Clinical Manifestations of Orbital Involvement in IgG4-Related Disease: A Retrospective Study of 573 Patients

Abstract Purpose: To investigate the clinical manifestations of orbital involvement in a large cohort of Chinese patients with IgG4-related disease (IgG4-RD). Methods: A total of 573 patients with IgG4-related disease were included. We described and compared the demographic, clinical, laboratory and histopathologic findings from 314 patients with IgG4-related ophthalmic disease (IgG4-ROD) and 259 with extra-ophthalmic IgG4-RD.Results: Male predominance was found significant in extra-ophthalmic IgG4-RD only. Patients with IgG4-ROD showed younger age at diagnosis and longer duration from onset till diagnosis. In patients with extra-ophthalmic IgG4-RD, the most commonly involved extra-ophthalmic organ was pancreas; while in IgG4-ROD patients, salivary gland was most frequently affected. Multivariate analysis exhibited IgG4-ROD was associated with allergy history, higher serum IgG4/IgG ratio, multiple organs involvement and sialoadenitis. Orbital images were reviewed in 173 (55.1%) IgG4-ROD patients. Fifty-one (29.5%) patients had multiple lesions. Lacrimal gland involvement was detected in 151 (87.3%) patients, followed by extraocular muscles (40, 23.1%), other orbital soft tissue (40, 23.1%) and trigeminal nerve (8, 4.6%). Biopsy was performed from various organs in 390 cases. A dense lymphoplasmacytic infiltration and fibrosis were the main feature in orbital specimens. Storiform fibrosis and obliterative phlebitis were absent in lacrimal gland.Conclusions: Lacrimal gland involvement was the most common orbital manifestation of IgG4-ROD. Patients with IgG4-ROD showed different characteristic in demographic, clinical, laboratory findings compared to patients with extra-ophthalmic IgG4-RD. These features might indicate potential differences in the pathogenesis of these two subgroups of IgG4-RD.

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Ophthalmic involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 573 patients

BMC Ophthalmology ◽

10.1186/s12886-021-02210-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Linyang Gan ◽

Xuan Luo ◽

Yunyun Fei ◽

Linyi Peng ◽

Jiaxin Zhou ◽

...

Keyword(s):

Lacrimal Gland ◽

Clinical Laboratory ◽

Clinical Manifestations ◽

Chinese Patients ◽

Obliterative Phlebitis ◽

Laboratory Findings ◽

Male Predominance ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4

Abstract Purpose To investigate the clinical manifestations of orbital involvement in a large cohort of Chinese patients with IgG4-related disease (IgG4-RD). Methods A total of 573 patients with IgG4-related disease were included. We described and compared the demographic, clinical, laboratory and histopathologic findings from 314 patients with IgG4-related ophthalmic disease (IgG4-ROD) and 259 with extra-ophthalmic IgG4-RD. Results Male predominance was found significant in extra-ophthalmic IgG4-RD only. Patients with IgG4-ROD showed younger age at diagnosis and longer duration from onset till diagnosis. In patients with extra-ophthalmic IgG4-RD, the most commonly involved extra-ophthalmic organ was pancreas; while in IgG4-ROD patients, salivary gland was most frequently affected. Multivariate analysis exhibited IgG4-ROD was associated with allergy history, higher serum IgG4/IgG ratio, multiple organs involvement and sialoadenitis. Orbital images were reviewed in 173 (55.1%) IgG4-ROD patients. Fifty-one (29.5%) patients had multiple lesions. Lacrimal gland involvement was detected in 151 (87.3%) patients, followed by extraocular muscles (40, 23.1%), other orbital soft tissue (40, 23.1%) and trigeminal nerve (8, 4.6%). Biopsy was performed from various organs in 390 cases. A dense lymphoplasmacytic infiltration and fibrosis were the main feature in orbital specimens. Storiform fibrosis and obliterative phlebitis were absent in lacrimal gland. Conclusions Lacrimal gland involvement was the most common orbital manifestation of IgG4-ROD. Patients with IgG4-ROD showed different characteristic in demographic, clinical, laboratory findings compared to patients with extra-ophthalmic IgG4-RD. These features might indicate potential differences in the pathogenesis of these two subgroups of IgG4-RD.

