|
1
|
Lai KKH, Ang TWX, Cheuk W, Kwok A, Lin M, Lustig Y, Selva D, Ben Simon G, Xing Y, Xu ZH, Yang HS, Chong KKL, Yuen HKL. Advances in understanding and management of IgG4-related ophthalmic disease. Asia Pac J Ophthalmol (Phila) 2024; 13:100101. [PMID: 39326526 DOI: 10.1016/j.apjo.2024.100101] [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: 03/21/2024] [Revised: 06/05/2024] [Accepted: 06/13/2024] [Indexed: 09/28/2024] Open
Abstract
Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is an emerging, immune-mediated fibroinflammatory orbital disease, characterized by tumefactive lesions with noticeable IgG4+ plasma cell infiltration and distinctive pathohistological features. This disease is often associated with elevated serum IgG4 concentrations. IgG4-ROD may affect any ophthalmic tissues, particularly the lacrimal gland, extraocular muscles, and trigeminal nerves. Although the exact pathogenic role of IgG4 antibodies remains unclear, B-cell depleting agents have been reported to be an effective treatment. The diverse clinical manifestations of IgG4-ROD complicate diagnosis, and without prompt treatment, visual-threatening complications such as optic neuropathy may arise. Recent advances in understanding and managing IgG4-ROD have revolutionized the diagnosis and treatment of this emerging disease. This review article aims to provide a comprehensive overview of the latest advancements in the field of IgG4-ROD.
Collapse
Affiliation(s)
- Kenneth Ka Hei Lai
- Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China
| | | | - Wah Cheuk
- Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China
| | - Angie Kwok
- Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China
| | - Ming Lin
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Yael Lustig
- The Goldschleger Eye Institute, Sheba Medical Center, Tel HaShomer, Israel
| | - Dinesh Selva
- South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Guy Ben Simon
- The Goldschleger Eye Institute, Sheba Medical Center, Tel HaShomer, Israel
| | - Yue Xing
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Ophthalmology, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Zhi Hui Xu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Hua Sheng Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Kelvin Kam Lung Chong
- Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong, China; Hong Kong Eye Hospital, Hong Kong, China; Eye Centre, The Chinese University of Hong Kong Medical Centre, Hong Kong, China.
| | - Hunter Kwok Lai Yuen
- Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Eye Hospital, Hong Kong, China.
| |
Collapse
|
|
2
|
Wheeler S, Andeen N, Reddy R. Isolated IgG4 related disease of the trachea. Respir Med Case Rep 2024; 49:102031. [PMID: 38712313 PMCID: PMC11070757 DOI: 10.1016/j.rmcr.2024.102031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 04/26/2024] [Indexed: 05/08/2024] Open
Abstract
IgG4 related disease (IgG4-RD) is a multisystem inflammatory disease and can affect several organs including salivary glands, orbits, lungs, pancreas, kidneys and lymph nodes. Up to 40 % of patients have allergic manifestations including asthma, chronic rhinosinusitis, eczema and asthma. Commonly pulmonary manifestations include pulmonary nodules ranging from <1 to 5 cm in diameter, interstitial opacities and mediastinal lymphadenopathy. Rarely, IgG4-RD presents as isolated tracheal disease. Symptoms include dyspnea and stridor due to airway narrowing. Diagnosis of IgG4-RD including tracheal IgG4-RD requires a biopsy. The histologic specimen is characterized by lymphoplasmacytic infiltrate with high density of IgG4 positive plasma cells, and storiform fibrosis (a cartwheel appearance of fibroblasts and inflammatory cells). Up to 30 % of patients with IgG4-RD have normal serum IgG4 levels. The mainstay of therapy is glucocorticoids for those with systemic disease. Rituximab is an alternative for those who cannot tolerate glucocorticoids or those with disease recurrence. Patients with tracheal disease often require balloon dilation. Recurrence is common in patients and up to two thirds of patients have residual disease despite treatment. These patients often require surgical resection of affected area for symptomatic relief.
Collapse
Affiliation(s)
- Sarah Wheeler
- Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Nicole Andeen
- Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Raju Reddy
- Division of Pulmonary, Allergy and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA
| |
Collapse
|
|
3
|
Joseph J, Prabhu V, Thomas M, Karuppusami R, Kodiatte TA, Michael R, Rymbai ML, Mathew J. Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease (IgG4-RD) patients from South Asia: preliminary data. Clin Rheumatol 2024; 43:1103-1110. [PMID: 38308685 DOI: 10.1007/s10067-023-06861-9] [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: 10/25/2023] [Revised: 12/15/2023] [Accepted: 12/26/2023] [Indexed: 02/05/2024]
Abstract
INTRODUCTION Fibrosis is a typical pathological characteristic in IgG4-RD patients and often irreversible. There exists a lack of suitable markers for detection of earlier onset of fibrosis in various organs in IgG4-RD patients. Hence, this study aims at analysing ambispectively the myofibroblasts and the pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis in South Asian patients. METHOD Archived biopsy samples of definite/probable/possible cases of IgG4-RD, classified according to diagnostic criteria, taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015-January 2020 were chosen for this study. The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by Hematoxylin & Eosin and Masson's Trichrome staining. Also, the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) were assessed by Immunohistochemistry and scored semi-quantitatively (+mild, ++moderate, +++ severe). Serum IL-33 levels were analysed by indirect Elisa (R & D Systems). RESULTS Myofibroblasts were present in 10/12 biopsy samples, in moderate levels in 4 (33%) and very high levels (+++) in 3 (25%) of the patients. IFN-gamma was expressed at low levels in 6 (50%) and absent in 6 (50%). All patients showed IL-33 expression with very high levels in tissue (6, 50%), as well as in serum samples. CONCLUSION The findings of this study reinforce the role of myofibroblasts and profibrotic cytokines like IL-33 in fibrosis of Ig4-RD patients, pointing to their potential as earlier predictive markers of onset and extent of fibrosis.
Collapse
Affiliation(s)
- Josna Joseph
- Department of Clinical Immunology & Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - V Prabhu
- Department of Clinical Immunology & Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India
| | - Meera Thomas
- Department of Pathology, Christian Medical College, Vellore, India
| | - Reka Karuppusami
- Department of Biostatistics, Christian Medical College, Vellore, India
| | | | - Rajiv Michael
- Head and Neck Surgery Unit I, Christian Medical College, Vellore, India
| | - Manbha L Rymbai
- Department of Hepatopancreaticobiliary (HPB) Surgery, Christian Medical College, Vellore, India
| | - John Mathew
- Department of Clinical Immunology & Rheumatology, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
| |
Collapse
|
|
4
|
Choi SJ, Ahn SM, Oh JS, Hong S, Lee CK, Yoo B, Kim YG. Serum IgG4 level during initial treatment as a predictor of relapse in IgG4-related disease. PLoS One 2023; 18:e0282852. [PMID: 36893163 PMCID: PMC9997947 DOI: 10.1371/journal.pone.0282852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 02/23/2023] [Indexed: 03/10/2023] Open
Abstract
INTRODUCTION We aimed to investigate the predictors of relapse in immunoglobulin G4-related disease (IgG4-RD), focusing on the serum IgG4 levels during initial treatment. METHODS We retrospectively recruited 57 patients with IgG4-RD who were treated with immunosuppressants and elevated serum IgG4 levels in a tertiary hospital between January 2011 and December 2020. They were followed up for ≥ 6 months after initiation of immunosuppressive therapy. Clinical and laboratory findings including serum IgG4 levels (reference value: 6-121 mg/dL) were compared between relapsed (n = 13) and non-relapsed (n = 44) groups. Multivariate Cox regression analysis was used to assess the predictors for relapse. We performed a Kaplan-Meier analysis with a log-rank test to evaluate the cumulative relapse rate for two years. RESULTS Median serum IgG4 levels at baseline were 321 mg/dL in the relapsed group and 299 mg/dL in the non-relapsed group. Serum IgG4 levels were normalized after six months in five (38.5%) relapsed and 28 (63.6%) non-relapsed patients. In multivariate Cox regression analysis, the normalization of serum IgG4 levels at six months was associated with a lower risk of relapse, with a hazard ratio of 0.232 (p = 0.019). Central nervous system involvement was associated with the relapse, with a hazard ratio of 21.130 (p = 0.015). The cumulative relapse rate for two years was lower in the normal serum IgG4 group at six months than in the elevated serum IgG4 group at six months (p = 0.027). CONCLUSION Our study suggests that normalization of serum IgG4 levels during immunosuppressive treatment for IgG4-RD independently predicts relapse-free outcomes. Thus, monitoring serum IgG4 levels might be used as a marker of prognosis.
