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Ujita W, Kamisawa T, Chiba K, Nakahodo J, Tabata H, Setoguchi K, Igarashi Y, Matsuda T. New insights into predictors of autoimmune pancreatitis relapse after steroid therapy. Scand J Gastroenterol 2024; 59:1202-1208. [PMID: 39257347 DOI: 10.1080/00365521.2024.2398771] [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: 07/04/2024] [Revised: 08/08/2024] [Accepted: 08/27/2024] [Indexed: 09/12/2024]
Abstract
OBJECTIVES While autoimmune pancreatitis (AIP) responds well to steroid therapy, the high relapse rate in type 1 AIP remains a critical problem. The present study examined predictors of relapse of type 1 AIP following steroid therapy. MATERIALS AND METHODS Nine factors potentially predictive of relapse were analyzed in 81 AIP patients receiving steroid therapy with follow-up ≥ 12 months. The rate of serum IgG4 decrease following steroid therapy was calculated by dividing the difference between serum IgG4 values before and at two months after the start of steroid by the IgG4 value before steroid. RESULTS A relapse occurred in 11 patients (13.5%) during a median of 38 months. Multivariate analysis revealed that the presence of IgG4-related retroperitoneal fibrosis (HR: 5.59; 95% CI: 1.42-22.0; p = 0.014) and the low rate of serum IgG4 decrease after steroid therapy (HR: 0.048; 95% CI: 0.005-0.46; p = 0.008) were significant, independent predictors of AIP relapse. The cut-off value based on receiver operating characteristic curve data for the rate of serum IgG4 decrease before and at two months after steroid therapy distinguishing patients with and without a relapse was 0.65. Using this cut-off value, the area under the curve, sensitivity, and specificity were found to be 0.63, 0.73, and 0.60, respectively. CONCLUSION The low rate of serum IgG4 decrease after the start of steroid therapy and the presence of IgG4-related retroperitoneal fibrosis were predictive of type 1 AIP relapse. Cautious, gradual tapering of steroid dosage and longer maintenance therapy are recommended for patients with these factors.
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Affiliation(s)
- Wataru Ujita
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Tokyo, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
- Center of IgG4-Related Disease, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kazuro Chiba
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
- Center of IgG4-Related Disease, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Jun Nakahodo
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Hiroki Tabata
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Keigo Setoguchi
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
- Center of IgG4-Related Disease, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Yoshinori Igarashi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Tokyo, Japan
| | - Takahisa Matsuda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, Tokyo, Japan
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Kurebayashi M, Hashimoto A, Kawachi M, Sawai S, Ono T, Tahara Y, Kuroda N, Yoshizawa N, Fuke H, Shimizu A. A case of ulcerative colitis with a variety of autoimmune diseases including ankylosing spondylitis, type 2 autoimmune pancreatitis, and primary sclerosing cholangitis. Clin J Gastroenterol 2024; 17:928-935. [PMID: 38861196 DOI: 10.1007/s12328-024-02001-1] [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: 09/29/2023] [Accepted: 06/05/2024] [Indexed: 06/12/2024]
Abstract
Ankylosing spondylitis (AS), primary sclerosing cholangitis (PSC), and autoimmune pancreatitis (AIP) are known as extraintestinal manifestations (EIMs) of ulcerative colitis (UC). A 74-year-old Japanese man visited our hospital because of white stool. He had been diagnosed with AS when he was 30 years old, and he was HLA-B27-positive. Based on various examination results, it was suspected that AIP had caused bile duct stricture. During the clinical course, he was diagnosed with UC and PSC. Then, AIP was diagnosed because he had localized pancreatic enlargement, irregular stenosis of the main pancreatic duct, PSC, and no tumor cells of pancreas. A patient with all four of these diseases, AS, AIP, PSC, and UC, is very rare. Therefore, we report a quite rare case with three EIMs (AS, PSC, and AIP) of UC.
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Affiliation(s)
- Marie Kurebayashi
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan.
| | - Akira Hashimoto
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Mizuki Kawachi
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Shoma Sawai
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Takahiro Ono
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Yuichi Tahara
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Naoki Kuroda
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Naohiko Yoshizawa
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Hiroyuki Fuke
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
| | - Atsuya Shimizu
- Department of Internal Medicine, Saiseikai Matsusaka General Hospital, 1-15-6 Asahimachi, Matsusaka-shi, Mie, 515-8557, Japan
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Li MZ, Guo T, Feng YL, Zhang SY, Bai XY, Wu X, Xu K, Yang AM. Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy. Hepatobiliary Pancreat Dis Int 2024; 23:393-398. [PMID: 37121837 DOI: 10.1016/j.hbpd.2023.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 04/14/2023] [Indexed: 05/02/2023]
Abstract
BACKGROUND A high prevalence of diabetes mellitus (DM) coexisting with autoimmune pancreatitis (AIP) is observed. However, evidence on the circumstances under which corticosteroid therapy (CST) for AIP improves or worsens DM is scarce. This study aimed to demonstrate and identify predictors of DM control under the influence of CST. METHODS Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed: pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as 'improvement' and 'non-improvement' (including 'no change' and 'exacerbation'). RESULTS Among 101 patients with type 1 AIP, 52 (51.5%) patients were complicated with DM at the time of AIP diagnosis, with 36 patients in the cDM group and 16 patients in the pDM group. The incidences of diffuse pancreatic swelling (72.2%) and pancreatic body/tail involvement (91.7%) were significantly higher in the cDM group than in both the pDM and nDM groups. Of the 52 patients with DM, CST was administered in 48 cases. Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase (GGT) level at AIP diagnosis [odds ratio (OR) = 0.032, 95% confidence interval (CI): 0.003-0.412, P = 0.008] and pancreatic atrophy after CST (OR = 0.027, 95% CI: 0.003-0.295, P = 0.003) were negatively associated with DM control improvement. CONCLUSIONS Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis. CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis, particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.
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Affiliation(s)
- Mei-Zi Li
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Tao Guo
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yun-Lu Feng
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Sheng-Yu Zhang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Xiao-Yin Bai
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Xi Wu
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Kai Xu
- Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Ai-Ming Yang
- Department of Gastroenterology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
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Jain AK, Sundaram S, Tyagi U, Kale A, Patkar S, Patil P, Deodhar K, Ramadwar M, Yadav S, Chaudhari V, Shrikhande S, Mehta S. IgG4-related disorders of the gastrointestinal tract: Experience from a tertiary care centre with systematic review of Indian literature. Indian J Gastroenterol 2024; 43:548-556. [PMID: 37823986 DOI: 10.1007/s12664-023-01437-6] [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: 05/12/2023] [Accepted: 07/24/2023] [Indexed: 10/13/2023]
Abstract
INTRODUCTION IgG4-related disease (IgG4-RD) is a rare disease entity in India. We aimed at studying the clinical profile of IgG4-RD of gastrointestinal tract (GIT) from our centre, while systematically reviewing data from India. METHODS Retrospective review of IgG4-RD of GIT was done using electronic medical records between January 2013 and July 2022. Literature search was done for studies of IgG4-RD of the GIT reported from India from 2000 till January 2023. Case series, case reports of IgG4-RD of GIT and case reports describing GIT with multi-organ involvement were included in the review. Primary outcome measure was response to treatment. Secondary outcome measure was relapse after remission. RESULTS Thirty-one patients were included with 71% (22/31) having autoimmune pancreatitis. The diagnosis was achieved on surgical specimen in 35% (11/31) patients. Steroid was given to 64% (20/31) patients with remission achieved in 70% (14/20) patients. Four patients exhibitted response to prolonged course of steroids with maintenance azathioprine. Relapse was seen in four (20%) patients who achieved remission. Of 731 articles screened, 48 studies (four case series and 44 case reports) were included in the literature review. Of 95 patients described, steroids were given to 65.2% (62/95), while surgery was done in 33.6% (32/95). Remission was seen in 96.6% (85/88) with relapse occurring in 11.4% (10/88) patients on follow-up. CONCLUSION One-third patients of IgG4-RD of GIT are diagnosed after surgery. Response to steroids is good with relapse occurring in up to 12% patients.
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Affiliation(s)
- Aadish Kumar Jain
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Sridhar Sundaram
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India.
| | - Unique Tyagi
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Aditya Kale
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Shraddha Patkar
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Prachi Patil
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
| | - Kedar Deodhar
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Mukta Ramadwar
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Subhash Yadav
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Vikram Chaudhari
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Shailesh Shrikhande
- Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, 400 012, India
| | - Shaesta Mehta
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Hospital, Homi Bhabha National Institute, Dr. E Borges Road, Parel, Mumbai, 400 012, India
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de Pretis N, Martinelli L, Palmeri E, Caldart F, Crucillà S, Zorzi A, Brillo A, Crinò SF, Conti Bellocchi MC, Bernardoni L, De Marchi G, Amodio A, Campagnola P, Ciccocioppo R, Gabbrielli A, Marcon A, Frulloni L. The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis. Pancreatology 2024; 24:538-544. [PMID: 38693038 DOI: 10.1016/j.pan.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND/OBJECTIVES Autoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. METHODS 312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). RESULTS One-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15-379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15-340) to 202 (40-387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. CONCLUSION The inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.
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Affiliation(s)
- Nicolò de Pretis
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy.
| | - Luigi Martinelli
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Enrico Palmeri
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Federico Caldart
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Crucillà
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Alberto Zorzi
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Alessandro Brillo
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | | | | | - Laura Bernardoni
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Antonio Amodio
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Pietro Campagnola
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Armando Gabbrielli
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Alessandro Marcon
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, University of Verona, Verona, Italy
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Zen Y. Autoimmune pancreatitis: Biopsy interpretation and differential diagnosis. Semin Diagn Pathol 2024; 41:79-87. [PMID: 38184420 DOI: 10.1053/j.semdp.2024.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 01/02/2024] [Indexed: 01/08/2024]
Abstract
Autoimmune pancreatitis (AIP) is classified into type 1 (IgG4-related) and type 2 (IgG4-unrelated) and the interpretation of pancreatic biopsy findings plays a crucial role in their diagnosis. Needle biopsy of type 1 AIP in the acute or subacute phase shows a diffuse lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and the infiltration of many IgG4-positive plasma cells. In a later phase, changes become less inflammatory and more fibrotic, making interpretations more challenging. Confirmation of the lack of 'negative' findings that are unlikely to occur in type 1 AIP (e.g., neutrophilic infiltration, abscess) is important to avoid an overdiagnosis. The number of IgG4-positive plasma cells increases to >10 cells/high-power field (hpf), and the IgG4/IgG-positive plasma cell ratio exceeds 40 %. However, these are minimal criteria and typical cases show >30 positive cells/hpf and a ratio >70 % even in biopsy specimens. Therefore, cases with a borderline increase in this number or ratio need to be diagnosed with caution. In cases of ductal adenocarcinoma, the upstream pancreas rarely shows type 1 AIP-like changes; however, the ratio of IgG4/IgG-positive plasma cells is typically <40 %. Although the identification of a granulocytic epithelial lesion (GEL) is crucial for type 2 AIP, this finding needs to be interpreted in conjunction with a background dense lymphoplasmacytic infiltrate. An isolated neutrophilic duct injury can occur in peritumoral or obstructive pancreatitis. Drug-induced pancreatitis in patients with inflammatory bowel disease often mimics type 2 AIP clinically and pathologically. IL-8 and PD-L1 are potential ancillary immunohistochemical markers for type 2 AIP, requiring validation studies.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK.
