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Facciorusso A, Crinò SF, Gkolfakis P, Spadaccini M, Arvanitakis M, Beyna T, Bronswijk M, Dhar J, Ellrichmann M, Gincul R, Hritz I, Kylänpää L, Martinez-Moreno B, Pezzullo M, Rimbaş M, Samanta J, van Wanrooij RLJ, Webster G, Triantafyllou K. Diagnostic work-up of bile duct strictures: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2025; 57:166-185. [PMID: 39689874 DOI: 10.1055/a-2481-7048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
1: ESGE recommends the combination of endoscopic ultrasound-guided tissue acquisition (EUS-TA) and endoscopic retrograde cholangiopancreatography (ERCP)-based tissue acquisition as the preferred diagnostic approach for tissue acquisition in patients with jaundice and distal extrahepatic biliary stricture in the absence of a pancreatic mass. 2: ESGE suggests that brushing cytology should be completed along with fluoroscopy-guided biopsies, wherever technically feasible, in patients with perihilar biliary strictures. 3: ESGE suggests EUS-TA for perihilar strictures when ERCP-based modalities yield insufficient results, provided that curative resection is not feasible and/or when cross-sectional imaging has shown accessible extraluminal disease. 4: ESGE suggests using standard ERCP diagnostic modalities at index ERCP. In the case of indeterminate biliary strictures, ESGE suggests cholangioscopy-guided biopsies, in addition to standard ERCP diagnostic modalities. Additional intraductal biliary imaging modalities can be selectively used, based on clinical context, local expertise, and resource availability.
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Affiliation(s)
- Antonio Facciorusso
- Experimental Medicine, Università del Salento, Lecce, Italy
- Clinical Effectiveness Research Group, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | | | - Paraskevas Gkolfakis
- Gastroenterology, "Konstantopoulio-Patision" General Hospital of Nea Ionia, Athens, Greece
| | | | - Marianna Arvanitakis
- Gastroenterology, Digestive Oncology and Hepatopancreatology, HUB Hôpital Erasme, Brussels, Belgium
| | - Torsten Beyna
- Internal Medicine, Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany
| | - Michiel Bronswijk
- Gastroenterology and Hepatology, Imelda Hospital, Bonheiden, Belgium
- Gastroenterology and Hepatology, KU Leuven University Hospitals Leuven, Leuven, Belgium
| | | | - Mark Ellrichmann
- Interdisciplinary Endoscopy, Medical Department I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Rodica Gincul
- Gastroenterology, Jean Mermoz Private Hospital, Lyon, France
| | - Istvan Hritz
- Centre for Therapeutic Endoscopy, Semmelweis University, Budapest, Hungary
| | - Leena Kylänpää
- Surgery, Helsinki Univeristy Central Hospital, Helsinki, Finland
| | | | | | - Mihai Rimbaş
- Gastroenterology, Colentina Clinical Hospital, Bucharest, Romania
- Internal Medicine Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | | | - Roy L J van Wanrooij
- Gastroenterology and Hepatology, Amsterdam UMC Locatie VUmc, Amsterdam, Netherlands
| | - George Webster
- Pancreatobiliary Medicine Unit, University College London, London, United Kingdom of Great Britain and Northern Ireland
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, 2nd Department of Internal Medicine, Propaedeutic, Medical School, National and Kapodistrian University of Athens, "Attikon" University General Hospital, Athens, Greece
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Furukawa M, Ishii Y, Tatsukawa Y, Nakamura S, Ikemoto J, Miyamoto S, Nakamura K, Yamashita Y, Iijima N, Okuda Y, Nomura R, Arihiro K, Hanada K, Oka S. Endoscopic Retrograde Cholangiopancreatography-Related Procedures for the Differential Diagnosis of Isolated Immunoglobin G4-Related Sclerosing Cholangitis and Perihilar Cholangiocarcinoma. Diagnostics (Basel) 2024; 14:1621. [PMID: 39125497 PMCID: PMC11311300 DOI: 10.3390/diagnostics14151621] [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: 06/03/2024] [Revised: 07/09/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND/PURPOSE Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). METHODS Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. RESULTS In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. CONCLUSIONS Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.
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Affiliation(s)
- Masaru Furukawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Yasutaka Ishii
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Yumiko Tatsukawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Shinya Nakamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Juri Ikemoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Sayaka Miyamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Kazuki Nakamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Yumiko Yamashita
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Noriaki Iijima
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Yasuhiro Okuda
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Risa Nomura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
| | - Koji Arihiro
- Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima 734-0037, Japan;
| | - Keiji Hanada
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima 722-0018, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan; (M.F.)
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Wu S, Wang H. IgG4-related digestive diseases: diagnosis and treatment. Front Immunol 2023; 14:1278332. [PMID: 37868965 PMCID: PMC10585276 DOI: 10.3389/fimmu.2023.1278332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 09/22/2023] [Indexed: 10/24/2023] Open
Abstract
IgG4-related digestive diseases encompass a group of chronic inflammatory disorders characterized by autoimmune reactions and fibrosis affecting multiple digestive organs. These diseases are identified by elevated serum levels of IgG4 and the presence of IgG4-positive plasma cell infiltration in the affected sites, along with storiform fibrosis, obliterative phlebitis, and eosinophilic infiltration. Although extensive research has been conducted, a comprehensive understanding of these conditions remains elusive. Current clinical diagnosis often relies on the application of integrated diagnostic criteria for IgG4-related diseases, combined with specific organ involvement criteria. Distinguishing them from malignancies poses considerable challenges. Moreover, further investigations are required to elucidate the underlying pathogenic mechanisms and explore potential therapeutic interventions. This review provides a systematic classification of IgG4-related digestive diseases while discussing their diagnostic strategies, clinical presentations, and treatment modalities. The comprehensive insights shared herein aim to guide clinicians in their practice and contribute to the advancement of knowledge in this field.
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Affiliation(s)
- Siyu Wu
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Haiqiang Wang
- Department of Internal Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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Caverenne L, Weichselbaum L, Van Hoof M, Deltenre P. An unusual cause of extrahepatic cholestasis associated with solid liver lesions: a case report. Acta Gastroenterol Belg 2023; 86:490-492. [PMID: 37814566 DOI: 10.51821/86.3.10393] [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] [Indexed: 10/11/2023]
Abstract
IgG4-related sclerosing cholangitis is a special type of cholangiopathy often associated with autoimmune pancreatitis. In this article, we report an unusual case of IgG4-SC limited to the common hepatic duct and associated with pseudo tumoral liver lesions, but without evidence of pancreatic involvement. Corticosteroid therapy was rapidly effective and allowed normalization of liver tests.
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Affiliation(s)
- L Caverenne
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - L Weichselbaum
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - M Van Hoof
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
| | - P Deltenre
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
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Cho SH, Song TJ, Park JS, Yoon JH, Yang MJ, Yoon SB, Lee JM, Lee YN, Kim SH, Choi EK, Park SW, Oh D, Park DH, Lee SS, Seo DW, Lee SK, Kim MH. Comparison of the long-term outcomes between proximal and distal IgG4-related sclerosing cholangitis: A multicenter cohort study. J Gastroenterol Hepatol 2023; 38:648-655. [PMID: 36710432 DOI: 10.1111/jgh.16136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 01/11/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is considered a biliary manifestation of IgG4-related diseases. However, there has been a controversy on the clinical outcomes according to the location of the involved bile duct. We therefore compared the clinical outcomes and long-term prognosis of IgG4-SC with proximal bile duct involvement (proximal IgG4-SC) and IgG4-SC with distal bile duct involvement (distal IgG4-SC). METHODS We reviewed the data of patients with IgG4-SC that were prospectively collected at 10 tertiary centers between March 2002 and October 2020. Clinical manifestations, outcomes, association with autoimmune pancreatitis (AIP), steroid-responsiveness, and relapse of IgG4-SC were evaluated. RESULTS A total of 148 patients (proximal IgG4-SC, n = 59; distal IgG4-SC, n = 89) were analyzed. The median age was 65 years (IQR, 56.25-71), and 86% were male. The two groups were similar in terms of jaundice at initial presentation (51% vs 65%; P = 0.082) and presence of elevated serum IgG4 (66% vs 70%; P = 0.649). The two groups showed significant differences in terms of steroid-responsiveness (91% vs 100%; P = 0.008), association with AIP (75% vs 99%; P = 0.001), and occurrence of liver cirrhosis (9% vs 1%; P = 0.034). During a median follow-up of 64 months (IQR, 21.9-84.7), the cumulative relapse-free survival was significantly different between the two groups (67% vs 79% at 5 years; P = 0.035). CONCLUSIONS Relapse of IgG4-SC frequently occurred during follow-up. Proximal IgG4-SC and distal IgG4-SC had different long-term outcomes in terms of steroid-responsiveness, occurrence of liver cirrhosis, and recurrence. It may be advantageous to determine the therapeutic and follow-up strategies according to the location of bile duct involvement.
