No overlap between IgG4-related disease and microscopic polyangiitis and granulomatosis with polyangiitis despite elevated serum IgG4 at diagnosis: a retrospective monocentric study

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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Salivary Gland Pathology in IgG4-Related Disease: A Comprehensive Review

Journal of Immunology Research ◽

10.1155/2018/6936727 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Ilaria Puxeddu ◽

Riccardo Capecchi ◽

Filippo Carta ◽

Antonio Gaetano Tavoni ◽

Paola Migliorini ◽

...

Keyword(s):

Salivary Glands ◽

Imaging Techniques ◽

Elevated Serum ◽

Clinical Aspects ◽

Related Disease ◽

Multiple Organs ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Organ Specific ◽

Clinical Pictures

IgG4-related disease (IgG4-RD) is a rare fibroinflammatory condition that can affect almost any organ, characterized by swollen lesions and often by eosinophilia and elevated serum IgG4 concentrations. The diagnosis of IgG4-RD is a challenging task: in fact, single or multiple organs can be affected and clinical, serological, and histological findings can be heterogeneous. In IgG4-RD, the involvement of salivary glands is observed in 27% to 53% of patients. Several organ-specific conditions, now recognized as different manifestations of IgG4-related sialadenitis (IgG4-RS), were viewed in the past as individual disease entities. The study of salivary glands may sometimes be complex, because of the number of pathological conditions that may affect them, often with overlapping clinical pictures. Integration of different imaging techniques is often required in the case of swelling of salivary glands, even though biopsy remains the gold standard for a definite diagnosis of IgG4-RS. Thus, in this review, we discuss new insights in the pathogenesis of IgG4-RD, focusing on its clinical aspects and the tools that are currently available for a correct differential diagnosis when the salivary glands are involved.

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IgG4-related disease in a patient with HIV infection

BMJ Case Reports ◽

10.1136/bcr-2018-226809 ◽

2019 ◽

Vol 12 (4) ◽

pp. e226809

Author(s):

Raquel Ron ◽

Ignacio Ruz-Caracuel ◽

Eugenia García ◽

María Luisa Montes-Ramírez

Keyword(s):

Lymph Nodes ◽

Elevated Serum ◽

Lung Damage ◽

Axillary Lymph Nodes ◽

Hiv Positive ◽

Axillary Lymph ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Igg4 Level

A 47-year-old HIV-positive man with good immune and virological status presented with chronic multiple enlarged lymph nodes, lung disease and eosinophilia. Radiologic tests showed enlarged cervical, thoracic and axillary lymph nodes, with interstitial lung damage. After several non-specific histologic studies, an elevated serum IgG4 level led us to request immunohistochemistry of a lymph node sample. The test confirmed the diagnosis of IgG4-related disease.

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Soluble Interleukin-2 Receptor: A Potential Marker for Monitoring Disease Activity in IgG4-Related Disease

Mediators of Inflammation ◽

10.1155/2018/6103064 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 12

Author(s):

A. F. Karim ◽

L. E. M. Eurelings ◽

R. D. Bansie ◽

P. M. van Hagen ◽

J. A. M. van Laar ◽

...

Keyword(s):

Disease Activity ◽

Interleukin 2 ◽

Elevated Serum ◽

Related Disease ◽

Interleukin 2 Receptor ◽

Igg4 Related Disease ◽

Potential Marker ◽

Potential Biomarker ◽

Serum Igg4 ◽

Soluble Interleukin 2 Receptor

Background. IgG4-related disease (IgG4-RD) is a fibroinflammatory condition. T-cells play a crucial role in the pathogenesis, and therefore, serum soluble interleukin-2 receptor (sIL-2R) may be a potential biomarker. Method. We studied the levels of sIL-2R in 26 histologically proven IgG4-RD patients with available serum sIL-2R and compared them to those in newly diagnosed and untreated sarcoidosis patients (n=78) and controls (n=101) and the serum sIL-2R levels in patients after treatment of IgG4-RD (n=15). The disease activity was measured using the IgG4-Related Disease Responder Index (IgG4-RD RI). Results. Median serum sIL-2R in IgG4-RD patients was 4667 pg/ml compared to 1515 pg/ml in controls (P<0.001) and 6050 pg/ml in sarcoidosis patients (P=0.004 compared to IgG4-RD). All IgG4-RD patients had elevated serum sIL-2R levels compared to the reference value of <2500 pg/ml in controls and 85% elevated serum IgG4; however, these did not correlate with each other. Both serum sIL-2R and IgG4 levels declined significantly after treatment (P=0.001 and P=0.01, resp.). Before treatment, serum sIL-2R level and IgG4-RD RI did not correlate with each other. However, the decrease in serum sIL-2R upon treatment did correlate significantly (P=0.04) with the decrease in disease activity assessed by IgG-RD RI. Conclusion. Serum sIL-2R is elevated in IgG4-RD reflecting the inflammatory process with enhanced T-cell activation. Furthermore, serum sIL-2R might serve as a potential marker of response to treatment in IgG4-RD.

