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Kamekura R, Sakamoto H, Yajima R, Yamamoto K, Okuni T, Yamamoto M, Takahashi H, Ichimiya S, Takano K. Recent Evidence of the Role of CD4 + T Cell Subsets in IgG4-related Disease. JMA J 2025; 8:40-47. [PMID: 39926068 PMCID: PMC11799721 DOI: 10.31662/jmaj.2024-0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 09/30/2024] [Indexed: 02/11/2025] Open
Abstract
CD4+ T cells, the so-called T helper cells, are one of the main players in the human immune system, which can regulate acquired immunity. Dysfunction of the acquired immune system induces various chronic inflammatory diseases such as malignancies and autoimmune diseases. IgG4-related disease (IgG4-RD) is also a chronic inflammatory disease that is characterized by elevated serum IgG4 concentration and infiltration of IgG4-positive plasma cells in affected tissues. Despite that remarkable advances in understanding the pathogenesis of IgG4-RD have been on the rise, the detailed mechanisms by which IgG4-RD develops are still unknown. In fact, CD4+ T cells abundantly infiltrate at lesions of IgG4-RD, and they are also associated with the pathogenesis of other refractory chronic inflammatory diseases. Therefore, our focus was on CD4+ T cells, and we previously reported the roles of their subsets including regulatory T cells, CD4 cytotoxic T lymphocytes, T follicular helper (Tfh) cells, T follicular regulatory cells, and T peripheral helper (Tph) cells in IgG4-RD. Among the subsets, Tph cells play an important role in generating ectopic lymphoid structures at inflammatory sites. Moreover, we found that circulating Tph cells are increased in IgG4-RD patients. Unlike Tfh cells, Tph cells express high levels of chemokine receptors and cytotoxic molecules. Thus, they can infiltrate affected tissues and exert a cytotoxic function. Additionally, our latest observations demonstrated that Tph cells interact with extrafollicular B cells in affected tissues. Hence, Tph cells may collaborate with a specific B-cell subset, and they play a role in the maintenance of persistent fibroinflammation in lesions of IgG4-RD. Tph cells may have an important role to play in the pathogenesis of not only IgG4-RD but also other chronic inflammatory diseases. This review summarizes and discusses the possible pathologic roles of CD4+ T cell subsets including Tph cells in IgG4-RD.
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Affiliation(s)
- Ryuta Kamekura
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
- Department of Human Immunology, Research Institute for Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroshi Sakamoto
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Ryoto Yajima
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Keisuke Yamamoto
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tsuyoshi Okuni
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Motohisa Yamamoto
- Division of Rheumatology, Center for Antibody and Vaccine Therapy, Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hiroki Takahashi
- Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shingo Ichimiya
- Department of Human Immunology, Research Institute for Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Kenichi Takano
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan
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Loganathan P, Siby N, Mohan BP, Gajendran M, Chandan S, Echavarria J, Saligram S, Adler DG. Efficacy of Rituximab in Autoimmune-Mediated IgG4 Pancreaticobiliary Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2024:00004836-990000000-00353. [PMID: 39331507 DOI: 10.1097/mcg.0000000000002078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 08/28/2024] [Indexed: 09/29/2024]
Abstract
BACKGROUND AND AIMS IgG4 pancreaticobilliary disease (IgG4-PBD) typically shows a rapid improvement with glucocorticoid treatment, yet most patients experience a recurrence. Rituximab (RTX) has emerged as a hopeful approach to prevent relapses in IgG4-PBD. Nevertheless, there is a lack of data on the efficacy and safety of RTX in IgG4-PBD. In this study, we aim to perform a systematic review and meta-analysis to study the pooled efficacy of RTX in this patient population. METHODS Multiple databases, including MEDLINE, SCOPUS, and Embase, were searched (in March 2024) using specific terms for studies evaluating the efficacy and safety of RTX in IgG4 pancreatic biliary disease. Outcomes of interest were relapse, remission, partial remission rates, and adverse events. Standard meta-analysis methods were used using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. RESULTS Twelve studies were included in the study (257 patients). The pooled rate of complete remission was 68% (54% to 80%), I2 =53%, respectively. The pooled relapse rate was 23% (13% to 36%), I2=64%. The pooled rate of total adverse events was 21% (12% to 35%), I2=52%. The pooled partial remission rate is 16% (7% to 32%), I2=25%. The pooled rate of complete and partial remission was 81% (66% to 90%), I2=75%. The pooled infusion reaction and infection were 12% (7% to 18%), I2=0% and 14% (8% to 22%), I2=16%, respectively. CONCLUSION RTX therapy appears effective in inducing and maintaining remission of pancreaticobiliary disease with a low rate of side effects. RTX presents as a promising treatment option for patients grappling with recurrent or unresponsive IgG4-related ailments. In addition, RTX emerges as an attractive alternative for individuals intolerant to steroids or experiencing IgG4-related disease relapses. Future studies comparing RTX with other immunomodulators will offer deeper insights into relapse factors and elucidate the appropriateness of utilizing this maintenance treatment following the initial flare.
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Affiliation(s)
| | - Ninette Siby
- Long School of Medicine, UT Health Science Center, San Antonio, TX
| | - Babu P Mohan
- Department of Orlando Gastroenterology and Hepatology, Orlando, FL
| | | | - Saurabh Chandan
- Department of Gastroenterology, CHI Creighton University School of Medicine, Omaha, NE
| | - Juan Echavarria
- Department of Gastroenterology, CHI Creighton University School of Medicine, Omaha, NE
| | - Shreyas Saligram
- Department of Gastroenterology, Digestive Healthcare Center, Hillsborough, NJ
| | - Douglas G Adler
- Department of Gastroenterology, Center for Advanced Therapeutic Endoscopy, Centura Health, Denver, CO
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Liu Y, Jin K, Yang Y, Yang A. Efficacy and safety of rituximab induction therapy and effect of rituximab maintenance for IgG4-related disease: a systematic review and meta-analysis. Eur J Intern Med 2024; 127:63-73. [PMID: 38871563 DOI: 10.1016/j.ejim.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/27/2024] [Accepted: 06/04/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Previous studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. METHODS The protocol was registered in the PROSPERO (CRD42023427352). PubMed, Embase, the Cochrane database, Scopus, and the Web of Science were interrogated to identify studies that evaluated the impact of RTX on prognosis in IgG4-RD. We explored the impact of various subgroups of factors on relapse outcomes and focused on the possible role of maintenance therapy in reducing relapse rates. The pooled incidence of adverse events of RTX therapy and the influencing factors have also been evaluated. RESULTS Eighteen studies comprising 374 patients (mean age 56.0 ± 8.7 years; male 73.7 %) with a mean follow-up duration of 23.4 ± 16.3 months were included. The pooled estimate of the response rate, complete remission rate, overall relapse rate, adverse event rate, and serious adverse event rate of RTX induction therapy were 97.3 % (95 % CI, 94.7 %-99.1 %), 55.8 % (95 % CI, 39.6 %-71.3 %), 16.9 % (95 % CI, 8.7 %-27.1 %), 31.6 % (95 % CI, 16.7 %-48.9 %) and 3.9 % (95 % CI, 0.8 %-8.9 %), respectively. In subgroup analysis, the pooled relapse rate was significantly lower in studies with maintenance than without maintenance (2.8% vs 21.5 %, p < 0.01). Pooled Kaplan-Meier relapse curves also demonstrated that RTX maintenance therapy provided a better prognosis. CONCLUSIONS RTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD.
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Affiliation(s)
- Yixiao Liu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Kehan Jin
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yingyun Yang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
| | - Aiming Yang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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de Pretis N, Martinelli L, Palmeri E, Caldart F, Crucillà S, Zorzi A, Brillo A, Crinò SF, Conti Bellocchi MC, Bernardoni L, De Marchi G, Amodio A, Campagnola P, Ciccocioppo R, Gabbrielli A, Marcon A, Frulloni L. The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis. Pancreatology 2024; 24:538-544. [PMID: 38693038 DOI: 10.1016/j.pan.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND/OBJECTIVES Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.