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Chen S, Wang G, Wu L, Chen D, Fang K, Liu W, Xu B, Zhai YQ, Li M. Potential Added Value of 18F-FDG PET Metabolic Parameters in Predicting Disease Relapse in Type 1 Autoimmune Pancreatitis. BMC Gastroenterol 2024; 24:37. [PMID: 38233765 PMCID: PMC10792883 DOI: 10.1186/s12876-023-03113-7] [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: 05/02/2023] [Accepted: 12/29/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND The predictive value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters for predicting AIP relapse is currently unknown. This study firstly explored the value of 18F-FDG PET/CT parameters as predictors of type 1 AIP relapse. METHODS This multicenter retrospective cohort study analyzed 51 patients who received 18F-FDG PET/CT prior to treatment and did not receive maintenance therapy after remission. The study collected baseline characteristics and clinical data and conducted qualitative and semi-quantitative analysis of pancreatic lesions and extrapancreatic organs. The study used three thresholds to select the boundaries of pancreatic lesions to evaluate metabolic parameters, including the maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and tumor-to-normal liver standard uptake value ratio (SUVR). Univariate and multivariate analyses were performed to identify independent predictors and build a recurrence prediction model. The model was internally validated using the bootstrap method and a nomogram was created for clinical application. RESULTS In the univariable analysis, the relapsed group showed higher levels of SUVmax (6.0 ± 1.6 vs. 5.2 ± 1.1; P = 0.047), SUVR (2.3 [2.0-3.0] vs. 2.0 [1.6-2.4]; P = 0.026), and TLG2.5 (234.5 ± 149.1 vs. 139.6 ± 102.5; P = 0.020) among the 18F-FDG PET metabolic parameters compared to the non-relapsed group. In the multivariable analysis, serum IgG4 (OR, 1.001; 95% CI, 1.000-1.002; P = 0.014) and TLG2.5 (OR, 1.007; 95% CI, 1.002-1.013; P = 0.012) were independent predictors associated with relapse of type 1 AIP. A receiver-operating characteristic curve of the predictive model with these two predictors demonstrated an area under the curve of 0.806. CONCLUSION 18F-FDG PET/CT metabolic parameters, particularly TLG2.5, are potential predictors for relapse in patients with type 1 AIP. A multiparameter model that includes IgG4 and TLG2.5 can enhance the ability to predict AIP relapse.
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Affiliation(s)
- Shengxin Chen
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
- Graduate School, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Guanyun Wang
- Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
- Nuclear Medicine Department, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, Xicheng District, Beijing, 100050, China
| | - Lang Wu
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Dexin Chen
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Kaixuan Fang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Wenjing Liu
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Baixuan Xu
- Department of Nuclear Medicine, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China
| | - Ya-Qi Zhai
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.
| | - Mingyang Li
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China.
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8
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Jaber F, Elfert K, Alsakarneh S, Beran A, Jaber M, Gangwani MK, Abboud Y. Clinical characteristics and outcomes of autoimmune pancreatitis based on serum immunoglobulin G4 levels: A single-center, retrospective cohort study. World J Gastroenterol 2023; 29:6161-6164. [PMID: 38186685 PMCID: PMC10768407 DOI: 10.3748/wjg.v29.i47.6161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 11/10/2023] [Accepted: 11/21/2023] [Indexed: 12/19/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a complex, poorly understood disease gaining increasing attention. "Clinical Characteristics and Outcome of AIP Based on Serum IgG4 levels," investigated AIP with a focus on serum immunoglobulin (Ig) G4 levels. The 213 patients with AIP were classified according to serum IgG4 levels: Abnormal (elevated) and normal. Patients with higher IgG4 levels exhibited a more active immune system and increased relapse rates. Beyond IgG4, the IgA levels and age independently contributed to relapse risk, guiding risk assessment and tailored treatments for better outcomes. However, limitations persist, such as no IgA correlation with IgG4 levels, absent data on autoantibody-positive AIP cases critical for Asian diagnostic criteria, and unexplored relapse rates in high serum IgG AIP by subtype. Genetic factors and family histories were not addressed. As the understanding and referral of seronegative AIPs increase, there's a growing need for commercially available, highly sensitive, and specific autoantibodies to aid in diagnosing individuals with low or absent serum IgG4 levels.
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Affiliation(s)
- Fouad Jaber
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas, MO 64108, United States
| | - Khaled Elfert
- Department of Internal Medicine, SBH Health System, New York, NY 10457, United States
| | - Saqr Alsakarneh
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas, MO 64108, United States
| | - Azizullah Beran
- Department of Gastroenterology, Indiana University, 420 University Blvd, Indianapolis, IN 46202, United States
| | - Mohammed Jaber
- Department of Medical Education, Al Azhar University School of Medicine, Gaza P.O.Box 108, Palestine
| | - Manesh Kumar Gangwani
- Department of Internal Medicine, The University of Toledo, Toledo, OH 43606, United States
| | - Yazan Abboud
- Department of Internal Medicine, Rutgers New Jersey Medical School, Newar, NJ 57873, United States
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9
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Li Y, Song H, Meng X, Li R, Leung PSC, Gershwin ME, Zhang S, Sun S, Song J. Autoimmune pancreatitis type 2 (idiopathic duct-centric pancreatitis): A comprehensive review. J Autoimmun 2023; 140:103121. [PMID: 37826920 DOI: 10.1016/j.jaut.2023.103121] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/20/2023] [Accepted: 10/02/2023] [Indexed: 10/14/2023]
Abstract
Autoimmune pancreatitis (AIP) is an uncommon fibro-inflammatory disorder precipitated by autoimmune/inflammatory reactions. Currently, there are two clinical subtypes of AIP (type 1 [AIP-1] and type 2 [AIP-2]) that correspond to two histologic descriptors (lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis, respectively). While our understanding of AIP-1 has evolved considerably over the years, little is known about AIP-2 due to its rarity, often leading to misdiagnosis, delayed treatment, and even unnecessary surgical resection. Compared to AIP-1, AIP-2 exhibits distinct clinical and histologic features. Because AIP-2 is a pancreas-restricted disease without a specific serum marker, the evaluation of histologic features (e.g., granulocytic epithelial lesions) is essential for an accurate diagnosis. Patients with AIP-2 respond well to glucocorticoids, with anti-tumor necrosis factor-alpha antibodies as a promising alternative therapy. The prognosis of AIP-2 is generally favorable and relapse is uncommon. Here, we provide an overview of our current knowledge on the clinical features, diagnosis, therapeutic regimens, prognosis, and putative mechanisms underlying AIP-2. Notably, the diagnostic differentiation between AIP-2, especially the mass-forming/focal type, and pancreatic cancer is important, but challenging. In this regard, endoscopic ultrasound-guided core biopsy has a key role, but novel diagnostic markers and modalities are clearly needed.
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Affiliation(s)
- Yang Li
- Department of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Hanyi Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Xiangzhen Meng
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Runzhuo Li
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China
| | - Patrick S C Leung
- Division of Rheumatology/Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA 95616 USA
| | - M Eric Gershwin
- Division of Rheumatology/Allergy and Clinical Immunology, School of Medicine, University of California, Davis, CA 95616 USA
| | - Shucheng Zhang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China.
| | - Siyu Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China.
| | - Junmin Song
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, PR China.
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Hajibandeh S, Jurdon R, Heaton E, Hajibandeh S, O'Reilly D. The risk of recurrent pancreatitis after first episode of acute pancreatitis in relation to etiology and severity of disease: A systematic review, meta-analysis and meta-regression analysis. J Gastroenterol Hepatol 2023; 38:1718-1733. [PMID: 37366550 DOI: 10.1111/jgh.16264] [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: 04/08/2023] [Accepted: 06/05/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND AND AIM The study aims to determine and quantify the stratified risk of recurrent pancreatitis (RP) after the first episode of acute pancreatitis in relation to etiology and severity of disease. METHODS A systematic review and meta-analysis in compliance with PRISMA statement standards was conducted. A search of electronic information sources was conducted to identify all studies investigating the risk of RP after the first episode of acute pancreatitis. Proportion meta-analysis models using random effects were constructed to calculate the weighted summary risks of RP. Meta-regression was performed to evaluate the effect of different variables on the pooled outcomes. RESULTS Analysis of 57,815 patients from 42 studies showed that the risk of RP after first episode was 19.8% (95% confidence interval [CI] 17.5-22.1%). The risk of RP was 11.9% (10.2-13.5%) after gallstone pancreatitis, 28.7% (23.5-33.9%) after alcohol-induced pancreatitis, 30.3% (15.5-45.0%) after hyperlipidemia-induced pancreatitis, 38.1% (28.9-47.3%) after autoimmune pancreatitis, 15.1% (11.6-18.6%) after idiopathic pancreatitis, 22.0% (16.9-27.1%) after mild pancreatitis, 23.9% (12.9-34.8%) after moderate pancreatitis, 21.6% (14.6-28.7%) after severe pancreatitis, and 6.6% (4.1-9.2%) after cholecystectomy following gallstone pancreatitis. Meta-regression confirmed that the results were not affected by the year of study (P = 0.541), sample size (P = 0.064), length of follow-up (P = 0.348), and age of patients (P = 0.138) in the included studies. CONCLUSIONS The risk of RP after the first episode of acute pancreatitis seems to be affected by the etiology of pancreatitis but not the severity of disease. The risks seem to be higher in patients with autoimmune pancreatitis, hyperlipidemia-induced pancreatitis, and alcohol-induced pancreatitis and lower in patients with gallstone pancreatitis and idiopathic pancreatitis.