Collapse
Affiliation(s)
- Su Jin Choi
- Department of Rheumatology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Soo Min Ahn
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ji Seon Oh
- Department of Information Medicine, Asan Medical Center, Seoul, South Korea
| | - Seokchan Hong
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Chang-Keun Lee
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Bin Yoo
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yong-Gil Kim
- Department of Rheumatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
- * E-mail:
| |
Collapse
|
|
5
|
Zhang S, Zhang J, Li Y, Jiao J. From Suspicion to Diagnosis: Analysis on the Clinical Characteristics of 37 Cases of IgG4-Related Disease (IgG4-RD) in Northeast China. J Inflamm Res 2022; 15:4487-4497. [PMID: 35966001 PMCID: PMC9365018 DOI: 10.2147/jir.s367211] [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: 03/23/2022] [Accepted: 07/08/2022] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION IgG4-related disease (IgG4-RD) mimics a variety of disorders, the final diagnosis is heavily dependent on the doctor's familiarity with the disease, most patients are expected to get a good prognosis by early diagnosis and timely treatment. METHODS Retrospective analysis was carried out on 147 patients tested for serum IgG4 because of suspected IgG4-RD. These cases were grouped as the IgG4-RD group and non-IgG4-RD group according to the diagnostic criteria proposed by the Japanese IgG4-RD research group and the American College of Rheumatology and the European Union of Rheumatology. Characteristics of these patients were investigated and analyzed. RESULTS The onset age of IgG4-RD was 57.29 ± 14.03 years old, male to female ratio of IgG4-RD was 1.31:1. The most commonly affected organs were the pancreas (48.6%), lymph nodes (40.5%) and biliary tract (35.1%), the proportion of patients with simultaneous involvement of multiple organs is as high as 83.2%. A history of allergy is more common in IgG4-RD patients (32.4% vs 14.5%), the optimal critical value of serum IgG4/IgG ratio for diagnosis of IgG4-RD was 0.09 (sensitivity 94.7%, specificity 91.7%) and the optimal threshold for IgG diagnosis of IgG4-RD was 15.25g/L (sensitivity 73.7%, specificity 77.8%) in this study. CONCLUSION IgG4-RD is often manifested as multiple organ involvement, and is most likely to involve the pancreas, biliary tract and lymph nodes. Most patients were diagnosed in other departments instead of rheumatology. Serum IgG4 level, especially IgG4/IgG ratio has a higher predictive value for IgG4-RD. Early diagnosis is the key point to improve the prognosis.
Collapse
Affiliation(s)
- Shanshan Zhang
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| | - Jun Zhang
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| | - Yifang Li
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| | - Jian Jiao
- Department of Gastroenterology & Hepatology, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China
| |
Collapse
|
|
6
|
Dugic A, Verdejo Gil C, Mellenthin C, Vujasinovic M, Löhr JM, Mühldorfer S. The Clinical Utility of Soluble Serum Biomarkers in Autoimmune Pancreatitis: A Systematic Review. Biomedicines 2022; 10:1511. [PMID: 35884816 PMCID: PMC9312496 DOI: 10.3390/biomedicines10071511] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/17/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, N-glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
Collapse
Affiliation(s)
- Ana Dugic
- Department of Gastroenterology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Medizincampus Oberfranken, 95445 Bayreuth, Germany;
- Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany
| | - Cristina Verdejo Gil
- Department of Gastroenterology, Hospital Universitario Fundación de Alcorcón, 28922 Madrid, Spain;
| | | | - Miroslav Vujasinovic
- Department of Upper Abdominal Diseases, Karolinska University Hospital, 14186 Stockholm, Sweden;
- Department of Medicine, Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden;
| | - J.-Matthias Löhr
- Department of Medicine, Huddinge, Karolinska Institutet, 14186 Stockholm, Sweden;
- Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institutet, 14186 Stockholm, Sweden
| | - Steffen Mühldorfer
- Department of Gastroenterology, Klinikum Bayreuth, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Medizincampus Oberfranken, 95445 Bayreuth, Germany;
- Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schloßplatz 4, 91054 Erlangen, Germany
| |
Collapse
|
|
7
|
Lin ZQ, Li X, Yang Y, Wang Y, Zhang XY, Zhang XX, Guo J. Nonfunctional pancreatic neuroendocrine tumours misdiagnosed as autoimmune pancreatitis: A case report and review of literature. World J Clin Cases 2022; 10:4886-4894. [PMID: 35801029 PMCID: PMC9198893 DOI: 10.12998/wjcc.v10.i15.4886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/29/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonfunctional pancreatic neuroendocrine tumours are difficult to diagnose in the early stage of disease due to a lack of clinical symptoms, but they can rarely manifest as autoimmune pancreatitis. Autoimmune pancreatitis is an uncommon disease that may cause recurrent acute pancreatitis and is therefore often regarded as a special type of chronic pancreatitis.
CASE SUMMARY We report a case of a 42-year-old female who had nonspecific upper abdominal pain for 4 years and radiological abnormalities of the pancreas that mimicked autoimmune pancreatitis. The symptoms and pancreatic imaging did not improve following 1 year of steroid therapy. Finally, pancreatic biopsy was performed through endoscopic ultrasonography-guided fine-needle aspiration biopsy, and nonfunctional pancreatic neuroendocrine tumours were ultimately diagnosed. Pancreatectomy has resolved her symptoms.
CONCLUSION Therefore, the differentiation of nonfunctional pancreatic neuroendocrine tumours from autoimmune pancreatitis is very important, although it is rare. We propose that endoscopic ultrasonography-guided fine-needle aspiration biopsy should be performed if imaging characteristics are equivocal or the diagnosis is in question.
Collapse
Affiliation(s)
- Zi-Qi Lin
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xin Li
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Yang
- Laboratory Medicine, West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yi Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Ying Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Xin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia Guo
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| |
Collapse
|
|
8
|
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.
Collapse
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.
| |
Collapse
|
|
9
|
Duggal L, Singh BG, Patel J, Gupta M, Grover AK, Jain N. IgG4-Related Disease: A Clinical Case Series From a Tertiary Care Center in India. J Clin Rheumatol 2022; 28:e56-e62. [PMID: 33105313 DOI: 10.1097/rhu.0000000000001591] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIM Immunoglobulin G4-related disease (IgG4-RD) is often an unrecognized, rare fibroinflammatory condition that can involve various organ systems. This study aimed to identify the different clinical patterns of this disease in a single center in North India. METHODS Patients were diagnosed on the basis of published diagnostic criteria for IgG4-RD. Patients' presenting complaints; epidemiologic profiles; and laboratory, radiologic, and histologic findings along with the treatment and outcomes were collected and analyzed. RESULTS In total, 70 patients were diagnosed with the disease. The female-to-male ratio was 0.94:1, and it increased with multiorgan involvement. The mean age of patients was 41.4 years, and the majority of the patients (65.7%) were younger than 50 years. Patients were diagnosed as possible (38.57%), probable (32.85%), and definite (28.57%) IgG4-RD. The incidence of the involvement of orbital and periorbital tissues was the highest (52.9%); however, 13% of the patients had multiple organ involvement. Patients with involvement of the retroperitoneal tissues and the lymph nodes were 8.5% and 5.7%, respectively. Increased serum IgG4 levels were found in 74.3% of the patients with single-organ involvement, whereas all patients with multiorgan involvement had increased IgG4 levels. The majority of patients (94.3%) required immunosuppressive medications along with corticosteroids. Azathioprine was the most commonly used (72.8%) immunosuppressive medication. Rituximab was used in 17.1% of the patients, of whom only one had multisystem involvement. CONCLUSIONS This study depicts the most common patterns of organ involvement, along with the epidemiologic, laboratory, histologic, and radiologic data and response to treatment, in IgG4-RD, with a definite ophthalmology referral bias.
Collapse
|
|
10
|
Shah S, Chamlagain R, Baral B, Shrestha S, Adhikari YR, Jha S. Retroperitoneal Fibrosis as a presentation with masked multiorgan involvement of IgG4-related disease-demystifying the diagnosis: A case report from Nepal. Clin Case Rep 2021; 9:e04769. [PMID: 34484785 PMCID: PMC8405527 DOI: 10.1002/ccr3.4769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/12/2021] [Accepted: 08/16/2021] [Indexed: 01/13/2023] Open
Abstract
The timely diagnosis of the disease helps in preventing the progression of RF and unnecessary interventions that may mislead the diagnosis. Biopsy and serum IgG4 both can be non-specific.
Collapse
Affiliation(s)
- Sangam Shah
- Maharajgunj Medical CampusInstitute of MedicineTribhuvan UniversityMaharajgunjNepal
| | | | - Bikash Baral
- Maharajgunj Medical CampusInstitute of MedicineTribhuvan UniversityMaharajgunjNepal
| | - Sanjib Shrestha
- Maharajgunj Medical CampusInstitute of MedicineTribhuvan UniversityMaharajgunjNepal
| | - Yagya Raj Adhikari
- Maharajgunj Medical CampusInstitute of MedicineTribhuvan UniversityMaharajgunjNepal
| | - Saket Jha
- Department of Internal MedicineInstitute of MedicineTribhuvan UniversityMaharajgunjNepal
| |
Collapse
|
|
11
|
Development of efficient on-bead protein elution process coupled to ultra-high performance liquid chromatography-tandem mass spectrometry to determine immunoglobulin G subclass and glycosylation for discovery of bio-signatures in pancreatic disease. J Chromatogr A 2020; 1621:461039. [PMID: 32295703 DOI: 10.1016/j.chroma.2020.461039] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/06/2020] [Accepted: 03/10/2020] [Indexed: 12/30/2022]
Abstract
Type 1 autoimmune pancreatitis (AIP) is a kind of IgG4-related disease in which higher IgG4 and total IgG levels have been found in patient serum. Due to the similar imaging features and laboratory parameters between AIP and pancreatic ductal adenocarcinoma (PDAC), a differential diagnosis is still challenging. Since IgG profiles can be potential bio-signatures for disease, we developed and validated a method which coupled on-bead enzymatic protein elution process to an efficient UHPLC-MS/MS method to determine IgG subclass and glycosylation. A stable-isotope labeled IgG was incorporated as internal standard to achieve accurate quantification. For calibration curves, the correlation coefficients for total IgG and the four IgG subclasses were higher than 0.995. Intraday (n = 5) and interday (n = 3) precisions of the peak area ratios of LLOQ, low, medium, and high QC samples were all less than 6.6% relative standard deviation (% RSD), and the accuracies were between 93.5 and 114.9%. Calibration curves, precision, and accuracy were also evaluated for 26 IgG glycopeptides. The method was applied to samples from healthy controls and patients with AIP and PDAC. Distinct IgG patterns were discovered among the groups, and 7 glycopeptides showed high potential in differentiating AIP and PDAC. The results demonstrated that the developed method is suitable for multi-feature analysis of human IgG, and the discovered IgG profiles can be used as bio-signatures for AIP and PDAC.
