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Sano T, Kikuta K, Takikawa T, Matsumoto R, Okazaki K, Takeyama Y, Masamune A. Serum IgG4-negative and IgG4-positive type 1 autoimmune pancreatitis present with different clinicopathological features: An analysis of a nationwide survey in Japan. Pancreatology 2025; 25:82-88. [PMID: 39643518 DOI: 10.1016/j.pan.2024.11.018] [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: 07/01/2024] [Revised: 11/04/2024] [Accepted: 11/24/2024] [Indexed: 12/09/2024]
Abstract
BACKGROUND/OBJECTIVE Elevated serum IgG4 (sIgG4) is a useful diagnostic marker of type 1 autoimmune pancreatitis (AIP). This study aimed to clarify the clinicopathological characteristics of the type 1 AIP patients without elevated sIgG4 levels. METHODS We analyzed the clinical data of patients registered in a nationwide epidemiological survey in Japan. AIP was diagnosed according to the International Consensus Diagnostic Criteria. Patients with sIgG4 levels ≥135 mg/dl at the diagnosis were classified as sIgG4-positive AIP, and those with sIgG4 levels <135 mg/dl were as sIgG4-negative AIP. RESULTS A total of 1285 patients with AIP were enrolled in this study; 1128 (87.8 %) had sIgG4-positive AIP and 157 (12.2 %) had sIgG4-negative AIP. Compared to patients with sIgG4-positive AIP, those with sIgG4-negative AIP more frequently experienced inflammatory bowel diseases (3.8 % vs. 0.4 %), and less frequently developed extrapancreatic lesions (53.5 % vs. 72.3 %), including sclerosing cholangitis (30.6 % vs. 40.7 %) and sialadenitis/dacryoadenitis (5.1 % vs. 24.7 %). Histopathological examinations were performed more frequently in patients with sIgG4-negative AIP. The criterion of abundant IgG4-positive plasma cells was less frequently fulfilled by patients with sIgG4-negative AIP (28.0 % vs. 43.1 %). A Kaplan-Meier analysis showed that relapse occurred less frequently in patients with sIgG4-negative AIP (P = 0.006). Results were similar even if the patients with AIP-not otherwise specified (n = 45) were excluded. CONCLUSIONS Patients with sIgG4-negative type 1 AIP and those with sIgG4-positive type 1 AIP present with different clinicopathological features which suggests heterogeneity of patients with type 1 AIP. Low serum IgG4 levels could indicate low disease activity in type 1 AIP.
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Affiliation(s)
- Takanori Sano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazuhiro Kikuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tetsuya Takikawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Ryotaro Matsumoto
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazuichi Okazaki
- Department of Internal Medicine, Kansai Medical University, Kori Hospital, Neyagawa, Japan
| | - Yoshifumi Takeyama
- Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
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2
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Yang X, Zhou H, Wang W, Yan C, Ji G. Recent advances in IgG4-related autoimmune pancreatitis. Pathol Res Pract 2024; 257:155331. [PMID: 38678849 DOI: 10.1016/j.prp.2024.155331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 04/16/2024] [Accepted: 04/24/2024] [Indexed: 05/01/2024]
Abstract
The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.
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Affiliation(s)
- Xisheng Yang
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Haikun Zhou
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Weidong Wang
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Chunyu Yan
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Gang Ji
- Department of Gastrointestinal Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
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3
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Czarnywojtek A, Agaimy A, Pietrończyk K, Nixon IJ, Vander Poorten V, Mäkitie AA, Zafereo M, Florek E, Sawicka-Gutaj N, Ruchała M, Ferlito A. IgG4-related disease: an update on pathology and diagnostic criteria with a focus on salivary gland manifestations. Virchows Arch 2024; 484:381-399. [PMID: 38316669 DOI: 10.1007/s00428-024-03757-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 01/12/2024] [Accepted: 01/29/2024] [Indexed: 02/07/2024]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ disorder characterized by a highly variable clinical presentation depending on the affected organ/s, extent of tumefactive fibroinflammatory lesions, and associated functional impairment. The disease pursues a chronic, relapsing, often asymptomatic course and hence may pose a significant diagnostic challenge. Diagnostic delay can lead to progressive fibrosis and irreversible organ damage resulting into significant morbidity and even mortality. Given its broad clinical spectrum, physicians of all specialties may be the first clinicians facing this diagnostic challenge. Outside the pancreatobiliary system, the head and neck represents the major site of IgG4-RD with variable organ-specific diffuse or mass-forming lesions. In up to 75% of cases, elevated serum IgG4 levels are observed, but this figure possibly underestimates the fraction of seronegative cases, as the disease manifestations may present metachronously with significant intervals. Together with negative serology, this can lead to misdiagnosis of seronegative cases. A standardized nomenclature and diagnostic criteria for IgG4-RD were established in 2012 and revised in 2020 facilitating scientific research and expanding the range of diseases associated with IgG4 abnormalities. In addition to orbital pseudotumor, dacryoadenitis, Riedel thyroiditis, sinonasal manifestations, and rare miscellaneous conditions, IgG4-related sialadenitis is one of the most frequent presentations in the head and neck region. However, controversy still exists regarding the relationship between sialadenitis and IgG4-RD. This review focuses on the clinicopathological features of IgG4-related sialadenitis and its contemporary diagnostic criteria.
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Affiliation(s)
- Agata Czarnywojtek
- Department of Pharmacology, Poznan University of Medical Sciences, 60-806, Poznan, Poland
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany
| | | | - Iain J Nixon
- Department of Otorhinolaryngology Head and Neck Surgery, NHS Lothian, Edinburgh, EH8 9YL, UK
| | - Vincent Vander Poorten
- Otorhinolaryngology-Head and Neck Surgery, KU Leuven University Hospitals, 3000, Leuven, Belgium
- Department of Oncology, Section Head and Neck Oncology, KU Leuven, 3000, Leuven, Belgium
| | - Antti A Mäkitie
- Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, and the Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland
| | - Mark Zafereo
- Department of Head & Neck Surgery, MD Anderson Cancer Center, Houston, TX, 77005, USA
| | - Ewa Florek
- Laboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, 60-806, Poznan, Poland.
| | - Nadia Sawicka-Gutaj
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Marek Ruchała
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355, Poznan, Poland
| | - Alfio Ferlito
- International Head and Neck Scientific Group, 35100, Padua, Italy
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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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5
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Ikeura T, Tomiyama T, Takaori A, Ito T, Nakamaru K, Masuda M, Hori Y, Tsukuda S, Sumimoto K, Mitsuyama T, Nakayama S, Shimatani M, Uchida K, Takaoka M, Okazaki K, Naganuma M. Long-term Outcomes after Steroid Pulse Therapy in Patients with Type 1 Autoimmune Pancreatitis. Intern Med 2023; 62:2931-2940. [PMID: 36889699 PMCID: PMC10641208 DOI: 10.2169/internalmedicine.0807-22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 01/26/2023] [Indexed: 03/09/2023] Open
Abstract
Objective Steroid pulse therapy is a regimen involving the intravenous administration of supra-pharmacological doses of corticosteroids in the short term. It is used to treat various inflammatory and autoimmune conditions. However, the strengths and limitations of steroid pulse therapy for induction of remission in type 1 autoimmune pancreatitis (AIP) are unknown. Methods Depending on the steroid therapy regimen administered, the 104 patients with type 1 AIP included in this retrospective study were divided into three groups: conventional oral prednisolone (PSL) regimen (PSL group), intravenous methylprednisolone (IVMP) pulse followed by oral PSL regimen (Pulse+PSL group), and IVMP pulse-alone regimen (Pulse-alone group). We then examined the relapse rate and adverse events among the three groups. Results The Kaplan-Meier estimates of the relapse rate at 36 months after steroid therapy were 13.6% in the PSL group, 13.3% in the Pulse+PSL group, and 46.2% in the Pulse-alone group. The log-rank test revealed that the relapse-free survival in the Pulse-alone group was significantly shorter than that in the PSL (p=0.024) and Pulse+PSL groups (p=0.014). The exacerbation of glucose tolerance after steroid therapy was less frequently observed in the Pulse-alone group (0%) than in the PSL group (17%, p=0.050) and Pulse+PSL groups (26%, p=0.011). Conclusion Although treatment with IVMP pulse alone resulted in unsatisfactory relapse prevention outcomes compared with conventional steroid therapy, the IVMP pulse-alone regimen might be an alternative treatment strategy for type 1 AIP from the perspective of avoiding adverse events from steroids.