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Affiliation(s)
- Shahab Hajibandeh
- Department of General Surgery, University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, UK
| | | | - Emily Heaton
- James Cook University Hospital, Middlesbrough, UK
| | - Shahin Hajibandeh
- Department of General Surgery, Royal Stoke University Hospital, Stoke-on-Trent, UK
| | - David O'Reilly
- Department of General Surgery, University Hospital of Wales, Cardiff and Vale NHS Trust, Cardiff, UK
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11
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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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Yu ZQ, Bai XY, Ruan GC, Han W, Xu TM, Zhang MY, Wang BM, Zhang YJ, Guo MY, Yang H. Autoimmune pancreatitis associated with inflammatory bowel diseases: A retrospectively bidirectional case-control study in China. J Dig Dis 2023; 24:452-460. [PMID: 37503771 DOI: 10.1111/1751-2980.13209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/02/2023] [Accepted: 07/25/2023] [Indexed: 07/29/2023]
Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) is a rare and enigmatic immune-mediated inflammatory disease. We aimed to investigate the prevalence, characteristics, and associated factors of AIP-inflammatory bowel disease (IBD) in China. METHODS A retrospective bidirectional case-control study was performed. The diagnoses of IBD and AIP were made based on the European Crohn's and Colitis Organization guidelines and the International Consensus Diagnostic Criteria. IBD controls were matched by age, sex, and IBD type at a ratio of 1:4, while AIP controls were matched by AIP types. RESULTS The age-standardized prevalence of AIP-IBD patients in the IBD and AIP population were 292.0 and 8151.93 per 100 000 population, respectively. IBD patients had a higher risk of AIP compared to non-IBD patients (odds ratio 8.4, 95% confidence interval 4.7-14.9, P < 0.0001), and AIP patients had a higher risk of developing IBD compared to the general population in China. The mean age at diagnosis of IBD and AIP was 34.83 years and 40.42 years. IBD was diagnosed before AIP in seven cases. The median total IBD and AIP duration was 43.5 months and 13.5 months. Use of mesalamine and tuberculosis were associated with AIP in IBD patients (P = 0.031). And fecal occult blood test was associated with IBD in AIP patients (P = 0.008). CONCLUSIONS Most AIP-IBD patients had ulcerative colitis and type 2 AIP. IBD patients are more likely to develop AIP compared to the general population, and vice versa. Use of mesalamine and tuberculosis infection were associated with AIP, and fecal occult blood test was associated with IBD.
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Affiliation(s)
- Zi Qing Yu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiao Yin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ge Chong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wei Han
- Department of Epidemiology and Biostatistics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Tian Ming Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Meng Yuan Zhang
- Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Bei Ming Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yu Jia Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ming Yue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Conti Bellocchi MC, Crinò SF, De Marchi G, De Pretis N, Ofosu A, Caldart F, Ciccocioppo R, Frulloni L. A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty? Biomedicines 2023; 11:biomedicines11051393. [PMID: 37239064 DOI: 10.3390/biomedicines11051393] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/01/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
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Affiliation(s)
| | - Stefano Francesco Crinò
- Diagnostic and Interventional Endoscopy of Pancreas, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Giulia De Marchi
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Nicolò De Pretis
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Andrew Ofosu
- Division of Gastroenterology and Hepatology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
| | - Federico Caldart
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Pancreas Institute, University of Verona, 37134 Verona, Italy
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14
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Ito T, Ikeura T, Notohara K, Masuda M, Nakamaru K, Nakayama S, Shimatani M, Takaoka M, Okazaki K, Naganuma M. A case of type 2 autoimmune pancreatitis with spontaneous remission. Clin J Gastroenterol 2023; 16:297-302. [PMID: 36696084 DOI: 10.1007/s12328-022-01753-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/27/2022] [Indexed: 01/26/2023]
Abstract
A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.
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Affiliation(s)
- Takashi Ito
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Tsukasa Ikeura
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan.
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Masataka Masuda
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Koh Nakamaru
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Shinji Nakayama
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Masaaki Shimatani
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | - Makoto Takaoka
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
| | | | - Makoto Naganuma
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1010, Japan
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15
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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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Choi SJ, Ahn SM, Oh JS, Hong S, Lee CK, Yoo B, Kim YG. Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease. PLoS One 2023; 18:e0282852. [PMID: 36893163 PMCID: PMC9997947 DOI: 10.1371/journal.pone.0282852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 02/23/2023] [Indexed: 03/10/2023] Open
Abstract
INTRODUCTION We aimed to investigate the predictors of relapse in immunoglobulin G4-related disease (IgG4-RD), focusing on the serum IgG4 levels during initial treatment. METHODS We retrospectively recruited 57 patients with IgG4-RD who were treated with immunosuppressants and elevated serum IgG4 levels in a tertiary hospital between January 2011 and December 2020. They were followed up for ≥ 6 months after initiation of immunosuppressive therapy. Clinical and laboratory findings including serum IgG4 levels (reference value: 6-121 mg/dL) were compared between relapsed (n = 13) and non-relapsed (n = 44) groups. Multivariate Cox regression analysis was used to assess the predictors for relapse. We performed a Kaplan-Meier analysis with a log-rank test to evaluate the cumulative relapse rate for two years. RESULTS Median serum IgG4 levels at baseline were 321 mg/dL in the relapsed group and 299 mg/dL in the non-relapsed group. Serum IgG4 levels were normalized after six months in five (38.5%) relapsed and 28 (63.6%) non-relapsed patients. In multivariate Cox regression analysis, the normalization of serum IgG4 levels at six months was associated with a lower risk of relapse, with a hazard ratio of 0.232 (p = 0.019). Central nervous system involvement was associated with the relapse, with a hazard ratio of 21.130 (p = 0.015). The cumulative relapse rate for two years was lower in the normal serum IgG4 group at six months than in the elevated serum IgG4 group at six months (p = 0.027). CONCLUSION Our study suggests that normalization of serum IgG4 levels during immunosuppressive treatment for IgG4-RD independently predicts relapse-free outcomes. Thus, monitoring serum IgG4 levels might be used as a marker of prognosis.
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Affiliation(s)
- Su Jin Choi
- Department of Rheumatology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Soo Min Ahn
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ji Seon Oh
- Department of Information Medicine, Asan Medical Center, Seoul, South Korea
| | - Seokchan Hong
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chang-Keun Lee
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Bin Yoo
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yong-Gil Kim
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- * E-mail:
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Joshi PV, Nikalje AM, Kulkarni M, Borde ND. AuntMinnie Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Leads to Diagnosis of Immunoglobulin G4-Related Disease. Indian J Nucl Med 2022; 37:376-378. [PMID: 36817190 PMCID: PMC9930466 DOI: 10.4103/ijnm.ijnm_80_22] [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: 05/04/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 12/03/2022] Open
Abstract
A 61-year-old male underwent fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) for evaluation of fever and weight loss with clinical suspicion of occult malignancy or tuberculosis. The scan showed hypermetabolism in bilateral submandibular salivary glands, biliary radicles, pancreas, bilateral kidneys, prostate, and multiple lymph nodes. Based on the concomitant involvement of these sites, suspicion of immunoglobulin G4 (IgG4)-related disease was raised in PET-CT report. Further evaluation with serum IgG4 levels and histopathology of the submandibular salivary gland confirmed the diagnosis of IgG4-related disease. The ability of FDG PET-CT to evaluate the whole-body status of disease played a crucial role in this case.
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Affiliation(s)
- Prathamesh Vijay Joshi
- Department of Nuclear Medicine and PET-CT, Kamalnayan Bajaj Hospital, Aurangabad, Maharashtra, India
| | - Anand Maruti Nikalje
- Department of Medicine, Intensive Care Unit, MGM Medical College & Hospital, Aurangabad, Maharashtra, India
| | - Mukta Kulkarni
- Department of Nuclear Medicine and PET-CT, Kamalnayan Bajaj Hospital, Aurangabad, Maharashtra, India
| | - Neha Deepak Borde
- Department of Pathology, Mgm Medical College & Hospital, Aurangabad, Maharashtra, India
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18
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Lee SC, Yang CH, Chang CT, Yu KH. Diagnostic Utility of Serum IgG4 in Autoimmune Pancreatitis: An Updated Comprehensive Systematic Review and Meta-analysis. J Clin Gastroenterol 2022; 56:810-817. [PMID: 34516462 DOI: 10.1097/mcg.0000000000001612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 07/30/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVES Despite many studies suggesting an association between serum immunoglobulin G4 (sIgG4) and autoimmune pancreatitis (AIP), the evidence of utility in differentiation between AIP and pancreatic cancer (PC) remain uncertain. METHODS The analysis based on published studies. Data were pooled by means of a random-effects model, and sensitivity, specificity, diagnostic odds ratios (DOR), areas under summary receiver operating characteristic curves were calculated. RESULTS In the included thirteen studies, sIgG4 were measured in 594 patients with AIP and 958 patients with PC. The pooled sensitivity, specificity, DOR, and area under the curve were 0.72 [95% confidence interval (CI): 0.68-0.75], 0.93 (95% CI: 0.92-0.95), 51.37 (95% CI: 23.20-113.74), and 0.91 (95% CI: 0.87-0.95). Subgroup analyses of the DORs for region and year: Asia, (112.10; 95% CI: 27.72-453.32), non-Asia (26.01; 95% CI: 12.38-54.65), and year before 2011 (107.61; 95% CI: 39.30-294.68), year after 2011 (26.96; 95% CI: 9.78-74.32). Overall, sIgG4 was associated with AIP, the result revealed a moderate sensitivity 0.72 and high specificity 0.93. In the meta-analysis, the pooled DOR of sIgG4 levels of 2-fold upper limit 50.44 was similar with the DOR 51.37 when 1-fold cut-off value, but the summary receiver operating characteristic was 0.755 and 0.91. The higher specificity (from 93% to 98%) derived from the cut-off value (from 130-140 to 260-280 mg/dL) for sIgG4 occurred at a significant reduction in sensitivity (from 72% to 43%). CONCLUSIONS The study revealed sIgG4 is a good marker of AIP. Screening of sIgG4 may help clinicians differentiate between AIP and PC, and the best cut-off value should be 140 rather than 280 mg/dL.
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Affiliation(s)
- Shih-Ching Lee
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan
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Lanzillotta M, Tacelli M, Falconi M, Arcidiacono PG, Capurso G, Della-Torre E. Incidence of endocrine and exocrine insufficiency in patients with autoimmune pancreatitis at diagnosis and after treatment: a systematic review and meta-analysis. Eur J Intern Med 2022; 100:83-93. [PMID: 35367110 DOI: 10.1016/j.ejim.2022.03.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Autoimmune pancreatitis (AIP) is a rare form of pancreatitis that may lead to endocrine and exocrine insufficiency if left untreated. AIP clinically responds to glucocorticoids (GCs) therapy, but multiple GCs courses are often required to maintain remission with detrimental effects on glycaemic control. OBJECTIVE In this systematic review and meta-analysis, we aimed to assess the rate of endocrine and of exocrine insufficiency at diagnosis and at follow up in patients with AIP as well as the impact of GC therapy on pancreatic function in the long-term. METHODS The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to August 2021 to identify studies reporting data on endocrine and exocrine insufficiency in patients with AIP. Pooled events were calculated using a random-effect model and expressed in terms of pooled prevalence rates. RESULTS A total of 6522 AIP patients and sixty-two studies were included in the analysis. The pooled estimate rate for the overall prevalence of diabetes in AIP at baseline was 37% (95% CI 32-42, I2 96%). The pooled prevalence rate of exocrine insufficiency was 45% (95%CI 32.9-57.4; I2 97%). The pooled estimate rate of diabetes at follow-up was 44% (95%CI 26.1-62.4) in studies where GCs were given to 100% of patients and 42% (95%CI 30.6-52.9) in studies where GCs were given to less than 100% of patients. CONCLUSION A large proportion of patients with AIP displays concomitant exocrine and endocrine insufficiency at the time of diagnosis. The incidence of diabetes at the longest available follow up tends to increase in patients treated with GCs.
