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Yang X, Zhou H, Wang W, Yan C, Ji G. Recent advances in IgG4-related autoimmune pancreatitis. Pathol Res Pract 2024; 257:155331. [PMID: 38678849 DOI: 10.1016/j.prp.2024.155331] [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: 03/14/2024] [Revised: 04/16/2024] [Accepted: 04/24/2024] [Indexed: 05/01/2024]
Abstract
The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.
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Affiliation(s)
- Xisheng Yang
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Haikun Zhou
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Weidong Wang
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Chunyu Yan
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Gang Ji
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
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2
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Wallace ZS, Katz G, Hernandez-Barco YG, Baker MC. Current and future advances in practice: IgG4-related disease. Rheumatol Adv Pract 2024; 8:rkae020. [PMID: 38601138 PMCID: PMC11003820 DOI: 10.1093/rap/rkae020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 12/28/2023] [Indexed: 04/12/2024] Open
Abstract
IgG4-related disease (IgG4-RD) is an increasingly recognized cause of fibroinflammatory lesions in patients of diverse racial and ethnic backgrounds and is associated with an increased risk of death. The aetiology of IgG4-RD is incompletely understood, but evidence to date suggests that B and T cells are important players in pathogenesis, both of which are key targets of ongoing drug development programmes. The diagnosis of IgG4-RD requires clinicopathological correlation because there is no highly specific or sensitive test. Glucocorticoids are highly effective, but their use is limited by toxicity, highlighting the need for studies investigating the efficacy of glucocorticoid-sparing agents. B cell-targeted therapies, particularly rituximab, have demonstrated benefit, but no randomized clinical trials have evaluated their efficacy. If untreated or under-treated, IgG4-RD can cause irreversible organ damage, hence close monitoring and consideration for long-term immunosuppression is warranted in certain cases.
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Affiliation(s)
- Zachary S Wallace
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Harvard University, Boston, MA, USA
| | - Guy Katz
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Harvard University, Boston, MA, USA
| | - Yasmin G Hernandez-Barco
- Harvard Medical School, Harvard University, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Matthew C Baker
- Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, USA
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3
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Zen Y. Autoimmune pancreatitis: Biopsy interpretation and differential diagnosis. Semin Diagn Pathol 2024; 41:79-87. [PMID: 38184420 DOI: 10.1053/j.semdp.2024.01.001] [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: 08/07/2023] [Accepted: 01/02/2024] [Indexed: 01/08/2024]
Abstract
Autoimmune pancreatitis (AIP) is classified into type 1 (IgG4-related) and type 2 (IgG4-unrelated) and the interpretation of pancreatic biopsy findings plays a crucial role in their diagnosis. Needle biopsy of type 1 AIP in the acute or subacute phase shows a diffuse lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and the infiltration of many IgG4-positive plasma cells. In a later phase, changes become less inflammatory and more fibrotic, making interpretations more challenging. Confirmation of the lack of 'negative' findings that are unlikely to occur in type 1 AIP (e.g., neutrophilic infiltration, abscess) is important to avoid an overdiagnosis. The number of IgG4-positive plasma cells increases to >10 cells/high-power field (hpf), and the IgG4/IgG-positive plasma cell ratio exceeds 40 %. However, these are minimal criteria and typical cases show >30 positive cells/hpf and a ratio >70 % even in biopsy specimens. Therefore, cases with a borderline increase in this number or ratio need to be diagnosed with caution. In cases of ductal adenocarcinoma, the upstream pancreas rarely shows type 1 AIP-like changes; however, the ratio of IgG4/IgG-positive plasma cells is typically <40 %. Although the identification of a granulocytic epithelial lesion (GEL) is crucial for type 2 AIP, this finding needs to be interpreted in conjunction with a background dense lymphoplasmacytic infiltrate. An isolated neutrophilic duct injury can occur in peritumoral or obstructive pancreatitis. Drug-induced pancreatitis in patients with inflammatory bowel disease often mimics type 2 AIP clinically and pathologically. IL-8 and PD-L1 are potential ancillary immunohistochemical markers for type 2 AIP, requiring validation studies.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK.
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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: 7] [Impact Index Per Article: 7.0] [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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Eder P, Verstock B, Culver E, Dragoni G, Kredel LI, Wypych J, de Paredes AGG, Kaniewska M, Leibovitzh H, Lobaton T, Truyens M, Oracz G, Giuseppe Ribaldone D, Starzyńska T, Badaoui A, Rahier JF, Bezzio C, Bossuyt P, Falloon K, Pugliese D, Frakes Vozzo C, Jess T, Larsen L, Olesen SS, Pal P, Chaparro M, Dror D, Ellul P, Gromny I, Janiak M, Maciejewska K, Peleg N, Bar-Gil Shitrit A, Szwed Ł, Talar-Wojnarowska R, Snir Y, Weisshof R, Zittan E, Miechowicz I, Goren I. Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study. J Crohns Colitis 2023; 17:1791-1799. [PMID: 37283545 PMCID: PMC10673810 DOI: 10.1093/ecco-jcc/jjad097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 04/05/2023] [Accepted: 06/06/2023] [Indexed: 06/08/2023]
Abstract
BACKGROUND Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.
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Affiliation(s)
- Piotr Eder
- Department of Gastroenterology, Dietetics, and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Bram Verstock
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Emma Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Oxford, NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Gabriele Dragoni
- Department of Gastroenterology, Careggi University Hospital, Florence, Italy
| | - Lea Isabell Kredel
- Division of Gastroenterology, Infectiology and Rheumatology, Medical Department, Charité-Universitätsmedizin, Berlin, Germany
| | - Joanna Wypych
- Department of Gastroenterology, Surgery and Nutrition, Copernicus Hospital, Gdansk, Poland
| | - Ana Garcia Garcia de Paredes
- Gastroenterology and Hepatology Department. Hospital Universitario Ramon y Cajal. Universidad de Alcala, IRYCIS, Madrid, Spain
| | - Magdalena Kaniewska
- Department of Gastroenterology with IBD Subdivision, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
| | - Haim Leibovitzh
- Zane Cohen Centre for Digestive Diseases, Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Department of Gastroenterology, Ghent University, Ghent, Belgium
| | - Marie Truyens
- Department of Internal Medicine and Pediatrics, Department of Gastroenterology, Ghent University, Ghent, Belgium
| | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Feeding Disorder and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland; Pediatric Gastroenterology Faculty, Centre of Postgraduate Medical Education, Warsaw, Poland
| | | | - Teresa Starzyńska
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Abdenor Badaoui
- Department of Gastroenterology, Université Catholique de Louvain, Yvoir, Belgium
| | - Jean-Francois Rahier
- Department of Gastroenterology, Université Catholique de Louvain, Yvoir, Belgium
| | - Cristina Bezzio
- Gastroenterology Unit, Rho Hospital, Rho (MI), ASST Rhodense, Garbagnate Milanese, Italy
| | - Peter Bossuyt
- Imelda GI Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium
| | - Katherine Falloon
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Daniela Pugliese
- CEMAD, IBD UNIT, Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy
| | - Catherine Frakes Vozzo
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Lone Larsen
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Center for Molecular Prediction of Inflammatory Bowel Disease – PREDICT, Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Schou Olesen
- Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Partha Pal
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad, India
| | - María Chaparro
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Dikla Dror
- Department of Gastroenterology, Galilee Medical Center, Nahariyya, Israel
| | - Pierre Ellul
- Division of Gastroenterology, Mater dei Hospital, Malta
| | - Iga Gromny
- Division of Dietetics, Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Maria Janiak
- Department of Gastroenterology and Hepatology, Medical University of Gdańsk, Gdańsk, Poland
| | - Katarzyna Maciejewska
- Department of Gastroenterology with IBD Subdivision, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
| | - Noam Peleg
- The Division of Gastroenterology, Rabin Medical Center, Petach Tikva, Israel, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ariella Bar-Gil Shitrit
- IBD MOM Unit, Digestive Diseases Institute, The Hebrew University of Jerusalem, Shaare Zedek Medical Center, Jerusalem, Israel
| | - Łukasz Szwed
- Private Gastroenterology Practice, Nowy Dwór Mazowiecki, Poland
| | | | - Yifat Snir
- Gastroenterology Department, Clalit Health Services, Tel Aviv District, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Roni Weisshof
- Gastroenterology Institute at Rambam Health Care Campus in Haifa, Haifa, Israel
| | - Eran Zittan
- Ellen and Pinchas Mamber Institute of Gastroenterology and Liver Diseases, IBD Unit, Emek Medical Center, Afula, Israel
| | - Izabela Miechowicz
- Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland
| | - Idan Goren
- Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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Li Y, Song H, Meng X, Li R, Leung PSC, Gershwin ME, Zhang S, Sun S, Song J. Autoimmune pancreatitis type 2 (idiopathic duct-centric pancreatitis): A comprehensive review. J Autoimmun 2023; 140:103121. [PMID: 37826920 DOI: 10.1016/j.jaut.2023.103121] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/20/2023] [Accepted: 10/02/2023] [Indexed: 10/14/2023]
Abstract
Autoimmune pancreatitis (AIP) is an uncommon fibro-inflammatory disorder precipitated by autoimmune/inflammatory reactions. Currently, there are two clinical subtypes of AIP (type 1 [AIP-1] and type 2 [AIP-2]) that correspond to two histologic descriptors (lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis, respectively). While our understanding of AIP-1 has evolved considerably over the years, little is known about AIP-2 due to its rarity, often leading to misdiagnosis, delayed treatment, and even unnecessary surgical resection. Compared to AIP-1, AIP-2 exhibits distinct clinical and histologic features. Because AIP-2 is a pancreas-restricted disease without a specific serum marker, the evaluation of histologic features (e.g., granulocytic epithelial lesions) is essential for an accurate diagnosis. Patients with AIP-2 respond well to glucocorticoids, with anti-tumor necrosis factor-alpha antibodies as a promising alternative therapy. The prognosis of AIP-2 is generally favorable and relapse is uncommon. Here, we provide an overview of our current knowledge on the clinical features, diagnosis, therapeutic regimens, prognosis, and putative mechanisms underlying AIP-2. Notably, the diagnostic differentiation between AIP-2, especially the mass-forming/focal type, and pancreatic cancer is important, but challenging. In this regard, endoscopic ultrasound-guided core biopsy has a key role, but novel diagnostic markers and modalities are clearly needed.