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Affiliation(s)
- Sung Hyun Cho
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Tae Jun Song
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Jin-Seok Park
- Division of Gastroenterology, Department of Internal Medicine, Inha University School of Medicine, Incheon, South Korea
| | - Jai Hoon Yoon
- Division of Gastroenterology, Department of Internal medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, South Korea
| | - Min Jae Yang
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, South Korea
| | - Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jae Min Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Yun Nah Lee
- Department of Gastroenterology, Soonchunhyang University School of Medicine, Bucheon, South Korea
| | - Seong-Hun Kim
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea
| | - Eun Kwang Choi
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, South Korea
| | - Se Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Gyeonggi-do, South Korea
| | - Dongwook Oh
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Do Hyun Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sang Soo Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Sung Koo Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Myung-Hwan Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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Nadi A, Benhayoun Y, Cherkaoui R, Delsa H, Rouibaa F. Case Series of Autoimmune Pancreatitis and IgG4-Related Sclerosing Cholangitis. Cureus 2022; 14:e26657. [PMID: 35949783 PMCID: PMC9357350 DOI: 10.7759/cureus.26657] [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] [Accepted: 07/08/2022] [Indexed: 11/05/2022] Open
Abstract
IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease that can involve any organ. The involvement of the pancreas and biliary tract is the most common and well-studied in the literature. It is characterized by a non-specific presentation, mimicking a malignant process. The goal was to look at the different clinical and paraclinical aspects of this disease, as well as the challenges that come from its management. It was made up of three observations of patients with IgG4-RD involving the biliary tract and pancreas. The first observation concerned intrahepatic biliary cholangitis that was accompanied by porto-mesenteric thrombosis, which was discovered by cholestatic jaundice on the 15th day after an appendectomy, and the patient improved under corticosteroids and anticoagulants. The second observation concerned an acute revelation of the disease. It was an acute attack of chronic pancreatitis of IgG4-RD. The main symptoms were pancreatic pain and exocrine pancreatic insufficiency, and corticosteroid therapy allowed remission. The third observation was related to autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis, revealed by jaundice with cholestasis. The patient acquired corticosteroid resistance and an adverse progression to decompensated cirrhosis, and liver transplantation was indicated. The clinical presentation of IgG4-RD is heterogeneous, as evidenced by our three clinical observations. There are still significant gaps in our understanding, particularly in terms of pathogenesis and factors that influence therapy response. Further observational and interventional research is needed to better manage this disease.
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Affiliation(s)
- Anass Nadi
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Yassamin Benhayoun
- Gastroenterology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Reda Cherkaoui
- Radiology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Hanane Delsa
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
| | - Fedoua Rouibaa
- Gastroenterology and Hepatology, Faculty of Medicine, Mohammed VI University of Health Sciences (UM6SS), Casablanca, MAR
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IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease. Can J Gastroenterol Hepatol 2021; 2021:1959832. [PMID: 34970512 PMCID: PMC8714375 DOI: 10.1155/2021/1959832] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/08/2021] [Accepted: 12/01/2021] [Indexed: 11/30/2022] Open
Abstract
IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.
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8
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Okaniwa S. Role of transabdominal ultrasound in the diagnosis of autoimmune pancreatitis. J Med Ultrason (2001) 2021; 48:525-536. [PMID: 34476654 DOI: 10.1007/s10396-021-01133-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 07/20/2021] [Indexed: 01/05/2023]
Abstract
The most important thing in the diagnosis of autoimmune pancreatitis (AIP) is to suspect the possibility of AIP. In the acute phase, diffuse pancreatic enlargement is a highly specific finding of AIP compared to focal enlargement. Though the sensitivity is low, high-frequency transducers can detect the capsule-like rim sign and penetrating duct sign. Those findings are characteristic of AIP and useful for differential diagnosis with pancreatic carcinoma. In focal AIP, both contrast-enhanced US showing iso/hypervascularity and elastography showing increased stiffness not only in the focal enlargement but also in the surrounding parenchyma are also useful for differential diagnosis. Furthermore, changes over time after the two-week steroid trial, such as resolution or measurable reduction in parenchymal enlargement and a decrease in the mean shear-wave velocity on elastography, are also cardinal features of AIP. Since AIP is a pancreatic manifestation in immunoglobulin G4-related disease, evaluation of other organs, including the biliary tract and salivary glands, is particularly useful in focal AIP. A characteristic US finding of bile ducts is three-layered (high-low-high pattern) wall thickening with a markedly thickened middle layer. US can also detect wall thickening of bile ducts, which show no abnormalities on cholangiography. These findings are useful for differential diagnosis with cholangiocarcinoma. Multiple hypoechoic areas in submandibular glands are characteristic US findings of sialadenitis in type 1 AIP, and the sensitivity is higher than that of physical examination. US can further contribute to the diagnosis of AIP by employing elastography and contrast-enhanced US in addition to high-frequency transducers.
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Affiliation(s)
- Shinji Okaniwa
- Department of Gastroenterology, Iida Municipal Hospital, 438 Yawata-machi, Iida, Nagano, 395-8502, Japan.
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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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10
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Okamura Y, Nishitai R, Sasaki N, An H, Fushitani M, Ota T, Morioka M, Kawaguchi K, Konishi S, Hamasu S, Manaka D. Intrahepatic bile duct rupture associated with IgG4-related sclerosing cholangitis presenting hepatic inflammatory pseudotumor. Clin J Gastroenterol 2021; 14:1530-1535. [PMID: 34312794 DOI: 10.1007/s12328-021-01487-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/21/2021] [Indexed: 12/12/2022]
Abstract
A 67-year-old man with a low-grade fever was found to have a 25-mm diameter tumor of the left hepatic umbilical portion. The tumor was accompanied by occlusion of the left portal vein. Positron emission tomography using fluorodeoxyglucose showed that the tumor had abnormally high metabolic activity. Magnetic resonance imaging revealed the left hepatic duct segmental narrowing. There was a mild elevation in serum IgG4 (206 mg/dL). Intrahepatic cholangiocarcinoma was suspected. Instead of planned hepatectomy, the patient was forced to undergo emergency surgery for biliary panperitonitis caused by intrahepatic bile duct rupture. Intraoperative ultrasonography revealed a hypoechoic tumor-like thickened Glissonean sheath and needle biopsy was performed. Histologic examination confirmed fibrous tissue with IgG4-positive plasma cell infiltration without neoplastic proliferation. He was diagnosed with IgG4-related sclerosing cholangitis (IgG4-SC) presenting hepatic inflammatory pseudotumor. After his general condition improved, he underwent left hepatectomy. Macroscopic findings showed extreme fibrosis of the Glissonean sheath of the umbilical portion, and diffuse granular lesion aggregated in the left lateral segment. Microscopic examination confirmed chronic cholangitis and dense portal fibrosis in the umbilical portion and diffuse xanthogranulomatous inflammation. This is the first case report of spontaneous rupture of the intrahepatic bile duct in patient with IgG4-SC.
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Affiliation(s)
- Yusuke Okamura
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan.
| | - Ryuta Nishitai
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Naoya Sasaki
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Hideo An
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Masashi Fushitani
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Takano Ota
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Michina Morioka
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Kiyotaka Kawaguchi
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Sayuri Konishi
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Shinya Hamasu
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
| | - Dai Manaka
- Department of Surgery, Kyoto Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto City, Kyoto, 615-8256, Japan
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Hori Y, Chari ST, Tsuji Y, Takahashi N, Inoue D, Hart PA, Uehara T, Horibe M, Yamamoto S, Satou A, Zhang L, Notohara K, Naitoh I, Nakazawa T. Diagnosing Biliary Strictures: Distinguishing IgG4-Related Sclerosing Cholangitis From Cholangiocarcinoma and Primary Sclerosing Cholangitis. Mayo Clin Proc Innov Qual Outcomes 2021; 5:535-541. [PMID: 34195545 PMCID: PMC8240333 DOI: 10.1016/j.mayocpiqo.2021.03.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023] Open
Abstract
Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.
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Key Words
- AIP, autoimmune pancreatitis
- CT, computed tomography
- ERC, endoscopic retrograde cholangiography
- ERCP, endoscopic retrograde cholangiopancreatography
- EUS, endoscopic ultrasound
- FNA, fine-needle aspiration
- IDUS, intraductal ultrasonography
- IgG4, immunoglobulin G4
- IgG4-RD, IgG4-related disease
- IgG4-SC, IgG4-related sclerosing cholangitis
- MRCP, magnetic resonance cholangiopancreatography
- MRI, magnetic resonance imaging
- PSC, primary sclerosing cholangitis
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Affiliation(s)
- Yasuki Hori
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Suresh T. Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Yoshihisa Tsuji
- Department of General Medicine, Sapporo Medical University, Sapporo, Japan
| | | | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Phil A. Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University, Matsumoto, Japan
| | - Masayasu Horibe
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Satoshi Yamamoto
- Department of Gastroenterology, Bantane Hospital, Fujita Health University, Nagoya, Japan
| | - Akira Satou
- Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan
| | - Lizhi Zhang
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Toyohara T, Nakazawa T, Zakharia K, Shimizu S, Miyabe K, Harada K, Notohara K, Yamada T, Hayashi K, Naitoh I, Hayashi K, Kataoka H. IgG4-related Sclerosing Cholangitis Complicated with Cholangiocarcinoma and Detected by Forkhead Box P3 Immunohistochemical Staining. Intern Med 2021; 60:859-866. [PMID: 33087673 PMCID: PMC8024973 DOI: 10.2169/internalmedicine.5920-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
An 80-year-old man was admitted due to biliary stricture with autoimmune pancreatitis. Although radiographical examinations suggested Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC), punched biopsies from the bile duct revealed adenocarcinoma. In the resected specimen, abundant N-terminus of Forkhead box P3 (Foxp3)-positive cells were localized in cholangiocarcinoma (CCA) tissue, while IgG4-positive cells were spread around the entire bile duct. Therefore, the case was diagnosed with IgG4-SC accompanied by CCA, not sporadic CCA. We herein report an informative case wherein IgG4-positive cells were abundant in CCA tissue and Foxp3 immunohistochemical staining allowed us to determine that this case had two entities.