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Affiliation(s)
- Nicolò de Pretis
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy.
| | - Luigi Martinelli
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Enrico Palmeri
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Federico Caldart
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Crucillà
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Alberto Zorzi
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Alessandro Brillo
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | | | | | - Laura Bernardoni
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Antonio Amodio
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Pietro Campagnola
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Armando Gabbrielli
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Alessandro Marcon
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
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Overbeek KA, Poulsen JL, Lanzillotta M, Vinge-Holmquist O, Macinga P, Demirci AF, Sindhunata DP, Backhus J, Algül H, Buijs J, Levy P, Kiriukova M, Goni E, Hollenbach M, Miksch RC, Kunovsky L, Vujasinovic M, Nikolic S, Dickerson L, Hirth M, Neurath MF, Zumblick M, Vila J, Jalal M, Beyer G, Frost F, Carrara S, Kala Z, Jabandziev P, Sisman G, Akyuz F, Capurso G, Falconi M, Arlt A, Vleggaar FP, Barresi L, Greenhalf B, Czakó L, Hegyi P, Hopper A, Nayar MK, Gress TM, Vitali F, Schneider A, Halloran CM, Trna J, Okhlobystin AV, Dagna L, Cahen DL, Bordin D, Rebours V, Mayerle J, Kahraman A, Rasch S, Culver E, Kleger A, Martínez-Moneo E, Røkke O, Hucl T, Olesen SS, Bruno MJ, Della-Torre E, Beuers U, Löhr JM, Rosendahl J. Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment. Clin Gastroenterol Hepatol 2024; 22:994-1004.e10. [PMID: 38184096 DOI: 10.1016/j.cgh.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 12/04/2023] [Accepted: 12/05/2023] [Indexed: 01/08/2024]
Abstract
BACKGROUND & AIMS Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
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Affiliation(s)
- Kasper A Overbeek
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
| | - Jakob L Poulsen
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Marco Lanzillotta
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Olof Vinge-Holmquist
- Department of Digestive Surgery, Akershus University Hospital, Loerenskog, Norway; Department of Digestive Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Peter Macinga
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - A Fatih Demirci
- Department of Internal Medicine, Marmara University Research and Education Hospital, Istanbul, Turkey
| | - Daniko P Sindhunata
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Johanna Backhus
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Hana Algül
- Department of Medicine II, Technische Universität München, München, Germany
| | - Jorie Buijs
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Philippe Levy
- Pancreatology Unit, APHP Beaujon Hospital, Clichy, France
| | - Mariia Kiriukova
- Department of Upper Gastrointestinal, Pancreatic, and Biliary Diseases, A.S. Loginov Moscow Clinical Research Center, Moscow, Russia
| | - Elisabetta Goni
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Marcus Hollenbach
- Division of Gastroenterology, Medical Department II - Oncology, Gastroenterology, Hepatology, Pulmonology, Infectious Diseases, University of Leipzig Medical Center, Leipzig, Germany
| | - Rainer C Miksch
- Department of General, Visceral, and Transplantation Surgery, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Lumir Kunovsky
- 2nd Department of Internal Medicine, Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Sara Nikolic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Luke Dickerson
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty at Mannheim, University of Heidelberg, Mannheim, Germany
| | - Markus F Neurath
- Department of Medicine I, Deutsches Zentrum Immuntherapie (DZI), Kussmaul Campus for Medical Research, University Erlangen-Nürnberg, Erlangen, Germany
| | - Malte Zumblick
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Josephine Vila
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | - Mustafa Jalal
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Georg Beyer
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Fabian Frost
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Silvia Carrara
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, Castellanza, Italy
| | - Zdenek Kala
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Petr Jabandziev
- Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Gurhan Sisman
- Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
| | - Filiz Akyuz
- Department of Gastroenterology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy & Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Alexander Arlt
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany; Department for Internal Medicine and Gastroenterology, University Hospital, Klinikum Oldenburg AöR, Oldenburg, Germany
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCSS-ISMETT), Palermo, Italy
| | - Bill Greenhalf
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - László Czakó
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary
| | - Peter Hegyi
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Pancreatic Diseases, Heart and Vascular Centre, Semmelweis University, Budapest, Hungary
| | - Andrew Hopper
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Manu K Nayar
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | - Thomas M Gress
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Francesco Vitali
- Department of Medicine I, Deutsches Zentrum Immuntherapie (DZI), Kussmaul Campus for Medical Research, University Erlangen-Nürnberg, Erlangen, Germany
| | - Alexander Schneider
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty at Mannheim, University of Heidelberg, Mannheim, Germany
| | - Chris M Halloran
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Jan Trna
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Center Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | | | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Djuna L Cahen
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Dmitry Bordin
- Department of Upper Gastrointestinal, Pancreatic, and Biliary Diseases, A.S. Loginov Moscow Clinical Research Center, Moscow, Russia; Department of Outpatient Therapy and Family Medicine, Tver State Medical University, Tver, Russia
| | | | - Julia Mayerle
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Alisan Kahraman
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Essen University Hospital, University of Duisberg-Essen, Essen, Germany
| | - Sebastian Rasch
- Department of Medicine II, Technische Universität München, München, Germany
| | - Emma Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Alexander Kleger
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Emma Martínez-Moneo
- Biocruces, Grupo Transplante Hepático, Osakidetza, Hospital Universitario Cruces, Servicio Aparato Digestivo, Barakaldo, Spain
| | - Ola Røkke
- Department of Digestive Surgery, Akershus University Hospital, Loerenskog, Norway; Faculty of Medicine, Campus Ahus, University of Oslo, Oslo, Norway
| | - Tomas Hucl
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Søren S Olesen
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Marco J Bruno
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Emanuel Della-Torre
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Ulrich Beuers
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - J-Matthias Löhr
- 2nd Department of Internal Medicine, Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle (Saale), Germany.
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Tsujimae M, Masuda A, Takagi M, Kato T, Nakano R, Fujita K, Hirata Y, Kakuyama S, Furumatsu K, Nakagawa T, Ogisu K, Fujigaki S, Iemoto T, Ezaki T, Yagi Y, Ikegawa T, Yamanaka K, Sato Y, Juri N, Kobayashi T, Sakai A, Shiomi H, Sanuki T, Arisaka Y, Okabe Y, Kodama Y. Relapse and side effects of steroid therapy beyond 3 years in autoimmune pancreatitis: A multicenter retrospective study. Pancreatology 2024; 24:223-231. [PMID: 38320953 DOI: 10.1016/j.pan.2024.01.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 01/12/2024] [Accepted: 01/14/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. METHODS In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. RESULTS Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). CONCLUSIONS Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.
