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Gleeson D, Bornand R, Brownlee A, Dhaliwal H, Dyson JK, Hails J, Henderson P, Kelly D, Mells GF, Miquel R, Oo YH, Sutton A, Yeoman A, Heneghan MA. British Society of Gastroenterology guidelines for diagnosis and management of autoimmune hepatitis. Gut 2025:gutjnl-2024-333171. [PMID: 40169244 DOI: 10.1136/gutjnl-2024-333171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Accepted: 10/22/2024] [Indexed: 04/03/2025]
Abstract
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease which, if untreated, often leads to cirrhosis, liver failure and death. The last British Society of Gastroenterology (BSG) guideline for the management of AIH was published in 2011. Since then, our understanding of AIH has advanced in many areas. This update to the previous guideline was commissioned by the BSG and developed by a multidisciplinary group. The aim of this guideline is to review and summarise the current evidence, in order to inform and guide diagnosis and management of patients with AIH and its variant syndromes. The main focus is on AIH in adults, but the guidelines should also be relevant to older children and adolescents.
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Affiliation(s)
- Dermot Gleeson
- Liver Unit, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Division of Clinical Medicine, School of Medicine and Population Science, University of Sheffield, Sheffield, UK
| | | | | | - Harpreet Dhaliwal
- Department of Gastroenterology, Manchester Royal Infirmary, Manchester, UK
| | - Jessica K Dyson
- Liver Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Janeane Hails
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
| | - Paul Henderson
- Royal Hospital for Children and Young People, Edinburgh, UK
| | - Deirdre Kelly
- Birmingham Women's & Children's Hospital, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - George F Mells
- Division of Gastroenterology and Hepatology, Addenbrooke's Hospital, Cambridge, UK
- Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK
| | - Rosa Miquel
- Liver Histopathology Laboratory, Institute of Liver Studies, King's College London, London, UK
| | - Ye H Oo
- Centre for Liver and Gastroenterology research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- NIHR Biomedical Research Centre, University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Rare Diseases, European Reference Network on Hepatological Diseases (ERN-RARE-LIVER) centre, Birmingham, UK
| | - Anthea Sutton
- Sheffield Centre for Health and Related Research, The University of Sheffield, Sheffield, UK
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Yasuda M, Shiokawa M, Kuwada T, Nishikawa Y, Nakanishi R, Takimoto I, Chikugo K, Yokode M, Muramoto Y, Matsumoto S, Nakamura T, Ota S, Matsumori T, Kuroda K, Hachiya T, Yamazaki H, Uza N, Kodama Y, Chiba T, Fujisawa T, Komori A, Abe M, Yamaguchi I, Matsuda F, Isayama H, Tanaka A, Seno H. Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study. J Gastroenterol 2025; 60:118-126. [PMID: 39549066 PMCID: PMC11717786 DOI: 10.1007/s00535-024-02169-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 10/31/2024] [Indexed: 11/18/2024]
Abstract
BACKGROUND Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities. METHODS Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA. RESULTS Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001). CONCLUSIONS We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.
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Affiliation(s)
- Muneji Yasuda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masahiro Shiokawa
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Takeshi Kuwada
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yoshihiro Nishikawa
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Risa Nakanishi
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Ikuhisa Takimoto
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Koki Chikugo
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masataka Yokode
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuya Muramoto
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shimpei Matsumoto
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takeharu Nakamura
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Sakiko Ota
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tomoaki Matsumori
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Keiko Kuroda
- Medical and Biological, Laboratories Co., Ltd., Nagoya, Japan
| | | | - Hajime Yamazaki
- Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norimitsu Uza
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Tsutomu Chiba
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
- Kansai Electric Power Hospital, Osaka, Japan
| | - Toshio Fujisawa
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Atsumasa Komori
- Clinical Research Center, NHO Nagasaki Medical Center, Nagasaki, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Izumi Yamaguchi
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Fumihiko Matsuda
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Evans S, Hofmann A. Autoimmune Biliary Diseases: A Review of Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, Immunoglobulin G4-Related Sclerosing Cholangitis, and Autoimmune Hepatitis. Surg Clin North Am 2024; 104:1249-1261. [PMID: 39448126 DOI: 10.1016/j.suc.2024.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
Autoimmune and immune-mediated biliary diseases represent a small proportion of biliary disorders, but owing to their progressive nature, lead to end-stage liver disease, necessitating liver transplantation for definitive management.
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Affiliation(s)
- Suzanne Evans
- Department of Pediatric and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, C3.163, Cincinnati, OH 45229, USA.
| | - Alana Hofmann
- Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, MSB 1464, Cincinnati, OH 45267, USA
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Li H, Wang R, Wang D, Tang Y, Liu X, Li H, Qi X. Case report: Isolated immunoglobulin G4-related sclerosing cholangitis misdiagnosed as hilar cholangiocarcinoma. Front Oncol 2024; 14:1385214. [PMID: 38846973 PMCID: PMC11153670 DOI: 10.3389/fonc.2024.1385214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 05/09/2024] [Indexed: 06/09/2024] Open
Abstract
Background Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma. Case presentation A 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor. Conclusion It is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.
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Affiliation(s)
- Hui Li
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Ran Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Dongyang Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Yufu Tang
- Department of Hepatobiliary Surgery, General Hospital of Northern Theater Command, Shenyang, China
| | - Xuantong Liu
- Department of Pathology, General Hospital of Northern Theater Command, Shenyang, China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
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Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M, Aziz Z, Bhatti ABH, Bangash TA, Butt AS, Butt OT, Dogar AW, Farooqi JI, Hanif F, Haider J, Haider S, Hassan SM, Jabbar AA, Khan AN, Khan MS, Khan MY, Latif A, Luck NH, Malik AK, Rashid K, Rashid S, Salih M, Saeed A, Salamat A, Tayyab GUN, Yusuf A, Zia HH, Naveed A. National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma. World J Gastroenterol 2024; 30:1018-1042. [PMID: 38577184 PMCID: PMC10989497 DOI: 10.3748/wjg.v30.i9.1018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
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Affiliation(s)
- Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan
| | - Irfan Ahmed
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
- University of Aberdeen, Aberdeen B24 3FX, United Kingdom
| | - Muhammad Atique
- Department of Pathology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Usman Iqbal Aujla
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | | | - Zeba Aziz
- Department of Oncology, Hameed Latif Hospital, Lahore 54000, Pakistan
| | - Abu Bakar Hafeez Bhatti
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Tariq Ali Bangash
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Osama Tariq Butt
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Abdul Wahab Dogar
- Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | - Javed Iqbal Farooqi
- Department of Medicine & Gastroenterology, Lifecare Hospital and Research Centre, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
| | - Faisal Hanif
- Department of Hepatopancreatobiliary & Liver Transplant, Bahria International Hospital, Lahore 54000, Pakistan
| | - Jahanzaib Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Siraj Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Syed Mujahid Hassan
- Department of Gastroenterology, Hepatology & Nutrition, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | | | - Aman Nawaz Khan
- Department of Radiology, Rehman Medical Institute, Peshawar 25000, Pakistan
| | - Muhammad Shoaib Khan
- Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi 46000, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amer Latif
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Nasir Hassan Luck
- Department of Gastroenterology, Sindh Institute of Urology and Transplantation, Karachi 75500, Pakistan
| | - Ahmad Karim Malik
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Kamran Rashid
- Rashid Nursing Home and Cancer Clinic, Rashid Nursing Home and Cancer Clinic, Rawalpindi 46000, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Abdullah Saeed
- Department of Radiology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amjad Salamat
- Department of Gastroenterology and Hepatology, Quaid-e-Azam International Hospital, Rawalpindi 44000, Pakistan
| | - Ghias-un-Nabi Tayyab
- Department of Gastroenterology and Hepatology, Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Aasim Yusuf
- Department of Internal Medicine, Division of Gastroenterology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore 54000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Ammara Naveed
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
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Park BU, Lee HE, Zhang L. Mimickers of immunoglobulin G4-related hepatobiliary disease on biopsy. Semin Diagn Pathol 2024; 41:95-107. [PMID: 38238218 DOI: 10.1053/j.semdp.2024.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 03/24/2024]
Abstract
With the growing recognition of IgG4-related hepatobiliary disease, establishing a definitive diagnosis relies mainly on a combination of clinical findings, serological markers, and imaging modalities. However, the role of histopathological evaluation remains indispensable, particularly in cases necessitating differential diagnosis or malignancy exclusion. While diagnosing IgG4-related hepatobiliary disease through surgical resection specimens is often straightforward, pathologists encounter substantial challenges when evaluating biopsies. The increasing rarity of surgical interventions exacerbates this due to improved disease recognition and suspicion. Numerous confounding factors, including the absence of the characteristic histologic features, limited tissue sample size, biopsy artifacts, and the limited value of IgG4 counts, further complicate the diagnostic process. Additionally, many other disorders exhibit clinical and histological features that overlap with IgG4-related disease, intensifying the complexity of interpreting biopsy specimens. This article explores the clinical and histomorphologic features of IgG4-related hepatobiliary disease and its potential mimickers. It offers valuable insights for pathologists and clinicians when confronted with biopsy specimens from hepatobiliary organs.