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Affiliation(s)
- Tsukasa Ikeura
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Takashi Tomiyama
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Ayaka Takaori
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Takashi Ito
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Koh Nakamaru
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Masataka Masuda
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Yuichi Hori
- Kansai Medical University Kori Hospital, Japan
| | | | - Kimi Sumimoto
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Japan
| | - Toshiyuki Mitsuyama
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Japan
| | - Shinji Nakayama
- Third Department of Internal Medicine, Kansai Medical University, Japan
| | - Masaaki Shimatani
- Division of Gastroenterology and Hepatology, Kansai Medical University Medical Center, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Japan
| | | | | | - Makoto Naganuma
- Third Department of Internal Medicine, Kansai Medical University, Japan
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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: 5] [Impact Index Per Article: 2.5] [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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Kim SH, Lee YC, Chon HK. Challenges for clinicians treating autoimmune pancreatitis: Current perspectives. World J Clin Cases 2023; 11:30-46. [PMID: 36687190 PMCID: PMC9846983 DOI: 10.12998/wjcc.v11.i1.30] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/31/2022] [Accepted: 12/19/2022] [Indexed: 01/04/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare disease clinically characterized by obstructive jaundice, unintentional weight loss, acute pancreatitis, focal pancreatic mass, and diabetes. AIP is classified into two subtypes - type 1 and type 2 - according to pathological findings, clinical features, and serology test results, but some cases may be defined as type not otherwise in the absence of pathological findings and inflammatory bowel disease. To address the differences in diagnostic criteria by country, standard diagnostic criteria for AIP were proposed in 2011 by an international consensus of expert opinions. Differential diagnosis of AIP from pancreatic ductal adenocarcinoma is important but remains challenging for clinicians. Fortunately, all subtypes of AIP show dramatic response to steroid treatment. This review discusses the current perspectives on the diagnosis and management of AIP in clinical practice.
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Affiliation(s)
- Seong-Hun Kim
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Yun Chae Lee
- Division of Gastroenterology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju 54907, South Korea
| | - Hyung Ku Chon
- Department of Internal Medicine, Institution of Wonkwang Medical Science, Wonkwang University School of Medicine and Hospital, Iksan 54538, South Korea
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The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review. Biomedicines 2022; 10:biomedicines10071511. [PMID: 35884816 PMCID: PMC9312496 DOI: 10.3390/biomedicines10071511] [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] [Received: 05/24/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
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9
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Yuan Y, Meng F, Ren H, Yue H, Xue K, Zhang R. Pathological count of IgG4-positive plasmacytes suggests extraophthalmic involvement and relapse in patients with IgG4-related ophthalmic disease: a retrospective study. Arthritis Res Ther 2022; 24:80. [PMID: 35365184 PMCID: PMC8973882 DOI: 10.1186/s13075-022-02757-2] [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: 01/27/2022] [Accepted: 03/01/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND IgG4-related ophthalmic disease (IgG4ROD) is a phenotype of IgG4-related disease (IgG4RD) with ophthalmic involvement. The pathological IgG4+ plasmacyte count has only been used for diagnosis. We aimed to explore its possible clinical value in the management of IgG4ROD. METHODS Fifty-five pathologically diagnosed IgG4ROD patients were included, and their clinical, pathological, serological, and radiological findings and treatment outcomes were reviewed and analyzed. The pathological IgG4+ plasmacyte counts in lesions from different anatomic sites were compared, and their association with serum IgG4 concentrations, systemic involvement, and relapse risk was analyzed. RESULTS The patients were divided into groups according to the anatomic site of their biopsied lesions, namely, the lacrimal gland, extraocular muscle, and orbital soft tissue. No significant difference was found in the pathological IgG4+ plasma cell counts among these groups (p = 0.975). The pathological IgG4+ plasmacyte count positively correlated with the IgG4 concentration in peripheral blood (R2 = 0.5469, p < 0.001). The serum IgG4 concentration and the pathological infiltrating IgG4+ plasmacyte count were significantly higher in patients with extraophthalmic involvement (p < 0.001 and p = 0.005, respectively). The areas under the receiver operating characteristic (ROC) curve (AUCs) of the serum IgG4 level and pathological IgG4+ plasmacyte count for identifying systemic involvement were 0.897 (p < 0.001) and 0.759 (p = 0.015), respectively. The patients with relapse had higher levels of serum IgG4, more germinal centers (GCs), and infiltrating IgG4+ plasmacytes in lesions. Multivariate Cox regression analysis revealed that a pathological IgG4+ plasmacyte count of > 150/high-power field (HPF) and an elevated serum IgG4 level of > 500 mg/dL were risk factors for relapse after steroid treatment. CONCLUSIONS Lesions from different ophthalmic sites in IgG4ROD patients have similar counts of IgG4+ and IgG+ plasmacytes. The quantity of pathological IgG4+ plasmacytes corresponded to the serum IgG4 concentration in patients with IgG4ROD and could be meaningful in identifying systemic involvement and predicting subsequent relapse.
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Affiliation(s)
- Yiqun Yuan
- Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.,Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.,NHC Key Laboratory of Myopia, Fudan University, Shanghai, China
| | - Fengxi Meng
- Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.,Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.,NHC Key Laboratory of Myopia, Fudan University, Shanghai, China
| | - Hui Ren
- Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.,Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.,NHC Key Laboratory of Myopia, Fudan University, Shanghai, China
| | - Han Yue
- Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.,Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.,NHC Key Laboratory of Myopia, Fudan University, Shanghai, China
| | - Kang Xue
- Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.,Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.,NHC Key Laboratory of Myopia, Fudan University, Shanghai, China
| | - Rui Zhang
- Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China. .,Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. .,NHC Key Laboratory of Myopia, Fudan University, Shanghai, China.
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10
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Goyal S, Sakhuja P. Autoimmune pancreatitis: Current perspectives. INDIAN J PATHOL MICR 2021; 64:S149-S159. [PMID: 34135159 DOI: 10.4103/ijpm.ijpm_59_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Over the last two decades, our knowledge and understanding regarding the pathogenesis and biology of autoimmune pancreatitis (AIP) have improved tremendously. Type 1 AIP or IgG4-related pancreatitis (IgG4-RP) is now believed to be the prototype of the multisystemic IgG4-related disease. In view of clinical features like obstructive jaundice and mass-forming lesions in the pancreas in elderly men, type 1 AIP often mimics pancreatic cancer. IgG4-related sclerosing cholangitis concomitantly involving the extrahepatic and intrahepatic biliary tree is the most common extrapancreatic involvement seen in up to 80% of these patients, which needs to distinguish from cholangiocarcinoma. Histology is characterised by lymphoplasmacytic inflammation, abundant IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. Apart from histology, high serum IgG4 levels, pancreatic parenchymal and duct imaging findings and other organ involvement aid in diagnosis especially in cases where definitive histology is not evident. Also, these parameters lay the foundation of various diagnostic criteria proposed over last few years. On the contrary, histology alone is the mainstay for establishing diagnosis of idiopathic duct-centric pancreatitis (IDCP) as it lacks any specific serological marker or imaging. Since both types of AIP respond dramatically to corticosteroid treatment, a biopsy is crucial to establish the preoperative diagnosis and to exclude malignancy so as to avoid unnecessary surgery. This review discusses the morphologic spectrum, treatment and prognosis of IgG4-RP and IDCP with an emphasis on approach to diagnosis with relevant histologic features, differential diagnoses and the challenges faced during biopsy interpretation.
