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Agboola AA, Mohamed KH, Syed M, Shiwlani S, Butt R, Reza RR, Haseeb M, Nasir H. Type 1 Autoimmune Pancreatitis Masquerading as Pancreatic Head Carcinoma. Cureus 2023; 15:e47471. [PMID: 38022068 PMCID: PMC10662655 DOI: 10.7759/cureus.47471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/22/2023] [Indexed: 12/01/2023] Open
Abstract
Obstructive jaundice is a joint clinical presentation with many etiologies, including pancreatic cancer and autoimmune pancreatitis (AIP). Differentiating between these two conditions is pivotal due to the divergent management approaches and prognoses. In this case report, we present a case of a 49-year-old female patient who presented with weight loss, intermittent chronic abdominal pain, and jaundice. She was initially suspected of having pancreatic cancer because of clinical presentation and imaging findings. However, she was ultimately diagnosed with Type 1 AIP due to histopathology findings and elevated immunoglobulin G4. This case highlights the complexities in diagnosis, the role of advanced imaging techniques and tissue sampling, and the lessons learned regarding managing this challenging clinical scenario.
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Affiliation(s)
| | - Khalid H Mohamed
- Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, GBR
| | - Maria Syed
- Surgery, Aga Khan University Hospital, Karachi, PAK
| | | | - Rowaida Butt
- Family Medicine, Avalon University School of Medicine, Ohio, USA
| | | | - Muhammad Haseeb
- Internal Medicine, Allama Iqbal Medical College, Lahore, PAK
- Internal Medicine, Bahria International Hospital, Lahore, PAK
| | - Hira Nasir
- Internal Medicine, Mayo Hospital, Lahore, PAK
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2
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Nikolic S, Panic N, Hintikka ES, Dani L, Rutkowski W, Hedström A, Steiner C, Löhr JM, Vujasinovic M. Efficacy and safety of rituximab in autoimmune pancreatitis type 1: our experiences and systematic review of the literature. Scand J Gastroenterol 2021; 56:1355-1362. [PMID: 34410885 DOI: 10.1080/00365521.2021.1963837] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/20/2021] [Accepted: 07/28/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Autoimmune pancreatitis (AIP) is a special form of pancreatitis that responds well to glucocorticoid (GC) treatment. Relapses of AIP are common. The anti-CD20 antibody rituximab (RTX) has shown promising results in GC refractory cases, but long-term data are scarce. The study aims to determine the clinical and imaging response to RTX and summarize the existing data on RTX therapy in patients with AIP type 1 in the literature. PATIENTS AND METHODS Retrospective analysis of electronic medical records was conducted. Additionally, we conducted a systematic review of the literature concerning RTX use in AIP type 1. RESULTS Twelve (11.7%) of 103 patients with AIP type 1 were treated with RTX during the study period: eight (66.7%) achieved complete and four (33.3%) partial remission. RTX was discontinued in one patient who developed fever and reactivation of latent tuberculosis. None of the remaining 11 patients relapsed during a median follow-up of 17 months. No significant differences were detected in baseline clinical characteristics or history of relapse between the patients who obtained complete and partial remission. Altogether, eight studies with 110 AIP type-1 patients treated with RTX were analyzed. Adverse effects ranged from 11-43% and the relapse-free period during follow-up (range 2-173 months) ranged from 38-94%. CONCLUSIONS Our results confirm that RTX is efficacious in the treatment of AIP type 1 by inducing remission and preventing relapse. In addition, there are few adverse effects of the treatment.
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Affiliation(s)
- Sara Nikolic
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
- Department of Gastroenterology, Division of Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia
| | - Nikola Panic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | | | - Lara Dani
- Rheumatology Division, Department of Medicine, Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Wiktor Rutkowski
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Aleksandra Hedström
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Corinna Steiner
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - J-Matthias Löhr
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
| | - Miroslav Vujasinovic
- Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
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Yoon SB, Moon SH, Kim JH, Park JW, Kim SE, Kim MH. Determination of the duration of glucocorticoid therapy in type 1 autoimmune pancreatitis: A systematic review and meta-analysis. Pancreatology 2021; 21:S1424-3903(21)00474-9. [PMID: 34090808 DOI: 10.1016/j.pan.2021.05.303] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/18/2021] [Accepted: 05/21/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND The indications for maintenance glucocorticoid therapy (MGT) and its duration after initial remission of type 1 autoimmune pancreatitis (AIP) remain controversial. In contrast to the Japanese treatment protocol, the Mayo protocol does not recommend MGT after initial remission. This study aimed to evaluate the relapse rate in patients with type 1 AIP according to the duration of glucocorticoid therapy. METHODS We conducted a systematic literature review up until November 30, 2020, and identified 40 studies reporting AIP relapse rates. The pooled relapse rates were compared between groups according to the protocol and duration of glucocorticoids (routine vs. no MGT; glucocorticoids ≤6 months vs. 6-12 months vs. 12-36 months vs. ≥ 36 months). The pooled rates of adverse events related to glucocorticoids were also evaluated. RESULTS Meta-analysis indicated calculated pooled relapse rates of 46.6% (95% confidence interval (CI), 38.9-54.3%) with glucocorticoids for ≤ 6 months, 44.3% (95% CI, 38.8-49.8%) for 6-12 months, 34.1% (95% CI, 28.6-39.7%) for 12-36 months, and 27.0% (95% CI, 23.4-30.6%) for ≥ 36 months. The rate of relapse was also significantly lower in patients with routine-use protocol of MGT (31.2%; 95% CI, 27.5-34.8%) than in patients with no MGT protocol (44.1%; 95% CI, 35.8-52.4%). Adverse events were comparable between groups. CONCLUSIONS The rate of relapse tended to decrease with extended durations of glucocorticoid therapy up to 36 months. Clinicians may decide the duration of glucocorticoids according to patient condition, including comorbidities and risk of relapse.