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Affiliation(s)
- Masahiro Tsujimae
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
| | - Megumi Takagi
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Takao Kato
- Department of Gastroenterology, Hyogo Prefectural Awaji Medical Center, Sumoto, Japan
| | - Ryota Nakano
- Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical University, Japan
| | - Koichi Fujita
- Department of Gastroenterology and Hepatology, Yodogawa Christian Hospital, Osaka, Japan
| | - Yuichi Hirata
- Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Saori Kakuyama
- Department of Gastroenterology, Takatsuki General Hospital, Takatsuki, Japan
| | - Keisuke Furumatsu
- Department of Gastroenterology, Akashi Medical Center, Akashi, Japan
| | - Takashi Nakagawa
- Department of Gastroenterology, Chibune General Hospital, Osaka, Japan
| | - Kyohei Ogisu
- Department of Gastroenterology, Nissei Hospital, Osaka, Japan
| | - Seiji Fujigaki
- Department of Gastroenterology, Hyogo Prefectural Harima Himeji Medical Center, Himeji, Japan
| | - Takao Iemoto
- Department of Gastroenterology, Kita-harima Medical Center, Ono, Japan
| | - Takeshi Ezaki
- Department of Gastroenterology, National Hospital Organization Kobe Medical Center, Kobe, Japan
| | - Yosuke Yagi
- Department of Internal Medicine, Shiso Municipal Hospital, Shiso, Japan
| | - Takuya Ikegawa
- Department of Gastroenterology, Japanese Red Cross Kobe Hospital, Kobe, Japan
| | - Kodai Yamanaka
- Department of Gastroenterology, Konan Medical Center, Kobe, Japan
| | - Yu Sato
- Department of Internal Medicine, Hyogo Prefectural Tamba Medical Center, Tamba, Japan
| | - Noriko Juri
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
| | - Hideyuki Shiomi
- Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical University, Japan
| | - Tsuyoshi Sanuki
- Department of Gastroenterology, Hyogo Prefectural Harima Himeji Medical Center, Himeji, Japan
| | | | - Yoshihiro Okabe
- Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan
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7
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Gallo C, Dispinzieri G, Zucchini N, Invernizzi P, Massironi S. Autoimmune pancreatitis: Cornerstones and future perspectives. World J Gastroenterol 2024; 30:817-832. [PMID: 38516247 PMCID: PMC10950636 DOI: 10.3748/wjg.v30.i8.817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/18/2023] [Accepted: 01/25/2024] [Indexed: 02/26/2024] Open
Abstract
Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.
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Affiliation(s)
- Camilla Gallo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Giulia Dispinzieri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Nicola Zucchini
- Department of Pathology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
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8
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Pădureanu V, Drăgoescu AN, Pădureanu R, Rośu MM, Rădulescu D, Dop D, For£ofoiu MC. Treatment approaches in autoimmune pancreatitis (Review). Biomed Rep 2024; 20:26. [PMID: 38259589 PMCID: PMC10801350 DOI: 10.3892/br.2023.1714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 12/11/2023] [Indexed: 01/24/2024] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease. There are two distinct types of AIP: AIP type 1 (AIP-1), a pancreatic manifestation of a multi-organ disease linked to immunoglobulin (Ig)G4, and AIP type 2 (AIP-2), a pancreas-specific disease unrelated to IgG4. The usual course of treatment for AIP is oral corticosteroid medication. Rituximab has also been recommended for recurrent AIP-1 in order to initiate remission and provide ongoing treatment. Immunomodulators such as azathioprine are used to keep certain patients in remission. Evaluation also takes into account a number of pharmacological alternatives, including biologic drugs like anti-tumor necrosis factor therapy, a safe and efficient second-line treatment for AIP-2 relapse or steroid dependence. Corticosteroids and immunosuppressants, which are poorly tolerated due to considerable side effects, are being replaced by other biologic drugs, which may offer a beneficial therapeutic alternative.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Alice Nicoleta Drăgoescu
- Department of Anaesthesiology and Intensive Care, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Maria Magdalena Rośu
- Department of Diabetes, Nutrition and Metabolic Diseases, County Clinical Emergency Hospital of Craiova, Craiova 200642, Romania
| | - Dumitru Rădulescu
- Department of Pediatrics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dalia Dop
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mircea Cătălin For£ofoiu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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9
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Kim SH, Lee YC, Chon HK. Challenges for clinicians treating autoimmune pancreatitis: Current perspectives. World J Clin Cases 2023; 11:30-46. [PMID: 36687190 PMCID: PMC9846983 DOI: 10.12998/wjcc.v11.i1.30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/31/2022] [Accepted: 12/19/2022] [Indexed: 01/04/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease clinically characterized by obstructive jaundice, unintentional weight loss, acute pancreatitis, focal pancreatic mass, and diabetes. AIP is classified into two subtypes - type 1 and type 2 - according to pathological findings, clinical features, and serology test results, but some cases may be defined as type not otherwise in the absence of pathological findings and inflammatory bowel disease. To address the differences in diagnostic criteria by country, standard diagnostic criteria for AIP were proposed in 2011 by an international consensus of expert opinions. Differential diagnosis of AIP from pancreatic ductal adenocarcinoma is important but remains challenging for clinicians. Fortunately, all subtypes of AIP show dramatic response to steroid treatment. This review discusses the current perspectives on the diagnosis and management of AIP in clinical practice.
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Affiliation(s)
- Seong-Hun Kim
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Yun Chae Lee
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Hyung Ku Chon
- Department of Internal Medicine, Institution of Wonkwang Medical Science, Wonkwang University School of Medicine and Hospital, Iksan 54538, South Korea
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10
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Mack S, Flattet Y, Bichard P, Frossard JL. Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence. World J Gastroenterol 2022; 28:6867-6874. [PMID: 36632320 PMCID: PMC9827582 DOI: 10.3748/wjg.v28.i48.6867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 10/31/2022] [Accepted: 11/16/2022] [Indexed: 12/26/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a type of immune-mediated pancreatitis subdivided into two subtypes, type 1 and type 2 AIP. Furthermore, type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4 (IgG4)-related disease. Nowadays, AIP is increasingly researched and recognized, although its diagnosis represents a challenge for several reasons: False positive ultrasound-guided cytological samples for a neoplastic process, difficult to interpret levels of IgG4, the absence of biological markers to diagnose type 2 AIP, and the challenging clinical identification of atypical forms. Furthermore, 60% and 78% of type 1 and type 2 AIP, respectively, are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer. As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging, obtaining a definitive diagnosis can therefore prove difficult, since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal. This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence, new serum markers, and new therapeutic approaches, while it also outlines the current management recommendations. A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse, although such an approach requires close collaboration between gastroenterologists, surgeons and radiologists. Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.
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Affiliation(s)
- Sahar Mack
- Division of Gastroenterology, Department of Medical Specialties, University Hospital of Geneva, Geneva 1205, Switzerland
| | - Yves Flattet
- Division of Gastroenterology, Department of Medical Specialties, University Hospital of Geneva, Geneva 1205, Switzerland
| | - Philippe Bichard
- Division of Gastroenterology, Department of Medical Specialties, University Hospital of Geneva, Geneva 1205, Switzerland
| | - Jean Louis Frossard
- Division of Gastroenterology, Department of Medical Specialties, University Hospital of Geneva, Geneva 1205, Switzerland
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11
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Nista EC, De Lucia SS, Manilla V, Schepis T, Pellegrino A, Ojetti V, Pignataro G, Zileri dal Verme L, Franceschi F, Gasbarrini A, Candelli M. Autoimmune Pancreatitis: From Pathogenesis to Treatment. Int J Mol Sci 2022; 23:12667. [PMID: 36293522 PMCID: PMC9604056 DOI: 10.3390/ijms232012667] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/14/2022] [Accepted: 10/18/2022] [Indexed: 11/05/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.
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Affiliation(s)
- Enrico Celestino Nista
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Sara Sofia De Lucia
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Vittoria Manilla
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Tommaso Schepis
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Pellegrino
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Veronica Ojetti
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giulia Pignataro
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Lorenzo Zileri dal Verme
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Franceschi
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Marcello Candelli
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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12
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de Pretis N, Amodio A, De Marchi G, Marconato E, Ciccocioppo R, Frulloni L. The role of serological biomarkers in the diagnosis and management of autoimmune pancreatitis. Expert Rev Clin Immunol 2022; 18:1119-1124. [PMID: 36125384 DOI: 10.1080/1744666x.2022.2125379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Autoimmune pancreatitis (AIP) is a fibroinflammatory disease of the pancreas. Type 1 AIP is the pancreatic manifestation of a systemic IgG4-related disease and is associated with serum elevation of IgG4, tissue infiltration of IgG4-positive plasma cells, and multiorgan involvement. Although serum IgG4 elevation is considered a useful diagnostic tool, the concomitant presence of more diagnostic criteria is needed to achieve diagnosis. No other biomarkers have been approved in clinical practice in type 1 AIP. Type 2 AIP is a pancreatic-specific disease associated with inflammatory bowel disease. No specific biomarkers for type 2 AIP have been identified. AREAS COVERED The role of serum IgG4 in the diagnosis, management and follow-up of patients with type 1 AIP. Moreover, data on other emerging biomarkers for type 1 and 2 AIP have been reported. EXPERT OPINION The diagnosis of AIP is challenging in clinical practice, especially for focal forms without multiorgan involvement, where distinction from pancreatic cancer can be difficult. Despite the strong association with type 1 AIP, serum IgG4 should only be measured when the suspicion for the disease is high, considering its limited sensitivity. New biomarkers with high diagnostic yield for both type 1 and type 2 AIP are needed.