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Affiliation(s)
- Surbhi Goyal
- Department of Pathology, GIPMER, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, GIPMER, New Delhi, India
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Maritati F, Peyronel F, Vaglio A. IgG4-related disease: a clinical perspective. Rheumatology (Oxford) 2020; 59:iii123-iii131. [DOI: 10.1093/rheumatology/kez667] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 12/10/2019] [Indexed: 12/11/2022] Open
Abstract
AbstractIgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. Common presentations include major salivary and lacrimal gland enlargement, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis and obliterative phlebitis. The precise pathogenic mechanisms of IgG4-RD are still unclear. CD4+ T and B cells, including IgG4-expressing plasmablasts, constitute the major inflammatory cell populations and are believed to cause organ damage and tissue fibrosis. The diagnosis of the disease may be challenging and should be based on specific histopathological findings, typical laboratory and radiological aspects and an appropriate clinical context. The first-line treatment of IgG4-RD is based on glucocorticoids, which are usually efficacious. However, B cell depletion induced by rituximab has also been found to induce remission in steroid-resistant disease or has been used as steroid-sparing agent for relapsing disease. This review provides an update on clinical and therapeutic aspects of IgG4-RD.
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Affiliation(s)
- Federica Maritati
- Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti, AnconaItaly
| | | | - Augusto Vaglio
- Nephrology and Dialysis Unit, Meyer Children’s University Hospital, Florence, Italy
- Department of Biomedical Clinical and Experimental Sciences, University of Firenze, Firenze, Italy
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Matsubayashi H, Ishiwatari H, Imai K, Kishida Y, Ito S, Hotta K, Yabuuchi Y, Yoshida M, Kakushima N, Takizawa K, Kawata N, Ono H. Steroid Therapy and Steroid Response in Autoimmune Pancreatitis. Int J Mol Sci 2019; 21:E257. [PMID: 31905944 PMCID: PMC6981453 DOI: 10.3390/ijms21010257] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 12/18/2019] [Accepted: 12/25/2019] [Indexed: 12/11/2022] Open
Abstract
Autoimmune pancreatitis (AIP), a unique subtype of pancreatitis, is often accompanied by systemic inflammatory disorders. AIP is classified into two distinct subtypes on the basis of the histological subtype: immunoglobulin G4 (IgG4)-related lymphoplasmacytic sclerosing pancreatitis (type 1) and idiopathic duct-centric pancreatitis (type 2). Type 1 AIP is often accompanied by systemic lesions, biliary strictures, hepatic inflammatory pseudotumors, interstitial pneumonia and nephritis, dacryoadenitis, and sialadenitis. Type 2 AIP is associated with inflammatory bowel diseases in approximately 30% of cases. Standard therapy for AIP is oral corticosteroid administration. Steroid treatment is generally indicated for symptomatic cases and is exceptionally applied for cases with diagnostic difficulty (diagnostic steroid trial) after a negative workup for malignancy. More than 90% of patients respond to steroid treatment within 1 month, and most within 2 weeks. The steroid response can be confirmed on clinical images (computed tomography, ultrasonography, endoscopic ultrasonography, magnetic resonance imaging, and 18F-fluorodeoxyglucose-positron emission tomography). Hence, the steroid response is included as an optional diagnostic item of AIP. Steroid treatment results in normalization of serological markers, including IgG4. Short- and long-term corticosteroid treatment may induce adverse events, including chronic glycometabolism, obesity, an immunocompromised status against infection, cataracts, glaucoma, osteoporosis, and myopathy. AIP is common in old age and is often associated with diabetes mellitus (33-78%). Thus, there is an argument for corticosteroid therapy in diabetes patients with no symptoms. With low-dose steroid treatment or treatment withdrawal, there is a high incidence of AIP recurrence (24-52%). Therefore, there is a need for long-term steroid maintenance therapy and/or steroid-sparing agents (immunomodulators and rituximab). Corticosteroids play a critical role in the diagnosis and treatment of AIP.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
- Genetic Medicine Promotion, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan
| | - Hirotoshi Ishiwatari
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Yoshihiro Kishida
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Sayo Ito
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Yohei Yabuuchi
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Naomi Kakushima
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Kohei Takizawa
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan; (H.I.); (K.I.); (Y.K.); (S.I.); (K.H.); (Y.Y.); (M.Y.); (N.K.); (K.T.); (N.K.); (H.O.)
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Abstract
OBJECTIVES Serum IgG4 level is a useful diagnostic marker of autoimmune pancreatitis (AIP); however, it is difficult to predict relapse. We investigated whether a change in serum IgG4 is predictive of AIP relapse during maintenance therapy. METHODS Seventy-three patients with AIP treated with steroids were divided into 3 groups according to their initial serum IgG4 levels: level 1 group (>2-fold upper limit), level 2 group (1- to 2-fold upper limit), and a normal group. The relapse rate and the prevalence of extrapancreatic lesions were compared between the 3 groups. The correlation between the relative rise of serum IgG4 levels and relapse during maintenance therapy was analyzed. RESULTS There were no differences in serum IgG4 levels in the presence or absence of relapse. The average number of extrapancreatic lesions was 1.02, 0.47, and 0.27 in level 1, level 2, and the normal group, respectively. The relative rise of serum IgG4 levels after steroid therapy was significantly higher in relapse than in nonrelapse cases. The area under the receiver operating characteristic curve of the relative rise of IgG4 levels for discriminating between the relapse and the nonrelapse cases was 0.85. CONCLUSIONS The relative rise of serum IgG4 levels after steroid therapy may provide an indication of relapse.
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Yadlapati S, Verheyen E, Efthimiou P. IgG4-related disease: a complex under-diagnosed clinical entity. Rheumatol Int 2017; 38:169-177. [PMID: 28681251 DOI: 10.1007/s00296-017-3765-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 06/28/2017] [Indexed: 12/11/2022]
Abstract
IgG4-related disease (IgG4-RD) encompasses a spectrum of complex fibro-inflammatory disorders which are often under diagnosed due to unfamiliarity by clinicians. A challenging multitude of clinical manifestations makes the diagnosis cumbersome. The primary clinical feature in IgG4-RD entails a tumor-like presentation coupled with tissue-destructive lesions. Histopathological findings include lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. These findings, in combination with elevated serum immunoglobulin G4 levels, are diagnostic in the setting of single- or multi-organ involvement. A closer understanding of the role of T cells and B cells in the increased production of IgG4 has led to a notion that IgG4 can act as a pathogen, anti-inflammatory agent, or rheumatoid factor. Glucocorticoids are the primary treatment modality; however, relapse is common with prolonged therapy. Alternatively, immunomodulatory agents are being increasingly used as therapy. The aim of this article is to raise awareness of IgG4-RD and review the diagnostic algorithm, as IgG4-RD often mimics a wide array of clinical conditions. In addition, we summarize the pathogenesis and current treatment guidelines of IgG4-RD for clinicians. Awareness and accurate diagnosis are crucial in preventing progression to chronic diseases, thereby diminishing disease-related morbidity and mortality.
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Affiliation(s)
- Sujani Yadlapati
- Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA
| | - Elijah Verheyen
- Department of Internal Medicine, St. Luke's-Roosevelt Hospital Center, New York, NY, USA
| | - Petros Efthimiou
- Division of Rheumatology, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY, USA.
- Weill Cornell Medical College, New York, NY, USA.
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Hara S, Kawano M, Mizushima I, Yamada K, Fujita K, Harada K, Matsumura M, Yamagishi M, Sato Y, Yamaguchi Y, Nakanuma Y, Nagata M. A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4-positive plasma cell infiltration. Mod Rheumatol 2017; 26:784-9. [PMID: 24884481 DOI: 10.3109/14397595.2014.916836] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.
