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Wu S, Wang H. IgG4-related digestive diseases: diagnosis and treatment. Front Immunol 2023; 14:1278332. [PMID: 37868965 PMCID: PMC10585276 DOI: 10.3389/fimmu.2023.1278332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 09/22/2023] [Indexed: 10/24/2023] Open
Abstract
IgG4-related digestive diseases encompass a group of chronic inflammatory disorders characterized by autoimmune reactions and fibrosis affecting multiple digestive organs. These diseases are identified by elevated serum levels of IgG4 and the presence of IgG4-positive plasma cell infiltration in the affected sites, along with storiform fibrosis, obliterative phlebitis, and eosinophilic infiltration. Although extensive research has been conducted, a comprehensive understanding of these conditions remains elusive. Current clinical diagnosis often relies on the application of integrated diagnostic criteria for IgG4-related diseases, combined with specific organ involvement criteria. Distinguishing them from malignancies poses considerable challenges. Moreover, further investigations are required to elucidate the underlying pathogenic mechanisms and explore potential therapeutic interventions. This review provides a systematic classification of IgG4-related digestive diseases while discussing their diagnostic strategies, clinical presentations, and treatment modalities. The comprehensive insights shared herein aim to guide clinicians in their practice and contribute to the advancement of knowledge in this field.
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Affiliation(s)
- Siyu Wu
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Haiqiang Wang
- Department of Internal Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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2
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Uchino K, Notohara K, Uehara T, Kuraishi Y, Itakura J, Matsukawa A. Utility of gastric biopsy in diagnosing IgG4-related gastrointestinal disease. Pathol Int 2020; 71:124-134. [PMID: 33378576 DOI: 10.1111/pin.13059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/27/2020] [Accepted: 11/30/2020] [Indexed: 01/13/2023]
Abstract
The utility of gastric biopsy for diagnosing immunoglobulin (Ig)G4-related gastrointestinal disease (IgG4-GID) remains unclear. Bottom-heavy plasmacytosis (BHP) is a distinct feature of IgG4-GID. To clarify the feasibility of using gastric biopsies to diagnose BHP in IgG4-GID, we analyzed the histological features and immunostaining of gastric biopsy specimens from 31 known IgG4-related disease (IgG4-RD) patients and we assessed the presence of BHP in 1696 consecutive routine gastric biopsies. Cases with both >10 IgG4-positive plasma cells per high-power field and an IgG4/IgG-positive ratio >40% were defined as IgG4-high. Ten of the 31 IgG4-RD patients were concluded to have IgG4-GID, in which IgG4-positive plasma cells were notably detected at the deeper part of the mucosa. Six cases displayed BHP whereas the remaining four cases showed transmural infiltration with concomitant Helicobacter pylori-associated gastritis. In addition to BHP, we identified two unique histologic features for IgG4-GID: plasmacytic aggregation in the muscularis mucosae and permeative plasmacytic infiltration between fundic glands in the non-atrophic mucosa. Six of the routine cases (0.35%) displayed BHP, including a case with IgG4-RD. IgG4-GID can be suspected by the presence of gastric biopsy specimens with characteristic histological features. Such cases are recommended to undergo further examinations to determine whether IgG4-RD is present.
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Affiliation(s)
- Kaori Uchino
- Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.,Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Nagano, Japan
| | - Yasuhiro Kuraishi
- Department of Gastroenterology, Shinshu University School of Medicine, Nagano, Japan
| | - Junya Itakura
- Department of Anatomic Pathology, Kurashiki Central Hospital, Okayama, Japan
| | - Akihiro Matsukawa
- Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
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Muto O, Tamakawa S, Takahashi K, Yokohama S, Takasoe A, Hirano F, Nishimura H, Saito H. IgG4-related Disease Manifesting as Gastroduodenal Ulcer Diagnosed by an Endoscopic Biopsy. Intern Med 2020; 59:2491-2497. [PMID: 32581158 PMCID: PMC7662039 DOI: 10.2169/internalmedicine.4483-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
A 26-year-old man was admitted to our hospital due to upper abdominal pain. He had previously been diagnosed with gastroduodenal ulcer at 23 and 25 years old and had been treated with proton-pump inhibitors. Endoscopic hemostasis and a biopsy were performed on the hemorrhagic gastroduodenal ulcers. Laboratory and pathologic examinations demonstrated elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into the gastroduodenal tissues. Based on the clinicopathologic findings and after excluding other causes, he was diagnosed with IgG4-related gastroduodenal ulcer. We herein report a rare case of IgG4-related disease manifesting as a gastroduodenal ulcer diagnosed by an endoscopic biopsy.