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Affiliation(s)
- Nicolò de Pretis
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Antonio Amodio
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Giulia De Marchi
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Eugenio Marconato
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Luca Frulloni
- Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
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13
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Analysis of Clinical, Serological, and Imaging Features of Autoimmune Pancreatitis and a Case-Control Study on Prognostic Factors in Response to Hormone Therapy. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:4829467. [PMID: 35854780 PMCID: PMC9288312 DOI: 10.1155/2022/4829467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/23/2022] [Indexed: 11/17/2022]
Abstract
Objective The paper aimed to analyze the clinical, serological, and imaging features of autoimmune pancreatitis (AIP) and the prognostic factors affecting hormone therapy. Methods A total of 106 patients with AIP enrolled in our hospital from March 2016 to August 2018 were treated with the hormone. The curative effect and recurrence were followed up. The patients were divided into relapse group (n = 42) and nonrelapse group (n = 64) according to the recurrence within 3 years after initial hormone therapy. The symptoms and signs, laboratory examination, and treatment were compared, and binary logistic regression was employed to explore the risk factors of AIP recurrence. Results Among the 106 patients included in this study, there were 78 males and 28 females, with a male-to-female ratio of 3:1. The average age of onset was 56.25 ± 8.87 years; the minimum age was 39 years; and the maximum age was 7 years. The main clinical symptoms were jaundice (67.92%), abdominal pain (48.11%), and abdominal distension (33.96%). In addition, there were symptoms of weight loss, nausea, vomiting, itching, and gray stool. Previous complications included 27.35% diabetes (29/106), 22.64% hypertension (24/106), 35.84% smoking (38/106), and 28.30% alcohol consumption (30/106). The serological characteristics were mainly the increase in serum IgG4 level; 92.45% (98/106) level was higher compared to the upper limit of normal value; the median level was 11.65 g/L; and the highest level was 35.79 g/L. A total of 88.67% (94/106) had an abnormal liver function. The results of imaging examination indicated that 58.49% (62/106) of extrapancreatic organs were involved, of which 46.22% (49/106) were the most common bile duct involvement. All the patients in the group reached a state of remission after hormone treatment. After the disease was relieved, the patients were followed up for 3 years. The recurrence rate was 39.62% (42/106), and the median time of recurrence (month) was 9 (range 2–36). The recurrence rates within 1, 2, and 3 years were 20.75%, 31.13%, and 39.62%, respectively. Among the recurrent patients, 52.38% (22/42) relapsed within 1 year, 78.57% (33/42) within 2 years, and 100.00% (42/42) within 3 years. Multivariate analysis showed that the short duration of glucocorticoid therapy and involvement of extrapancreatic organs were risk factors for relapse after glucocorticoid therapy in patients with type I AIP. Conclusion Type 1 AIP is more common in middle-aged and elderly men. The clinical symptoms of jaundice, abdominal pain, and abdominal distension are common, often accompanied by involvement of extrapancreatic organs, of which bile duct involvement is the most common. Type 1 AIP glucocorticoid treatment acceptance and disease remission are better, but the recurrence rate is higher after glucocorticoid treatment. Patients with a short time of glucocorticoid treatment and involvement of extrapancreatic organs may have a higher risk of recurrence.
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14
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Yue Z, Tong F, Chen Y, Shen Y, Li J, Zeng C, Diao J, Chen X, Wei R. Risk factors for
IgG4
‐related disease relapse: A systematic review and meta‐analysis. Scand J Immunol 2022. [DOI: 10.1111/sji.13200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Affiliation(s)
- Zifan Yue
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Fei Tong
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Yuqing Chen
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Ya Shen
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Jian Li
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Chengcheng Zeng
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Jiale Diao
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Xinxin Chen
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
| | - Ruili Wei
- Department of Ophthalmology Shanghai Changzheng Hospital Shanghai China
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15
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Nikolic S, Lanzillotta M, Panic N, Brismar TB, Moro CF, Capurso G, Della Torre E, Löhr J, Vujasinovic M. Unraveling the relationship between autoimmune pancreatitis type 2 and inflammatory bowel disease: Results from two centers and systematic review of the literature. United European Gastroenterol J 2022; 10:496-506. [PMID: 35526270 PMCID: PMC9427095 DOI: 10.1002/ueg2.12237] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 04/14/2022] [Indexed: 11/07/2022] Open
Abstract
INTRODUCTION The relationship between autoimmune pancreatitis (AIP) type 2 and inflammatory bowel disease (IBD) has been established and previously described within International Consensus Diagnostic Criteria. However, it is unknown if the presence of IBD changes the natural disease course of AIP type 2. Our aim was to investigate the association between AIP type 2 and IBD as well as to systematically summarize all the existing evidence in the literature. METHODS Electronic medical record analysis was conducted in two centers (in Stockholm, Sweden, and Milan, Italy; records dated between January 2001 and June 2021). Additionally, we conducted a systematic review of the literature. RESULTS A total of 35 patients (18 females, 51.4%) fulfilled the diagnostic criteria of AIP type 2 and were included in the study. A diagnosis of IBD was established in 29 patients (82.8%), ulcerative colitis in 17 (58.6%) and Crohn's disease in 11 (37.9%). Median follow-up was 54 months. AIP patients with IBD commonly presented with abdominal pain and/or acute pancreatitis at diagnosis, the latter was prevailing in concomitant and later IBD onset. These patients more frequently used steroids, but there were no differences in relapse rates. Concomitant onset of IBD was associated with the development of diabetes mellitus. There were no cases of colon or pancreatic malignancy during follow-up. In our systematic analysis, a total of 693 AIP type 2 patients were included from 24 single-center retrospective studies and 8 multicenter retrospective studies. A diagnosis of IBD was reported in 330 (47.8%) patients. Relapse rate was 20.0%. CONCLUSIONS Clinical and radiological remission of AIP type 2 was high, while the cumulative incidence of relapse is around 20%. Our results show that concomitance of IBD imposes no obvious risk of a different disease course for AIP type 2.
