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Bertolini M, Buono F, Galli A, Bagnasco D, Guastini L, Feltri M, Canevari FRM. Are there atypical sites of IgG4 related disease in head and neck region? Personal experience and literature review. Eur Arch Otorhinolaryngol 2025:10.1007/s00405-024-09188-6. [PMID: 39798025 DOI: 10.1007/s00405-024-09188-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 12/21/2024] [Indexed: 01/13/2025]
Abstract
PURPOSE Immunoglobulin G4-related disease (IgG4-RD) is a complex systemic fibroinflammatory condition with different clinical manifestations affecting multiple organ systems. Despite its rarity, the disease presents diagnostic and therapeutic challenges due to its mimicry of malignancies and other immune-mediated disorders. The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease is the current state of art to confirm the diagnosis of IgG4-RD even in the absence of histological analysis. However, this classification excludes atypical sites, focusing on the more typical ones, even in case of histological confirmation. In the ENT field, several localizations of this disease have been described. METHODS We report two clinical cases at the Otolaryngology Unit of IRCCS San Martino Hospital, Genoa affected by IgG4-RD arising in atypical sides of the head and neck region. Additionally, we perform a clinical review of the current literature. DISCUSSION The review provides an extensive overview of IgG4-RD, encompassing epidemiology, clinical manifestations, diagnostic approaches, and therapeutic strategies. We discuss the evolution of diagnostic criteria, emphasizing the necessity of interdisciplinary collaboration among clinicians, radiologists, and pathologists for accurate diagnosis. Diagnostic imaging plays a crucial role, with characteristic radiological patterns aiding in the identification of affected organs. However, definitive diagnosis often requires histopathological confirmation, highlighting the importance of biopsy in challenging cases. We also focus on the treatment of IgG4-RD which poses significant challenges, with glucocorticoids remaining the cornerstone of therapy. Emerging steroid-sparing agents such as rituximab and Dupilumab, show promising results in refractory or recurrent disease. CONCLUSIONS IgG4-RD is a multisystemic fibroinflammatory disease that can potentially affect any part of the body. The 2019 ACR/EULAR 3-stage classification criteria for IgG4-RD considers only a few head and neck sites. Therefore, it is of paramount importance that neurosurgeons, head and neck surgeons, and oral and maxillofacial pathologists are familiar with the clinicopathological manifestations of IgG4-RD in these sites to avoid misdiagnosis and inappropriate treatment, which can lead to a decrease in patients' quality of life. To our knowledge, there are no risk factors or genetic predispositions. Further studies are needed to elucidate the pathophysiology of IgG4-RD with the aim of providing a targeted therapy that could spare steroid-related effects and reduce relapses.
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Affiliation(s)
- Melania Bertolini
- Department of Otolaryngology and Head and Neck Surgery, IRCSS AOU San Martino, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy.
| | - Francesco Buono
- Department of Otolaryngology and Head and Neck Surgery, IRCSS AOU San Martino, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Alice Galli
- Department of Otolaryngology and Head and Neck Surgery, IRCSS AOU San Martino, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Diego Bagnasco
- Department of Internal Medicine, Allergy & Respiratory Diseases, IRCCS AOU San Martino-IST, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Luca Guastini
- Department of Otolaryngology and Head and Neck Surgery, IRCSS AOU San Martino, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Monica Feltri
- Unit of Pathology, IRCCS AOU San Martino-IST, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy
| | - Frank Rikki Mauritz Canevari
- Department of Otolaryngology and Head and Neck Surgery, IRCSS AOU San Martino, University of Genoa, Largo Rosanna Benzi 10, 16132, Genoa, Italy
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Shimada R, Yamada Y, Okamoto K, Murakami K, Motomura M, Takaki H, Fukuzawa K, Asayama Y. Pancreatic volume change using three dimensional-computed tomography volumetry and its relationships with diabetes on long-term follow-up in autoimmune pancreatitis. World J Radiol 2024; 16:644-656. [PMID: 39635311 PMCID: PMC11612800 DOI: 10.4329/wjr.v16.i11.644] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/07/2024] [Accepted: 09/23/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND Several studies found that early pancreatic atrophy detected by computed tomography (CT) within 6 months was associated with a high incidence of diabetes in patients with type-1 autoimmune pancreatitis (AIP) receiving steroid therapy; however, no long-term follow-up studies have been performed. AIM To investigate pancreatic volume (PV) changes using three dimensional (3D)-CT volumetry and their relationship with IgG4 and diabetes in patients with AIP. METHODS This retrospective study included 33 patients with type-1 AIP receiving steroid therapy. Patients were divided into diffuse (D-type) and mass-forming type (M-type) AIP. PV was determined by semi-automated 3D-CT volumetry, and changes between initial and follow-up values were calculated. The relationship between PV and serum IgG4 levels was analyzed by Spearman's rank correlation. The PV atrophy ratio compared with the presumed normal PV at the time of last follow-up CT and its relationship with diabetes were investigated. RESULTS There were 16 D-type and 17 M-type patients with long-term follow-up (mean, 95.8 months). The regression curve of mean relative PV change reduced exponentially and rapidly during the first 25 months and then more slowly in both groups. The overall cumulative pancreas re-enlargement rates at 1, 3, 5, 7 and 10 years were 6.1%, 12.2%, 29.2%, 47.5% and 55.0%, respectively. There was a moderate-to-very strong positive correlation (ρ ≥ 0.4) between PV and serum IgG4 levels in nine (9/13, 69.2%) patients. All 33 patients showed pancreatic atrophy (mean 59.3%) after long-term follow-up. Patients with D-type AIP had a significantly higher atrophy rate and higher incidence of diabetes than M-type patients (P < 0.05). CONCLUSION PV change initially reduced exponentially and then more slowly and is considered an important factor associated with diabetes. Serum IgG4 levels were positively correlated with PV during follow-up.
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Affiliation(s)
- Ryuichi Shimada
- Department of Radiology, Oita University Faculty of Medicine, Yufu 879-5593, Oita, Japan
| | - Yasunari Yamada
- Department of Radiology, Oita Red Cross Hospital, Oita 870-0033, Oita, Japan
| | - Kazuhisa Okamoto
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu 879-5593, Oita, Japan
| | - Kazunari Murakami
- Department of Gastroenterology, Oita University Faculty of Medicine, Yufu 879-5593, Oita, Japan
| | - Mitsuteru Motomura
- Department of Hepato-Biliary-Pancreatic Internal Medicine, Oita Red Cross Hospital, Oita 870-0033, Oita, Japan
| | - Hajime Takaki
- Department of Radiology, Oita Red Cross Hospital, Oita 870-0033, Oita, Japan
| | - Kengo Fukuzawa
- Department of Surgery, Oita Red Cross Hospital, Oita 870-0033, Oita, Japan
| | - Yoshiki Asayama
- Department of Radiology, Oita University Faculty of Medicine, Yufu 879-5593, Oita, Japan
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Kim D, Jeong S, Lew H. Unraveling the Clinical Features and Outcomes of IgG4-Related Ophthalmic Disease. J Clin Med 2024; 13:3780. [PMID: 38999348 PMCID: PMC11242082 DOI: 10.3390/jcm13133780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 06/10/2024] [Accepted: 06/24/2024] [Indexed: 07/14/2024] Open
Abstract
Background/Objectives: IgG4-related ophthalmic disease (IgG4-ROD), characterized by lymphoplasmacytic infiltration, fibrosis, and elevated IgG4 levels, presents diagnostic challenges while offering insights into immune-mediated inflammatory disorders. The aim of this study was to comprehensively examine the clinical features and outcomes of IgG4-ROD. Materials and Methods: A retrospective study was conducted on 33 patients diagnosed with IgG4-ROD, fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The demographic characteristics of the IgG4-ROD patients were compared with those of 37 patients diagnosed with IgG4-related disease (IgG4-RD) in departments other than ophthalmology (IgG4-nonROD) at the same hospital during the same period. The patients diagnosed with IgG4-ROD were initially treated with glucocorticosteroid (GCS) monotherapy, GCS combined with steroid-sparing agents (SSAs; mycophenolate mofetil, azathioprine, hydroxychloroquine), biologic agent (rituximab) monotherapy, or watchful waiting. The primary outcome was the assessed treatment response at 6 months, and the secondary outcome was the evaluation of recurrence at 1 year after initial treatment. A response was evaluated as the absence of ocular signs and symptoms, either clinically or radiologically. Results: Eyelid swelling (17 patients, 51.5%) was the most common symptom, and lacrimal gland (17 patients, 51.5%) was the most frequent site of involvement. The response rate for GCS monotherapy was 33.3% (3 out of 9 patients), while the response rate for GCS combined with SSA was 60.0% (9 out of 15 patients). The lacrimal gland group demonstrated a significantly higher treatment response compared to the non-lacrimal gland group (66.7% vs. 20.0%, p = 0.013), and the combination of GCS and SSA resulted in a significantly higher treatment response than the GCS monotherapy (77.8% vs. 33.3%, p = 0.045). The group including hydroxychloroquine (HCQ), which comprised 5 out of 33 patients (15.2%), showed no recurrence at 1 year. Conclusions: The combination therapy of GCS and SSA for IgG4-ROD can be considered an effective treatment approach and HCQ could be considered as a potential adjunctive therapy for IgG4-ROD.
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Affiliation(s)
- Doah Kim
- Department of Ophthalmology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 13496, Gyeonggi-do, Republic of Korea;
| | - SangYoon Jeong
- Department of Rheumatology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 13496, Gyeonggi-do, Republic of Korea;
| | - Helen Lew
- Department of Ophthalmology, Bundang CHA Medical Center, CHA University, Bundang-gu, Seongnam 13496, Gyeonggi-do, Republic of Korea;
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Overbeek KA, Poulsen JL, Lanzillotta M, Vinge-Holmquist O, Macinga P, Demirci AF, Sindhunata DP, Backhus J, Algül H, Buijs J, Levy P, Kiriukova M, Goni E, Hollenbach M, Miksch RC, Kunovsky L, Vujasinovic M, Nikolic S, Dickerson L, Hirth M, Neurath MF, Zumblick M, Vila J, Jalal M, Beyer G, Frost F, Carrara S, Kala Z, Jabandziev P, Sisman G, Akyuz F, Capurso G, Falconi M, Arlt A, Vleggaar FP, Barresi L, Greenhalf B, Czakó L, Hegyi P, Hopper A, Nayar MK, Gress TM, Vitali F, Schneider A, Halloran CM, Trna J, Okhlobystin AV, Dagna L, Cahen DL, Bordin D, Rebours V, Mayerle J, Kahraman A, Rasch S, Culver E, Kleger A, Martínez-Moneo E, Røkke O, Hucl T, Olesen SS, Bruno MJ, Della-Torre E, Beuers U, Löhr JM, Rosendahl J. Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment. Clin Gastroenterol Hepatol 2024; 22:994-1004.e10. [PMID: 38184096 DOI: 10.1016/j.cgh.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 12/04/2023] [Accepted: 12/05/2023] [Indexed: 01/08/2024]
Abstract
BACKGROUND & AIMS Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.