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Affiliation(s)
- Osamu Muto
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Susumu Tamakawa
- Department of Pathology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Kenji Takahashi
- Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Japan
| | - Shiro Yokohama
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Ai Takasoe
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Fuminori Hirano
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Hideo Nishimura
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
| | - Hiroki Saito
- Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan
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Nakata R, Uehara T, Iwaya M, Asaka S, Kobayashi S, Sugano M, Higuchi K, Kusama Y, Nakazawa K, Nakaguro M, Kobayashi M, Tateishi A, Makino M, Kawaguchi K, Maejima T, Ishii K, Sano K, Shimojo H, Hori A, Otsuki T, Hamano H, Kawa S, Ota H. Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis. Int J Surg Pathol 2020; 28:844-849. [PMID: 32456567 DOI: 10.1177/1066896920924781] [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: 11/17/2022]
Abstract
BACKGROUND. Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS. We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS. Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION. AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.
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Affiliation(s)
- Rie Nakata
- 168943Matsumoto Kyoritsu Hospital, Matsumoto, Japan
| | | | - Mai Iwaya
- 13056Shinshu University, Matsumoto, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | - Kenji Sano
- 36910Iida Municipal Hospital, Iida, Japan
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Tsai MK, Kuo CW, Chang LC. IgG4-related myositis. QJM 2019; 112:872-873. [PMID: 31393592 DOI: 10.1093/qjmed/hcz195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Indexed: 11/13/2022] Open
Affiliation(s)
- M-K Tsai
- From the Department of Internal Medicine, Armed Forces Taichung General Hospital, No. 348, Sec. 2, Zhongshan Rd., Taiping Dist., Taichung City 411, Taiwan (R.O.C)
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 114, Taiwan (R.O.C)
| | - C-W Kuo
- From the Department of Internal Medicine, Armed Forces Taichung General Hospital, No. 348, Sec. 2, Zhongshan Rd., Taiping Dist., Taichung City 411, Taiwan (R.O.C)
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 114, Taiwan (R.O.C)
| | - L-C Chang
- From the Department of Internal Medicine, Armed Forces Taichung General Hospital, No. 348, Sec. 2, Zhongshan Rd., Taiping Dist., Taichung City 411, Taiwan (R.O.C)
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 114, Taiwan (R.O.C)
- Department of Nutrition, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., South Dist., Taichung City 402, Taiwan (R.O.C)
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Chandra P, Nath S, Jain D. Pancreatitis, Cholangitis, and Gastritis: The Triumvirate of Immunoglobulin G4-Related Disease Identified Simultaneously on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography. Indian J Nucl Med 2019; 34:335-337. [PMID: 31579227 PMCID: PMC6771203 DOI: 10.4103/ijnm.ijnm_110_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Immunoglobulin G4-related disease (IgG4) is an immune-mediated fibro-inflammatory entity which affects multiple organs, most frequently the pancreas. Although extrapancreatic inflammations are commonly seen in 18F-fluorodeoxyglucose positron emission tomography/computed tomography of majority of these patients at follow-up, simultaneous involvement of the gastric/biliary tract at presentation is rare. Here, we present imaging findings of a patient who presented with obstructive jaundice and initially thought to be due to cholangiocarcinoma, but was subsequently diagnosed as an IgG4-related inflammation.
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Affiliation(s)
- Piyush Chandra
- Department of Nuclear Medicine, MIOT International, Chennai, Tamil Nadu, India
| | - Satish Nath
- Department of Nuclear Medicine, MIOT International, Chennai, Tamil Nadu, India
| | - Deepti Jain
- Department of Pathology, MIOT International, Chennai, Tamil Nadu, India
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A rare presentation of IgG4 related disease as a gastric antral lesion: Case report and review of the literature. Int J Surg Case Rep 2018; 51:244-247. [PMID: 30218821 PMCID: PMC6138857 DOI: 10.1016/j.ijscr.2018.08.065] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 08/25/2018] [Accepted: 08/28/2018] [Indexed: 02/07/2023] Open
Abstract
IgG4RD is a newly recognized systemic disease affecting nearly every organ. IgG4RD presenting as a gastric mass is extremely rare. Preoperative biopsy is mandatory for definitive diagnosis. When diagnosed before surgery, the treatment is medical with IV steroids. Introduction Immunoglobulin G4 related disease is a recently recognized systemic fibro-inflammatory disorder affecting virtually every organ in the body, characterized by lympho-plasmacytic dense infiltrates rich in IgG4 positive plasmacytes along with storiform fibrosis, inconstantly associated with elevated serum IgG4 levels. Few cases of Immunoglobulin G4 related disease occurring solely in the stomach have been published. Presentation of case We herein present a rare case of a 57 year old male patient presenting with an incidentally discovered asymptomatic pre-pyloric submucosal gastric lesion confused with a gastro-intestinal stromal tumor with failed endoscopic biopsy attempts due to tumor mobility. The patient underwent wedge resection of the lesion which was diagnosed postoperatively as Immunoglobulin G4 related disease. Discussion Immunoglobulin G4 related disease presenting as a solitary lesion in the stomach is a very rare condition. It should be kept in the differential diagnosis of a submucosal mass or polyp. The treatment is medical with systemic steroid therapy. Conclusion Obtaining a tissue biopsy is of extreme importance to avoid unnecessary surgery.