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Affiliation(s)
- Yang Li
- Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Hanyi Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Xiangzhen Meng
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Runzhuo Li
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Patrick S C Leung
- Division of Rheumatology/Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA 95616 USA
| | - M Eric Gershwin
- Division of Rheumatology/Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA 95616 USA
| | - Shucheng Zhang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China.
| | - Siyu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China.
| | - Junmin Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China.
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Yu ZQ, Bai XY, Ruan GC, Han W, Xu TM, Zhang MY, Wang BM, Zhang YJ, Guo MY, Yang H. Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China. J Dig Dis 2023; 24:452-460. [PMID: 37503771 DOI: 10.1111/1751-2980.13209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/02/2023] [Accepted: 07/25/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. METHODS A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. RESULTS The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). CONCLUSIONS Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.
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Affiliation(s)
- Zi Qing Yu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiao Yin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ge Chong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wei Han
- Department of Epidemiology and Biostatistics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Tian Ming Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Meng Yuan Zhang
- Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bei Ming Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yu Jia Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ming Yue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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8
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Ito T, Ikeura T, Notohara K, Masuda M, Nakamaru K, Nakayama S, Shimatani M, Takaoka M, Okazaki K, Naganuma M. A case of type 2 autoimmune pancreatitis with spontaneous remission. Clin J Gastroenterol 2023; 16:297-302. [PMID: 36696084 DOI: 10.1007/s12328-022-01753-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/27/2022] [Indexed: 01/26/2023]
Abstract
A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.
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Affiliation(s)
- Takashi Ito
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Tsukasa Ikeura
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan.
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Masataka Masuda
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Koh Nakamaru
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Shinji Nakayama
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Masaaki Shimatani
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Makoto Takaoka
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | | | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
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9
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Zavrtanik H, Tomažič A. Is Surgery in Autoimmune Pancreatitis Always a Failure? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020193. [PMID: 36837395 PMCID: PMC9961097 DOI: 10.3390/medicina59020193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/14/2023] [Accepted: 01/15/2023] [Indexed: 01/21/2023]
Abstract
Autoimmune pancreatitis is a rare form of chronic pancreatitis of presumed autoimmune etiology. Due to significant overlap in clinical and imaging characteristics, misdiagnosis as a pancreatic malignancy is common. As a result, a significant number of patients undergo a major pancreatic resection, associated with considerable morbidity, for a disease process that generally responds well to corticosteroid therapy. In the past ten years, important advances have been made in understanding the disease. Several diagnostic criteria have been developed to aid in diagnosis. Despite this, pancreatic resection may still be required in a subset of patients to reliably exclude pancreatic malignancy and establish a definite diagnosis of autoimmune pancreatitis. This article aimed to define the role of surgery in autoimmune pancreatitis, if any. For this purpose, published case series of patients with a diagnosis of autoimmune pancreatitis, based on the histopathological examination of surgical specimens, were reviewed and patients' clinical, radiological and serological details were assessed. At the end, histopathologic examinations of patients who underwent pancreatic resection at our department in the last 10 years were retrospectively reviewed in order to identify patients with autoimmune pancreatitis and assess their clinical characteristics.
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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: 2] [Impact Index Per Article: 1.0] [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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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:ijms232012667. [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
- Correspondence:
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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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Bezzio C, Della Corte C, Vernero M, Di Luna I, Manes G, Saibeni S. Inflammatory bowel disease and immune-mediated inflammatory diseases: looking at the less frequent associations. Therap Adv Gastroenterol 2022; 15:17562848221115312. [PMID: 35924080 PMCID: PMC9340394 DOI: 10.1177/17562848221115312] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 07/06/2022] [Indexed: 02/04/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) often have other immune-mediated inflammatory diseases (IMIDs), and the prevalence of any IMID is higher in IBD patients than in the general population. IBD and other IMIDs involve alterations in innate and adaptive immune responses. Their co-occurrence depends on shared immune and inflammatory processes, pathogenic mechanisms, and genetic and environmental risk factors, including drugs, especially tumor necrosis factor inhibitors. The more common IMIDs associated with IBD have been widely described, so this review focuses on the less frequent associations. The IMIDs discussed here are skin disorders (psoriasis, atopic dermatitis, vitiligo, epidermolysis bullosa acquisita, cutaneous polyarteritis nodosa, and hidradenitis suppurativa), hepato-pancreatic diseases (autoimmune hepatitis, granulomatous hepatitis, and autoimmune pancreatitis), endocrine diseases (autoimmune thyroid diseases, and type 1 diabetes mellitus), multiple sclerosis, and respiratory diseases (asthma, bronchiectasis, and interstitial pneumonia). The early detection of IMIDs in IBD patients is important to prevent their deleterious clinical course and limit their psychological impact. Care for IBD patients with IMIDs should be multispecialist, with a single therapeutic strategy instead of treating each disease separately.
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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: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [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
Affiliation(s)
- Sara Nikolic
- Department of Medicine Huddinge Karolinska Institutet Stockholm Sweden
- Department of Gastroenterology Clinic for Internal Medicine University Medical Centre Maribor Maribor Slovenia
| | - Marco Lanzillotta
- Università Vita‐Salute San Raffaele IRCCS San Raffaele Scientific Institute Milan Italy
- Unit of Immunology Rheumatology, Allergy and Rare Diseases (Unirar) IRCCS San Raffaele Scientific Institute, ss Milan Milan Italy
| | - Nikola Panic
- Faculty of Medicine University of Belgrade Digestive Endoscopy Unit University Clinic “Dr Dragisa Misovic” Belgrade Serbia
| | - Torkel B. Brismar
- Department of Radiology Karolinska University Hospital Stockholm Sweden
| | - Carlos Fernández Moro
- Department of Clinical Pathology and Cancer Diagnostics Karolinska University Hospital Stockholm Sweden
| | - Gabriele Capurso
- Division of Pancreatic Surgery 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 (Unirar) IRCCS San Raffaele Scientific Institute, ss Milan Milan Italy
| | - J.‐Matthias Löhr
- Department of Upper Digestive Diseases Karolinska University Hospital Stockholm Sweden
- Department of Clinical Science Intervention, and Technology (CLINTEC) Karolinska Institutet Stockholm Sweden
| | - Miroslav Vujasinovic
- Department of Medicine Huddinge Karolinska Institutet Stockholm Sweden
- Department of Upper Digestive Diseases Karolinska University Hospital Stockholm Sweden
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Notohara K. Biopsy diagnosis of type 1 autoimmune pancreatitis: Does it bring a conclusion or confusion? DEN OPEN 2022; 2:e82. [PMID: 35310716 PMCID: PMC8828250 DOI: 10.1002/deo2.82] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 11/10/2021] [Indexed: 05/11/2023]
Abstract
A biopsy-based diagnosis of type 1 autoimmune pancreatitis (AIP) is now feasible via an endoscopic ultrasound-guided fine-needle biopsy, but there are potential issues to address. The benefits of acquiring large tissue samples include more successful immunostaining for Immunoglobulin G4 and more identifications of storiform fibrosis, obliterative phlebitis, and the ductal lesions of type 1 AIP. However, storiform fibrosis may not be present in all the type 1 AIP lesions. An interobserver agreement study revealed only slight-to-moderate agreement among pathologists diagnosing the histological findings of type 1 AIP. Potential reasons for disagreement are the different time phases of the inflammation (which result in heterogeneous histological pictures), a focal appearance of the typical histological findings, and the different definitions used by pathologists. We have thus devised guidance for diagnosing type 1 AIP based on biopsy tissues. In this guidance, we define each histological finding of type 1 AIP, for example, storiform fibrosis as a swirling arrangement of inflammatory cells, spindle-shaped cells, and delicate collagens as a unit. The necessity of elastic stains for identifying obliterative phlebitis is explained, with examples of mimickers. Another important purpose of a biopsy in type 1 AIP cases is differentiation from pancreatic ductal adenocarcinoma (PDAC). In this situation, acinar-ductal metaplasia observed in type 1 AIP is a mimicker of PDAC and should not be confused. For the resolution of potential disagreements among pathologists, a multi-disciplinary approach with the collaboration of clinicians, radiologists, and pathologists is necessary to avoid confusion.
