drainage: consider performing biliary drainage in patients with IgG4-related sclerosing cholangitis having obstructive jaundice due to biliary stenosis. C 6. Follow-up and surveillance Indications for referral: refer patients with complex IgG4-related sclerosing cholangitis or with suspected malignancy to a specialist multidisciplinary meeting for review. B Follow-up: obtain periodic assessment of symptoms, analysis of objective findings such as jaundice, biochemistry tests, serum IgG/IgG4 levels, and imaging findings after initiating and discontinuing steroid therapy. Attempt to identify relapse, exclude malignancy, and control adverse reactions to corticosteroids while managing the clinical course of these patients. B Management of relapse: Re-administer and increase the dose of corticosteroids for the treatment of patients with a relapse of IgG4-related sclerosing cholangitis. B Consider offering immunomodulatory drugs and rituximab in some patients with a relapse of IgG4-related sclerosing cholangitis. C References 1. Chapman MH, Thorburn D, Hirschfield GM et al. British Society of Gastroenterology and UK PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019 Aug;68 8 1356 1378. Open 2. Kamisawa T, Nakazawa T, Tazuma S et al. Clinical practice guidelines for IgG4-related sclerosing cholangitis. J Hepatobiliary Pancreat Sci. 2019 Jan;26 1 9 42. Open 3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on Sclerosing Cholangitis. J Hepatol. 2022 May 31;S0168 8278 22 00326 9. Open 4. Hirotaka Ohara, Kazuichi Okazaki, Hirohito Tsubouchi et al. Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012. J Hepatobiliary Pancreat Sci. 2012 Sep;19 5 536 42. Open https://web.pathway.md/diseases/recH8y0BYPZWlc2XV 5/5