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Affiliation(s)
- Tadashi Toyohara
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Kais Zakharia
- Division of Gastroenterology and Hepatology, University of Iowa, USA
| | - Shuya Shimizu
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Katsuyuki Miyabe
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Kenichi Harada
- Department of Human Pathology, Kanazawa University School of Medicine, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Japan
| | - Tomohiro Yamada
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Katsumi Hayashi
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Kazuki Hayashi
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
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Velegraki M, Vardas E, Dervenis C, Fragaki M, Nikolaou P, Mpitouli A, Kazamias G, Sepsa A, Giannikaki E, Paspatis GA. IgG4-related sclerosing cholangitis: not always an obvious entity. Ann Gastroenterol 2021; 34:594-596. [PMID: 34276201 PMCID: PMC8276355 DOI: 10.20524/aog.2021.0610] [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: 11/23/2020] [Accepted: 12/11/2020] [Indexed: 12/04/2022] Open
Abstract
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is a distinct type of cholangitis, currently recognized as a biliary manifestation of IgG4-related disease. We present a case of type 3 IgG4-SC in a patient with normal IgG4 serum levels, surgically treated for suspicion of cholangiocarcinoma. This case highlights that differentiating between isolated IgG4-SC and cholangiocarcinoma can present a challenging diagnostic dilemma.
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Affiliation(s)
- Magdalini Velegraki
- Department of Gastroenterology, Venizeleion General Hospital, Heraklion (Magdalini Velegraki, Emmanouil Vardas, Maria Fragaki, Pinelopi Nikolaou, Afroditi Mpitouli, Gregorios A. Paspatis)
| | - Emmanouil Vardas
- Department of Gastroenterology, Venizeleion General Hospital, Heraklion (Magdalini Velegraki, Emmanouil Vardas, Maria Fragaki, Pinelopi Nikolaou, Afroditi Mpitouli, Gregorios A. Paspatis)
| | - Christos Dervenis
- Hepatobiliary and Pancreatic Surgery Clinic, Metropolitan Hospital, Athens (Christos Dervenis)
| | - Maria Fragaki
- Department of Gastroenterology, Venizeleion General Hospital, Heraklion (Magdalini Velegraki, Emmanouil Vardas, Maria Fragaki, Pinelopi Nikolaou, Afroditi Mpitouli, Gregorios A. Paspatis)
| | - Pinelopi Nikolaou
- Department of Gastroenterology, Venizeleion General Hospital, Heraklion (Magdalini Velegraki, Emmanouil Vardas, Maria Fragaki, Pinelopi Nikolaou, Afroditi Mpitouli, Gregorios A. Paspatis)
| | - Afroditi Mpitouli
- Department of Gastroenterology, Venizeleion General Hospital, Heraklion (Magdalini Velegraki, Emmanouil Vardas, Maria Fragaki, Pinelopi Nikolaou, Afroditi Mpitouli, Gregorios A. Paspatis)
| | - George Kazamias
- Department of Histopathology, Venizeleion General Hospital, Heraklion (George Kazamias, Elpida Giannikaki)
| | - Athanasia Sepsa
- Department of Histopathology, Metropolitan Hospital, Athens (Athanasia Sepsa), Greece
| | - Elpida Giannikaki
- Department of Histopathology, Venizeleion General Hospital, Heraklion (George Kazamias, Elpida Giannikaki)
| | - Gregorios A Paspatis
- Department of Gastroenterology, Venizeleion General Hospital, Heraklion (Magdalini Velegraki, Emmanouil Vardas, Maria Fragaki, Pinelopi Nikolaou, Afroditi Mpitouli, Gregorios A. Paspatis)
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14
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Nasser R, Gilshtein H, Mansour S, Yasin K, Borzellino G, Khuri S. Isolated Type Immunoglobulin G4 Sclerosing Cholangitis: The Misdiagnosed Cholangiocarcinoma. J Clin Med Res 2021; 13:75-81. [PMID: 33747321 PMCID: PMC7935625 DOI: 10.14740/jocmr4428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 01/21/2021] [Indexed: 12/13/2022] Open
Abstract
Immunoglobulin G4 sclerosing cholangitis (IgG4-SC), firstly described in 2004, is the biliary manifestation of a recently described multisystem immune-mediated disease known as IgG4-related disease. IgG4-SC is a unique and rare type of cholangitis of unknown etiology and its precise prevalence rate is still unclear. It is characterized by bile duct wall thickening and high levels of systemic serum IgG4 plasma cells. Differential diagnoses for IgG4-SC include benign (primary sclerosing cholangitis) as well as malignant (extra-hepatic cholangiocarcinoma) diseases. Discrimination between these entities is very important, due to the fact that they have different biological behaviors and different therapeutic strategies. The rare IgG4-SC subgroup with its puzzling manifestations carries a hefty diagnostic challenge for the treating physicians, and inaccurate diagnosis can lead to unnecessary morbid surgical procedures. With the paucity and relative weakness of available data in the current literature, one needs to carefully review all available parameters. A low threshold of suspicion is required to try and prevent missing IgG4-SC. IgG4-SC is highly responsive to steroid treatment, especially during the early inflammatory phase, while delay in management could lead to fibrosis and organ dysfunction. On the other hand, cholangiocarcinoma is treated by means of surgery and/or chemotherapeutic agents.
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Affiliation(s)
- Roni Nasser
- Gastroenterology and Hepatology Department, Rambam Health Care Campus, Haifa, Israel
| | - Hayim Gilshtein
- Colorectal Surgery Unit, General Surgery Department, Rambam Health Care Campus, Haifa, Israel
| | - Subhi Mansour
- HPB and Surgical Oncology Unit, General Surgery Department, Rambam Health Care Campus, Haifa, Israel
| | - Kamel Yasin
- Gastroenterology and Hepatology Department, Rambam Health Care Campus, Haifa, Israel
| | | | - Safi Khuri
- HPB and Surgical Oncology Unit, General Surgery Department, Rambam Health Care Campus, Haifa, Israel
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15
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Mačinga P, Jarošová J, Špičák J, Hucl T. [Immunoglobulin G4-related disease in gastroenterology]. VNITRNI LEKARSTVI 2021; 67:76-83. [PMID: 34074105 DOI: 10.36290/vnl.2021.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
IgG4-related disease is a recently defined clinical entity that can manifest itself in any organ. The most common gastrointestinal manifestations are diseases of the pancreas (autoimmune pancreatitis type 1) and biliary tree (IgG4-associated cholangitis); involvement of liver parenchyma is uncommon and the affection of tubular organs is very rare. IgG4-related pancreatitis and cholangitis can mimic malignancies in their clinical presentation. Diagnosis is often difficult and requires careful evaluation of the combination of symptoms, serology and imaging findings, while adhering to the established diagnostic criteria. The first line of treatment is the administration of corticoids and the remission is achieved in the vast majority of patients. In case of contraindication, intolerance or failure of corticotherapy, patients should receive B cell depletion therapy (rituximab). Based on the available knowledge, monotherapy with other immunosuppressants is not considered to be sufficiently effective. Some patients may benefit from maintenance treatment to prevent relapse, which is otherwise common in both IgG4-related pancreatitis and cholangitis. Recognized IgG4-related disease has a good prognosis, but some patients develop irreversible fibrotic changes in the affected organ with consequent dysfunction; the possible association of the disease with a higher risk of malignancy has not yet been reliably elucidated.
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16
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Mawardi M, Alalwan A, Fallatah H, Abaalkhail F, Hasosah M, Shagrani M, Alghamdi M, Alghamdi A. Cholestatic liver disease: Practice guidelines from the Saudi Association for the Study of Liver diseases and Transplantation. Saudi J Gastroenterol 2021. [PMCID: PMC8411950 DOI: 10.4103/sjg.sjg_112_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Cholestatic liver diseases (CLDs) are a group of diseases characterized by jaundice and cholestasis as the main presentation with different complications, which have considerable impact on the liver and can lead to end-stage liver disease, cirrhosis, and liver-related complications. In the last few years, tremendous progress has been made in understanding the pathophysiology, diagnosis, and treatment of patients with these conditions. However, several aspects related to the management of CLDs remain deficient and unclear. Due to the lack of recommendations that can help in the management, treatment of those conditions, the Saudi Association for the Study of Liver diseases and Transplantation (SASLT) has created a task force group to develop guidelines related to CLDs management in order to provide a standard of care for patients in need. These guidelines provide general guidance for health care professionals to optimize medical care for patients with CLDs for both adult and pediatric populations, in association with clinical judgments to be considered on a case-by-case basis. These guidelines describe common CLDs in Saudi Arabia, with recommendations on the best approach for diagnosis and management of different diseases based on the Grading of Recommendation Assessment (GRADE), combined with a level of evidence available in the literature.