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Affiliation(s)
- Kenji Notohara
- Department of Anatomic PathologyKurashiki Central HospitalOkayamaJapan
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Notohara K, Kamisawa T, Furukawa T, Fukushima N, Uehara T, Kasashima S, Iwasaki E, Kanno A, Kawashima A, Kubota K, Kuraishi Y, Motoya M, Naitoh I, Nishino T, Sakagami J, Shimizu K, Tomono T, Aishima S, Fukumura Y, Hirabayashi K, Kojima M, Mitsuhashi T, Naito Y, Ohike N, Tajiri T, Yamaguchi H, Fujiwara H, Ibuki E, Kobayashi S, Miyaoka M, Nagase M, Nakashima J, Nakayama M, Oda S, Taniyama D, Tsuyama S, Watanabe S, Ikeura T, Kawa S, Okazaki K. Concordance of the histological diagnosis of type 1 autoimmune pancreatitis and its distinction from pancreatic ductal adenocarcinoma with endoscopic ultrasound-guided fine needle biopsy specimens: an interobserver agreement study. Virchows Arch 2022; 480:565-575. [PMID: 34820715 DOI: 10.1007/s00428-021-03236-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 09/25/2021] [Accepted: 11/07/2021] [Indexed: 10/28/2022]
Abstract
The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss' к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.
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Affiliation(s)
- Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan.
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Satomi Kasashima
- Department of Clinical Laboratory Science, Graduate School of Health Science, Kanazawa University, Kanazawa, Japan
| | - Eisuke Iwasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
- Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan
| | - Atsuhiro Kawashima
- Department of Diagnostic Pathology, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan
| | - Kensuke Kubota
- Depatment of Endoscopy, Yokohama City University Hospital, Yokohama, Japan
| | - Yasuhiro Kuraishi
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masayo Motoya
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takayoshi Nishino
- Department of Gastroenterology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan
| | - Junichi Sakagami
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Fukuchiyama City Hospital, Fukuchiyama, Japan
| | - Kyoko Shimizu
- Department of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Teruko Tomono
- Department of Gastroenterology, Kyoto University Hospital, Kyoto, Japan
| | - Shinichi Aishima
- Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kenichi Hirabayashi
- Department of Pathology, Tokai University School of Medicine, Isehara, Japan
| | - Motohiro Kojima
- Division of Pathology, Research Center for Innovative Oncology, National Cancer Center, Kashiwa, Japan
| | - Tomoko Mitsuhashi
- Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan
| | - Yoshiki Naito
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
- Division of Pathology, Shizuoka Cancer Center, Sunto-gun, Japan
| | - Takuma Tajiri
- Department of Diagnostic Pathology, Tokai University Hachioji Hospital, Hachioji, Japan
| | | | - Hideyo Fujiwara
- Department of Pathology, Kawasaki Medical School, Kurashiki, Japan
| | - Emi Ibuki
- Department of Diagnostic Pathology, Kagawa University, Kita-gun, Japan
| | - Shota Kobayashi
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masashi Miyaoka
- Department of Pathology, Tokai University School of Medicine, Isehara, Japan
| | - Mamiko Nagase
- Department of Organ Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Junko Nakashima
- Department of Pathology, Kochi Medical School, Kochi University, Nangoku, Japan
| | - Masamichi Nakayama
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Shinsuke Oda
- Department of Diagnostic Pathology, Tottori Prefectural Central Hospital, Tottori, Japan
| | - Daiki Taniyama
- Molecular Pathology, Hiroshima University, Hiroshima, Japan
| | - Sho Tsuyama
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | | | - Tsukasa Ikeura
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Japan
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Conti Bellocchi MC, Marconato E, Lamonaca L, Cattani Mottes M, Ciccocioppo R, Carrara S, de Pretis N, Gabbrielli A, Crinò SF, Frulloni L. The features and clinical outcomes of inflammatory bowel disease associated with autoimmune pancreatitis: A greater awareness is needed. Medicine (Baltimore) 2022; 101:e28602. [PMID: 35089195 PMCID: PMC8797592 DOI: 10.1097/md.0000000000028602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/29/2021] [Indexed: 01/05/2023] Open
Abstract
The prevalence of inflammatory bowel disease (IBD) has been described in 5% to 40% of autoimmune pancreatitis (AIP) patients. The aim of our study was to evaluate the prevalence, endoscopic features, and outcome of IBD in association with AIP.A retrospective analysis including all consecutive patients with AIP and a histological diagnosis of IBD from 2010 to 2020 was performed. Demographical data, AIP, and IBD features, as well as clinical course, were recorded.Among 267 AIP patients, 45 were diagnosed with ulcerative colitis (UC) (27 men, mean age 31.6), all with a diagnosis of type 2 AIP. The most frequent presentation of AIP was acute pancreatitis (55.5%). Both diffuse (51.1%) and focal (48.9%) pancreatic involvement were observed. The AIP relapse rate was 11.1% over a mean follow-up of 55 months. In 69% of patients, the interval time between the diagnosis of AIP and UC was <1 year. When UC was present at AIP onset, UC was in clinical remission in 50% of patients. Fecal calprotectin levels, when available, were elevated in 86.6% of these patients. Mostly, mild-moderate pancolitis was initially diagnosed (55.5%). During follow-up, escalation therapy for UC was required in 40% of patients after a mean time of 45 months. Two patients (4.4%) underwent colectomy.The prevalence of UC in AIP patients was 17%. Mild pancolitis with a low rate of colectomy was found. Greater awareness is needed to avoid a delayed diagnosis of UC, and the dosage of fecal calprotectin levels could have a role in this setting.
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Affiliation(s)
- Maria Cristina Conti Bellocchi
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Eugenio Marconato
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Laura Lamonaca
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano, Italy
| | - Martina Cattani Mottes
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano, Italy
| | - Nicolo’ de Pretis
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Armando Gabbrielli
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Stefano Francesco Crinò
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
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Notohara K. Histological features of autoimmune pancreatitis and IgG4-related sclerosing cholangitis with a correlation with imaging findings. J Med Ultrason (2001) 2021; 48:581-594. [PMID: 34669070 DOI: 10.1007/s10396-021-01148-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/03/2021] [Indexed: 12/12/2022]
Abstract
Autoimmune pancreatitis (AIP) is characterized by a tumefactive inflammatory lesion resembling pancreatic carcinoma. Type 1 AIP is a pancreatic manifestation of IgG4-related disease characterized by unique histological features that can be identified on imaging. The capsule-like rim, which is a collar of hypertrophic lesion surrounding the pancreas, consists of lymphoplasmacytic infiltration and fibrosis, and storiform fibrosis is often identified. Hypertrophic lesions of various microscopic architectures such as the ducts, veins (obliterative phlebitis), arteries (periarteritis), and nerves are observed without parenchymal damage. The pancreatic lobules keep their contours, but the acinar cells are diminished and replaced by numerous inflammatory cells. These features provide clues to arrive at a diagnosis of type 1 AIP and to distinguish it from pancreatic carcinoma on imaging. In contrast, type 2 AIP is an epithelium-centered inflammation involving the ducts and lobules. Neutrophilic infiltration in the epithelium and/or lumens (granulocytic epithelial lesion) is a characteristic finding. Lobular swelling due to inflammation is the cause of pancreatic enlargement. IgG4-related sclerosing cholangitis is histologically similar to the hypertrophic ductal lesion in type 1 AIP and characterized by wall thickening due to inflammation and luminal stenosis. The epithelium is intact, which is different from bile duct carcinomas and primary sclerosing cholangitis, the latter of which is characterized by inflammation targeting the epithelium. Although the histological features of type 1 AIP and IgG4-related sclerosing cholangitis are unique, the biopsy diagnosis of these diseases has limitations, which should be recognized by clinicians.
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Affiliation(s)
- Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, 710-8602, Japan.