Collapse
|
|
12
|
Zhou Y, Shao L, Ruan W, Jin J, Xu H, Ying K, Wu X. Pulmonary vascular involvement of IgG4-related disease: Case series with a PRISMA-compliant systemic review. Medicine (Baltimore) 2019; 98:e14437. [PMID: 30732204 PMCID: PMC6380675 DOI: 10.1097/md.0000000000014437] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 12/29/2018] [Accepted: 01/16/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized, immune-mediated chronic fibrotic inflammation that can involve almost all organs, causing tumefaction and dysfunction. Its presence in pulmonary circulation is underestimated and has not yet been investigated. OBJECTIVES We describe a representative IgG4-RD patient with pulmonary artery stenosis and pulmonary embolism, leading to reversible pulmonary hypertension. Literature review of IgG4-RD with pulmonary circulation involvement was conducted. DATA SOURCES References for this review were identified through searches via PubMed, EBSCO, and Web of Science for published articles before November 2016. RESULTS There were 15 published cases of IgG4-RD with pulmonary vascular involvement, 3 with pulmonary arteritis, 2 with pulmonary artery aneurysm, 3 with pulmonary artery stenosis, 1 with obliterative phlebitis, and 1 with pulmonary embolism. Possible immunity and inflammation mechanisms were summarized. CONCLUSIONS IgG4-RD with pulmonary vascular involvement is rare. Echocardiogram and contrast-enhanced chest CT are helpful to screen the disease. Clinical manifestations were found from asymptomatic to dyspnea or even syncope. And nearly all cases had more than 1 organ affected, with significantly increased serum IgG4 levels. PET/CT aided in identifying affected organs and determining candidate biopsy sites. More awareness is urged to evaluate the pulmonary vascular manifestations of this disease.
Collapse
Affiliation(s)
- Yong Zhou
- Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
- Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA
| | - Lingyan Shao
- Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Wenjing Ruan
- Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Joy Jin
- Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA
| | - Hangdi Xu
- Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Kejing Ying
- Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xiaohong Wu
- Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| |
Collapse
|
|
13
|
Arai H, Toda N, Kamimatsuse R, Nishioka K, Endo S, Akiyama S, Maruyama S, Matsubara T, Yokoi H, Yanagita M. A Refractory Case of Secondary Membranous Nephropathy Concurrent with IgG4-related Tubulointerstitial Nephritis. Intern Med 2018; 57:2873-2877. [PMID: 29709946 PMCID: PMC6207830 DOI: 10.2169/internalmedicine.0836-18] [Citation(s) in RCA: 4] [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: 12/24/2022] Open
Abstract
A 58-year-old man with type 1 autoimmune pancreatitis was referred to nephrologists for severe proteinuria. Laboratory data revealed a high serum IgG4 level, hypoalbuminemia, and massive proteinuria, which were compatible with nephrotic syndrome. The renal pathological findings confirmed the diagnosis of secondary membranous nephropathy concurrent with IgG4-related tubulointerstitial nephritis. Despite the improvement of interstitial markers, the proteinuria was refractory to prednisolone, requiring cyclosporine to achieve complete remission. Membranous nephropathy is a rare manifestation of IgG4-related kidney disease. This case shows that the therapeutic response to prednisolone significantly differs between glomerular lesions and interstitial lesions of IgG4-related kidney disease.
Collapse
Affiliation(s)
- Hiroyuki Arai
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
| | - Naohiro Toda
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
| | - Ryo Kamimatsuse
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
- Department of Nephrology, Kyoto City Hospital, Japan
| | - Keisuke Nishioka
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
- Department of Nephrology, Osaka Red Cross Hospital, Japan
| | - Shuichiro Endo
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
| | - Shinichi Akiyama
- Division of Nephrology, Department of Internal Medicine, Nagoya University, Graduate School of Medicine, Japan
| | - Shoichi Maruyama
- Division of Nephrology, Department of Internal Medicine, Nagoya University, Graduate School of Medicine, Japan
| | - Takeshi Matsubara
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
| | - Hideki Yokoi
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
| | - Motoko Yanagita
- Department of Nephrology, Kyoto University, Graduate School of Medicine, Japan
| |
Collapse
|
|
14
|
Slim D, Gunawardena H, Calvert JM, Daly RS, Plummeridge MJ, Medford AR. IgG4-related pulmonary disease: the protean impersonator? J R Coll Physicians Edinb 2018; 48:130-133. [PMID: 29992203 DOI: 10.4997/jrcpe.2018.207] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
IgG4-related disease is an immune-mediated fibro-inflammatory disease, characterised by distinct pathological features. An increasing number of clinical phenotypes are described, from single-organ disease to a multisystem disorder, which can present to a variety of different specialities. Recognition is key; its protean manifestations can mimic other inflammatory diseases, infection and malignancy. Here, we present three cases to highlight the importance of being familiar with this condition in its various forms.
Collapse
Affiliation(s)
- D Slim
- North Bristol Lung Centre, Southmead Hospital, Bristol, UK
| | - H Gunawardena
- North Bristol Lung Centre, Southmead Hospital, Bristol, UK
| | - J M Calvert
- North Bristol Lung Centre, Southmead Hospital, Bristol, UK
| | - R S Daly
- North Bristol Lung Centre, Southmead Hospital, Bristol, UK
| | | | - A R Medford
- North Bristol Lung Centre & University of Bristol, Brunel Building, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK,
| |
Collapse
|
|
15
|
Hong JW, Kang S, Song MK, Ahn CJ, Sa HS. Clinicoserological factors associated with response to steroid treatment and recurrence in patients with IgG4-related ophthalmic disease. Br J Ophthalmol 2018; 102:1591-1595. [DOI: 10.1136/bjophthalmol-2017-311519] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Revised: 01/19/2018] [Accepted: 01/23/2018] [Indexed: 12/31/2022]
Abstract
PurposeTo investigate the factors associated with response to steroid treatment and recurrence in patients with IgG4-related ophthalmic disease (ROD).MethodsTwenty-eight patients with biopsy-proven IgG4-ROD treated between March 2010 and January 2017 were included in this retrospective study. Clinical features, serum IgG4 levels, systemic involvement, treatments and treatment outcome, factors associated with response to treatment and recurrence were assessed.ResultThirteen men and 15 women (mean age 50.8 years) were evaluated over mean follow-up period of 27.3 months. Elevated serum IgG4 levels (>1.35 g/L) and systemic disease were noted in 9 (32%) and 18 patients (64%), respectively. The lacrimal gland was involved in all patients, and 22 patients (78.6%) had bilateral involvement. Most patients (82%) responded well to systemic steroids, but 12 (43%) relapsed after the initial steroid treatment, requiring additional therapies to achieve remission. Complete response to initial steroid treatment was associated with elevated serum IgG4 levels before treatment (P=0.001) and bilateral orbital involvement (P=0.050). Recurrence was associated with elevated serum IgG4 levels before treatment (P=0.007), lower dose (P=0.057) and shorter duration of initial steroids (P=0.042). Patients with recurrence eventually required significantly more steroids than those without recurrence (P=0.011).ConclusionsPatients with IgG4-ROD responded well to systemic steroid treatment, but recurrence was common, particularly among those with elevated serum IgG4 levels and shorter duration of initial steroid treatment. Low-dose maintenance treatment with systemic steroids should be considered to avoid recurrence in patients with elevated serum IgG4 levels.
Collapse
|
|
16
|
Thewjitcharoen Y, Krittiyawong S, Porramatikul S, Wanothayaroj E, Lekpittaya N, Jeamjiraprasert J, Nakasatien S, Himathongkam T. A study of serum IgG4 levels in the clinical metamorphosis of autoimmune thyroid disease. J Clin Transl Endocrinol 2017; 8:35-40. [PMID: 29067257 PMCID: PMC5651342 DOI: 10.1016/j.jcte.2017.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 04/26/2017] [Accepted: 05/05/2017] [Indexed: 12/24/2022] Open
Abstract
Background Measurement of serum IgG4 had been suggested to distinguish the unique subtypes of autoimmune thyroid disease (AITD) which demonstrated patterns of fluctuating between hyperthyroidism and hypothyroidism. However, the clinical utility of serum IgG4 measurement is inconclusive due to few studies having addressed these unusual patients compared with the specificity of serum IgG4 in healthy patients. Aim To investigate whether elevated serum IgG4 levels could be used as a marker to identify fluctuating AITD patients. Materials and Methods 20 AITD patients who evolved from hyperthyroid Graves’ disease to spontaneous hypothyroidism or vice versa were compared with 40 healthy subjects, 40 patients with hyperthyroid Graves’ disease (GD) and 40 patients with subclinical or overt hypothyroid Hashimoto’s thyroiditis (HT). Serum levels of total IgG and IgG4 were measured and the proportion of elevated serum IgG4 levels (defined by serum IgG4 levels ≥ 135 mg/dL) was compared with control patients. Results A series of 20 Thai patients with clinical evolution of AITD was analyzed with a median follow-up at 92 months (range 3–380 months). Elevated serum IgG4 levels were not found in fluctuating AITD patients but were found in 5% of the control GD patients, 2.5% of the control HT, and 2.5% of healthy subjects which were not statistically significant between each group. Conclusion Our results contrasted with those of previous studies from Japan which reported elevated serum IgG4 as a marker to identify subset of AITD patients. At present, the clinical utility of serum IgG4 measurements in AITD is inconclusive and requires further investigation.