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17
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Lei L, Li L, Song WY, Liu H. IgG4-related sclerosing cholangitis suspected of being malignant tumors: A case series. Shijie Huaren Xiaohua Zazhi 2020; 28:1206-1211. [DOI: 10.11569/wcjd.v28.i23.1206] [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] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of IgG4-related disease (IRD). IgG4-SC often has the characteristics of localized thickening of the bile duct wall, dilation of the bile duct, and obstructive jaundice, which are similar to those of biliary and pancreatic malignancies and often lead to delayed diagnosis or even misdiagnosis clinically.
AIM To improve the clinicians' understanding of IgG4-SC and avoid its misdiagnosis by analyzing the clinical characteristics, diagnosis, and treatment of five cases of IgG4-SC.
METHODS A retrospective analysis was performed on five cases of IgG4-SC suspected of being space-occupying lesions of the porta hepatis, ampulla, and pancreas at admission. Patient information, including age, gender, symptoms, signs, past medical history, and the process of diagnosis and treatment, was collected.
RESULTS Four cases showed obstructive jaundice and imaging identified one case of high level biliary obstruction and three cases of low level obstruction, which suggested the possibility of malignancy. The obstruction sites were located in the porta hepatis, pancreatic head, or ampulla. One case was found to have a mass at the neck of the pancreas by physical examination. All five patients had bile duct inflammation, swelling of the pancreas, or space-occupying lesions in the imaging examination. Laboratory examinations revealed elevated bilirubin, mainly direct bilirubin, accompanied by liver dysfunction. Serum IgG4 levels were significantly increased and tumor markers were normal or slightly elevated. Four patients were diagnosed with IgG4-SC by multidisciplinary consultation, and one patient was diagnosed by pathological examination after surgery.
CONCLUSION Multidisciplinary consultation is an important strategy in diagnosing IgG4-SC and avoiding misdiagnosis.
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Affiliation(s)
- Li Lei
- Seventh Department of Health Care, the Second Medical Center of PLA General Hospital, Beijing 100700, China
| | - Li Li
- Integrated Traditional Chinese and Western Medicine Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Wen-Yan Song
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Hui Liu
- Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
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18
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Abid H, Alaoui MEHHBE, Lamrani MYA, Figuigui M, Ahmed BC, Lahmidani N, Yousfi ME, Benajah DA, Maaroufi M, Abkari ME, Ibrahimi SA, Aqodad N. [IgG4-related disease: about 3 cases]. Pan Afr Med J 2020; 36:364. [PMID: 33235641 PMCID: PMC7666702 DOI: 10.11604/pamj.2020.36.364.24835] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 07/29/2020] [Indexed: 01/11/2023] Open
Abstract
IgG4-Related disease (IgG4-RD), formerly known as IgG4-related autoimmune polyexocrinopathy, is a new condition including Plasminogen Activator Inhibitor-1 (PAI-1). It can affect different organs (central nervous system, salivary glands, thyroid, lungs, pancreas, bile ducts, liver, digestive tract, kidneys, prostate, etc.) with symptoms depending on the organ that is affected. It is more common in men older than 50 years of age. Its incidence and prevalence are poorly known because it is an uncommon disease. It is most common in Asia, accounting for only 20-30% of PAI in the Western world. Diagnosis is based on histological examination which shows dense lymphoplasmocytic infiltration in the organ affected associated with IgG4-positive plasma cells (immunohistochemistry), organ fibrosis and obliterating venulitis, all this in the context of increased serum IgG4 levels in more than 80% of cases. Patients are sensitive to corticosteroid therapy, with a high risk of relapse after discontinuation of corticosteroid therapy. This leads to the use of immunomodulators, mainly: thiopurines (azathioprine or 6-mercaptopurine), methotrexate and more recently rituximab, which can also be used as induction therapy. Given recent advances, accurate histological and clinical criteria are currently known to limit inappropriate management such as surgery. However, knowledge gaps remain concerning: pathophysiology, identification of specific biomarkers other than IgG4, natural history of the disease and long-term cancer risk assessment, performances of diagnostic tools such as endoscopic ultrasound-guided pancreatic biopsy. As well, consensual international management should be defined in the early stages of the disease and when patients develop recurrences. The purpose of this study was to report 3 cases of IgG4-Related disease on the basis of clinical and radiological criteria as well as therapeutic response.
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Affiliation(s)
- Hakima Abid
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | | | - Moulay Youssef Alaoui Lamrani
- Service de Radiologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc.,Faculté de Médecine et de Pharmacie, Université Sidi Mohammed Ben Abdellah, Fès, Maroc
| | - Mouna Figuigui
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Beiba Cheikh Ahmed
- Service de Radiologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc.,Faculté de Médecine et de Pharmacie, Université Sidi Mohammed Ben Abdellah, Fès, Maroc
| | - Nada Lahmidani
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Mounia El Yousfi
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Dafr-Allah Benajah
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Mustapha Maaroufi
- Service de Radiologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc.,Faculté de Médecine et de Pharmacie, Université Sidi Mohammed Ben Abdellah, Fès, Maroc
| | - Mohammed El Abkari
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Sidi Adil Ibrahimi
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Nourdin Aqodad
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Ibn Zohr, Agadir, Maroc
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19
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IgG4 subclass and gamma-glutamyl transferase in children with ulcerative colitis with primary sclerosing cholangitis and without sclerosing cholangitis. Clin Exp Hepatol 2020; 5:285-288. [PMID: 31893239 PMCID: PMC6935853 DOI: 10.5114/ceh.2019.89119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 07/03/2019] [Indexed: 12/12/2022] Open
Abstract
Aim of the study Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which could be associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The aim of this study was to compare GGT and IgG4 levels among children with UC with PSC and without PSC. Material and methods In this cross sectional study children with UC with PSC and UC without PSC were included. Serum immunoglobulin G4 (IgG4) and gamma-glutamyl transpeptidase (GGT) levels of the 90 UC patients with and without concomitant PSC were measured. Children with serum IgG4 concentration > 175 mg/dl were considered to have elevated IgG4. Results Elevated serum IgG4 was found in 8 of 30 (26.6%) patients with PSC vs. 3 of 60 (5.0%) patients without PSC. Compared with the group without symptoms of PSC, the group with PSC showed significantly higher levels of aspartate aminotransferases (AST; 22.5 U/l vs. 70.0 U/l, p < 0.001), alkaline phosphatase (ALP; 359.0 U/l vs. 602.0 U/l, p < 0.001), and IgG4 (56.0 vs. 73.0, p = 0.02). The odd ratio of the elevated IgG4 and GGT in predicting PSC was 6.9 (95% CI: 1.6-28.4) and 18 (95% CI: 5.7-55.9), respectively. Conclusions AST, alanine aminotransferase (ALT), GGT, ALP, and serum IgG4 were significantly higher in UC patients with sclerosing cholangitis (SC) compared to UC patients without SC. GGT and IgG-4 measurements are recommended for evaluation of UC.
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20
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Dalekos GN, Gatselis NK. Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases. Arch Immunol Ther Exp (Warsz) 2019; 67:197-211. [PMID: 31165900 DOI: 10.1007/s00005-019-00550-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Accepted: 05/31/2019] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting also the uncertainties and the potential new eras of the research agenda.
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Affiliation(s)
- George N Dalekos
- Institute of Internal Medicine and Hepatology, Larissa, Greece.
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece.