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Abstract
Autoimmune pancreatitis (AIP) has attracted much attention in the last two decades, and due to the diagnostic value of immunoglobulin G4 (IgG4), the number of cases diagnosed in clinical practice has markedly increased. However, in contrast to prototypic IgG4-related type 1 AIP, a minor subtype of AIP, referred to as type 2 AIP, is less widely known and has thus not yet been characterized in detail. Type 2 AIP is unrelated to IgG4 and is a completely distinct entity from type 1 AIP. One confusing factor is that the two types of AIP share patterns of clinical presentation (e.g., acute pancreatitis and painless jaundice) and imaging abnormalities (e.g., diffuse or segmental enlargement). Since there are currently no established serum markers, the diagnosis of type 2 AIP is highly challenging and requires the tissue confirmation of neutrophilic injury to the pancreatic ducts, a finding designated as a granulocytic epithelial lesion. Approximately one-third of cases are associated with inflammatory bowel disease, particularly ulcerative colitis; however, the pathological relationship between these two conditions has not yet been clarified. Unanswered questions relate to its pathophysiology, the potential development of a similar granulocytic injury in other organs, and the characteristics of pediatric cases. This review summarizes consensus and controversies surrounding type 2 AIP, with the aim of increasing awareness and highlighting the unmet needs of this underrecognized condition.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital & King's College London, London, UK
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20
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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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21
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Pancreatic Associated Manifestations in Pediatric Inflammatory Bowel Diseases. Genes (Basel) 2021; 12:genes12091372. [PMID: 34573354 PMCID: PMC8465218 DOI: 10.3390/genes12091372] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 08/28/2021] [Accepted: 08/29/2021] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic relapsing inflammatory conditions of the gastrointestinal tract, encompassing Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBD-U). They are currently considered as systemic disorders determined by a set of genetic predispositions, individual susceptibility and environmental triggers, potentially able to involve other organs and systems than the gastrointestinal tract. A large number of patients experiences one or more extraintestinal manifestations (EIMs), whose sites affected are mostly represented by the joints, skin, bones, liver, eyes, and pancreas. Pancreatic abnormalities are not uncommon and are often underestimated, encompassing acute and chronic pancreatitis, autoimmune pancreatitis, exocrine pancreatic insufficiency and asymptomatic elevation of pancreatic enzymes. In most cases they are the result of environmental triggers. However, several genetic polymorphisms may play a role as precipitating factors or contributing to a more severe course. The aim of this paper is to provide an updated overview on the available evidence concerning the etiology, pathogenesis and clinical presentation of pancreatic diseases in IBD pediatric patients.
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Qureshi A, Ghobrial Y, De Castro J, Siami-Namini K, Newman KA. Autoimmune pancreatitis - What we know and what do we have to know? Autoimmun Rev 2021; 20:102912. [PMID: 34280553 DOI: 10.1016/j.autrev.2021.102912] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 05/28/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Ammar Qureshi
- Eisenhower Health, Internal Medicine Residency Program, 39000 Bob Hope Dr, Rancho Mirage, CA 92270, United States of America.
| | - Youssef Ghobrial
- Eisenhower Health, Internal Medicine Residency Program, 39000 Bob Hope Dr, Rancho Mirage, CA 92270, United States of America
| | - Joline De Castro
- Eisenhower Health, Internal Medicine Residency Program, 39000 Bob Hope Dr, Rancho Mirage, CA 92270, United States of America
| | - Koushan Siami-Namini
- Eisenhower Health, Department of Pathology, 39000 Bob Hope Dr, Rancho Mirage, CA 92270, United States of America.
| | - Kam A Newman
- University of California, Riverside (UCR), School of Medicine, Eisenhower Health, Internal Medicine Residency Program, Division of Rheumatology, 39000 Bob Hope Dr, Rancho Mirage, CA 92270, United States of America.
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23
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Facciorusso A, Barresi L, Cannizzaro R, Antonini F, Triantafyllou K, Tziatzios G, Muscatiello N, Hart PA, Wani S. Diagnostic yield of endoscopic ultrasound-guided tissue acquisition in autoimmune pancreatitis: a systematic review and meta-analysis. Endosc Int Open 2021; 9:E66-E75. [PMID: 33403238 PMCID: PMC7775812 DOI: 10.1055/a-1293-7279] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 09/28/2020] [Indexed: 02/08/2023] Open
Abstract
Background and study aims There is limited evidence on the diagnostic performance of endoscopic ultrasound (EUS)-guided tissue acquisition in autoimmune pancreatitis (AIP). The aim of this meta-analysis was to provide a pooled estimate of the diagnostic performance of EUS-guided fine-needle aspiration (FNA) and fine-needle biopsy (FNB) in patients with AIP. Patients and methods Computerized bibliographic search was performed through January 2020. Pooled effects were calculated using a random-effects model by means of DerSimonian and Laird test. Primary endpoint was diagnostic accuracy compared to clinical diagnostic criteria. Additional outcomes were definitive histopathology, pooled rates of adequate material for histological diagnosis, sample adequacy, mean number of needle passes. Diagnostic sensitivity and safety data were also analyzed. Results Fifteen studies with 631 patients were included, of which four were prospective series and one randomized trial. Overall diagnostic accuracy of EUS tissue acquisition was 54.7 % (95 % confidence interval, 40.9 %-68.4 %), with a clear superiority of FNB over FNA (63 %, 52.7 % to 73.4 % versus 45.7 %, 26.5 %-65 %; p < 0.001). FNB provided level 1 of histological diagnosis in 44.2 % of cases (30.8 %-57.5 %) as compared to 21.9 % (10 %-33.7 %) with FNA ( P < 0.001). The rate of definitive histopathology of EUS tissue sampling was 20.7 % (12.9 %-28.5 %) and it was significantly higher with FNB (24.3 %, 11.8 %-36.8 %) as compared to FNA (14.7 %, 5.4 %-23.9 %; P < 0.001). Less than 1 % of subjects experienced post-procedural acute pancreatitis. Conclusion The results of this meta-analysis demonstrate that the diagnostic performance of EUS-guided tissue acquisition is modest in patients with AIP, with an improved performance of FNB compared to FNA.
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Affiliation(s)
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS – ISMETT), Palermo, Italy
| | - Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Filippo Antonini
- Gastroenterology and Endoscopy Unit, Marche Polytechnic University, A. Murri Hospital, Fermo, Italy
| | - Konstantinos Triantafyllou
- Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Tziatzios
- Hepatogastroenterology Unit, Second Department of Internal Medicine – Propaedeutic, Research Institute and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Phil A. Hart
- Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
| | - Sachin Wani
- University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
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24
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Pattabathula K, Waters PS, Hwang J, Bettington M, Singh M, Bryant RD, Cavallucci DJ, O'Rourke N. Diagnostic and therapeutic considerations in biopsy-proven type 2 autoimmune pancreatitis: comparative analysis with biopsy-proven type 1 autoimmune pancreatitis. ANZ J Surg 2020; 91:907-914. [PMID: 33369858 DOI: 10.1111/ans.16445] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 10/26/2020] [Accepted: 11/03/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Autoimmune processes are now an increasingly recognized cause of acute and chronic pancreatitis. Autoimmune pancreatitis is a rare, benign pathology with two distinct clinicopathologic subtypes. The aim of this study was to compare the presentation, diagnostic considerations and outcomes of patients with biopsy-proven type 1 and 2 autoimmune pancreatitis (AIP). METHODS A retrospective review of the Queensland Health pathology database of histologically proven AIP was conducted. Parameters compared included demographics, diagnostic criterion and post-treatment outcomes. RESULTS Twenty-three patients had a confirmed histological diagnosis of AIP (type 1 = 13, type 2 = 10). Patients with type 2 AIP were younger (median age 49 versus 59 years, P < 0.05). There was no significant difference in gender distribution of disease at presentation. Type 2 AIP presented with significant increased focal pancreatic changes on cross-sectional imaging (80% versus 54%, P < 0.05). Serum IgG4 levels were raised (>1.40 g/L) in 69% of patients with type 1 AIP and not detected in type 2 (P < 0.01). Concurrent underlying inflammatory bowel disease was present in a higher proportion of type 2 AIP (40% versus 15%, P < 0.05). A significantly increased proportion of patients with type 2 AIP underwent surgical resection (70% versus 30%, P < 0.05). Conservative management was utilized in more patients with type 1 disease (54% versus 30%). On follow-up, two patients have experienced symptomatic relapse at 6-18 months. CONCLUSIONS Diagnostic challenges do exist and clinicians must suspect 2 type AIP in young, serum IgG4-negative inflammatory bowel disease patients with recurrent pancreatitis.
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Affiliation(s)
- Krishna Pattabathula
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Peadar S Waters
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Jason Hwang
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Mark Bettington
- Department of Histopathology, Envoi Pathology, Brisbane, Queensland, Australia
| | - Mahendra Singh
- Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Richard D Bryant
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - David J Cavallucci
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Department of Surgery, Wesley Hospital, Brisbane, Queensland, Australia
| | - Nicholas O'Rourke
- Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,Department of Surgery, Wesley Hospital, Brisbane, Queensland, Australia
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25
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Ishikawa T, Kawashima H, Ohno E, Iida T, Suzuki H, Uetsuki K, Yamada K, Yashika J, Yoshikawa M, Gibo N, Aoki T, Kataoka K, Mori H, Fujishiro M. Risks and characteristics of pancreatic cancer and pancreatic relapse in autoimmune pancreatitis patients. J Gastroenterol Hepatol 2020; 35:2281-2288. [PMID: 32583452 DOI: 10.1111/jgh.15163] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/28/2020] [Accepted: 06/22/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM We examined the differences in the risks and characteristics of pancreatic relapse (PR) and pancreatic cancer (PC) in patients with autoimmune pancreatitis (AIP). METHODS We retrospectively reviewed 123 type 1 AIP patients with a median follow-up of 55 months (interquartile range, 27-98). The following items were evaluated: (i) cumulative relapse rates and risk factors, (ii) the incidence of PC, (iii) PR versus PC, and (iv) outcomes after the appearance of morphological changes in the pancreas (focal enlargement, apparent mass lesions, or main pancreatic duct dilation). RESULTS (i) The cumulative PR rates were 1.7% within 1 year, 11.5% within 3 years, and 22.6% within 5 years. Lack of maintenance therapy, IgG4-related sclerosing cholangitis, and IgG4-related kidney disease were identified as independent predictors of relapse. (ii) Two patients (1.6%) were diagnosed with PC at 17 and 22 months after initial AIP diagnosis. (iii) Thirteen (59.1%) and four (18.2%) patients with PR had focal enlargement and main pancreatic duct dilation, respectively. The median CA19-9 level at initial diagnosis was significantly higher in PC patients (21 vs 220.5 U/mL, P = 0.014). (iv) Eight PR patients underwent endoscopic ultrasound-guided fine-needle aspiration, none of whom had malignant findings. PC was diagnosed by ultrasound-guided fine-needle aspiration in both cancer patients. CONCLUSIONS Although the incidence of PC is low, it may mimic PR in AIP patients. Surveillance is important, and when morphological changes occur, biopsy and evaluation of serum IgG4 and CA19-9 levels (particularly if the levels were high before) should be considered.