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Affiliation(s)
- Kasper A Overbeek
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
| | - Jakob L Poulsen
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Marco Lanzillotta
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Olof Vinge-Holmquist
- Department of Digestive Surgery, Akershus University Hospital, Loerenskog, Norway; Department of Digestive Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Peter Macinga
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - A Fatih Demirci
- Department of Internal Medicine, Marmara University Research and Education Hospital, Istanbul, Turkey
| | - Daniko P Sindhunata
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Johanna Backhus
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Hana Algül
- Department of Medicine II, Technische Universität München, München, Germany
| | - Jorie Buijs
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Philippe Levy
- Pancreatology Unit, APHP Beaujon Hospital, Clichy, France
| | - Mariia Kiriukova
- Department of Upper Gastrointestinal, Pancreatic, and Biliary Diseases, A.S. Loginov Moscow Clinical Research Center, Moscow, Russia
| | - Elisabetta Goni
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Marcus Hollenbach
- Division of Gastroenterology, Medical Department II - Oncology, Gastroenterology, Hepatology, Pulmonology, Infectious Diseases, University of Leipzig Medical Center, Leipzig, Germany
| | - Rainer C Miksch
- Department of General, Visceral, and Transplantation Surgery, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Lumir Kunovsky
- 2nd Department of Internal Medicine, Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Sara Nikolic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Luke Dickerson
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty at Mannheim, University of Heidelberg, Mannheim, Germany
| | - Markus F Neurath
- Department of Medicine I, Deutsches Zentrum Immuntherapie (DZI), Kussmaul Campus for Medical Research, University Erlangen-Nürnberg, Erlangen, Germany
| | - Malte Zumblick
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Josephine Vila
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | - Mustafa Jalal
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Georg Beyer
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Fabian Frost
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Silvia Carrara
- Gastrointestinal Endoscopy Unit, Humanitas Mater Domini, Castellanza, Italy
| | - Zdenek Kala
- Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Petr Jabandziev
- Department of Pediatrics, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Gurhan Sisman
- Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey
| | - Filiz Akyuz
- Department of Gastroenterology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy & Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Alexander Arlt
- Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany; Department for Internal Medicine and Gastroenterology, University Hospital, Klinikum Oldenburg AöR, Oldenburg, Germany
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCSS-ISMETT), Palermo, Italy
| | - Bill Greenhalf
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - László Czakó
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary
| | - Peter Hegyi
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Division of Pancreatic Diseases, Heart and Vascular Centre, Semmelweis University, Budapest, Hungary
| | - Andrew Hopper
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
| | - Manu K Nayar
- HPB Unit, Freeman Hospital, Newcastle Upon Tyne, United Kingdom
| | - Thomas M Gress
- Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Marburg, Germany
| | - Francesco Vitali
- Department of Medicine I, Deutsches Zentrum Immuntherapie (DZI), Kussmaul Campus for Medical Research, University Erlangen-Nürnberg, Erlangen, Germany
| | - Alexander Schneider
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty at Mannheim, University of Heidelberg, Mannheim, Germany
| | - Chris M Halloran
- Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Jan Trna
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Center Institute, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | | | - Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Djuna L Cahen
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Dmitry Bordin
- Department of Upper Gastrointestinal, Pancreatic, and Biliary Diseases, A.S. Loginov Moscow Clinical Research Center, Moscow, Russia; Department of Outpatient Therapy and Family Medicine, Tver State Medical University, Tver, Russia
| | | | - Julia Mayerle
- Department of Medicine II, University Hospital, Ludwig Maximilian University Munich, Munich, Germany
| | - Alisan Kahraman
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Essen University Hospital, University of Duisberg-Essen, Essen, Germany
| | - Sebastian Rasch
- Department of Medicine II, Technische Universität München, München, Germany
| | - Emma Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Alexander Kleger
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Emma Martínez-Moneo
- Biocruces, Grupo Transplante Hepático, Osakidetza, Hospital Universitario Cruces, Servicio Aparato Digestivo, Barakaldo, Spain
| | - Ola Røkke
- Department of Digestive Surgery, Akershus University Hospital, Loerenskog, Norway; Faculty of Medicine, Campus Ahus, University of Oslo, Oslo, Norway
| | - Tomas Hucl
- Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Søren S Olesen
- Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Marco J Bruno
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Emanuel Della-Torre
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), San Raffaele Scientific Institute, Milan, Italy
| | - Ulrich Beuers
- Department of Gastroenterology & Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - J-Matthias Löhr
- 2nd Department of Internal Medicine, Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; Department of Surgery, University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle (Saale), Germany.
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Kim JG, Jang S, Lee J, Ju JH, Kim WU, Park SH, Kwok SK. A single-centre retrospective study of factors affecting steroid-free remission of immunoglobulin G4-related disease conducted in South Korea: A notable outcome after complete resection. Mod Rheumatol 2024; 34:614-620. [PMID: 37022150 DOI: 10.1093/mr/road034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 03/03/2023] [Accepted: 03/23/2023] [Indexed: 04/07/2023]
Abstract
OBJECTIVES Few studies have examined factors affecting steroid-free remission (SFR) in patients with immunoglobulin G4-related disease (IgG4-RD). The aim of this study was to investigate clinical factors affecting SFR in IgG4-RD. METHODS The medical records of 68 patients who met the 2020 revised comprehensive diagnostic criteria for IgG4-RD were reviewed retrospectively. SFR was defined as remission maintained for at least 6 months without corticosteroids. Cox regression analysis was performed to examine the associations between SFR and various clinical factors. The relapse rate after SFR was examined using the log-rank test. RESULTS After a median follow-up of 36 months, 30.9% (21/68) of patients with IgG4-RD achieved SFR. Multivariate Cox regression analysis revealed that IgG4-RD diagnosed by complete resection rather than by common diagnostic procedures was the only factor positively associated with SFR (hazard ratio, 7.41; 95% confidence interval, 2.23-24.60; P = .001). Furthermore, relapse after attainment of SFR was significantly less common in the group that underwent complete resection than in the group that did not undergo complete resection (log-rank P = .006). CONCLUSIONS Patients with IgG4-RD diagnosed by complete resection had a higher likelihood of achieving SFR and a lower rate of relapse after attaining SFR.
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Affiliation(s)
- Jung Gon Kim
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Rheumatology, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea
| | - Sunhee Jang
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jennifer Lee
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ji Hyeon Ju
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Wan-Uk Kim
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung-Hwan Park
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung-Ki Kwok
- Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Czarnywojtek A, Agaimy A, Pietrończyk K, Nixon IJ, Vander Poorten V, Mäkitie AA, Zafereo M, Florek E, Sawicka-Gutaj N, Ruchała M, Ferlito A. IgG4-related disease: an update on pathology and diagnostic criteria with a focus on salivary gland manifestations. Virchows Arch 2024; 484:381-399. [PMID: 38316669 DOI: 10.1007/s00428-024-03757-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/12/2024] [Accepted: 01/29/2024] [Indexed: 02/07/2024]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.
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Affiliation(s)
- Agata Czarnywojtek
- Department of Pharmacology, Poznan University of Medical Sciences, 60-806, Poznan, Poland
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany
| | | | - Iain J Nixon
- Department of Otorhinolaryngology Head and Neck Surgery, NHS Lothian, Edinburgh, EH8 9YL, UK
| | - Vincent Vander Poorten
- Otorhinolaryngology-Head and Neck Surgery, KU Leuven University Hospitals, 3000, Leuven, Belgium
- Department of Oncology, Section Head and Neck Oncology, KU Leuven, 3000, Leuven, Belgium
| | - Antti A Mäkitie
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, and the Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland
| | - Mark Zafereo
- Department of Head & Neck Surgery, MD Anderson Cancer Center, Houston, TX, 77005, USA
| | - Ewa Florek
- Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, 60-806, Poznan, Poland.
| | - Nadia Sawicka-Gutaj
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Alfio Ferlito
- International Head and Neck Scientific Group, 35100, Padua, Italy
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7
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Gallo C, Dispinzieri G, Zucchini N, Invernizzi P, Massironi S. Autoimmune pancreatitis: Cornerstones and future perspectives. World J Gastroenterol 2024; 30:817-832. [PMID: 38516247 PMCID: PMC10950636 DOI: 10.3748/wjg.v30.i8.817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/18/2023] [Accepted: 01/25/2024] [Indexed: 02/26/2024] Open
Abstract
Autoimmune pancreatitis (AIP) is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas, leading to inflammation and fibrosis. Although AIP is rare, its incidence is increasing and is often misdiagnosed as other pancreatic diseases. AIP is commonly classified into two types. Type 1 AIP (AIP-1) is typically associated with elevated serum immunoglobulin G4 (IgG4) levels and systemic manifestations, while type 2 AIP is typically a more localized form of the disease, and may coexist with other autoimmune disorders, especially inflammatory bowel diseases. Additionally, there is emerging recognition of a third type (type 3 AIP), which refers to immunotherapy-triggered AIP, although this classification is still gaining acceptance in medical literature. The clinical manifestations of AIP mainly include painless jaundice and weight loss. Elevated serum IgG4 levels are particularly characteristic of AIP-1. Diagnosis relies on a combination of clinical, laboratory, radiological, and histological findings, given the similarity of AIP symptoms to other pancreatic disorders. The mainstay of treatment for AIP is steroid therapy, which is effective in most cases. Severe cases might require additional imm-unosuppressive agents. This review aims to summarize the current knowledge of AIP, encompassing its epidemiology, etiology, clinical presentation, diagnosis, and treatment options. We also address the challenges and controversies in diagnosing and treating AIP, such as distinguishing it from pancreatic cancer and managing long-term treatment, highlighting the need for increased awareness and knowledge of this complex disease.
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Affiliation(s)
- Camilla Gallo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Giulia Dispinzieri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Nicola Zucchini
- Department of Pathology, Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, Fondazione IRCCS San Gerardo dei Tintori; University of Milano-Bicocca, Monza 20900, Italy
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8
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Pădureanu V, Drăgoescu AN, Pădureanu R, Rośu MM, Rădulescu D, Dop D, For£ofoiu MC. Treatment approaches in autoimmune pancreatitis (Review). Biomed Rep 2024; 20:26. [PMID: 38259589 PMCID: PMC10801350 DOI: 10.3892/br.2023.1714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 12/11/2023] [Indexed: 01/24/2024] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease. There are two distinct types of AIP: AIP type 1 (AIP-1), a pancreatic manifestation of a multi-organ disease linked to immunoglobulin (Ig)G4, and AIP type 2 (AIP-2), a pancreas-specific disease unrelated to IgG4. The usual course of treatment for AIP is oral corticosteroid medication. Rituximab has also been recommended for recurrent AIP-1 in order to initiate remission and provide ongoing treatment. Immunomodulators such as azathioprine are used to keep certain patients in remission. Evaluation also takes into account a number of pharmacological alternatives, including biologic drugs like anti-tumor necrosis factor therapy, a safe and efficient second-line treatment for AIP-2 relapse or steroid dependence. Corticosteroids and immunosuppressants, which are poorly tolerated due to considerable side effects, are being replaced by other biologic drugs, which may offer a beneficial therapeutic alternative.
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Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Alice Nicoleta Drăgoescu
- Department of Anaesthesiology and Intensive Care, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Maria Magdalena Rośu
- Department of Diabetes, Nutrition and Metabolic Diseases, County Clinical Emergency Hospital of Craiova, Craiova 200642, Romania
| | - Dumitru Rădulescu
- Department of Pediatrics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dalia Dop
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mircea Cătălin For£ofoiu
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Ikeura T, Tomiyama T, Takaori A, Ito T, Nakamaru K, Masuda M, Hori Y, Tsukuda S, Sumimoto K, Mitsuyama T, Nakayama S, Shimatani M, Uchida K, Takaoka M, Okazaki K, Naganuma M. Long-term Outcomes after Steroid Pulse Therapy in Patients with Type 1 Autoimmune Pancreatitis. Intern Med 2023; 62:2931-2940. [PMID: 36889699 PMCID: PMC10641208 DOI: 10.2169/internalmedicine.0807-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 01/26/2023] [Indexed: 03/09/2023] Open
Abstract
Objective Steroid pulse therapy is a regimen involving the intravenous administration of supra-pharmacological doses of corticosteroids in the short term. It is used to treat various inflammatory and autoimmune conditions. However, the strengths and limitations of steroid pulse therapy for induction of remission in type 1 autoimmune pancreatitis (AIP) are unknown. Methods Depending on the steroid therapy regimen administered, the 104 patients with type 1 AIP included in this retrospective study were divided into three groups: conventional oral prednisolone (PSL) regimen (PSL group), intravenous methylprednisolone (IVMP) pulse followed by oral PSL regimen (Pulse+PSL group), and IVMP pulse-alone regimen (Pulse-alone group). We then examined the relapse rate and adverse events among the three groups. Results The Kaplan-Meier estimates of the relapse rate at 36 months after steroid therapy were 13.6% in the PSL group, 13.3% in the Pulse+PSL group, and 46.2% in the Pulse-alone group. The log-rank test revealed that the relapse-free survival in the Pulse-alone group was significantly shorter than that in the PSL (p=0.024) and Pulse+PSL groups (p=0.014). The exacerbation of glucose tolerance after steroid therapy was less frequently observed in the Pulse-alone group (0%) than in the PSL group (17%, p=0.050) and Pulse+PSL groups (26%, p=0.011). Conclusion Although treatment with IVMP pulse alone resulted in unsatisfactory relapse prevention outcomes compared with conventional steroid therapy, the IVMP pulse-alone regimen might be an alternative treatment strategy for type 1 AIP from the perspective of avoiding adverse events from steroids.