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Affiliation(s)
- Seung Bae Yoon
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung-Hoon Moon
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea.
| | - Jong Hyeok Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Ji Won Park
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea; Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, South Korea
| | - Myung-Hwan Kim
- Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea
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Zhang W, Stone JH. Management of IgG4-related disease. THE LANCET. RHEUMATOLOGY 2019; 1:e55-e65. [PMID: 38229361 DOI: 10.1016/s2665-9913(19)30017-7] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 07/14/2019] [Accepted: 07/18/2019] [Indexed: 12/12/2022]
Abstract
IgG4-related disease was unrecognised as a unified disease entity until this century, yet in a short period of time the disease has been appreciated to have a worldwide distribution, and its clinical, pathological, and radiological features have been described in considerable detail. The disease has strong organ predilections, and many of the clinical presentations of disease are increasingly familiar to both generalists and specialists. Early recognition of IgG4-related disease is crucial because although the disease is highly treatable, it can lead to serious organ damage and even death if undiagnosed until advanced stages. Its indolent nature often makes diagnosis challenging, and IgG4-related disease is one of the great mimickers of other diseases in the current era. Glucocorticoids are an effective treatment for IgG4-related disease, but their long-term use is problematic in a disease that frequently affects middle-aged to elderly individuals and often leads to pancreatic dysfunction. Our understanding of the pathophysiology of the disease is surprisingly advanced given the relatively recent recognition of this condition. Insights into disease pathophysiology offer the possibility of a variety of targeted treatment approaches. Looking ahead, biological therapies could profoundly alter the way in which IgG4-related disease is managed, permitting the use of specific therapies that are tailored to patients' clinical phenotypes.
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Affiliation(s)
- Wen Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Beijing, China
| | - John H Stone
- Rheumatology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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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] [MESH Headings] [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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Frulloni L, de Pretis N, Amodio A. Maintenance therapy in autoimmune pancreatitis: a weak light into the darkness. ANNALS OF TRANSLATIONAL MEDICINE 2017; 5:367. [PMID: 28936461 DOI: 10.21037/atm.2017.07.06] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Luca Frulloni
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Nicolò de Pretis
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
| | - Antonio Amodio
- Department of Medicine, Pancreas Institute, University of Verona, Verona, Italy
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de Pretis N, Amodio A, Bernardoni L, Campagnola P, Capuano F, Chari ST, Crinò S, Gabbrielli A, Massella A, Topazian M, Frulloni L. Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis. Clin Transl Gastroenterol 2017; 8:e90. [PMID: 28448071 PMCID: PMC5543465 DOI: 10.1038/ctg.2017.17] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 02/11/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES Steroids are used to induce remission in autoimmune pancreatitis (AIP). Low-dosage steroid therapy or immunosuppressant (IMs) has been proposed as maintenance therapy to prevent AIP relapse. Few and conflicting data have been published on the efficacy of azathioprine (AZA) in preventing AIP relapse. The aim of this study was to evaluate the indication and efficacy of AZA as maintenance therapy to prevent disease relapse in AIP. METHODS Patients suffering from AIP diagnosed according to the ICDC in type 1, type 2, and not otherwise specified (NOS) were divided in those treated with AZA (AZA+ group) as maintenance therapy and not treated with maintenance therapy (AZA- group). Exclusion criteria were: previous pancreatic surgery, other autoimmune diseases as indication for AZA treatment, and use of IMs different from AZA. Drug safety, clinical and instrumental outcome of AZA+ patients were evaluated. RESULTS A total of 23 patients (18 Males and 5 Females, mean age 54±11 years) in AZA+ group and 97 (58 Males and 39 Females, mean age 45±18 years) in AZA- group were compared. In AZA+ group, patients were significantly older (P=0.043), type 1 AIP was more frequently diagnosed (87 vs. 51%, P=0.006), sIgG4 higher (758±625 vs. 311±409 mg/dl, P<0.001), other organ involvement (OOI) more frequently observed (83 vs. 48%, P=0.002), with higher frequency of relapse before AZA treatment (78 vs. 14%, P<0.001). Three patients in AZA+ group required drug discontinuation because of adverse events. Twenty patients were therefore evaluated for outcome. Six out of 20 patients (30%) relapsed after 24±15 months (5 in pancreas and 1 on biliary tract). They were retreated with steroids and continued AZA. Two out of 6 patients (33%) had a second relapse,after respectively 11 months (in pancreas and kidney) and 22 months (in kidney). CONCLUSIONS AZA is an effective and safe treatment to prevent AIP relapses.