Collapse
|
|
17
|
Baptista B, Casian A, Gunawardena H, D'Cruz D, Rice CM. Neurological Manifestations of IgG4-Related Disease. Curr Treat Options Neurol 2017; 19:14. [PMID: 28374231 PMCID: PMC5378735 DOI: 10.1007/s11940-017-0450-9] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OPINION STATEMENT IgG4-related disease (IgG4-RD) is a multisystem inflammatory disorder. Early recognition of IgG4-RD is important to avoid permanent organ dysfunction and disability. Neurological involvement by IgG4-RD is relatively uncommon, but well recognised-hypertrophic pachymeningitis and hypophysitis are the most frequent manifestations. Although the nervous system may be involved in isolation, this more frequently occurs in conjunction with involvement of other systems. Elevated circulating levels of IgG4 are suggestive of the condition, but these are not pathognomonic and exclusion of other inflammatory disorders including vasculitis is required. Wherever possible, a tissue diagnosis should be established. The characteristic histopathological changes include a lymphoplasmacytoid infiltrate, storiform fibrosis and obliterative phlebitis. IgG4-RD typically responds well to treatment with glucocorticoids, although relapse is relatively common and treatment with a steroid-sparing agent or rituximab may be required. Improved understanding of the pathogenesis of IgG4-RD is likely to lead to the development of more specific disease treatments in the future.
Collapse
Affiliation(s)
| | - Alina Casian
- Louise Coote Unit, Guy's and St Thomas NHS Foundation Trust, London, UK
| | - Harsha Gunawardena
- Department of Rheumatology, Brunel Building, Southmead Hospital, Bristol, UK
- Musculoskeletal Research Unit, Learning and Research Building, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK
| | - David D'Cruz
- Louise Coote Unit, Guy's and St Thomas NHS Foundation Trust, London, UK
- Division of Immunology, Infection and Inflammatory Diseases, King's College London, New Hunt's House, Guy's Campus, Great Maze Pond, London, SE1 1UL, UK
| | - Claire M Rice
- School of Clinical Sciences, Level 1, Learning and Research Building, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK.
- Department of Neurology, Brunel Building, Southmead Hospital, Bristol, UK.
| |
Collapse
|
|
18
|
Cao L, Chen YB, Zhao DH, Shi WF, Meng S, Xie LX. Pulmonary function tests findings and their diagnostic value in patients with IgG4-related disease. J Thorac Dis 2017; 9:547-554. [PMID: 28449462 DOI: 10.21037/jtd.2017.02.73] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect most organs. To date, there have been no detailed assessments of pulmonary function in patients with IgG4-RD. In this study, we investigated pulmonary function in IgG4-RD patients and evaluated the value of pulmonary function tests (PFTs) in diagnosing IgG4-related respiratory disease (IgG4-RRD). METHODS This was a retrospective study of 17 patients with IgG4-RD. The patients were divided into two groups: IgG4-RRD group and IgG4-related disease extrapulmonary involvement (IgG4-RDEI) group. The PFT results were compared between the two groups. RESULTS All patients in the IgG4-RRD group had pulmonary dysfunction. Five of 8 (62.5%) patients in the IgG4-RDEI group had pulmonary dysfunction, despite having normal thoracic computed tomography scans and no respiratory symptoms. Patients in both groups showed restrictive ventilatory dysfunction and abnormal diffusing capacity, and two patients in the IgG4-RRD group had obstructive ventilatory dysfunction. The incidence of diffusing capacity of the lung for carbon monoxide per liter of alveolar volume (DLCO/VA) decrease were significantly higher in the IgG4-RRD group than in the IgG4-RDEI group (P=0.029). DLCO/VA were significantly higher in the IgG4-RDEI than in the IgG4-RRD group (P=0.044), but otherwise, there were no significant differences. We report the first finding of a negative correlation between pulmonary diffusing capacity and total serum concentrations of IgG and IgG subclasses (IgG4, IgG3 and IgG2). CONCLUSIONS DLCO/VA plays an important role for detecting lung involvement in IgG4-RD patients. The patient with high serum IgG may be more prone to respiratory involvement.
Collapse
Affiliation(s)
- Lu Cao
- Department of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Yi-Bing Chen
- Department of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Da-Hui Zhao
- Department of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Wen-Fang Shi
- Department of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Song Meng
- Department of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| | - Li-Xin Xie
- Department of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing 100853, China
| |
Collapse
|
|
19
|
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.
Collapse
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.
| |
Collapse
|
|
20
|
Horie K, Tada N, Yamaguchi K, Inazawa K, Endo M, Inoue N. Immunoglobulin G4-related constrictive pericarditis identified by cytological examination of pericardial effusion: a case report. J Med Case Rep 2016; 10:359. [PMID: 27998302 PMCID: PMC5175317 DOI: 10.1186/s13256-016-1159-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 11/24/2016] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Immunoglobulin G4-related disease is increasingly recognized as a systemic autoimmune disorder characterized by immunoglobulin G4-positive lymphocyte infiltration. Organ biopsy and histopathology are the most important diagnostic methods; however, the significance of a cytological examination in immunoglobulin G4-related disease cases is still unclear. CASE PRESENTATION A 73-year-old Asian man who was a former tobacco smoker presented with progressive exertional dyspnea, systemic edema, and pericardial effusion. A cytological examination of his pericardial effusion detected three or four plasma cells per high-power field by Giemsa staining. Moreover, immunoglobulin G4-positive plasma cells were detected by immunostaining. Cardiac catheterization after pericardiocentesis revealed that both ventricular pressure traces showed an early diastolic dip and plateau. Positron-emission tomography with 18F-fluorodeoxyglucose imaging revealed inflammatory foci in his pericardium. A surgical pericardiectomy was performed and the resultant specimen showed significant immunoglobulin G4-positive plasma cell infiltration and marked fibrous thickening of his pericardium; therefore, a diagnosis of constrictive pericarditis due to immunoglobulin G4-related disease was made. Oral administration of 0.6-mg/kg/day prednisolone resolved his heart failure and he was discharged on foot 1 week later. CONCLUSION Our experience with this case indicates that cytological examination of pericardial effusion was useful in the diagnosis of immunoglobulin G4-related disease.
Collapse
Affiliation(s)
- Kazunori Horie
- Department of Cardiovascular Medicine, Sendai Kousei Hospital, Sendai, Miyagi, Japan. .,Division of Cardiovascular Medicine, Sendai Kousei Hospital, 4-15 Hirose-cho, Aoba-ku, Sendai, Miyagi, 980-0873, Japan.
| | - Norio Tada
- Department of Cardiovascular Medicine, Sendai Kousei Hospital, Sendai, Miyagi, Japan
| | | | - Keitarou Inazawa
- Department of Respiratory Surgery, Sendai Kousei Hospital, Sendai, Miyagi, Japan
| | - Mareyuki Endo
- Department of Pathology, Sendai Kousei Hospital, Sendai, Miyagi, Japan
| | - Naoto Inoue
- Department of Cardiovascular Medicine, Sendai Kousei Hospital, Sendai, Miyagi, Japan
| |
Collapse
|
|
21
|
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.
Collapse
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
| |
Collapse
|
|
22
|
Ewing DE, Hammer RD. IgG4-related disease simulating Hodgkin lymphoma in a child. HUMAN PATHOLOGY: CASE REPORTS 2016. [DOI: 10.1016/j.ehpc.2015.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
|
|
23
|
Woo YJ, Kim JW, Yoon JS. Clinical implications of serum IgG 4 levels in patients with IgG 4-related ophthalmic disease. Br J Ophthalmol 2016; 101:256-260. [PMID: 27215743 DOI: 10.1136/bjophthalmol-2016-308592] [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] [Received: 02/22/2016] [Revised: 04/04/2016] [Accepted: 05/01/2016] [Indexed: 12/24/2022]
Abstract
AIMS The present study aimed to investigate the clinical implications of serum IgG4 levels in patients with IgG4-related ophthalmic disease (ROD). METHODS The medical records of 31 patients who met the diagnostic criteria for IgG4-ROD were retrospectively reviewed. Twenty-five patients whose serum IgG4 levels could be identified were included. Clinical manifestations and serum IgG4 levels before and after corticosteroid treatment were obtained. Factors associated with relapse were evaluated by comparing the features of patients with disease relapse with those of patients without relapse. RESULTS Twenty-four patients were 'definite' and one was 'probable' for IgG4-ROD according to the diagnostic criteria. Serum IgG4 levels were higher in patients with systemic involvement (p=0.046). All patients improved clinically after corticosteroid treatment. Serum IgG4 levels decreased after steroid treatment (p=0.005) and normalised in nine patients. In cases of relapse, serum IgG4 levels increased along with the aggravation of symptoms (p=0.047). Serum IgG4 levels that were still elevated (≥135 mg/dL) after steroid treatment (p=0.034) and cessation of steroid treatment during disease remission (p=0.043) were predictive factors for IgG4-ROD relapse. CONCLUSIONS Serum IgG4 level can be considered an adjunctive marker for treatment response in IgG4-ROD. Patients with serum IgG4 levels that remain elevated after steroid treatment should be carefully observed for relapse. A continuing maintenance dose of oral steroid is recommended to prevent relapse, even when clinical remission is achieved.