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Affiliation(s)
- Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Takashi Tomiyama
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Ayaka Takaori
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Takashi Ito
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Koh Nakamaru
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Masataka Masuda
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Yuichi Hori
- Kansai Medical University Kori Hospital, Japan
| | | | - Kimi Sumimoto
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Japan
| | - Toshiyuki Mitsuyama
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Japan
| | - Shinji Nakayama
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Masaaki Shimatani
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Japan
| | | | | | - Makoto Naganuma
- Third Department of Internal Medicine, Kansai Medical University, Japan
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10
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Zhou GZ, Zeng JQ, Wang L, Liu M, Meng K, Wang ZK, Zhang XL, Peng LH, Yan B, Pan F. Clinical characteristics and outcome of autoimmune pancreatitis based on serum immunoglobulin G4 level: A single-center, retrospective cohort study. World J Gastroenterol 2023; 29:5125-5137. [PMID: 37744294 PMCID: PMC10514754 DOI: 10.3748/wjg.v29.i35.5125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 07/21/2023] [Accepted: 09/01/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) has been linked with elevated immunoglobulin (Ig) G4 levels. The characteristics and outcomes of AIP based on serum markers have not been fully evaluated. AIM To compare clinical features, treatment efficacy, and outcome of AIP based on serum IgG4 levels and analyze predictors of relapse. METHODS A total of 213 patients with AIP were consecutively reviewed in our hospital from 2006 to 2021. According to the serum IgG4 level, all patients were divided into two groups, the abnormal group (n = 148) with a high level of IgG4 [> 2 × upper limit of normal (ULN)] and the normal group (n = 65). The t-test or Mann-Whitney U test was used to compare continuous variables. Categorical parameters were compared by the χ2 test or Fisher's exact test. Kaplan-Meier curves and log-rank tests were established to assess the cumulative relapse rates. Univariate and multivariate analyses were used to investigate potential risk factors of AIP relapse. RESULTS Compared with the normal group, the abnormal group had a higher average male age (60.3 ± 10.4 vs 56.5 ± 12.9 years, P = 0.047); higher level of serum total protein (72.5 ± 7.9 g/L vs 67.2 ± 7.5 g/L, P < 0.001), IgG4 (1420.5 ± 1110.9 mg/dL vs 252.7 ± 106.6 mg/dL, P < 0.001), and IgE (635.6 ± 958.1 IU/mL vs 231.7 ± 352.5 IU/mL, P = 0.002); and a lower level of serum complement C3 (100.6 ± 36.2 mg/dL vs 119.0 ± 45.7 mg/dL, P = 0.050). In addition, a lower number of cases with abnormal pancreatic duct and pancreatic atrophy (23.6% vs 37.9%, P = 0.045; 1.6% vs 8.6%, P = 0.020, respectively) and a higher rate of relapse (17.6% vs 6.2%, P = 0.030) were seen in the abnormal group. Multivariate analyses revealed that serum IgG4 [(> 2 × ULN), hazard ratio (HR): 3.583; 95% confidence interval (CI): 1.218-10.545; P = 0.020] and IgA (> 1 × ULN; HR: 5.908; 95%CI: 1.199-29.120; P = 0.029) and age > 55 years (HR: 2.383; 95%CI: 1.056-5.378; P = 0.036) were independent risk factors of relapse. CONCLUSION AIP patients with high IgG4 levels have clinical features including a more active immune system and higher relapse rate. Several factors, such as IgG4 and IgA, are associated with relapse.
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Affiliation(s)
- Guan-Zhou Zhou
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Jia-Qi Zeng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Chinese PLA Medical School, Beijing 100853, China
| | - Lei Wang
- Department of Rheumatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Miao Liu
- Department of Statistics and Epidemiology, Graduate School, Chinese PLA General Hospital, Beijing 100853, China
| | - Ke Meng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Zi-Kai Wang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Xiu-Li Zhang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Li-Hua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Bin Yan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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11
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Kiyoshita Y, Ishii Y, Serikawa M, Hanada K, Sasaki T, Fujimoto Y, Yamaguchi A, Hirao K, Noma B, Minami T, Okazaki A, Yukutake M, Mouri T, Tsuboi T, Tatsukawa Y, Nakamura S, Hirano T, Ikemoto J, Saeki S, Tamura Y, Miyamoto S, Furukawa M, Nakmura K, Yamashita Y, Iijima N, Oka S. Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study. BMC Gastroenterol 2023; 23:295. [PMID: 37667191 PMCID: PMC10478447 DOI: 10.1186/s12876-023-02939-5] [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: 04/14/2023] [Accepted: 08/29/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. METHODS We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18-36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors. RESULTS After discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001). CONCLUSIONS A high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.
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Affiliation(s)
- Yusuke Kiyoshita
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Masahiro Serikawa
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Keiji Hanada
- Department of Gastroenterology, Onomichi General Hospital, Hiroshima, Japan
| | - Tamito Sasaki
- Department of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Yoshifumi Fujimoto
- Department of Gastroenterology, Hiroshima General Hospital, Hiroshima, Japan
| | - Atsushi Yamaguchi
- Department of Gastroenterology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
| | - Ken Hirao
- Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Bunjiro Noma
- Department of Gastroenterology, Kure Kyosai Hospital, Hiroshima, Japan
| | - Tomoyuki Minami
- Department of Gastroenterology, Hiroshima Red Cross & Atomic-bomb Survivors Hospital, Hiroshima, Japan
| | - Akihito Okazaki
- Department of Gastroenterology, National Hospital Organization Higashihiroshima Medical Center, Hiroshima, Japan
| | - Masanobu Yukutake
- Department of Gastroenterology, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Teruo Mouri
- Department of Gastroenterology, Chugoku Rosai Hospital, Hiroshima, Japan
| | - Tomofumi Tsuboi
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yumiko Tatsukawa
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Nakamura
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tetsuro Hirano
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Juri Ikemoto
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Sho Saeki
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yosuke Tamura
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Sayaka Miyamoto
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Masaru Furukawa
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kazuki Nakmura
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yumiko Yamashita
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Noriaki Iijima
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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12
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Cheng YC, Chiang CL, Huang CW. IgG4-Related Disease Mimicking Unilateral Urothelial Carcinoma: A Rare Case Report and Literature Review. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2023; 16:11795476231180481. [PMID: 37332833 PMCID: PMC10272671 DOI: 10.1177/11795476231180481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 05/19/2023] [Indexed: 06/20/2023]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune-mediated disorder with heterogeneous multiorgan manifestations. Early identification and treatment of IgG4-RD are crucial for organ function recovery. Rarely, IgG4-RD manifests as a unilateral renal pelvic soft tissue mass that may be misdiagnosed as urothelial malignancy, resulting in invasive surgical intervention and organ damage. Here we present a 73-year-old man who had a right ureteropelvic mass with hydronephrosis detected by enhanced computed tomography. Right upper tract urothelial carcinoma and lymph node metastasis was highly suggested based on the image findings. However, IgG4-RD was suspected due to his past history of bilateral submandibular lymphadenopathy, nasolacrimal duct obstruction, as well as a high serum IgG4 level of 861 mg/dL. The ureteroscopy with tissue biopsy showed no evidence of urothelial malignancy. His lesions and symptoms improved after glucocorticoid treatment. Hence, a diagnosis of IgG4-RD was made, with the phenotype of classic Mikulicz syndrome with systemic involvement. The manifestation of IgG4-RD as a unilateral renal pelvic mass is rare and should be kept in mind. A ureteroscopic biopsy and serum IgG4 level measurement can help in the diagnosis of IgG4-RD in patients with a unilateral renal pelvic lesion.
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Affiliation(s)
- Yu-Chieh Cheng
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chia-Ling Chiang
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Wei Huang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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13
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Tanaka Y, Stone JH. Perspectives on current and emerging therapies for immunoglobulin G4-related disease. Mod Rheumatol 2023; 33:229-236. [PMID: 36408992 DOI: 10.1093/mr/roac141] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 10/20/2022] [Accepted: 11/06/2022] [Indexed: 11/23/2022]
Abstract
Understanding of the pathophysiology of immunoglobulin G4-related disease (IgG4-RD) over the last dozen years has opened the door to a variety of targeted treatment approaches. Glucocorticoids are an effective treatment for IgG4-RD if used at a sufficiently high dose, but disease flares are common during or after glucocorticoid tapers and these medications seldom lead to long-term, treatment-free remissions. Moreover, their long-term use in a disease that frequently affects middle-aged to elderly individuals and often causes major pancreatic damage leads to a narrow therapeutic index. Biological therapies offer the possibility of effective disease control with fewer treatment-associated side effects. Promising avenues of investigation include B-cell depletion, immunomodulation of B-cell subsets, interference with co-stimulation, Bruton's tyrosine kinase inhibition, and Signaling lymphocytic activation molecule F7-directed treatment.
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Affiliation(s)
- Yoshiya Tanaka
- The First Department of Internal Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan
| | - John H Stone
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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14
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Yoshifuji H, Umehara H. Glucocorticoids in the treatment of IgG4-related disease-Prospects for new international treatment guidelines. Mod Rheumatol 2023; 33:252-257. [PMID: 35993488 DOI: 10.1093/mr/roac097] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/31/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibro-inflammatory disease that may cause dysfunction in various organs. Worldwide multidisciplinary experts attending the Fourth International Symposium on IgG4-Related Disease in Japan in 2021 discussed treatments for IgG4-RD, especially glucocorticoid (GC) therapy. This review describes the efficacy, safety, and cost of treatments for IgG4-RD based on findings presented at the international symposium. A medium dose of GC was considered appropriate for the initial treatment of IgG4-RD. A randomized controlled trial and an open-label prospective study have shown that long-term maintenance GC therapy (prednisolone ≥ 5 mg/day) could prevent disease relapse. In addition, two open-label randomized controlled trials reported the effects of combinational use of GC and synthetic immunosuppressive agents, mycophenolate mofetil and leflunomide, on relapse prevention. Moreover, an open-label single-arm study showed an excellent rate of clinical response to rituximab. Many observational studies have shown the efficacy of an appropriate GC regimen in patients with IgG4-RD. Synthetic immunosuppressive agents and a molecular-targeted agent can be potent alternatives to GCs, but additional studies are required comparing their efficacy, risk of infection, and costs.
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Affiliation(s)
- Hajime Yoshifuji
- Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hisanori Umehara
- Center for RA and Autoimmune Diseases, Nagahama City Hospital, Nagahama, Shiga, Japan
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15
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Kurita Y, Kubota K, Suzuki K, Yagi S, Hasegawa S, Sato T, Hosono K, Kobayashi N, Endo I, Nakajima A. Request for biliary drainage for IgG4-SC could be waived before steroid administration? JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:392-400. [PMID: 36031808 DOI: 10.1002/jhbp.1230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 07/27/2022] [Accepted: 08/05/2022] [Indexed: 12/07/2022]
Abstract
BACKGROUND In IgG4-related sclerosing cholangitis (IgG4-SC), the necessity of biliary drainage (BD) is unclear. In this study, we aimed to retrospectively investigate the improvement of liver damage and jaundice in cases of IgG4-SC with and without BD, before starting steroids. METHODS A total of 52 patients with IgG4-SC were investigated in the study. The study endpoints were the normalization rate of alkaline phosphatase (ALP)/total bilirubin (T-Bil) after 8 weeks of steroids, with and without BD. RESULTS Propensity score matching was performed based on ALP and T-Bil, and 28 patients were included. There were 14 patients each in the BD and non-BD groups. Before initiation of steroids, the mean ALP in the BD group and the non-BD group was 378/461 (P = .541); the mean T-Bil was 2.5/1.8 (P = .401). Eight weeks after initiation of steroids, ALP improvement rate in the BD group/non-BD group was 69.2%/61.5% (P = 1.000), and T-Bil improvement rate was 100%/100% (P = Ns). CONCLUSIONS Steroids for IgG4-SC could prove effective in improving liver damage and jaundice, regardless of the presence or absence of BD. BD for IgG4-SC aimed to improve jaundice may not be necessary.
