Clinical Characteristics and Therapeutic Response of Immunoglobulin G4-Related Disease: a Retrospective Study of 127 Chinese Patients

Abstract Background & Aims: Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse.Methods: We collected baseline data of eligible patients with IgG4-RD and analyzed clinical feature by interview and review of medical records. The patients who received medical therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse. Result: Totally 127 IgG4-RD patients, including 92 males and 35 females, were included in the present study. The median age at diagnosis was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Patients classified as pancreato-hepatobiliary group had highest aminotransferase, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin level (all p＜0.05). Mikulicz syndrome and systemic involvement group had the highest IgG-RI score, serum globulin, IgG and IgG4 level. Among 92 patients who received medical therapy with at least 3 months follow-up,76 received glucocorticoids (GC) alone or in combination with immunosuppressive agents and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Wheras16 patients did not take GC, among them, 6 patients achieved remission with one patient relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria, GC monotherapy and GC withdrawal were independent predictors for relapse.Conclusion: Different phenotypes of IgG4-RD showed different demographic and serological features. The risk factors of relapse were GC withdrawal, GC monotherapy and higher score of ACR/EULAR IgG4-RD Classification Criteria.

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Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort

Rheumatology ◽

10.1093/rheumatology/kez669 ◽

2020 ◽

Vol 59 (8) ◽

pp. 2115-2123 ◽

Cited By ~ 1

Author(s):

Yanying Liu ◽

Qiaozhu Zeng ◽

Lijuan Zhu ◽

Jingyuan Gao ◽

Ziqiao Wang ◽

...

Keyword(s):

Risk Factors ◽

Relapse Rate ◽

Unstable Condition ◽

Serum Igg4 Level ◽

Related Disease ◽

Igg4 Related Disease ◽

Younger Age ◽

Serum Igg4 ◽

History Of ◽

Igg4 Level

Abstract Objectives Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition. Methods We performed a retrospective study of 277 IgG4-RD patients at Peking University People’s Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition. Results The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different. Conclusion The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.

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Abstract 12071: Serum Immunoglobulin G4 Level is an Independent Predictor of Major Adverse Cardiovascular Events After Percutaneous Coronary Intervention over Long-Term Follow-Up

Circulation ◽

10.1161/circ.132.suppl_3.12071 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Aiko Sakamoto ◽

Nobukazu Ishizaka ◽

Jiro Ando ◽

Ryozo Nagai ◽

Issei Komuro

Keyword(s):

Coronary Intervention ◽

Serum Levels ◽

Major Adverse Cardiovascular Events ◽

Immunoglobulin G4 ◽

Serum Igg4 Level ◽

Percutaneous Coronary ◽

Serum Igg4 ◽

Long Term Follow Up ◽

Igg4 Level

Background: Inflammatory processes contribute to the development of atherosclerosis. However, it remains unclear whether immunoglobulin G4 (IgG4)-related immuno-inflammation may affect the progression of cardiovascular disease. We therefore analyzed the relationship between serum IgG4 level and future major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). Methods: We measured serum levels of IgG4 in 562 patients (mean age, 66.9 ± 10.3 years) who underwent coronary angiography from October 2005 to September 2008. Furthermore, a total of 108 patients who subsequently received first PCI were followed-up for a median period of 2721 days (interquartile range [IR] 1591-3183). MACE was defined as cardiac death, acute coronary syndrome, cerebral stroke, and target vessel revascularization. Results: Serum levels of IgG4 were significantly higher in patients with coronary artery disease (34.1 mg/dL, IR 18.7-58.9) than in those without (30.5 mg/dL, IR 15.8-50.3, P=0.045). Among patients who received PCI, 40 (37.0%) patients developed MACE during the follow-up period. Patients with serum IgG4 levels of median or greater (≥37.2 mg/dL) had a significantly higher risk of MACE than those with serum IgG4 levels below median (log-rank test, P=0.017). In Cox regression analysis using age, gender, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, smoking, and serum levels of high-sensitivity C-reactive protein (hsCRP) as covariates, serum IgG4 level was an independent predictor of MACE (hazard ratio 2.39 per 100 mg/dL increase, 95% confidence interval 1.41-4.07, P=0.001). Conclusions: Elevated serum IgG4 level at baseline significantly predicted MACE after PCI, as well as present coronary stenosis, over long-term follow-up even among patients without apparent IgG4-related disease. IgG4-related immuno-inflammation may play a certain role in the progression of coronary atherosclerosis.

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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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A Case of Immunoglobulin G4-Related Disease with Extensive Multiorgan Involvements

Case Reports in Rheumatology ◽

10.1155/2015/392893 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Kazuhiko Higashioka ◽

Kenji Yoshida ◽

Kensuke Oryoji ◽

Kazuo Kamada ◽

Shinichi Mizuki ◽

...