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Affiliation(s)
- Nicolò de Pretis
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Antonio Amodio
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Pietro Campagnola
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Fabiana Capuano
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Suresh T Chari
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Stefano Crinò
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Armando Gabbrielli
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Arianna Massella
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Luca Frulloni
- Gastroenterology Unit, Department of Medicine, Pancreas Center, University of Verona, Verona, Italy
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Masamune A, Nishimori I, Kikuta K, Tsuji I, Mizuno N, Iiyama T, Kanno A, Tachibana Y, Ito T, Kamisawa T, Uchida K, Hamano H, Yasuda H, Sakagami J, Mitoro A, Taguchi M, Kihara Y, Sugimoto H, Hirooka Y, Yamamoto S, Inui K, Inatomi O, Andoh A, Nakahara K, Miyakawa H, Hamada S, Kawa S, Okazaki K, Shimosegawa T. Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis. Gut 2017; 66:487-494. [PMID: 27543430 DOI: 10.1136/gutjnl-2016-312049] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Revised: 07/23/2016] [Accepted: 07/26/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Corticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP. DESIGN We conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5-7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis. RESULTS Between April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed. CONCLUSIONS Maintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks. TRIAL REGISTRATION NUMBER UMIN000001818; Results.
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Affiliation(s)
- Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Kazuhiro Kikuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ichiro Tsuji
- Division of Epidemiology, Department of Health Informatics and Public Health, Tohoku University School of Public Health, Graduate School of Medicine, Sendai, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tatsuo Iiyama
- Integrated Center for Advanced Medical Technologies (ICAM-Tech), Kochi Medical School, Kochi, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yuichi Tachibana
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tetsuhide Ito
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan
| | - Hideaki Hamano
- Medical Informatics Division and Internal Medicine, Gastroenterology, Shinshu University Hospital, Matsumoto, Japan
| | - Hiroaki Yasuda
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Junichi Sakagami
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Mitoro
- Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan
| | - Masashi Taguchi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | | | - Hiroyuki Sugimoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Satoshi Yamamoto
- Department of Gastroenterology, Second Teaching Hospital, Fujita Health University, Nagoya, Japan
| | - Kazuo Inui
- Department of Gastroenterology, Second Teaching Hospital, Fujita Health University, Nagoya, Japan
| | - Osamu Inatomi
- Department of Medicine, Shiga University of Medical Science, Otsu, Japan
| | - Akira Andoh
- Department of Medicine, Shiga University of Medical Science, Otsu, Japan
| | - Kazuyuki Nakahara
- Department of Gastroenterology, Kumamoto Regional Medical Center, Kumamoto, Japan
| | - Hiroyuki Miyakawa
- Department of Bilio-Pancreatology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Shin Hamada
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Shigeyuki Kawa
- Center for Health, Safety, and Environmental Management, Shinshu University, Matsumoto, Japan
| | - Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Autoimmune Pancreatitis Masquerading as Pancreatic Cancer: when in Doubt, Cut It Out. J Gastrointest Cancer 2017; 49:365-372. [PMID: 28197777 DOI: 10.1007/s12029-017-9924-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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10
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Karimi S, Bharill P. Autoimmune Pancreatitis: A Case of Atypical Radiographic Findings. Case Rep Gastroenterol 2016; 10:581-588. [PMID: 27920645 PMCID: PMC5121540 DOI: 10.1159/000448988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 08/09/2016] [Indexed: 01/11/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare pancreatic disorder that can present as a manifestation of a broader systemic inflammatory disease known as immunoglobulin G4-related systemic disease (IGG4-RSD). AIP is divided into two subtypes based on clinical, radiological, and histological findings. The disease can be mistaken for pancreatic cancer because of overlapping clinical and radiological findings, but early recognition can help avoid unnecessary surgery. We present a case of a 65-year-old female with suspected acute gallstone pancreatitis found to have AIP based on serology, radiological findings, and response to steroids.