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Affiliation(s)
- Satoshi Hara
- a Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan.,b Department of Kidney and Vascular Pathology , Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Ibaraki , Japan
| | - Mitsuhiro Kawano
- a Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Ichiro Mizushima
- a Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Kazunori Yamada
- a Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Kentaro Fujita
- c Department of Respiratory Medicine , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Kenichi Harada
- d Department of Human Pathology , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Masami Matsumura
- e Division of General Medicine, Center for Community Medicine, Jichi Medical University School of Medicine , Tochigi , Japan
| | - Masakazu Yamagishi
- f Division of Cardiology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Yasuharu Sato
- g Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | | | - Yasuni Nakanuma
- d Department of Human Pathology , Kanazawa University Graduate School of Medicine , Kanazawa, Ishikawa , Japan
| | - Michio Nagata
- b Department of Kidney and Vascular Pathology , Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Ibaraki , Japan
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Takayama R, Ueno T, Saeki H. Immunoglobulin G4-related disease and its skin manifestations. J Dermatol 2017; 44:288-296. [DOI: 10.1111/1346-8138.13723] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 11/04/2016] [Indexed: 12/24/2022]
Affiliation(s)
- Ryoko Takayama
- Department of Dermatology; Graduate School of Medicine; Nippon Medical School; Tokyo Japan
| | - Takashi Ueno
- Department of Dermatology; Graduate School of Medicine; Nippon Medical School; Tokyo Japan
| | - Hidehisa Saeki
- Department of Dermatology; Graduate School of Medicine; Nippon Medical School; Tokyo Japan
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Pelkmans LG, Hendriksz TR, Westenend PJ, Vermeer HJ, van Bommel EFH. Elevated serum IgG4 levels in diagnosis and treatment response in patients with idiopathic retroperitoneal fibrosis. Clin Rheumatol 2017; 36:903-912. [PMID: 28105551 DOI: 10.1007/s10067-017-3542-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 01/08/2017] [Accepted: 01/11/2017] [Indexed: 12/24/2022]
Abstract
Idiopathic retroperitoneal fibrosis (iRPF) may be a manifestation of IgG4-related disease. Measuring serum IgG4 (sIgG4) may be of value in monitoring iRPF, but this has scarcely been evaluated. It is unknown if tamoxifen (TMX) affects sIgG4 levels. We performed a prospective inception cohort study of 59 patients with untreated (re)active iRPF stratified by elevated (>1.4 g/L) or normal sIgG4 level. Changes in sIgG4 levels following TMX initiation and, if treatment failed, during subsequent corticosteroid (CS) treatment were analyzed. The median sIgG4 level was 1.1 g/L (interquartile range (IQR) 0.4-2.2); 24 patients (40%) had elevated sIgG4 level. Patients with elevated sIgG4 tended to present with higher ESR (46 vs. 34 mm/h; P = 0.08) and more frequent locoregional lymphadenopathy adjacent to the mass (41.7 vs. 20.0%; P = 0.08). sIgG4 also correlated with ESR (ρ = 0.26; P = 0.05) and serum creatinine (SC) (ρ = 0.26; P = 0.04). Following TMX initiation, sIgG4 level decreased, particularly when achieving treatment success (P < 0.01). Odds ratio for TMX treatment success in patients with elevated sIgG4 level was 0.77 (95% CI 0.53-1.14; P = 0.19). After adjusting for age, sex, and SC, the odds ratio was 0.78 (95% CI 0.51-1.18; P = 0.24). ROC curve analyses of sIgG4 on a continuous scale and treatment success showed an AUC of 0.62. Treatment success and concurrent sIgG4 decrease (P < 0.01) were achieved in 78% of patients who converted to CS therapy. Patients with elevated sIgG4 level may be more inflammatory than patients with normal sIgG4 level, but this needs further study. TMX affects sIgG4 levels, but to a lesser extent than CSs. sIgG4 cannot be used as an outcome prediction tool, irrespective of which cutoff value was chosen.
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Affiliation(s)
- L G Pelkmans
- Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands
- National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer Hospital, PO Box 444, NL-3300 AK, Dordrecht, The Netherlands
| | - T R Hendriksz
- Department of Radiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - P J Westenend
- Department of Pathology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - H J Vermeer
- Result Laboratory, Albert Schweitzer Hospital, Dordrecht, The Netherlands
| | - E F H van Bommel
- Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
- National Center of Expertise Retroperitoneal Fibrosis, Albert Schweitzer Hospital, PO Box 444, NL-3300 AK, Dordrecht, The Netherlands.
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Assessment of the Rate of Decrease in Serum IgG4 Level of Autoimmune Pancreatitis Patients in Response to Initial Steroid Therapy as a Predictor of Subsequent Relapse. Pancreas 2016; 45:1341-6. [PMID: 27171510 DOI: 10.1097/mpa.0000000000000633] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) responds well to steroid therapy but frequently relapses after discontinuing the steroid. It is difficult to know which cases are most likely to relapse. The aim of this study was to investigate the relation between the rate of decrease in serum IgG4 level after initial steroid therapy and a relapse. METHODS The subjects were 47 AIP patients who received steroid therapy. We calculated the difference between their serum IgG4 levels before and 2 months after the start of therapy, and their rate of decrease in serum IgG4 level after treatment (Δ') by dividing the difference between the 2 values by the number of days between them. RESULTS The rates of decrease were significantly higher in the nonrelapse groups than in the relapse groups. A receiver operating characteristic curve showed that the area under the curve for the Δ' value was 0.781, and that at the Δ' cutoff value of 10.7, the sensitivity and the specificity of the Δ' value for discriminating between the 2 groups were 0.846 and 0.632, respectively. CONCLUSIONS Our data suggest that the rate of decrease in serum IgG4 level may be a useful predictor of a relapse of AIP after steroid therapy.
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Haldar D, Cockwell P, Richter AG, Roberts KJ, Hirschfield GM. An overview of the diagnosis and management of immunoglobulin G4-related disease. CMAJ 2016; 188:953-961. [PMID: 27325130 PMCID: PMC5026513 DOI: 10.1503/cmaj.151402] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Affiliation(s)
- Debashis Haldar
- Centre for Liver Research (Haldar, Hirschfield), National Institute for Health Research Liver Biomedical Research Unit, University of Birmingham; Department of Renal Medicine (Cockwell), Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston; Institute of Immunology and Immunotherapy (Haldar, Richter, Hirschfield), College of Medical and Dental Sciences, University of Birmingham; Department of Hepatobiliary Surgery (Roberts), Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, UK
| | - Paul Cockwell
- Centre for Liver Research (Haldar, Hirschfield), National Institute for Health Research Liver Biomedical Research Unit, University of Birmingham; Department of Renal Medicine (Cockwell), Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston; Institute of Immunology and Immunotherapy (Haldar, Richter, Hirschfield), College of Medical and Dental Sciences, University of Birmingham; Department of Hepatobiliary Surgery (Roberts), Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, UK
| | - Alex G Richter
- Centre for Liver Research (Haldar, Hirschfield), National Institute for Health Research Liver Biomedical Research Unit, University of Birmingham; Department of Renal Medicine (Cockwell), Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston; Institute of Immunology and Immunotherapy (Haldar, Richter, Hirschfield), College of Medical and Dental Sciences, University of Birmingham; Department of Hepatobiliary Surgery (Roberts), Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, UK
| | - Keith J Roberts
- Centre for Liver Research (Haldar, Hirschfield), National Institute for Health Research Liver Biomedical Research Unit, University of Birmingham; Department of Renal Medicine (Cockwell), Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston; Institute of Immunology and Immunotherapy (Haldar, Richter, Hirschfield), College of Medical and Dental Sciences, University of Birmingham; Department of Hepatobiliary Surgery (Roberts), Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, UK
| | - Gideon M Hirschfield
- Centre for Liver Research (Haldar, Hirschfield), National Institute for Health Research Liver Biomedical Research Unit, University of Birmingham; Department of Renal Medicine (Cockwell), Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston; Institute of Immunology and Immunotherapy (Haldar, Richter, Hirschfield), College of Medical and Dental Sciences, University of Birmingham; Department of Hepatobiliary Surgery (Roberts), Queen Elizabeth Hospital Birmingham, University Hospital Birmingham, Edgbaston, Birmingham, UK
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Egner W, Swallow K, Lock RJ, Patel D. Falsely low immunoglobulin (Ig)G4 in routine analysis: how not to miss IgG4 disease. Clin Exp Immunol 2016; 186:57-63. [PMID: 27125474 DOI: 10.1111/cei.12805] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2016] [Indexed: 12/16/2022] Open
Abstract
Immunoglobulin (Ig)G4 disease can have apparently 'normal' levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 0·64 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning.