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Thoracic Involvement in IgG4-Related Disease

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0039-1700995 ◽

2020 ◽

Vol 41 (02) ◽

pp. 202-213 ◽

Cited By ~ 1

Author(s):

Marta Casal Moura ◽

Ria Gripaldo ◽

Misbah Baqir ◽

Jay H. Ryu

Keyword(s):

Clinical Laboratory ◽

Wide Spectrum ◽

The Body ◽

Obliterative Phlebitis ◽

Immunoglobulin G4 ◽

Related Disease ◽

First Line Therapy ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Histopathologic Features

AbstractImmunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that has been recognized to involve virtually any organ in the body and typically manifests mass-like lesions (tumefactive). Although initial reports of this disease (autoimmune pancreatitis [AIP]) were described in the Japanese population, it has since been reported worldwide. It is most commonly seen in adults of middle age or older, more often men than women. The pathogenesis of IgG4-RD is largely unknown, but genetic factors, microorganisms, and autoimmunity are thought to play important roles. Serum IgG4 concentration is elevated in the majority of patients with IgG4-RD but is a nonspecific finding. Characteristic histopathologic features include dense lymphoplasmacytic infiltrate, fibrosis (often in storiform pattern), and obliterative phlebitis. Lung involvement in IgG4-RD was first reported in 2004 in two patients with AIP and coexisting interstitial lung disease. Since then, a wide spectrum of intrathoracic involvement has been reported and includes not only parenchymal lung diseases but also pleural, airway, vascular, and mediastinal lesions. Thoracic involvement in IgG4-RD is often found incidentally during the workup of extrathoracic lesions but can sometimes be the presenting abnormality. The diagnosis of IgG4-RD requires correlation of clinical, laboratory, imaging, and histopathologic features. Glucocorticoids are the first-line therapy but other options including B cell depletion are being investigated. IgG4-RD is generally associated with an indolent clinical course and most patients improve with glucocorticoid therapy.

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Clinical case of membranous nephropathy in a patient with IgG4-related disease

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2020-24-4-110-121 ◽

2020 ◽

Vol 24 (4) ◽

pp. 110-121

Author(s):

M. O. Pyatchenkov ◽

O. A. Vorobyeva ◽

A. N. Belskykh ◽

M. V. Zakharov ◽

M. Y. Dendrikova

Keyword(s):

Nephrotic Syndrome ◽

Membranous Nephropathy ◽

Elevated Serum ◽

Clinical Manifestations ◽

The Body ◽

Related Disease ◽

Igg4 Related Disease ◽

Pathologic Features ◽

Wide Range ◽

Serum Igg4

IgG4-related disease (IgG4-RD) currently is considered as a chronic fibroinflammatory immune-mediated multisystemic condition of unidentified etiology, which can imitate a wide range of malignant, infectious, rheumatologic, and other diseases. It can affect almost any organ system in the body synchronously or sequentially, but the most often affected are the pancreas, hepatobiliary tract, periorbital structures, salivary glands, kidneys, and lymph nodes. The most frequent renal manifestations of IgG4-RD is IgG4-related tubulointerstitial nephritis. Membranous nephropathy is the most common glomerular disease accompanied by IgG4-RD. Regardless of the organ localization, patients with IgG4-RD are characterized by elevated serum IgG4, but this laboratory abnormality is not specific and can be changed in other diseases. In all suspected cases of IgG4-RD the diagnosis should be confirmed by histological examination. Characteristic pathologic features include diffuse or focal lymphoplasmacytic infiltration with prominent IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. Patients with IgG4- RD usually have an excellent clinical response to glucocorticoids, but relapse rates after steroid withdrawal are high, which may require additional use of immunosuppressants or rituximab. Due to the low prevalence and multitude of clinical manifestations the disease often remains underdiagnosed on time. This case report describes middle-aged patients with a history of chronic recurrent pancreatitis complicated by the nephrotic syndrome. Kidney biopsy showed membranous nephropathy and diagnosis IgG4-RD with multiorgan involvement was made. Partial remission was achieved on corticosteroid therapy. The presented case clearly demonstrates the difficulties of diagnosis and treatment of IgG4-RD. IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with nephrotic syndrome accompanied by multiorgan dysfunction.