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Affiliation(s)
- Takuya Ishikawa
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tadashi Iida
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hirotaka Suzuki
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kota Uetsuki
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Yamada
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Jun Yashika
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masakatsu Yoshikawa
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Noriaki Gibo
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshinori Aoki
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kunio Kataoka
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroshi Mori
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Chen L, Orr CE, Wang T. Prevalence of histological features resembling autoimmune pancreatitis in neoplastic pancreas resections. Histopathology 2020; 77:673-677. [PMID: 32608526 DOI: 10.1111/his.14197] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 06/25/2020] [Indexed: 02/06/2023]
Abstract
AIMS Types 1 and 2 autoimmune pancreatitis (AIP) can mimic pancreatic neoplasia. Due to the small quantity of tissue in mass-targeted pancreas biopsies, inflammatory features may raise the differential of AIP. However, the frequency of AIP-like histology in neoplastic pancreas is not well characterised. Therefore, the specificity of inflammatory lesions on biopsy with respect to the diagnosis of AIP is uncertain. METHODS AND RESULTS Neoplastic pancreas resections performed at our institution between 2008 and 2019 were retrospectively reviewed. Features of AIP types 1 and 2 were assessed in the non-neoplastic areas. If features of immunoglobulin (Ig)G4-associated AIP were seen, IgG4 immunohistochemistry was performed. We identified 163 neoplastic pancreas resections. Of these, 34 had one or more types of inflammatory lesions in non-neoplastic pancreatic tissue. Dense lymphoplasmacytic inflammation mimicking type 1 AIP was found in six cases with mild to moderately increased IgG4-positive plasma cells. Neutrophilic infiltrates in small intralobular ducts were found in 20 cases. Mild extralobular ductitis or duct microabscess was found in 10 specimens. Marked neutrophilic duct destruction that resembled granulocytic epithelial lesions was found in 12 cases. Some cases showed multiple features. CONCLUSION Approximately 20% of neoplastic pancreas resections showed focal areas that could raise the differential of AIP. More cases showed neutrophilic predominant inflammation as seen in type 2 autoimmune pancreatitis, compared to dense lymphoplasmacytic infiltrates seen in type 1 AIP. Pathologists must be cautious when making a diagnosis of AIP on biopsy tissue based on histological findings alone.
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Affiliation(s)
- Lina Chen
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
| | - Christine E Orr
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
| | - Tao Wang
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
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Abstract
PURPOSE OF REVIEW Type 2 autoimmune pancreatitis (AIP) is a rare inflammatory disease of the pancreas. Very few data have been published on this particular subtype, which differs from the 'classical' IgG4-related type 1 AIP in terms of pathological features, epidemiology and risk of relapse. The aim of the current review is to summarize the available literature, suggesting a diagnostic and therapeutic approach to this disease. RECENT FINDINGS Based on the International Consensus Diagnostic Criteria, to achieve a 'definitive' diagnosis of type 2 AIP, histology is required. If a definitive histological diagnosis is lacking (not-performed or inconclusive), concomitant presence of inflammatory bowel disease (IBD) and effective response to steroids are needed for a 'probable' diagnosis of type 2 AIP. SUMMARY Type 2 AIP is a selective pancreatic disease, without association to other organ involvement. The lack of validated serological markers makes the diagnosis challenging in clinical practice, particularly in focal forms. A careful evaluation of the clinical profile (especially of a concomitant IBD), associated with an accurate imaging, might help in clinical practice to suspect type 2 AIP. Response to steroids is crucial to achieve diagnosis in patients without a diagnostic histology.
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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: 3] [Impact Index Per Article: 0.6] [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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29
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Detlefsen S, Olesen SS. Sialadenitis in a patient with ulcerative colitis and autoimmune pancreatitis type 2. Pathol Res Pract 2020; 216:153072. [PMID: 32825945 DOI: 10.1016/j.prp.2020.153072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/11/2020] [Accepted: 06/17/2020] [Indexed: 01/07/2023]
Abstract
Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that has been increasingly recognised over the last decades and shows a good response to corticosteroid treatment. Two different forms of AIP have been characterized. Type 1 AIP is the pancreatic manifestation of IgG4-related disease and often affects multiple organ systems. In contrast, type 2 AIP is confined to the pancreas and involvement of extra-pancreatic organs has previously only very rarely been reported, except for an association with inflammatory bowel disease. The hallmark lesion of type 2 AIP is the granulocyte epithelial lesion (GEL), showing infiltration of neutrophilic granulocytes in the epithelium of pancreatic ducts and their accumulation in the duct lumen. We present a 61-year-old female patient who underwent pancreaticoduodenectomy with a postoperative histological diagnosis of type 2 AIP. Three months later, she underwent colectomy and was diagnosed with ulcerative colitis. One year later, she presented with swelling and pain of the right-sided submandibular salivary gland which was resected. Sialadenitis with lymphoplasmacytic inflammation, obliterative phlebitis, fibrosis and frequent accumulation of neutrophilic granulocytes in ducts, reminiscent of GELs, without IgG4-positivity or epitheloid cell granulomas, was found. Later, she presented with swelling and pain related to the left-sided submandibular gland, which resolved after steroid treatment. We describe the clinical, histological and immunohistochemical findings in this patient. It may be hypothesized that the sialadenitis may represent a rare extrapancreatic manifestation of, alternatively a rare association with, type 2 AIP or ulcerative colitis.
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Affiliation(s)
- Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
| | - Søren Schou Olesen
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
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30
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Abstract
OBJECTIVES Fibrosing pancreatitis (FP) shares clinical features with autoimmune pancreatitis (AIP), although both entities have not been definitely linked. This study aimed to assess the presence of AIP criteria in an historic FP patient cohort and investigate the clinical features, management, and long-term outcomes of pediatric FP (P-FP). METHODS Clinical data of 14 P-FP patients from Toronto and 42 P-FP cases from a literature review were collected and compared to pediatric AIP (P-AIP). Toronto P-FP patients were recontacted to assess their current health status using a brief questionnaire. RESULTS Jaundice and abdominal pain were the symptoms at presentation in 44 of 56 (79%) and 50 of 56 (89%) P-FP patients, respectively. Common findings on cross sectional imaging were an enlarged pancreas head with narrowing of the distal common bile duct (51/54, 94%). Histopathology mainly showed gland fibrosis (39/39, 100%). Three of twelve (25%) P-FP patients had elevated IgG4 in serum. None of the patients were treated with corticosteroids, but some underwent surgical or endoscopic intervention. Toronto patients were followed for a median of 13.6 years (interquartile range: 2.9-22.8). Complications during follow-up included exocrine pancreatic insufficiency (3/14, 21%) and pancreatic gland atrophy (5/13, 38%); but none of the patients had disease relapse or developed diabetes type 3c. Five (5/14, 36%) patients developed other immune-mediated diseases over time. CONCLUSIONS Clinical features of patients with P-FP resembled those recently described in a subgroup of P-AIP presenting with jaundice. Long-term outcome of these patients is generally good, with or without invasive interventions. As some patients may develop exocrine pancreatic insufficiency and/or other immune-mediated diseases, ongoing clinical monitoring is recommended.