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Affiliation(s)
- Byoung Uk Park
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Hee Eun Lee
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States
| | - Lizhi Zhang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, United States.
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Sohal A, Kayani S, Kowdley KV. Primary Sclerosing Cholangitis: Epidemiology, Diagnosis, and Presentation. Clin Liver Dis 2024; 28:129-141. [PMID: 37945154 DOI: 10.1016/j.cld.2023.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Primary sclerosing cholangitis (PSC) is considered an immunologically mediated disease. However, some of its features are not consistent with the typical profile of autoimmune conditions. PSC is characterized by progressive biliary fibrosis that may ultimately result in the eventual development of cirrhosis. In recent years, multiple studies have reported that the incidence and prevalence of this disease are on the rise. Consequently, patients are often diagnosed without symptoms or signs of advanced liver disease, although many still present with signs of decompensated liver disease. This article discusses the epidemiology, clinical presentation, and diagnostic workup in patients with PSC.
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Affiliation(s)
- Aalam Sohal
- Liver Institute Northwest, , 3216 Northeast 45th Place, Suite 212, Seattle, WA 98105, USA
| | - Sanya Kayani
- Avera McKennan Hospital and University Health Center, Sioux Falls, SD, USA
| | - Kris V Kowdley
- Liver Institute Northwest, , 3216 Northeast 45th Place, Suite 212, Seattle, WA 98105, USA; Elson Floyd College of Medicine, Spokane, WA, USA.
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Möller K, Braden B, Culver EL, Jenssen C, Zadeh ES, Alhyari A, Görg C, Ignee A, Hocke M, Dong Y, Sun S, Faiss S, Dietrich CF. Secondary sclerosing cholangitis and IgG4-sclerosing cholangitis - A review of cholangiographic and ultrasound imaging. Endosc Ultrasound 2023; 12:181-199. [PMID: 36588352 PMCID: PMC10237613 DOI: 10.4103/eus-d-22-00208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 12/08/2022] [Indexed: 01/01/2023] Open
Abstract
Sclerosing cholangitis (SC) represents a spectrum of chronic progressive cholestatic diseases of the intrahepatic and/or extrahepatic biliary system characterized by patchy inflammation, fibrosis, and stricturing. Primary and secondary SC must be distinguished given the different treatment modalities, risks of malignancy, and progression to portal hypertension, cirrhosis, and hepatic failure. This review focuses on secondary SC and the pathogenic mechanisms, risk factors, clinical presentation, and novel imaging modalities that help to distinguish between these conditions. We explore the detailed use of cholangiography and ultrasound imaging techniques.
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Affiliation(s)
- Kathleen Möller
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Barbara Braden
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | - Emma L. Culver
- Translational Gastroenterology Unit, Oxford University Hospitals, Oxford, UK
| | - Christian Jenssen
- Department of Internal Medicine, Krankenhaus Märkisch Oderland GmbH, Strausberg, Wriezen, Germany
- Brandenburg Institute of Clinical Medicine at Medical University Brandenburg, Neuruppin, Germany
| | - Ehsan Safai Zadeh
- Interdisciplinary Center of Ultrasound Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Marburg, Germany
| | - Amjad Alhyari
- Interdisciplinary Center of Ultrasound Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Marburg, Germany
| | - Christian Görg
- Interdisciplinary Center of Ultrasound Diagnostics, University Hospital Giessen and Marburg, Philipps University Marburg, Marburg, Germany
| | - André Ignee
- Department of Internal Medicine – Gastroenterology and Rheumatology; Klinikum Wuerzburg Mitte, Wuerzburg, Germany
| | - Michael Hocke
- Medical Department II, Helios Klinikum Meiningen, Meiningen, Germany
| | - Yi Dong
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyu Sun
- Department of Endoscopy Center, Shengjing Hospital of China Medical University, Liaoning Province, China
| | - Siegbert Faiss
- Medical Department I/Gastroenterology, Sana Hospital Lichtenberg, Berlin, Germany
| | - Christoph F. Dietrich
- Department of Internal Medicine (DAIM), Hirslanden Private Hospital, Beau Site, Salem und Permanence, Bern, Switzerland
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Clinical Characteristics and Potential Mechanisms in Patients with Abnormal Liver Function Indices and Elevated Serum IgG4. Can J Gastroenterol Hepatol 2022; 2022:7194826. [PMID: 36060522 PMCID: PMC9436615 DOI: 10.1155/2022/7194826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21. METHODS Clinical data (age, sex, past history, clinical manifestations, laboratory tests, imaging, diagnosis, and treatment) and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. RESULTS Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients (n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment. CONCLUSIONS Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease.
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Pria HD, Torres US, Faria SC, Velloni FG, Caiado AH, Tiferes DA, D'Ippolito G. Practical Guide for Radiological Diagnosis of Primary and Secondary Sclerosing Cholangitis. Semin Ultrasound CT MR 2022; 43:490-509. [DOI: 10.1053/j.sult.2022.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Kemp W, Majeed A, Mitchell J, Majumdar A, Tse E, Skoien R, Croagh D, Dev A, Gao H, Weltman M, Craig P, Stuart K, Cheng W, Edmunds S, Lee E, Sood S, Metz A, Thompson A, Sinclair M, Beswick L, Nicoll A, Riordan S, Braund A, Muller K, MacQuillan G, Sandanayake N, Shackel N, Roberts SK. Management, outcomes and survival of an Australian IgG4-SC cohort: The MOSAIC study. Liver Int 2021; 41:2934-2943. [PMID: 34392596 DOI: 10.1111/liv.15036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/21/2021] [Accepted: 08/06/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS IgG4 sclerosing cholangitis (IgG4-SC) is the biliary component of the multisystem IgG4-related disease. We aimed to investigate the clinical features, demographics, treatment response and outcomes of IgG4-SC in a large Australian cohort. METHODS We conducted nationwide retrospective cohort via the Australian Liver Association Clinical Trials Network (ALA-CRN). 39 sites were invited to participate. IgG4-SC was defined by the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Data were collected on patient demographic, clinical and laboratory information, presenting features, response to therapy and clinical outcomes. RESULTS 67 patients meet inclusion criteria from 22 sites. 76% were male with mean age of 63.3 ± 14.5 years and a median IgG4 level of 3.6 g/L [0.09-67.1]. The most frequent presenting symptom was jaundice (62%) and abdominal pain (42%) and Type 1 biliary stricturing (52%) at the distal common bile duct was the most frequent biliary tract finding. Prednisolone was used as a primary treatment in 61 (91%) and partial or complete response occurred in 95% of subjects. Relapse was common (42%) in those who ceased medical therapy. After a median follow up of 3.9 years there was one hepatocellular carcinoma and no cholangiocarcinomas. CONCLUSIONS Our study confirms the preponderance of IgG4-SC in males and highlights the steroid response nature of this condition although relapse is common after steroid cessation. Progression to malignancy was uncommon.
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Affiliation(s)
- William Kemp
- Alfred Hospital, Melbourne, VIC, Australia
- Monash University, Melbourne, VIC, Australia
| | - Ammar Majeed
- Alfred Hospital, Melbourne, VIC, Australia
- Monash University, Melbourne, VIC, Australia
| | | | - Avik Majumdar
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Edmund Tse
- Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Richard Skoien
- Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | | | - Anouk Dev
- Monash Medical Centre, Melbourne, VIC, Australia
| | - Hugh Gao
- Monash Medical Centre, Melbourne, VIC, Australia
| | | | | | | | | | | | - Eric Lee
- Westmead Hospital, Sydney, NSW, Australia
| | | | - Andrew Metz
- Royal Melbourne Hospital, Melbourne, VIC, Australia
| | | | | | | | | | | | - Alicia Braund
- Gold Coast University Hospital, Gold Coast, QLD, Australia
| | - Kate Muller
- Flinders Medical Centre, Adelaide, SA, Australia
| | | | | | | | - Stuart Keith Roberts
- Alfred Hospital, Melbourne, VIC, Australia
- Monash University, Melbourne, VIC, Australia
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12
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Song S, Jo S. Isolated mass-forming IgG4-related sclerosing cholangitis masquerading as extrahepatic cholangiocarcinoma: A case report. World J Clin Cases 2021; 9:8773-8781. [PMID: 34734055 PMCID: PMC8546832 DOI: 10.12998/wjcc.v9.i29.8773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 07/20/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND IgG4-related sclerosing cholangitis (IgG4-RSC) is an uncommon benign disease, and its rarer, isolated and mass-forming subtype poses a significant challenge to differential diagnosis from cholangiocarcinoma of the extrahepatic bile duct. We herein report a case of isolated IgG4-RSC with an obstructing bile duct mass, for which extrahepatic bile duct resection was performed under the impression of proximal common bile duct (CBD) cancer.