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Affiliation(s)
- W Egner
- Department of Immunology and Protein Reference Unit, Sheffield.,Immunochemistry and Allergy (IIA), Sheffield Teaching Hospitals NHS Trust, UK NEQAS Immunology, Sheffield
| | - K Swallow
- Department of Immunology and Protein Reference Unit, Sheffield
| | - R J Lock
- Immunology and Immunogenetics, North Bristol NHS Trust, Bristol
| | - D Patel
- Immunochemistry and Allergy (IIA), Sheffield Teaching Hospitals NHS Trust, UK NEQAS Immunology, Sheffield
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Brito-Zerón P, Kostov B, Bosch X, Acar-Denizli N, Ramos-Casals M, Stone JH. Therapeutic approach to IgG4-related disease: A systematic review. Medicine (Baltimore) 2016; 95:e4002. [PMID: 27368010 PMCID: PMC4937924 DOI: 10.1097/md.0000000000004002] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
To review the reported evidence on the therapeutic management of IgG4-related disease (IgG4-RD) in clinical practice.A systematic search of the literature was conducted. The primary outcome measured was the rate of efficacy of first-line therapeutic approaches. Secondary outcomes measured included the rate of disease relapse, the outcome of untreated patients, the rate of patients without drug therapy at the end of follow-up, the rate of side effects, and mortality. The MOOSE, AHRQ, STROBE, and GRACE recommendations/statements were followed.The results of the systematic search strategy yielded 62 studies that included a total of 3034 patients. Complete information about first-line therapeutic regimens was detailed in 1952 patients, including glucocorticoid-based regimens in 1437 (74%), drug-free regimens in 213 (11%), and other therapies in 38 (2%). No therapy (wait and see management) was reported in 264 (13%) patients. The efficacy of monotherapy with glucocorticoids was specified in 1220 patients, of whom 97% had a therapeutic response. Relapses, however, were reported in 464/1395 (33%) patients despite typically short follow-up periods. Therapeutic efficacy was reported in 219/231 (95%) of relapses treated with glucocorticoids, 56/69 (81%) of those treated with azathioprine, 16/22 (72%) of those treated with other immunosuppressive agents, and in the 9 cases treated with rituximab (100%). In 14 studies, the authors detailed the outcome of 159/246 patients with wait-and-see management; spontaneous improvement or resolution was reported in 68 (43%) cases. Wide heterogeneity was observed with respect to the first-line therapeutic approaches used for the different organ-specific disease subsets, including significant differences in the mean dose of glucocorticoids used.Nearly 70% of reported IgG4-RD patients are treated with oral glucocorticoids in monotherapy. However, the therapeutic management is heavily influenced by geographical, epidemiological, and clinical factors, especially with respect to the predominant organ affected. The frequency of glucocorticoid failure to induce sustained remissions both during and after treatment and the assessment of glucocorticoid toxicity in IgG4-RD require further study.
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Affiliation(s)
- Pilar Brito-Zerón
- Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA-Sanitas
- Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX
- Department of Autoimmune Diseases, ICMiD, Hospital Clínic
| | - Belchin Kostov
- Consorci d’Atenció Primària de Salut Barcelona Esquerre (CAPS-BE)
- Transverse Group for Research in Primary Care, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
| | - Xavier Bosch
- Department of Internal Medicine, ICMiD, Hospital Clínic, Barcelona, Spain
| | - Nihan Acar-Denizli
- Department of Statistics, Faculty of Science and Letters, Mimar Sinan Fine Arts University, Istanbul, Turkey
| | - Manuel Ramos-Casals
- Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX
- Department of Autoimmune Diseases, ICMiD, Hospital Clínic
- Department of Medicine, University of Barcelona, Barcelona, Spain
- Correspondence: Manuel Ramos-Casals, Servei de Malalties Autoimmunes, Hospital Clínic, C/Villarroel, 170, 08036-Barcelona, Spain (e-mail: )
| | - John H. Stone
- Harvard Medical School and Department of Medicine (Division of Rheumatology, Allergy, and Immunology), Massachusetts General Hospital, Boston, MA
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Brito-Zerón P, Bosch X, Ramos-Casals M, Stone JH. IgG4-related disease: Advances in the diagnosis and treatment. Best Pract Res Clin Rheumatol 2016; 30:261-278. [DOI: 10.1016/j.berh.2016.07.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 07/17/2016] [Indexed: 02/08/2023]
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Matsubayashi H, Iwai T, Matsui T, Wada T, Kawata N, Ito H, Sasaki K, Uesaka K, Ono H. Pancreatic cystic lesions with atypical steroid response should be carefully managed in cases of autoimmune pancreatitis. J Gastroenterol Hepatol 2016. [PMID: 26207936 DOI: 10.1111/jgh.13051] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIM Pancreatic cysts have been reported in cases with autoimmune pancreatitis (AIP) and are often treated by corticosteroid; however, their response to steroid has not been determined fully. We aimed to see the incidence and steroid response of pancreatic cysts and the features of cysts without proper response in cases with AIP. METHODS Fifty-eight AIP cases were analyzed for the incidence and associated factors of pancreatic cystic lesions (≥ 10 mm). Of these, 47 cases, determined for steroid response, were retrospectively investigated for the factors associated with cyst change by corticosteroid therapy. RESULTS At initial diagnosis, 17 pancreatic cystic lesions were recognized in 13 cases (22.4%) of AIP, with an average size of 30 mm (range: 11-130 mm), associated with higher incidence of elevated serum amylase (38.5% vs 11.1%, P = 0.02). Of these 13 cases, nine cases with 10 cystic lesions underwent steroid therapy in our hospital. All of seven unilocular cysts were dramatically shrunken or vanished in a few months; meanwhile, three cases with multilocular cysts showed scarcely any steroid response (P = 0.008). Of these three cases, two cases were revealed to accompany pancreatic ductal carcinoma, in contrast to null of seven unilocular cysts (P = 0.07). CONCLUSIONS Pancreatic cystic lesions are sometimes recognized in cases with AIP, and most unilocular cysts can be minimized by corticosteroids. However, clinicians must be alert for atypical pancreatic cysts, such as multilocular cysts or cysts without obvious steroid response.
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Affiliation(s)
| | - Tomohiro Iwai
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Toru Matsui
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takuya Wada
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Noboru Kawata
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hiroaki Ito
- Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Keiko Sasaki
- Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
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Yabuuchi Y, Matsubayashi H, Matsuzaki M, Shiomi A, Moriguchi M, Kawamura I, Ito I, Ono H. Colovesical fistula caused by glucocorticoid therapy for IgG4-related intrapelvic mass. World J Clin Cases 2015; 3:1000-1004. [PMID: 26677450 PMCID: PMC4677080 DOI: 10.12998/wjcc.v3.i12.1000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 08/19/2015] [Accepted: 10/13/2015] [Indexed: 02/05/2023] Open
Abstract
IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an IgG4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography (CT) incidentally depicted left hydronephrosis with an ill-demarcated intrapelvic mass lesion. This lesion was histologically diagnosed as IgG4-RD by open biopsy, and peroral steroid therapy was initiated. One month after starting steroids, a colovesical fistula was detected by follow-up CT. A colostomy and urethral catheterization were emergently performed. The patient recovered and the mass lesion was drastically minimized by the initiation of glucocorticoids; however, he still needs urethral catheterization. IgG4-RD develops in various systemic organs and generally responds well to steroids. Clinicians must be watchful for the complications of responses to corticosteroids, such as fistulization, when the mass lesion of IgG4-RD is adjacent to multiple luminal organs.
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Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, Stone JH. IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis Rheumatol 2015; 67:2466-75. [PMID: 25988916 DOI: 10.1002/art.39205] [Citation(s) in RCA: 447] [Impact Index Per Article: 44.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2014] [Accepted: 05/12/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect nearly any organ. Prior studies have focused on individual cases of IgG4-RD or small case series. This study was undertaken to report detailed clinical and laboratory findings in a larger group of patients with IgG4-RD whose diagnosis was established by strict clinicopathologic correlation. METHODS The baseline features of 125 patients with biopsy-proven IgG4-RD were reviewed. The diagnosis was confirmed by pathologists' review, based on consensus diagnostic criteria and correlation with clinicopathologic features. Disease activity and damage were assessed using the IgG4-RD Responder Index (RI). Flow cytometry was used to assess levels of circulating plasmablasts. RESULTS Of the 125 patients, 107 had active disease and 86 were not receiving treatment for IgG4-RD. Only 51% of the patients with active disease had elevated serum IgG4 concentrations. However, patients with active disease and elevated serum IgG4 concentrations were older, had a higher IgG4-RD RI score, a greater number of organs involved, lower complement levels, higher absolute eosinophil counts, and higher IgE levels compared to those with active disease but normal serum IgG4 concentrations (P < 0.01 for all comparisons). The correlation between IgG4+ plasmablast levels and the IgG4-RD RI of disease activity (Spearman's ρ = 0.45, P = 0.003) was stronger than the correlation between total plasmablast levels and the IgG4-RD RI. Seventy-six (61%) of the patients were male, but no significant differences according to sex were observed with regard to disease severity, organ involvement, or serum IgG4 concentrations. Treatment with glucocorticoids failed to produce sustained remission in 77% of patients. CONCLUSION Nearly 50% of this patient cohort with biopsy-proven, clinically active IgG4-RD had normal serum IgG4 concentrations. Elevations in the serum IgG4 concentration appeared to identify a subset of patients with a more severe disease phenotype. In addition, the levels of IgG4+ plasmablasts correlated well with the extent of disease activity.