Collapse
Affiliation(s)
- Young Jun Woo
- Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Ji Won Kim
- Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea
| | - Jin Sook Yoon
- Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
24
|
Sun X, Liu H, Feng R, Peng M, Hou X, Wang P, Wang H, Xu W, Shi J. Biopsy-proven IgG4-related lung disease. BMC Pulm Med 2016; 16:20. [PMID: 26809651 PMCID: PMC4727342 DOI: 10.1186/s12890-016-0181-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 01/13/2016] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve single or multiple organs. Biopsy-proven lung involvement of this disease is occasionally reported, but not well understood. METHODS Patients with the diagnosis of biopsy-proven IgG4-related lung disease (IgG4-RLD) from Peking Union Medical College Hospital between January 2011 and July 2015 were retrospectively analyzed. Age, sex, clinical symptoms, laboratory findings, pulmonary function test results, chest CT tests, positron emission tomography (PET) examinations, treatments and prognoses were retrieved from medical records and analyzed. RESULTS Seventeen patients were included in this study (mean age: 44.8 ± 15.0 years). Ten patients were diagnosed via surgery, and 7 patients were diagnosed via percutaneous transthoracic core-needle lung biopsy. Extrapulmonary involvement was observed in only one patient. The clinical symptoms included cough, fever, dyspnea, chest pain and hemoptysis. The serum IgG4 concentration was elevated in 7/13 patients (mean: 1955 ± 1968 mg/L). The chest CT findings included mainly nodules and masses with spiculated borders, alveolar consolidations with air bronchograms, and ground glass opacities with or without reticular opacities. PET scans indicated increased standardized uptake values, and 7/8 patients were correctly diagnosed with benign inflammation. Corticosteroids and immunosuppressants were administered to 14/17 patients and effectively alleviated the disease. CONCLUSIONS In biopsy-proven IgG4-RLD, a normal serum IgG4 concentration is commonly seen, while extrapulmonary involvement is infrequent. Alveolar consolidation with air bronchograms is an important imaging finding of IgG4-RLD, which has not been emphasized before.
Collapse
Affiliation(s)
- Xuefeng Sun
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China.
| | - Hongrui Liu
- Department of Pathology, Peking Union Medical College Hospital, Beijing, China
| | - Ruie Feng
- Department of Pathology, Peking Union Medical College Hospital, Beijing, China
| | - Min Peng
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China
| | - Xiaomeng Hou
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China
| | - Ping Wang
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China
| | - Hanping Wang
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China
| | - Wenbing Xu
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China
| | - Juhong Shi
- Department of Respiratory Medicine, Peking Union Medical College Hospital, 100730, Beijing, China.
| |
Collapse
|
|
25
|
Type 2 autoimmune pancreatitis: case report of a 9-year-old female and a review of the literature. Clin J Gastroenterol 2015; 8:421-5. [PMID: 26590828 DOI: 10.1007/s12328-015-0615-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 10/27/2015] [Indexed: 12/14/2022]
Abstract
We report a case of autoimmune pancreatitis in a 9-year-old female who presented with persistent epigastric pain for 3 weeks. Magnetic resonance cholangiopancreatography (MRCP) showed both intrahepatic and extrahepatic biliary ductal dilatation. The common bile duct, along with the pancreatic duct, was noted to be dilated. Labs showed normal IgG and IgG4 levels and negative for autoimmune antibodies. Endoscopic ultrasound revealed the pancreatic head to be enlarged and surrounded by hypoechoic and lobulated lymph nodes. Biopsy of the pancreatic head showed chronic mildly active inflammation with fibrosis, acinar atrophy, and lymphocytic infiltrate. A diagnosis of autoimmune pancreatitis (AIP) was made, and she was treated with prednisone. The patient's symptoms improved quickly, and follow-up MRCP showed resolution of inflammatory changes and intrahepatic and pancreatic ductal dilatation.
Collapse
|
|
26
|
Cortés-Romera M, Sabaté-Llobera A, Gámez-Cenzano C, Torras-Ambròs J. Utilidad de la PET/TC en la enfermedad por IgG4. Med Clin (Barc) 2015; 145:321-2. [DOI: 10.1016/j.medcli.2014.11.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Revised: 11/11/2014] [Accepted: 11/20/2014] [Indexed: 10/24/2022]
|
|
27
|
Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, Chari ST, Della-Torre E, Frulloni L, Goto H, Hart PA, Kamisawa T, Kawa S, Kawano M, Kim MH, Kodama Y, Kubota K, Lerch MM, Löhr M, Masaki Y, Matsui S, Mimori T, Nakamura S, Nakazawa T, Ohara H, Okazaki K, Ryu JH, Saeki T, Schleinitz N, Shimatsu A, Shimosegawa T, Takahashi H, Takahira M, Tanaka A, Topazian M, Umehara H, Webster GJ, Witzig TE, Yamamoto M, Zhang W, Chiba T, Stone JH. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol 2015; 67:1688-99. [PMID: 25809420 DOI: 10.1002/art.39132] [Citation(s) in RCA: 665] [Impact Index Per Article: 66.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 03/19/2015] [Indexed: 02/06/2023]
Affiliation(s)
- A Khosroshahi
- Emory University School of Medicine, Atlanta, Georgia
| | | | - J L Crowe
- University of Tennessee College of Medicine, Chattanooga
| | - T Akamizu
- Wakayama Medical University, Tokyo, Japan
| | - A Azumi
- Kobe Kaisei Hospital, Kobe, Japan
| | - M N Carruthers
- University of British Columbia, Vancouver, British Columbia, Canada
| | | | | | | | - H Goto
- Tokyo Medical University, Tokyo, Japan
| | - P A Hart
- The Ohio State University Medical College and The Ohio State University Wexner Medical Center, Columbus
| | - T Kamisawa
- Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - S Kawa
- Shinshu University, Matsumoto, Japan
| | - M Kawano
- Kanazawa University Graduate School of Medical Sciences and Kanazawa University Hospital, Kanazawa, Japan
| | - M H Kim
- University of Ulsan College of Medicine and Asan Medical Center, Ulsan, Republic of Korea
| | - Y Kodama
- Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - K Kubota
- Yokohama City University and Yokohama City University Hospital, Yokohama, Japan
| | - M M Lerch
- University of Greifswald Medical School, Greifswald, Germany
| | - M Löhr
- Karolinska Institutet, Stockholm, Sweden
| | - Y Masaki
- Kanazawa Medical University, Kanazawa, Japan
| | - S Matsui
- University of Toyama, Toyama, Japan
| | - T Mimori
- Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - S Nakamura
- Kyushu University and Kyushu University Dental Hospital, Fukuoka, Japan
| | - T Nakazawa
- Nagoya City University Graduate School of Medicine, Nagoya, Japan
| | - H Ohara
- Nagoya City University Graduate School of Medicine, Nagoya, Japan
| | - K Okazaki
- Kansai Medical University, Hirakata, Japan
| | - J H Ryu
- Mayo Clinic, Rochester, Minnesota
| | - T Saeki
- Nagaoka Red Cross Hospital, Nagaoka, Japan
| | - N Schleinitz
- Aix-Marseille Université, Assistance Publique Hôpitaux de Marseille, Marseille, France
| | - A Shimatsu
- National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | | | - H Takahashi
- Sapporo Medical University School of Medicine, Sapporo, Japan
| | - M Takahira
- Kanazawa University Graduate School of Medical Sciences and Kanazawa University Hospital, Kanazawa, Japan
| | - A Tanaka
- Teikyo University School of Medicine, Tokyo, Japan
| | | | - H Umehara
- Kanazawa Medical University, Kanazawa, Japan
| | - G J Webster
- University College London and University College London Hospitals, London, UK
| | | | - M Yamamoto
- Sapporo Medical University School of Medicine, Sapporo, Japan
| | - W Zhang
- Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China
| | - T Chiba
- Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - J H Stone
- Massachusetts General Hospital, Boston
| | -
- Japanese Ministry of Health, Labor, and Welfare, Amgen, and Genetech
| |
Collapse
|
|
28
|
Rodriguez EA, Williams FK. A mass in the junction of the body and tail of the pancreas with negative IgG4 serology: IgG4-related disease with negative serology. AMERICAN JOURNAL OF CASE REPORTS 2015; 16:305-9. [PMID: 26001036 PMCID: PMC4447198 DOI: 10.12659/ajcr.893300] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Patient:Female, 55 Final Diagnosis: Autoimmune pancreatitis Symptoms: Abdominal pain • weight loss Medication: Prednisone Clinical Procedure: Admitted to the hospital Specialty: Gastroenterology and Hepatology
Collapse
Affiliation(s)
- Eduardo A Rodriguez
- Department of Internal Medicine, University of Miami Palm Beach Regional Campus, Atlantis, FL, USA
| | - Frederick K Williams
- Department of Internal Medicine, University of Miami Palm Beach Regional Campus, Atlantis, FL, USA
| |
Collapse
|
|
29
|
Lazos-Ochoa M. Some histopathological aspects of the disease related to IgG-4. REVISTA MÉDICA DEL HOSPITAL GENERAL DE MÉXICO 2015. [DOI: 10.1016/j.hgmx.2015.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
|
|
30
|
Seo J, Song IJ, Lee S, Jeong HJ, Kim HM, Koh BS, Park SH. A Case of Constrictive Pericarditis due to Immunoglobulin G4-Related Disease. Korean Circ J 2015; 45:161-4. [PMID: 25810739 PMCID: PMC4372983 DOI: 10.4070/kcj.2015.45.2.161] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Revised: 04/25/2014] [Accepted: 07/13/2014] [Indexed: 12/24/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) can involve any organ. The majority of reported cases involve IgG4-RD of the biliary tract or pancreas, while only two cases of pericarditis have been reported. A 58-year-old man visited the outpatient clinic of our institution with a seven-day history of progressive dyspnea. Based on his transthoracic echocardiogram and transesophageal echocardiogram, he was diagnosed with constrictive pericarditis. The histopathology of his pericardiectomy revealed the cause of constrictive pericarditis to be IgG4-RD. Prednisolone (40 mg) was initiated after the pericardiectomy. As the patient's symptoms resolved, he was discharged and followed-up on an outpatient basis. This is the first case report of constrictive pericarditis caused by IgG4-RD in Korea.