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31
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Oh D, Song TJ, Moon SH, Kim JH, Lee NJ, Hong SM, Lee JS, Jo SJ, Cho DH, Park DH, Lee SS, Seo DW, Lee SK, Kim MH. Type 2 Autoimmune Pancreatitis (Idiopathic Duct-Centric Pancreatitis) Highlighting Patients Presenting as Clinical Acute Pancreatitis: A Single-Center Experience. Gut Liver 2020; 13:461-470. [PMID: 30970429 PMCID: PMC6622566 DOI: 10.5009/gnl18429] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/04/2018] [Accepted: 11/10/2018] [Indexed: 12/15/2022] Open
Abstract
Background/Aims Type 2 autoimmune pancreatitis (AIP) has been considered extremely rare in East Asia. This study aimed to clarify the prevalence, clinical characteristics and radiological findings of type 2 AIP highlighting patients presenting as acute pancreatitis in a single center. Methods Type 2 AIP patients were classified according to International Consensus Diagnostic Criteria. Radiological findings were compared between type 2 AIP presenting as acute pancreatitis and gallstone pancreatitis. Results Among 244 patients with AIP, 27 (11.1%) had type 2 AIP (definite, 15 [55.5%] and probable 12 [44.5%]). The median age of patients with type 2 AIP was 29 years (interquartile range, 20 to 39 years). Acute pancreatitis was the most common initial presentation (n=17, 63%) while obstructive jaundice was present in only one patient. Ulcerative colitis (UC) was associated with type 2 AIP in 44.4% (12/27) of patients. Radiological pancreatic imaging such as delayed enhancement of diffusely enlarged pancreas, homogeneous enhancement of focal enlargement/mass, absent/minimal peripancreatic fat infiltration or fluid collection, and multifocal main pancreatic duct narrowings were helpful for differentiating type 2 AIP from gallstone pancreatitis. During follow-up (median, 32.3 months), two patients (2/25, 8%) experienced relapse. Conclusions In South Korea, type 2 AIP is not as rare as previously thought. Overall, the clinical profile of type 2 AIP was similar to that of Western countries. Type 2 AIP should be considered in young UC patients with acute pancreatitis of uncertain etiology.
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Affiliation(s)
- Dongwook Oh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Jun Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Jin Hee Kim
- Departments of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Nam Joo Lee
- Departments of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joune Seup Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seok Jung Jo
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Hui Cho
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hyun Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Soo Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Koo Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Myung-Hwan Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Yeh TS, Lin TA, Chen TC, Tseng JH. Autoimmune pancreatitis type 2: Mimicking pancreatic cancer. FORMOSAN JOURNAL OF SURGERY 2020. [DOI: 10.4103/fjs.fjs_104_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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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: 22] [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: 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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de Pretis N, Vieceli F, Brandolese A, Brozzi L, Amodio A, Frulloni L. Autoimmune pancreatitis not otherwise specified (NOS): Clinical features and outcomes of the forgotten type. Hepatobiliary Pancreat Dis Int 2019; 18:576-579. [PMID: 31248720 DOI: 10.1016/j.hbpd.2019.05.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 05/29/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is a well-recognized fibroinflammatory disease of the pancreas. Despite the significant number of studies published on AIP type 1 and 2, no studies have been focused on AIP type not otherwise specified (NOS) and therefore very little is known about clinical features and long-term outcomes of these patients. The aim of this study was to investigate clinical and radiological features of AIP type NOS-patients. METHODS Patients classified as AIP type NOS at clinical onset included in our database prospectively maintained since 1995 were evaluated. Epidemiological, clinical data were collected and analyzed. RESULTS Forty-six patients were included in the study. The clinical onset was mainly characterized by weight loss, jaundice and acute pancreatitis. Eight patients (17.4%) were reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. Seven patients (15.2%) experienced relapse after steroid treatment but only one (2.2%) needed immunosuppressive drugs because of recurrent relapses. CONCLUSIONS AIP type NOS shares clinical features similar to AIP type 2 and a relevant proportion of patients was reclassified as AIP type 2 during follow-up because of the development of ulcerative colitis. The risk of relapse is low but not irrelevant.
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Affiliation(s)
- Nicolò de Pretis
- Gastroenterology Unit, Pancreas Center, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy.
| | - Filippo Vieceli
- Gastroenterology Unit, Pancreas Center, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Alessandro Brandolese
- Gastroenterology Unit, Pancreas Center, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Lorenzo Brozzi
- Gastroenterology Unit, Pancreas Center, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Antonio Amodio
- Gastroenterology Unit, Pancreas Center, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Pancreas Center, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy
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Zen Y, Deshpande V. Tumefactive Inflammatory Diseases of the Pancreas. THE AMERICAN JOURNAL OF PATHOLOGY 2019; 189:82-93. [PMID: 30558726 DOI: 10.1016/j.ajpath.2018.05.022] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/16/2018] [Accepted: 05/29/2018] [Indexed: 02/06/2023]
Abstract
Advances in the past two decades have resulted in the recognition of several tumefactive pancreatic lesions that, on histologic evaluation, show a varying combination of inflammation and fibrosis. Autoimmune pancreatitis, the prototypic tumefactive pancreatic fibroinflammatory lesion, is composed of two distinct diseases, type 1 autoimmune pancreatitis and the less common type 2 autoimmune pancreatitis. Although designated as autoimmune pancreatitis, the two diseases show little morphologic or pathogenic overlap. In type 1 disease, subsets of T lymphocytes (type 2 helper T cells, regulatory T cells, and T follicular helper 2 cells) are hypothesized to drive the inflammatory reaction. The B-cell response is characterized by an oligoclonal expansion of plasmablasts, with dominant clones that vary among patients and distinct clones that emerge at the time of relapse. Although the precise role of IgG4 in this condition remains uncertain, recent studies suggest that other IgG subclasses (eg, IgG1) may mediate the immune reactions, whereas IgG4 represents a response to dampen excessive inflammation. A recent study of type 2 autoimmune pancreatitis highlights the role of CXCL8 (alias IL-8), with duct epithelium and infiltrating T lymphocytes expressing this chemokine; the latter may contribute to the distinct form of neutrophilic inflammation in this disease. The review also highlights other forms of mass-forming chronic pancreatitis: follicular pancreatitis, groove pancreatitis, and those associated with rheumatologic diseases.
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Affiliation(s)
- Yoh Zen
- Department of Diagnostic Pathology, Kobe University, Kobe, Japan
| | - Vikram Deshpande
- The James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Massachusetts.
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Management of Autoimmune Pancreatitis. Clin Gastroenterol Hepatol 2019; 17:1937-1939. [PMID: 31042584 DOI: 10.1016/j.cgh.2019.04.052] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 04/16/2019] [Accepted: 04/19/2019] [Indexed: 02/07/2023]
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The Etiology of Pancreatic Manifestations in Patients with Inflammatory Bowel Disease. J Clin Med 2019; 8:jcm8070916. [PMID: 31247968 PMCID: PMC6679036 DOI: 10.3390/jcm8070916] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 06/18/2019] [Accepted: 06/21/2019] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an idiopathic chronic and recurrent condition that comprises Crohn's disease and ulcerative colitis. A pancreatic lesion is one of the extraintestinal lesions in patients with IBD. Acute pancreatitis is the representative manifestation, and various causes of pancreatitis have been reported, including those involving adverse effects of drug therapies such as 5-aminosalicylic acid and thiopurines, gall stones, gastrointestinal lesions on the duodenum, iatrogenic harm accompanying endoscopic procedures such as balloon endoscopy, and autoimmunity. Of these potential causes, autoimmune pancreatitis (AIP) is a relatively newly recognized disease and is being increasingly diagnosed in IBD. AIP cases can be divided into type 1 cases involving lymphocytes and IgG4-positive plasma cells, and type 2 cases primarily involving neutrophils; the majority of AIP cases complicating IBD are type 2. The association between IBD and chronic pancreatitis, exocrine pancreatic insufficiency, pancreatic cancer, etc. has also been suggested; however, studies with high-quality level evidence are limited, and much remains unknown. In this review, we provide an overview of the etiology of pancreatic manifestation in patients with IBD.
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Tacelli M, Celsa C, Magro B, Barresi L, Guastella S, Capurso G, Frulloni L, Cabibbo G, Cammà C. Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17:1061-1072.e8. [PMID: 30312787 DOI: 10.1016/j.cgh.2018.09.051] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 09/20/2018] [Accepted: 09/22/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Risk for relapse after induction of remission with steroid therapy has been studied extensively in patients with autoimmune pancreatitis (AIP), but findings have been equivocal. We performed a systematic review and meta-analysis to estimate the relapse rate of AIP after initial remission after steroid treatment and to identify factors associated with relapse. METHODS Three reviewers searched MEDLINE, SCOPUS, and EMBASE until July 2018 to identify studies on rate of relapse of AIP after induction of remission with steroid therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random-effects model. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Thirty-six studies met the inclusion criteria for meta-analysis. The median follow-up time was 40.8 months. Fifty-two percent of patients were classified as having type 1 AIP. The pooled estimate of relapse rate was 33% (95% CI, 30%-37%). A higher proportion of patients with type 1 AIP had a relapse compared with patients with type 2 AIP (37.5% vs 15.9%; P < .001). We found significant heterogeneity among studies (P < .01). Long-term maintenance therapy with steroids and study quality were associated independently with AIP relapse, after we adjusted for year of publication by multivariate meta-regression. CONCLUSIONS In a systematic review and meta-analysis, we found that a large proportion of patients with AIP treated successfully with steroid induction therapy had a relapse (33%)-particularly patients with type 1 AIP (37%). Maintenance steroid therapy lasting longer than 1 year could reduce risk of relapse. However, the data characterizing relapse rates are of limited quality, indicating the need for randomized controlled trials and new immunosuppressive drugs.