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Affiliation(s)
| | - Vikram Deshpande
- Massachusetts General Hospital and Harvard Medical School, Boston
| | - Hamid Mattoo
- Massachusetts General Hospital Cancer Center, Boston
| | | | | | - Shiv Pillai
- Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston
| | - John H Stone
- Massachusetts General Hospital and Harvard Medical School, Boston
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Efficacy of Steroid Pulse Therapy for Autoimmune Pancreatitis Type 1: A Retrospective Study. PLoS One 2015; 10:e0138604. [PMID: 26381760 PMCID: PMC4575182 DOI: 10.1371/journal.pone.0138604] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Accepted: 08/31/2015] [Indexed: 01/12/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is treatable with steroids, but relapse is frequent. The efficacy of steroid pulse therapy has been shown for various autoimmune diseases, but has not become established therapy. In this study, we reviewed the efficacy of steroid pulse therapy in 24 subjects who were diagnosed with AIP type 1 at our hospital. Patient characteristics, time-course of serum IgG4, and the cumulative relapse-free survival rate were compared between patients who received oral steroid therapy (oral group) and those who were treated with steroid pulse therapy (pulse group). Serum IgG4 was reduced significantly after therapy in both groups and the 5-year cumulative relapse-free survival rates in the two groups did not differ significantly (oral group 46.9%, pulse group 77.8%). However, in a subset of cases with diffuse pancreatic swelling, this rate was significantly lower in the oral group (33.3% vs. 100.0%, p = 0.046). These results suggest that steroid pulse therapy is effective for prevention of relapse in AIP patients with diffuse pancreatic swelling.
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Stone JH, Brito-Zerón P, Bosch X, Ramos-Casals M. Diagnostic Approach to the Complexity of IgG4-Related Disease. Mayo Clin Proc 2015; 90:927-39. [PMID: 26141331 DOI: 10.1016/j.mayocp.2015.03.020] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Revised: 03/30/2015] [Accepted: 03/31/2015] [Indexed: 12/24/2022]
Abstract
IgG4-related disease (IgG4-RD) is a systemic disease characterized by the infiltration of IgG4-bearing plasma cells and, more importantly, distinctive histopathological features: storiform fibrosis, obliterative phlebitis, a lymphoplasmacytic infiltrate, and mild-to-moderate tissue eosinophilia. The diagnostic approach is complex and relies on the coexistence of various clinical, laboratory, and histopathological findings, none of which is pathognomonic in and of itself. IgG4-related disease should be suspected in patients presenting with unexplained enlargement or swelling of 1 or more organs or tissue organs. Four laboratory abnormalities often provide initial clues to the diagnosis of IgG4-RD: peripheral eosinophilia, hypergammaglobulinemia, elevated serum IgE levels, and hypocomplementemia. Elevated serum IgG4 levels provided critical information in identifying the first cases of IgG4-RD, but recent studies have reported substantial limitations to the measurement of serum IgG4 concentrations, precluding reliance on serum IgG4 concentrations for diagnostic purposes. In contrast, new studies have suggested a promising role of flow cytometry studies in the diagnosis and longitudinal management of IgG4-RD. Demonstration of the classic histopathological features of IgG4-RD remains crucial to diagnosis in most cases, and biopsy proof is preferred strongly by most disease experts before the initiation of treatment. Of note, the multiorgan nature of IgG4-RD was first established in 2003. This review intends to provide most recent knowledge about the clinical, laboratory, radiological, and pathological characteristics of IgG4-RD that may guide the physician to establish an early diagnosis. We searched PubMed and MEDLINE for relevant articles published between January 1, 2000, and November 1, 2014, using the search terms IgG4 and IgG4-related.
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Affiliation(s)
- John H Stone
- Harvard Medical School, Boston, MA; Department of Medicine, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA.
| | - Pilar Brito-Zerón
- Josep Font Laboratory of Autoimmune Diseases, CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Spain
| | - Xavier Bosch
- Department of Internal Medicine (ICMiD), Hospital Clínic, University of Barcelona, Spain
| | - Manuel Ramos-Casals
- Josep Font Laboratory of Autoimmune Diseases, CELLEX-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Spain
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Li M, Zhou Q, Yang K, Brigstock DR, Zhang L, Xiu M, Sun L, Gao RP. Rare case of Helicobacter pylori-positive multiorgan IgG4-related disease and gastric cancer. World J Gastroenterol 2015; 21:3429-3434. [PMID: 25805956 PMCID: PMC4363779 DOI: 10.3748/wjg.v21.i11.3429] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 11/17/2014] [Accepted: 12/22/2014] [Indexed: 02/06/2023] Open
Abstract
A 61-year-old male from Northeast China presented with a 2-mo history of abdominal distension, pruritus and jaundice. Laboratory testing revealed an elevated serum IgG4 level. A computed tomography scan showed a typical feature of autoimmune pancreatitis (AIP) and cholecystocholangitis. Early gastric cancer was incidentally discovered when endoscopic untrasound-guided fine needle aspiration (EUS-FNA) of the pancreas was carried out. The patient underwent radical subtotal gastrectomy for gastric cancer combined with cholecystectomy. Helicobacter pylori (H. pylori) and IgG4-positive plasmacytes were detected in gastric cancer tissue, pancreatic EUS-FNA sample and resected gallbladder specimen by immunohistochemistry. The patient was diagnosed with H. pylori-positive IgG4-related AIP and sclerosing cholecystocholangitis as well as H. pylori-positive gastric cancer. He responded well to steroid therapy and remains healthy with no signs of recurrence at one year follow-up. We speculate that H. pylori might act as a trigger via direct or indirect action in the initiation of onset of gastric cancer and multiorgan IgG4-related disease.
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Abstract
IgG4-related disease (IgG4-RD) is an emerging immune-mediated disease with the capability of involving essentially any organ. The epidemiology of this disease has not been explored in detail. A majority of patients reported in the literature to date are from Japan, but the condition has been described all across the world and there is no strong evidence to suggest a predilection for Asian populations. The mean age at diagnosis is approximately 60 years and there is a decided male predominance for many clinical features, with an overall male:female ratio of 8:3. A cardinal feature of IgG4-RD is single or multiple organ swelling that often raises concern for malignancy. IgG4-RD should be suspected in patients presenting with unexplained enlargement or swelling of one or more organs. Presenting features vary substantially according to the specialty to which patients present first; in addition, the disease can be diagnosed unexpectedly in pathological specimens or identified incidentally on radiology studies. Involvement of major organs is common and IgG4-RD may lead to organ failure, particularly in the pancreas, liver and biliary tree, kidneys, thyroid gland, lungs, and aorta. The diagnosis of IgG4-RD relies on the coexistence of various clinical, laboratory and histopathological findings, although none is pathognomonic by itself.