Keyword(s):

Retroperitoneal Fibrosis ◽

Elevated Serum ◽

Clinical Findings ◽

Organ Involvement ◽

Immunoglobulin G4 ◽

Serum Igg4 Level ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Igg4 Level

We report a case of IgG4-related disease (IgG4-RD) with multiple ten-organ involvement. This case showed many clinical findings, such as bilateral swelling of salivary and lacrimal glands, autoimmune pancreatitis, interstitial nephritis, retroperitoneal fibrosis, periaortitis, systemic swelling of lymph nodes, pulmonary lesions, splenomegaly, and jejunal lesions. He was suspected as having SLE or malignant lymphoma but diagnosed as having IgG4-RD by the elevated serum IgG4 level and histological findings from kidney and lymph node. We report a case of IgG4-RD with multiple ten-organ involvement that was successfully treated with prednisolone therapy.

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Malignancy Risk of Immunoglobin G4-related Disease: Evidence From a Large Cohort Multicenter Study

10.21203/rs.3.rs-263200/v1 ◽

2021 ◽

Author(s):

Yanying Liu ◽

Jiangnan Fu ◽

Xiaoran Ning ◽

Huijuan Li ◽

Xiangbo Ma ◽

...

Keyword(s):

Risk Factors ◽

Prediction Model ◽

Autoimmune Pancreatitis ◽

Chinese Population ◽

Chinese Patients ◽

Immunoglobulin G4 ◽

Malignancy Risk ◽

Related Disease ◽

Multicenter Cohort ◽

General Chinese Population

Abstract Objective: To evaluate the prevalence of malignancies in a multicenter cohort of Chinese patients with immunoglobulin G4-related disease (IgG4-RD) and to identify the related risk factors of malignancy in IgG4-RD patients. Methods: We retrospectively analyzed 602 IgG4-RD patients who were recruited in 5 medical centers from 2009 to 2020. Standardized prevalence ratios (SPRs) against general Chinese population were calculated along with 95% confidence intervals (CIs). We identified the risk factors of malignancy in IgG4-RD and calculated the odds ratios (ORs) of different factors. Then, we developed and validated a prediction model for malignancy risk of IgG4-RD based on our cohort. Results: We observed a significantly increased prevalence of total malignancies in this cohort compared to general Chinese population (SPR 8.66 [95%CI 5.84, 12.31]). Logistic regression analysis indicated that eosinophil percentage (OR 1.096 [95%CI 1.019-1.179], P=0.016), serum albumin to globulin ratio (AGR) (OR 0.185 [95%CI 0.061-0.567], P=0.002) and autoimmune pancreatitis (OR 2.400 [95%CI 1.038-5.549], P=0.041) were three independent risk factors of malignancy in IgG4-RD patients. Four predictors were included in our final prediction model: age at IgG4-RD diagnosis, eosinophil percentage, AGR and autoimmune pancreatitis. The nomogram performed well in the internal validation cohort, with a concordance index (C-index) of 0.738.Conclusion: A significantly increased prevalence of total malignancies were observed in our multicenter cohort. Eosinophil percentage and autoimmune pancreatitis are risk factors, whereas AGR is negatively associated with malignancy in IgG4-RD. A prediction model for malignancy risk of IgG4-RD was first developed and validated in our study.

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Evaluate the Differences in CT Features and Serum IgG4 Levels between Lymphoma and Immunoglobulin G4-Related Disease of the Orbit

Journal of Clinical Medicine ◽

10.3390/jcm9082425 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2425

Author(s):

Wei-Hsin Yuan ◽

Anna Fen-Yau Li ◽

Shu-Yi Yu ◽

Ying-Yuan Chen ◽

Chia-Hung Wu ◽

...

Keyword(s):

Elevated Serum ◽

Hounsfield Unit ◽

Immunoglobulin G4 ◽

Related Disease ◽

Serum Igg4 ◽

Orbital Lymphoma ◽

Serum Igg Levels ◽

Igg Level ◽

Ct Features ◽

Higher Sensitivity

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)—characterized as tumors mimicking malignant orbital lymphoma (OL)—responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. Results: Significantly related to IgG4-ROD (all p < 0.05) were the presence of lesions with regular borders, presence of multiple lesions—involving both lacrimal glands on CT scans—higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674–1.000, p = 0.005] vs. 0.766 [95% CI: 0.615–0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518–0.997] vs. 0.75 [95% CI: 0.509–0.913]), higher specificity (0.813 [95% CI: 0.544–0.960] vs. 0.778 [95% CI: 0.578–0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5). Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.

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SAT0532 POSITIVE DISEASE-SPECIFIC AUTOANTIBODIES LOWER DIAGNOSTIC SENSITIVITY BUT HAVE LITTLE CLINICAL SIGNIFICANCE IN DIAGNOSING IgG4-RELATED DISEASE USING THE 2019 ACR/EULAR CLASSIFICATION CRITERIA IN DAILY CLINICAL PRACTICE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3177 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1224.1-1224

Author(s):

I. Mizushima ◽

T. Yamano ◽

H. Kawahara ◽

S. Hibino ◽

R. Nishioka ◽

...