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Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey. J Gastroenterol 2018; 53:845-853. [PMID: 29222587 DOI: 10.1007/s00535-017-1420-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 11/28/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease; IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. METHODS Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. RESULTS Overall, the IgG4 counts (87-345/high-power field) and IgG4/IgG-positive ratio were high (44-115%). The demographic findings included advanced age among the patients (55-80 years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible cases of IgG4-RD because of the histologic findings and lack of OOI. CONCLUSIONS IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer. Characteristic histologic findings are observed in the muscularis propria and gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers of IgG4-GID.
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9
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Al-Mujaini A, Al-Khabori M, Shenoy K, Wali U. Immunoglobulin G4-Related Disease: An Update. Oman Med J 2018; 33:97-103. [PMID: 29657677 DOI: 10.5001/omj.2018.20] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized immune-mediated condition comprised of a collection of disorders that share specific pathological, serological, and clinical features. IgG4-RD is a fibroinflammatory condition with a tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of serum IgG4, which may affect virtually every organ and tissue. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, or involvement of other orbital tissue. Hypophysitis or pachymeningitis may manifest as cranial neuropathies. The diagnosis of IgG4-RD is based on a typical clinical scenario, supportive laboratory test, expected radiological characteristics, and distinct histopathological and immunohistochemical features. Corticosteroids and immunosuppressives form the mainline treatment.
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Affiliation(s)
- Abdullah Al-Mujaini
- Department of Ophthalmology, College of Medicine and Health Sciences, Sultan Qaboos University Hospital, Muscat, Oman
| | - Murtadha Al-Khabori
- Department of Hematology, College of Medicine and Health Sciences, Sultan Qaboos University Hospital, Muscat, Oman
| | - Kashinatha Shenoy
- Department of Ophthalmology, College of Medicine and Health Sciences, Sultan Qaboos University Hospital, Muscat, Oman
| | - Upender Wali
- Department of Ophthalmology, College of Medicine and Health Sciences, Sultan Qaboos University Hospital, Muscat, Oman
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Culver EL, Smit WL, Evans C, Sadler R, Cargill T, Makuch M, Wang LM, Ferry B, Klenerman P, Barnes E. No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort. Pancreatology 2017; 17:395-402. [PMID: 28412148 PMCID: PMC5459459 DOI: 10.1016/j.pan.2017.04.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/02/2017] [Accepted: 04/04/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Helicobacter pylori (H.pylori) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. METHODS Clinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP. RESULTS 85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1-4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC. CONCLUSIONS In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD. KEYWORDS FOR ABSTRACT Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.
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Affiliation(s)
- Emma L Culver
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
| | - Wouter L Smit
- Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK; Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Caroline Evans
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Ross Sadler
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Tamsin Cargill
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
| | - Mateusz Makuch
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK
| | - Lai-Mun Wang
- Department of Cellular Pathology, John Radcliffe Hospital, Oxford, UK
| | - Berne Ferry
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Paul Klenerman
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
| | - Eleanor Barnes
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
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Katabathina VS, Khalil S, Shin S, Lath N, Menias CO, Prasad SR. Immunoglobulin G4-Related Disease: Recent Advances in Pathogenesis and Imaging Findings. Radiol Clin North Am 2017; 54:535-51. [PMID: 27153787 DOI: 10.1016/j.rcl.2015.12.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a novel, immune-mediated, multisystem disease characterized by the development of tumefactive lesions in multiple organs. IgG4-RD encompasses many fibroinflammatory diseases that had been thought to be confined to single organs. Delayed diagnosis or misdiagnosis as malignancies leading to aggressive treatment may be averted by identification of the multisystem nature of IgG4-RD. Most cases show exquisite response to steroid therapy; steroid-resistant cases are being treated by novel therapeutic agents, including B-cell depleting agents such as rituximab. Cross-sectional imaging studies play a pivotal role in the initial diagnosis, assessing response to therapy and long-term surveillance.
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Affiliation(s)
- Venkata S Katabathina
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
| | - Suhare Khalil
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Sooyoung Shin
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Narayan Lath
- Department of Radiology, Singapore General Hospital, Outram road, Singapore 169608, Singapore
| | | | - Srinivasa R Prasad
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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12
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Abstract
IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, which is characterized by a tendency to form tumefactive lesions, increased serum levels of IgG4, and massive infiltration of IgG4-positive plasma cells with storiform fibrosis and/or obliterative phlebitis. Patients with IgG4-RD have frequently multiorgan involvements such as the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, and retroperitoneum. IgG4-RD mainly affects middle-aged to elderly men except for involvement in lachrymal and salivary glands, so-called Mikulicz's disease. The clinical manifestations of IgG4-RD depend on individually involved organs and respond well to steroid, but the prognosis still remains unclear. Some patients develop serious complications such as obstructive jaundice due to hepatic, gallbladder, or pancreatic lesions; hydronephrosis due to retroperitoneal fibrosis; or respiratory symptoms due to pulmonary lesions. Nomenclatures of individual organ manifestation of IgG4-RD have been internationally consented.