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Affiliation(s)
- Yusuke Kurita
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Kensuke Kubota
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Ko Suzuki
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Shin Yagi
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Sho Hasegawa
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Takamitsu Sato
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | - Kunihiro Hosono
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
| | | | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Hospital, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama, Japan
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16
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Lee JE, Hwang SH. A Case of IgG4-Related Disease With Sinonasal Involvement Presenting With Decreased Visual Acuity. JOURNAL OF RHINOLOGY 2023; 30:48-52. [PMID: 39664706 PMCID: PMC11524364 DOI: 10.18787/jr.2023.00008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 01/30/2023] [Accepted: 02/01/2023] [Indexed: 04/01/2023] Open
Abstract
IgG4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by IgG4-positive plasma cell and T lymphocyte infiltration of multiple organs. It commonly involves the pancreas, lacrimal glands, and salivary glands, and it has been rarely reported in the sinonasal cavity. We herein report the case of a 47-year-old male patient whose chief complaint was decreased visual acuity. A tumefactive mass was found on imaging studies, originating from the sinonasal cavity and invading the orbit, kidney, and meninges. The mass was resected through endoscopic sinus surgery and was pathologically confirmed to be IgG4-RD. The patient was treated with steroid therapy and showed clinical improvement.
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Affiliation(s)
- Ju Eun Lee
- Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Se Hwan Hwang
- Department of Otolaryngology-Head and Neck Surgery, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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17
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Kim SH, Lee YC, Chon HK. Challenges for clinicians treating autoimmune pancreatitis: Current perspectives. World J Clin Cases 2023; 11:30-46. [PMID: 36687190 PMCID: PMC9846983 DOI: 10.12998/wjcc.v11.i1.30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/31/2022] [Accepted: 12/19/2022] [Indexed: 01/04/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease clinically characterized by obstructive jaundice, unintentional weight loss, acute pancreatitis, focal pancreatic mass, and diabetes. AIP is classified into two subtypes - type 1 and type 2 - according to pathological findings, clinical features, and serology test results, but some cases may be defined as type not otherwise in the absence of pathological findings and inflammatory bowel disease. To address the differences in diagnostic criteria by country, standard diagnostic criteria for AIP were proposed in 2011 by an international consensus of expert opinions. Differential diagnosis of AIP from pancreatic ductal adenocarcinoma is important but remains challenging for clinicians. Fortunately, all subtypes of AIP show dramatic response to steroid treatment. This review discusses the current perspectives on the diagnosis and management of AIP in clinical practice.
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Affiliation(s)
- Seong-Hun Kim
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Yun Chae Lee
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Hyung Ku Chon
- Department of Internal Medicine, Institution of Wonkwang Medical Science, Wonkwang University School of Medicine and Hospital, Iksan 54538, South Korea
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18
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Shibata K, Motozono C, Nagae M, Shimizu T, Ishikawa E, Motooka D, Okuzaki D, Izumi Y, Takahashi M, Fujimori N, Wing JB, Hayano T, Asai Y, Bamba T, Ogawa Y, Furutani-Seiki M, Shirai M, Yamasaki S. Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b. Nat Commun 2022; 13:6948. [PMID: 36376329 PMCID: PMC9663695 DOI: 10.1038/s41467-022-34802-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/08/2022] [Indexed: 11/16/2022] Open
Abstract
MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.
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Affiliation(s)
- Kensuke Shibata
- grid.268397.10000 0001 0660 7960Department of Microbiology and Immunology, Graduate School of Medicine, Yamaguchi University, Ube, 755-8505 Japan ,grid.177174.30000 0001 2242 4849Department of Ophthalmology, Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan ,grid.136593.b0000 0004 0373 3971Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan
| | - Chihiro Motozono
- grid.136593.b0000 0004 0373 3971Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan ,grid.274841.c0000 0001 0660 6749Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, 860-0871 Japan
| | - Masamichi Nagae
- grid.136593.b0000 0004 0373 3971Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, 565-0871 Japan
| | - Takashi Shimizu
- grid.136593.b0000 0004 0373 3971Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan
| | - Eri Ishikawa
- grid.136593.b0000 0004 0373 3971Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, 565-0871 Japan
| | - Daisuke Motooka
- grid.136593.b0000 0004 0373 3971Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan
| | - Daisuke Okuzaki
- grid.136593.b0000 0004 0373 3971Single Cell Genomics, Human Immunology, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Suita, 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan
| | - Yoshihiro Izumi
- grid.177174.30000 0001 2242 4849Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582 Japan
| | - Masatomo Takahashi
- grid.177174.30000 0001 2242 4849Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582 Japan
| | - Nao Fujimori
- grid.177174.30000 0001 2242 4849Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan
| | - James B. Wing
- grid.136593.b0000 0004 0373 3971Laboratory of Human Immunology (Single Cell Immunology), World Premier International Immunology Frontier Research Center, Osaka University, Suita, 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Laboratory of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, 565-0871 Japan
| | - Takahide Hayano
- grid.268397.10000 0001 0660 7960Department of Systems Bioinformatics, Graduate School of Medicine, Yamaguchi University, Ube, 755-8505 Japan
| | - Yoshiyuki Asai
- grid.268397.10000 0001 0660 7960Department of Systems Bioinformatics, Graduate School of Medicine, Yamaguchi University, Ube, 755-8505 Japan
| | - Takeshi Bamba
- grid.177174.30000 0001 2242 4849Division of Metabolomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582 Japan
| | - Yoshihiro Ogawa
- grid.177174.30000 0001 2242 4849Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582 Japan ,grid.419082.60000 0004 1754 9200Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology, Tokyo, 100-0004 Japan ,grid.27476.300000 0001 0943 978XDepartment of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601 Japan
| | - Makoto Furutani-Seiki
- grid.268397.10000 0001 0660 7960Systems Biochemistry in Pathology and Regeneration, Graduate School of Medicine, Yamaguchi University, Ube, 755-8505 Japan
| | - Mutsunori Shirai
- grid.268397.10000 0001 0660 7960Department of Microbiology and Immunology, Graduate School of Medicine, Yamaguchi University, Ube, 755-8505 Japan
| | - Sho Yamasaki
- grid.136593.b0000 0004 0373 3971Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Suita, 565-0871 Japan ,grid.177174.30000 0001 2242 4849Division of Molecular Design, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582 Japan ,grid.136304.30000 0004 0370 1101Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, 260-8673 Japan
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19
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Nista EC, De Lucia SS, Manilla V, Schepis T, Pellegrino A, Ojetti V, Pignataro G, Zileri dal Verme L, Franceschi F, Gasbarrini A, Candelli M. Autoimmune Pancreatitis: From Pathogenesis to Treatment. Int J Mol Sci 2022; 23:12667. [PMID: 36293522 PMCID: PMC9604056 DOI: 10.3390/ijms232012667] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/14/2022] [Accepted: 10/18/2022] [Indexed: 11/05/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.
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Affiliation(s)
- Enrico Celestino Nista
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Sara Sofia De Lucia
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Vittoria Manilla
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Tommaso Schepis
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Pellegrino
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Veronica Ojetti
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giulia Pignataro
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Lorenzo Zileri dal Verme
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Franceschi
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Marcello Candelli
- Department of Emergency, Anesthesiological, and Reanimation Sciences, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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20
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Ashihara N, Ota M, Fujinaga Y, Ozawa M, Kuraishi Y, Watanabe T, Hamano H, Joshita S, Kawa S, Umemura T. The levels of IL-1β and soluble IL-1 receptors in patients with IgG4-related periaortitis/periarteritis. Adv Med Sci 2022; 67:257-261. [PMID: 35785599 DOI: 10.1016/j.advms.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 06/16/2022] [Accepted: 06/17/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE IgG4-related disease (IgG4-RD) is a chronic fibrotic inflammatory and an immune-mediated disease characterized by high serum IgG4 concentration and IgG4-bearing plasma cell infiltration in affected organs. IgG4-related periaortitis/periarteritis is a recently identified disease entity in IgG4-RD that affects the cardiovascular system, and its pathogenesis and characteristics remain unclear. The inflammatory cytokine IL-1β is involved in a variety of cellular activities including inflammation, fibrosis, and angiogenesis. The present study compared the levels of the inflammatory cytokine IL-1β and two soluble IL-1 receptors, IL-1R1 and IL-1R2, between IgG4-RD patients with and without IgG4-related periaortitis/periarteritis. METHODS The patients with IgG4-related periaortitis/periarteritis (n = 38), those without (n = 66) and healthy (n = 33) were recruited to measure cytokines of IL-1β and soluble receptors (sIL-1R1 and sIL-1R2) in sera by ELISA assay. RESULTS Serum IgG4 was significantly higher in patients with periaortitis/periarteritis compared to non-periaortitis/periarteritis (p = 0.0074), while serum IL-1β was significantly lower in patients with periaortitis/periarteritis (p = 0.00037). The three groups did not show significant difference in sIL1-R1, while sIL-1R2 in the periaortitis/periarteritis and healthy group was higher than in the group without periaortitis/periarteritis (p = 0.00001). CONCLUSIONS The characteristic changes in IL-1β, sIL-1R1, and sIL-1R2 levels in IgG4-RD patients with and without IgG4-related periaortitis/periarteritis may indicate an active phase of the inflammatory process in these diseases.
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Affiliation(s)
- Norihiro Ashihara
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Masao Ota
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan.
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Makiko Ozawa
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yasuhiro Kuraishi
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Takayuki Watanabe
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Hideaki Hamano
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Satoru Joshita
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Japan
| | - Takeji Umemura
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan
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21
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Dugic A, Verdejo Gil C, Mellenthin C, Vujasinovic M, Löhr JM, Mühldorfer S. The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review. Biomedicines 2022; 10:1511. [PMID: 35884816 PMCID: PMC9312496 DOI: 10.3390/biomedicines10071511] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
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Affiliation(s)
- Ana Dugic
- Department of Gastroenterology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Medizincampus Oberfranken, 95445 Bayreuth, Germany;
- Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany
| | - Cristina Verdejo Gil
- Department of Gastroenterology, Hospital Universitario Fundación de Alcorcón, 28922 Madrid, Spain;
| | | | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, 14186 Stockholm, Sweden;
- Department of Medicine, Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden;
| | - J.-Matthias Löhr
- Department of Medicine, Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden;
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 14186 Stockholm, Sweden
| | - Steffen Mühldorfer
- Department of Gastroenterology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Medizincampus Oberfranken, 95445 Bayreuth, Germany;
- Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany
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22
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Carrasco Rodríguez R, García Fontán EM, Blanco Ramos M, Magdalena Benavides LJ, Otero Lozano D, Moldes Rodriguez M, Cañizares Carretero MA. Inflammatory pseudotumor and myofibroblastic inflammatory tumor. Diagnostic criteria and prognostic differences. Cir Esp 2022; 100:329-335. [PMID: 35577280 DOI: 10.1016/j.cireng.2022.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 03/13/2021] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) are two very rare entities that were formerly included in the same category; however, today they are considered two different diseases due to the neoplastic origin of the IMT. Our objective is to share our experience in the management of these two types of tumors that we must take into account in the differential diagnosis of pulmonary masses or nodules. METHODS Thirteen patients with a pathological diagnosis of IPT and IMT who underwent surgery between 2008 and 2019 were retrospectively studied. We recorded the pre and postoperative information of each one, as well as the survival analysis. RESULTS Of the 13 patients, 8 were men and 5 women. The mean age of presentation was 53,5 years. An atypical segmentectomy was performed in 6 patients; a lobectomy was necessary in 6 and a pneumonectomy in 1 case. In all cases a complete resection was achieved. Diagnosis was possible thanks to histology, immunohistochemical (IHQ) and fluorescent in situ hybridization (FISH) techniques determining the expression of IgG4 and the rearrangement of ALK, respectively. After a median follow up of 49 months, we didn't find any loco-regional or distant recurrence in the patients studied. CONCLUSION IPT and IMT are rare tumors with a very good prognostic. The diagnosis of both entities is based mainly on specific anatomopathological techniques. Surgery has, in most cases, both a diagnostic and therapeutic role.