CASE SUMMARY A 79-year-old male was admitted for jaundice that had developed 1 mo prior. There was no family history for autoimmune diseases or biliary cancer. Computed tomography (CT) and magnetic resonance cholangiopancreaticography revealed a short segmental concentric wall thickening of the proximal CBD with diffuse dilatation of the bile duct to the periphery. The endoscopic biopsy specimen showed no malignant cells. Positron emission tomography-CT showed a focal hypermetabolic lesion (SUVmax 4.2) in and around the proximal CBD area. With the impression of proximal CBD cancer, we performed segmental resection of the extrahepatic bile duct. Histopathology demonstrated marked sclerosis with diffuse lymphoplasmacytic infiltration and some eosinophils. Immunohistochemical staining for IgG4 showed increased positivity in some areas (up to 30/high-power field) and IgG4+/IgG+ cell ratio as 30%-50%. Pathologists’ impression was IgG4-related sclerosing disease. Follow-up serum IgG4 levels were continuously elevated; however, no evidence of relapse or other organ involvement related to IgG4-RSC presented.
CONCLUSION Isolated and mass-forming IgG4-RSC displays striking similarity with cholangiocarcinoma. To avoid unnecessary major surgery, high index of suspicion is needed.
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Affiliation(s)
- Sanghyun Song
- Department of Surgery, Dankook University Hospital, Cheonan 31116, Chungnam Province, South Korea
| | - Sungho Jo
- Department of Surgery, Dankook University Hospital, Cheonan 31116, Chungnam Province, South Korea
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13
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Yamamura M, Sato Y, Takahashi K, Nguyen Canh H, Li Z, Kimoto T, Terasaki S, Harada K. Hilar cholangiocarcinoma with extensive immunoglobulin G4 reaction. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2021; 14:987-992. [PMID: 34646417 PMCID: PMC8493266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 07/28/2021] [Indexed: 06/13/2023]
Abstract
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that can involve multiple organs. It is often challenging to distinguish IgG4-related sclerosing cholangitis (IgG4-SC) from cholangiocarcinoma because of overlap in their clinical findings. A 75-year-old man presented to a hospital for a detailed examination of the elevation of some biliary enzymes. Radiographic examination revealed segmental bile duct with wall thickening of the common hepatic bile duct, and dilation of the peripheral branches. Transampullary biopsy showed a non-specific inflammatory reaction with several IgG4-positive cell infiltrations. There were no signs of malignancy. The liver biopsy showed bile duct injury accompanied by IgG4-positive cell infiltration. We then performed bile duct biopsy and finally diagnosed the patient with cholangiocarcinoma. We should remember that the IgG4 reaction is neither completely sensitive nor specific for IgG4-RD and avoid resting solely on the IgG4 reaction to precisely distinguish IgG4-SC from cholangiocarcinoma.
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Affiliation(s)
- Minako Yamamura
- Department of Human Pathology, Kanazawa University Graduate School of MedicineKanazawa, Japan
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of MedicineKanazawa, Japan
| | - Kenta Takahashi
- Department of Human Pathology, Kanazawa University Graduate School of MedicineKanazawa, Japan
| | - Hiep Nguyen Canh
- Department of Human Pathology, Kanazawa University Graduate School of MedicineKanazawa, Japan
| | - Zihan Li
- Department of Human Pathology, Kanazawa University Graduate School of MedicineKanazawa, Japan
| | - Tatsuya Kimoto
- Department of Radiology, Japan Red Cross Kanazawa HospitalKanazawa, Japan
| | - Shuichi Terasaki
- Department of Gastroenterology, Japan Red Cross Kanazawa HospitalKanazawa, Japan
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of MedicineKanazawa, Japan
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14
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Naitoh I, Nakazawa T. Classification and Diagnostic Criteria for IgG4-Related Sclerosing Cholangitis. Gut Liver 2021; 16:28-36. [PMID: 34380781 PMCID: PMC8761932 DOI: 10.5009/gnl210116] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/06/2021] [Accepted: 06/14/2021] [Indexed: 11/20/2022] Open
Abstract
IgG4-related sclerosing cholangitis (IgG4-SC) can be classified into four types based on cholangiographic findings and regions of biliary stricture. This cholangiographic classification is useful to differentiate IgG4-SC from mimickers including cholangiocarcinoma, primary sclerosing cholangitis, and pancreatic cancer. Autoimmune pancreatitis (AIP) is a valuable clue for the diagnosis of IgG4-SC because the two are frequently found in association with each other. Two sets of diagnostic criteria for IgG4-SC have been proposed. In Japan, the clinical diagnostic criteria 2020 were recently developed. These clinical diagnostic criteria include narrowing of the intrahepatic and/or extrahepatic bile duct, thickening of the bile duct wall, serological findings, pathological findings, other organ involvement, and effectiveness of steroid therapy. When these criteria are applied, IgG4-SC is initially classified as associated or not associated with AIP, and cholangiographic classification is used for differential diagnosis. In most instances, IgG4-SC can be diagnosed on the basis of clinical diagnostic criteria. However, it is challenging to diagnose isolated IgG4-SC or IgG4-SC not associated with AIP. Here, we review the classification and diagnostic criteria for IgG4-SC, specifically focusing on the clinical diagnostic criteria 2020 and a large IgG4-SC case series from a nationwide survey in Japan.
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Affiliation(s)
- Itaru Naitoh
- Department of Gastroenterology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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15
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IgG4-related disease. Rev Esp Med Nucl Imagen Mol 2021. [DOI: 10.1016/j.remnie.2021.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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16
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Simó-Perdigó M, Martinez-Valle F. IgG4 related disease. Rev Esp Med Nucl Imagen Mol 2021; 40:107-114. [PMID: 33547020 DOI: 10.1016/j.remn.2020.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/23/2020] [Accepted: 12/25/2020] [Indexed: 11/27/2022]
Abstract
IgG4-related disease (ER-IgG4) is a recognised systemic disease. It was described after patients diagnosed with autoimmune pancreatitis showed signs of extra-pancreatic disease. The clinical manifestation of these patients is subacute and is manifested by the appearance of pseudotumoral lesions, or inflammatory or fibrous tumours. Sometimes it can be serious as in the case of patients with cholangitis or large vessel vasculitis. Diagnostic criteria include, among others, serum IgG4 elevation and/or histological parameters. The 18F-FDG-PET/CT is useful in the initial diagnosis, biopsy guidance as well as in the assessment of response to therapy. It usually responds to steroid therapy.
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Affiliation(s)
- M Simó-Perdigó
- Servicio de Medicina Nuclear, Hospital Vall d'Hebron, Barcelona, España.
| | - F Martinez-Valle
- Servicio de Medicina Interna, Unidad de Enfermedades Sistémicas, Hospital Universitario Vall d'Hebron, Barcelona, España
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17
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IgG4-related disease in the abdomen and pelvis: atypical findings, pitfalls, and mimics. Abdom Radiol (NY) 2020; 45:2485-2499. [PMID: 32300834 DOI: 10.1007/s00261-020-02526-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
IgG4-related disease (IgG4-RD) is a systemic, autoimmune, fibroinflammatory disease that can cause multi-organ damage. Although there have been many trials and studies since its recognition in 2003, there is still much that is unknown. Furthermore, IgG4-RD can affect any organ in the body and often has many mimics and alternative diagnoses, which can make for a challenging workup. Imaging plays a substantial role in the diagnosis of IgG4-RD and is often the first occasion where IgG4-RD comes into consideration. Thus, knowledge about the imaging findings of various manifestations of IgG4-RD can aid in the diagnosis and have a significant impact on patient management. In this article, we review the wide array of imaging findings, both typical and atypical, as well as possible mimics of IgG4-RD in the abdomen and pelvis.
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18
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Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis. Diagnostics (Basel) 2020; 10:diagnostics10050268. [PMID: 32365686 PMCID: PMC7277921 DOI: 10.3390/diagnostics10050268] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Revised: 04/23/2020] [Accepted: 04/27/2020] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is characterized by idiopathic biliary stricture followed by progressive cholestasis and fibrosis. When diagnosing PSC, its differentiation from other types of sclerosing cholangitis and cholangiocarcinoma is necessary. The cholangioscopic findings of PSC have not been investigated sufficiently. PSC and IgG4-related sclerosing cholangitis are difficult to distinguish by peroral cholangioscopy (POCS), but POCS is useful for excluding cholangiocarcinoma. POCS findings vary according to the condition and stage of disease. In the active phase, findings such as mucosal erythema, ulceration, fibrinous white exudate, and an irregular surface are observed and may reflect strong inflammation in the biliary epithelium. On the other hand, findings such as scarring, pseudodiverticula, and bile duct stenosis appear in the chronic phase and may reflect fibrosis and stenosis resulting from repeated inflammation. Observation of inside the bile duct by POCS might confirm the current PSC activity. Because POCS offers not only information regarding the diagnosis of PSC and PSC-associated cholangiocarcinoma but also the current statuses of biliary inflammation and stenosis, POCS could significantly contribute to the diagnosis and treatment of PSC once the characteristic findings of PSC are confirmed by future studies.