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13
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Sarkar A, Pitchumoni CS. The protean manifestations of IgG4-RD in gastrointestinal disorders. Dis Mon 2015; 61:493-515. [DOI: 10.1016/j.disamonth.2015.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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14
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Kawano H, Ishii A, Kimura T, Takahashi T, Hironaka H, Kawano M, Yamaguchi M, Oishi K, Kubo M, Matsui S, Notohara K, Ikeda E. IgG4-related disease manifesting the gastric wall thickening. Pathol Int 2015; 66:23-8. [DOI: 10.1111/pin.12364] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 10/20/2015] [Indexed: 12/17/2022]
Affiliation(s)
- Hiroo Kawano
- Department of Laboratory Science, Faculty of Health Science; Yamaguchi University Graduate School of Medicine; Ube Japan
| | - Aya Ishii
- Department of Pathology; Yamaguchi University Graduate School of Medicine; Ube Japan
| | - Tokuhiro Kimura
- Department of Pathology; Yamaguchi University Graduate School of Medicine; Ube Japan
| | | | - Hideharu Hironaka
- Department of Surgery; Saiseikai Yamaguchi Hospital; Yamaguchi Japan
| | - Michitaka Kawano
- Department of Internal Medicine; Saiseikai Yamaguchi Hospital; Yamaguchi Japan
| | - Michiya Yamaguchi
- Department of Dermatology; Yamaguchi University Graduate School of Medicine; Ube Japan
| | - Keiji Oishi
- Department of Internal medicine; Ube Medical Center; Ube Japan
| | - Makoto Kubo
- Department of Medicine and Clinical Science; Yamaguchi University Graduate School of Medicine; Ube Japan
| | - Shoko Matsui
- Health Administration Center; Toyama University; Toyama Japan
| | - Kenji Notohara
- Department of Anatomic Pathology; Kurashiki Central Hospital; Kurashiki Japan
| | - Eiji Ikeda
- Department of Pathology; Yamaguchi University Graduate School of Medicine; Ube Japan
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15
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Deshpande V. IgG4-Related Disease of the Gastrointestinal Tract: A 21st Century Chameleon. Arch Pathol Lab Med 2015; 139:742-9. [PMID: 26030243 DOI: 10.5858/arpa.2014-0181-ra] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT Immunoglobulin G4 (IgG4)-related disease is a systemic fibroinflammatory disease capable of affecting virtually any organ. Although the pancreas and hepatobiliary system are commonly affected, involvement of the tubular gut is unusual. The pancreatic manifestations of this disease (autoimmune pancreatitis) often mimic pancreatic carcinoma, whereas the hepatobiliary manifestations are mistaken for cholangiocarcinoma or primary sclerosing cholangitis. The characteristic histologic features include a dense lymphoplasmacytic infiltrate, storiform-type fibrosis, and obliterative phlebitis. An increase in IgG4(+) plasma cells and an IgG4 to IgG ratio of more than 40% are considered obligatory components of the diagnostic algorithm. OBJECTIVE To review the challenges associated with the diagnosis of IgG4-related disease of the gastrointestinal tract. DATA SOURCES A review of pertinent literature, along with the author's personal experience, based on institutional and consultation materials. CONCLUSION The complete spectrum of histologic changes is seldom captured in a biopsy specimen, and thus, the histopathology findings are best interpreted within the overall clinical context. Increased IgG4(+) plasma cells are identified in a variety of benign and malignant diseases of the gastrointestinal tract.
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Affiliation(s)
- Vikram Deshpande
- From the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston
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16
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Abstract
IgG4-related disease (IgG4-RD) is relatively a new growing entity of immune-mediated origin, characterized by a mass-forming lesion, the infiltration of IgG4-positive plasma cells and occasionally elevated serum IgG4. It is considered to be both a systemic inflammation and sclerosing disease. The most common manifestations are parotid and lacrimal swelling, lymphadenopathy and autoimmune pancreatitis. Sclerosing cholangitis and retroperitoneal fibrosis are among the other mentioned frequent manifestations. The diagnosis should be approved histo-pathologically but other conditions such as lymphoma should be carefully excluded. Patients with IgG4-RD respond beneficially to glucocorticoid therapy especially when given at early onset stages. In some cases, the combination of immunosuppressive agents is required.