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Affiliation(s)
- Sara Nikolic
- Department of Medicine HuddingeKarolinska InstitutetStockholmSweden
- Department of GastroenterologyClinic for Internal MedicineUniversity Medical Centre MariborMariborSlovenia
| | - Marco Lanzillotta
- Università Vita‐Salute San RaffaeleIRCCS San Raffaele Scientific InstituteMilanItaly
- Unit of ImmunologyRheumatology, Allergy and Rare Diseases (Unirar)IRCCS San Raffaele Scientific Institute, ss MilanMilanItaly
| | - Nikola Panic
- Faculty of MedicineUniversity of BelgradeDigestive Endoscopy UnitUniversity Clinic “Dr Dragisa Misovic”BelgradeSerbia
| | - Torkel B. Brismar
- Department of RadiologyKarolinska University HospitalStockholmSweden
| | - Carlos Fernández Moro
- Department of Clinical Pathology and Cancer DiagnosticsKarolinska University HospitalStockholmSweden
| | - Gabriele Capurso
- Division of Pancreatic Surgery and Endosonography DivisionPancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteMilanItaly
| | - Emanuel Della Torre
- Università Vita‐Salute San RaffaeleIRCCS San Raffaele Scientific InstituteMilanItaly
- Unit of ImmunologyRheumatology, Allergy and Rare Diseases (Unirar)IRCCS San Raffaele Scientific Institute, ss MilanMilanItaly
| | - J.‐Matthias Löhr
- Department of Upper Digestive DiseasesKarolinska University HospitalStockholmSweden
- Department of Clinical ScienceIntervention, and Technology (CLINTEC)Karolinska InstitutetStockholmSweden
| | - Miroslav Vujasinovic
- Department of Medicine HuddingeKarolinska InstitutetStockholmSweden
- Department of Upper Digestive DiseasesKarolinska University HospitalStockholmSweden
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16
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Lanzillotta M, Tacelli M, Falconi M, Arcidiacono PG, Capurso G, Della-Torre E. Incidence of endocrine and exocrine insufficiency in patients with autoimmune pancreatitis at diagnosis and after treatment: a systematic review and meta-analysis. Eur J Intern Med 2022; 100:83-93. [PMID: 35367110 DOI: 10.1016/j.ejim.2022.03.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is a rare form of pancreatitis that may lead to endocrine and exocrine insufficiency if left untreated. AIP clinically responds to glucocorticoids (GCs) therapy, but multiple GCs courses are often required to maintain remission with detrimental effects on glycaemic control. OBJECTIVE In this systematic review and meta-analysis, we aimed to assess the rate of endocrine and of exocrine insufficiency at diagnosis and at follow up in patients with AIP as well as the impact of GC therapy on pancreatic function in the long-term. METHODS The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to August 2021 to identify studies reporting data on endocrine and exocrine insufficiency in patients with AIP. Pooled events were calculated using a random-effect model and expressed in terms of pooled prevalence rates. RESULTS A total of 6522 AIP patients and sixty-two studies were included in the analysis. The pooled estimate rate for the overall prevalence of diabetes in AIP at baseline was 37% (95% CI 32-42, I2 96%). The pooled prevalence rate of exocrine insufficiency was 45% (95%CI 32.9-57.4; I2 97%). The pooled estimate rate of diabetes at follow-up was 44% (95%CI 26.1-62.4) in studies where GCs were given to 100% of patients and 42% (95%CI 30.6-52.9) in studies where GCs were given to less than 100% of patients. CONCLUSION A large proportion of patients with AIP displays concomitant exocrine and endocrine insufficiency at the time of diagnosis. The incidence of diabetes at the longest available follow up tends to increase in patients treated with GCs.
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Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Matteo Tacelli
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuel Della-Torre
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Long-Term Follow-Up and Immunomonitoring of Relapsing Type 1 Autoimmune Pancreatitis Treated With Rituximab. Pancreas 2022; 51:452-462. [PMID: 35835119 DOI: 10.1097/mpa.0000000000002048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES To evaluate the efficacy and safety of rituximab in relapsing type 1 autoimmune pancreatitis especially the long-term clinical and immunologic impacts. METHODS All consecutive patients with type 1 autoimmune pancreatitis were retrospectively included. The rituximab protocol was induction therapy of 375 mg·m -2 intravenous weekly for 4 weeks, followed by 500 mg intravenous every 6 months for 2 years. The follow-up included clinical examinations, biological tests, positron emission tomography scan, and immunomonitoring of lymphocyte CD 19+. RESULTS Among the 43 patients included, 15 received rituximab induction therapy, followed by maintenance in 10 cases because of 1 or more relapses after steroids (whether or not followed by immunosuppressants) and multiple organ involvement. All patients had a clinical, biological and morphological response, a deep and persistent drop in serum immunoglobulin G4 levels, an extinction of both pancreatic and extra pancreatic hypermetabolic positron emission tomography scan signals, and a depletion of B lymphocyte CD19+. No relapse occurred during the follow-up (62.8 ± standard error of the mean of 11.1 months). CONCLUSIONS Rituximab is an effective treatment for type 1 autoimmune pancreatitis that provides a rapid strong clinical, biological, and morphological response, which persists after discontinuation without any safety issues.
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18
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Beyer G, Hoffmeister A, Michl P, Gress TM, Huber W, Algül H, Neesse A, Meining A, Seufferlein TW, Rosendahl J, Kahl S, Keller J, Werner J, Friess H, Bufler P, Löhr MJ, Schneider A, Lynen Jansen P, Esposito I, Grenacher L, Mössner J, Lerch MM, Mayerle J. S3-Leitlinie Pankreatitis – Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – September 2021 – AWMF Registernummer 021-003. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:419-521. [PMID: 35263785 DOI: 10.1055/a-1735-3864] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Georg Beyer
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Ludwig-Maximilians-Universität München, Deutschland
| | - Albrecht Hoffmeister
- Bereich Gastroenterologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Deutschland
| | - Patrick Michl
- Universitätsklinik u. Poliklinik Innere Medizin I mit Schwerpunkt Gastroenterologie, Universitätsklinikum Halle, Deutschland
| | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Deutschland
| | - Wolfgang Huber
- Comprehensive Cancer Center München TUM, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Deutschland
| | - Hana Algül
- Comprehensive Cancer Center München TUM, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Deutschland
| | - Albrecht Neesse
- Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Deutschland
| | - Alexander Meining
- Medizinische Klinik und Poliklinik II Gastroenterologie und Hepatologie, Universitätsklinikum Würzburg, Deutschland
| | | | - Jonas Rosendahl
- Universitätsklinik u. Poliklinik Innere Medizin I mit Schwerpunkt Gastroenterologie, Universitätsklinikum Halle, Deutschland
| | - Stefan Kahl
- Klinik für Innere Medizin m. Schwerpkt. Gastro./Hämat./Onko./Nephro., DRK Kliniken Berlin Köpenick, Deutschland
| | - Jutta Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - Jens Werner
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, Deutschland
| | - Helmut Friess
- Klinik und Poliklinik für Chirurgie, Klinikum rechts der Isar, München, Deutschland
| | - Philip Bufler
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Deutschland
| | - Matthias J Löhr
- Department of Gastroenterology, Karolinska, Universitetssjukhuset, Stockholm, Schweden
| | - Alexander Schneider
- Klinik für Gastroenterologie und Hepatologie, Klinikum Bad Hersfeld, Deutschland
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Irene Esposito
- Pathologisches Institut, Heinrich-Heine-Universität und Universitätsklinikum Duesseldorf, Duesseldorf, Deutschland
| | - Lars Grenacher
- Conradia Radiologie München Schwabing, München, Deutschland
| | - Joachim Mössner
- Bereich Gastroenterologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Deutschland
| | - Markus M Lerch
- Klinik für Innere Medizin A, Universitätsmedizin Greifswald, Deutschland.,Klinikum der Ludwig-Maximilians-Universität (LMU) München, Deutschland
| | - Julia Mayerle
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Ludwig-Maximilians-Universität München, Deutschland
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Löhr JM, Vujasinovic M, Rosendahl J, Stone JH, Beuers U. IgG4-related diseases of the digestive tract. Nat Rev Gastroenterol Hepatol 2022; 19:185-197. [PMID: 34750548 DOI: 10.1038/s41575-021-00529-y] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/22/2021] [Indexed: 12/15/2022]
Abstract
IgG4-related conditions affecting the digestive tract are part of a multi-organ fibro-inflammatory disorder termed IgG4-related disease (IgG4-RD), with autoimmune pancreatitis and IgG4-related cholangitis being the most prominent manifestations. Gastrointestinal symptoms include jaundice, weight loss, abdominal pain, biliary strictures, and pancreatic and hepatic masses that mimic malignant diseases. IgG4-RD manifestations occur less frequently elsewhere in the digestive tract, namely in the oesophagus, retroperitoneum or intestine. Evidence-based European guidelines frame the current state-of-the-art in the diagnosis and management of IgG4-related digestive tract disease. Diagnosis is based on histology (if available), imaging, serology, other organ involvement and response to therapy (HISORt criteria). Few biomarkers beyond serum IgG4 concentrations are reliable. The first-line therapy (glucocorticoids) is swiftly effective but disease flares are common at low doses or after tapering. Second-line therapy might consist of other immunosuppressive drugs such as thiopurines or rituximab. Further trials, for example, of anti-CD19 drugs, are ongoing. Although an association between IgG4-RD and the development of malignancies has been postulated, the true nature of this relationship remains uncertain at this time.