| | - Nikolaos K Gatselis
- Institute of Internal Medicine and Hepatology, Larissa, Greece
- Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, 41110, Larissa, Greece
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21
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Sokol EV, Cherkasova MV, Torgashina AV. The diagnostic value of serum IgG4 for the diagnosis of IgG4-related disease: and is that so great? MODERN RHEUMATOLOGY JOURNAL 2019. [DOI: 10.14412/1996-7012-2019-1-52-57] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- E. V. Sokol
- V.A. Nasonova Research Institute of Rheumatology
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22
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Kamisawa T, Nakazawa T, Tazuma S, Zen Y, Tanaka A, Ohara H, Muraki T, Inui K, Inoue D, Nishino T, Naitoh I, Itoi T, Notohara K, Kanno A, Kubota K, Hirano K, Isayama H, Shimizu K, Tsuyuguchi T, Shimosegawa T, Kawa S, Chiba T, Okazaki K, Takikawa H, Kimura W, Unno M, Yoshida M. Clinical practice guidelines for IgG4-related sclerosing cholangitis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:9-42. [PMID: 30575336 PMCID: PMC6590186 DOI: 10.1002/jhbp.596] [Citation(s) in RCA: 94] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IgG4‐related sclerosing cholangitis (IgG4‐SC) is a distinct type of cholangitis frequently associated with autoimmune pancreatitis and currently recognized as a biliary manifestation of IgG4‐related disease. Although clinical diagnostic criteria of IgG4‐SC were established in 2012, differential diagnosis from primary sclerosing cholangitis and cholangiocarcinoma is sometimes difficult. Furthermore, no practical guidelines for IgG4‐SC are available. Because the evidence level of most articles retrieved through searching the PubMed, Cochrane Library, and Igaku Chuo Zasshi databases was below C based on the systematic review evaluation system of clinical practice guidelines MINDS 2014, we developed consensus guidelines using the modified Delphi approach. Three committees (a guideline creating committee, an expert panelist committee for rating statements according to the modified Delphi method, and an evaluating committee) were organized. Eighteen clinical questions (CQs) with clinical statements were developed regarding diagnosis (14 CQs) and treatment (4 CQs). Recommendation levels for clinical statements were set using the modified Delphi approach. The guidelines explain methods for accurate diagnosis, and safe and appropriate treatment of IgG4‐SC.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan, Komagome Hospital, Tokyo, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Hiroshima University Graduate School of Biomedical & Health Science, Hiroshima, Japan
| | - Yoh Zen
- Department of Diagnostic Pathology, Kobe University, Kobe, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Hirotaka Ohara
- Department of Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takashi Muraki
- Department of Medicine, Gastroenterology, Shinshu University, Matsumoto, Nagano, Japan
| | - Kazuo Inui
- Department of Gastroenterology, Second Teaching Hospital, Fujita Health University, Nagoya, Japan
| | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan
| | - Takayoshi Nishino
- Department of Gastroenterology, Tokyo Womens' Medical University Yachiyo Medical Center, Yachiyo, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kensuke Kubota
- Department of Endoscopy, Yokohama City University Hospital, Yokohama, Japan
| | - Kenji Hirano
- Department of Gastroenterology, Tokyo Takanawa Hospital, Tokyo, Japan
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Kyoko Shimizu
- Department of Gastroenterology, Tokyo Womens' Medical University, Tokyo, Japan
| | | | - Tooru Shimosegawa
- Division of Gastroenterology, South-Miyagi Medical Center, Ohgawara, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Matsumoto, Japan
| | | | - Kazuichi Okazaki
- The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Moriguchi, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Wataru Kimura
- Faculty of Medicine, Departments of Gastroenterology and Gastroenterological, General, Breast, and Thyroid Surgery, Yamagata University, Yamagata, Japan
| | - Michiaki Unno
- Division of Hepato-Biliary Pancreatic Surgery, Tohoku University Graduate School, of Medicine, Sendai, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, School of Medicine, International University of Health and Welfare, Ichikawa, Japan
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Sedki M, Levy C. Update in the Care and Management of Patients with Primary Sclerosing Cholangitis. Curr Gastroenterol Rep 2018; 20:29. [PMID: 29886518 DOI: 10.1007/s11894-018-0635-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
PURPOSE OF REVIEW Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease for which specific medical therapy is not available. The goals of treatment are primarily early detection and management of complications. In this review, we discuss novel therapies under evaluation and provide the foundation for surveillance strategies. RECENT FINDINGS Drugs under investigation include norursodeoxycholic acid, nuclear receptor agonists, anti-fibrotics, antibiotics, and anti-inflammatory drugs. Endoscopic therapy is indicated for symptomatic dominant strictures and in the work-up of malignancies. Recently, the use of stents was associated with an increased rate of complications compared to balloon dilatation; and long-term stenting should be avoided. Malignancies currently account for most of the PSC-related mortality. Many drugs are emerging for the treatment of PSC but liver transplantation is the only treatment modality shown to prolong survival. PSC recurrence occurs in up to 35% of transplanted allografts within a median of 5 years. Surveillance for hepatobiliary and colorectal malignancies is indicated.
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Affiliation(s)
- Mai Sedki
- Department of Internal Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL, USA
| | - Cynthia Levy
- Division of Hepatology, University of Miami Miller School of Medicine, 1500 NW 12th Avenue, Suite 1101, Miami, FL, USA.
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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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Xiao J, Xu P, Li B, Hong T, Liu W, He X, Zheng C, Zhao Y. Analysis of clinical characteristics and treatment of immunoglobulin G4-associated cholangitis: A retrospective cohort study of 39 IAC patients. Medicine (Baltimore) 2018; 97:e9767. [PMID: 29465558 PMCID: PMC5842017 DOI: 10.1097/md.0000000000009767] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [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
Immunoglobulin (Ig)G4-associated cholangitis (IAC) is one of the common organ manifestations of IgG4-related systemic disease (ISD). IAC and autoimmune pancreatitis (AIP) may mimic sclerosing cholangitis, cholangiocarcinoma, or pancreatic carcinoma. Diagnosis is based on a combination of clinical, biochemical, radiological, and histological findings.To study the clinical presentation of and treatment strategy for IAC, we reviewed clinical, serologic, and imaging characteristics, as well as treatment response, in 39 patients with IAC. The majority of patients were men (82%). Clinical features on presentation included obstructive jaundice in 26 patients (67%) and abdominal pain in 20 (51%). Positive IgG4 immunostaining was seen in 27 patients. The median serum IgG4 level before treatment was 769.4 mg/dL (range, 309.1-1229.7 mg/dL). After the steroid therapy, the median serum IgG4 level in 23 patients was 247.0 mg/dL (range, 139.0-355.0 mg/dL). Cholangiograms were available in 36 (92%) patients. Stenosis of the lower part of the common bile duct was found in 26 of 39 patients. Stenosis was diffusely distributed in the intra- and extrahepatic bile ducts in 14 of 39 patients. Additionally, strictures of the bile duct were detected in the hilar hepatic lesions in 27 of 39 patients. AIP was the most frequent comorbidity (35/39 in this study) of IAC. Other affected organs included eyes (n = 6), salivary glands (sialadenitis, n = 10), lymph nodes (mediastinal and axillary, n = 3), kidneys (n = 2), and the retroperitoneum (retroperitoneal fibrosis, n = 2).Regarding treatment, 29 patients were treated with steroids, of whom one underwent pancreatoduodenectomy, and one underwent choledochojejunostomy. Eight patients were treated with biliary stents. The remaining 19 patients took prednisolone alone. Eight patients achieved spontaneous resolution. Four patients with suspected pancreatic cancer or cholangiocarcinoma underwent surgery, including 2 patients who also received postoperative steroids. All patients were regularly followed up for 9 to 36 months. Only 2 patients in the steroids treatment group relapsed to manifest obstructive jaundice and high serum IgG4 levels. These 2 patients were treated with steroids and biliary stents, resulting in complete remission.We also review the diagnostic and therapeutic management and discuss recent pathophysiological findings, which might aid in understanding the molecular mechanisms contributing to IAC and other manifestations of IgG4-related diseases (IgG4-RD). Biomarkers that are more accurate are needed to correctly diagnose IAC and prevent misdiagnoses and unnecessary therapeutic interventions.
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Development of a scoring system for differentiating IgG4-related sclerosing cholangitis from primary sclerosing cholangitis. J Gastroenterol 2017; 52:483-493. [PMID: 27470434 DOI: 10.1007/s00535-016-1246-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 07/17/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUND Recent research has shown that a substantial number of patients with primary sclerosing cholangitis (PSC) can also have elevated serum/tissue IgG4. The aim of our study was to develop a simple scoring system for the discrimination of IgG4-related sclerosing cholangits (IgG4-SC) from PSC. METHODS Patients with IgG4-SC (n = 39) and PSC (n = 76) who had intrahepatic/hilar strictures were included. Candidate-differentiating variables included patient age, other organ involvement (OOI), inflammatory bowel disease, serum IgG4, and cholangiographic features. A scoring system was developed on the basis of these variables, and its performance was internally validated using a bootstrapping-based method. RESULTS The scoring system in the final model included age (<30 years, 0 points; 30-39 years, 1 point; 40-49 years, 2 points; 50-59 years, 3 points; ≥60 years, 4 points), OOI (no, 0 points; yes, 3 points), and beaded appearance (yes, 0 points; no, 2 points). The patients were classified according to their total score into three categories: 0-4 points, probable PSC; 5-6 points, indicating diagnostic steroid trial; 7-9 points, probable IgG4-SC. The discrimination between IgG4-SC and PSC using the scoring system was excellent (area under the receiver operating characteristic curve, 0.986). CONCLUSIONS A reliable differentiation of IgG4-SC from PSC can be made using the scoring system presented here. We suggest the diagnosis of IgG4-SC at a cutoff of 7 points or higher and the indication of diagnostic steroid trial at 5 or 6 points. External validation of our scoring system is warranted.
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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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Abstract
Autoimmune biliary diseases are poorly understood but important to recognize. Initially, autoimmune biliary diseases are asymptomatic but may lead to progressive cholestasis with associated ductopenia, portal hypertension, cirrhosis, and eventually liver failure. The three main forms of autoimmune biliary disease are primary biliary cirrhosis, primary sclerosing cholangitis, and IgG4-associated cholangitis. Although some overlap may occur between the three main autoimmune diseases of the bile ducts, each disease typically affects a distinct demographic group and requires a disease-specific diagnostic workup. For all the autoimmune biliary diseases, imaging provides a means to monitor disease progression, assess for complications, and screen for the development of hepatobiliary malignancies that are known to affect patients with these diseases. Imaging is also useful to suggest or corroborate the diagnosis of primary sclerosing cholangitis and IgG4-associated cholangitis. We review the current literature and emphasize radiological findings and considerations for these autoimmune diseases of the bile ducts.
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30
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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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Xu WL, Ling YC, Wang ZK, Deng F. Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis. Sci Rep 2016; 6:32035. [PMID: 27558881 PMCID: PMC4997323 DOI: 10.1038/srep32035] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Accepted: 08/02/2016] [Indexed: 12/13/2022] Open
Abstract
An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78-90%; the pooled specificity was 93% with a 95% CI of 90-95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD.