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Arnason T, Brown IS, Goldsmith JD, Anderson W, O'Brien BH, Wilson C, Winter H, Lauwers GY. Collagenous gastritis: a morphologic and immunohistochemical study of 40 patients. Mod Pathol 2015; 28:533-44. [PMID: 25234289 DOI: 10.1038/modpathol.2014.119] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2014] [Revised: 07/14/2014] [Accepted: 07/22/2014] [Indexed: 12/13/2022]
Abstract
Collagenous gastritis is a rare condition defined histologically by a superficial subepithelial collagen layer. This study further characterizes the morphologic spectrum of collagenous gastritis by evaluating a multi-institutional series of 40 patients (26 female and 14 male). The median age at onset was 16 years (range 3-89 years), including 24 patients (60%) under age 18. Twelve patients (30%) had associated celiac disease, collagenous sprue, or collagenous colitis. Hematoxylin and eosin slides were reviewed in biopsies from all patients and tenascin, gastrin, eotaxin, and IgG4/IgG immunohistochemical stains were applied to a subset. The distribution of subepithelial collagen favored the body/fundus in pediatric patients and the antrum in adults. There were increased surface intraepithelial lymphocytes (>25 lymphocytes/100 epithelial cells) in five patients. Three of these patients had associated celiac and/or collagenous sprue/colitis, while the remaining two had increased duodenal lymphocytosis without specific etiology. An eosinophil-rich pattern (>30 eosinophils/high power field) was seen in 21/40 (52%) patients. Seven patients' biopsies demonstrated atrophy of the gastric corpus mucosa. Tenascin immunohistochemistry highlighted the subepithelial collagen in all 21 specimens evaluated and was a more sensitive method of collagen detection in biopsies from two patients with subtle subepithelial collagen. No increased eotaxin expression was identified in 16 specimens evaluated. One of the twenty-three biopsies tested had increased IgG4-positive cells (100/high power field) with an IgG4/IgG ratio of 55%. In summary, collagenous gastritis presents three distinct histologic patterns including a lymphocytic gastritis-like pattern, an eosinophil-rich pattern, and an atrophic pattern. Eotaxin and IgG4 were not elevated enough to implicate these pathways in the pathogenesis. Tenascin immunohistochemistry can be used as a sensitive method of collagen detection.
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Affiliation(s)
- Thomas Arnason
- 1] Gastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA [2] Division of Anatomical Pathology, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada
| | - Ian S Brown
- 1] Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia [2] Envoi Pathology, Brisbane, QLD, Australia
| | - Jeffrey D Goldsmith
- Department of Pathology, Children's Hospital Boston, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | | | | | - Claire Wilson
- Providence Alaska Medical Center, Anchorage, AK, USA
| | - Harland Winter
- Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA
| | - Gregory Y Lauwers
- Gastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Uehara T, Hamano H, Kawa S, Kobayashi Y, Yoshizawa A, Oki K, Nakata R, Kobayashi A, Sano K, Ota H. Comparison of histopathological features of pancreatic carcinoma and type 1 autoimmune pancreatitis. Pathol Int 2015; 64:51-7. [PMID: 24629172 DOI: 10.1111/pin.12136] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 01/13/2014] [Indexed: 12/24/2022]
Abstract
Type 1 autoimmune pancreatitis (AIP-1) is an immunoglobulin G (IgG)-4-related disease (IgG4-RD), characterized by elevated serum immunoglobulin G4 (IgG4) and infiltration by IgG4(+) plasma cells. Pancreatic carcinoma (PC) sometimes shows infiltration by IgG4(+) plasma cells, but details have been unclear. We compared pathological findings and expression of IgG4 and IgG in fibroses in 18 PC patients to those from 9 AIP-1 patients. Fibroses were divided into areas of ductal adenocarcinoma (DA) and obstructive pancreatitis (OP). Serum IgG4 levels were lower than the cut-off value in all PC patients with no IgG4-RD. Diffuse lymphoplasmacytic infiltration and eosinophil infiltration were characteristic of fibroses in PC. Though AIP-1 samples often had storiform fibrosis even in biopsies, PC did not show storiform fibrosis. Ratios of IgG4(+) plasma cells/IgG(+) plasma cells (IgG4/IgG ratios) in DA and OP were significantly lower than in AIP-1. However, high-density IgG4(+) plasma cell foci were detected in PC fibroses, particularly around peripheral nerves, vessels, and lymphoid follicles; between lobules and invasion fronts; and within neutrophilic abscesses. In conclusion, the IgG4/IgG ratio is useful in distinguishing PC from AIP-1, and should be evaluated in three or more areas, as PC can show localized high-density IgG4(+) plasma cell areas.
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Affiliation(s)
- Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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Recent advances in the diagnosis and management of autoimmune pancreatitis. AJR Am J Roentgenol 2014; 202:1007-21. [PMID: 24758653 DOI: 10.2214/ajr.13.11247] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Autoimmune pancreatitis (AIP) is a rare chronic relapsing steroid-responsive fibroinflammatory disorder of the pancreas that is likely caused by immune dysregulation. It is now thought that AIP consists of two distinct clinicopathologic syndromes currently designated as types 1 and 2. CONCLUSION A current update on etiopathogenesis, pathology, and clinical and imaging findings of AIP is provided with an emphasis on diagnosis and management.