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Affiliation(s)
- J-Matthias Löhr
- Department for Upper Digestive Diseases, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
| | - Miroslav Vujasinovic
- Department for Upper Digestive Diseases, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - John H Stone
- Division of Rheumatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ulrich Beuers
- Department of Gastroenterology & Hepatology, Amsterdam University Medical Centers, Location AMC, Amsterdam, Netherlands
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20
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Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020. J Gastroenterol 2022; 57:225-245. [PMID: 35192048 PMCID: PMC8938398 DOI: 10.1007/s00535-022-01857-9] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/28/2022] [Indexed: 02/04/2023]
Abstract
In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.
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21
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A Transient Treatable Tumor of the Pancreas. Dig Dis Sci 2022; 67:76-80. [PMID: 34623577 DOI: 10.1007/s10620-021-07261-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/03/2021] [Indexed: 12/09/2022]
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Masood M. Autoimmune pancreatitis: What we know so far. JGH Open 2021; 6:3-10. [PMID: 35071782 PMCID: PMC8762623 DOI: 10.1002/jgh3.12688] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 11/12/2021] [Accepted: 11/20/2021] [Indexed: 12/19/2022]
Abstract
Autoimmune pancreatitis (AIP) is a rare, often‐missed disease that involves inflammation of the pancreas and strictures of the pancreatic duct. Its prevalence and incidence in the United States remain scarce. The disease has a varied presentation and often mimics pancreatic malignancy, which can make the diagnosis challenging. Most patients have an excellent response to corticosteroid therapy. Immunomodulators may be used in some cases. Rituximab is an effective, emerging treatment in steroid‐refractory cases. This study aims to review the two distinct types of AIP and provide a detailed analysis of the diagnostic approach and treatment modalities.
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Affiliation(s)
- Muaaz Masood
- Department of Internal Medicine Medical College of Georgia at Augusta University Augusta Georgia USA
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23
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Nikolic S, Panic N, Hintikka ES, Dani L, Rutkowski W, Hedström A, Steiner C, Löhr JM, Vujasinovic M. Efficacy and safety of rituximab in autoimmune pancreatitis type 1: our experiences and systematic review of the literature. Scand J Gastroenterol 2021; 56:1355-1362. [PMID: 34410885 DOI: 10.1080/00365521.2021.1963837] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/20/2021] [Accepted: 07/28/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Autoimmune pancreatitis (AIP) is a special form of pancreatitis that responds well to glucocorticoid (GC) treatment. Relapses of AIP are common. The anti-CD20 antibody rituximab (RTX) has shown promising results in GC refractory cases, but long-term data are scarce. The study aims to determine the clinical and imaging response to RTX and summarize the existing data on RTX therapy in patients with AIP type 1 in the literature. PATIENTS AND METHODS Retrospective analysis of electronic medical records was conducted. Additionally, we conducted a systematic review of the literature concerning RTX use in AIP type 1. RESULTS Twelve (11.7%) of 103 patients with AIP type 1 were treated with RTX during the study period: eight (66.7%) achieved complete and four (33.3%) partial remission. RTX was discontinued in one patient who developed fever and reactivation of latent tuberculosis. None of the remaining 11 patients relapsed during a median follow-up of 17 months. No significant differences were detected in baseline clinical characteristics or history of relapse between the patients who obtained complete and partial remission. Altogether, eight studies with 110 AIP type-1 patients treated with RTX were analyzed. Adverse effects ranged from 11-43% and the relapse-free period during follow-up (range 2-173 months) ranged from 38-94%. CONCLUSIONS Our results confirm that RTX is efficacious in the treatment of AIP type 1 by inducing remission and preventing relapse. In addition, there are few adverse effects of the treatment.
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Affiliation(s)
- Sara Nikolic
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
- Department of Gastroenterology, Division of Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
| | - Nikola Panic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | | | - Lara Dani
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Wiktor Rutkowski
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Aleksandra Hedström
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Corinna Steiner
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - J-Matthias Löhr
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
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Abstract
OBJECTIVE Rituximab (RTX) has been proposed for the induction of remission and maintenance therapy in relapsing type 1 autoimmune pancreatitis (AIP). The aim of the study was to describe the use of RTX as maintenance therapy for patients with type 1 AIP. METHODS Patients with type 1 AIP based on the International Consensus Diagnostic Criteria and treated with RTX were selected from our database. Two doses of RTX (1000 mg each) were administered 15 days apart and repeated after 6 months. RESULTS Eighteen patients were treated with RTX as maintenance therapy. Of these, the involvement of other organs was observed in 16 patients (89%). Eight of the 18 patients (44%) relapsed during follow-up. Median time to relapse after the last infusion was 30 months (range, 12-35 months). No disease relapse was observed in the first year after the last infusion. Probability of disease relapse was 80% between 1 and 3 years from initial treatment. No adverse effects were observed. CONCLUSIONS Rituximab seems be safe and effective for maintenance therapy of type 1 AIP during the first year after completing RTX infusion. However, the probability of disease relapse is high within 1 and 3 years from the last infusion.
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25
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Masaki Y, Nakase H, Tsuji Y, Nojima M, Shimizu K, Mizuno N, Ikeura T, Uchida K, Ido A, Kodama Y, Seno H, Okazaki K, Nakamura S, Masamune A. The clinical efficacy of azathioprine as maintenance treatment for autoimmune pancreatitis: a systematic review and meta-analysis. J Gastroenterol 2021; 56:869-880. [PMID: 34426870 PMCID: PMC8382580 DOI: 10.1007/s00535-021-01817-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/04/2021] [Indexed: 02/04/2023]
Abstract
The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.
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Affiliation(s)
- Yoshiharu Masaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
| | - Yoshihisa Tsuji
- Department of General Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masanori Nojima
- Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kyoko Shimizu
- Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tsukasa Ikeura
- The Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yuzo Kodama
- Department of Gastroenterology, Kobe University, Kobe, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | | | - Seiji Nakamura
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Lanzillotta M, Della-Torre E, Wallace ZS, Stone JH, Karadag O, Fernández-Codina A, Arcidiacono PG, Falconi M, Dagna L, Capurso G. Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis. Pancreatology 2021; 21:1395-1401. [PMID: 34244040 DOI: 10.1016/j.pan.2021.06.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/22/2021] [Accepted: 06/29/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment. METHODS The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates. RESULTS Seven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5-93.9) with no heterogeneity (I2 = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5-40.3) with moderate heterogeneity (I2 = 51%). A higher rate of relapse (35.9%, 95%CI 17.3-60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8-53) with substantial heterogeneity (I2 = 73.6%). No publication bias was observed. CONCLUSION Treatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.
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Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Emanuel Della-Torre
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - John H Stone
- Rheumatology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Omer Karadag
- Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Hacettepe University, Sihhiye-Ankara, Turkey
| | - Andreu Fernández-Codina
- Rheumatology Division and General Internal Medicine division-Windsor Campus, Western University, 268 Grosvenor St, D2-191, Rheumatology Centre, St. Joseph's Health Care, London, Ontario, Canada
| | - Paolo Giorgio Arcidiacono
- Division of Pancreatic Surgery and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Lorenzo Dagna
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Division of Pancreatic Surgery and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
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Yoon SB, Moon SH, Kim JH, Park JW, Kim SE, Kim MH. Determination of the duration of glucocorticoid therapy in type 1 autoimmune pancreatitis: A systematic review and meta-analysis. Pancreatology 2021; 21:S1424-3903(21)00474-9. [PMID: 34090808 DOI: 10.1016/j.pan.2021.05.303] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/18/2021] [Accepted: 05/21/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy. METHODS We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6-12 months vs. 12-36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated. RESULTS Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9-54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8-49.8%) for 6-12 months, 34.1% (95% CI, 28.6-39.7%) for 12-36 months, and 27.0% (95% CI, 23.4-30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5-34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8-52.4%). Adverse events were comparable between groups. CONCLUSIONS The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.