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Affiliation(s)
- Wen-Long Xu
- Department of Clinical Laboratory, Baoshan Branch of Shanghai Huashan Hospital, Baoshan Renhe Hospital, Shanghai 200431, China
| | - Ying-Chun Ling
- Department of Clinical Laboratory, Shaoxing Seventh People's Hospital, Zhejiang Shaoxing 312000, China
| | - Zhi-Kai Wang
- Department of Clinical Laboratory, Shanghai Family Planning Hospital, Shanghai 200032, China
| | - Fang Deng
- Department of Clinical Laboratory, Anhui Provincial Tumor Hospital, Anhui Hefei 230031, China
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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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Hao M, Liu M, Fan G, Yang X, Li J. Diagnostic Value of Serum IgG4 for IgG4-Related Disease: A PRISMA-compliant Systematic Review and Meta-analysis. Medicine (Baltimore) 2016; 95:e3785. [PMID: 27227950 PMCID: PMC4902374 DOI: 10.1097/md.0000000000003785] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Many studies about serum IgG4 for the diagnosis of IgG4-related disease (IgG4-RD) have been reported. However, these studies had relatively small sample sizes and the diagnostic accuracy values varied much between them.The aim of this study was to perform a meta-analysis to evaluate the diagnostic value of serum IgG4 for IgG4-RD.We conducted a search of relevant articles using MEDLINE, EMBASE, Web of Science, SCOPUS, and Cochrane Library databases published before December 2015.Studies those assessed the diagnostic accuracy of serum IgG4 for IgG4-RD and those provided the cut-off value for serum IgG4 were included.Data were synthesized using the random-effect model. Statistical analysis was performed using STATA with the MIDAS module and Meta-DiSc 1.4 software.A total of 9 case-control studies were analyzed, which included 1235 patients with IgG4-RD and 5696 overall controls. The pooled estimate, for a cut-off value ranged from 135 to 144 mg/dL, produced a sensitivity of 87.2% (95% CI, 85.2-89.0%) and a specificity of 82.6% (95% CI, 81.6-83.6%). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 6.48 (95% CI, 3.98-10.57), 0.14 (95% CI, 0.09-0.21), and 45.15 (95% CI, 23.41-87.06), respectively. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was 0.94 (0.92-0.96). When a cut-off value of 2-fold the upper limit of normal was used (ranged from 270 to 280 mg/dL), the pooled sensitivity was 63% (95% CI, 60.0-66.0%), and the specificity was 94.8% (95% CI, 94.1-95.4%). The PLR, NLR, and DOR were 13.3 (95% CI, 7.39-24.0), 0.41 (95% CI, 0.29-0.58) and 33.42 (95% CI, 13.88-80.43), respectively. The AUC of the SROC was 0.92 (0.90-0.94).Only a relatively small number of studies were included, and significant heterogeneity was observed in this meta-analysis.Serum IgG4 is a modestly effective marker to diagnose IgG4-RD. Doubling the cut-off value for IgG4 could not improve the overall test characteristics. A high specificity inevitably accompanies with a significant sacrifice in sensitivity.
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Affiliation(s)
- Mingju Hao
- From the National Center for Clinical Laboratories (MH, GF, XY, JL), Beijing Hospital; Graduate School (MH, GF, XY, JL), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing; Department of Clinical Laboratory (MH), Qianfo Mountain Hospital of Shandong University; and Department of Clinical Laboratory (ML), Jinan Dermatosis Prevention and Control Hospital, Jinan, People's Republic of China
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Yata M, Suzuki K, Furuhashi N, Kawakami K, Kawai Y, Naganawa S. Comparison of the multidetector-row computed tomography findings of IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma. Clin Radiol 2016; 71:203-10. [PMID: 26703117 DOI: 10.1016/j.crad.2015.10.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 08/30/2015] [Accepted: 10/20/2015] [Indexed: 01/13/2023]
Abstract
AIM To compare the multidetector-row computed tomography (MDCT) findings of IgG4-related sclerosing cholangitis (IgG4-SC) and extrahepatic cholangiocarcinoma (EH-CCA). MATERIALS AND METHODS Two radiologists who had no knowledge of the patients' clinical information retrospectively evaluated the CT findings of patients with IgG4-SC (n=33) and EH-CCA (n=39) on a consensus basis. Another radiologist measured the biliary lesions. IgG4-SC was diagnosed using the Japan Biliary Association criteria (2012) or the Mayo Clinic's HISORt criteria. EH-CCA was diagnosed based on surgical findings. RESULTS Compared with EH-CCA, IgG4-SC exhibited the following findings significantly more frequently: (a) wall thickening alone, (b) concentric wall thickening, (c) smooth inner margins, (d) homogeneous attenuation in the arterial phase, (e) a lesion involving the intrapancreatic bile duct, (f) smooth outer margins, (g) fully visible lumen, (h) a funnel-shaped proximal bile duct, (i) skip lesions, and (j) abnormal pancreatic findings. Conversely, (k) dual-layered attenuation in all phases was significantly more common in EH-CCA. The specificity values of parameters (e-k) were >80%. Regarding dimensions, (l) the biliary lesions were longer in IgG4-SC than in EH-CCA. (m) The diameters of the dilated proximal common bile duct and (n) the dilated proximal intrahepatic bile duct were smaller in IgG4-SC than in EH-CCA. CONCLUSION A number of CT findings are useful for differentiating between IgG4-SC and EH-CCA. CT findings (e-k) are particularly useful for this purpose.
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Affiliation(s)
- M Yata
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
| | - K Suzuki
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - N Furuhashi
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - K Kawakami
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
| | - Y Kawai
- Department of Diagnostic Radiology, Japanese Red Cross Nagoya Daiichi Hospital, 3-15 Michishita-cho, Nakamura-ku, Nagoya, Aichi 453-8511, Japan
| | - S Naganawa
- Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
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Nayagam JS, Pereira SP, Devlin J, Harrison PM, Joshi D. Controversies in the management of primary sclerosing cholangitis. World J Hepatol 2016; 8:265-272. [PMID: 26925200 PMCID: PMC4757649 DOI: 10.4254/wjh.v8.i5.265] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Revised: 10/13/2015] [Accepted: 01/22/2016] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) remains a rare but significant disease, which affects mainly young males in association with inflammatory bowel disease. There have been few advances in the understanding of the pathogenesis of the condition and no therapeutics with proven mortality benefit aside from liver transplantation. There remain areas of controversy in the management of PSC which include the differentiation from other cholangiopathies, in particular immunoglobulin G4 related sclerosing cholangitis, the management of dominant biliary strictures, and the role of ursodeoxycholic acid. In addition, the timing of liver transplantation in PSC remains difficult to predict with standard liver severity scores. In this review, we address these controversies and highlight the latest evidence base in the management of PSC.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic progressive disease, usually associated with underlying inflammatory bowel diseases (IBDs), with a prevalence of 60-80% in western countries. Herein, we review the current knowledge about the association between PSC and IBD in terms of clinical approach and long-term patient management. A PubMed search was conducted for English-language publications from 2000 through 2015 using the following keywords: primary sclerosing cholangitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, diagnosis, therapy, follow-up, and epidemiology. In terms of diagnosis, liver function tests and histology are currently used. The medical treatment options for PSC associated with IBD do not differ from the cases of PSC alone, and include ursodeoxycholic acid and immunosuppressive agents. These treatments do not seem to improve survival, even if ursodeoxycholic acid given at low doses may be chemopreventive against colorectal cancer (CRC). Liver transplantation is the only potential curative therapy for PSC with reported survival rates of 85 and 70% at 5 and 10 years after transplant; however, there is a risk for PSC recurrence, worsening of IBD activity, and de-novo IBD occurrence after liver transplantation. PSC-IBD represents an important public health concern, especially in view of the increased risk for malignancy, including CRC. Long-life annual surveillance colonoscopy is usually recommended, although the exact timescale is still unclear. Further studies are required both to clarify whether annual colonoscopy is cost-effective, especially in younger patients, and to identify potential pharmaceutical agents and genetic targets that may retard disease progression and protect against CRC.
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Smit WL, Culver EL, Chapman RW. New Thoughts on Immunoglobulin G4-Related Sclerosing Cholangitis. Clin Liver Dis 2016; 20:47-65. [PMID: 26593290 DOI: 10.1016/j.cld.2015.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the multisystem IgG4-related disease. IgG4-SC presents with biliary strictures and/or masses that can bear a striking similarity to other malignant and inflammatory diseases. Diagnosis is based on a combination of clinical, biochemical, radiological, and histologic findings with careful exclusion of malignant disease. Corticosteroids are the mainstay of treatment with good clinical, biochemical, and radiological responses. This review provides a comprehensive overview of the current knowledge of the prevalence, clinical features, radiology and histology findings, diagnosis, treatment, natural history, and pathophysiology of IgG4-SC.
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Affiliation(s)
- Wouter L Smit
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
| | - Roger W Chapman
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK.
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Abstract
Intraductal ultrasonography (IDUS) provides real-time, cross-sectional imaging of pancreatobiliary ducts and surrounding structures during endoscopic retrograde cholangiopancreatography using a high-frequency ultrasound (US) transducer. Hence, IDUS has been considered a sensitive tool in the evaluation of suspicious choledocholithiasis and neoplasms, to help distinguish between benign and malignant bile duct strictures or wall thickness, and to assess tumor extension and invasion depth. With the rapid development and enriched choices of sensitive diagnostic modalities include but are not limited to endoscopic US, peroral cholangioscopy, and confocal laser endomicroscopy, it is needed to systematically assess the role of IDUS in the investigation of pancreatobiliary diseases. Some new developments and innovative use of IDUS techniques will be discussed in this paper with the review of literature.