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Affiliation(s)
| | | | | | | | - Daniel Otero Lozano
- Servicio de Cirugía Torácica, Hospital Álvaro Cunqueiro, Vigo, Pontevedra, Spain
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23
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Long-Term Follow-Up and Immunomonitoring of Relapsing Type 1 Autoimmune Pancreatitis Treated With Rituximab. Pancreas 2022; 51:452-462. [PMID: 35835119 DOI: 10.1097/mpa.0000000000002048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES To evaluate the efficacy and safety of rituximab in relapsing type 1 autoimmune pancreatitis especially the long-term clinical and immunologic impacts. METHODS All consecutive patients with type 1 autoimmune pancreatitis were retrospectively included. The rituximab protocol was induction therapy of 375 mg·m -2 intravenous weekly for 4 weeks, followed by 500 mg intravenous every 6 months for 2 years. The follow-up included clinical examinations, biological tests, positron emission tomography scan, and immunomonitoring of lymphocyte CD 19+. RESULTS Among the 43 patients included, 15 received rituximab induction therapy, followed by maintenance in 10 cases because of 1 or more relapses after steroids (whether or not followed by immunosuppressants) and multiple organ involvement. All patients had a clinical, biological and morphological response, a deep and persistent drop in serum immunoglobulin G4 levels, an extinction of both pancreatic and extra pancreatic hypermetabolic positron emission tomography scan signals, and a depletion of B lymphocyte CD19+. No relapse occurred during the follow-up (62.8 ± standard error of the mean of 11.1 months). CONCLUSIONS Rituximab is an effective treatment for type 1 autoimmune pancreatitis that provides a rapid strong clinical, biological, and morphological response, which persists after discontinuation without any safety issues.
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Beyer G, Hoffmeister A, Michl P, Gress TM, Huber W, Algül H, Neesse A, Meining A, Seufferlein TW, Rosendahl J, Kahl S, Keller J, Werner J, Friess H, Bufler P, Löhr MJ, Schneider A, Lynen Jansen P, Esposito I, Grenacher L, Mössner J, Lerch MM, Mayerle J. S3-Leitlinie Pankreatitis – Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – September 2021 – AWMF Registernummer 021-003. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:419-521. [PMID: 35263785 DOI: 10.1055/a-1735-3864] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Georg Beyer
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Ludwig-Maximilians-Universität München, Deutschland
| | - Albrecht Hoffmeister
- Bereich Gastroenterologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Deutschland
| | - Patrick Michl
- Universitätsklinik u. Poliklinik Innere Medizin I mit Schwerpunkt Gastroenterologie, Universitätsklinikum Halle, Deutschland
| | - Thomas Mathias Gress
- Klinik für Gastroenterologie und Endokrinologie, Universitätsklinikum Gießen und Marburg, Deutschland
| | - Wolfgang Huber
- Comprehensive Cancer Center München TUM, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Deutschland
| | - Hana Algül
- Comprehensive Cancer Center München TUM, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, München, Deutschland
| | - Albrecht Neesse
- Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Deutschland
| | - Alexander Meining
- Medizinische Klinik und Poliklinik II Gastroenterologie und Hepatologie, Universitätsklinikum Würzburg, Deutschland
| | | | - Jonas Rosendahl
- Universitätsklinik u. Poliklinik Innere Medizin I mit Schwerpunkt Gastroenterologie, Universitätsklinikum Halle, Deutschland
| | - Stefan Kahl
- Klinik für Innere Medizin m. Schwerpkt. Gastro./Hämat./Onko./Nephro., DRK Kliniken Berlin Köpenick, Deutschland
| | - Jutta Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - Jens Werner
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, Deutschland
| | - Helmut Friess
- Klinik und Poliklinik für Chirurgie, Klinikum rechts der Isar, München, Deutschland
| | - Philip Bufler
- Klinik für Pädiatrie m. S. Gastroenterologie, Nephrologie und Stoffwechselmedizin, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Deutschland
| | - Matthias J Löhr
- Department of Gastroenterology, Karolinska, Universitetssjukhuset, Stockholm, Schweden
| | - Alexander Schneider
- Klinik für Gastroenterologie und Hepatologie, Klinikum Bad Hersfeld, Deutschland
| | - Petra Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin, Deutschland
| | - Irene Esposito
- Pathologisches Institut, Heinrich-Heine-Universität und Universitätsklinikum Duesseldorf, Duesseldorf, Deutschland
| | - Lars Grenacher
- Conradia Radiologie München Schwabing, München, Deutschland
| | - Joachim Mössner
- Bereich Gastroenterologie, Klinik und Poliklinik für Onkologie, Gastroenterologie, Hepatologie Pneumologie und Infektiologie, Universitätsklinikum Leipzig, Deutschland
| | - Markus M Lerch
- Klinik für Innere Medizin A, Universitätsmedizin Greifswald, Deutschland.,Klinikum der Ludwig-Maximilians-Universität (LMU) München, Deutschland
| | - Julia Mayerle
- Medizinische Klinik und Poliklinik II, LMU Klinikum, Ludwig-Maximilians-Universität München, Deutschland
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Kamisawa T. Immunoglobulin G4-related Disease: A New Systemic Disease Emerging in Japan. JMA J 2022; 5:23-35. [PMID: 35224257 PMCID: PMC8826784 DOI: 10.31662/jmaj.2021-0113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 10/05/2021] [Indexed: 11/16/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum IgG4 levels. In 2003, IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with autoimmune pancreatitis. IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically, IgG4-RD occurs when an autoantigen triggers an immune response characterized by Th2 predominance with increased production of cytokines, such as interleukin 4 (IL-4), IL-5, IL-10, IL-13, and tumor growth factor-β (TGF-β), in the affected organ. IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating IgG4-RD from malignant tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against Rheumatism classification criteria for IgG4-RD have high diagnostic sensitivity and specificity. IgG4-RD generally responds well to treatment with steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of steroids. In Japan, low-dose steroid maintenance therapy is usually given to prevent a relapse. B-cell depletion with rituximab is effective in patients resistant to or dependent on steroids. Most patients with IgG4-RD who receive steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse, fibrosis development, and associated malignancies, have not been clearly defined. Therefore, novel treatment strategies, including rituximab, need to be tested in international randomized controlled clinical trials.
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Affiliation(s)
- Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
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Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020. J Gastroenterol 2022; 57:225-245. [PMID: 35192048 PMCID: PMC8938398 DOI: 10.1007/s00535-022-01857-9] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 01/28/2022] [Indexed: 02/04/2023]
Abstract
In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.
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Timeus F, Calvo MM, Caci AM, Gallone GO, Vittone F. IgG4-related chronic sclerosing sialadenitis in a child with recurrent parotitis: a case report. BMC Pediatr 2021; 21:586. [PMID: 34930210 PMCID: PMC8691005 DOI: 10.1186/s12887-021-03004-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 11/13/2021] [Indexed: 11/10/2022] Open
Abstract
Background IgG4-related disease (IgG4-RD) includes a group of immune-mediated diseases histologically characterized by lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children. Here we report the case of IgG4-related sialadenitis in a six-year-old patient previously diagnosed as juvenile recurrent parotitis. Case presentation A six-year-old patient was referred to our Centre for left parotid swelling of 4 × 3 cm, that was tender, soft in consistency, with overlying red and warm skin. His general condition was good but he was subfebrile; general examination revealed mild enlargement of left cervical lymph nodes. In the last 2 years he had had five episodes of parotitis, diagnosed by another pediatric Center as juvenile recurrent parotitis. On ultrasound examination the left parotid gland appeared enlarged, inhomogeneous, with a colliquative intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests showed an increase of white blood cells and anti-VCA IgM and IgG positivity, with anti-EBNA e anti-EA I negativity. The patient was initially treated with oral antibiotics, but after 10 days the parotid became fluctuating, requiring surgical biopsy and drainage. Postoperative course was regular, with complete remission under oral antibiotic and steroid therapy. Microbiological tests, including cultures for aerobic and anaerobic bacteria, mycobacteria and Bartonella, were negative. Surprisingly, histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltrate with polyclonal plasma cells mostly expressing IgG4 immunoglobulins. Thus, the diagnosis of IgG4 related chronic sialadenitis in recurrent parotitis and recent EBV infection was made. Conclusions IgG4-related sialadenitis is very unusual in children. Histology plays a key role in diagnosis, considering that up to 30% of patients have normal serum IgG4 levels, as shown in our case. The lack of previous histological data makes it impossible to attribute our patient’s previous episodes of parotitis to IgG4-RD, though it is a very consistent possibility.
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Zhang F, Xu J, Zhu Y, Wu Q, Xie X, Shi Y. "Stomach mass" as the first manifestation of IgG4-related disease: a case report. BMC Gastroenterol 2021; 21:442. [PMID: 34819033 PMCID: PMC8611923 DOI: 10.1186/s12876-021-02013-y] [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: 05/22/2021] [Accepted: 11/03/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND IgG4-related disease mainly manifests as organomegaly and is accompanied by tissue fibrosis (Mimori, Mod Rheumatol 29(2):213, 2019) which is frequently confused with tumour (Dawei et al., J Gastroenterol Hepatol 29(12):1375-8, 2020). There are few reports with of IgG4-related disease with the first clinical manifestation involving the stomach. CASE PRESENTATION We present the case of 46-year-old male patient with a "stomach tumour" as the first manifestation of IgG4-related disease. Gastroscopy showed a mass in the stomach, however, the pathology result was chronic inflammation with IgG4 positivity. CT scans of abdomen showed that the stomach wall was thick, the head of the pancreas was swollen, and retroperitoneal fibrosis was severe.The serum IgG4 level was 75 g/L (normal range 0.03-2.01 g/L).After treatment with methylprednisolone for one month, the symptoms were greatly relieved. CONCLUSIONS To reduce the suffering of patients and relieve their financial burden, we should consider the possibility of IgG4-related disease when the initial manifestation is a stomach mass.
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Affiliation(s)
- Fulong Zhang
- Department of Gastroenterology, HangZhou Xixi Hospital, 2 Hengbu Street, Xihu District, HangZhou, 310032, China
| | - Jing Xu
- Department of Gastroenterology, HangZhou Xixi Hospital, 2 Hengbu Street, Xihu District, HangZhou, 310032, China.
| | - Yuandong Zhu
- Department of Gastroenterology, HangZhou Xixi Hospital, 2 Hengbu Street, Xihu District, HangZhou, 310032, China
| | - Qianneng Wu
- Department of Gastroenterology, HangZhou Xixi Hospital, 2 Hengbu Street, Xihu District, HangZhou, 310032, China
| | - Xincheng Xie
- Department of Gastroenterology, HangZhou Xixi Hospital, 2 Hengbu Street, Xihu District, HangZhou, 310032, China
| | - Yan Shi
- Department of Gastroenterology, HangZhou Xixi Hospital, 2 Hengbu Street, Xihu District, HangZhou, 310032, China
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Wang MM, Wang YD, Li L, Wu J, Wei N, Wang CH, Guo CM, Su H, Liu H. Clinical characteristics of autoimmune pancreatitis: Analysis of 19 cases and a literature review. Shijie Huaren Xiaohua Zazhi 2021; 29:1230-1236. [DOI: 10.11569/wcjd.v29.i21.1230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is an immune-mediated disease characterized by pancreatic enlargement, lymphoplasmic cell infiltration, and storiform fibrosis. The pathogenesis is not clear, the epidemiological data in China is still limited, the clinical manifestations are mostly non-specific, and the onset is insidious. Therefore, summarizing the clinical characteristics and prognosis of the disease can guide its diagnosis and treatment in the future.