Keyword(s):

Clinical Practice ◽

False Negative ◽

Classification Criteria ◽

Daily Clinical Practice ◽

Exclusion Criterion ◽

Inclusion Criteria ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Disease Specific

Background:Recently, the 2019 ACR/EULAR classification criteria for IgG4-related disease (IgG4-RD) were published mainly to identify more homogeneous subjects for inclusion in clinical trials and observational studies [1]. However, although their high specificity is presumed to be useful to differentiate IgG4-RD from various mimickers, their value in daily clinical practice needs to be evaluated.Objectives:This study aimed to clarify the usefulness of the 2019 ACR/EULAR classification criteria for IgG4-RD and characteristics of false-negative patients in daily clinical practice.Methods:We retrospectively reviewed the medical records of 162 patients with IgG4-RD and 130 consecutive non-IgG4-RD patients (mimickers) diagnosed by experts whose serum IgG4 levels were measured at a single center in Japan. Using the collected data, we calculated sensitivity, specificity, and fulfillment rates for the entry criteria, exclusion criteria, and threshold of inclusion criteria points. In addition, to clarify the characteristics of false-negative cases in IgG4-RD, we performed an intergroup comparison of their clinical features including disease-specific autoantibodies.Results:Both the patients with IgG4-RD and mimickers were relatively old (66 and 65 years) with male predominance (67% and 60%). The final diagnoses of mimickers mainly consisted of cancer, lymphoma, vasculitis, sarcoidosis, multicentric Castleman’s disease, and atherosclerotic or infectious aortic aneurysm. The classification criteria had a sensitivity of 72.8% and a specificity of 100%. Of the 44 false-negative cases, one did not fulfill the entry criteria, 20 fulfilled one exclusion criterion, and 27 did not achieve sufficient inclusion criteria points. Compared with the true-positive cases, the false-negative cases had significantly fewer affected organs, lower serum IgG4 levels, higher serum CH50 levels, and lower prevalence of salivary/lacrimal gland and renal parenchymal lesions. They were also less likely to have had biopsies (61% vs 97%). Of note, positivity of disease-specific autoantibodies including SSA/Ro antibody, ANCA, ds-DNA antibody, and ACPA was the most common exclusion criterion fulfilled in 18 patients, only 2 of whom were diagnosed with a specific autoimmune disease (rheumatoid arthritis) complicated by IgG4-RD. The remaining 16 patients had no specific clinical symptoms related to such autoantibodies. In addition, compared with IgG4-RD patients without disease-specific autoantibodies, the 18 patients with them had almost equal serum IgG4 and complement levels, number of affected organs, and histopathology and immunostaining scores despite higher serum IgG and CRP levels.Conclusion:The present study suggests that the 2019 ACR/EULAR classification criteria for IgG4-RD has excellent diagnostic specificity and moderate sensitivity in daily clinical practice. Positive disease-specific autoantibodies alone, which lowered the sensitivity in this study, may have little clinical significance concerning the diagnosis of IgG4-RD.References:[1]Wallace ZS et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 2020 Jan;79(1):77-87.Disclosure of Interests:None declared

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Usefulness of measuring serum IgG4 level as diagnostic and treatment marker in IgG4-related disease

Japanese Journal of Clinical Immunology ◽

10.2177/jsci.35.30 ◽

2012 ◽

Vol 35 (1) ◽

pp. 30-37 ◽

Cited By ~ 6

Author(s):

Motohisa YAMAMOTO ◽

Norihiro NISHIMOTO ◽

Tetsuya TABEYA ◽

Yasuyoshi NAISHIRO ◽

Keisuke ISHIGAMI ◽

...

Keyword(s):

Serum Igg4 Level ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Igg4 Level

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Immunoglobulin G4-related disease - diagnostic dilemma and importance of clinical judgement: a case report

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20204922 ◽

2020 ◽

Vol 8 (11) ◽

pp. 4144

Author(s):

Jagadeesh Chandrasekaran ◽

Phani Krishna Machiraju

Keyword(s):

Early Recognition ◽

Elevated Serum ◽

Antineutrophil Cytoplasmic Antibodies ◽

Inflammatory Disorder ◽

Imaging Features ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

The Right

Immunoglobulin G4 (IgG4)-related disease is a multi-organ, immune-mediated, fibro-inflammatory disorder characterized by tumefactive masses in the affected organs. Incidence and prevalence of IgG4-related disease (RD) are not clearly known and have slight male preponderance. It often involves multiple organs at the time of presentation or over the course of disease mimicking malignancy, Sjogren's syndrome, antineutrophil cytoplasmic antibodies associated vasculitis, infections. A thorough workup is needed to rule out these mimickers. A 33-year-old gentleman presented to us with history of progressive swelling in the right peri-orbital region for four years. On evaluation, abdominal imaging was notable for the sausage-shaped pancreas and hypoenchancing nodules in bilateral kidneys. Histological examination of right lacrimal gland revealed lymphoplasmacytic infiltrate and storiform fibrosis. Serum IgG4 levels were normal, and immunostaining was negative. A diagnosis of IgG4-RD was suggested because of multi-organ involvement, classical radiological and histopathological features. Awareness about IgG4-RD, an under-recognized entity is essential, as it is treatable, and early recognition may help in a favourable outcome. Appropriate use of clinicopathological, serological and imaging features in the right clinical context may help in accurate diagnosis. Elevated serum IgG4 levels and biopsy are not mandatory for the diagnosis.

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