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Affiliation(s)
- Bo Sun
- Department of Gastroenterology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Bing Hu
- Department of Gastroenterology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Li P, Chen H, Deng C, Wu Z, Lin W, Zeng X, Zhang W, Zhang F, Li Y. Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related disease in Chinese population. Mod Rheumatol 2015; 26:583-7. [PMID: 26565780 DOI: 10.3109/14397595.2015.1117171] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE This study was performed to better know diagnosis associated with serum IgG4 concentration, and to explore the possibility for development of a serum IgG4 for IgG4-related disease (IgG4-RD) in Chinese populations. METHODS We studied retrospectively 497 IgG4 serum subclass measurements from Peking Union Medical College Hospital during the four-year period, including 242 IgG4-RD, 130 other diseases and 125 healthy individuals. RESULTS Serum IgG4 concentrations were significantly higher in IgG4-RD than in other pathologies (1662.9 ± 3760.9 mg/L, p < 0.001) and healthy individuals (538.2 ± 458.6 mg/L, p < 0.001). There were no significant differences in serum IgG4 level between other pathologies group and healthy individuals (p = 0.075). Among the 242 IgG4-RD patients analyzed, serum IgG4 concentrations were normal in 46 patients (19.0%). We found 32 patients (24.6%) with elevated serum IgG4 levels among the 130 patients who suffered from other pathologies. There were seven (5.6%) with serum IgG4 over 1350 mg/L in healthy individuals. The ROC curve analysis revealed that the optimal sensitivity and specificity were 80.0% and 88.2%, respectively, at the concentration of 1575 mg/L for Chinese patients. CONCLUSIONS Our study demonstrated that serum IgG4 elevation was not specific of IgG4-RD. Further studies are needed to define the sensibility and specificity of IgG4 values for the diagnosis of IgG4-RD.
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Affiliation(s)
- Ping Li
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Hua Chen
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Chuiwen Deng
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Ziyan Wu
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Wei Lin
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Xiaofeng Zeng
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Wen Zhang
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Fengchun Zhang
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
| | - Yongzhe Li
- a Department of Rheumatology and Clinical Immunology , Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China
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Zhang YA, Shen XZ, Zhu JM, Liu TT. Extensive Metastatic Cholangiocarcinoma Associated With IgG4-Related Sclerosing Cholangitis Misdiagnosed as Isolated IgG4-Related Sclerosing Cholangitis: A Case Report and Literature Review. Medicine (Baltimore) 2015; 94:e2052. [PMID: 26559312 PMCID: PMC4912306 DOI: 10.1097/md.0000000000002052] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
As cholangiographic features of IgG4-related sclerosing cholangitis (IgG4-SC) resemble those of cholangiocarcinoma, it is highly confusing between the 2 conditions on the basis of cholangiographic findings. This study presents a case of extensive metastatic cholangiocarcinoma with IgG4-SC misdiagnosed as isolated IgG4-SC, and reviews recent studies of the 2 diseases.A 56-year-old man with no family history of malignant tumors or liver diseases presented with recurrent mild abdominal pain and distention for 3 months. Magnetic resonance cholangiopancreatography showed a 3.7 cm nodular lesion with unclear boundary in segment VI of the liver. Serum IgG4 and CA19-9 were slightly elevated. Histopathological examination was consistent with the consensus statement on the pathology of IgG4-SC. IgG4-SC was thus considered. Due to his mild symptoms, glucocorticoid was not given at first. However, 3 months after his first admission, he had more severe abdominal pain and further elevated serum CA19-9. Actually he was found suffering from extensive metastatic cholangiocarcinoma with IgG4-SC by exploratory laparotomy.The present case serves as a reminder that extensive metastatic cholangiocarcinoma with or without IgG4-SC may be misdiagnosed as an isolated IgG4-SC case if one relies solely on elevated serum and tissue IgG4 levels. We emphasize on the importance of repeated core needle biopsy or exploratory laparoscopy/laparotomy before immunosuppressive drugs are given, and on follow-up of imaging findings and serum CA19-9 once immunosuppressive therapy is started.
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Affiliation(s)
- Yi-An Zhang
- From Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China (YAZ, XZS, JMZ, TTL); Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China (XZS); and Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, China (XZS)
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Stone JH, Brito-Zerón P, Bosch X, Ramos-Casals M. Diagnostic Approach to the Complexity of IgG4-Related Disease. Mayo Clin Proc 2015; 90:927-39. [PMID: 26141331 DOI: 10.1016/j.mayocp.2015.03.020] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 03/30/2015] [Accepted: 03/31/2015] [Indexed: 12/24/2022]
Abstract
IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.
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Affiliation(s)
- John H Stone
- Harvard Medical School, Boston, MA; Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA.
| | - Pilar Brito-Zerón
- Josep Font Laboratory of Autoimmune Diseases, CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Spain
| | - Xavier Bosch
- Department of Internal Medicine (ICMiD), Hospital Clínic, University of Barcelona, Spain
| | - Manuel Ramos-Casals
- Josep Font Laboratory of Autoimmune Diseases, CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Spain
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Naitoh I, Nakazawa T, Hayashi K, Miyabe K, Shimizu S, Kondo H, Nishi Y, Yoshida M, Umemura S, Hori Y, Kato A, Okumura F, Sano H, Ohara H, Joh T. Comparison of intraductal ultrasonography findings between primary sclerosing cholangitis and IgG4-related sclerosing cholangitis. J Gastroenterol Hepatol 2015; 30:1104-9. [PMID: 25594435 DOI: 10.1111/jgh.12894] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/04/2015] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND AIM Comparisons of intraductal ultrasonography (IDUS) findings between primary sclerosing cholangitis (PSC) and IgG4-related sclerosing cholangitis (IgG4-SC) have not been elucidated. We aimed to clarify the differences in transpapillary IDUS findings between PSC and IgG4-SC. METHODS We retrospectively compared transpapillary IDUS findings between 15 patients with PSC and 35 patients with IgG4-SC between 2004 and 2014. RESULTS IDUS findings of circular-asymmetric wall thickness, irregular inner margin, diverticulum-like outpouching, unclear outer margin, heterogeneous internal echo, and disappearance of three layers were significantly higher in PSC than in IgG4-SC (P < 0.001). Irregular inner margin, diverticulum-like outpouching, and disappearance of three layers were specific IDUS findings for PSC compared to IgG4-SC. Diverticulum-like outpouching on IDUS and endoscopic retrograde cholangiogram (ERC) was observed in 10 (67%) and five (33%) of 15 patients with PSC, respectively. However, based on IDUS and ERC, diverticulum-like outpouching was not observed in any patient with IgG4-SC. All five patients with diverticulum-like outpouching on ERC had diverticulum-like outpouching on IDUS, and five (50%) of 10 patients without diverticulum-like outpouching on ERC had diverticulum-like outpouching on IDUS. CONCLUSIONS The IDUS findings differed between PSC and IgG4-SC. Irregular inner margin, diverticulum-like outpouching, and disappearance of three layers are specific IDUS findings for PSC compared to IgG4-SC. IDUS is a more useful procedure than ERC for the early detection of diverticulum-like outpouching.
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Affiliation(s)
- Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Nakazawa T, Ikeda Y, Kawaguchi Y, Kitagawa H, Takada H, Takeda Y, Makino I, Makino N, Naitoh I, Tanaka A. Isolated intrapancreatic IgG4-related sclerosing cholangitis. World J Gastroenterol 2015; 21:1334-1343. [PMID: 25632210 PMCID: PMC4306181 DOI: 10.3748/wjg.v21.i4.1334] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2014] [Revised: 07/29/2014] [Accepted: 09/05/2014] [Indexed: 02/06/2023] Open
Abstract
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently associated with type 1 autoimmune pancreatitis (AIP). Association with AIP can be utilized in the diagnosis of IgG4-SC. However, some cases of IgG4-SC are isolated from AIP, which complicates the diagnosis. Most of the reported cases of isolated IgG4-SC displayed hilar biliary strictures, whereas isolated IgG4-SC with intrapancreatic biliary stricture is very rare. Recently, we have encountered 5 isolated intrapancreatic IgG4-SC cases that were not associated with AIP, three of which were pathologically investigated after surgical operation. They all were males with a mean age of 74.2 years. The pancreas was not enlarged in any of these cases. No irregular narrowing of the main pancreatic duct was found. Bile duct wall thickening in lesions without luminal stenosis was detected by abdominal computed tomography in all five cases, by endoscopic ultrasonography in two out of four cases and by intraductal ultrasonography in all three cases. In three cases, serum IgG4 levels were within the normal limits. The mean serum IgG4 level measured before surgery was 202.1 mg/dL (4 cases). Isolated intrapancreatic IgG4-SC is difficult to diagnose, especially if the IgG4 level remains normal. Thus, this type of IgG4-SC should be suspected in addition to cholangiocarcinoma and pancreatic cancer if stenosis of intrapancreatic bile duct is present.