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Affiliation(s)
- Shawhin Karimi
- Department of Medicine, University of Pittsburgh Medical Center - Mercy Hospital, Pittsburgh, Pa., USA
| | - Parth Bharill
- Division of Gastroenterology, University of Pittsburgh Medical Center - Mercy Hospital, Pittsburgh, Pa., USA
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Rousselin C, Pontana F, Puech P, Lambert M. Diagnostics différentiels des aortites inflammatoires. Rev Med Interne 2016; 37:256-63. [DOI: 10.1016/j.revmed.2016.02.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Accepted: 02/04/2016] [Indexed: 12/24/2022]
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12
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Vasaitis L. IgG4-related disease: A relatively new concept for clinicians. Eur J Intern Med 2016; 27:1-9. [PMID: 26481243 DOI: 10.1016/j.ejim.2015.09.022] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2015] [Revised: 07/09/2015] [Accepted: 09/30/2015] [Indexed: 02/08/2023]
Abstract
IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy. The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression. About 30-50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a "capsule-like rim" surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD. This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD.
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Affiliation(s)
- Lilian Vasaitis
- Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
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Sarkar A, Pitchumoni CS. The protean manifestations of IgG4-RD in gastrointestinal disorders. Dis Mon 2015; 61:493-515. [DOI: 10.1016/j.disamonth.2015.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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IgG4 antibodies in autoimmune polyglandular disease and IgG4-related endocrinopathies: pathophysiology and clinical characteristics. Curr Opin Pediatr 2014; 26:493-9. [PMID: 24905103 DOI: 10.1097/mop.0000000000000107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE OF REVIEW This review discusses the IgG4-related disease spectrum (IgG4-RD), the autoimmune polyglandular syndromes (APS), the association of IgG4 with APS, and possible pathobiology. RECENT FINDINGS IgG4-RD is a multiorgan autoimmune disorder characterized by fibrous inflammation, IgG4-positive plasma cell infiltration in affected tissues, and elevated serum concentrations of IgG4. IgG4-RD can affect any organ and has a heterogeneous presentation. Consensus criteria for diagnosis in specific organs have been established. The recognition and diagnosis of IgG4-RD are crucial because the disease responds favorably to immunosuppression (e.g., glucocorticoids, rituximab). The precise mechanisms leading to disease are unknown, but IgG4 antibodies may undergo a half antibody exchange, which renders them incapable of activating the complement pathway. SUMMARY Despite significant advances in disease recognition and treatment strategies, the disorder remains poorly understood. The precise role of IgG4, whether it is protective or pathogenic, is still being debated.
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O’Reilly DA, Malde DJ, Duncan T, Rao M, Filobbos R. Review of the diagnosis, classification and management of autoimmune pancreatitis. World J Gastrointest Pathophysiol 2014; 5:71-81. [PMID: 24891978 PMCID: PMC4025075 DOI: 10.4291/wjgp.v5.i2.71] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 04/17/2014] [Indexed: 02/06/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, with as yet undetermined incidence and prevalence in the general population. Our understanding of it continues to evolve. In the last few years, 2 separate subtypes have been identified: type 1 AIP has been recognised as the pancreatic manifestation of a multiorgan disease, named immunoglobulin G4 (IgG4)-related disease while type 2 AIP is a pancreas specific disorder not associated with IgG4. International criteria for the diagnosis of AIP have been defined: the HISORt criteria from the Mayo clinic, the Japan consensus criteria and, most recently, the international association of pancreatology “International Consensus Diagnostic Criteria”. Despite this, in clinical practice it can still be very difficult to confirm the diagnosis and differentiate AIP from a pancreatic cancer. There are no large studies into the long-term prognosis and management of relapses of AIP, and there is even less information at present regarding the Type 2 AIP subtype. Further studies are necessary to clarify the pathogenesis, treatment and long-term outcomes of this disease. Critically for clinicians, making the correct diagnosis and differentiating the disease from pancreatic cancer is of the utmost importance and the greatest challenge.
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The great mimicker: IgG4-related disease. Clin Rheumatol 2013; 32:1267-73. [PMID: 23877485 DOI: 10.1007/s10067-013-2326-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 06/26/2013] [Indexed: 12/13/2022]
Abstract
IgG4-related disease is defined as a multi-organ systemic disorder with pathological findings affecting a wide range of organ systems. The condition unifies a large number of clinical diagnoses previously considered as being confined to single organ systems. At present, several issues related to its pathophysiology remained controversial, including the natural history of the disease, the pathogenic role of IgG4, and its use as a biomarker. Glucocorticoids are considered the treatment of choice for remission induction of IgG4-related disease manifestations; however, concerns regarding duration of therapy and management of refractory disease remained to be elucidated.
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Abstract
Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes.
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Affiliation(s)
- Gyanprakash A. Ketwaroo
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Sunil Sheth
- Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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Abstract
IgG4-associated cholangitis is the hepatobiliary manifestation of a recently characterized inflammatory systemic disease, associated with increased IgG4 serum levels and IgG4-positive lymphoplasmacytic infiltration. Often, patients present with obstructive jaundice, and imaging reveals stenoses of the extrahepatic or intrahepatic bile ducts, often in association with parenchymal pancreatic findings and irregularities of the pancreatic duct. The histologic findings include lymphoplasmacytic infiltrates, on occasion resulting in tumefactive lesions (which can mimic malignancy), obliterative phlebitis, and fibrotic changes. Steroid treatment is the mainstay of management, but relapse is common after discontinuation of therapy or during tapering of steroids and may require further treatment.