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Uehara T, Hamano H, Suga T, Kawa S, Yoshizawa A, Kobayashi Y, Murata K, Oki K, Sano K, Onodera R, Ota H. Inflammation of colon adenoma in the setting of type 1 autoimmune pancreatitis. Pathol Int 2014; 64:67-74. [DOI: 10.1111/pin.12139] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Accepted: 01/19/2014] [Indexed: 12/24/2022]
Affiliation(s)
- Takeshi Uehara
- Department of Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Hideaki Hamano
- Division of Medical Informatics; Shinshu University Hospital; Matsumoto Japan
| | - Tomoaki Suga
- Gastroenterology, Department of Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Shigeyuki Kawa
- Center for Health, Safety and Environmental Management; Shinshu University; Matsumoto Japan
| | - Akihiko Yoshizawa
- Department of Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Yukihiro Kobayashi
- Department of Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Kazuya Murata
- Department of Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Keiko Oki
- Department of Laboratory Medicine; Shinshu University Hospital; Matsumoto Japan
| | - Kenji Sano
- Department of Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Rie Onodera
- Department of Biomedical Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
| | - Hiroyoshi Ota
- Department of Laboratory Medicine; Shinshu University School of Medicine; Matsumoto Japan
- Department of Laboratory Medicine; Iwate Medical University School of Medicine; Morioka Japan
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Koizumi S, Kamisawa T, Kuruma S, Tabata T, Chiba K, Iwasaki S, Endo Y, Kuwata G, Koizumi K, Shimosegawa T, Okazaki K, Chiba T. Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases? World J Gastroenterol 2013; 19:5769-5774. [PMID: 24124321 PMCID: PMC3793131 DOI: 10.3748/wjg.v19.i35.5769] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 05/30/2013] [Accepted: 07/19/2013] [Indexed: 02/06/2023] Open
Abstract
In immunoglobulin G4 (IgG4)-related disease (RD), organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs. Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis, it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD, because none of the following is observed in these lesions: a mass-like formation; dense fibrosis; or obliterative phlebitis. Based on our review of the literature, there appear to be two types of IgG4-related gastrointestinal disease. One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach, consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells, which usually show submucosal spreading. The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach, colon, and major duodenal papilla, showing polypoid or mass-like lesions. Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose. It is of utmost importance to rule out malignancy. However, these lesions may respond to steroid therapy. To avoid unnecessary resection, IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.
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Abstract
IgG4-related disease, a newly established multisystemic disease can affect virtually every organ. Histologically, it is characterized by the presence of a dense lymphoplasmacytic infiltrate, storiform-type fibrosis, and obliterative phlebitis. The disease shows elevated serum and tissue IgG4. The pancreas and hepatobiliary tract are involved far more commonly than the tubular gut. This review summarizes the clinical and pathologic features of the gastrointestinal manifestations of IgG4-related disease and discusses the wide spectrum of diseases that this entity may mimic.
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Affiliation(s)
- Madelyn Lew
- Department of Pathology, Massachusetts General Hospital, 55 Fruit street, Boston, MA 02114, USA
| | - Vikram Deshpande
- Department of Pathology, Massachusetts General Hospital, 55 Fruit street, Boston, MA 02114, USA.
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The similarity of Type 1 autoimmune pancreatitis to pancreatic ductal adenocarcinoma with significant IgG4-positive plasma cell infiltration. J Gastroenterol 2013; 48:751-61. [PMID: 23053421 DOI: 10.1007/s00535-012-0677-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 08/23/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND High serum immunoglobulin G4 (IgG4) levels and infiltration of IgG4-positive cells are characteristic of Type 1 autoimmune pancreatitis (AIP). We previously reported that increased regulatory T cells (Tregs) may regulate IgG4 production in AIP. Although an increased serum IgG4 concentration is observed in some patients with pancreatic ductal adenocarcinoma (PDA), clarification is still necessary. We have therefore studied the correlations between IgG4-positive cells and Tregs in patients with PDA. SUBJECTS AND METHODS A total of 21 PDA and nine AIP patients were enrolled in our study. The numbers and ratios of Tregs, IgG4-positive, and IgG-positive cells immunohistochemically stained with anti-Foxp3, IgG4, and IgG antibodies, respectively, were counted in three areas of resected pancreata in PDA, peritumoral pancreatitis (PT), and obstructive pancreatitis (OP). RESULTS In PDA, PT, OP area, the number of IgG4-Positive cells (5.183 ± 1.061, 2.250 ± 0.431, 4.033 ± 1.018, respectively; p < 0.05) and the ratio of IgG4/IgG (0.391 ± 0.045, 0.259 ± 0.054, 0.210 ± 0.048, respectively; p < 0.05) were significantly lower than those in AIP (21.667 ± 2.436 and 0.306 ± 0.052, respectively). The numbers of IgG4-positive cells did not differ significantly among the three areas of resected pancreata examined. However, the IgG4/IgG (0.391 ± 0.045) and Foxp3/monocyte (0.051 ± 0.008) ratios in PDA area were significantly (p < 0.05) higher than those in OP area (IgG4/IgG: 0.210 ± 0.048; oxp3/monocyte: 0.0332 ± 0.005), but not in PT area. Of the 21 cases of PDA, the ratio of IgG4/IgG was >40 % in nine (43%), six (29%) and three (14%) cases in PDA, PT and OP area, respectively. Foxp3 and IgG4 were positively correlated in OP area, but not in PDA and PT area. CONCLUSIONS Clinicians should be careful when basing a differential diagnosis of PDA and AIP on the numbers of IgG4-positive cells and the ratio of IgG4/IgG, especially when determined using a small biopsied sample.