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Kanno A, Masamune A, Shimosegawa T. Endoscopic approaches for the diagnosis of autoimmune pancreatitis. Dig Endosc 2015; 27:250-8. [PMID: 25115499 DOI: 10.1111/den.12343] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 08/04/2014] [Indexed: 12/21/2022]
Abstract
Autoimmune pancreatitis (AIP) is characterized by diffuse pancreatic enlargement and irregular narrowing of the main pancreatic duct (MPD). Immunoglobulin (Ig)G4-related sclerosing cholangitis (IgG4-SC) associated with AIP frequently appears as a bile duct stricture. Therefore, it is important to differentiate AIP and IgG4-SC from pancreatic cancer and cholangiocarcinoma or primary sclerosing cholangitis, respectively. Endoscopy plays a central role in the diagnosis of AIP and IgG4-SC because it provides imaging of the MPD and bile duct strictures as well as the ability to obtain tissue samples for histological evaluations. Diffuse irregular narrowing of MPD on endoscopic retrograde cholangiopancreatography (ERCP) is rather specific to AIP, but localized narrowing of the MPD is often difficult to differentiate from MPD stenosis caused by pancreatic cancer. A long stricture (>1/3 the length of the MPD) and lack of upstream dilatation from the stricture (<5 mm) might be key features of AIP on ERCP. Some cholangiographic features, such as segmental strictures, stric tures of the lower bile duct, and long strictures with prestenotic dilatation, are more common in IgG4-SC than in cholangiocarcinoma. Endoscopic ultrasonography (EUS) reveals diffuse hypoechoic pancreatic enlargement, sometimes with hypoechoic inclusions, in patients with AIP. In addition, EUS-elastography and contrast-enhanced harmonic EUS have been developed with promising results. The usefulness of EUS-guided fine-needle aspiration has been increasingly recognized for obtaining adequate tissue samples for the histological diagnosis of AIP. Further improvement of endoscopic procedures and devices will contribute to more accurate diagnosis of AIP and IgG4-SC.
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Affiliation(s)
- Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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46
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Ryu JK. Diagnosis of immunoglobulin g4-related sclerosing cholangitis. Clin Endosc 2014; 47:476-7. [PMID: 25505711 PMCID: PMC4260093 DOI: 10.5946/ce.2014.47.6.476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 10/17/2014] [Indexed: 11/22/2022] Open
Affiliation(s)
- Ji Kon Ryu
- Division of Gastroenterology, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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47
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Joshi D, Webster GJM. Biliary and hepatic involvement in IgG4-related disease. Aliment Pharmacol Ther 2014; 40:1251-61. [PMID: 25312536 DOI: 10.1111/apt.12988] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 07/30/2014] [Accepted: 09/24/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND IgG4-related disease (IgG4-RD) is a multi-systemic disorder. IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the disease, often in association with autoimmune pancreatitis (AIP). Hepatic manifestations of IgG4-RD are less well described within the literature. AIM To examine and present an overview of IgG4-RD with a focus on the biliary and hepatic manifestations. METHODS An electronic search using Medline was performed. Search items included 'IgG4 multi-system disease, IgG4 associated cholangitis, IgG4 associated liver disease and autoimmune pancreatitis (AIP)'. RESULTS IgG4-RD is characterised by an IgG4-positive lymphoplasmacytic tissue infiltrate, storiform fibrosis and an obliterative phlebitis. The HISORt criteria may be used to establish the diagnosis and incorporate a multi-disciplinary approach involving histology, radiology, serum IgG4 levels and response to steroid therapy. IgG4-SC is the commonest extrapancreatic manifestation of type-1 AIP, while the hepatic manifestations remain poorly defined. Important differential diagnoses include primary sclerosing cholangitis, secondary sclerosing cholangitis, cholangiocarcinoma and pancreatic carcinoma. Current treatment regimens remain ill defined although steroid therapy is used first line unless contraindicated. Patients with relapsing disease or multifocal disease should be considered for azathioprine. Available data would also suggest a role for rituximab. CONCLUSIONS IgG4-related sclerosing cholangitis is a common manifestation of IgG4-related disease which requires a multi-disciplinary approach to establish the diagnosis. Differentiating IgG4-related sclerosing cholangitis from other conditions, both benign and malignant, is challenging, but vital. Steroids remain the mainstay of treatment. Our understanding of the pathogenesis of the hepatic manifestations of IgG4-related disease continues to evolve.
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Affiliation(s)
- D Joshi
- Department of Gastroenterology, University College Hospital, London, UK
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48
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Abstract
IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease with the capability of involving essentially any organ. The epidemiology of this disease has not been explored in detail. A majority of patients reported in the literature to date are from Japan, but the condition has been described all across the world and there is no strong evidence to suggest a predilection for Asian populations. The mean age at diagnosis is approximately 60 years and there is a decided male predominance for many clinical features, with an overall male:female ratio of 8:3. A cardinal feature of IgG4-RD is single or multiple organ swelling that often raises concern for malignancy. IgG4-RD should be suspected in patients presenting with unexplained enlargement or swelling of one or more organs. Presenting features vary substantially according to the specialty to which patients present first; in addition, the disease can be diagnosed unexpectedly in pathological specimens or identified incidentally on radiology studies. Involvement of major organs is common and IgG4-RD may lead to organ failure, particularly in the pancreas, liver and biliary tree, kidneys, thyroid gland, lungs, and aorta. The diagnosis of IgG4-RD relies on the coexistence of various clinical, laboratory and histopathological findings, although none is pathognomonic by itself.
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49
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Boonstra K, Culver EL, de Buy Wenniger LM, van Heerde MJ, van Erpecum KJ, Poen AC, van Nieuwkerk KMJ, Spanier BWM, Witteman BJM, Tuynman HARE, van Geloven N, van Buuren H, Chapman RW, Barnes E, Beuers U, Ponsioen CY. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology 2014; 59:1954-63. [PMID: 24375491 PMCID: PMC4489327 DOI: 10.1002/hep.26977] [Citation(s) in RCA: 122] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 12/17/2013] [Indexed: 02/06/2023]
Abstract
UNLABELLED The recent addition of immunoglobulin (Ig)G4-associated cholangitis (IAC), also called IgG4-related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n = 73) and PSC (n = 310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n = 22). sIgG4 levels were elevated above the upper limit of normal (ULN = >1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11-19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4 × ULN (sIgG4 > 5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31-55). However, in patients with a sIgG4 between 1 × and 2 × ULN (n = 38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51-95), a specificity of 74% (95% CI: 57-86), a PPV of 55% (95% CI: 33-75), and a negative predictive value of 90% (95% CI: 73-97). CONCLUSION Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and <2.8 g/L, incorporating the IgG4/IgG1 ratio with a cutoff at 0.24 in the diagnostic algorithm significantly improved PPV and specificity. We propose a new diagnostic algorithm based on IgG4/IgG1 ratio that may be used in clinical practice to distinguish PSC from IAC.
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Affiliation(s)
- Kirsten Boonstra
- Department of Gastroenterology and Hepatology, Academic Medical CenterAmsterdam, the Netherlands
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe HospitalOxford, United Kingdom
| | | | - Marianne J van Heerde
- Department of Gastroenterology and Hepatology, Erasmus University Medical CenterRotterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center UtrechtUtrecht, the Netherlands
| | - Alexander C Poen
- Department of Gastroenterology and Hepatology, Isala ClinicsZwolle, the Netherlands
| | - Karin MJ van Nieuwkerk
- Department of Gastroenterology and Hepatology, VU Medical CenterAmsterdam, the Netherlands
| | - BW Marcel Spanier
- Department of Gastroenterology and Hepatology, Rijnstate HospitalArnhem, the Netherlands
| | - Ben JM Witteman
- Department of Gastroenterology and Hepatology, Gelderse Vallei HospitalEde, the Netherlands
| | - Hans ARE Tuynman
- Department of Gastroenterology and Hepatology, Medical Center AlkmaarAlkmaar, the Netherlands
| | - Nan van Geloven
- Clinical Research Unit, Academic Medical CenterAmsterdam, the Netherlands
| | - Henk van Buuren
- Department of Gastroenterology and Hepatology, Erasmus University Medical CenterRotterdam, the Netherlands
| | - Roger W Chapman
- Translational Gastroenterology Unit, John Radcliffe HospitalOxford, United Kingdom
| | - Eleanor Barnes
- Translational Gastroenterology Unit, John Radcliffe HospitalOxford, United Kingdom,Oxford NIHR Biomedical Research Center, and NDM, University of OxfordOxford, United Kingdom
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Academic Medical CenterAmsterdam, the Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical CenterAmsterdam, the Netherlands
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Nakazawa T, Naitoh I, Hayashi K, Sano H, Miyabe K, Shimizu S, Joh T. Inflammatory bowel disease of primary sclerosing cholangitis: A distinct entity? World J Gastroenterol 2014; 20:3245-3254. [PMID: 24696608 PMCID: PMC3964396 DOI: 10.3748/wjg.v20.i12.3245] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Revised: 10/04/2013] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
This is a review of the characteristic findings of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) and their usefulness in the diagnosis of sclerosing cholangitis. PSC is a chronic inflammatory disease characterized by idiopathic fibrous obstruction and is frequently associated with IBD. IBD-associated with PSC (PSC-IBD) shows an increased incidence of pancolitis, mild symptoms, and colorectal malignancy. Although an increased incidence of pancolitis is a characteristic finding, some cases are endoscopically diagnosed as right-sided ulcerative colitis. Pathological studies have revealed that inflammation occurs more frequently in the right colon than the left colon. The frequency of rectal sparing and backwash ileitis should be investigated in a future study based on the same definition. The cholangiographic findings of immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) are similar to those of PSC. The rare association between IBD and IgG4-SC and the unique characteristics of PSC-IBD are useful findings for distinguishing PSC from IgG4-SC.
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