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19
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Matsubara T, Kozaka K, Matsui O, Nakanuma Y, Uesaka K, Inoue D, Yoneda N, Yoshida K, Kitao A, Yokka A, Koda W, Gabata T, Kobayashi S. Peribiliary glands: development, dysfunction, related conditions and imaging findings. Abdom Radiol (NY) 2020; 45:416-436. [PMID: 31707436 DOI: 10.1007/s00261-019-02298-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Peribiliary glands are minute structures that are distributed along the intrahepatic large bile ducts, extrahepatic bile duct, and cystic duct. These glands regulate many physiological functions, such as enzyme secretion. Pancreatic exocrine tissues and enzymes are often observed in peribiliary glands; thus, peribiliary glands are involved in enzyme secretion. As such, these glands can be affected by conditions such as IgG4-related sclerosing cholangitis based on commonalities with their pancreatic counterparts. Cystic changes in peribiliary glands can occur de novo, as part of a congenital syndrome, or secondary to insults such as alcoholic cirrhosis. Biliary tree stem/progenitor cells have recently been identified in peribiliary glands. These cells are involved in turnover and regeneration of biliary epithelia as well as in sclerosing reactions in some pathological conditions, such as primary sclerosing cholangitis and hepatolithiasis. Notably, hepatolithiasis is involved in mucin secretion by the peribiliary glands. Additionally, these cells are associated with the manifestation of several neoplasms, including intraductal papillary neoplasm, cystic micropapillary neoplasm, and cholangiocarcinoma. Normal peribiliary glands themselves are particularly small structures that cannot be recognized using any available imaging modalities; however, these glands are closely associated with several diseases, as mentioned above, which have typical imaging features. Therefore, knowledge of the basic pathophysiology of peribiliary glands is helpful for understanding biliary diseases associated with the peribiliary glands.
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20
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Tanaka A. IgG4-Related Sclerosing Cholangitis and Primary Sclerosing Cholangitis. Gut Liver 2020; 13:300-307. [PMID: 30205418 PMCID: PMC6529173 DOI: 10.5009/gnl18085] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 07/02/2018] [Accepted: 07/02/2018] [Indexed: 12/13/2022] Open
Abstract
Sclerosing cholangitis (SC) is defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis and currently includes three categories: primary sclerosing cholangitis (PSC), secondary cholangitis, and IgG4-related sclerosing cholangitis (IgG4-SC). SC categories share similar clinical features, such as cholestasis. Patients with SC present with cholestatic symptoms, including jaundice and pruritus, and blood tests reveal elevation of cholestatic enzymes. Cholangiography, endoscopic or magnetic, is inevitably required for making a diagnosis. Although the presentation of IgG4-SC and PSC are similar, the comorbidities, treatment response, and outcomes differ significantly, and therefore, it is strongly advisable to be familiar with these two diseases to make a correct diagnosis. Differentiation of cholangiocarcinoma from IgG4-SC and PSC is also extremely important. In this review, the clinical characteristics, comorbidities, treatment and outcomes of IgG4-SC and PSC will be outlined based on experience mainly from Japan.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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21
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Nwaduru C, Pillai A. Serum negative immunoglobulin G4-associated cholangiopathy mimicking hilar cholangiocarcinoma: A case report and review. INTERNATIONAL JOURNAL OF HEPATOBILIARY AND PANCREATIC DISEASES 2020. [DOI: 10.5348/100087z04cn2020cr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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22
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Bowlus CL, Lim JK, Lindor KD. AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review. Clin Gastroenterol Hepatol 2019; 17:2416-2422. [PMID: 31306801 DOI: 10.1016/j.cgh.2019.07.011] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/19/2019] [Accepted: 07/08/2019] [Indexed: 02/07/2023]
Abstract
DESCRIPTION The purpose of this clinical practice update is to define key principles in the surveillance of hepatobiliary cancers including cholangiocarcinoma, gallbladder adenocarcinoma, and hepatocellular carcinoma in patients with primary sclerosing cholangitis (PSC). METHODS The recommendations outlined in this expert review are based on available published evidence including observational studies and systematic reviews, and incorporates expert opinion where applicable. BEST PRACTICE ADVICE 1: Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age. BEST PRACTICE ADVICE 2: Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months BEST PRACTICE ADVICE 3: Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC. BEST PRACTICE ADVICE 4: Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture. BEST PRACTICE ADVICE 5: Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma. BEST PRACTICE ADVICE 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20. BEST PRACTICE ADVICE 7: The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm. BEST PRACTICE ADVICE 8: Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.
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Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Davis, California.
| | - Joseph K Lim
- Section of Digestive Diseases, Yale Liver Center, Yale University School of Medicine, New Haven, Connecticut
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona; Arizona State University, Phoenix, Arizona
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Abstract
OBJECTIVE. The purpose of this article is to present the pathologic and clinical features of IgG4-related sclerosing cholangitis (ISC), illustrate the associated imaging findings, and discuss treatment of the disorder. CONCLUSION. ISC is an inflammatory disorder involving the biliary system and resulting in strictures. Although often associated with autoimmune pancreatitis, it may be an isolated disease. Differentiation of ISC from other forms of cholangitis and cholangiocarcinoma is difficult but necessary for management. Imaging is important in diagnosing and assessing the extent of disease and planning a management strategy.
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Abstract
Immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) is a biliary tract manifestation of IgG4-related diseases (IgG4-RD); a subgroup of SC defined as a condition with progressive stenosis and destruction of the bile ducts due to diffuse inflammation and fibrosis. IgG4-SC is clinically characterized by the (a) chronic elevation of cholestatic enzyme levels, (b) significant elevation of serum IgG4 levels, (c) diffuse or segmental narrowing of intra and/or extra hepatic bile ducts with thickening of the bile duct wall in imaging studies, (d) marked lymphoplasmacytic and IgG4-positive plasma cell infiltration and fibrosis in histology, (e) presence of IgG4-RD in other organs, mainly involving autoimmune pancreatitis, and (f) excellent response to corticosteroids. The diagnosis of IgG4-SC is based on a combination of these findings. Although the IgG4-SC diagnosis is different from that of primary sclerosing cholangitis (PSC) or biliary and pancreatic malignancies, it is extremely important to diagnose or suspect IgG4-SC appropriately; as the incorrect diagnosis of PSC or malignant diseases may lead to the progression of fibrosis in patients due to untreated chronic cholestasis, or to unnecessary major surgical resections. Although its etiology remains unclear, recent studies of IgG4-SC have attempted to clarify the roles of the IgG4 molecule and novel autoantibodies detected in patients with IgG4-SC.
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Affiliation(s)
- Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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25
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Minaga K, Watanabe T, Chung H, Kudo M. Autoimmune hepatitis and IgG4-related disease. World J Gastroenterol 2019; 25:2308-2314. [PMID: 31148902 PMCID: PMC6529891 DOI: 10.3748/wjg.v25.i19.2308] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/13/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
IgG4-related disease (IgG4-RD) is a chronic-fibroinflammatory disorder affecting a wide range of organs. Elevation of serum IgG4 concentrations and abundant infiltration of IgG4-expressing plasma cells are key diagnostic features of this autoimmune disease. Although common organ involvement of IgG4-RD includes the salivary glands, pancreas, and bile duct, hepatic involvement is less well established. Recently, five studies identified a subtype of autoimmune hepatitis (AIH), called IgG4-associated AIH (IgG4-AIH). IgG4-AIH is diagnosed based on significant accumulation of IgG4-expressing plasmacytes in the liver in patients who met the diagnostic criteria for classical AIH. Although four of the five reports regarded IgG4-AIH based on hepatic accumulation of IgG4-positive cells alone, one report diagnosed IgG4-AIH based on both hepatic accumulation of IgG4-positive cells and elevated serum concentrations of IgG4. IgG4-AIH diagnosed based on the latter criteria may be a hepatic manifestation of IgG4-RD whereas IgG4-AIH diagnosed based on the former criteria may be a subtype of AIH. In this review article, we summarize and discuss clinicopathological features of IgG4-AIH.
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Affiliation(s)
- Kosuke Minaga
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
| | - Tomohiro Watanabe
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
| | - Hobyung Chung
- Department of Gastroenterology and Hepatology, Kobe City General Hospital, Chuo-ku, Kobe 650-0047, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
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26
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El-Nayir M, Subramanian A, Ali Z, Howlett D. IgG4-mediated sclerosing fibroinflammatory disease presenting as inflammatory breast malignancy. BJR Case Rep 2019; 5:20180041. [PMID: 31555465 PMCID: PMC6750634 DOI: 10.1259/bjrcr.20180041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 12/23/2018] [Accepted: 01/03/2019] [Indexed: 12/24/2022] Open
Abstract
IgG4-mediated sclerosing fibroinflammatory disease is a rare systemic disease which has the ability to form masses in multiple organs and may mimic malignancy. In this case we describe a 53-year-old female who presented with clinical and imaging findings in her right breast consistent with inflammatory breast carcinoma and associated right axillary nodal mass. She underwent CT which also uncovered a left thyroid mass and suggested both masses were possibly malignancies. She proceeded to ultrasound-guided core biopsy of each, which showed an appearance characteristic of IgG4-mediated sclerosing fibroinflammatory disease. The patient was treated with steroids with good outcome. This is the first described case of this condition presenting in this way to our knowledge and this diagnosis should be considered in patients with similar presentations.