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IgG4-related disease-like fibrosis as an indicator of IgG4-related lymphadenopathy. Ann Diagn Pathol 2013; 17:416-20. [PMID: 23702322 DOI: 10.1016/j.anndiagpath.2013.04.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2013] [Revised: 03/30/2013] [Accepted: 04/18/2013] [Indexed: 01/06/2023]
Abstract
The significance of IgG4-related diseases including IgG4-related lymphadenopathy has recently been recognized worldwide. Inflammatory pseudotumors in lymph nodes, as well as in other organs, are also recognized as IgG4-related diseases. Only a few case reports have described IgG4-related lymphadenopathy with fibrosis (IgG4-fibrosing lymphadenopathy), and IgG4-fibrosing lymphadenopathy has not been compared clinicopathologically with non-IgG4-related lymphadenopathy with fibrosis. We have evaluated the pathologic features in 13 patients with IgG4-fibrosing lymphadenopathy, including IgG4 and IgG expression in lymph nodes, and compared these features with those of patients with non-IgG4-related lymphadenopathy with fibrosis with reactive inguinal lymphadenopathy and focal fibrosis and lymph nodes at least 10 mm in diameter. IgG4-fibrosing lymphadenopathy was characterized by lymphoplasmacytic and eosinophilic infiltration, many IgG4-positive plasma cells in fibrotic areas, and high serum IgG4 concentrations. The IgG4-positive/IgG-positive plasma cell ratio was significantly higher in the IgG4-fibrosing lymphadenopathy than in the non-IgG4-fibrosing lymphadenopathy group. The presence of even minor fibrosis with characteristics of IgG4-related disease such as IgG4-fibrosing lymphadenopathy may facilitate the diagnosis of IgG4-related lymphadenopathy.
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Okazaki K, Uchida K, Ikeura T, Takaoka M. Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system. J Gastroenterol 2013; 48:303-14. [PMID: 23417598 PMCID: PMC3698437 DOI: 10.1007/s00535-012-0744-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Accepted: 12/16/2012] [Indexed: 02/04/2023]
Abstract
Recently, IgG4-related disease (IgG4-RD) has been recognized as a novel clinical entity with multiorgan involvement and unknown origin, associated with abundant infiltration of IgG4-positive cells. The Japanese research committee, supported by the Ministry of Health, Labor and Welfare of Japan, unified many synonyms for these conditions to the term "IgG4-RD" in 2009. The international symposium on IgG4-RD endorsed the comprehensive nomenclature as IgG4-RD, and proposed the individual nomenclatures for each organ system manifestations in 2011. Although the criteria for diagnosing IgG4-RD have not yet been established, proposals include the international pathological consensus (IPC) and the comprehensive diagnostic criteria (CDC) for IgG4-RD for general use, and several organ-specific criteria for organ-specialized physicians, e.g., the International consensus diagnostic criteria (ICDC) and the revised clinical diagnostic criteria in 2011 by the Japan Pancreas Society (JPS-2011) for type1 AIP; the Clinical Diagnostic Criteria 2012 for IgG4-sclerosing cholangitis (IgG4-SC-2012); the diagnostic criteria for IgG4-positive Mikulicz's disease by the Japanese Society for Sjogren's syndrome; and diagnostic criteria for IgG4-related kidney disease by the Japanese Society of Nephrology. In cases of probable or possible IgG4-RD diagnosed by the CDC, organ-specific diagnostic criteria should be concurrently used according to a diagnosis algorithm for IgG4-RD, with referral to a specialist.