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Affiliation(s)
- Marco Lanzillotta
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Matteo Tacelli
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Division of Pancreatic Surgery and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emanuel Della-Torre
- Università Vita-Salute San Raffaele, IRCCS San Raffaele Scientific Institute, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
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20
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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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21
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Jin Q, Ge Y, Chen X, Tan C, Huang Z, Wang B, Zhang B, Peng Q, Wang X, Wang G. The Clinical Phenotype of Chinese Patients With Autoimmune Pancreatitis Differs Significantly From Western Patients. Front Med (Lausanne) 2022; 9:771784. [PMID: 35321468 PMCID: PMC8935039 DOI: 10.3389/fmed.2022.771784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 01/31/2022] [Indexed: 11/29/2022] Open
Abstract
Aim To characterize the clinical features of autoimmune pancreatitis (AIP) in China and compare differences between our Chinese cohort and Western cohorts. Methods This was a retrospective study of patients with AIP that was carried out in the China-Japan Friendship Hospital between January 2010 and April 2021. We included a total of 50 patients (46 males and 4 females) aged between 27 and 86 years who fulfilled the international Consensus Diagnostic (ICD) Criteria. For comparative purposes, we included data from seven representative Western cohorts. Result When comparing Chinese and Western patients, we found that obstructive jaundice was the most frequent initial symptom (68 vs. 43%, P < 0.001). Extra-pancreatic organ involvement was more common in Chinese patients (68 vs. 30%, P < 0.001). Sclerosing cholangitis was the most frequent extrapancreatic lesion (48 vs. 24%, P = 0.001). The elevation of serum IgG4 was more obvious in our cohort (86 vs. 49%, P < 0.001). Conversely, the rates of ANA-positivity were significantly higher in Western populations (17 vs. 50%, P = 0.006). With regards to imaging, diffuse swelling was significantly more common in China (44 vs. 27%, P = 0.021). Steroid therapy was used more frequently in our Chinese patients (84 vs. 59%, P = 0.001). The steroid-response rate was also significantly higher in our Chinese patients (85 vs. 54%, P = 0.001); However, the rate of resection was higher in Western cohorts (2 vs. 31%, P < 0.001). There was no significant difference between the two populations with regards to recurrence rate (33 vs. 33%, P = 1.000). Conclusion This study identified significant differences between Chinese and Western populations of patients with AIP. Within the Chinese population, AIP was more likely to have jaundice and extra-pancreatic organ involvement, and elevated serum IgG4 levels. Chinese patients were also showed favorable responses to treatment with glucocorticoids.
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Affiliation(s)
- Qiwen Jin
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Yongpeng Ge
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Xixia Chen
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Chang Tan
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Zhenguo Huang
- Department of Radiology, China-Japan Friendship Hospital, Beijing, China
| | - Bei Wang
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Bo Zhang
- Department of Ultrasound, China-Japan Friendship Hospital, Beijing, China
| | - Qinglin Peng
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Xiaodi Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Guochun Wang
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
- *Correspondence: Guochun Wang
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Persistent enlargement of the pancreatic gland after glucocorticoid therapy increases the risk of relapse in IgG4-related autoimmune pancreatitis. Clin Rheumatol 2022; 41:1709-1718. [PMID: 35175447 DOI: 10.1007/s10067-022-06091-5] [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: 12/06/2021] [Revised: 01/26/2022] [Accepted: 01/31/2022] [Indexed: 11/03/2022]
Abstract
OBJECTIVES This study aims to clarify the relationship between the changes of pancreatic size after glucocorticoid (GC) therapy and relapse in IgG4-related autoimmune pancreatitis (AIP). METHODS We prospectively enrolled 205 newly diagnosed IgG4-related AIP patients. 145 patients were followed up for more than 3 years. These patients were divided into three groups according to the changes of pancreatic size after treatment of 6 months: pancreatic swelling, normal size, and pancreatic atrophy. Baseline clinical and laboratory parameters were compared among three groups. Kaplan-Meier survival analysis was performed in the 134 patients based on GC therapy. Besides, Cox regression analysis and logistic regression analysis were performed to identify risk factors associated with relapse and the potential variables affecting changes of pancreatic size after treatment. RESULTS Age at diagnosis, white blood cell count, and serum IgG1 level at baseline were significantly different among the three groups. After treatment of 6 months, the pancreas of most patients (n = 81, 55.9%) could return to normal size, while persistent pancreatic swelling was found in 24.1% patients (n = 35), and atrophy was observed in 20.0% of the patients (n = 29). Kaplan-Meier survival analysis presented patients with pancreatic swelling after 6 months of GC therapy were more likely to relapse in the follow-up of 3 years. Persistent pancreatic swelling after treatment and salivary gland involvement at baseline were independent risk variables associated with relapse in IgG4-related AIP patients, while GC-based therapy was a protective factor of relapse. Logistic regression analysis revealed that older age at diagnosis was associated with pancreatic atrophy and higher baseline serum IgG1 level was associated with pancreatic swelling after treatment of 6 months. CONCLUSIONS Patients with persistent pancreatic swelling after GC-based therapy of 6 months were more likely to relapse in the follow-up of 3 years. Older age at diagnosis and higher baseline serum IgG1 level were potential variables associated with pancreatic atrophy or swelling after treatment of 6 months. Key Points • Patients with persistent pancreatic swelling after glucocorticoid-based therapy were more likely to relapse in IgG4-related autoimmune pancreatitis. • Older age at diagnosis was associated with pancreatic atrophy after glucocorticoid-based therapy. • Higher baseline serum IgG1 level was associated pancreatic swelling after glucocorticoid-based therapy.
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23
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Conti Bellocchi MC, Marconato E, Lamonaca L, Cattani Mottes M, Ciccocioppo R, Carrara S, de Pretis N, Gabbrielli A, Crinò SF, Frulloni L. The features and clinical outcomes of inflammatory bowel disease associated with autoimmune pancreatitis: A greater awareness is needed. Medicine (Baltimore) 2022; 101:e28602. [PMID: 35089195 PMCID: PMC8797592 DOI: 10.1097/md.0000000000028602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/29/2021] [Indexed: 01/05/2023] Open
Abstract
The prevalence of inflammatory bowel disease (IBD) has been described in 5% to 40% of autoimmune pancreatitis (AIP) patients. The aim of our study was to evaluate the prevalence, endoscopic features, and outcome of IBD in association with AIP.A retrospective analysis including all consecutive patients with AIP and a histological diagnosis of IBD from 2010 to 2020 was performed. Demographical data, AIP, and IBD features, as well as clinical course, were recorded.Among 267 AIP patients, 45 were diagnosed with ulcerative colitis (UC) (27 men, mean age 31.6), all with a diagnosis of type 2 AIP. The most frequent presentation of AIP was acute pancreatitis (55.5%). Both diffuse (51.1%) and focal (48.9%) pancreatic involvement were observed. The AIP relapse rate was 11.1% over a mean follow-up of 55 months. In 69% of patients, the interval time between the diagnosis of AIP and UC was <1 year. When UC was present at AIP onset, UC was in clinical remission in 50% of patients. Fecal calprotectin levels, when available, were elevated in 86.6% of these patients. Mostly, mild-moderate pancolitis was initially diagnosed (55.5%). During follow-up, escalation therapy for UC was required in 40% of patients after a mean time of 45 months. Two patients (4.4%) underwent colectomy.The prevalence of UC in AIP patients was 17%. Mild pancolitis with a low rate of colectomy was found. Greater awareness is needed to avoid a delayed diagnosis of UC, and the dosage of fecal calprotectin levels could have a role in this setting.
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Affiliation(s)
- Maria Cristina Conti Bellocchi
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Eugenio Marconato
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Laura Lamonaca
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano, Italy
| | - Martina Cattani Mottes
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Rachele Ciccocioppo
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Silvia Carrara
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano, Italy
| | - Nicolo’ de Pretis
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Armando Gabbrielli
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Stefano Francesco Crinò
- Department of Medicine, Gastroenterology and Digestive Endoscopy Unit, Pancreas Institute, University of Verona, Verona, Italy
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Update on classification, diagnosis, and management of immunoglobulin G4-related disease. Chin Med J (Engl) 2022; 135:381-392. [PMID: 34985023 PMCID: PMC8869566 DOI: 10.1097/cm9.0000000000001891] [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: 11/26/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.
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Ammer-Herrmenau C, Ellenrieder V, Neesse A. [Chronic pancreatitis: update diagnostic and therapeutic concepts]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:1131-1138. [PMID: 34798674 DOI: 10.1055/a-1659-4636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Chronic pancreatitis (CP) is a frequent cause for hospitalization and is associated with impaired quality of life and reduced overall survival. The German Society for Gastroenterology (DGVS) has recently completed the S3-Guideline "Pancreatitis" that summarizes key findings on epidemiology, diagnostic and therapeutic concepts for acute and chronic pancreatitis. Here, we recapitulate the most relevant findings for clinicians regarding CP. RESULTS The most common cause of CP is chronic alcohol abuse, other causes are hereditary pancreatitis, autoimmune pancreatitis, hyperparathyroidism and idiopathic forms. Apart from the classical hereditary pancreatitis (PRSS1 mutation), a number of genetic associations have been discovered over the last years that are associated with an increased risk to develop idiopathic CP. The conservative management of CP is focused on the appropriate management of exocrine and endocrine insufficiency, and the prevention and treatment of secondary complications such as osteoporosis, vitamin deficiencies and malnutrition. Local complications (bile duct stenosis, duodenal stenosis, pseudocysts and chronic pain) should be managed in multidisciplinary teams in specialized pancreas centres with expert surgeons, radiologists and gastroenterologists. Infected or symptomatic pseudocysts should be primarily addressed by endoscopic drainage. In contrast, patients with chronic pain, dilated pancreas duct and opioid use should be considered for early surgical intervention. CONCLUSION Chronic pancreatitis is associated with increased morbidity and mortality and often leads to hospital admissions. The clinical management of complex patients with local complications requires an interdisciplinary approach to tailor available therapeutic modalities depending on the stage of the disease and pre-existing comorbidities.