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Affiliation(s)
| | | | - Zainab Ali
- East Sussex Healthcare NHS Trust, Eastbourne, UK
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27
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Gonzalez HH, Skrove JL, Rosen S, Sobrado J. A Curious Case of Autoimmune Pancreatitis with IgG4-related Sclerosing Cholangitis. Cureus 2019; 11:e4153. [PMID: 31058036 PMCID: PMC6488342 DOI: 10.7759/cureus.4153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is a novel entity that belongs to the immune-mediated fibroinflammatory class of IgG4-related diseases (IgG4-RD). IgG4-SC is noted to be one of the most frequent manifestations of extra-pancreatic disease among IgG4-RD, which is significantly different from primary SC (PSC) and cholangiocarcinoma (CC) as is evident in the varied approaches to treatment. IgG4-RD includes IgG4-SC and autoimmune pancreatitis (AIP). Herein, we presented a case of IgG4-SC in a patient with obstructive jaundice secondary to AIP. We have also discussed the current recommendations for diagnostic and treatment modalities, with an emphasis on the issues that arise in obtaining a definitive classification of disease.
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Affiliation(s)
- Hector H Gonzalez
- Internal Medicine, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, USA
| | - Jamie L Skrove
- Internal Medicine, Larkin Community Hospital, South Miami, USA
| | - Seth Rosen
- Gastroenterology, Larkin Community Hospital, South Miami, USA
| | - Javier Sobrado
- Internal Medicine, Larkin Community Hospital, South Miami, USA
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Schranz M, Lucà MG, D’Antiga L, Fagiuoli S. The Liver in Systemic Illness. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019:361-396. [DOI: 10.1007/978-3-319-96400-3_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Martínez-Valle F, Riveiro-Barciela M, Salcedo MT, Merino-Casabiel X, Fernández-Codina A, Torres ID, Esteban R, Buti M. Sclerosing Cholangitis Related to IgG4: Not Always a Curable Entity. Ann Hepatol 2019; 18:215-219. [PMID: 31113593 DOI: 10.5604/01.3001.0012.7916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 07/06/2017] [Indexed: 02/04/2023]
Abstract
IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.
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Affiliation(s)
- Fernando Martínez-Valle
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Xavier Merino-Casabiel
- Abdominal Imaging Unit, Radiology Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - Andreu Fernández-Codina
- Systemic Autoimmune Diseases Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - Inés de Torres
- Pathology Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - María Buti
- Liver Unit, Internal Medicine Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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Shichi S, Einama T, Suzuki M, Matsui H, Kanazawa R, Shibuya K, Suzuki T, Matsuzawa F, Nakachi K, Hashimoto T, Kondo N, Abe H, Taketomi A. Rare case of idiopathic sclerosing cholangitis, which was difficult to distinguish from cholangiocarcinoma: A case report. Exp Ther Med 2018; 16:5224-5226. [PMID: 30546416 PMCID: PMC6256851 DOI: 10.3892/etm.2018.6832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 09/28/2018] [Indexed: 11/29/2022] Open
Abstract
It is often difficult to correctly diagnose patients who present with dilation of the bile duct. Cholangiocarcinoma, primary sclerosing cholangitis (PSC) and immunoglobulin (Ig)G4-related sclerosing cholangitis must be considered as potential diagnoses for these cases. The current study presents a 73-year-old female patient who presented with a high fever and abdominal pain. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography revealed stenosis and dilation of the intrahepatic bile duct without solid components. It was suspected that the patient had intrahepatic cholangiocarcinoma. A left liver lobectomy, cholecystectomy and distal gastrectomy combined with a D2 lymph node dissection were performed. A pathological examination of the liver revealed increased fibrosis in the stroma, irregular bile duct dilation and clusters of inflamed lymph cells. No carcinoma or IgG4-positive plasma cells were observed and the typical findings of PSC were not detected. Based on these clinical and pathological results, the diagnosis was idiopathic sclerosing cholangitis, which is particularly rare. It is often difficult to preoperatively differentiate between cholangiocarcinoma and benign bile duct stenosis.
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Affiliation(s)
- Shunsuke Shichi
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Takahiro Einama
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan.,Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
| | - Mayu Suzuki
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Hiroki Matsui
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Ryo Kanazawa
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Kazuaki Shibuya
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan.,Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
| | - Takashi Suzuki
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan.,Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
| | - Fumihiko Matsuzawa
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan.,Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
| | - Kohei Nakachi
- Department of Gastroenterology, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Taku Hashimoto
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Nobuo Kondo
- GeneticLab Co., Ltd., Sapporo, Hokkaido 060-0009, Japan
| | - Hironori Abe
- Department of Surgery, Hokkaido Social Work Association Obihiro Hospital, Obihiro, Hokkaido 080-0805, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan
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IgG4-Related Sclerosing Cholangitis Involving the Intrahepatic Bile Ducts Diagnosed with Liver Biopsy. Case Rep Pathol 2018; 2018:2309293. [PMID: 30305974 PMCID: PMC6165622 DOI: 10.1155/2018/2309293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Revised: 07/15/2018] [Accepted: 08/14/2018] [Indexed: 11/18/2022] Open
Abstract
IgG4-related disease is characterized by lymphoplasmacytic inflammation and fibrosis, often leading to mass-forming lesions in different organs. When IgG4-related disease affects the bile ducts, it is called IgG4-related sclerosing cholangitis. A 74-year-old male complained of dysphagia and abdominal pain. Endoscopic retrograde cholangiography and magnetic resonance cholangiography revealed bile duct changes suspicious of a bile duct carcinoma or cholangitis. Liver biopsy showed storiform fibrosis, lymphoplasmacytic infiltration, obliterative phlebitis, and a portal-based inflammatory nodule with expansion of a portal tract. Hot spots revealed 339 IgG4-positive cells per high power field (HPF) and an IgG4/IgG ratio of 72%. Eight months earlier, an inguinal lymph node had been removed, showing expanded interfollicular zones and increased plasma cells. Hot spots revealed 593 IgG4-positive cells and an IgG4/IgG ratio of 92%. The serum IgG4 of the patient was elevated nearly 10 times upper limit of normal. The diagnosis of IgG4-related sclerosing cholangitis associated with IgG4-related lymphadenopathy was made. There was good response to treatment with prednisolone and azathioprine. The differentiation of IgG4-related sclerosing cholangitis from primary sclerosing cholangitis and bile duct carcinoma is often difficult. Liver biopsy only rarely contributes to this setting, but we describe and report in detail a case where liver biopsy showed a portal-based inflammatory nodule with the characteristic features of this disease.
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Mittelstaedt A, Meier PN, Dankoweit-Timpe E, Christ B, Jaehne J. IgG4-related sclerosing cholangitis mimicking hilar cholangiocarcinoma (Klatskin tumor): a case report of a challenging disease and review of the literature. Innov Surg Sci 2018; 3:157-163. [PMID: 31579779 PMCID: PMC6604574 DOI: 10.1515/iss-2018-0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Accepted: 04/19/2018] [Indexed: 12/22/2022] Open
Abstract
Background Even though IgG4-related disease has gained increased attention worldwide, the diagnosis remains challenging. IgG4-related sclerosing cholangitis (IgG4-SC) is not well described in the western hemisphere and may mimic cholangiocarcinoma (CC), especially when occurring without other symptoms such as, e.g. concurrent pancreatitis or retroperitoneal fibrosis. We present a case to add further information to the diagnosis and treatment of this challenging disease. Case report A 60-year-old male patient presented with painless jaundice. Prior medical history showed diabetes mellitus type I, high blood pressure, and deep vein thrombosis. Diagnostic investigations were strongly suspicious of a Klatskin tumor, although biopsies were inconclusive. The tumor marker Carbohydrate Antigen 19-9 (CA 19-9) was elevated. Prior to the recommended surgery, the patient had two second opinions in two different university hospitals, both arguing for surgery as well. The patient received hilar resection with right hemihepatectomy. During the postoperative course, some major complications occurred, i.e. recurrent pleural effusion, abscess in the liver resection area, sepsis, ileus, and restricted liver metabolism. Treatment with prednisolone did not show any improvement. Approximately 3 months after surgery, the patient died in consequence of acute respiratory failure. Histology showed no signs of CC, but IgG4-SC could be diagnosed. Conclusion In the case of preoperative signs of CC, differential diagnosis of IgG4-SC needs to be considered, in particular, in cases with missing histologic proof of malignant disease.