AIM To analyze the clinical manifestation, serology, imaging features, diagnostic methods, and therapy of autoimmune pancreatitis (AIP).
METHODS A retrospective study was conducted on 19 patients with AIP, who visited the Beijing Shijitan Hospital of Capital Medical University from January 2011 to May 2020. AIP was diagnosed according to the international consensus diagnostic criteria (ICDC) established at the 2010 Congress of the International Association of Pancreatology.
RESULTS The sex ratio (male-to-female) was 16:3. The mean age was 71.0 ± 10.7 years. All of the cases met the diagnostic criteria for AIP type 1. The common symptoms in patients with AIP were obstructive jaundice, hyperglycemia, weight loss, anorexia, fatigue, and abdominal distension. Complications mostly involved the bile duct, lymph nodes, and thyroid gland. IgG4 was increased in 16 patients, all higher than twice normal upper limit; bilirubin was increased in 11 patients; CA199 was increased significantly in 11 patients, but decreased significantly after treatment (P < 0.05). Ultrasound can be used as a screening examination for AIP. CT and MRI were the most importantly used imaging modalities in AIP, and the typical signs were diffuse or local enlargement of the pancreas. EUS also had clinical diagnostic value. The majority of the patients (16/19) received glucocorticoid therapy, six of which were treated with immunosuppressive agents. Two cases were untreated. One case was misdiagnosed and underwent surgery. Most of the patients (14/16) who were treated with steroid had alleviated clinical symptoms and radiological signs, of whom one relapsed, and one died from unknown cause. There was no significant change in the two untreated patients during the follow-up period. One case died after surgery.
CONCLUSION AIP is a rare clinical disease, and its clinical manifestations and serological indicators are not specific.
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Affiliation(s)
- Miao-Miao Wang
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Ya-Dan Wang
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Li Li
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Jing Wu
- Department of Gastroenterology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, China
| | - Nan Wei
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Cang-Hai Wang
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Chun-Mei Guo
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Hui Su
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Hong Liu
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
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Meng QQ, Gao Y, Hu LH, Qian W, Lin H, Zhang YR, Pan J, Li ZS, Xin L, Wang LW. Limited Role of Endoscopic Biliary Drainage Before Steroid Treatment for Autoimmune Pancreatitis With Significant Obstructive Jaundice. Pancreas 2021; 50:e65-e66. [PMID: 34714290 DOI: 10.1097/mpa.0000000000001883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Qian-Qian Meng
- Digestive Endoscopy Center, Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China or
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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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Lee GC, Moon SH. [Recent Updates of Immunoglobulin G4-related Pancreatobiliary Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 75:257-263. [PMID: 32448857 DOI: 10.4166/kjg.2020.75.5.257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 04/16/2020] [Accepted: 04/16/2020] [Indexed: 11/03/2022]
Abstract
Type 1 autoimmune pancreatitis and IgG4-related sclerosing cholangitis (IgG4-SC) are the pancreatobiliary manifestations of IgG4-related disease. IgG4-related disease is a newly named fibroinflammatory condition that is characterized by tumefactive lesions that contain dense lymphoplasmacytic infiltrates rich in IgG4-positive cells and often by elevated serum IgG4 concentrations. IgG4-related pancreatobiliary disease is often disguised as pancreatobiliary malignancies owing to its tumefactive nature and clinical presentations, such as obstructive jaundice. The differentiation of IgG4-SC from primary sclerosing cholangitis is also essential because of the significant differences in treatment responses and prognosis. A timely diagnosis of IgG4-related pancreatobiliary disease can lead clinicians to prescribe adequate glucocorticoid treatment that can reverse the pancreatobiliary duct strictures and obstructive jaundice. On the other hand, the diagnosis of IgG4-related pancreatobiliary disease is sometimes challenging because there is no single diagnostic clinical test. The diagnosis of IgG4-related pancreatobiliary disease rests on fulfilling the diagnostic criteria, including imaging, serology, other organ involvement, histology, and response to steroids. Approximately 50% of patients with IgG4-related pancreatobiliary disease experience relapse, despite IgG4-related pancreatobiliary disease showings a favorable short-term prognosis after glucocorticoid therapy. To reduce the relapse, long maintenance treatment for 3 years may be necessary. The purposes of this review were to emphasize the clinical problem of diagnosing IgG4-related pancreatobiliary disease as well as to highlight the use of the published guidelines for the diagnosis and management of IgG4-related pancreatobiliary disease.
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Affiliation(s)
- Gyu-Chul Lee
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
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Yoon SB, Moon SH, Kim JH, Park JW, Kim SE, Kim MH. Determination of the duration of glucocorticoid therapy in type 1 autoimmune pancreatitis: A systematic review and meta-analysis. Pancreatology 2021; 21:S1424-3903(21)00474-9. [PMID: 34090808 DOI: 10.1016/j.pan.2021.05.303] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/18/2021] [Accepted: 05/21/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy. METHODS We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6-12 months vs. 12-36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated. RESULTS Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9-54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8-49.8%) for 6-12 months, 34.1% (95% CI, 28.6-39.7%) for 12-36 months, and 27.0% (95% CI, 23.4-30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5-34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8-52.4%). Adverse events were comparable between groups. CONCLUSIONS The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.
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Affiliation(s)
- Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea.
| | - Jong Hyeok Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Ji Won Park
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Myung-Hwan Kim
- Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea
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Sekito T, Ishii Y, Serikawa M, Tsuboi T, Kawamura R, Tsushima K, Nakamura S, Hirano T, Fukiage A, Mori T, Ikemoto J, Kiyoshita Y, Saeki S, Tamura Y, Miyamoto S, Chayama K. The role of apparent diffusion coefficient value in the diagnosis of localized type 1 autoimmune pancreatitis: differentiation from pancreatic ductal adenocarcinoma and evaluation of response to steroids. Abdom Radiol (NY) 2021; 46:2014-2024. [PMID: 33386451 DOI: 10.1007/s00261-020-02907-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 12/05/2020] [Accepted: 12/07/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE The aim of this study was to clarify the usefulness of the apparent diffusion coefficient (ADC) value in the differential diagnosis of localized autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC) and the evaluation of response to steroids. METHODS This study retrospectively analyzed 40 patients with localized AIP and 71 patients with PDAC who underwent abdominal MRI with DWI (b = 0 and 1000 s/mm2). Their ADC values at the lesion sites and five MRI findings useful for diagnosing AIP were evaluated. In addition, ADC values before and after steroid therapy were compared in 28 patients with localized AIP. RESULTS The median ADC value was significantly lower for localized AIP than for PDAC (1.057 × 10-3 vs 1.376 × 10-3 mm2/s, P < 0.001). In the ROC curve analysis, the area under the curve was 0.957 and optimal cut-off value of ADC for differentiating localized AIP from PDAC was 1.188 × 10-3 mm2/s. ADC value ≤ 1.188 × 10-3 mm2/s showed the highest sensitivity and accuracy among the MRI findings (92.6% and 90.7%, respectively), and when combined with one or more other MRI findings, showed 96.3% specificity. The median ADC values before and after steroid therapy (mean 7.9 days) were 1.061 × 10-3 and 1.340 × 10-3 mm2/s, respectively, and ADC values were significantly elevated after steroid induction (P < 0.001). CONCLUSION The measurement of ADC values was useful for the differential diagnosis of localized AIP and PDAC and for the early determination of the effect of steroid therapy.
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Affiliation(s)
- Tsuyoshi Sekito
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tomofumi Tsuboi
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ryota Kawamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ken Tsushima
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shinya Nakamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Tetsuro Hirano
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Ayami Fukiage
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takeshi Mori
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Juri Ikemoto
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yusuke Kiyoshita
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Sho Saeki
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yosuke Tamura
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Sayaka Miyamoto
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
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Mukai K, Nishida T, Adachi S, Matsumoto K, Osugi N, Sugimoto A, Nakamatsu D, Yamamoto M, Fukui K, Tamura H, Inada M. Immunoglobulin G4-Hepatopathy with Acute Hepatitis-Like Onset and Marked Centrilobular Necrosis: Clinicopathologically Unique Pattern of Hepatic Injury Related to Immunoglobulin G4-Related Disease. Case Rep Gastroenterol 2021; 15:720-728. [PMID: 34594172 PMCID: PMC8436635 DOI: 10.1159/000516313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 03/19/2021] [Indexed: 11/22/2022] Open
Abstract
A 69-year-old man presented with jaundice and appetite loss. Blood analyses showed elevated aminotransferase levels, hyperbilirubinemia, positivity for antinuclear antibody, elevated immunoglobulin (Ig) G4 levels, and negativity for hepatitis virus markers. Additionally, computed tomography revealed a focal enlargement of the pancreatic body and enhancement of the peripheral bile ducts. Liver biopsy showed interface hepatitis, supporting a clinical diagnosis of autoimmune hepatitis (AIH). Immunohistochemistry revealed that IgG4-bearing plasma cells accounted for more than 60% of the IgG-bearing plasma cells in the portal area. Then, we started oral prednisolone therapy. After tapering, serum transaminase levels became elevated again, and we had to adjust the dose. Azathioprine maintenance therapy was necessary to prevent relapse. We herein report a case of IgG4-hepatopathy with a clinical course similar to that of AIH with acute onset.
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Affiliation(s)
- Kaori Mukai
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Tsutomu Nishida
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Shiro Adachi
- Department of Pathology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Kengo Matsumoto
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Naoto Osugi
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Aya Sugimoto
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Dai Nakamatsu
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Masashi Yamamoto
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Koji Fukui
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Hiromi Tamura
- Department of Pathology, Toyonaka Municipal Hospital, Toyonaka, Japan
| | - Masami Inada
- Department of Gastroenterology and Hepatology, Toyonaka Municipal Hospital, Toyonaka, Japan
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36
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Carrasco Rodríguez R, García Fontán EM, Blanco Ramos M, Juaneda Magdalena Benavides L, Otero Lozano D, Moldes Rodriguez M, Cañizares Carretero MA. Inflammatory pseudotumor and myofibroblastic inflammatory tumor. Diagnostic criteria and prognostic differences. Cir Esp 2021; 100:S0009-739X(21)00112-3. [PMID: 33896608 DOI: 10.1016/j.ciresp.2021.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 03/01/2021] [Accepted: 03/13/2021] [Indexed: 10/21/2022]
Abstract
INTRODUCTION Inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT) are two very rare entities that were formerly included in the same category; however, today they are considered two different diseases due to the neoplastic origin of the IMT. Our objective is to share our experience in the management of these two types of tumors that we must take into account in the differential diagnosis of pulmonary masses or nodules. METHODS Thirteen patients with a pathological diagnosis of IPT and IMT who underwent surgery between 2008 and 2019 were retrospectively studied. We recorded the pre and postoperative information of each one, as well as the survival analysis. RESULTS Of the 13 patients, 8 were men and 5 women. The mean age of presentation was 53,5 years. An atypical segmentectomy was performed in 6 patients; a lobectomy was necessary in 6 and a pneumonectomy in 1 case. In all cases a complete resection was achieved. Diagnosis was possible thanks to histology, immunohistochemical (IHQ) and fluorescent in situ hybridization (FISH) techniques determining the expression of IgG4 and the rearrangement of ALK, respectively. After a median follow up of 49 months, we didńt find any loco-regional or distant recurrence in the patients studied. CONCLUSION IPT and IMT are rare tumors with a very good prognostic. The diagnosis of both entities is based mainly on specific anatomopathological techniques. Surgery has, in most cases, both a diagnostic and therapeutic role.