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Affiliation(s)
- Christoph Ammer-Herrmenau
- Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Volker Ellenrieder
- Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Göttingen, Germany
| | - Albrecht Neesse
- Klinik für Gastroenterologie, gastrointestinale Onkologie und Endokrinologie, Universitätsmedizin Göttingen, Göttingen, Germany
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Abstract
Autoimmune pancreatitis (AIP) has attracted much attention in the last two decades, and due to the diagnostic value of immunoglobulin G4 (IgG4), the number of cases diagnosed in clinical practice has markedly increased. However, in contrast to prototypic IgG4-related type 1 AIP, a minor subtype of AIP, referred to as type 2 AIP, is less widely known and has thus not yet been characterized in detail. Type 2 AIP is unrelated to IgG4 and is a completely distinct entity from type 1 AIP. One confusing factor is that the two types of AIP share patterns of clinical presentation (e.g., acute pancreatitis and painless jaundice) and imaging abnormalities (e.g., diffuse or segmental enlargement). Since there are currently no established serum markers, the diagnosis of type 2 AIP is highly challenging and requires the tissue confirmation of neutrophilic injury to the pancreatic ducts, a finding designated as a granulocytic epithelial lesion. Approximately one-third of cases are associated with inflammatory bowel disease, particularly ulcerative colitis; however, the pathological relationship between these two conditions has not yet been clarified. Unanswered questions relate to its pathophysiology, the potential development of a similar granulocytic injury in other organs, and the characteristics of pediatric cases. This review summarizes consensus and controversies surrounding type 2 AIP, with the aim of increasing awareness and highlighting the unmet needs of this underrecognized condition.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital & King's College London, London, UK
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Masaki Y, Nakase H, Tsuji Y, Nojima M, Shimizu K, Mizuno N, Ikeura T, Uchida K, Ido A, Kodama Y, Seno H, Okazaki K, Nakamura S, Masamune A. The clinical efficacy of azathioprine as maintenance treatment for autoimmune pancreatitis: a systematic review and meta-analysis. J Gastroenterol 2021; 56:869-880. [PMID: 34426870 PMCID: PMC8382580 DOI: 10.1007/s00535-021-01817-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/04/2021] [Indexed: 02/04/2023]
Abstract
The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.
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Affiliation(s)
- Yoshiharu Masaki
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
| | - Yoshihisa Tsuji
- Department of General Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Masanori Nojima
- Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kyoko Shimizu
- Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tsukasa Ikeura
- The Third Department of Internal Medicine, Kansai Medical University, Hirakata, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yuzo Kodama
- Department of Gastroenterology, Kobe University, Kobe, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | | | - Seiji Nakamura
- Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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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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Serum IgG4 levels at diagnosis can predict unfavorable outcomes of untreated patients with IgG4-related disease. Sci Rep 2021; 11:13341. [PMID: 34172819 PMCID: PMC8233326 DOI: 10.1038/s41598-021-92814-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 06/16/2021] [Indexed: 12/12/2022] Open
Abstract
The outcomes of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) who are not treated are unclear. This study aimed to clarify these outcomes and identify the factors related to them. We retrospectively evaluated various clinical features including laboratory data and involved organs at diagnosis in 107 patients with IgG4-RD, who were followed up for more than 6 months, at a single center in Japan. We compared the clinical features of the 27 untreated patients with those of the 80 patients treated with glucocorticoid. The patient outcomes were investigated, and logistic regression analysis was performed to identify factors related to them. The patients comprised 73 men and 34 women (median age 67 years). The untreated patients had significantly lower IgG4-RD responder index (9 vs. 12) and fewer affected organs (1 vs. 3) than did those treated with glucocorticoid. Of these 27 patients, 8 experienced deterioration of IgG4-RD after the diagnosis. In the age- and sex-adjusted logistic regression analysis, serum IgG4 elevation (per 100 mg/dL, odds ratio 1.194, 95% confidence interval 1.017–1.402) was the only significant factor related to disease deterioration in untreated patients with IgG4-RD, whereas not serum IgG4 levels (per 100 mg/dL, odds ratio 0.995, 95% confidence interval 0.921–1.075) but history of allergy (OR 3.134, 95% confidence interval 1.094–8.977, P = 0.033) related to deterioration in patients who underwent treatment. Serum IgG4 levels may be a useful predictor of unfavorable outcomes in untreated patients with IgG4-RD, who tend to have fewer affected organs and lower IgG4-RD responder index.
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Suzuki H, Ishikawa T, Ohno E, Iida T, Uetsuki K, Yashika J, Yamada K, Yoshikawa M, Furukawa K, Nakamura M, Honda T, Ishigami M, Kawashima H, Fujishiro M. An initial trial of quantitative evaluation of autoimmune pancreatitis using shear wave elastography and shear wave dispersion in transabdominal ultrasound. Pancreatology 2021; 21:682-687. [PMID: 33648879 DOI: 10.1016/j.pan.2021.02.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 02/09/2021] [Accepted: 02/14/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES We aimed to examine therapeutic efficacy and prognosis prediction of autoimmune pancreatitis (AIP) using shear wave elastography (SWE) and shear wave dispersion (SWD) in transabdominal ultrasound (US). METHODS The subjects were 23 patients with diffuse type 1 AIP who underwent SWE and SWD, and 34 controls with a normal pancreas. Elasticity and dispersion were defined as the pancreatic elastic modulus (PEM) and dispersion slope, respectively. PEM and dispersion slope were compared between AIP and control cases, and the short-term therapeutic effect and long-term prognosis were examined. RESULTS PEM (30.9 vs. 6.6 kPa, P < 0.001) and dispersion slope (15.3 vs. 13.0 (m/sec)/kHz, P = 0.011) were significantly higher in AIP cases than in controls. Among the 17 AIP patients followed-up in two weeks after treatment, these parameters were 12.7 kPa and 10.5 (m/sec)/kHz with median decrease rate of 37.2% and 32.8%, respectively, which were significantly higher than the change in the size of pancreatic parenchyma (14.4%, P = 0.026). Fourteen of these subjects were followed up for >12 months, during which 2 had relapse; diabetes improved in 5 and worsened in 2; in 60% of cases, the pancreatic parenchyma was atrophied. The % change in PEM after two weeks was tended to be higher in non-atrophy cases. CONCLUSION SWE and SWD measurement in US may be useful for quantitative assessment of AIP and evaluation of short-term treatment efficacy.
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Affiliation(s)
- Hirotaka Suzuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Takuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Eizaburo Ohno
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Tadashi Iida
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Kota Uetsuki
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Jun Yashika
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Kenta Yamada
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Masakatsu Yoshikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
| | - Hiroki Kawashima
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan.
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 65 Tsuruma-Cho, Showa-ku, Nagoya City, 466-8550, Japan
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A Follow-Up Study of a European IgG4-Related Disease Cohort Treated with Rituximab. J Clin Med 2021; 10:jcm10061329. [PMID: 33807051 PMCID: PMC8004657 DOI: 10.3390/jcm10061329] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/08/2021] [Accepted: 03/09/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. METHODS We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. RESULTS Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. CONCLUSION RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6-9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy.
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Mačinga P, Jarošová J, Špičák J, Hucl T. [Immunoglobulin G4-related disease in gastroenterology]. VNITRNI LEKARSTVI 2021; 67:76-83. [PMID: 34074105 DOI: 10.36290/vnl.2021.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
IgG4-related disease is a recently defined clinical entity that can manifest itself in any organ. The most common gastrointestinal manifestations are diseases of the pancreas (autoimmune pancreatitis type 1) and biliary tree (IgG4-associated cholangitis); involvement of liver parenchyma is uncommon and the affection of tubular organs is very rare. IgG4-related pancreatitis and cholangitis can mimic malignancies in their clinical presentation. Diagnosis is often difficult and requires careful evaluation of the combination of symptoms, serology and imaging findings, while adhering to the established diagnostic criteria. The first line of treatment is the administration of corticoids and the remission is achieved in the vast majority of patients. In case of contraindication, intolerance or failure of corticotherapy, patients should receive B cell depletion therapy (rituximab). Based on the available knowledge, monotherapy with other immunosuppressants is not considered to be sufficiently effective. Some patients may benefit from maintenance treatment to prevent relapse, which is otherwise common in both IgG4-related pancreatitis and cholangitis. Recognized IgG4-related disease has a good prognosis, but some patients develop irreversible fibrotic changes in the affected organ with consequent dysfunction; the possible association of the disease with a higher risk of malignancy has not yet been reliably elucidated.
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Kuraishi Y, Uehara T, Watanabe T, Ashihara N, Ozawa M, Kanai K, Kawa S. Corticosteroids prevent the progression of autoimmune pancreatitis to chronic pancreatitis. Pancreatology 2020; 20:1062-1068. [PMID: 32800575 DOI: 10.1016/j.pan.2020.07.408] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 07/05/2020] [Accepted: 07/28/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVES Patients with autoimmune pancreatitis (AIP) sometimes progress to chronic pancreatitis (CP). We evaluated the ability of corticosteroids to prevent the progression to CP. METHODS We defined patients with definitive findings of CP (stones in the main pancreatic duct [MPD] or multiple pancreatic calcifications) as having severe calcification (SC). A total of 145 AIP patients were enrolled. We measured the duration between AIP diagnosis and SC development and retrospectively compared the time to SC development between patients with and without steroids. Multivariate analysis for factors associated with SC were performed. RESULTS Nineteen (13%) patients progressed to SC. Since 95 patients had pancreatic head swelling and SC was found in these patients only, our analysis focused mainly on these at-risk populations. In Kaplan-Meier analysis limited to patients with pancreatic head swelling, the incidence of SC was significantly lower in patients with steroids than in those without (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.07-0.52; p < 0.001). Multivariate testing of patients with pancreatic head swelling confirmed that steroid therapy was significantly associated with a lower incidence of SC (HR 0.11, 95% CI 0.03-0.34; p < 0.001), while MPD dilation at AIP diagnosis was related to a higher incidence of SC (HR 4.02, 95% CI 1.43-11.7; p = 0.009). CONCLUSIONS Corticosteroids appeared to prevent progression to CP in AIP patients, especially in those with pancreatic head swelling. Patients with both pancreatic head swelling and MPD dilation at diagnosis have a higher incidence of progression to CP. Steroid therapy is suggested for these high-risk cases.