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Affiliation(s)
- Anke Mittelstaedt
- Clinic for General and Digestive Surgery, Center for Endocrine, Oncologic and Metabolic Surgery, DIAKOVERE Henriettenstift, Marienstraße 72-90, D-30171 Hannover, Germany
| | - Peter N Meier
- Clinic for Gastroenterology, DIAKOVERE Henriettenstift, Marienstraße 72-90, D-30171 Hannover, Germany
| | | | - Beate Christ
- Clinic for Diagnostic and Interventional Radiology, DIAKOVERE Henriettenstift, Marienstraße 72-90, D-30171 Hannover, Germany
| | - Joachim Jaehne
- Clinic for General and Digestive Surgery, Center for Endocrine, Oncologic and Metabolic Surgery, DIAKOVERE Henriettenstift, Marienstraße 72-90, D-30171 Hannover, Germany
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Dong X, Huo N, Wu Z, Wang G, Wang H, Zhao H. A case report of immunoglobulin G4-related sclerosing cholangitis with multiple relapse. Medicine (Baltimore) 2018; 97:e0700. [PMID: 29742724 PMCID: PMC5959437 DOI: 10.1097/md.0000000000010700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is classified as a biliary tract manifestation of immunoglobulin G4-related disease (IgG4-RD). Glucocorticoid is the first-line therapy for most patients, but the optimal starting dose, adequate maintaining dose and withdrawal time remain disputable. PATIENT CONCERNS An elderly male patient presented to our hospital with neoplasms of the bile duct and pancreas at first visit in December 2011. Further examination revealed bile duct stenosis and obstruction, and elevated serum IgG4 level. DIAGNOSES A diagnosis of IgG4-SC was established by examination results and effectiveness of steroid therapy, although IgG4-positive plasma cells were seldom seen in the liver sample. INTERVENTIONS Prednisolone was started from 40 mg daily, tapered gradually, and totally withdrawn after 22 months of treatment. OUTCOMES A new-onset cholangitis was detected 2 months later. Prednisolone 10 mg daily was administered again. Prednisolone was reduced to 5 mg every other day without consultation with his doctor 1 year ago in May 2017, then he presented to our hospital again with recurrent abdominal pain and jaundice. LESSONS IgG4-SC is a protean condition and can be distinguished from primary sclerosing cholangitis, malignancy, and other inflammatory disorders based on 4 clinical criteria. Serum IgG4/IgG1 ratio is a practicable diagnostic algorithm to distinguish PSC from IgG4-SC. The dose and duration of glucocorticoid for treatment should be adjusted according to clinical situations, and proper maintaining dose is essential for a better prognosis.
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Affiliation(s)
- Xiaoqin Dong
- Department of Infectious Diseases, Center for Liver Disease
| | - Na Huo
- Department of Infectious Diseases, Center for Liver Disease
| | - Zhao Wu
- Department of Infectious Diseases, Center for Liver Disease
| | - Guiqiang Wang
- Department of Infectious Diseases, Center for Liver Disease
| | - He Wang
- Department of Radiology, Peking University First Hospital, Beijing, China
| | - Hong Zhao
- Department of Infectious Diseases, Center for Liver Disease
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Tan L, Guan X, Zeng T, Wu S, Zheng W, Fu H, Long T, Wang Q, Meng Y, Tian Y, Yu J, Chen J, Li H, Cao L. The significance of serum IgG 4 and CA19-9, autoantibodies in diagnosis and differential diagnosis of IgG 4-related sclerosing cholangitis. Scand J Gastroenterol 2018; 53:206-211. [PMID: 29272982 DOI: 10.1080/00365521.2017.1416159] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To investigate the value of serum levels of IgG4 and CA19-9, and autoantibodies in the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC). METHODS We detected the serum IgG4 and CA19-9 of 45 IgG4-SC patients, 173 non-IgG4-SC patients and 48 healthy controls by immunoassay and chemiluminescence, respectively, with antinuclear antibody (ANA), anti-neutrophil antibody (ANCA), anti-smooth muscle antibody (SMA) and anti-mitochondrial antibody (AMA) level detected by indirect immunofluorescence. Then analyze the detection results. RESULTS (1) The positive rates of ANA, ANCA, SMA and AMA in patients with IgG4-SC were 40%, 6.67%, 0 and 2.22%. Among them, the positive rate of ANA was significantly higher than that of the healthy control group (p < .01), and the positive rate of ANA, ANCA, SMA and AMA were significantly different from that of the non-IgG4-SC group (p < .05). (2) Serum levels of IgG4 and CA19-9 increased significantly in patients with IgG4-SC compared with the healthy controls (p < .01). The areas under the ROC curve (AUC) of IgG4 and CA19-9 were 0.9750 and 0.6498, respectively (p < .05). CONCLUSION The high levels of serum IgG4 and CA19-9, and autoantibodies detections are of great important clinical value in diagnosis and differential diagnosis of IgG4-SC.
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Affiliation(s)
- Liming Tan
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
| | - Xiaolin Guan
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Tingting Zeng
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
| | - Sifan Wu
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Wei Zheng
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Huiying Fu
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Tingting Long
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Qiaohua Wang
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Yimei Meng
- b College of Public Health , Nanchang University , Nanchang , Jiangxi , China
| | - Yongjian Tian
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
| | - Jianlin Yu
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
| | - Juanjuan Chen
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
| | - Hua Li
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
| | - Liping Cao
- a Key Laboratory of Laboratory Medicine in Jiangxi Province, Department of the Clinical Laboratory , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China
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Martínez-Valle F, Orozco-Gálvez O, Fernández-Codina A. Update in ethiopathogeny, diagnosis and treatment of the IgG4 related disease. Med Clin (Barc) 2017; 151:18-25. [PMID: 29241876 DOI: 10.1016/j.medcli.2017.10.034] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 10/17/2017] [Accepted: 10/18/2017] [Indexed: 02/06/2023]
Abstract
IgG4 related disease (IgG4-RD) is probably an autoimmune pathology of unknown etiology. Diverse interactions participate in its pathogen between the adaptive and innate immune systems, activating lymphocytes B and T which trigger the inflammatory cascade, which culminates in fibrosis of the organs and their malfunction. It can affect a multitude of organs simultaneously. The diagnosis is based on the correlation of clinical findings with anatomopathological results (lymphoplasmocitary infiltrate, storiform fibrosis, obliterative phlebitis and IgG4+plasmatic cell count) and with the presence of elevated IgG4 in serum, depending on the criteria used. Corticoids and rituximab are among the few validated treatments available. There are multiple biomarkers and treatments in development. In this review, we aim to go over the principal pathogenic and clinical characteristics of IgG4-RD, as well as its handling, in accordance with the available scientific evidence.
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Affiliation(s)
- Fernando Martínez-Valle
- Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Vall Hebron, Universitat Autònoma de Barcelona, Barcelona, España; Vall d'Hebron Institut de Recerca, Barcelona, España.
| | - Olimpia Orozco-Gálvez
- Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Vall Hebron, Universitat Autònoma de Barcelona, Barcelona, España
| | - Andreu Fernández-Codina
- Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Universitario Vall Hebron, Universitat Autònoma de Barcelona, Barcelona, España; Vall d'Hebron Institut de Recerca, Barcelona, España; Rheumatology Division, Department of Medicine, University of Western Ontario, London, Ontario, Canadá
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36
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Hu HJ, Zhou RX, Shrestha A, Zhou Y, Li FY. Puzzle and Challenge in Differentiating Immunoglobulin G4-related Cholangitis from Hilar Cholangiocarcinoma. Chin Med J (Engl) 2017; 130:2641-2642. [PMID: 29067965 PMCID: PMC5678268 DOI: 10.4103/0366-6999.217086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Affiliation(s)
- Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Rong-Xing Zhou
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Anuj Shrestha
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China; Department of General Surgery, Gandaki Medical College, Pokhara 33700, Nepal
| | - Yong Zhou
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
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Abstract
BACKGROUND IgG4-related diseases are rare systemic multiorgan diseases and can thus affect any organ system. The incidence of diagnosis has significantly increased due to increasing awareness. OBJECTIVE In the abdomen the hepatopancreaticobiliary system provides an essential organ system for the expression of IgG4-associated autoimmune diseases. The focus here is autoimmune pancreatitis type 1 but IgG4-associated sclerosing cholangitis and IgG4-associated hepatopathy, which can also occur in combination are less well-known. METHODS Various mostly Asiatic, histologically-based diagnostic systems, such as HISORt or international consensus diagnostic criteria (ICDC) are available for the diagnostics of hepatopancreaticobiliary IgG4-related autoimmune diseases, in which imaging techniques playing an increasingly important role. RESULTS In addition to generalized organ swelling further morphological and also functional imaging criteria have become increasingly well-known for autoimmune pancreatitis, such as late enhancement or the imaging response to steroid therapy. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERP) can provide valuable information for the diagnostics of IgG4-related diseases in the hepatopancreaticobiliary system. CONCLUSION IgG4-related autoimmune diseases of the hepatopancreaticobiliary system are a rare group of diseases in which increasing knowledge of the radiological appearance also leads to an increasingly frequency of diagnosis. IgG4-related diseases must be distinguished from non-necrotizing pancreatitis and pancreatic cancer, which is often difficult but has significant therapeutic consequences for the patients.
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Affiliation(s)
- L Grenacher
- Diagnostik München, Augustenstraße 115, 80798, München, Deutschland.