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Affiliation(s)
- Marina G Silveira
- Division of Gastroenterology and Hepatology, Louis Stokes Cleveland VAMC, Case Medical Center, 10701 East Boulevard, 111E (W), Cleveland, OH 44106, USA.
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Abstract
OPINION STATEMENT Having diagnosed a patient as having IgG4-related disease, I would have a low threshold for recommending immune-suppressive treatment, and would make that recommendation for any patient with vascular involvement. My initial approach would be prednisone at 40-60 mg/day with a plan to reduce the dose every two weeks, e.g., 40, 30, 20, 15, 10, 7.5, 5, and 2.5 mg for 2 weeks each. In the event of relapse, I would double the current prednisone dose, slow the taper, and add azathioprine, anticipating using that drug for one year if the patient were to remain in remission. In the event or subsequent relapse, I would stop azathioprine and use rituximab. In a patient with large artery involvement, I would consult a vascular surgeon soon after diagnosis, anticipating a need for surgical repair.
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Affiliation(s)
- Paul A Monach
- Vasculitis Center and Section of Rheumatology, Boston University School of Medicine, 72 East Concord Street, E-533, Boston, MA, 02118, USA,
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Liu B, Li J, Yan LN, Sun HR, Liu T, Zhang ZX. Retrospective study of steroid therapy for patients with autoimmune pancreatitis in a Chinese population. World J Gastroenterol 2013; 19:569-574. [PMID: 23382638 PMCID: PMC3558583 DOI: 10.3748/wjg.v19.i4.569] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 12/27/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the optimal steroid therapeutic strategy for autoimmune pancreatitis (AIP).
METHODS: This study was conducted retrospectively in two large institutions in China. Patients with clinically, radiologically and biochemically diagnosed AIP were enrolled. The performed radiological investigations and biochemical tests, the regimen of the given steroid treatment, remission and relapse whether with and without steroid therapy were analyzed.
RESULTS: Twenty-eight patients with AIP received steroid treatment, while 40 patients were treated surgically by pancreatoduodenectomy, distal pancreatectomy and choledochojejunostomy, radiofrequency ablation for the enlarged pancreatic head, percutaneous transhepatic biliary drainage and endoscopic biliary drainage. The starting oral prednisolone dose was 30 mg/d in 18 (64.3%) patients and 40 mg/d in 10 (35.7%) patients administered for 3 wk. The remission rate of AIP patients with steroid treatment (96.4%) was significantly higher than in those without steroid treatment (75%). Maintenance therapy (oral prednisolone dose 5 mg/d) was performed after remission for at least 6-12 mo to complete the treatment course. Similarly, the relapse rate was significantly lower in AIP patients with steroid treatment (28.6%) than in those without steroid treatment (42.5%). Steroid re-treatment was effective in all relapsed patients with or without steroid therapy.
CONCLUSION: Steroid therapy should be considered in all patients with active inflammatory phase of AIP. However, the optimal regimen still should be trailed in larger numbers of patients with AIP.
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21
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Proctor RD, Rofe CJ, Bryant TJC, Hacking CN, Stedman B. Autoimmune pancreatitis: an illustrated guide to diagnosis. Clin Radiol 2012. [PMID: 23177083 DOI: 10.1016/j.crad.2012.08.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Autoimmune pancreatitis (AIP) remains one of the rarer forms of pancreatitis but has become increasingly well recognized and widely diagnosed as it is an important differential, particularly due to the dramatic response to appropriate therapy. It is now best considered as part of a multisystem disease and the notion of "IgG4-related systemic sclerosing disease" has become widely recognized as the number of extra-pancreatic associations of AIP grows. More recently AIP has been classified into two subtypes: lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) with distinct geographical, age and sex distributions for the two subtypes, in addition to different pathological characteristics. The role of imaging is crucial in AIP and should be considered in conjunction with clinical, serological, and histopathological findings to make the diagnosis. Radiologists are uniquely placed to raise the possibility of AIP and aid the exclusion of significant differentials to allow the initiation of appropriate management and avoidance of unnecessary intervention. Radiological investigation may reveal a number of characteristic imaging findings in AIP but appearances can vary considerably and the focal form of AIP may appear as a pancreatic mass, imitating pancreatic carcinoma. This review will illustrate typical and atypical appearances of AIP on all imaging modes. Emphasis will be placed on the imaging features that are likely to prove useful in discriminating AIP from other causes prior to histopathological confirmation. In addition, examples of relevant differential diagnoses are discussed and illustrated.