Collapse
Affiliation(s)
- Jiwon Seo
- Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea
| | - In Ji Song
- Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea
| | - Sak Lee
- Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyeon Joo Jeong
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Hye Min Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
| | - Beom Seok Koh
- Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Ha Park
- Division of Cardiology, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
|
31
|
Lin YH, Yen SH, Tsai CC, Kao SC, Lee FL. Adjunctive Orbital Radiotherapy for Ocular Adnexal IgG4-related Disease: Preliminary Experience in Patients Refractory or Intolerant to Corticosteroid Therapy. Ocul Immunol Inflamm 2014; 23:162-7. [PMID: 25010381 DOI: 10.3109/09273948.2014.928735] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To present the clinical outcomes of combined orbital radiotherapy and systemic corticosteroid for patients with refractory ocular adnexal IgG4-related disease. METHODS We retrospectively reviewed 3 patients with histopathologically confirmed ocular adnexal IgG4-related disease who had been refractory or intolerant to corticosteroid therapy and treated with adjunctive orbital radiotherapy (2000 cGy; 10 fractions). Clinical improvement was assessed by monitoring the patient's ability to taper corticosteroid to discontinuation and by follow-up radiologic examination. RESULTS All 3 patients had a favorable response to adjunctive radiotherapy with improvement of the clinical symptoms and radiologic abnormalities. Systemic corticosteroid was tapered and discontinued in all patients successfully. There were no adverse effects of treatment or recurrence after a mean follow-up of 19 months. CONCLUSION Adjunctive radiotherapy can help to achieve stable disease and cessation of systemic corticosteroid in patients with refractory ocular adnexal IgG4-related disease.
Collapse
Affiliation(s)
- Yu-Hao Lin
- Department of Ophthalmology, Taipei Veterans General Hospital and National Yang-Ming University , Taipei , Taiwan and
| | | | | | | | | |
Collapse
|
|
32
|
Okazaki K, Kawa S, Kamisawa T, Ito T, Inui K, Irie H, Nishino T, Notohara K, Nishimori I, Tanaka S, Nishiyama T, Suda K, Shiratori K, Tanaka M, Shimosegawa T. Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 I. Concept and diagnosis of autoimmune pancreatitis. J Gastroenterol 2014; 49:567-88. [PMID: 24639057 DOI: 10.1007/s00535-014-0942-2] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Accepted: 02/02/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND In response to the proposal of the international consensus diagnostic criteria (ICDC) for autoimmune pancreatitis (AIP) and the Japanese diagnostic criteria in 2011, the 2009 Japanese consensus guidelines for managing AIP required revision. METHODS Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Fifteen specialists for AIP extracted the specific clinical statements from 1,843 articles published between 1963 and 2012 (obtained from Pub Med and a secondary database, and developed the CQs and statements. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid. RESULTS The professional committee created 13 CQs and statements for the current concept and diagnosis of AIP, 6 for extra-pancreatic lesions, 6 for differential diagnosis, and 11 for treatment. CONCLUSION After evaluation by the moderators, amendments to the Japanese consensus guidelines for AIP have been proposed for 2013.
Collapse
Affiliation(s)
- Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan,
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Khosroshahi A, Cheryk LA, Carruthers MN, Edwards JA, Bloch DB, Stone JH. Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4-Related Disease. Arthritis Rheumatol 2013; 66:213-7. [DOI: 10.1002/art.38193] [Citation(s) in RCA: 90] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2013] [Accepted: 09/05/2013] [Indexed: 12/24/2022]
Affiliation(s)
- Arezou Khosroshahi
- Emory University School of Medicine, Atlanta, Georgia, and Massachusetts General Hospital and Harvard Medical School; Boston
| | | | | | | | - Donald B. Bloch
- Massachusetts General Hospital and Harvard Medical School; Boston
| | - John H. Stone
- Massachusetts General Hospital and Harvard Medical School; Boston
| |
Collapse
|
|
34
|
Abstract
IgG4-related orbital disease (IgG4-ROD) is a recently described condition that may account for a significant proportion of idiopathic lymphoplasmacytic or sclerotic orbital lesions. This study is the first meta-analysis of published cases and reveals several differences between IgG4-related disease affecting the orbit and that affecting the pancreas. IgG4-ROD affects a slightly younger group of patients, affects men and women approximately equally, is commonly associated with salivary gland lesions, is associated with a relatively higher serum IgG4 and may confer an increased risk of non-Hodgkin Lymphoma. Its pathogenesis may involve an immune response to antigen exposure in the upper aerodigestive tract.
Collapse
Affiliation(s)
- Nicholas Andrew
- South Australian Institute of Ophthalmology and Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South AustraliaInstitute of Medical and Veterinary Science, Department of Surgical Pathology, Adelaide, South Australia
| | | | | |
Collapse
|
|
35
|
Ochoa ML, Gabiño López B, Cabello RR, Feregrino RR. IgG4-related multiorgan disease: report of the first autopsy case. BMJ Case Rep 2013; 2013:bcr2013009636. [PMID: 23645656 PMCID: PMC3669849 DOI: 10.1136/bcr-2013-009636] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease (IgG4RD) is a chronic recurring fibro-inflammatory pathology that is considered to be of autoimmune origin. Histopathology is considered to be the gold standard method for diagnosis. IgG4RD affects multiple organs. IgG4RD was first identified in the pancreas and was called autoimmune pancreatitis (AIP). During the following years, the disease spectrum was expanded and it was realised that the extrapancreatic lesions can precede, coexist or appear after the diagnosis of AIP. At present, several illnesses such as Mikulicz disease, Küttner tumour, multifocal fibrosclerosis, etc, are considered to be part of the IgG4RD spectrum. The symptoms of the disease tend to appear over months and years and diagnosis is achieved on average 13.5 months (4-60 months) after the onset. The purpose of this report was to provide information about a case that was sadly fatal but that permitted a complete histopathological study of the damaged tissues.
Collapse
Affiliation(s)
- Minerva Lazos Ochoa
- Department of Pathology, Hospital General de México, Mexico City, Mexico DF, Mexico
| | | | - Raúl Romero Cabello
- Department of Infectology, Hospital General de México, Mexico City, Mexico DF, Mexico
- Faculty of Medicine, UNAM, Mexico City, Mexico
| | - Raúl Romero Feregrino
- Department of Infectology, Instituto para el Desarrollo integral de la Salud (IDISA), Mexico City, Mexico DF, Mexico
| |
Collapse
|
|
36
|
|
|
37
|
Al-Zubidi N, Oku H, Verner-Cole E, Chévez-Barrios P, Tonari M, Kurimoto T, Tsuji M, Ikeda T, Lee AG. Immunoglobulin G4-positive Sclerosing Idiopathic Orbital Inflammation: New Neuro-ophthalmological Presentations. Neuroophthalmology 2013; 37:24-30. [PMID: 28163752 DOI: 10.3109/01658107.2012.752853] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Accepted: 08/17/2012] [Indexed: 12/22/2022] Open
Abstract
We report two rare cases of biopsy proven Immunoglobulin G4-related sclerosing orbital inflammation (IgG4SOI). The first case had intracranial involvement which, to our knowledge, is the first IgG4SOI case with serum cerebrospinal fluid abnormalities and the second case had an unusual presentation of a compressive optic neuropathy and systemic lymphadenopathy.