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Affiliation(s)
- Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea.
| | - Jong Hyeok Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Ji Won Park
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Myung-Hwan Kim
- Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea
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A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab. J Clin Med 2021; 10:jcm10061329. [PMID: 33807051 PMCID: PMC8004657 DOI: 10.3390/jcm10061329] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. METHODS We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. RESULTS Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. CONCLUSION RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6-9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy.
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Ammer-Herrmenau C, Ellenrieder V, Neesse A. [Diagnosis and Treatment of Chronic Pancreatitis]. Dtsch Med Wochenschr 2021; 146:237-245. [PMID: 33592659 DOI: 10.1055/a-1221-7236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Chronic pancreatitis is a complex chronic inflammatory condition that results in pancreas fibrosis and calcification with subsequent exocrine and endocrine insufficiency. Alcohol and nicotine are the most prevalent risk factors, however, recent studies have increasingly discovered genetic associations that increase the risk to develop chronic pancreatitis. Here, we discuss different etiologies of the disease including autoimmune pancreatitis, and present evidence-based diagnostic and therapeutic approaches. In particular, we highlight the interdisciplinary and interventional management of local complications such as pseudocysts, pancreatic duct stones, biliary duct and pancreatic duct stenosis and persistent pain.
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Abstract
Glucocorticoids are the first-line drug for the remission induction therapy of immunoglobulin (Ig) G4-related disease. Achieving drug-free remission using glucocorticoids alone is difficult, however, and many patients require maintenance therapy with glucocorticoids and immunosuppressants. Studies have recently found that the number of peripheral memory B cells and plasmablasts is increased in IgG4-related disease and have indicated the efficacy of rituximab, which, in remission induction therapy, rapidly reduces serum IgG4 levels and has the tapering effect of glucocorticoids. Rituximab has been shown to reduce the risk of relapse more than oral immunosuppressants such as azathioprine. However, maintaining drug-free remission is difficult with a single course of rituximab alone, and many cases require maintenance therapy with rituximab. This article outlines the potential of B-cell targeted therapy, focusing on the efficacy, and safety of rituximab for IgG4-related disease.
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Affiliation(s)
- Motohisa Yamamoto
- Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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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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Pelaez-Luna M, Soriano-Rios A, Lira-Treviño AC, Uscanga-Domínguez L. Steroid-responsive pancreatitides. World J Clin Cases 2020; 8:3411-3430. [PMID: 32913848 PMCID: PMC7457102 DOI: 10.12998/wjcc.v8.i16.3411] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/03/2020] [Accepted: 07/30/2020] [Indexed: 02/05/2023] Open
Abstract
Autoimmune pancreatitis has received considerable attention, especially due to the marked effect of corticosteroid therapy on its clinical course. Knowledge, especially regarding type 1 autoimmune pancreatitis, has significantly increased over the last decades, and despite significant differences in pathophysiology and outcomes, both type 1 and 2 autoimmune pancreatitis are still considered different types of the same disease. Some have proposed a different nomenclature reflecting these differences. Although the term steroid-responsive pancreatitides may be interpreted as synonymous to type 1 and 2 autoimmune pancreatitis, these are not the only pancreatic conditions that show a response to steroid therapy. Acute pancreatitis caused by vasculitis and connective tissue diseases and acute pancreatitis secondary to checkpoint inhibitors or programmed cell death receptor antibody-mediated blockage cancer therapy may also benefit from steroid treatment. This review presents current concepts on these disorders, aiming to increase awareness, analyze similarities and differences, and propose a new nomenclature that reflects their specific particularities, clustering them under the term "steroid-responsive pancreatitides".
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Affiliation(s)
- Mario Pelaez-Luna
- Research Division School of Medicine, Universidad Nacional Autonoma de México, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Andrea Soriano-Rios
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Ana C Lira-Treviño
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Luis Uscanga-Domínguez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
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Lanzillotta M, Vinge-Holmquist O, Overbeek KA, Poulsen JL, Demirci AF, Macinga P, Löhr M, Rosendahl J. PrescrAIP: A Pan-European Study on Current Treatment Regimens of Auto-Immune Pancreatitis. Front Med (Lausanne) 2020; 7:408. [PMID: 32850908 PMCID: PMC7419461 DOI: 10.3389/fmed.2020.00408] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 06/29/2020] [Indexed: 12/22/2022] Open
Abstract
Introduction: Treatment of autoimmune pancreatitis (AIP) is based solely on consensus and has yet to become standardized. Consequently, therapeutic regimens vary greatly between countries and centers, and largely depend on the experience of the physician. At this moment, the optimal regimen for inducing disease remission and preventing relapse is unknown. Objectives: The primary objective of this study is to describe current treatment regimens used in Europe, and to compare their effectiveness in inducing remission and preventing and treating relapse. The secondary objectives are: to identify risk factors for relapse; to assess the diagnostic accuracy of the Unified-AIP criteria; to assess the performance of the M-ANNHEIM score for predicting relapse; and to assess long-term outcomes including pancreatic exocrine insufficiency and pancreatic cancer. Methods: This is an international, retrospective, observational cohort study, performed in over 40 centers from 16 European countries. Eligible are all patients diagnosed with AIP from 2005 onwards, regardless of the used diagnostic criteria. Data on study subjects will be retrieved from the hospital's electronic medical records and registered with a standardized, web-based, electronic case report form (eCRF). To compare the effectiveness of treatment regimens in inducing remission, preventing relapse, and treating relapse, subjects will be stratified in groups based on: type of therapy; initial therapy dose; cumulative therapy dose; therapy tapering speed and duration; and having received maintenance therapy or not. Ethics and Dissemination: Ethical and/or institutional review board approvals are obtained by all participating centers according to local regulations. The study complies with the General Data Protection Regulation (GDPR). All manuscripts resulting from the study will be submitted to peer-reviewed journals. Conclusion: This is the first pan-European retrospective registry for AIP. It will produce the first large-scale data on treatment of European patients with AIP, providing answers on the use and effectiveness of treatment regimens. In the future, this collaboration may provide a network for continuation into a prospective European registry.
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Affiliation(s)
- Marco Lanzillotta
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Olof Vinge-Holmquist
- Department of Gastroenterological Surgery, Akershus University Hospital, Loerenskog, Norway
| | - Kasper A Overbeek
- Department of Gastroenterology & Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Jakob L Poulsen
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - A Fatih Demirci
- Department of Internal Medicine, Marmara University Research and Education Hospital, Istanbul, Turkey
| | - Peter Macinga
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czechia
| | - Matthias Löhr
- Gastroenterology and Hepatology, Gastrocentrum, Karolinska University Hospital, Karolinska Universitetssjukhuset, Stockholm, Sweden
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle (Saale), Germany
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Miranda-Zazueta G, González-Regueiro JA, García-Juárez I, Moctezuma-Velázquez C, López-Díaz FJ, Pérez-González B, Uscanga-Domínguez LF, Peláez-Luna M. Pharmacologic management of patients with hepatic and pancreatic diseases that involve immunosuppressive therapies. Position statement within the framework of the SARS-CoV-2 (COVID-19) pandemic. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:312-320. [PMID: 32620315 PMCID: PMC7298481 DOI: 10.1016/j.rgmx.2020.06.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/31/2020] [Accepted: 06/11/2020] [Indexed: 12/13/2022]
Abstract
The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) virus. COVID-19 affected more than 6million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.
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Affiliation(s)
- G Miranda-Zazueta
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - J A González-Regueiro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - I García-Juárez
- Departamento de Gastroenterología, Unidad de Hepatología y Trasplante Hepático, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - C Moctezuma-Velázquez
- Departamento de Gastroenterología, Unidad de Hepatología y Trasplante Hepático, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - F J López-Díaz
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - B Pérez-González
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - L F Uscanga-Domínguez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - M Peláez-Luna
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México.