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Affiliation(s)
| | | | | | | | - Daniel Otero Lozano
- Servicio de Cirugía Torácica, Hospital Álvaro Cunqueiro, Vigo, Pontevedra, España
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Lanzillotta M, Fernàndez-Codina A, Culver E, Ebbo M, Martinez-Valle F, Schleinitz N, Della-Torre E. Emerging therapy options for IgG4-related disease. Expert Rev Clin Immunol 2021; 17:471-483. [PMID: 33689549 DOI: 10.1080/1744666x.2021.1902310] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Awareness of IgG4-related disease (IgG4-RD) is increasing worldwide and specialists are now familiar with most of its clinical manifestations and mimickers. IgG4-RD promptly responds to glucocorticoids and repeated courses are typically used to induce and maintain remission because the disease relapses in most patients. If left untreated, it can lead to organ dysfunction, organ failure and death. Advancement in our understanding of IgG4-RD pathogenesis is leading to the identification of novel therapeutic targets and emerging treatments are now setting the stage for personalized therapies for the future. AREAS COVERED This review focuses on emerging treatment options for IgG4-RD based on our advancing understanding of disease pathophysiology. Research was performed in the English literature on Pubmed and clinicaltrials.gov databases. EXPERT OPINION Glucocorticoids remain the first-line induction treatment for the multi-organ manifestations of IgG4-RD. Alternative immunosuppressive agents for maintaining remission are warranted in order to avoid long-term steroid toxicity, and to offer a more mechanistic and personalized therapeutic strategy. Targeting B and T-lymphocyte activation represents the most promising approach, but randomized controlled trials are eagerly awaited to confirm positive preliminary experiences reported in case series and small cohort studies.
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Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy.,Unit of Immunology, Rheumatology, Allergy and Rare Diseases (Unirar), IRCCS San Raffaele Scientific Institute, ss Milan, Italy
| | - Andreu Fernàndez-Codina
- Internal Medicine Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.,Rheumatology Division and General Internal Medicine division-Windsor Campus, Western University, 268 Grosvenor St, D2-191, Rheumatology Centre, St. Joseph´s Health Care, London, Ontario, Canada
| | - Emma Culver
- Translational Gastroenterology Unit, University of Oxford, Oxford,UK.,Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Mikael Ebbo
- Département De Médecine Interne, Centre De Référence Constitutif Des Cytopénies Auto-immunes De L'adulte (CERECAI), Hôpital De La Timone, Aix-Marseille Université, Assistance publique-Hôpitaux De Marseille, Marseille, France
| | | | - Nicolas Schleinitz
- Département De Médecine Interne, Centre De Référence Constitutif Des Cytopénies Auto-immunes De L'adulte (CERECAI), Hôpital De La Timone, Aix-Marseille Université, Assistance publique-Hôpitaux De Marseille, Marseille, France
| | - 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, Italy
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38
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Guyot A, Lequeu JB, Dransart-Rayé O, Chevallier O, Nguyen M, Charles PE, Mouillot T, Manfredi S, Degand T. [Management of acute pancreatitis. A literature review]. Rev Med Interne 2021; 42:625-632. [PMID: 33676780 DOI: 10.1016/j.revmed.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 12/02/2020] [Accepted: 01/09/2021] [Indexed: 12/07/2022]
Abstract
The management of acute pancreatitis is now fairly codified, with specific recommendations developed by expert groups. These recommendations deal in particular with the minimum initial assessment, recognized severity scores, initial medical management with hyperhydration, preventive anticoagulation, early refeeding, delays in imaging and management of complications. In this work, we have tried to bring together the various recommendations, articles and studies dealing with this subject, based more particularly on European recommendations, in order to guide the management of acute pancreatitis in current practice.
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Affiliation(s)
- A Guyot
- Service d'hépato-gastro-entérologie, CHU de Dijon F.-Mitterrand Dijon-Bourgogne, 14, rue Paul-Gaffarel, 21000 Dijon, France.
| | - J B Lequeu
- Chirurgie viscérale, digestive et endocrinienne, CHU de Dijon, Dijon, France.
| | - O Dransart-Rayé
- Département d'anesthésie réanimation, CHU de Dijon, Dijon, France.
| | - O Chevallier
- Département de radiologie diagnostique et thérapeutique, CHU de Dijon, Dijon, France.
| | - M Nguyen
- Département d'anesthésie réanimation, CHU de Dijon, Dijon, France.
| | - P E Charles
- Médecine intensive réanimation, CHU de Dijon, Dijon, France.
| | - T Mouillot
- Service d'hépato-gastro-entérologie, CHU de Dijon F.-Mitterrand Dijon-Bourgogne, 14, rue Paul-Gaffarel, 21000 Dijon, France.
| | - S Manfredi
- Service d'hépato-gastro-entérologie, CHU de Dijon F.-Mitterrand Dijon-Bourgogne, 14, rue Paul-Gaffarel, 21000 Dijon, France.
| | - T Degand
- Service d'hépato-gastro-entérologie, CHU de Dijon F.-Mitterrand Dijon-Bourgogne, 14, rue Paul-Gaffarel, 21000 Dijon, France.
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Spatola L, Ravera F, Sghirlanzoni MC, Verdesca S, Menegotto A, Querques M, Camozzi ML, Colombo V, Minetti EE. An enigmatic case of IgG4-related nephropathy and an updated review of the literature. Clin Exp Med 2021; 21:493-500. [PMID: 33683496 DOI: 10.1007/s10238-021-00696-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 02/12/2021] [Indexed: 10/22/2022]
Abstract
IgG4-related disease (IgG4-RD) is still an underestimated disorder which affects multiple organs, and its recognition as a distinct clinical disease has been only proved in the recent decades. The renal involvement has been documented in approximately 15% of patients with IgG4-RD, and the typical manifestation is a tubulo-interstitial nephritis. The main histological findings in IgG4-RD are typically a dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and frequently elevated IgG4 serum levels. Herein we report our atypical and peculiar clinical presentation of an IgG4-related nephropathy (IgG4-RN) and the remarkable response to rituximab (RTX) treatment at the renal imaging with computerized tomography assessment. The current nephrological evidences support the renal function recovery after steroids or steroids plus RTX therapy, even if the renal imaging data are not always shown. In a complex and enigmatic clinical scenario such as the IgG4-RN, both the renal biopsy and the renal imaging before and after the immunosuppressive therapy become mandatory tools to thoroughly define the diagnosis, the management and the response to the immunological therapy.
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Affiliation(s)
- Leonardo Spatola
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy.
| | - Federica Ravera
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Maria Chiara Sghirlanzoni
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Simona Verdesca
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Alberto Menegotto
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Marialuisa Querques
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Mario Livio Camozzi
- Division of Pathology, ASST Grande Ospedale Territoriale Niguarda, 20162, Milan, Italy
| | - Valeriana Colombo
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
| | - Enrico Eugenio Minetti
- Division of Nephrology, Dialysis and Renal Transplantation, ASST Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy
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Abstract
Glucocorticoids are the first-line drug for the remission induction therapy of immunoglobulin (Ig) G4-related disease. Achieving drug-free remission using glucocorticoids alone is difficult, however, and many patients require maintenance therapy with glucocorticoids and immunosuppressants. Studies have recently found that the number of peripheral memory B cells and plasmablasts is increased in IgG4-related disease and have indicated the efficacy of rituximab, which, in remission induction therapy, rapidly reduces serum IgG4 levels and has the tapering effect of glucocorticoids. Rituximab has been shown to reduce the risk of relapse more than oral immunosuppressants such as azathioprine. However, maintaining drug-free remission is difficult with a single course of rituximab alone, and many cases require maintenance therapy with rituximab. This article outlines the potential of B-cell targeted therapy, focusing on the efficacy, and safety of rituximab for IgG4-related disease.
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Affiliation(s)
- Motohisa Yamamoto
- Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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41
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Ronchetti S, Ayroldi E, Ricci E, Gentili M, Migliorati G, Riccardi C. A Glance at the Use of Glucocorticoids in Rare Inflammatory and Autoimmune Diseases: Still an Indispensable Pharmacological Tool? Front Immunol 2021; 11:613435. [PMID: 33584696 PMCID: PMC7874096 DOI: 10.3389/fimmu.2020.613435] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 12/04/2020] [Indexed: 12/11/2022] Open
Abstract
Since their discovery, glucocorticoids (GCs) have been used to treat almost all autoimmune and chronic inflammatory diseases, as well as allergies and some forms of malignancies, because of their immunosuppressive and anti-inflammatory effects. Although GCs provide only symptomatic relief and do not eliminate the cause of the pathology, in the majority of treatments, GCs frequently cannot be replaced by other classes of drugs. Consequently, long-term treatments cause adverse effects that may, in turn, lead to new pathologies that sometimes require the withdrawal of GC therapy. Therefore, thus far, researchers have focused their efforts on molecules that have the same efficacy as that of GCs but cause fewer adverse effects. To this end, some GC-induced proteins, such as glucocorticoid-induced leucine zipper (GILZ), have been used as drugs in mouse models of inflammatory pathologies. In this review, we focus on some important but rare autoimmune and chronic inflammatory diseases for which the biomedical research investment in new therapies is less likely. Additionally, we critically evaluate the possibility of treating such diseases with other drugs, either GC-related or unrelated.
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Affiliation(s)
- Simona Ronchetti
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Emira Ayroldi
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Erika Ricci
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Marco Gentili
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Graziella Migliorati
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Carlo Riccardi
- Pharmacology Division, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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IgG4-related disease manifesting as symptoms of appendicitis: Case report and literature review. Clin J Gastroenterol 2021; 14:626-632. [PMID: 33460019 DOI: 10.1007/s12328-020-01337-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Accepted: 12/29/2020] [Indexed: 10/22/2022]
Abstract
Immunoglobulin G subclass 4 (IgG4)-related disease is a recently described fibroinflammatory condition. Reports of appendix involvement are extremely limited. A young man with abdominal pain and symptoms of acute appendicitis accompanied by the finding of an appendix-dependent tumor during surgery is presented. Histopathological study revealed lymphoplasmocytic infiltrate, storiform fibrosis and obliterative phlebitis. The number of IgG4-positive plasma cells was greater than 50 per high power field. Postsurgical steroid treatment and radiological findings are also described.
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43
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Floreani A, Okazaki K, Uchida K, Gershwin ME. IgG4-related disease: Changing epidemiology and new thoughts on a multisystem disease. J Transl Autoimmun 2020; 4:100074. [PMID: 33490938 PMCID: PMC7806798 DOI: 10.1016/j.jtauto.2020.100074] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/19/2020] [Accepted: 12/10/2020] [Indexed: 02/07/2023] Open
Abstract
IgG4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with peculiar histopathologic changes that can affect various organs. In 2012 its unified nomenclature was published, which allows to abandon other synonymous names. Up to now, only little is known about its epidemiology around the world. However, although it is generally considered a rare condition, the number of patients with IgG4-RD is increasing enormously. Likewise, the annual number of publications on this subject has increased progressively. The spectrum of clinical manifestations in IgG4-RD is highly variable, depending on the severity of the disease as well as the presence of organ(s) involvement. This review gives an overview on changing epidemiology of IgG4-RD focusing the attention on the large cohorts of patients published in the literature.