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Affiliation(s)
- Matteo Tacelli
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Ciro Celsa
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Bianca Magro
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Salvatore Guastella
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and Endoscopic Ultrasonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute (Istituto di Ricovero e Cura a Carattere Scientifico), Vita Salute San Raffaele University, Milan, Italy
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Calogero Cammà
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy.
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Guda NM, Trikudanathan G, Freeman ML. Idiopathic recurrent acute pancreatitis. Lancet Gastroenterol Hepatol 2019; 3:720-728. [PMID: 30215363 DOI: 10.1016/s2468-1253(18)30211-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 06/15/2018] [Accepted: 06/15/2018] [Indexed: 12/19/2022]
Abstract
Idiopathic recurrent acute pancreatitis is clinically challenging and has substantial socioeconomic consequences. Investigations are expensive and often reveal little about the cause of the disease. Little is known about the interaction between genetic, environmental, anatomical, and other factors that contribute to the disease. Data on the efficacy, safety, and long-term outcomes of endoscopic therapies are scarce. The effect of idiopathic recurrent pancreatitis on quality of life is often underestimated. A more thorough examination of the causes of the disease and the roles of other associated risk factors is needed, as are well designed clinical studies with robust and objectively measurable outcomes. Ideally, evaluation of the causes of disease and therapy should be done only in specialised centres, should follow a protocol, and all outcomes should be formally assessed.
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Affiliation(s)
- Nalini M Guda
- School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA; Aurora Saint Luke's Medical Center, Milwaukee, WI, USA.
| | - Guru Trikudanathan
- Department of Gastroenterology, University of Minnesota, Minneapolis, MN, USA
| | - Martin L Freeman
- Division of Gastroenterology, Hepatology, and Nutrition, Advanced Endoscopy Fellowship, and Islet Autotransplantation, University of Minnesota, Minneapolis, MN, USA
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Obaitan I, Hayat U, Hashmi H, Trikudanathan G. Imaging in pancreatitis: current status and recent advances. Expert Opin Orphan Drugs 2018. [DOI: 10.1080/21678707.2018.1536539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Affiliation(s)
- Itegbemie Obaitan
- Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Umar Hayat
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Hiba Hashmi
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
| | - Guru Trikudanathan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN, USA
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Suk Lee Y, Kim NH, Hyuk Son J, Wook Kim J, Ki Bae W, Kim KA, Sung Lee J. Type 2 Autoimmune Pancreatitis with Crohn's Disease. Intern Med 2018; 57:2957-2962. [PMID: 29526939 PMCID: PMC6232013 DOI: 10.2169/internalmedicine.0213-17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Accepted: 01/05/2018] [Indexed: 12/11/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a distinct subtype of pancreatitis, which is classified into type 1 and 2 based on the clinicopathological features. According to the international consensus diagnostic criteria, pancreas resection or core biopsy specimens are recommended to make an accurate histological evaluation. However, the usefulness of endoscopic ultrasonography (EUS) guided fine needle aspiration (FNA) for histological evaluation has also been reported. Furthermore, the simultaneous presentation of type 2 AIP and Crohn's disease (CD) is very rare, especially in the Asian population. Therefore, we herein report a case of type 2 AIP with CD, which was diagnosed using EUS guided FNA with a 22-gauge needle.
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Affiliation(s)
- Yoon Suk Lee
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
| | - Nam-Hoon Kim
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
| | - Jun Hyuk Son
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
| | - Jung Wook Kim
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
| | - Won Ki Bae
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
| | - Kyung-Ah Kim
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
| | - June Sung Lee
- Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Korea
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Rana SS, Gupta R, Nada R, Gupta P, Basher R, Mittal BR, Sharma RK, Rawat A. Clinical profile and treatment outcomes in autoimmune pancreatitis: a report from North India. Ann Gastroenterol 2018; 31:506-512. [PMID: 29991897 PMCID: PMC6033754 DOI: 10.20524/aog.2018.0267] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 03/24/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is a rare disease, and data from countries like India concerning its clinical presentation and long-term outcomes are scarce. We retrospectively evaluated the clinical presentation, imaging features and treatment outcomes of patients with AIP. METHODS We carried out a retrospective analysis of our database to identify patients diagnosed with and treated for AIP at our unit in a tertiary care hospital in North India. RESULTS Eighteen patients with AIP (mean age: 54.9±11.1 years; 13 male) were evaluated. Of these, 9 (50%) patients had probable type 1 AIP, 2 (11%) patients probable type 2 AIP, and 4 (22%) definite type 1 AIP. Patients with type 2 AIP were significantly younger than patients with type 1 (40.0±2.8 vs. 58.4±9.6 years). In type 1 AIP, other organ involvement was observed in 3/18 (17%) patients, whereas both patients with type 2 AIP had coexisting ulcerative colitis. The diagnosis of AIP was made after resective surgery in 6/18 (33.0%) patients. An accurate diagnosis of AIP could be made in all patients who underwent resection or core biopsy, but cytological examination after endoscopic ultrasound-guided fine-needle aspiration could not provide a definitive diagnosis in any patient. Initial treatment with steroids was given to 12 (67%) patients, with a 100% response, but the disease relapsed in 5/13 (38%) patients over a mean follow-up period of 34.2±21.6 weeks. CONCLUSION AIP is not rare in India and the majority of clinical manifestations, imaging features, treatment response and long-term outcomes are similar to those reported in the literature.
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Affiliation(s)
- Surinder S Rana
- Department of Gastroenterology (Surinder S. Rana, Pankaj Gupta, Ravi kumar Sharma), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Rajesh Gupta
- Department of Surgery (Rajesh Gupta), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Ritambhra Nada
- Department of Histopathology (Ritambhra Nada), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Pankaj Gupta
- Department of Gastroenterology (Surinder S. Rana, Pankaj Gupta, Ravi kumar Sharma), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Rajinder Basher
- Department of Nuclear Medicine (Rajinder Basher, Bhagwat R. Mittal), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Bhagwat R Mittal
- Department of Nuclear Medicine (Rajinder Basher, Bhagwat R. Mittal), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Ravi Kumar Sharma
- Department of Gastroenterology (Surinder S. Rana, Pankaj Gupta, Ravi kumar Sharma), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
| | - Amit Rawat
- Department of Pediatrics (Amit Rawat), Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh India
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de Pretis N, Amodio A, Frulloni L. Updates in the field of autoimmune pancreatitis: a clinical guide. Expert Rev Gastroenterol Hepatol 2018; 12:705-709. [PMID: 29923430 DOI: 10.1080/17474124.2018.1489230] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Autoimmune Pancreatitis (AIP) is a peculiar form of pancreatitis different from all other type of pancreatitis ('one like no one pancreatitis') and characterized by a dramatic response to steroids. AIP can be classified histologically in type 1, included in a larger group of diseases named IgG4-related disease, and type 2. At imaging, AIP may involve all (diffuse form) or only a part (focal form) of the pancreatic gland. Areas covered: In this article, the clinical approach to diagnosis and different therapeutic strategies of this complicated disease are reviewed. Literature search was undertaken using PubMed database entering autoimmune pancreatitis [title] or IgG4-related diseases [title], and selecting the more relevant papers for diagnosis and therapy of AIP in clinical practice. We focus on diagnosis of AIP in focal and diffuse form, and how to achieve diagnosis for type 1 and type 2 AIP. We finally analyzed the different strategies proposed in induction of remission and maintenance therapy (long-term low-dose steroids, immunosuppressants or biologics). Expert commentary: The main issue in clinical practice is how to achieve the diagnosis. A second key point is how to prevent the disease relapse.
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Affiliation(s)
- Nicolò de Pretis
- a Department of Medicine, Pancreas Institute , University of Verona , Verona , Italy
| | - Antonio Amodio
- a Department of Medicine, Pancreas Institute , University of Verona , Verona , Italy
| | - Luca Frulloni
- a Department of Medicine, Pancreas Institute , University of Verona , Verona , Italy
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45
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Hafezi-Nejad N, Singh VK, Fung C, Takahashi N, Zaheer A. MR Imaging of Autoimmune Pancreatitis. Magn Reson Imaging Clin N Am 2018; 26:463-478. [PMID: 30376982 DOI: 10.1016/j.mric.2018.03.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Autoimmune pancreatitis (AIP) is characterized by autoimmune inflammatory destruction of the pancreatic tissue. Imaging plays an essential role in the diagnosis. AIP type 1 is the pancreatic manifestation of immunoglobulin G4 (IgG4)-related disease and is associated with IgG4-positive plasma cell infiltration and fibrosis of multiple organ systems. Type 2 is a related disease with pancreatic inflammation with or without concurrent inflammatory bowel disease. The authors demonstrate the imaging findings that are associated with the pancreatic and extra-pancreatic manifestations of AIP. They emphasize the common MR imaging and magnetic resonance cholangiopancreatography findings to help make the diagnosis of AIP.