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Barresi L, Tacelli M, Crinò SF, Attili F, Petrone MC, De Nucci G, Carrara S, Manfredi G, Capurso G, De Angelis CG, Crocellà L, Fantin A, Dore MF, Garribba AT, Tarantino I, De Pretis N, Pagliari D, Rossi G, Manes G, Preatoni P, Barbuscio I, Tuzzolino F, Traina M, Frulloni L, Costamagna G, Arcidiacono PG, Buscarini E, Pezzilli R, Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO), Italian Association for the Study of the Pancreas (AISP). Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency. United European Gastroenterol J 2020; 8:705-715. [PMID: 32397913 PMCID: PMC7437084 DOI: 10.1177/2050640620924302] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 04/03/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice. OBJECTIVES The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy. METHODS Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy. RESULTS One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%. CONCLUSIONS In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.
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Affiliation(s)
- Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Matteo Tacelli
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.), University of Palermo, Palermo, Italy
| | - Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University Hospital of Verona, Verona, Italy
| | - Fabia Attili
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
| | - Maria Chiara Petrone
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano, Italy
| | - Germana De Nucci
- Gastroenterology and Digestive Endoscopy Unit, ASST Rhodense, Garbagnate Milanese Hospitals, Milano, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center-IRCCS Rozzano (MI), Italy
| | - Guido Manfredi
- Gastroenterology and Digestive Endoscopy Department, Maggiore Hospital, ASST Crema, Crema, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano, Italy
- Digestive and Liver Disease Unit, S. Andrea Hospital, Roma, Italy
| | | | - Lucia Crocellà
- Gastroenterology Unit, Mauriziano Umberto I Hospital, Torino, Italy
| | - Alberto Fantin
- Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Division, Azienda Ospedaliera di Padova, University of Padova, Padua, Italy
| | | | | | - Ilaria Tarantino
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Nicolò De Pretis
- Gastroenterology unit, Pancreas center, University of Verona, Verona, Italy
| | - Danilo Pagliari
- Division of Internal Medicine and Gastroenterology & Pancreatic Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Universita’ del Sacro Cuore, Roma, Italy
| | - Gemma Rossi
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano, Italy
| | - Gianpiero Manes
- Gastroenterology and Digestive Endoscopy Unit, ASST Rhodense, Garbagnate Milanese Hospitals, Milano, Italy
| | - Paoletta Preatoni
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center-IRCCS Rozzano (MI), Italy
| | - Ilenia Barbuscio
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
- Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Division, Azienda Ospedaliera di Padova, University of Padova, Padua, Italy
| | - Fabio Tuzzolino
- Research Office, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
| | - Mario Traina
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Luca Frulloni
- Gastroenterology unit, Pancreas center, University of Verona, Verona, Italy
| | - Guido Costamagna
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Centre for Endoscopic Research Therapeutics and Training-CERTT, Università del SacroCuore, Roma, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano, Italy
| | - Elisabetta Buscarini
- Gastroenterology and Digestive Endoscopy Department, Maggiore Hospital, ASST Crema, Crema, Italy
| | - Raffaele Pezzilli
- Pancreas Unit, Department of Gastroenterology, Sant’Orsola Polyclinic, Bologna, Italy
| | - Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO), Italian Association for the Study of the Pancreas (AISP)
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.), University of Palermo, Palermo, Italy
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, University Hospital of Verona, Verona, Italy
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano, Italy
- Gastroenterology and Digestive Endoscopy Unit, ASST Rhodense, Garbagnate Milanese Hospitals, Milano, Italy
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center-IRCCS Rozzano (MI), Italy
- Gastroenterology and Digestive Endoscopy Department, Maggiore Hospital, ASST Crema, Crema, Italy
- Digestive and Liver Disease Unit, S. Andrea Hospital, Roma, Italy
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
- Gastroenterology Unit, Mauriziano Umberto I Hospital, Torino, Italy
- Department of Surgical, Oncological and Gastroenterological Sciences, Gastroenterology Division, Azienda Ospedaliera di Padova, University of Padova, Padua, Italy
- Gastroenterology Unit, Brotzu Hospital, Cagliari, Italy
- Gastroenterology Unit, AUSL Romagna, Ravenna, Italy
- Gastroenterology unit, Pancreas center, University of Verona, Verona, Italy
- Division of Internal Medicine and Gastroenterology & Pancreatic Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Universita’ del Sacro Cuore, Roma, Italy
- Research Office, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), Palermo, Italy
- Centre for Endoscopic Research Therapeutics and Training-CERTT, Università del SacroCuore, Roma, Italy
- Pancreas Unit, Department of Gastroenterology, Sant’Orsola Polyclinic, Bologna, Italy
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Pharmacologic management of patients with hepatic and pancreatic diseases that involve immunosuppressive therapies. Positioning within the framework of the SARS-CoV-2 (COVID-19) pandemic. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2020. [PMCID: PMC7832058 DOI: 10.1016/j.rgmxen.2020.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. COVID-19 affected close to 2 million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.
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Löhr JM, Beuers U, Vujasinovic M, Alvaro D, Frøkjær JB, Buttgereit F, Capurso G, Culver EL, de-Madaria E, Della-Torre E, Detlefsen S, Dominguez-Muñoz E, Czubkowski P, Ewald N, Frulloni L, Gubergrits N, Duman DG, Hackert T, Iglesias-Garcia J, Kartalis N, Laghi A, Lammert F, Lindgren F, Okhlobystin A, Oracz G, Parniczky A, Mucelli RMP, Rebours V, Rosendahl J, Schleinitz N, Schneider A, van Bommel EFH, Verbeke CS, Vullierme MP, Witt H, the UEG guideline working group. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J 2020; 8:637-666. [PMID: 32552502 PMCID: PMC7437085 DOI: 10.1177/2050640620934911] [Citation(s) in RCA: 133] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 05/04/2020] [Indexed: 12/12/2022] Open
Abstract
The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.
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Affiliation(s)
- J-Matthias Löhr
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
| | - Miroslav Vujasinovic
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Frank Buttgereit
- Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division Pancreas Translational and Clinical Research Center IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, ISABIAL, Alicante, Spain
| | - Emanuel Della-Torre
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Disease (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Nils Ewald
- Institute of Endocrinology, Diabetology and Metabolism, Johannes Wesling University hospital, Minden, Germany and Justus Liebig University Giessen, Giessen, Germany
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman, Ukraine
| | - Deniz Guney Duman
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Nikolaos Kartalis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Andrea Laghi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, Sant’Andrea Hospital, Rome, Italy
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Fredrik Lindgren
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden
| | | | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
| | - Andrea Parniczky
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Insitute of Pediatrics, Budapest, Hungary
| | | | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, Clichy, Université de Paris, France
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - Nicolas Schleinitz
- Département de Médicine Interne Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France
| | - Alexander Schneider
- Department of Gastroenterology and Hepatology, Klinikum Bad Hersfeld, Bad Hersfeld, Germany
| | - Eric FH van Bommel
- Department of Internal Medicine, Dutch National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer hospital, Dordrecht, the Netherlands
| | | | | | - Heiko Witt
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Paediatric Nutritional Medicine, Technische Universität München, Freising, Germany
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Matsubayashi H, Ishiwatari H, Imai K, Kishida Y, Ito S, Hotta K, Yabuuchi Y, Yoshida M, Kakushima N, Takizawa K, Kawata N, Ono H. Steroid Therapy and Steroid Response in Autoimmune Pancreatitis. Int J Mol Sci 2019; 21:E257. [PMID: 31905944 PMCID: PMC6981453 DOI: 10.3390/ijms21010257] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 12/18/2019] [Accepted: 12/25/2019] [Indexed: 12/11/2022] Open
Abstract
Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33-78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24-52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
- Genetic Medicine Promotion, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan
| | - Hirotoshi Ishiwatari
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Yoshihiro Kishida
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Sayo Ito
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Yohei Yabuuchi
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Naomi Kakushima
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
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