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Affiliation(s)
- Yasuhiro Kuraishi
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
| | - Takayuki Watanabe
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Norihiro Ashihara
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Makiko Ozawa
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Keita Kanai
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Nagano, Japan
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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: 13] [Impact Index Per Article: 2.6] [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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Pelaez-Luna M, Soriano-Rios A, Lira-Treviño AC, Uscanga-Domínguez L. Steroid-responsive pancreatitides. World J Clin Cases 2020; 8:3411-3430. [PMID: 32913848 PMCID: PMC7457102 DOI: 10.12998/wjcc.v8.i16.3411] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/03/2020] [Accepted: 07/30/2020] [Indexed: 02/05/2023] Open
Abstract
Autoimmune pancreatitis has received considerable attention, especially due to the marked effect of corticosteroid therapy on its clinical course. Knowledge, especially regarding type 1 autoimmune pancreatitis, has significantly increased over the last decades, and despite significant differences in pathophysiology and outcomes, both type 1 and 2 autoimmune pancreatitis are still considered different types of the same disease. Some have proposed a different nomenclature reflecting these differences. Although the term steroid-responsive pancreatitides may be interpreted as synonymous to type 1 and 2 autoimmune pancreatitis, these are not the only pancreatic conditions that show a response to steroid therapy. Acute pancreatitis caused by vasculitis and connective tissue diseases and acute pancreatitis secondary to checkpoint inhibitors or programmed cell death receptor antibody-mediated blockage cancer therapy may also benefit from steroid treatment. This review presents current concepts on these disorders, aiming to increase awareness, analyze similarities and differences, and propose a new nomenclature that reflects their specific particularities, clustering them under the term “steroid-responsive pancreatitides”.
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Affiliation(s)
- Mario Pelaez-Luna
- Research Division School of Medicine, Universidad Nacional Autonoma de México, Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Andrea Soriano-Rios
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Ana C Lira-Treviño
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
| | - Luis Uscanga-Domínguez
- Department of Gastroenterology, National Institute of Medical Sciences and Nutrition "Salvador Zubiran" Mexico City 14000, Mexico
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Löhr JM, Beuers U, Vujasinovic M, Alvaro D, Frøkjær JB, Buttgereit F, Capurso G, Culver EL, de-Madaria E, Della-Torre E, Detlefsen S, Dominguez-Muñoz E, Czubkowski P, Ewald N, Frulloni L, Gubergrits N, Duman DG, Hackert T, Iglesias-Garcia J, Kartalis N, Laghi A, Lammert F, Lindgren F, Okhlobystin A, Oracz G, Parniczky A, Mucelli RMP, Rebours V, Rosendahl J, Schleinitz N, Schneider A, van Bommel EF, Verbeke CS, Vullierme MP, Witt H. European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations. United European Gastroenterol J 2020; 8:637-666. [PMID: 32552502 DOI: 10.1177/2050640620934911] [Citation(s) in RCA: 128] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.
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Affiliation(s)
- J-Matthias Löhr
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
| | - Miroslav Vujasinovic
- Department of Upper Gastrointestinal Diseases, Karolinska University Hospital, Stockholm, Sweden and Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | | | - Frank Buttgereit
- Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Berlin, Germany
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division Pancreas Translational and Clinical Research Center IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital and Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, ISABIAL, Alicante, Spain
| | - Emanuel Della-Torre
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Unit of Immunology, Rheumatology, Allergy and Rare Disease (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Enrique Dominguez-Muñoz
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Nils Ewald
- Institute of Endocrinology, Diabetology and Metabolism, Johannes Wesling University hospital, Minden, Germany and Justus Liebig University Giessen, Giessen, Germany
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Natalya Gubergrits
- Department of Internal Medicine, Donetsk National Medical University, Lyman, Ukraine
| | - Deniz Guney Duman
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Julio Iglesias-Garcia
- Department of Gastroenterology and Hepatology, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
| | - Nikolaos Kartalis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden
| | - Andrea Laghi
- Department of Surgical and Medical Sciences and Translational Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Fredrik Lindgren
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Karolinska University Hospital, Stockholm, Sweden
| | | | - Grzegorz Oracz
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Andrea Parniczky
- Institute for Translational Medicine, Szentágothai Research Centre, Medical School, University of Pécs, Pécs, Hungary; Heim Pál National Insitute of Pediatrics, Budapest, Hungary
| | | | - Vinciane Rebours
- Pancreatology Department, Beaujon Hospital, Clichy, Université de Paris, France
| | - Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University, Halle, Germany
| | - Nicolas Schleinitz
- Département de Médicine Interne Timone, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France
| | - Alexander Schneider
- Department of Gastroenterology and Hepatology, Klinikum Bad Hersfeld, Bad Hersfeld, Germany
| | - Eric Fh van Bommel
- Department of Internal Medicine, Dutch National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer hospital, Dordrecht, the Netherlands
| | | | | | - Heiko Witt
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin, Paediatric Nutritional Medicine, Technische Universität München, Freising, Germany
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- See list at the end of this article
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Detlefsen S, Olesen SS. Sialadenitis in a patient with ulcerative colitis and autoimmune pancreatitis type 2. Pathol Res Pract 2020; 216:153072. [PMID: 32825945 DOI: 10.1016/j.prp.2020.153072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 06/11/2020] [Accepted: 06/17/2020] [Indexed: 01/07/2023]
Abstract
Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that has been increasingly recognised over the last decades and shows a good response to corticosteroid treatment. Two different forms of AIP have been characterized. Type 1 AIP is the pancreatic manifestation of IgG4-related disease and often affects multiple organ systems. In contrast, type 2 AIP is confined to the pancreas and involvement of extra-pancreatic organs has previously only very rarely been reported, except for an association with inflammatory bowel disease. The hallmark lesion of type 2 AIP is the granulocyte epithelial lesion (GEL), showing infiltration of neutrophilic granulocytes in the epithelium of pancreatic ducts and their accumulation in the duct lumen. We present a 61-year-old female patient who underwent pancreaticoduodenectomy with a postoperative histological diagnosis of type 2 AIP. Three months later, she underwent colectomy and was diagnosed with ulcerative colitis. One year later, she presented with swelling and pain of the right-sided submandibular salivary gland which was resected. Sialadenitis with lymphoplasmacytic inflammation, obliterative phlebitis, fibrosis and frequent accumulation of neutrophilic granulocytes in ducts, reminiscent of GELs, without IgG4-positivity or epitheloid cell granulomas, was found. Later, she presented with swelling and pain related to the left-sided submandibular gland, which resolved after steroid treatment. We describe the clinical, histological and immunohistochemical findings in this patient. It may be hypothesized that the sialadenitis may represent a rare extrapancreatic manifestation of, alternatively a rare association with, type 2 AIP or ulcerative colitis.
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Affiliation(s)
- Sönke Detlefsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
| | - Søren Schou Olesen
- Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
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Rebours V, Lévy P. Pancreatic and biliary tract involvement in IgG4-related disease. Presse Med 2020; 49:104015. [PMID: 32234378 DOI: 10.1016/j.lpm.2020.104015] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 04/25/2019] [Accepted: 07/04/2019] [Indexed: 02/07/2023] Open
Abstract
The diagnosis and treatment of pancreatic and biliary tract involvement in IgG4 disease can be challenging for physicians. A French series shows that the pancreas is the most frequently involved organ in systemic IgG4 disease. Pancreatitis may be found in more than 50% of patients with IgG4 disease and the biliary tract is involved in one third. Pancreatic or biliary involvement may be isolated, metachronous or synchronous of other IgG4-related organ injuries. Pancreatitis related to IgG4 disease is called autoimmune pancreatitis (AIP) type 1. The diagnosis is mainly suspected in the presence of symptoms and morphological features. Changes observed on conventional imaging are not typical and are usually similar to lesions observed in autoimmune pancreatitis type 2. AIP type 1 can also sometimes have a clinical or morphological presentation that mimics pancreatic cancer, especially pseudo-tumoral forms, associated with obstructive jaundice, weight loss and fatigue. Thus, the first challenge is to confirm the diagnosis of autoimmune pancreatitis and to exclude cancer. The AIP type must then be determined to decide on the most appropriate treatment.
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Affiliation(s)
- Vinciane Rebours
- Pancreatology unit, Inserm, UMR 1149, pancreatic rare diseases (PaRaDis), centre de reference de maladies rares, Beaujon hospital, 100, boulevard Gal-Leclerc, 92110 Clichy, France.
| | - Philippe Lévy
- Pancreatology unit, Inserm, UMR 1149, pancreatic rare diseases (PaRaDis), centre de reference de maladies rares, Beaujon hospital, 100, boulevard Gal-Leclerc, 92110 Clichy, France
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Hedegaard Jensen G, Mortensen MB, Klöppel G, Nielsen MFB, Nielsen O, Detlefsen S. Utility of pVHL, maspin, IMP3, S100P and Ki67 in the distinction of autoimmune pancreatitis from pancreatic ductal adenocarcinoma. Pathol Res Pract 2020; 216:152925. [PMID: 32273198 DOI: 10.1016/j.prp.2020.152925] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 03/12/2020] [Accepted: 03/14/2020] [Indexed: 01/07/2023]
Abstract
Morphology plays an important role in the distinction of autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC). However, we aimed to determine the utility of immunohistochemical tumor markers to contribute in the distinction of these entities. In surgical specimens with AIP (n = 20), PDAC (n = 20) and normal pancreas (n = 20), the expression of pVHL, maspin, IMP3, S100P and Ki67 was examined. We evaluated intralobular reactive ducts / acinoductal metaplasia (ILDs) and extralobular ducts (ELDs) in AIP, neoplastic glands in PDAC, and ductal epithelium in the normal pancreas, using a five-tiered scoring system. The Ki67 hot spot index (Ki67-HSPI) was determined manually and using automated digital imaging analysis of virtual double stains of Ki67 and CK8. Besides, sequential dual-immunohistochemical staining of maspin/pVHL, maspin/IMP3 and Ki67/maspin was performed in a subset of the specimens. Strong overexpression of IMP3, maspin, S100P and Ki67 and loss of pVHL was observed in PDAC compared to AIP and normal pancreas. In AIP however, focal and weak aberrant expression was observed with the following proportions in ILDs/ELDs: pVHL in 45 %/85 %, maspin in 30 %/70 %, IMP3 in 55 %/5%, S100P in 10 %/35 % and Ki67-HSPI >20 % in 15 %/70 %. At least two markers were aberrantly expressed in ILDs/ELDs in 45 %/60 %. The aberrant expression was more pronounced in type 2 AIP compared to type 1. In conclusion, our data indicate that pVHL, maspin, IMP3, S100P and Ki67 can be focal and weak aberrantly expressed in AIP. However, when used as a panel, these markers seem to be useful for the differentiation of AIP from PC.