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Affiliation(s)
- Nima Hafezi-Nejad
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA
| | - Vikesh K Singh
- Department of Internal Medicine, Pancreatitis Center, Johns Hopkins Medical Institutions, 1800 Orleans Street, Sheikh Zayed Tower, Baltimore, MD 21287, USA; Division of Gastroenterology, Johns Hopkins University, School of Medicine, 1800 Orleans Street, Sheikh Zayed Tower, Baltimore, MD 21287, USA
| | - Christopher Fung
- Department of Radiology and Diagnostic Imaging, University of Alberta, 2J2.00 WC Mackenzie Health Sciences Centre, 8440 112 Street Northwest, Edmonton, Alberta T6G 2R7, Canada
| | - Naoki Takahashi
- Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Atif Zaheer
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA; Department of Internal Medicine, Pancreatitis Center, Johns Hopkins Medical Institutions, 1800 Orleans Street, Sheikh Zayed Tower, Baltimore, MD 21287, USA.
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46
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Párniczky A, Abu-El-Haija M, Husain S, Lowe M, Oracz G, Sahin-Tóth M, Szabó FK, Uc A, Wilschanski M, Witt H, Czakó L, Grammatikopoulos T, Rasmussen IC, Sutton R, Hegyi P. EPC/HPSG evidence-based guidelines for the management of pediatric pancreatitis. Pancreatology 2018; 18:146-160. [PMID: 29398347 DOI: 10.1016/j.pan.2018.01.001] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 01/01/2018] [Accepted: 01/04/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pediatric pancreatitis is an underdiagnosed disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has increased, it is now 3.6-13.3 cases per 100,000 children. Up-to-date evidence based management guidelines are lacking for the pediatric pancreatitis. The European Pancreatic Club, in collaboration with the Hungarian Pancreatic Study Group organized a consensus guideline meeting on the diagnosis and management of pancreatitis in the pediatric population. METHODS Pediatric Pancreatitis was divided into three main clinical categories: acute pancreatitis, acute recurrent pancreatitis and chronic pancreatitis. Fifteen relevant topics (acute pancreatitis: diagnosis; etiology; prognosis; imaging; complications; therapy; biliary tract management; acute recurrent pancreatitis: diagnosis; chronic pancreatitis: diagnosis, etiology, treatment, imaging, intervention, pain, complications; enzyme replacement) were defined. Ten experts from the USA and Europe reviewed and summarized the available literature. Evidence was classified according to the GRADE classification system. RESULTS Within fifteen topics, forty-seven relevant clinical questions were defined. The draft of the updated guideline was presented and discussed at the consensus meeting held during the 49th Meeting of European Pancreatic Club, in Budapest, on July 1, 2017. CONCLUSIONS These evidence-based guidelines provides the current state of the art of the diagnosis and management of pediatric pancreatitis.
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Affiliation(s)
- Andrea Párniczky
- Heim Pál Children's Hospital, Budapest, Hungary; Institute for Translational Medicine, University of Pécs, Pécs, Hungary
| | - Maisam Abu-El-Haija
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Sohail Husain
- Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mark Lowe
- Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA
| | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Miklós Sahin-Tóth
- Department of Molecular and Cell Biology, Center for Exocrine Disorders, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, USA
| | - Flóra K Szabó
- Division of Gastroenterology and Nutrition, Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, USA
| | - Aliye Uc
- Division of Pediatric Gastroenterology, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Michael Wilschanski
- Pediatric Gastroenterology Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
| | - Heiko Witt
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Paediatric Nutritional Medicine, Technische Universität München, Freising, Germany
| | - László Czakó
- First Department of Medicine, University of Szeged, Szeged, Hungary
| | - Tassos Grammatikopoulos
- Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, United Kingdom; Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London, London, United Kingdom
| | | | - Robert Sutton
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Liverpool Pancreatitis Research Group, Royal Liverpool University Hospital, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Péter Hegyi
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary; First Department of Medicine, University of Szeged, Szeged, Hungary.
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47
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Lorenzo D, Maire F, Stefanescu C, Gornet JM, Seksik P, Serrero M, Bournet B, Marteau P, Amiot A, Laharie D, Trang C, Coffin B, Bellaiche G, Cadiot G, Reenaers C, Racine A, Viennot S, Pauwels A, Bouguen G, Savoye G, Pelletier AL, Pineton de Chambrun G, Lahmek P, Nahon S, Abitbol V. Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2018; 16:59-67. [PMID: 28782667 DOI: 10.1016/j.cgh.2017.07.033] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 06/11/2017] [Accepted: 07/07/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. METHODS We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. RESULTS We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029). CONCLUSIONS In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.
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Affiliation(s)
- Diane Lorenzo
- Departement of Hepato-Gastroenterology, Hôpital Cochin, AP-HP, Paris, France.
| | - Frédérique Maire
- Departement of Hepato-Gastroenterology, Hôpital Beaujon, AP-HP, Clichy La Garenne, France
| | - Carmen Stefanescu
- Departement of Hepato-Gastroenterology, Hôpital Beaujon, AP-HP, Clichy La Garenne, France
| | - Jean-Marc Gornet
- Departement of Hepato-Gastroenterology, Hôpital Saint Louis, AP-HP, Paris, France
| | - Philippe Seksik
- Departement of Hepato-Gastroenterology, Hôpital Saint Antoine, AP-HP, Paris, France
| | - Mélanie Serrero
- Departement of Hepato-Gastroenterology, Hôpital Nord, AP-HM, Marseille, France
| | - Barbara Bournet
- Departement of Hepato-Gastroenterology, Hôpital Rangueil, Toulouse, France
| | - Philippe Marteau
- Departement of Hepato-Gastroenterology, Hôpital Saint Antoine, AP-HP, Paris, France
| | - Aurelien Amiot
- Departement of Hepato-Gastroenterology, Hôpital Henri Mondor, AP-HP, Créteil, France
| | - David Laharie
- Departement of Hepato-Gastroenterology, Hôpital Haut-Lévêque, Pessac, France
| | - Caroline Trang
- Departement of Hepato-Gastroenterology, CHU Nantes, Nantes, France
| | - Benoit Coffin
- Departement of Hepato-Gastroenterology, Hôpital Louis Mourier, AP-HP, Colombes, France
| | - Guy Bellaiche
- Departement of Hepato-Gastroenterology, CH d'Aulnay, Aulnay sous-bois, France
| | - Guillaume Cadiot
- Departement of Hepato-Gastroenterology, CHU Reims, Reims, France
| | | | - Antoine Racine
- Departement of Hepato-Gastroenterology, CHU du Kremlin Bicêtre, AP-HP, Kremlin Bicêtre, France
| | | | - Arnaud Pauwels
- Departement of Hepato-Gastroenterology, CH Gonesse, Gonesse, France
| | | | - Guillaume Savoye
- Departement of Hepato-Gastroenterology, CHU Rouen, Rouen, France
| | | | | | - Pierre Lahmek
- Departement of Hepato-Gastroenterology, CH Montfermeil, Montfermeil, France
| | - Stéphane Nahon
- Departement of Hepato-Gastroenterology, CH Montfermeil, Montfermeil, France
| | - Vered Abitbol
- Departement of Hepato-Gastroenterology, Hôpital Cochin, AP-HP, Paris, France
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Petzold G, Ellenrieder V, Neesse A. Autoimmune Pancreatitis in Germany: Rare but Relevant. Digestion 2017; 96:185-186. [PMID: 28957805 DOI: 10.1159/000481251] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 09/03/2017] [Indexed: 02/04/2023]
Affiliation(s)
- Golo Petzold
- Department of Gastroenterology and Gastrointestinal Oncology, University Medical Centre Göttingen, Göttingen, Germany
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49
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Editorial: Autoimmune Pancreatitis in Children: Is This a New Subtype of Disease or Early-Onset Idiopathic Duct-Centric Chronic Pancreatitis? Am J Gastroenterol 2017; 112:1613-1614. [PMID: 28978971 DOI: 10.1038/ajg.2017.236] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 06/08/2017] [Indexed: 12/11/2022]
Abstract
The term autoimmune pancreatitis (AIP) encompasses two distinct steroid-responsive pancreatitides, type 1 AIP and idiopathic duct-centric pancreatitis (IDCP) (or type 2 AIP). The current study describes cases of both AIP subtypes in a pediatric population. A comparison of the clinical profile of the described cohort with published data strongly suggests the majority of patients in the current cohort had IDCP. Since relapse rates in IDCP are low and long-term maintenance therapy is not required for IDCP, this has implications for prognosis and therapy. However, longer follow-up is needed to more accurately determine if onset during childhood leads to a different disease course.
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50
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IL-8 Expression in Granulocytic Epithelial Lesions of Idiopathic Duct-centric Pancreatitis (Type 2 Autoimmune Pancreatitis). Am J Surg Pathol 2017; 41:1129-1138. [PMID: 28614208 DOI: 10.1097/pas.0000000000000891] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (P<0.001). In immunostaining, IL-8 expression was detected in the ductal/ductular epithelium (11/13; 85%) and infiltrating neutrophils or lymphocytes (12/12; 100%) in type 2 AIP, but was almost entirely negative in type 1 AIP (n=13; both, P<0.001). Although obstructive pancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (P<0.001 and 0.020, respectively). The presence of either GELs or IL-8-positive epithelium discriminated type 2 AIP from type 1 AIP or obstructive pancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.
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