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AB1036 CLINICAL MANIFESTATIONS, CLINICAL COURSE, AND OUTCOMES OF IMMUNOGLOBULIN G4 RELATED DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1206 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1809.1-1809

Author(s):

W. Katchamart ◽

K. Phaopraphat ◽

P. Ngamjanyaporn ◽

P. Narongroeknawin ◽

N. Kasitanon

Keyword(s):

Disease Duration ◽

Immunosuppressive Agents ◽

Clinical Manifestations ◽

Systemic Autoimmune Disease ◽

Immunoglobulin G4 ◽

Serum Igg4 Level ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Igg4 Level

Background:Immunoglobulin G4 related disease (IgG4-RD) is an uncommon chronic systemic autoimmune disease, pathologically characterized by lymphoplasma cell, IgG4 plasma cell or storiform fibrosis infiltration with elevated serum IgG4 level. IgG4-RD is a new disease and not widely recognized.Objectives:The aim of this study was to describe clinical manifestations and outcomes of IgG4-RD in Thai patientsMethods:This multicenter retrospective cohort study included patients who aged ≥ 18 years and were diagnosed with IgG4-RD according to 2011 comprehensive or consensus diagnostic criteria, between 2000 and 2019 in four academic centers in Thailand. Baseline characteristic, laboratory and pathologic findings, treatments, and outcomes were systematically reviewed.Results:Of the 110 patients included, 71% were male with mean age (SD) of 59.6 (13.3) years and median disease duration (IQR) of 28.8 (14.6-53.5) months. Single organ involvement was observed in 60 patients (54.5%). The most common presenting organ involvement was the orbit (29%), followed by the salivary glands (19%), lacrimal glands (18%), bile duct (16%), and pancreas (11%). The most frequently affected organs were the orbits (34%), followed by the salivary glands (26%), lacrimal glands (20%), bile duct (19%), and lymph nodes (19%). Ninety-six percent (96%) had IgG4 level of more than 135 mg/dl at presentation. Most patients (92%) were treated with corticosteroid (CS) alone or in combination with immunosuppressive agents. Azathioprine (47%) and methotrexate (11%) were the most commonly used immunosuppressive agents. Additionally, 20% required surgery, and 6.4% underwent stent insertion. One-fourth (26%) were in remission with successfully CS tapering, while 37%, and 29% had complete, and partial response. Nevertheless, 22% relapse with median time to relapse (IQR) of 22.2 (12.8-41.1) months. Relapse was common in patients with orbital (p = 0.001) and lung (p= 0.007) involvement, and patients with longer disease duration (median 44.1 and 23.1 months, P=0.001), while serum IgG4 level was insignificantly higher in relapse group (median 1,085 vs. 850 mg/dL, p=0.28).Conclusion:IgG4-RD is a chronic systemic autoimmune disease with diverse manifestations, response to treatment, and outcomes. Most patients responded well to CS and immunosuppressive agents with notable relapse rate, while minority required surgery or mechanical intervention.References:[1]Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH. Clinical phenotypes of IgG4-related Disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78(3):406-12.[2]Martinez-Valle F, Fernandez-Codina A, Pinal-Fernandez I, Orozco-Galvez O, Vilardell-Tarres M. IgG4- related disease: Evidence from six recent cohorts. Autoimmun Rev. 2017;16(2):168-72Acknowledgments:NoneDisclosure of Interests:None declared

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IgG4 Related Disease of The Larynx Mimicking Malignancy: A Case Report and Review of the Literature

10.21203/rs.3.rs-250953/v1 ◽

2021 ◽

Author(s):

Sevda Akyol ◽

Ozlem Saraydaroglu ◽

Omer Afsin Ozmen

Keyword(s):

Plasma Cells ◽

Clinical Laboratory ◽

Review Of The Literature ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Storiform Fibrosis ◽

Lymphoplasmacytic Infiltration ◽

Igg4 Level

Abstract Objectives: Immunoglobulin G4–related disease is characterized by increased serum IgG4 level, enlargement in the relevant organs and histopathologically intense storiform fibrosis, lymphoplasmacytic infiltration rich in IgG4 positive plasma cells, and obliterative phlebitis.Methods and Results: In this report, a patient who underwent a laryngeal biopsy with a pre-diagnosis of malignancy, but had findings consistent with immunoglobulin G4–related disease in the biopsy sample, is described.Conclusion: Immunoglobulin G4–related disease can be seen in very rare localizations. It should be kept in mind in differential diagnosis when tissues especially containing inflammation rich in plasma cells are encountered. Clinical, laboratory and pathological correlation is extremely important in the diagnosis of an IgG4-related disease.

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IgG4-related aortitis/periaortitis and periarteritis: a distinct spectrum of IgG4-related disease

10.21203/rs.3.rs-16955/v1 ◽

2020 ◽

Author(s):

Linyi Peng ◽

Panpan Zhang ◽

Jieqiong Li ◽

Zheng Liu ◽

Hui Lu ◽

...