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Urologic manifestations of IgG4-related disease

Revista Mexicana de Urología ◽

10.48193/rmu.v80i5.610 ◽

2020 ◽

Vol 80 (5) ◽

pp. 1-10

Author(s):

Benjamin Enrique Montaño Roca ◽

Davide Vanacore ◽

Gustavo Gallegos Sánchez ◽

César Eduardo Rosales Velázquez ◽

Guillermo Enrique Ruvalcaba Oceguera ◽

...

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Aged Patients ◽

Related Disease ◽

Igg4 Related Disease ◽

Lymphoplasmacytic Infiltrate ◽

Urinary Tract Symptoms ◽

Serum Igg4 ◽

Inflammatory Pseudotumors ◽

Clinically Significant

IgG4-related disease (IgG4-RD) is a clinical entity characterized by elevated serum IgG4 and tumor-like inflammation, with tissue infiltration by IgG4 and plasma cells. IgG4-RD is rare, but clinically significant, and its urologic manifestations have been reported in the literature. The present review covers a broad spectrum, describing the pathologies related to the area of urology. In 2003, Terumi Kamisawa was the first to recognize IgG4-RD, characterized by multiorgan lesions in patients with autoimmune pancreatitis and classified as an inflammatory and fibrotic entity with a dense lymphoplasmacytic infiltrate, positive for IgG4.(1–3) It presents in middle-aged patients, between 59-68 years of age, with no clear distribution by sex, (4–6) and has different clinical presentations. The main urologic manifestations are inflammatory pseudotumors and lower urinary tract symptoms. The present article offers a clear, general overview of the disease, encompassing its pathophysiology, diagnosis, and treatment, from the perspective of urology.

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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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Elevated Serum IgG4 Level is a Poor Predictor of the Diagnosis of IgG4-Related Disease

The American Journal of Gastroenterology ◽

10.14309/00000434-201210001-00245 ◽

2012 ◽

Vol 107 ◽

pp. S105-S106

Author(s):

Taiwo Ngwa ◽

David Murray ◽

Ryan Law ◽

Suresh Chari

Keyword(s):

Elevated Serum ◽

Serum Igg4 Level ◽

Related Disease ◽

Igg4 Related Disease ◽

Poor Predictor ◽

Serum Igg4 ◽

Igg4 Level

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IgG4-Related Disease: A Multispecialty Condition

Case Reports in Rheumatology ◽

10.1155/2014/723493 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3

Author(s):

Iuri Usêda Santana ◽

Emanuela Pimenta da Fonseca ◽

Mittermayer Barreto Santiago

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Diffuse Abdominal Pain ◽

Related Disease ◽

Igg4 Related Disease ◽

Lymphoplasmacytic Infiltrate ◽

Serum Igg4 ◽

Polyclonal Hypergammaglobulinemia ◽

History Of ◽

Systemic Condition

IgG4-related disease (IgG4-RD) is a recently recognized group of conditions, characterized by tumor-like swelling of involved organs, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, variable degrees of fibrosis, and elevated serum IgG4 concentrations. Currently IgG4-RD is recognized as a systemic condition that can affect several organs and tissues. Herein we report the case of a 34-year-old male patient who was admitted to our hospital with diffuse abdominal pain, weight loss, and painful stiffness in his neck. He had a history of tumoral mass of the left maxillary region, right palpebral ptosis with protrusion of the eyeball, and chronic dry cough for about 6 years. Laboratory tests revealed polyclonal hypergammaglobulinemia and increased serum IgG4 levels. Immunohistochemical staining of the maxillary biopsy was compatible with IgG4-RD. He had an excellent response to corticosteroid therapy. This case highlights that IgG4-RD should be included in the differential diagnosis with multisystem diseases.

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Long-term effects of intensive B cell depletion therapy in severe cases of IgG4-related disease with renal involvement

Immunologic Research ◽

10.1007/s12026-020-09163-3 ◽

2020 ◽

Vol 68 (6) ◽

pp. 340-352

Author(s):

Giacomo Quattrocchio ◽

Antonella Barreca ◽

Andrea Demarchi ◽

Roberta Fenoglio ◽

Michela Ferro ◽

...

Keyword(s):

B Cells ◽

B Lymphocyte ◽

Plasma Cells ◽

Renal Involvement ◽

Elevated Serum ◽

Long Term Effects ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Storiform Fibrosis

AbstractIgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

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