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Affiliation(s)
- R D Proctor
- Department of Clinical Radiology, Royal Cornwall Hospitals NHS Trust, Truro, UK
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IgG4-related systemic disease: Report of a case in an elderly patient. Eur Geriatr Med 2012. [DOI: 10.1016/j.eurger.2012.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Autoantibodies in autoimmune pancreatitis. Int J Rheumatol 2012; 2012:940831. [PMID: 22844291 PMCID: PMC3403403 DOI: 10.1155/2012/940831] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2011] [Revised: 04/19/2012] [Accepted: 04/21/2012] [Indexed: 12/24/2022] Open
Abstract
Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.
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Sah RP, Chari ST. Autoimmune pancreatitis: an update on classification, diagnosis, natural history and management. Curr Gastroenterol Rep 2012; 14:95-105. [PMID: 22350841 DOI: 10.1007/s11894-012-0246-8] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Autoimmune Pancreatitis (AIP) is a recently recognized chronic fibro-inflammatory disease of the pancreas. Although rare, its recognition continues to increase worldwide. Patients often present with painless obstructive jaundice mimicking pancreatic cancer. Two subtypes of AIP are known-type 1 is a multi-organ disease associated with IgG4; type 2 appears to be a pancreas-specific disorder. Dramatic response to steroid treatment is characteristic of both forms. A non-invasive diagnosis of type 1 AIP may be possible using diagnostic criteria (in ~70% cases) while diagnosis of type 2 requires histology. These subtypes differ in natural history- type 1 often relapses while initial reports suggest that type 2 does not. Long term complications include endocrine and exocrine insufficiency and in case of type 1, disease relapses and complications from extra-pancreatic involvement. Neither form affects long term survival. The treatment and follow-up guidelines continue to evolve with our increasing experience in AIP.
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Affiliation(s)
- Raghuwansh P Sah
- Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN 55905, USA
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25
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Hermet M, Kémény JL, Guettrot-Imbert G, Delèvaux I, Aumaître O, André M. Maladie fibrosclérosante à IgG4. Presse Med 2012; 41:682-94. [DOI: 10.1016/j.lpm.2011.10.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 10/04/2011] [Accepted: 10/10/2011] [Indexed: 02/08/2023] Open
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Distinguishing autoimmune pancreatitis from pancreaticobiliary cancers: current strategy. Ann Surg 2012; 255:248-58. [PMID: 21997803 DOI: 10.1097/sla.0b013e3182324549] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
OBJECTIVE A review of the literature to identify current modalities for the diagnosis of autoimmune pancreatitis (AIP) with the objective of establishing a strategy to distinguish it from pancreaticobiliary cancers. BACKGROUND Pancreatic and biliary manifestations of AIP mimic pancreaticobiliary cancers. Misdiagnosis of AIP can result in major surgery for a steroid-responsive disease. METHODS A review of the literature was performed to identify recent advances in the diagnosis of AIP and evaluate outcomes with various diagnostic strategies to minimize operative intervention for an autoimmune disease. RESULTS Diagnostic criteria for AIP are based on histology, imaging, serology, extrapancreatic organ involvement, and response to steroid therapy. The most commonly involved extrapancreatic sites are bile duct, kidney, and retroperitoneum. The Mayo Clinic diagnostic strategy utilizes core biopsy of the pancreas and the Japanese strategy depends on a characteristic pancreatogram. The rate of operative intervention was similar with both strategies and none of the patients with cancer received steroid therapy. Immunoglobulin G subtype 4 (IgG4)-associated cholangitis mimics cholangiocarcinoma and presence of more than 10 IgG4-positive plasma cells/high power field on endoscopic biopsy of the bile duct was diagnostic for AIP in 88% patients. Biliary complications and early relapse are common after surgical resection and immunomodulatory drugs can maintain long-term remission. CONCLUSION Criteria based on histology, imaging, endoscopy, serology, extrapancreatic organ involvement, and response to steroid therapy improve the diagnostic yield for AIP. Application of diagnostic and therapeutic protocols by a multidisciplinary team will optimize outcomes with a decline in the rate of operative intervention for AIP, a steroid-responsive disease with propensity for relapse.