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Ikeura T, Manfredi R, Zamboni G, Negrelli R, Capelli P, Amodio A, Caliò A, Colletta G, Gabbrielli A, Benini L, Okazaki K, Vantini I, Frulloni L. Application of international consensus diagnostic criteria to an Italian series of autoimmune pancreatitis. United European Gastroenterol J 2014; 1:276-84. [PMID: 24917972 DOI: 10.1177/2050640613495196] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 05/21/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND International consensus diagnostic criteria (ICDC) have been proposed to classify autoimmune pancreatitis (AIP) in type 1, type 2, or not otherwise specified. OBJECTIVE Aim was to apply the ICDC to an Italian series of patients to evaluate the incidence and clinical profiles among different subtypes of AIP. METHODS we re-evaluated and classified 92 patients diagnosed by Verona criteria, according to the ICDC. RESULTS Out of 92 patients, 59 (64%) were diagnosed as type 1, 17 (18%) as type 2, and 15 (16%) as not otherwise specified according to the ICDC. A significant difference between type 1 and type 2 were found for age (54.5 ± 14.5 vs. 34.4 ± 13.9 respectively; p < 0.0001), male sex (76 vs. 47%; p = 0.007), jaundice (66 vs. 18%; p = 0.002) and acute pancreatitis (9 vs. 47%; p < 0.0001), elevated serum IgG4 levels (85 vs. 7%; p < 0.0001), inflammatory bowel disease (8 vs. 82%; < 0.0001), and relapse of the disease (34 vs. 6%; p = 0.058). Imaging and response to steroids in the not-otherwise-specified group were similar to type 1 and 2. CONCLUSIONS Type 1 has a different clinical profile from type 2 autoimmune pancreatitis. The not-otherwise-specified group has peculiar clinical features which are shared both with type 1 or type 2 groups.
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Li A, Wang Y, Deng Z. Concurrent autoimmune pancreatitis and primary biliary cirrhosis: a rare case report and literature review. BMC Gastroenterol 2014; 14:10. [PMID: 24410827 PMCID: PMC3897989 DOI: 10.1186/1471-230x-14-10] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2013] [Accepted: 12/26/2013] [Indexed: 12/12/2022] Open
Abstract
Background Both autoimmune pancreatitis (AIP) and primary biliary cirrhosis (PBC) are related to various diseases. But the concurrence of AIP and PBC is extremely rare, with only 2 cases reported. Here we report the concurrence of AIP and PBC in a Chinese patient for the first time. Case presentation A 65-year-old male was admitted to our hospital with jaundice, pruritus, mild abdominal pain and darkening urine. Serum alkaline phosphatase, γ-glutamyltransferase, bilirubin and IgG4 were prominently elevated. The antimitochondrial antibody was positive. Radiological examination revealed diffusive enlargement of the pancreas. Pancreatic biopsy showed lymphoplasmacytic infiltration, fibrosis and abundant IgG4+ plasma cells. The patient was diagnosed with AIP and PBC. Nasobiliary tube was placed to facilitate biliary drainage. A combination therapy of steroid and UDCA was administered and the patient was gradually recovered, during which the patient was complicated with biliary infecion, herpes zoster and pulmonary abscess. Conclusion We present this case together with literature evidence to support the concurrence of AIP and PBC, share our experience of using combination therapy with steroid and UDCA, and raise the awareness of infectious complications in immunosuppressed patients.
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Affiliation(s)
| | - Yongjie Wang
- Department of Gastroenterology, Sir Run Run Shaw Hospital Affiliated to Medical School, Zhejiang University, Hangzhou, Zhejiang Province 310016, China.
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Affiliation(s)
- Miyu Tajima
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
- Department of Cardiology, Sakakibara Heart Institute
| | | | - Yukio Hiroi
- Department of Cardiology, National Center for Global Health and Medicine
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Matsubayashi H, Yoneyama M, Nanri K, Sugimoto S, Shinjo K, Kakushima N, Tanaka M, Ito S, Takao M, Ono H. Determination of steroid response by abdominal ultrasound in cases with autoimmune pancreatitis. Dig Liver Dis 2013; 45:1034-40. [PMID: 23906519 DOI: 10.1016/j.dld.2013.06.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 06/08/2013] [Accepted: 06/18/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Abdominal ultrasound is the most convenient modality for examining the morphology of the pancreas without physical stress. Steroid response is one of the key features of autoimmune pancreatitis; however, visualizing this response has not been evaluated using ultrasonography. METHODS Thirty-three consecutive autoimmune pancreatitis cases were retrospectively investigated for pancreatic and extrapancreatic lesions by ultrasonography before steroid therapy (n=33) and at two weeks (n=28) and one month (n=19) after starting oral steroid treatment. RESULTS Steroid treatment resulted in obvious shrinkage of the pancreatic lesion in 86% of the cases at two weeks and in 97% until one month. The maximum thickness of the pancreatic lesion was reduced from 28 to 22 mm in two weeks (P<0.0001), and pancreatic echographic findings improved in one month. Swelling of the peripancreatic lymph node was recognized in 48% and the aortic wall thickness in 12%, mostly reduced in two weeks (P=0.005). One case of definitive autoimmune pancreatitis revealed a steroid response only by following endoscopic retrograde cholangiopancreatography but not by ultrasonography or computed tomography. CONCLUSIONS Abdominal ultrasound revealed a steroid response in most cases of autoimmune pancreatitis within two weeks. Ultrasonography is suitable for initial confirmation of a steroid response; however, atypical cases showing insufficient response or not fulfilling criteria should undergo further examination.
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Resheq YJ, Quaas A, von Renteln D, Schramm C, Lohse AW, Lüth S. Infiltration of peritumoural but tumour-free parenchyma with IgG4-positive plasma cells in hilar cholangiocarcinoma and pancreatic adenocarcinoma. Dig Liver Dis 2013; 45:859-65. [PMID: 23602806 DOI: 10.1016/j.dld.2013.03.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 02/18/2013] [Accepted: 03/08/2013] [Indexed: 02/05/2023]
Abstract
BACKGROUND Recently, new guidelines for diagnosing IgG4-associated cholangitis have been published devaluing the diagnostic significance of IgG4-positive plasma cells and steroid trials. We sought to evaluate the utility of IgG4-positive plasma cells in discriminating IgG4-associated cholangitis from hilar cholangiocarcinoma and autoimmune pancreatitis from pancreatic adenocarcinoma under conditions when malignancy is likely to be missed. METHODS Resection specimens obtained from patients with hilar cholangiocarcinoma, pancreatic adenocarcinoma or hepatocellular carcinoma were re-evaluated for IgG4-positivity. Histological analysis focussed on peritumoural but tumour-free sections. Perioperative biochemical and clinical data were reviewed. RESULTS Nineteen patients with hilar cholangiocarcinoma and 29 patients with pancreatic adenocarcinoma were eligible for histological re-evaluation. Six of 19 (32%) patients with hilar cholangiocarcinoma and 5 of 29 (17%) patients with pancreatic adenocarcinoma were IgG4-positive (≥20 IgG4-positive plasma cells per high power field). Patients with IgG4-positive hilar cholangiocarcinoma showed significantly higher levels of serum total bilirubin (3.6mg/dl vs. 1.8mg/dl; P<0.05) and serum alanine-aminotransferase (median 343U/l vs. 63U/l, P<0.05) compared to IgG4-negative patients with hilar cholangiocarcinoma. CONCLUSIONS IgG4-positive plasma cells are of limited utility especially in distinguishing hilar cholangiocarcinoma from IgG4-associated cholangitis even when combined with clinical parameters and may be misleading under conditions when malignancy is missed.
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Affiliation(s)
- Yazid J Resheq
- I. Department of Medicine, University Medical Centre Hamburg-Eppendorf, Germany.
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Matsubayashi H, Uesaka K, Kanemoto H, Aramaki T, Nakaya Y, Kakushima N, Ono H. Reduction of splenic volume by steroid therapy in cases with autoimmune pancreatitis. J Gastroenterol 2013; 48:942-50. [PMID: 23076542 DOI: 10.1007/s00535-012-0692-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2012] [Accepted: 09/17/2012] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Splenomegaly is sometimes recognized in autoimmune diseases and chronic pancreatitis; however, it has not yet been studied in autoimmune pancreatitis (AIP). The current study analyzed splenic volume and its associated factors in cases with AIP. METHODS Splenic volume was measured using computed tomography (CT) volumetric analysis in 46 cases with AIP and compared with 92 age- and gender-matched controls, and 46 disease controls (liver cirrhosis). Forty-six cases of chronic pancreatitis were also analyzed. Cases with AIP were investigated for factors associated with splenic volume and splenic volume change in response to steroid therapy. RESULTS Splenic volume was significantly larger in AIP (149 ± 86 ml) than in controls (97 ± 38 ml) and in CP (108 ± 79 ml) (P < 0.0001 and 0.0002), and was smaller than in disease controls (222 ± 134 ml) (P = 0.003). In AIP cases, splenic volume was associated with age and gender (P = 0.04 and 0.02), and splenomegaly was recognized in 20 % (9/46) of cases. Abnormal uptake of (18)F-fluorodeoxyglucose was not detected in the spleen by positron emission tomography. Splenic vein (SpV) was frequently involved in AIP (67 %), but was all recanalized after steroid therapy. Splenic volume in cases with AIP was minimized to 77 % of the original (122 ± 40 ml) (P < 0.0001) and this trend was remarkable in cases with splenomegaly (66 %). In AIP, high serum IL-2 receptor level, diffuse pancreatic enlargement, and SpV stenosis were significantly associated with splenic shrinkage due to steroid treatment (P = 0.002, 0.02, and 0.03). CONCLUSIONS Splenomegaly was sometimes recognized in cases with AIP; however, these cases can be treated with steroids, especially in cases with diffuse pancreatic swelling and SpV stenosis.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka, 411-8777, Japan.