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Affiliation(s)
| | - Michael Bau Mortensen
- HPB Section, Department of Surgery, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Günter Klöppel
- Department of Pathology, Consultation Center of Pancreatic and Endocrine Tumors, Technical University Munich, Munich, Germany
| | | | - Ole Nielsen
- Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Sönke Detlefsen
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Department of Pathology, Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
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Oh D, Song TJ, Moon SH, Kim JH, Lee NJ, Hong SM, Lee JS, Jo SJ, Cho DH, Park DH, Lee SS, Seo DW, Lee SK, Kim MH. Type 2 Autoimmune Pancreatitis (Idiopathic Duct-Centric Pancreatitis) Highlighting Patients Presenting as Clinical Acute Pancreatitis: A Single-Center Experience. Gut Liver 2020; 13:461-470. [PMID: 30970429 PMCID: PMC6622566 DOI: 10.5009/gnl18429] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/04/2018] [Accepted: 11/10/2018] [Indexed: 12/15/2022] Open
Abstract
Background/Aims Type 2 autoimmune pancreatitis (AIP) has been considered extremely rare in East Asia. This study aimed to clarify the prevalence, clinical characteristics and radiological findings of type 2 AIP highlighting patients presenting as acute pancreatitis in a single center. Methods Type 2 AIP patients were classified according to International Consensus Diagnostic Criteria. Radiological findings were compared between type 2 AIP presenting as acute pancreatitis and gallstone pancreatitis. Results Among 244 patients with AIP, 27 (11.1%) had type 2 AIP (definite, 15 [55.5%] and probable 12 [44.5%]). The median age of patients with type 2 AIP was 29 years (interquartile range, 20 to 39 years). Acute pancreatitis was the most common initial presentation (n=17, 63%) while obstructive jaundice was present in only one patient. Ulcerative colitis (UC) was associated with type 2 AIP in 44.4% (12/27) of patients. Radiological pancreatic imaging such as delayed enhancement of diffusely enlarged pancreas, homogeneous enhancement of focal enlargement/mass, absent/minimal peripancreatic fat infiltration or fluid collection, and multifocal main pancreatic duct narrowings were helpful for differentiating type 2 AIP from gallstone pancreatitis. During follow-up (median, 32.3 months), two patients (2/25, 8%) experienced relapse. Conclusions In South Korea, type 2 AIP is not as rare as previously thought. Overall, the clinical profile of type 2 AIP was similar to that of Western countries. Type 2 AIP should be considered in young UC patients with acute pancreatitis of uncertain etiology.
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Affiliation(s)
- Dongwook Oh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Jun Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea
| | - Jin Hee Kim
- Departments of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Nam Joo Lee
- Departments of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joune Seup Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seok Jung Jo
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Hui Cho
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hyun Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Soo Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Koo Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Myung-Hwan Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Soliman H, Vullierme MP, Maire F, Hentic O, Ruszniewski P, Lévy P, Rebours V. Risk factors and treatment of relapses in autoimmune pancreatitis: Rituximab is safe and effective. United European Gastroenterol J 2019; 7:1073-1083. [PMID: 31662864 DOI: 10.1177/2050640619862459] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 06/10/2019] [Indexed: 12/24/2022] Open
Abstract
Background and aims Steroid therapy is the first-line treatment for autoimmune pancreatitis but relapses are frequent. The aims were to assess the efficacy and the safety of immunomodulator treatments for relapsing autoimmune pancreatitis and rituximab in particular and to identify relapsing risk factors. Methods Patients followed for autoimmune pancreatitis from 2000 to 2016 were included. Data were retrospectively analysed regarding autoimmune pancreatitis treatment. Results In total, 162 patients with autoimmune pancreatitis type 1 (n = 92) and type 2 (n = 70) were included (median follow-up: 3 years (0.5-14). Relapse occurred in 46.5% of patients with autoimmune pancreatitis type 1 (vs 19.3% in autoimmune pancreatitis 2; p < 0.001). Risk factors of relapse were cholangitis, initial use of steroids, other organ involvement and chronic pancreatitis in autoimmune pancreatitis type 1 and initial use of steroids, tobacco consumption and chronic pancreatitis for autoimmune pancreatitis type 2. Overall, 21 patients were treated with immunomodulators (azathioprine, n = 19, or methotrexate, n = 2) for relapses. The efficiency rate was 67%. A total of 17 patients were treated with rituximab, with two perfusions at 15 days apart. The efficacy was 94% (16/17), significantly better than immunomodulator drugs (p = 0.03), with a median follow-up of 20 months (11-44). Only two patients needed two supplementary perfusions. Conclusion In relapsing autoimmune pancreatitis, rituximab is more efficient than immunomodulator drugs and shows better tolerance.
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Affiliation(s)
- Heithem Soliman
- Pancreatology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
| | - Marie-Pierre Vullierme
- Radiology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
| | - Frédérique Maire
- Pancreatology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
| | - Olivia Hentic
- Pancreatology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
| | - Philippe Ruszniewski
- Pancreatology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
| | - Philippe Lévy
- Pancreatology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
| | - Vinciane Rebours
- Pancreatology department, Beaujon Hospital, France and Paris-Diderot University, Clichy, France
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Tacelli M, Celsa C, Magro B, Barresi L, Guastella S, Capurso G, Frulloni L, Cabibbo G, Cammà C. Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019; 17:1061-1072.e8. [PMID: 30312787 DOI: 10.1016/j.cgh.2018.09.051] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 09/20/2018] [Accepted: 09/22/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Risk for relapse after induction of remission with steroid therapy has been studied extensively in patients with autoimmune pancreatitis (AIP), but findings have been equivocal. We performed a systematic review and meta-analysis to estimate the relapse rate of AIP after initial remission after steroid treatment and to identify factors associated with relapse. METHODS Three reviewers searched MEDLINE, SCOPUS, and EMBASE until July 2018 to identify studies on rate of relapse of AIP after induction of remission with steroid therapy. A pooled estimate was calculated using the DerSimonian and Laird method for a random-effects model. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Thirty-six studies met the inclusion criteria for meta-analysis. The median follow-up time was 40.8 months. Fifty-two percent of patients were classified as having type 1 AIP. The pooled estimate of relapse rate was 33% (95% CI, 30%-37%). A higher proportion of patients with type 1 AIP had a relapse compared with patients with type 2 AIP (37.5% vs 15.9%; P < .001). We found significant heterogeneity among studies (P < .01). Long-term maintenance therapy with steroids and study quality were associated independently with AIP relapse, after we adjusted for year of publication by multivariate meta-regression. CONCLUSIONS In a systematic review and meta-analysis, we found that a large proportion of patients with AIP treated successfully with steroid induction therapy had a relapse (33%)-particularly patients with type 1 AIP (37%). Maintenance steroid therapy lasting longer than 1 year could reduce risk of relapse. However, the data characterizing relapse rates are of limited quality, indicating the need for randomized controlled trials and new immunosuppressive drugs.
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Affiliation(s)
- Matteo Tacelli
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Ciro Celsa
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Bianca Magro
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Luca Barresi
- Endoscopy Service, Department of Diagnostic and Therapeutic Services, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione (Mediterranean Institute for Transplantation and Highly Specialized Therapies), Palermo, Italy
| | - Salvatore Guastella
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and Endoscopic Ultrasonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute (Istituto di Ricovero e Cura a Carattere Scientifico), Vita Salute San Raffaele University, Milan, Italy
| | - Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy
| | - Calogero Cammà
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine, University of Palermo, Palermo, Italy.
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Combination Therapy with Empagliflozin and Insulin Results in Successful Glycemic Control: A Case Report of Uncontrolled Diabetes Caused by Autoimmune Pancreatitis and Subsequent Steroid Treatment. Case Rep Endocrinol 2019; 2019:9415347. [PMID: 30895163 PMCID: PMC6393920 DOI: 10.1155/2019/9415347] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 02/01/2019] [Indexed: 12/24/2022] Open
Abstract
A 66-year-old Japanese male presented with thirst, polyuria, and hemoglobin A1c and postprandial glucose levels (13.1% and 529 mg/dL, respectively) that indicated severe hyperglycemia. Based on his high immunoglobulin G4 level and the results of magnetic resonance imaging and magnetic resonance cholangiopancreatography, we diagnosed him with autoimmune pancreatitis. Insulin was initiated to control his diabetes. One month later, the patient commenced on prednisolone therapy for the treatment of autoimmune pancreatitis, after which his total insulin dosage increased to a maximum of 52 units/day. When the prednisolone dosage was later tapered, the patient's total dosage of insulin was reduced to 42 units/day. However, he had gained 3.6 kg from the start of prednisolone therapy, and 42 units/day was insufficient for maintaining glycemic control. Thus, empagliflozin, a sodium-dependent glucose transporter 2 (SGLT2) inhibitor, was added. Thereafter, we were able to reduce the patient's total dosage of insulin; it was eventually discontinued with good glycemic control and weight loss. Such results suggest that the combination of insulin with an SGLT2 inhibitor may be a viable option for the treatment of diabetic patients on prednisolone therapy.
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Ishii Y, Serikawa M, Sasaki T, Fujimoto Y, Yamaguchi A, Ogawa T, Noma B, Okazaki A, Yukutake M, Ishigaki T, Chayama K. Impact of sclerosing dacryoadenitis/sialadenitis on relapse during steroid therapy in patients with type 1 autoimmune pancreatitis. Scand J Gastroenterol 2019; 54:259-264. [PMID: 30915865 DOI: 10.1080/00365521.2019.1577489] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Steroids are the first-line drugs for induction of remission in patients with type 1 autoimmune pancreatitis (AIP), and the usefulness of steroid maintenance therapy to prevent relapse has recently been reported. However, even during steroid therapy, a relatively large percentage of patients relapse and the predictive factors for relapse have not yet been elucidated. The aim of this study was to clarify the predictive factors for relapse of AIP patients during steroid therapy. MATERIALS AND METHODS The medical records of 76 patients with type 1 AIP with continued steroid therapy after induction of remission were analyzed retrospectively. The relapse rate during steroid therapy was evaluated, and the risk factors for relapse were investigated by univariate and multivariate analysis of clinical factors. RESULTS Relapse occurred in 28.9% (22/76) of the patients. The cumulative relapse rates were 10.5% at 1 year, 25.0% at 3 years, 34.9% at 5 years, and 43.0% at 10 years. In multivariate analysis, presence of sclerosing dacryoadenitis/sialadenitis at the time of initial diagnosis of AIP was an independent risk factor for relapse (HR 3.475, p = .009). The cumulative relapse rates of patients with sclerosing dacryoadenitis/sialadenitis reached 21.4% at 1 year, 56.0% at 3 years, and 78.0% at 5 years. CONCLUSIONS Sclerosing dacryoadenitis/sialadenitis was a predictive factor for relapse in type 1 AIP during steroid therapy; in such cases, strict follow-up is necessary with relapse in mind.