Collapse
Affiliation(s)
- Nagham Al-Zubidi
- Department of Ophthalmology, The Methodist Hospital Houston, TX USA
| | - Hidehiro Oku
- Department of Ophthalmology, Osaka Medical College Osaka Japan
| | | | | | - Patricia Chévez-Barrios
- The Department of Pathology and Laboratory Medicine, The Methodist Hospital; Department of Pathology and Laboratory Medicine and Ophthalmology, Weill Cornell Medical College, Retinoblastoma Center of Houston; Department of Ophthalmology, Baylor College of Medicine; Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer CenterHouston, TXUSA
| | - Masahiro Tonari
- Department of Ophthalmology, Osaka Medical College Osaka Japan
| | - Takuji Kurimoto
- Department of Ophthalmology, Osaka Medical College Osaka Japan
| | - Motomu Tsuji
- Department of Pathology, Osaka Medical College Osaka Japan
| | - Tsunehiko Ikeda
- Department of Ophthalmology, Osaka Medical College Osaka Japan
| | - Andrew G Lee
- Department of Ophthalmology, The Methodist HospitalHouston, TXUSA; Department of Ophthalmology, Baylor College of Medicine; Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medical CollegeHoustonTX; Department of Ophthalmology, The University of Iowa Hospitals and ClinicsIowa City, IA; Department of Ophthalmology, The University of Texas Medical BranchGalveston, TXUSA
| |
Collapse
|
|
38
|
Stone JH, Khosroshahi A, Deshpande V, Chan JKC, Heathcote JG, Aalberse R, Azumi A, Bloch DB, Brugge WR, Carruthers MN, Cheuk W, Cornell L, Castillo CFD, Ferry JA, Forcione D, Klöppel G, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, Masaki Y, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani D, Sato Y, Smyrk T, Stone JR, Takahira M, Umehara H, Webster G, Yamamoto M, Yi E, Yoshino T, Zamboni G, Zen Y, Chari S. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. ACTA ACUST UNITED AC 2013; 64:3061-7. [PMID: 22736240 DOI: 10.1002/art.34593] [Citation(s) in RCA: 480] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- John H Stone
- Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Abstract
Concepts about IgG4-related disease (IgG4-RD) are now emerging swiftly. The condition has been identified in virtually every organ system, and its features are often excellent mimickers of malignancies, infections, and other immune-mediated disorders. Recommendations for nomenclature were proposed by the Organizing Committee of the 2011 International IgG4-related disease Symposium, and guidelines for the pathologic diagnosis of this condition have been published by an international group of experts. Experience with treatment regimens is growing. Glucocorticoids and B-cell depletion strategies both appear to be effective and are the subject of ongoing studies. This article reviews the current thought and understanding of this disease with regard to nomenclature, organ system involvement, and approaches to therapy.
Collapse
Affiliation(s)
- John H Stone
- Rheumatology Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
| |
Collapse
|
|
40
|
Cheuk W, Chan JKC. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol 2012; 29:226-34. [PMID: 23068302 DOI: 10.1053/j.semdp.2012.07.001] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Lymphadenopathy is a common occurrence in IgG4-related disease; it can appear before, concurrent with, or after the diagnosis of this disease, which is characterized by tumefactive sclerosing inflammatory lesions predominantly affecting extranodal sites, such as the pancreas, salivary gland, and lacrimal gland. Although multiple lymph node groups are commonly involved, constitutional symptoms are absent. The lymph nodes can show a broad morphologic spectrum, including multicentric Castleman disease-like (type I), follicular hyperplasia (type II), interfollicular expansion (type III), progressive transformation of germinal centers (type IV), and inflammatory pseudotumor-like (type V). All are characterized by an increase in IgG4+ plasma cells (>100 per high power field) and IgG4/IgG ratio (>40%). IgG4-related lymphadenopathy is both an underdiagnosed and overdiagnosed entity. The former is because of the fact that this entity has not been characterized until recently, while the latter results from pathologists' enthusiasm in diagnosing "new" entities and the lack of specificity of the morphologic and immunophenotypic features of IgG4-related lymphadenopathy. It is prudent to render this diagnosis only for patients with known IgG4-related disease or in the presence of corroborating clinical and laboratory findings (such as elderly men, systemic lymphadenopathy, elevated serum IgG4, IgG, and IgE but not IgM and IgA, and low titers of autoantibodies). Outside these circumstances, a descriptive diagnosis of "reactive lymphoid hyperplasia with increased IgG4+ cells" accompanied by a recommendation for follow-up will be appropriate because IgG4-related disease will likely ensue only in a minority of such patients.
Collapse
Affiliation(s)
- Wah Cheuk
- Department of Pathology, Queen Elizabeth Hospital, Hong Kong, SAR, China
| | | |
Collapse
|
|
41
|
Zhang X, Zhang X, Li W, Jiang L, Zhang X, Guo Y, Wang X. Clinical analysis of 36 cases of autoimmune pancreatitis in China. PLoS One 2012; 7:e44808. [PMID: 23028628 PMCID: PMC3445578 DOI: 10.1371/journal.pone.0044808] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Accepted: 08/14/2012] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND To improve the early identification of autoimmune pancreatitis in China by a retrospective analysis of clinical data from AIP patients. METHODOLOGY/PRINCIPAL FINDINGS The analysis included 36 patients admitted by the surgery department of our hospital from January 2003 to October 2011 whose postoperative pathological confirmations were consistent with the histological criteria of Honolulu Consensus Document. The clinical phenotypes associated with the histopathologic patterns of LPSP and IDCP were referred to as type 1 and type 2 of AIP, respectively. A retrospective analysis of clinical features, serological data, pathological findings and imageological records was performed in line with the subtypes of AIP. Type 1 showing a sex predilection (males) was commonly more dominant than type 2 in all AIP. Type 2 without a gender predilection was, on average, a decade younger than type 1. Type 1 was inferior to type 2 in ALT, ALP and γ-GT with statistical significance (P = 0.044, 0.025 and 0.013). Type 1 was inferior to type 2 in AST with difference close to statistical significance (P = 0.072). Histopathology revealed frequent lymphoplasmacytic infiltration with less frequent infiltration of neutrophils, eosinophils and fibroblasts. Diffuse and intensive interstitial fibrosis could be seen. The changes of pancreatic head were more frequently seen in type 2 than in type 1 (P = 0.05). Plasma cells staining of IgG4 at a density of over 30 or more cells per high-power field appeared to be a specific finding in China with type 1. Imageology found a diffusely or focally enlarged pancreas, most frequently a mass or enlargement in the pancreatic head, characteristic capsule-like rim, calcification or pancreatic calculus and cystic degeneration. CONCLUSIONS/SIGNIFICANCE AIP is a unique type of chronic pancreatitis and has distinctive serological, pathological and imageological characteristics, which should be used for differentiation from pancreatic cancer.
Collapse
Affiliation(s)
- Xingang Zhang
- Department of Rheumatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
| | | | | | | | | | | | | |
Collapse
|
|
42
|
IgG4-related sclerosing disease of the small bowel presenting as necrotizing mesenteric arteritis and a solitary jejunal ulcer. Am J Surg Pathol 2012; 36:929-34. [PMID: 22367294 DOI: 10.1097/pas.0b013e3182495c96] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Since first described in the mid 1990s, there has been burgeoning literature on IgG4-related sclerosing disease. The number of sites that may be involved is ever increasing, with the pancreas, salivary glands, and lymph nodes being the most commonly affected organs. There are no well-documented cases arising in the gastrointestinal tract. In this report, we present the first case to our knowledge of IgG4-related sclerosing disease involving the small bowel with a distinctly unusual clinicopathologic presentation. A previously well 46-year-old woman presented with a 2-year history of intermittent abdominal pain with recent worsening due to small bowel obstruction. Following imaging, which showed jejunitis with surrounding mesenteric inflammatory changes, she proceeded to a segmental small bowel resection. The resected jejunum revealed an isolated, stenosing chronic ulcer associated with a necrotizing mesenteric arteritis. A transmural inflammatory infiltrate rich in IgG4 plasma cells was seen in the wall of the bowel and mesenteric artery. Abundant IgG4 interfollicular plasma cells were also identified in a mesenteric lymph node. The serum IgG4 level was elevated at >800 mg/dL (reference range 8 to 140 mg/dL). Although phlebitis is an almost constant feature of this disease, arteritis is not described other than in the lung and aorta. In this report, we also discuss the diagnostic pitfalls and the differential diagnoses that should be considered when this condition arises in the gastrointestinal tract.
Collapse
|
|
43
|
Culver EL, Bateman AC. IgG4-related disease: can non-classical histopathological features or the examination of clinically uninvolved tissues be helpful in the diagnosis? J Clin Pathol 2012; 65:963-9. [PMID: 22685258 DOI: 10.1136/jclinpath-2012-200932] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
IgG4-related disease (IgG4-RD) is an increasingly recognised inflammatory and fibrosing condition that commonly shows multisystem involvement. The disease may mimic malignancy and other inflammatory or immune-mediated disorders, but usually has a good response to corticosteroid therapy, underlining the requirement for recognition of the condition. Accurate diagnosis requires careful interpretation of varying combinations of serum IgG4 levels, radiological features and characteristic histopathological appearances within an appropriate clinical setting. The presence of 'classical' histopathological features together with an elevated tissue IgG4+ plasma cell count and IgG4 to IgG ratio is often diagnostic and at the very least can strongly support a clinicopathological diagnosis of IgG4-RD. The authors describe the most recent diagnostic criteria for IgG4-RD, especially the histopathological features. The authors then discuss the merits of examining tissues that may be more easily obtainable than those that commonly show the 'classical' histopathological features, but within which not all of these 'diagnostic' features may be present. The authors conclude that while a combination of 'classical' histopathological features and an elevated tissue IgG4+ plasma cell count is the gold standard for diagnosis, examination of tissues that show some but not all of these features can, in the appropriate context, provide useful supporting evidence for a clinicopathological diagnosis of IgG4-RD.
Collapse
Affiliation(s)
- Emma L Culver
- Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | | |
Collapse
|
|
44
|
Abstract
The rapidly emerging disorder now known as IgG(4)-related disease (IgG(4)-RD) includes a variety of clinical entities once regarded as being entirely separate diseases. Manifestations of IgG(4)-RD have now been reported in essentially all organ systems. Regardless of which organ is involved, tissue biopsies reveal striking histopathological similarities. The hallmark pathology findings are diffuse lymphoplasmacytic infiltrates, abundant IgG(4)-positive plasma cells, modest tissue eosinophilia, and extensive fibrosis. Tumorous swelling and obliterative phlebitis are other frequently observed features. Polyclonal elevations of serum IgG(4) are found in approximately 70% of patients. Many questions pertaining to the etiology, pathophysiology, epidemiology, clinical features, therapy, disease monitoring, and long-term outcomes remain to be addressed. This paper focuses on the clinical and pathological features of IgG(4)-RD.