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Paik WH, Ryu JK, Park JM, Song BJ, Park JK, Kim YT, Lee K. Clinical and pathological differences between serum immunoglobulin G4-positive and -negative type 1 autoimmune pancreatitis. World J Gastroenterol 2013; 19:4031-4038. [PMID: 23840149 PMCID: PMC3703191 DOI: 10.3748/wjg.v19.i25.4031] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Revised: 04/01/2013] [Accepted: 04/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify clinical and pathological differences between serum immunoglobulin G4 (IgG4)-positive (SIP) and IgG4-negative (SIN) type 1 autoimmune pancreatitis (AIP) in South Korea.
METHODS: AIP was diagnosed by the international consensus diagnostic criteria. The medical records and pathology were retrospectively reviewed and IgG4-positive cells were counted in a high power field (HPF). Type I AIP was defined as a high serum level of IgG4 or histological finding. SIN type 1 AIP was defined as a histological evidence of type 1 AIP and a normal serum IgG4 level. The clinical and pathological findings were compared between the two groups. The analysis was performed using Student’s t test, Fischer’s exact test and Mann-Whitney’s U test. A P value of < 0.05 was considered statistically significant. As repeated comparison was made, P values of less than 5% (P < 0.05) were considered significant.
RESULTS: Twenty five patients with definite type 1 AIP (19 histologically and six serologically diagnosed cases) were enrolled. The mean tissue IgG4 concentrations were significantly higher in SIP than SIN group (40 cells per HPF vs 18 cells per HPF, P = 0.02). Among eight SIN patients, the tissue IgG4 concentrations were less than 15 cells per HPF in most of cases, except one. The sensitivity of serum IgG4 was 68% (17 SIP and eight SIN AIP). Other organ involvement was more frequently associated with SIP than SIN AIP (59% vs 26%, P = 0.016). However, the relapse rate and diffuse swelling of the pancreas were not associated with serum IgG4 level. The concentrations of IgG4-positive cells per HPF were higher in SIP than SIN AIP (40 vs 18, P = 0.02).
CONCLUSION: The sensitivity of serum IgG4 was 68% in type 1 AIP. High serum IgG4 level was associated with other organ involvement and tissue IgG4 concentration but did not affect the relapse rate in type 1 AIP.
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Guma M, Firestein GS. IgG4-related diseases. Best Pract Res Clin Rheumatol 2013; 26:425-38. [PMID: 23040358 DOI: 10.1016/j.berh.2012.07.001] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2012] [Accepted: 07/16/2012] [Indexed: 02/08/2023]
Abstract
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fascinating condition recognised as a systemic disease in 2003 [1,2]. The first link between autoimmunity affecting the pancreas, elevated serum IgG4 concentrations and large numbers of IgG4-positive plasma cells in pancreatic tissue was described only 2 years earlier [3]. Since then, many diseases that have long been viewed organ-specific are now considered within the spectrum of IgG4-RD. Practically any organ can be affected, having in common a key pathological feature consisting in dense lymphocyte and plasma cell infiltrate rich in IgG4-positive plasma cells, storiform fibrosis and often an elevated serum IgG4 concentration. While good clinical response to steroid therapy is observed, immunosuppressive or B-cell depleting therapy can be required. It is important to distinguish the IgG4-RD from traditional organ-specific autoimmune disease to guide therapy.
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Affiliation(s)
- Monica Guma
- Division of Rheumatology, Allergy and Immunology, UC San Diego, School of Medicine, La Jolla, CA, USA.
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Ozaslan E. Comment to "characteristics of autoimmune pancreatitis based on serum IgG4 level". Dig Liver Dis 2012; 44:884; author reply 884-5. [PMID: 22647395 DOI: 10.1016/j.dld.2012.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2012] [Revised: 04/13/2012] [Accepted: 04/15/2012] [Indexed: 12/11/2022]
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Author reply: Comment to “Characteristics of autoimmune pancreatitis based on serum IgG4 level”. Dig Liver Dis 2012. [DOI: 10.1016/j.dld.2012.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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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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Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes. Mod Pathol 2012; 25:956-67. [PMID: 22481280 DOI: 10.1038/modpathol.2012.54] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4(+) progressively transformed germinal centers should be included in the IgG4-related disease spectrum.
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Matsubayashi H, Sasaki K, Nagata K, Kanemoto H, Kiuchi R, Ono H. Pancreatic carcinoma mimicking diffuse-type autoimmune pancreatitis: important diagnostic role of pancreatic juice cytology using endoscopic naso-pancreatic drainage. J Dig Dis 2012; 13:287-90. [PMID: 22500792 DOI: 10.1111/j.1751-2980.2012.00584.x] [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] [Indexed: 12/11/2022]
Affiliation(s)
- Hiroyuki Matsubayashi
- Division of Endoscopy, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka, Japan.
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The Utility of Serum IgG4 Concentrations as a Biomarker. Int J Rheumatol 2012; 2012:198314. [PMID: 22536256 PMCID: PMC3321274 DOI: 10.1155/2012/198314] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Accepted: 01/17/2012] [Indexed: 12/18/2022] Open
Abstract
IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.
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Imai K, Matsubayashi H, Fukutomi A, Uesaka K, Sasaki K, Ono H. Endoscopic ultrasonography-guided fine needle aspiration biopsy using 22-gauge needle in diagnosis of autoimmune pancreatitis. Dig Liver Dis 2011; 43:869-74. [PMID: 21733766 DOI: 10.1016/j.dld.2011.05.021] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2011] [Revised: 05/23/2011] [Accepted: 05/29/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUNDS The effectiveness of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has not been fully evaluated in the diagnosis of autoimmune pancreatitis (AIP). AIM To evaluate the effectiveness of EUS-FNA using 22-gauge needles in the diagnosis of AIP. METHODS EUS-FNA was examined in 85 patients with pancreatic mass, including 64 patients with pancreatic cancer and 21 patients with AIP. We investigated ability of EUS-FNA using 22-gauge needle for the differential diagnosis between AIP and pancreatic cancer. We also compared the factors concerning FNA procedures (number of needle passes, size of lesion, device, and amount of obtained pancreatic tissue) between two diseases. RESULTS Tissues obtained from 21 patients with AIP, although none of them demonstrated histology suspicious for malignancy, did not show histological evidence definitive for AIP. The amount of obtained pancreatic tissue was almost equal between two diseases in each pancreatic location. Sensitivity, specificity, overall accuracy, and negative predictive value of histological diagnosis of pancreatic cancer were 92.2%, 100%, 94.1%, and 80.8%, respectively. CONCLUSION EUS-FNA using 22-gauge needle distinguished benign from malignant pancreatic mass with >90% of accuracy, regardless of the location. Hence, it was helpful for the clinical diagnosis of AIP, however not providing satisfactory samples for the histological diagnosis of AIP.
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Affiliation(s)
- Kenichiro Imai
- Division of Endoscopy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan
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Frulloni L, Lunardi C. Serum IgG4 in autoimmune pancreatitis: a marker of disease severity and recurrence? Dig Liver Dis 2011; 43:674-5. [PMID: 21763225 DOI: 10.1016/j.dld.2011.06.010] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2011] [Accepted: 06/07/2011] [Indexed: 02/07/2023]
Affiliation(s)
- Luca Frulloni
- Department of Medicine, University of Verona, Italy.
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