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28
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Clinicopathologic features and treatment outcomes in Cronkhite-Canada syndrome: support for autoimmunity. Dig Dis Sci 2012; 57:496-502. [PMID: 21881972 DOI: 10.1007/s10620-011-1874-9] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2011] [Accepted: 08/12/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS Cronkhite-Canada syndrome (CCS) is a noninherited condition, associated with high morbidity, and characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. All features may respond to immunosuppressive therapy, but little is known about the etiology. An autoimmune origin has been suggested but not proved. From a retrospectively selected cohort, we evaluated clinicopathologic features, including immunostaining for IgG4 (an antibody associated with autoimmunity), and therapeutic outcomes in a cohort of CCS patients to provide further insights into this disease. METHODS Cases included 14 consecutive CCS patients seen at the Mayo Clinic on whom tissue and follow-up were available. All histology was reviewed by an expert gastrointestinal pathologist. Immunostaining for IgG4 was performed on 42 polyps from CCS cases and on control tissues, including 46 histologically similar hamartomas [from juvenile polyposis syndrome (JPS)] and 20 normal mucosae (six stomach, three small bowel, and 11 colon). Clinical features and treatment outcomes were descriptive. RESULTS All CCS cases had both upper and lower gastrointestinal polyps; most had typical dermatologic features of alopecia, hyperpigmentation, and onychodystrophy; and most had evidence of protein-losing enteropathy. Ten patients (71%) had adenomatous polyps and 2 (14%) had colorectal cancer. IgG4 immunostaining was positive (>5 cells/HPF) in 52% of CCS polyps compared to 12% of JPS polyps (P = 0.001); IgG4 staining was negative in all other control tissues. Of 11 CCS patients treated with oral corticosteroids, 91% achieved remission. Relapse was common with steroid tapering. Five patients who initially responded to corticosteroids were maintained in remission on azathioprine (2 mg/kg/day) with no relapse after a median of 4.5 years. CONCLUSIONS Immunostaining for the autoimmune-related IgG4 antibody is significantly increased in CCS polyps compared to disease and normal control tissues. Furthermore, immunosuppression by corticosteroids or long-term azathioprine may eradicate or lessen manifestations of CCS. These histologic findings and treatment responses are consistent with an autoimmune mechanism underlying CCS.
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The spectrum of sclerosing cholangitis and the relevance of IgG4 elevations in routine practice. Am J Gastroenterol 2012; 107:56-63. [PMID: 22068666 DOI: 10.1038/ajg.2011.375] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES American Association for the Study of Liver Diseases (AASLD) guidance recommends measurement of IgG4 in patients with sclerosing cholangitis (SC). The objective of this study was to evaluate this by analyzing our SC practice. METHODS Characteristics were collected on 168 patients with radiological or biopsy proven SC; IgG4 was measured and magnetic resonance cholangiopancreatography studies were reviewed. RESULTS In all, 49% of patients were females and 55% had inflammatory bowel disease. Large duct disease was present in 63%, small duct disease in 8%, overlap with AIH in 11%, and secondary SC in 18%. Secondary etiologies included autoimmune pancreatitis (AIP) (8%), intra-hepatic cholelithiasis (3%), portal vein thrombosis (2%), and neonatal Kasai (2%). In all, 101 patients had sufficient radiology and serology for re-evaluation. IgG4 was elevated (>104 mg/dl) in 22% of patients. This was associated with male gender (73%; P=0.016), a past history of pancreatitis (27% vs. 5%; P=0.007), a higher alkaline phosphatase (ALP) value, median 338.5 U/l vs. 160 (P=0.005), and a higher primary sclerosing cholangitis (PSC) Mayo risk score, mean 0.6 vs. -0.2 (P=0.0008). Prior biliary intervention was more likely (36 vs. 13%; P=0.023), while abnormal pancreatic imaging was noted in 15%, more frequently if IgG4 was elevated (40 vs. 8%; P=0.0007). After excluding those with pancreatic disease on magnetic resonance imaging, 14 patients had elevated IgG4. This group had higher ALP 379 U/l vs. 155.5 (P=0.0006), aspartate aminotransferase (AST) 72.5 U/l vs. 34 (P=0.0005), alanine aminotransferase (ALT) 90.5 U/l vs. 36 (P=0.004), and PSC Mayo risk score values 0.4 vs. -0.2 (P=0.017). CONCLUSIONS SC is a heterogeneous liver injury. IgG4 testing may be clinically important in all patients, since it appears to identify a distinct patient population, more so than just those with AIP.
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Zen Y, Bogdanos DP, Kawa S. Type 1 autoimmune pancreatitis. Orphanet J Rare Dis 2011; 6:82. [PMID: 22151922 PMCID: PMC3261813 DOI: 10.1186/1750-1172-6-82] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 12/07/2011] [Indexed: 02/07/2023] Open
Abstract
Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed to be involved in the underlying immune reaction. IgG4 antibodies have two unique biological functions, Fab-arm exchange and a rheumatoid factor-like activity, both of which may play immune-defensive roles. However, the exact role of IgG4 in this disease still remains to be clarified. It seems important to recognize this unique entity given that the disease is treatable with steroids.
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Affiliation(s)
- Yoh Zen
- Institute of Liver Studies, King's College Hospital and King's College London School of Medicine, Denmark Hill, London SE5 9RS, UK.