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Affiliation(s)
- Annarosa Floreani
- Scientific Consultant IRCCS Negrar, Verona, Italy
- Senior Scholar, University of Padova, Italy
| | - Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - M. Eric Gershwin
- Division of Rheumatology Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA
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Abid H, Alaoui MEHHBE, Lamrani MYA, Figuigui M, Ahmed BC, Lahmidani N, Yousfi ME, Benajah DA, Maaroufi M, Abkari ME, Ibrahimi SA, Aqodad N. [IgG4-related disease: about 3 cases]. Pan Afr Med J 2020; 36:364. [PMID: 33235641 PMCID: PMC7666702 DOI: 10.11604/pamj.2020.36.364.24835] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 07/29/2020] [Indexed: 01/11/2023] Open
Abstract
IgG4-Related disease (IgG4-RD), formerly known as IgG4-related autoimmune polyexocrinopathy, is a new condition including Plasminogen Activator Inhibitor-1 (PAI-1). It can affect different organs (central nervous system, salivary glands, thyroid, lungs, pancreas, bile ducts, liver, digestive tract, kidneys, prostate, etc.) with symptoms depending on the organ that is affected. It is more common in men older than 50 years of age. Its incidence and prevalence are poorly known because it is an uncommon disease. It is most common in Asia, accounting for only 20-30% of PAI in the Western world. Diagnosis is based on histological examination which shows dense lymphoplasmocytic infiltration in the organ affected associated with IgG4-positive plasma cells (immunohistochemistry), organ fibrosis and obliterating venulitis, all this in the context of increased serum IgG4 levels in more than 80% of cases. Patients are sensitive to corticosteroid therapy, with a high risk of relapse after discontinuation of corticosteroid therapy. This leads to the use of immunomodulators, mainly: thiopurines (azathioprine or 6-mercaptopurine), methotrexate and more recently rituximab, which can also be used as induction therapy. Given recent advances, accurate histological and clinical criteria are currently known to limit inappropriate management such as surgery. However, knowledge gaps remain concerning: pathophysiology, identification of specific biomarkers other than IgG4, natural history of the disease and long-term cancer risk assessment, performances of diagnostic tools such as endoscopic ultrasound-guided pancreatic biopsy. As well, consensual international management should be defined in the early stages of the disease and when patients develop recurrences. The purpose of this study was to report 3 cases of IgG4-Related disease on the basis of clinical and radiological criteria as well as therapeutic response.
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Affiliation(s)
- Hakima Abid
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | | | - Moulay Youssef Alaoui Lamrani
- Service de Radiologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc.,Faculté de Médecine et de Pharmacie, Université Sidi Mohammed Ben Abdellah, Fès, Maroc
| | - Mouna Figuigui
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Beiba Cheikh Ahmed
- Service de Radiologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc.,Faculté de Médecine et de Pharmacie, Université Sidi Mohammed Ben Abdellah, Fès, Maroc
| | - Nada Lahmidani
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Mounia El Yousfi
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Dafr-Allah Benajah
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Mustapha Maaroufi
- Service de Radiologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc.,Faculté de Médecine et de Pharmacie, Université Sidi Mohammed Ben Abdellah, Fès, Maroc
| | - Mohammed El Abkari
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Sidi Adil Ibrahimi
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Hassan II, Fès, Maroc
| | - Nourdin Aqodad
- Service d´Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire Ibn Zohr, Agadir, Maroc
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Noguchi K, Nakai Y, Mizuno S, Hirano K, Kanai S, Suzuki Y, Inokuma A, Sato T, Hakuta R, Ishigaki K, Saito K, Saito T, Hamada T, Takahara N, Kogure H, Isayama H, Koike K. Role of Endoscopic Ultrasonography-Guided Fine Needle Aspiration/Biopsy in the Diagnosis of Autoimmune Pancreatitis. Diagnostics (Basel) 2020; 10:diagnostics10110954. [PMID: 33203118 PMCID: PMC7698022 DOI: 10.3390/diagnostics10110954] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/12/2020] [Accepted: 11/12/2020] [Indexed: 12/12/2022] Open
Abstract
Type 1 autoimmune pancreatitis (AIP) is histologically characterized by lymphoplasmacytic sclerosing pancreatitis (LPSP). Recently, the diagnostic yield of endoscopic ultrasonography-guided fine needle aspiration/biopsy (EUS-FNA/B) for AIP has been reported. However, its role in the diagnostic flow of AIP is not fully elucidated. We retrospectively reviewed 53 consecutive patients who were suspected with AIP and underwent EUS-FNA/B. We evaluated the contribution of EUS-FNA/B to the diagnosis of AIP before considering response to steroid therapy among patients with diffuse enlargement of the pancreas and those with focal enlargement, respectively. Twenty-two patients showed diffuse pancreatic enlargement and 31 showed focal enlargement. The final diagnosis was definitive AIP in 32 patients, probable AIP in 2, possible AIP in 1, and mass-forming focal pancreatitis in 18. There was no change in diagnosis after EUS-FNA/B among patients with diffuse pancreatic enlargement, while diagnosis changed in 38.7% (12/31) among those with focal enlargement—there was a probable to definitive diagnosis in 4 patients, unspecified to definitive in 3, and unspecified to probable in 5. EUS-FNB provided a significantly higher sensitivity for typical pathological findings of LPSP than EUS-FNA, and 10 patients were diagnosed as pathologically definitive AIP by EUS-FNB, though none were by EUS-FNA (p = 0.002). EUS-FNA/B was useful in the diagnosis of focal type AIP, and steroid therapy could be introduced after the diagnosis was confirmed. Meanwhile, EUS-FNA/B provided no contribution to diagnosis of diffuse type AIP. EUS-FNB showed a higher diagnostic yield than FNA.
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Affiliation(s)
- Kensaku Noguchi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Yousuke Nakai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
- Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital, Tokyo 113-8655, Japan
- Correspondence: ; Tel.: +81-3-3815-5411; Fax: +81-3-5800-8812
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Kenji Hirano
- Department of Gastroenterology, Tokyo Takanawa Hospital, Tokyo 108-8606, Japan;
| | - Sachiko Kanai
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Yukari Suzuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Akiyuki Inokuma
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Tatsuya Sato
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Ryunosuke Hakuta
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Kazunaga Ishigaki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Kei Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Tomotaka Saito
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Naminatsu Takahara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Hirofumi Kogure
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
| | - Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo 113-8531, Japan;
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan; (K.N.); (S.M.); (S.K.); (Y.S.); (A.I.); (T.S.); (R.H.); (K.I.); (K.S.); (T.S.); (T.H.); (N.T.); (H.K.); (K.K.)
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Blaho M, Dítě P, Kunovský L, Kianička B. Autoimmune pancreatitis - An ongoing challenge. Adv Med Sci 2020; 65:403-408. [PMID: 32805624 DOI: 10.1016/j.advms.2020.07.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 04/15/2020] [Accepted: 07/13/2020] [Indexed: 02/07/2023]
Abstract
Autoimmune pancreatitis is a rare form of chronic pancreatitis. The first descriptions of the disease date back to the 1990s. Etiology is multifactorial, with the use of genetic, environmental and complex immunological mechanisms. It is classified into two subtypes. Type 1 is part of a group of diseases called IgG4-related disease. Clinically is autoimmune pancreatitis manifested by icterus and abdominal discomfort. It can rarely present as acute pancreatitis. There is also a completely asymptomatic form of the disease. The diagnosis is based on abnormalities in histology, imaging methods, serology, the involvement of other organs in relation to IgG4-related disease, and a significant positive response to corticosteroid therapy. Differential diagnosis between the focal form of autoimmune pancreatitis and pancreatic cancer can be complicated, with endosonography playing an important role. In the treatment, we use corticosteroids and other immunosuppressants including biological therapy. Patients with the asymptomatic disease should also be treated to prevent late complications and exocrine and endocrine insufficiency. In addition to drug treatment, endoscopic and/or surgical treatment may be necessary. Even after recovery, the disease can relapse. The relationship between autoimmune pancreatitis and malignancies has not been clearly confirmed. The goal of this review is to provide a comprehensive look at autoimmune pancreatitis and translate latest scientific knowledge into clinical practice.
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Affiliation(s)
- Martin Blaho
- Department of Internal Medicine, Department of Gastroenterology, University Hospital Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; Department of Internal Medicine II - Gastroenterology and Geriatrics, Faculty of Medicine, Palacký University Olomouc and University Hospital, Olomouc, Czech Republic
| | - Petr Dítě
- Department of Internal Medicine, Department of Gastroenterology, University Hospital Ostrava, Ostrava, Czech Republic; Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Lumír Kunovský
- Department of Gastroenterology and Internal Medicine, University Hospital Brno, Brno, Czech Republic; Department of Surgery, University Hospital Brno, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Bohuslav Kianička
- Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2nd Department of Internal Medicine, Department of Gastroenterology, St. Anne's University Hospital, Brno, Czech Republic.
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Tumour of the orbit and pterygopalatine fossa: delayed recognition of possible IgG4-related disease. Contemp Oncol (Pozn) 2020; 24:136-139. [PMID: 32774140 PMCID: PMC7403764 DOI: 10.5114/wo.2020.97638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 06/07/2020] [Indexed: 01/13/2023] Open
Abstract
Introduction IgG4-related disease (IgG4-RD) is a systemic fibrotic-inflammatory disease characterised by elevated serum concentration of IgG4 and tissue infiltration by plasma cells. IgG4-RD is a newly recognised fibro-inflammatory condition, characterised by organ mass lesions, special histopathological appearance, and - often but not always - elevated serum IgG4 concentrations. IgG4-RD is a separate, clinically distinct disease entity, but, due to its heterogeneous manifestation, it is a subject of interest of physicians of various specialties. Histopathological examination is the gold standard in the diagnosis. Case report In the paper we discuss the case of a 13-year-old patient who had been diagnosed with fully symptomatic IgG4-RD nine years after initial manifestation. Although IgG4-RD is diagnosed markedly more often in adults than in children, in this case report we would like to emphasise that the disease may also occur in paediatric patients, and it constitutes both a diagnostic and therapeutic challenge in this age group. Conclusions IgG4-RD is a poorly recognised disease, especially in the paediatric population. To the best of our knowledge, case reports on IgG4-RD in paediatric patients available in the literature are sparse. The non-specific and heterogeneous manifestation may hinder the diagnostic process, and in some cases the disease is diagnosed accidentally, especially when it is asymptomatic. Since 2015, the first-line treatment in IgG4-RD has been glucocorticoids; however, combination therapies should not be underestimated as another method to achieve permanent remission.
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Samji V, Haykal T, Danish R, Bachuwa G. A Case of an IgG4-Related Disease Mimicking Malignancy and Resolving With Steroids. Cureus 2020; 12:e9476. [PMID: 32874805 PMCID: PMC7455463 DOI: 10.7759/cureus.9476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
A 77-year-old African American female was referred to oncology for evaluation of an adrenal fossa mass detected on computed tomography scan of the abdomen and pelvis (CT-scan A/P) that was ordered as a work-up for painless hematuria. Further evaluation by positron emission tomography (PET) scan showed hypermetabolic masses in the left suprarenal and right iliac region. The biopsy of the right iliac mass was consistent with IgG4-related disease (IgG4RD). It was supported by an elevated serum IgG4 level. She was treated with prednisone with a good response.
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Abstract
IgG4 related disease was recognized as a unified disease entity only 15 years ago. Awareness of IgG4 related disease has increased worldwide since then, and specialists are now familiar with most of its clinical manifestations. Involvement of the pancreato-biliary tract, retroperitoneum/aorta, head and neck, and salivary glands are the most frequently observed disease phenotypes, differing in epidemiological features, serological findings, and prognostic outcomes. In view of this multifaceted presentation, IgG4 related disease represents a great mimicker of many neoplastic, inflammatory, and infectious conditions. Histopathology remains key to diagnosis because reliable biomarkers are lacking. Recently released classification criteria will be invaluable in improving early recognition of the disease. IgG4 related disease is highly treatable and responds promptly to glucocorticoids, but it can lead to end stage organ failure and even death if unrecognized. Prolonged courses of corticosteroids are often needed to maintain remission because the disease relapses in most patients. Rapid advancement in our understanding of the pathophysiology of IgG4 related disease is leading to the identification of novel therapeutic targets and possible personalized approaches to treatment.
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Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gaia Mancuso
- 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, 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, Milan, Italy
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50
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Fernández-Codina A, Orozco-Gálvez O, Martínez-Valle F. Therapeutic Options in IgG4-Related Disease. CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY 2020. [DOI: 10.1007/s40674-020-00147-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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