Keyword(s):

Thoracic Aorta ◽

Abdominal Aorta ◽

Iliac Artery ◽

Treatment Efficacy ◽

Male Predominance ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Type 3

Abstract Background: Large vessels could be involved in IgG4-related disease(IgG4-RD).This study aimed to clarify the clinical features and evaluate the treatment efficacy for IgG4-RD with aortitis/periaortitis and periarteritis (PAO/PA). Methods: This study enrolled 587 IgG4-RD patients in a prospective cohort with a follow-up time for more than 6 months. The distribution of IgG4-related PAO/PA was classified into four types: type 1, thoracic aorta; type 2a, abdominal aorta; type 2b, abdominal aorta and iliac artery; type 2c, iliac artery; type 3, thoracic and abdominal aorta; type 4, other arteries. Patient’s demographic data, clinical characteristics, laboratory parameters, and treatment efficacy were analyzed. Results: Of 587 IgG4-RD patients, 89(15.2%) had PAO/PA. The average age was 58.3±11.1 years, with male predominance (85.4%). Vessels affected were as follows: abdominal aorta (83.1%), iliac artery (70.8%), thoracic aorta (13.5%) and other vessels (13.5%). The most prevalent distribution type of IgG4-related PAO/PA was type 2b, with 74 (83.1%) patients, followed by type 2a, type 2c, type 3, and type 1. 55 (61.8%) PAO/PA patients had hydronephrosis, with renal insufficiency occurred in 43 (48.3%), and 31 (34.8%) PAO/PA patients had D-J stent drainage due to severe ureteral obstruction. After treatment with glucocorticoid and immunosuppressants, 82% patients achieved a remission with shrinking of perivascular mass. Conclusions: IgG4-RD with PAO/PA was distinct from non-PAO/PA in demographic features, organs involvement distribution, inflammatory markers, serum IgG4 and IgE. The most common affected vessel was abdominal aorta, and most patients responded well with treatment.

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The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21145082 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5082

Author(s):

Song-Chou Hsieh ◽

Chieh-Yu Shen ◽

Hsien-Tzung Liao ◽

Ming-Han Chen ◽

Cheng-Han Wu ◽

...

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Clinical Manifestations ◽

Malignant Neoplasms ◽

Th2 Response ◽

Obliterative Phlebitis ◽

Inflammatory Reactions ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4

IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.

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Presenting IgG4-related disease: an emerging entity in Pakistan

10.21203/rs.3.rs-424267/v1 ◽

2021 ◽

Author(s):

Lena Jafri ◽

Sadori Khawaja ◽

Bilal Hashmi ◽

Saira Fatima ◽

Om Parkash ◽

...

Keyword(s):

Clinical Laboratory ◽

Tertiary Care ◽

The Body ◽

Clinical Feature ◽

Care Hospital ◽

Related Disease ◽

Igg4 Related Disease ◽

Group I ◽

Serum Igg4 ◽

Group Ii

Abstract Background IgG4 related disease (IgG4-RD) is a spectrum of immune mediated disorder involving various organs of the body. In this study the clinical spectrum of possible IgG4-RD was explored. Methods Subjects tested for serum IgG4 and all biopsies of subjects with suspected IgG4-RD received at the clinical laboratory of a tertiary care hospital from April 2015 to December 2019 were included. Medical charts of subjects registered were reviewed and telephonic interviews were conducted. Subjects were divided into two groups: group I had biochemical evidence of IgG4-RD while group II had histopathological evidence of IgG4-RD. “Comprehensive diagnostic criteria for IgG4-RD, 2011” was used for labeling patients as possible, probable and definitive IgG4-RD. Results A total of 177 study subjects were recruited in the current study. Group I included 10 children and 105 adults whereas group II had 5 children and 57 adults. Out of the total 177 subjects definitive, probable and possible IgG4-RD were seen in (n = 2, 1.1%), (n = 61, 34.4%) and (n = 114, 64.4) subjects respectively. The commonest organs involved in all the study subjects were pancreas (57.6%), submandibular gland (12.4%) and liver (6.2%). Conclusion The clinical feature of IgG4-RD include single or multiple organ involvement with pancreas being the most frequently affected organ in the current population. Amalgamation of clinical, biochemical and histopathological findings are essential for the IgG4-RD, although none is pathognomonic by itself.

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