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Ebbo M, Grados A, Daniel L, Vély F, Harlé JR, Pavic M, Schleinitz N. [IgG4-related systemic disease: emergence of a new systemic disease? Literature review]. Rev Med Interne 2011; 33:23-34. [PMID: 21955722 DOI: 10.1016/j.revmed.2011.08.012] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Revised: 08/22/2011] [Accepted: 08/24/2011] [Indexed: 02/08/2023]
Abstract
Hyper-IgG4 syndrome, or IgG4-related systemic disease (IgG4-RSD), has been recently characterized by the association of a focal or diffuse enlargement in one or more organs, elevated levels of serum IgG4 and histopathological findings including "storiform" fibrosis and prominent infiltration of lymphocytes and IgG4-positive plasma cells. Pancreas was the first organ involved with sclerosing pancreatitis (or autoimmune pancreatitis). Since this first description, many extrapancreatic lesions have been described, even in the absence of pancreatitis and include sialadenitis, lacrimal gland inflammation, lymphadenopathy, aortitis, sclerosing cholangitis, tubulointerstitial nephritis, retroperitoneal fibrosis or inflammatory pseudotumors. Multiorgan lesions can occur synchronously or metachronously in a same patient, usually after 50 years of age. They all share common histopathological findings. The disease often responds well to corticosteroid therapy. In this literature review on IgG4-RSD, we present historical, epidemiological and clinical characteristics, and we review the biological and histological diagnostic criteria. To date there is no international validated diagnostic criteria. Pathophysiological hypothesis and therapeutic approaches are also discussed.
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Affiliation(s)
- M Ebbo
- Service de médecine interne, hôpital de La Conception, Assistance publique-Hôpitaux de Marseille, Marseille cedex 5, France.
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Abstract
PURPOSE OF REVIEW IgG4-related systemic disease (IgG4-RSD) is a systemic fibroinflammatory condition that can affect any organ system. Prompt recognition and management of this disease process are necessary to prevent sclerosis and permanent organ damage. Here, we review the advances in treatment approaches to IgG4-RSD. RECENT FINDINGS Most information regarding treatment is derived from retrospective case series of patients with autoimmune pancreatitis (AIP), and follow-up periods have generally been short. A variety of IgG4-RSD presentations respond rapidly to glucocorticoid treatment. Glucocorticoids have become a standard therapy for AIP, but the indications requiring treatment as well as the appropriate starting dose and duration of therapy remain controversial. The importance of maintenance of glucocorticoids following remission induction is debatable. As our knowledge grows regarding other organ manifestations of IgG4-RSD with longer follow-ups, the necessity of steroid-sparing agents to manage frequent relapses becomes clear. SUMMARY The natural history and long-term prognosis of IgG4-RSD are not well understood. Large prospective studies and randomized controlled trials of patients with wide spectrum manifestations of IgG4-RSD are required to support better approaches to treatment.
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Affiliation(s)
- Arezou Khosroshahi
- Rheumatology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
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Abstract
PURPOSE OF REVIEW IgG4-related systemic disease (ISD) is a recently recognized syndrome affecting multiple organs. Autoimmune pancreatitis (AIP) is the pancreatic manifestation of ISD and mimics pancreatic cancer. Current data show frequent association with serum IgG4 elevation and other serologic abnormalities. Here we explore the diagnostic and possible prognostic utility and pathogenetic implications of serologic abnormalities in ISD. RECENT FINDINGS Serum IgG4 elevations (>140 mg/dl) are seen in 70-80% of AIP patients and also in 5% of normal population and 10% of pancreatic cancer making it an unsuitable single marker for diagnosis. However, when combined with other features of AIP, it can be of great diagnostic value though its utility in monitoring of therapy or as a marker or predictor of relapse is limited. Several other antibodies have been identified in AIP against pancreas-specific antigens like trypsinogens I and II, pancreatic secretory trypsin inhibitor (PSTI) and plasminogen binding protein (PBP) and other nonpancreas-specific antigens. Anti-PBP antibodies appear to have potential diagnostic utility but require further validation. SUMMARY No single serologic marker is diagnostic of ISD. Serum IgG4 elevation has convincing diagnostic utility when combined with other disease features although its value in disease monitoring may be limited.
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Abstract
PURPOSE OF REVIEW To summarize the existing knowledge of autoimmune pancreatitis (AIP) and to review the progress made in the diagnosis and treatment of AIP in the past year. RECENT FINDINGS The term 'AIP' appears to encompass at least two distinct subtypes, type 1 and type 2. Type 1 AIP is the pancreatic manifestation of a systemic fibroinflammatory disease called immunoglobulin G4-associated systemic disease. Type 2 AIP affects younger patients, does not have a gender predilection and is associated with normal serum immunoglobulin G4 levels. Existing criteria are geared toward diagnosis of type 1; type 2 AIP can be definitively diagnosed only on pancreatic histology. Both subtypes respond to corticosteroid therapy. However, there are no standardized protocols for initial treatment or management and prevention of relapses in AIP. A novel antibody for AIP has recently been identified and its performance needs validation from other centers. Newly published strategies for differentiating AIP from pancreatic cancer are available. SUMMARY AIP is a rare disease whose recognition and understanding are evolving. Much needs to be elucidated with regard to its cause, pathogenesis, treatment of relapse and long-term outcomes. A multidisciplinary team, familiar with the disease, is critical in making the correct diagnosis.
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