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Affiliation(s)
- Yasutaka Ishii
- a Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences , Hiroshima University , Hiroshima , Japan
| | - Masahiro Serikawa
- a Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences , Hiroshima University , Hiroshima , Japan
| | - Tamito Sasaki
- b Department of Gastroenterology , Hiroshima Prefectural Hospital , Hiroshima , Japan
| | - Yoshifumi Fujimoto
- c Department of Gastroenterology , Hiroshima General Hospital , Hiroshima , Japan
| | - Atsushi Yamaguchi
- d Department of Gastroenterology , National Hospital Organization Kure Medical Center and Chugoku Cancer Center , Hiroshima , Japan
| | - Tsuneyoshi Ogawa
- e Department of Internal Medicine , Hiroshima City Hiroshima Citizens Hospital , Hiroshima , Japan
| | - Bunjiro Noma
- f Department of Gastroenterology , Kure Kyosai Hospital , Hiroshima , Japan
| | - Akihito Okazaki
- g Department of Gastroenterology , Hiroshima Red Cross & Atomic-bomb Survivors Hospital , Hiroshima , Japan
| | - Masanobu Yukutake
- h Department of Gastroenterology , Hiroshima City Asa Citizens Hospital , Hiroshima , Japan
| | - Takashi Ishigaki
- i Department of Gastroenterology , National Hospital Organization Higashihiroshima Medical Center , Hiroshima , Japan
| | - Kazuaki Chayama
- a Department of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Sciences , Hiroshima University , Hiroshima , Japan
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Goodman RR, Jong MK, Davies JE. Concise review: The challenges and opportunities of employing mesenchymal stromal cells in the treatment of acute pancreatitis. Biotechnol Adv 2019; 42:107338. [PMID: 30639517 DOI: 10.1016/j.biotechadv.2019.01.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Revised: 01/02/2019] [Accepted: 01/07/2019] [Indexed: 02/08/2023]
Abstract
To date only small animal models have been employed to assess the effect of mesenchymal stromal cell (MSC) therapy on acute pancreatitis (AP), the most common cause of hospitalization for gastrointestinal diseases worldwide. We outline the challenges inherent in the small animal models of AP. We also point to specific benefits afforded by the adoption of larger animal models. The potential for MSC therapeutics in the treatment of AP was recognized over a decade ago. With sharper focus on the form of AP and development of new MSC delivery routes in larger animals, we believe the challenge can be engaged.
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Affiliation(s)
- Robbie R Goodman
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto M5S 3G9, Canada
| | - Madelaine K Jong
- Faculty of Dentistry, University of Toronto, Toronto M5G 1G6, Canada
| | - John E Davies
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, Toronto M5G 1G6, Canada.
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Risk Factors for Pancreatic Stone Formation in Type 1 Autoimmune Pancreatitis: A Long-term Japanese Multicenter Analysis of 624 Patients. Pancreas 2019; 48:49-54. [PMID: 30540679 DOI: 10.1097/mpa.0000000000001210] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP. METHODS Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation. RESULTS Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones. CONCLUSIONS The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.
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Tsang KFP, Oppong WK, Leeds SJ, Bekkali LHN, Nayar KM. Does IgG4 level at the time of diagnosis correlate with disease outcome in IgG4-Related disease? Pancreatology 2019; 19:177-181. [PMID: 30509569 DOI: 10.1016/j.pan.2018.10.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 10/26/2018] [Accepted: 10/28/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Serum IgG4 level is used as a diagnostic criterion for immunoglobulin G4-related disease (IgG4-RD) but whether it predicts disease progression is unclear. Aim of the study was to investigate if serum IgG4 level at the time of diagnosis correlates with disease outcome. METHODS Patients with a definitive diagnosis of IgG4-RD were included in this study. They were divided into two groups - Group 1: Elevated serum IgG4 at diagnosis and Group 2: Normal serum IgG4 at diagnosis. Outcome parameters including multiple organ involvement, exocrine and endocrine dysfunction, relapse and mortality were compared. Data was subanalysed for outcomes on 2 levels of serum IgG4 cut-off - A: The upper limit of normal (ULN) and B: Twice the ULN. RESULTS Of 47 patients, 31 (66%) patients had elevated serum IgG4 at diagnosis. There was no statistically significant difference between the two groups in any of the outcome parameters. Data analysed with the serum IgG4 levels > ULN showed no difference between the 2 groups for any of the outcome parameters. However, when the serum IgG4 cut-off was set to twice the ULN, there was a significantly higher rate of disease relapse (42.9% vs 11.5%, p = 0.02) and pancreatic exocrine insufficiency (PEI) (76.2% vs 42.3%, p = 0.041). CONCLUSION Raised serum IgG4 greater than two times the ULN was significantly associated with disease relapse and PEI in patients with IgG4-RD. Larger multicentre studies with longer follow-up are required to corroborate these findings and define the role and cut-off value of serum IgG4 in outcomes of IgG4-RD.
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Affiliation(s)
- K F Patrick Tsang
- HPB Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne, NE7 7DN, UK
| | - W Kofi Oppong
- HPB Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne, NE7 7DN, UK
| | - S John Leeds
- HPB Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne, NE7 7DN, UK
| | - L H Noor Bekkali
- HPB Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne, NE7 7DN, UK
| | - K Manu Nayar
- HPB Unit, Freeman Hospital, Freeman Road, Newcastle Upon Tyne, NE7 7DN, UK.
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Vujasinovic M, Valente R, Maier P, von Beckerath V, Haas SL, Arnelo U, Del Chiaro M, Kartalis N, Pozzi-Mucelli RM, Fernandez-Moro C, Verbeke CS, Yu J, Ye W, Löhr JM. Diagnosis, treatment and long-term outcome of autoimmune pancreatitis in Sweden. Pancreatology 2018; 18:900-904. [PMID: 30236651 DOI: 10.1016/j.pan.2018.09.003] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 09/05/2018] [Accepted: 09/12/2018] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Autoimmune pancreatitis (AIP) is a pancreatic inflammatory process characterized by a strong inflammatory cell infiltration and two histopathologically distinct subtypes: type 1 and type 2. Diagnosis is often challenging and requires a combination of clinical, laboratory and imaging data. AIP can mimic pancreatic tumours leading to unnecessary resections if not correctly diagnosed. Short- and long-term outcomes of AIP have been poorly investigated so far and no large series have been previously reported from Sweden. METHODS A single-centre, retrospective, cohort study of patients with histologically confirmed or highly probable diagnosis of AIP according to ICDC criteria. Demographic, clinical and radiological characteristics, type of treatment and its outcomes were collected and analysed. RESULTS Seventy-one patients with AIP (87% with type 1), were evaluated at Karolinska University Hospital between 2004 and 2018; 49% males, mean age 49 years (range 44-53). Among them, 28% were histologically confirmed, 35% presented with jaundice, 22% with acute pancreatitis, 39% had non-specific symptoms such as weight loss or abdominal pain, 84% showed other organ involvement (OOI). Radiologically, 76% showed a focal pancreatic enlargement, 27% diffuse enlargement, 27% signs of acute pancreatitis and 10% of chronic pancreatitis. Overall, 58 patients (81%) underwent treatment with different medications: 46 (79%) cortisone, 7 (12%) azathioprine, 5 (8%) other immunosuppressive drugs. Twenty-six (36%) underwent biliary stenting and 12 (16%) were given surgery. In total, 47% of patients developed pancreatic exocrine insufficiency (PEI), of whom 76% had a severe form (faecal elastase-1 < 100 μg/g) and 21% of patients developed diabetes mellitus (pancreatic endocrine insufficiency), of whom 73% required insulin. CONCLUSIONS AIP is a challenging disease for diagnosis and treatment. Cortisone treatment is generally successful and provides clinical remission in the large majority of patients (>90%). In the further course of the disease, a considerable number of patients develop PEI and diabetes. Only one-quarter of patients exhibit on imaging the characteristic "sausage-like" pancreas (diffuse enlargement), approximately three-quarters had a focal mass that could be misdiagnosed as pancreatic malignancy.
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Affiliation(s)
- Miroslav Vujasinovic
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Roberto Valente
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden; Department for Digestive Diseases, Sapienza University of Rome, Rome, Italy
| | - Pia Maier
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | | | - Stephan L Haas
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Urban Arnelo
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Marco Del Chiaro
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Nikolaos Kartalis
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Raffaella Maria Pozzi-Mucelli
- Department of Abdominal Radiology, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | | | - Caroline Sophie Verbeke
- Department of Pathology, Karolinska University Hospital, Stockholm, Sweden; Department of Pathology, University of Oslo, Oslo, Norway
| | - Jingru Yu
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - J Matthias Löhr
- Department for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden.
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49
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Abstract
OBJECTIVES Oral corticosteroid treatment is the standard therapy for autoimmune pancreatitis (AIP) and is highly effective. However, relapse may occur during maintenance therapy (MT). We aimed to clarify the predictive factors for relapse after 3 years of MT for use in deciding on the continuation of long-term MT. METHODS Among 56 retrospectively recruited AIP patients who received corticosteroid remission induction therapy followed by MT for a minimum of 5 years, 38 subjects were enrolled after exclusion criteria and divided into the relapse group of patients who experienced relapse after 3 years of MT and the nonrelapse group of patients who did not. RESULTS According to multivariate analysis, at least 4 other organ involvement numbers at diagnosis (hazard ratio, 5.82; 95% confidence interval, 1.203-28.192) and IgG of 1400 mg/dL or greater at 3 years of MT (hazard ratio, 4.41; 95% confidence interval, 1.096-17.790) were predictive factors for relapse after MT for 3 years, with patients exhibiting both predictive factors having a higher cumulative relapse rate than those with 1 or fewer predictive factor. CONCLUSIONS We uncovered 2 predictive factors for AIP relapse after 3 years of MT. These findings will assist in deciding corticosteroid therapy regimens at 3 years of MT to minimize AIP relapse risk and adverse corticosteroid effects.
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50
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Abstract
Type 1 autoimmune pancreatitis (AIP) is an IgG-4-related systemic disease that can manifest as a pancreatic disorder or another disorder of presumed autoimmune origin. Type 2 disease is typically characterized by absent IgG-4-positive cells. As patients often present with acute pancreatitis, obstructive jaundice, or pancreatic mass, it is imperative to exclude malignancy, a more common diagnosis. AIP may respond to corticosteroids, and has a strong association with other immune-mediated diseases. Recent literature suggests the benefit of immune-modulating therapy, including rituximab, although no consensus exists. This review covers the essentials of diagnosis, but focuses primarily on management of AIP.
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Affiliation(s)
- Kamraan Madhani
- Department of Medicine, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; Department of Medicine, Waterbury Internal Medicine Residency Program, Waterbury Hospital, Yale New Haven Hospital, Main 3, 64 Robbins Street, Waterbury, CT 06708, USA
| | - James J Farrell
- Section of Digestive Diseases, Yale University School of Medicine, Yale Center for Pancreatic Disease, Yale University, LMP 1080, 15 York Street, New Haven, CT 06510, USA.
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