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Affiliation(s)
- Kazuichi Okazaki
- The Third Department of Internal Medicine Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka 573-1197 Japan
| | - Kazushige Uchida
- The Third Department of Internal Medicine Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka 573-1197 Japan
| | - Tsukasa Ikeura
- The Third Department of Internal Medicine Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka 573-1197 Japan
| | - Makoto Takaoka
- The Third Department of Internal Medicine Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka 573-1197 Japan
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Atypical manifestations of IgG4-related sclerosing disease in the abdomen: imaging findings and pathologic correlations. AJR Am J Roentgenol 2013; 200:102-12. [PMID: 23255748 DOI: 10.2214/ajr.12.8783] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The purpose of this essay is to illustrate a variety of atypical imaging manifestations of IgG4-related sclerosing disease in the abdomen and to correlate the imaging and pathologic findings. CONCLUSION In rare instances, IgG4-related sclerosing disease manifests atypical features in various organs in the abdomen. It is important that radiologists be aware of the typical and atypical features of this disease to provide timely effective treatment.
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Kim DH, Kim J, Park DH, Lee JH, Choi KD, Lee GH, Jung HY, Kim JH. Immunoglobulin G4-related inflammatory pseudotumor of the stomach. Gastrointest Endosc 2012; 76:451-2. [PMID: 21981816 DOI: 10.1016/j.gie.2011.07.061] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2011] [Accepted: 07/27/2011] [Indexed: 02/08/2023]
Affiliation(s)
- Do Hoon Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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Immunoglobulin G4 immunostaining of gastric, duodenal, or colonic biopsies is not helpful for the diagnosis of autoimmune pancreatitis. Clin Gastroenterol Hepatol 2012; 10:91-4. [PMID: 21946123 DOI: 10.1016/j.cgh.2011.09.008] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 08/23/2011] [Accepted: 09/10/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The aim of this study was to evaluate the specificity of the infiltration of digestive tract mucosa by immunoglobulin (Ig) G4-positive plasma cells in patients with autoimmune pancreatitis (AIP), as compared with normal or inflammatory mucosa. METHODS Plasma cell infiltration, CD138 and IgG4 immunostaining of digestive biopsies were compared in 4 groups of patients: AIP type 1 (n = 19); AIP type 2 (n = 4) with inflammatory bowel disease (IBD); IBD without pancreatic disorders (n = 20); and controls (n = 26). RESULTS With AIP type 1 versus controls, more plasma cells were present in the gastric mucosa of AIP (P = .02) without difference concerning IgG4+ plasma cells at any biopsy site. With AIP type 1 versus IBD, colonic mucosa was more often abnormal (P = .004), and more CD138 (P = .02) and IgG4 plasma cells (P = .0002) were counted in the colon biopsies of IBD. With AIP type 2 versus IBD, no difference for plasma cell and IgG4 infiltration was found. CONCLUSIONS IgG4-positive plasma cells are not more numerous in the digestive mucosa of AIP patients than in controls, but they are more abundant in the colon of IBD patients than in AIP patients.
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Abstract
PURPOSE OF REVIEW The spectrum of IgG4-related systemic disease (IgG4-RSD) continues to widen. At most of the sites involved by this condition, the clinical presentation can mimic neoplasm. Pathologic assessment of small biopsies can be critical to proper management. This review summarizes the histologic features of IgG4-RSD and the role of immunohistochemistry of IgG4 in the diagnosis. RECENT FINDINGS The review period saw further expansion of the list of sites putatively involved by IgG4-RSD, with new, or more detailed, entries related to lung, lymph nodes, stomach, and thyroid. A tentative consensus was reached on the issue of subtypes of autoimmune pancreatitis. The role of immunohistochemistry for IgG4 as an adjunct to the diagnosis of IgG4-RSD was further clarified. SUMMARY Sclerosing lymphoplasmacytic inflammation at almost any site can represent a manifestation of IgG4-RSD. There are several histologic features that can suggest the diagnosis. Immunohistochemistry for IgG4 is a useful diagnostic test to further support the diagnosis.
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Abstract
PURPOSE OF REVIEW To summarize the existing knowledge of various clinical presentations of IgG4-related systemic disease (IgG4-RSD) and to review the evolving list of organs affected by IgG4-RSD. RECENT FINDINGS The term IgG4-RSD encompasses a variety of clinical entities once regarded as being entirely separate diseases. The list of organs associated with this condition is growing steadily. Tissue biopsies reveal striking histopathological similarity, regardless of which organ is involved, although subtle differences across organs exist. Diffuse lymphoplasmacytic infiltrates, presence of abundant IgG4-positive plasma cells and extensive fibrosis are the hallmark pathology findings. Tumorous swelling, eosinophilia, and obliterative phlebitis are other frequently observed features. Polyclonal elevations of serum IgG4 are found in most but not all patients. SUMMARY IgG4-RSD is an underrecognized condition about which knowledge is now growing rapidly. Yet there remain many unknowns with regard to its cause, pathogenesis, various clinical presentations, approach to treatment, disease monitoring, and long-term outcomes. A wide variety of organs can be involved in IgG4-RSD. Clinicians should be aware of this entity and consider the diagnosis in the appropriate settings.
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Current world literature. Curr Opin Rheumatol 2010; 23:125-30. [PMID: 21124095 DOI: 10.1097/bor.0b013e3283422cce] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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