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Geary K, Yazici C, Seibold A, Guzman G. IgG4-Related Cholangiopathy and Its Mimickers: A Case Report and Review Highlighting the Importance of Early Diagnosis. Int J Surg Pathol 2017; 26:165-173. [PMID: 28905689 DOI: 10.1177/1066896917730902] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Immunoglobulin (Ig) G4 (IgG4)-related disease is a recently described clinical entity that can involve multiple organs. It is an autoimmune disorder characterized by a dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. A key distinguishing factor is its dramatic response to steroid therapy. Although best described in cases of autoimmune pancreatitis, IgG4-related disease has also been implicated in patients with cholangitis and is now commonly referred to as IgG4-related cholangiopathy. It is characterized by elevated serum IgG4 levels, an IgG4-positive plasma cell infiltration with storiform fibrosis/obliterative phlebitis of the bile duct wall, and a response to steroids. It is crucial to differentiate IgG4-related cholangiopathy from its mimickers, such as primary biliary cholangitis, secondary biliary cholangitis, primary sclerosing cholangitis, secondary sclerosing cholangitis, and cholangiocarcinoma, because treatment modalities and outcomes of IgG4-related cholangiopathy differ significantly from these disorders. Here, we present an interesting case of IgG4-related cholangiopathy, discuss clinical and pathological features crucial to its early diagnosis, and compare and contrast this condition with its potentially confounding mimickers.
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Affiliation(s)
- Kyle Geary
- 1 University of Illinois at Chicago, IL, USA
| | | | - Anita Seibold
- 2 University of North Carolina at Chapel Hill, NC, USA
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Sun L, Li HY, Brigstock DR, Gao RP. IgG4-related sclerosing cholangitis and chronic sclerosing sialadenitis mimicking cholangiocarcinoma and neck malignancy. Hepatobiliary Pancreat Dis Int 2017; 16:443-445. [PMID: 28823378 DOI: 10.1016/s1499-3872(17)60042-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Li Sun
- Department of Hepatic-biliary-pancreatic Medicine, First Hospital of Jilin University, Changchun 130021, China
| | - Hong-Yan Li
- Department of Hepatic-biliary-pancreatic Medicine, First Hospital of Jilin University, Changchun 130021, China
| | - David R Brigstock
- The Research Institute at Nationwide Children's Hospital and Division of Pediatric Surgery, Department of Surgery, The Ohio State University, Columbus, OH 43205, USA
| | - Run-Ping Gao
- Department of Hepatic-biliary-pancreatic Medicine, First Hospital of Jilin University, Changchun 130021, China.
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The 2016 diagnostic criteria for primary sclerosing cholangitis. J Gastroenterol 2017; 52:838-844. [PMID: 27921168 DOI: 10.1007/s00535-016-1286-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 11/07/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown cause that is characterized pathologically by an inflammatory and fibrotic process centered on the epithelium, leading to diffuse biliary stenosis and increased wall thickness throughout the intra- and extra-hepatic biliary trees. A nationwide survey in Japan revealed several differences in the clinical aspects of PSC between Japan and Western countries. PSC was recently designated an intractable hepatobiliary disease in Japan. The aim of this study was to establish Japanese diagnostic criteria for PSC according to the current Japanese conditions. METHODS The Intractable Hepato-Biliary Diseases Study Group in Japan of the Committee of Research on Measures for Intractable Diseases established a working group consisting of researchers specializing in PSC and proposed the 2016 Japanese diagnostic criteria for PSC. RESULTS The diagnostic criteria consisted of the major and minor items. Major items are directly related to bile duct changes based on biliary tract imaging and an increased alkaline phosphatase level. Minor items consist of an association with inflammatory bowel disease and liver histology. CONCLUSION The diagnostic criteria for PSC are useful for general physicians in practice.
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Xiao J, Li G, Yang G, Jia C, Li B. Case report: A female case of isolated IgG4-related sclerosing cholangitis mimicking cholangiocarcinoma. Medicine (Baltimore) 2017; 96:e6542. [PMID: 28422840 PMCID: PMC5406056 DOI: 10.1097/md.0000000000006542] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
RATIONALE IgG4-related disease is a newly recognized fibroinflammatory disorder, characterized by tumefactive lesions, storiform fibrosis and IgG4-positive plasma cells infiltration. IgG4-related sclerosing cholangitis (IgG4-SC) is the most common extrapancreatic manifestation of IgG4-related disease, but it is frequently associated with autoimmune pancreatitis(AIP). Only few case was reported to be diagnosed with IgG4-SC in the absence of AIP, with a striking male preponderance. Here we report a female case of isolated IgG4 related sclerosing cholangitis mimicking cholangiocarcinoma. PATIENT CONCERNS A 58-year-old woman complaint of one-month history of jaundice and right upper quadrant discomfort, and the biliary reconstruction showed full-length wall thickening and segmental stenosis. DIAGNOSES Cholangiocarcinoma was then diagnosed. INTERVENTIONS Choledochoplasty was performed, followed by Roux-en-Y anastomosis. OUTCOMES However, pathological examination revealed IgG4-related sclerosing cholangitis (IgG4-SC) and the retrospective measurement of serum IgG4 was 346 mg/dL post-operatively. The patient was followed for another nine monthswithout recurrence. LESSONS The differential diagnosis between cholangiocarcinoma and IgG4-SC is challenging due to significant overlap of clinical manifestations, lab tests and imaging characteristics. However, as an afterthought of this case, typical cholangiocarcinoma rarely presents full-length wall thickening. What the case taught us was pre-operative IgG4 measurement for patients with long bile duct involvement was highly recommended in order to rule out IgG4-SC.
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Affiliation(s)
| | | | | | - Congwei Jia
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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Liu W, Chen W, He X, Qu Q, Hong T, Li B. Poor response of initial steroid therapy for IgG4-related sclerosing cholangitis with multiple organs affected. Medicine (Baltimore) 2017; 96:e6400. [PMID: 28328835 PMCID: PMC5371472 DOI: 10.1097/md.0000000000006400] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
IgG4-related sclerosing cholangitis (IgG4-SC) is a rare biliary manifestation in which many other organs might be affected. The purpose of our study was to investigate the different clinical characteristics and initial steroid response between IgG4-SC patients with and without other organs affected.A series of patients with IgG4-SC in the period from January 2006 to December 2015 at our hospital were included. The pancreas and major salivary glands were screened, and the initial corticosteroid therapy was given. Clinical information was collected and analyzed including demographics, clinical presentation, IgG4 serology, imaging features, and treatment outcomes.The study identified 72 IgG4-SC patients, including 60 males and 12 females. The mean age was 59.8 years old. Among these IgG4-SC patients, 10 patients had only bile duct involved, 42 patients had 2 organs involved and 20 patients had multiple organs involved. In patients with multiple organs involved, more complaints were given (mean 2.9 kinds), higher serum IgG4 levels were found (23458 ± 19402.7 mg/L), and more stricture lesions of biliary tract were shown. All 72 patients exhibited a disease response within 4 to 6 weeks of starting steroids. The remission rate in the multiple lesions group was lower (60%), and the recurrence rate is higher (83.3%). The relapse-free survival was 20.0 months in the single lesion group, which is longer than that in the multiple lesions group (3.1 months, P < 0.05).The IgG4-SC patients with multiple organs affected had more complaints, higher serum IgG4 levels, and poor response to initial steroids.
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Rungsakulkij N, Sornmayura P, Tannaphai P. Isolated IgG4-related sclerosing cholangitis misdiagnosed as malignancy in an area with endemic cholangiocarcinoma: a case report. BMC Surg 2017; 17:17. [PMID: 28202062 PMCID: PMC5311850 DOI: 10.1186/s12893-017-0214-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 02/10/2017] [Indexed: 12/15/2022] Open
Abstract
Background The most common cause of perihilar obstruction is cholangiocarcinoma, especially in Thailand. Benign perihilar stricture represents less than 20% of cases. IgG4-related disease and IgG4-related sclerosing cholangitis, however, have been receiving increased recognition. Isolated IgG4-related sclerosing cholangitis is less common. The preoperative diagnosis of IgG4-related sclerosing cholangitis without pancreatic involvement is very difficult because the clinical presentation and preoperative evaluation are extremely difficult to distinguish from perihilar cholangiocarcinoma. Case presentation We report the case of a 56-year-old man who presented with obstructive jaundice with preoperative imaging showing proximal common bile duct obstruction. He underwent right lobe liver hepatectomy with extrahepatic bile duct resection and regional lymph node dissection due to high suspicion of malignancy. The pathological report showed severe acute and chronic inflammation of the bile duct with morphology and immunohistochemistry suggestive of IgG4-related sclerosing cholangitis. Conclusions IgG4-related sclerosing cholangitis with perihilar obstruction should be considered even in areas where cholangiocarcinoma is endemic.