Collapse
|
|
45
|
Abstract
Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.
Collapse
Affiliation(s)
- Mukul Divatia
- Department of Pathology, The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA
| | - Sun A Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Y. Ro
- Department of Pathology, The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
- National Cancer Center, Goyang, Korea
- The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| |
Collapse
|
|
46
|
Navaneethan U, Bennett AE, Venkatesh PGK, Lian L, Hammel J, Patel V, Kiran RP, Remzi FH, Shen B. Tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouch-anal anastomosis. J Crohns Colitis 2011; 5:570-6. [PMID: 22115377 DOI: 10.1016/j.crohns.2011.05.011] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Revised: 05/24/2011] [Accepted: 05/24/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is reported to be associated with autoimmune pancreatitis. The aim of the study was to investigate serum IgG4 and tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouches. METHODS Ninety-seven consecutive persistent symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic from January to December 2010 were included in the study. Serum IgG4 was measured at the time of presentation. All patients underwent pouchoscopy with pouch biopsies immunostained for IgG4+ plasma cells. Patients with ≥10 per high-power field of IgG4+ plasma cells were considered positive for the stain. RESULTS Twenty-eight (28.9%) patients had positive IgG4 immunostaining of pouch and/or afferent limb biopsy, while the remaining 69 patients (71.1%) were IgG4 negative. Demographic and symptoms were similar between the two groups. The median serum IgG4 in the IgG4 positive group was 21.3 (interquartile range 0-41.3) mg/dL vs. 0 (interquartile range 0-18) in the IgG4 negative group. (p=0.04). On multivariate analysis, the Pouchitis Disease Activity Index (PDAI) endoscopy score in the pouch (odds ratio [OR] 1.66, 95% confidence interval [CI]: 1.21-2.29, p=0.002) and number of concomitant autoimmune disorders (OR 3.04, 95% CI: 1.22-7.53, p=0.017) were independent risk factors for the presence of IgG4+ plasma cell infiltration. CONCLUSIONS Increased IgG4+ plasma cells were found in 1/4 of IPAA patients with persistent symptoms. The presence of tissue infiltration of IgG4+ plasma cells appeared to be associated with chronic pouch inflammation and concurrent autoimmune disorders.
Collapse
|
|
47
|
Navaneethan U, Liu X, Bennett AE, Walsh RM, Venkatesh PGK, Shen B. IgG4-associated ampullitis and cholangiopathy in Crohn's disease. J Crohns Colitis 2011; 5:451-6. [PMID: 21939919 DOI: 10.1016/j.crohns.2011.03.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2011] [Revised: 03/12/2011] [Accepted: 03/12/2011] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) is reported to be associated with autoimmune pancreatitis and IgG4-related sclerosing disease. We report a case of a 28 year old African American male with a long history of upper gastrointestinal tract Crohn's disease (CD) with multiple surgeries who developed medically refractory disease with small bowel obstruction. He had abnormal liver function tests with imaging evidence of chronic pancreatitis and ampullary inflammatory process. He underwent Whipple's procedure. Histopathological evaluation of surgical specimens of the ampulla and distal common bile duct showed accumulation of IgG4-positive plasma cells in the lamina propria. Preoperative endoscopic biopsies also showed chronic active enteritis involving the duodenum and jejunum with increased IgG4-expressing plasma cell infiltration. His serum IgG4 was 164 mg/dL. The association of IgG4-expressing plasma cell accumulation in the gastrointestinal tract with IBD in patients with hepatobiliary manifestation may have pathogenetic, diagnostic and therapeutic implications.
Collapse
Affiliation(s)
- Udayakumar Navaneethan
- Department of Gastroenterology/Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
| | | | | | | | | | | |
Collapse
|
|
48
|
Abstract
PURPOSE To clarify the features of gallium-67 (Ga-67) imaging typical of IgG4-related disease. METHODS We retrospectively investigated 14 patients diagnosed with IgG4-related disease who underwent Ga-67 scintigraphy in our hospital between January 2005 and May 2010. Of these, 13 patients who underwent gallium scintigraphy before steroid therapy were enrolled in this study. The patient population comprised 11 men and 2 women with age ranging from 47 to 76 years (mean age, 61.9 years). RESULTS Among the 13 patients, significant accumulation of Ga-67 was detected in the bilateral pulmonary hila in 10 patients (77%), pancreas in 10 (77%), salivary glands in 7 (54%), lacrimal glands in 7 (54%), periaortic lesions in 2 (15%), and lung parenchyma in 1 (8%) patient. High accumulation of Ga-67 in the salivary glands was observed in the parotid glands in 3 cases and in the submandibular glands in 6 cases, with the following pattern: normal parotid gland uptake and symmetrical submandibular gland uptake in 2 cases; symmetrical high accumulation in both parotid and submandibular glands in 1 case; symmetrical high accumulation in parotid glands and normal submandibular gland uptake in 1 case; symmetrical uptake by parotid glands and asymmetric uptake by submandibular glands in 1 case; normal parotid gland uptake and asymmetric submandibular gland uptake in 1 case; and asymmetric parotid gland uptake and symmetrical parotid gland uptake in 1 case. CONCLUSION Characteristic patterns of gallium uptake would be helpful for diagnosis, detection of involved lesions, and differential diagnosis in patients with IgG4-related disease to avoid unnecessary surgery.
Collapse
|
|
49
|
Rollins-Raval MA, Felgar RE, Krasinskas AM, Roth CG. Increased Numbers of IgG4-Positive Plasma Cells May Rarely Be Seen in Lymph Nodes of Patients Without IgG4-Related Sclerosing Disease. Int J Surg Pathol 2011; 20:47-53. [DOI: 10.1177/1066896911420562] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
IgG4-related sclerosing disease (IRSD) is a steroid-responsive fibroinflammatory disorder characterized by increased IgG4+ cells. Nodal involvement usually lacks the dense sclerosis seen in extranodal sites, with histologic patterns overlapping with other reactive processes. Twenty-six lymph nodes showing IRSD-related histologic patterns were evaluated for IgG and IgG4 positive cells by immunohistochemistry and correlated with the clinical features. Cases included 7 Castleman disease–like cases (type I pattern), 10 follicular hyperplasia (type II), and 9 plasmacytosis (type III). The mean numbers of IgG4+ cells per high-power field (HPF) were 4.8 (I), 8.4 (II), and 26.6(III), and the mean IgG4/IgG ratios were 0.05 (I), 0.04 (II), and 0.08 (III). Using >50 IgG4+cells/HPF and IgG4/IgG ratio of >0.4 for absolute and relative increases, only 1 case fulfilled both criteria for increased IgG4+ cells, a patient with Hashimoto’s thyroiditis without clinical evidence of IRSD. The results suggest that increased IgG4+ cells may rarely be seen in non-IRSD lymph nodes.
Collapse
|
|
50
|
Elevated serum IgG4 is associated with chronic antibiotic-refractory pouchitis. J Gastrointest Surg 2011; 15:1556-61. [PMID: 21725838 DOI: 10.1007/s11605-011-1587-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2011] [Accepted: 06/10/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIM We recently reported mucosal infiltration of IgG4-expressing plasma cells in a patient with chronic antibiotic-refractory pouchitis (CARP). The role of serum IgG4 in the pathogenesis and clinical course of ileal pouch disorders has not been investigated. We hypothesized that IgG4-mediated autoimmunity may be a contributing factor in for CARP. The aims of the study were to investigate the prevalence of elevated serum IgG4 in symptomatic patients with ileal pouches and to characterize clinical features of pouch disorders in these patients. METHODS A total of 124 consecutive symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic were enrolled in the study from January to October 2010. Serum IgG4 was measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between the study (with serum IgG4 ≥112 mg/dl) and control (with serum IgG4 <112 mg/dl) groups. RESULTS There were ten patients (8.0%) with high serum IgG4 in the study group, while the remaining 114 (92%) patients were in the control group. The prevalence of elevated serum IgG4 in this series was 8%. None of the patients had a confirmed diagnosis of autoimmune pancreatitis. The median serum IgG4 in the study group was 144.5 vs. 14 mg/dl in the control group. The mean age of patients in the study and control groups was 35.5 ± 14.5 and 42.0 ± 13.2 years, respectively (p = 0.137). Two patients in the study group (20.0%) had concurrent autoimmune disorders as compared to 19 patients (16.7%) in the control group (p = 0.788). Three (30.0%) patients in the study group had coexisting primary sclerosing cholangitis (PSC) in contrast to 15 (13.2%) in the control group (p = 0.147). Among the study group patients, five (50.0%) had CARP and one (10%) had Crohn's disease (CD) of the pouch, while in the control group, 23 (20.2%) had CARP and 24 (21.1%) patients had CD of the pouch (p = 0.273). CARP was more commonly seen in patients with high serum IgG4 than patients with a normal IgG4 (50.0% vs. 20.2%, p = 0.03). CONCLUSIONS Approximately 8% of pouch patients presenting with symptoms of pouch dysfunction to our clinic had elevated serum IgG4. Patients with elevated serum IgG4 were more likely to have CARP.
Collapse
|