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Affiliation(s)
- Narongsak Rungsakulkij
- Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.
| | - Pattana Sornmayura
- Department of Pathology, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
| | - Penampai Tannaphai
- Department of Radiology, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
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Li Y, Zhou L, Zhao X, Song W, Karunaratna N, Wang B. The importance of IgG4 screening in patients diagnosed with primary sclerosing cholangitis in the past: A case rediagnosed as IgG4-SC after 10 years. Medicine (Baltimore) 2016; 95:e5628. [PMID: 27977604 PMCID: PMC5268050 DOI: 10.1097/md.0000000000005628] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
RATIONALE While primary sclerosing cholangitis (PSC) has been recognized for decades, immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) has been correctly diagnosed only in recent years. PSC and IgG4-SC show similar clinical symptoms, serologic markers, and imaging results, but the treatment strategies and prognosis of patients differ. PATIENT CONCERNS Here, we present the case report of a patient diagnosed with PSC for 10 years and rediagnosed with IgG4-SC recently, to emphasize the importance of screening serum IgG4 levels in patients with previous diagnosis of PSC. DIAGNOSES A 57-year-old woman with 10-year history of PSC was hospitalized due to pruritus. In 2004, the patient underwent cholecystectomy and cholangioenterostomy because of unexplained jaundice with pancreatic swelling. In the last 10 years, her liver enzyme levels were continuously elevated. The latest liver function profile showed elevated alanine aminotransferase, aspartate aminotransferase, and total bilirubin. IgG4 was 3.69 (0.03-2.01 g/L). Immunohistochemical staining of the surgical specimen showed >10 IgG4-positive plasma cells per high-power field, and IgG4+/IgG+ plasma cells >40%. INTERVENTIONS AND OUTCOMES She was treated with prednisone 40 mg once-daily and the dose was gradually tapered. The patient remains well after 18 months. LESSONS SUBSECTIONS Patients with IgG4-SC may be misdiagnosed as PSC due to lack of IgG4 screening. It is important to perform IgG4 screening in patients diagnosed as PSC. Steroid is effective to prevent disease progression in these patients.
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Affiliation(s)
- Yanni Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University
| | - Lu Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University
| | - Xin Zhao
- Department of Radiology, Tianjin Medical University General Hospital, Tianjin Medical University
| | - Wenjing Song
- Department of Pathology, Tianjin Medical University General Hospital, Tianjin Medical University
| | - Nathasha Karunaratna
- Department of Postgraduate, International School of Tianjin Medical University, Tianjin, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University
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Abstract
Differentiating benign and malignant biliary strictures is a challenging and important clinical scenario. The typical presentation is indolent and involves elevation of liver enzymes, constitutional symptoms, and obstructive jaundice with or without superimposed or recurrent cholangitis. While overall the most common causes of biliary strictures are malignant, including cholangiocarcinoma and pancreatic adenocarcinoma, benign strictures encompass a wide spectrum of etiologies including iatrogenic, autoimmune, infectious, inflammatory, and congenital. Imaging plays a crucial role in evaluating strictures, characterizing their extent, and providing clues to the ultimate source of biliary obstruction. While ultrasound is a good screening tool for biliary ductal dilatation, it is limited by a poor negative predictive value. Magnetic resonance cholangiopancreatography is more than 95% sensitive and specific for detecting biliary strictures with the benefit of precise anatomic localization. Other commonly employed imaging modalities include endoscopic retrograde cholangiopancreatography with endoscopic ultrasound, contrast-enhanced CT, and cholangiography. First-line treatment of benign biliary strictures is endoscopic dilation and stenting. In patients with anatomy that precludes endoscopic cannulation, percutaneous biliary drain insertion and balloon dilation is preferred.
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Affiliation(s)
- Ashley Altman
- Department of Radiology, The University of Chicago, Chicago, Illinois
| | - Steven M Zangan
- Department of Radiology, The University of Chicago, Chicago, Illinois
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Li ZF, Fan HJ, Sun LJ, Song M. Advances in research of immunoglobulin G4-related sclerosing cholangitis. Shijie Huaren Xiaohua Zazhi 2016; 24:4156-4161. [DOI: 10.11569/wcjd.v24.i30.4156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is a special form of cholangitis. As an autoimmune disease, IgG4-related sclerosing cholangitis has no specific clinical manifestations, and its pathogenesis remains unclear. In patients with this disease, serum concentration of IgG4 is elevated, intrahepatic or extrahepatic bile duct stenosis associated with biliary wall thickening is often revealed by biliary imaging, autoimmune diseases such as autoimmune pancreatitis may be present, and massive IgG4 positive plasma cell infiltration and widespread bile duct wall fibrosis are often showed by histopathological examination. It is often difficult to differentiate IgG4-related sclerosing cholangitis from primary sclerosing cholangitis, secondary sclerosing cholangitis and bile duct cancer. However, the disease is sensitive to hormone therapy. This article will review the current advances in research of IgG4-related sclerosing cholangitis.
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Abstract
IgG4-related hepatobiliary diseases are part of a multiorgan fibroinflammatory condition termed IgG4-related disease, and include IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy. These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies. Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. However, a gold standard diagnostic test is lacking, warranting the identification of more specific disease markers. Novel assays - such as the serum IgG4:IgG1 ratio and IgG4:IgG RNA ratio (which distinguish IgG4-SC from PSC with high serum IgG4 levels), and plasmablast expansion to recognize IgG4-SC with normal serum IgG4 levels - require further validation. Steroids and other immunosuppressive therapies can lead to clinical and radiological improvement when given in the inflammatory phase of the disease, but evidence for the efficacy of treatment regimens is limited. Progressive fibrosclerotic disease, liver cirrhosis and an increased risk of malignancy are now recognized outcomes. Insights into the genetic and immunological features of the disease have increased over the past decade, with an emphasis on HLAs, T cells, circulating memory B cells and plasmablasts, chemokine-mediated trafficking, as well as the role of the innate immune system.
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Diagnostic performance of imaging criteria for distinguishing autoimmune cholangiopathy from primary sclerosing cholangitis and bile duct malignancy. ACTA ACUST UNITED AC 2016; 40:3052-61. [PMID: 26350286 DOI: 10.1007/s00261-015-0543-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVE To determine the diagnostic performance of imaging criteria for distinguishing Ig-G4-associated autoimmune cholangiopathy (IAC) from primary sclerosing cholangitis (PSC) and bile duct malignancy. METHODS A medical records search between January 2008 and October 2013 identified 10 patients (8 M, 2 F, mean age 61 years, range 34-82) with a clinical diagnosis of IAC. Fifteen cases of PSC (6 M, 9 F, mean age 50, range 22-65) and 15 cases of biliary malignancy (7 M, 8 F, mean age 65, range 48-84) were randomly selected for comparative analysis. Three abdominal radiologists independently reviewed MRI with MRCP (n = 32) or CT (n = 8) and ERCP (n = 8) for the following IAC imaging predictors: single-wall bile duct thickness >2.5 mm, continuous biliary involvement, gallbladder involvement, liver disease, peribiliary mass, or pancreatic and renal abnormalities. Each radiologist provided an imaging-based diagnosis (IAC, PSC, or cancer). Imaging predictor sensitivity, specificity, accuracy, and association with IAC using Fisher's exact test. Inter-reader agreement determined using Fleiss' kappa statistics. RESULTS For diagnosis of IAC, sensitivities and specificities were high (70-93%). Pancreatic abnormality was strongest predictor for distinguishing IAC from PSC and cancer, with high diagnostic performance (70-80% sensitivity, 87-97% specificity), significant association (p < 0.01), and moderate inter-reader agreement (κ = 0.59). Continuous biliary involvement was moderately predictive (50-100% sensitivity, 53-83% specificity) and trended toward significant association in distinguishing from PSC (p = 0.01-0.19), but less from cancer (p = 0.06-0.62). CONCLUSION It remains difficult to distinguish IAC from PSC or bile duct malignancy based on imaging features alone. The presence of pancreatic abnormalities, including peripancreatic rind, atrophy, abnormal enhancement, or T2 signal intensity, strongly favors a diagnosis of IAC.
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IgG4-associated sclerosing cholangitis masquerading as hilar cholangiocarcinoma. Indian J Gastroenterol 2016; 35:315-8. [PMID: 27439915 DOI: 10.1007/s12664-016-0672-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Accepted: 06/30/2016] [Indexed: 02/04/2023]
Abstract
IgG4-sclerosing cholangitis (IgG4-SC) commonly presents with type 1 autoimmune pancreatitis. Isolated IgG4-SC is rare. Differentiating IgG4-SC from cholangiocarcinoma preoperatively is challenging due to overlapping radio-clinical manifestations and difficult preoperative histology. We present three cases preoperatively diagnosed and surgically treated as hilar cholangiocarcinoma. First and second cases presented with cholangiocarcinoma with portal vein involvement and third with a malignant-appearing hilar stricture. On histopathology, IgG4-SC was diagnosed in the first two cases. Third patient had raised serum IgG4, and histopathology was inconclusive for IgG4-SC and negative for malignancy. However, she responded to steroid therapy.
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Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma. Med Mol Morphol 2016; 49:189-202. [PMID: 27350291 DOI: 10.1007/s00795-016-0143-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 06/04/2016] [Indexed: 12/17/2022]
Abstract
Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.
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