scholarly journals Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kazuichi Okazaki ◽  
Hisanori Umehara
Keyword(s):  
Diagnostic Criteria ◽  
Plasma Cells ◽  
Elevated Serum ◽  
Serum Levels ◽  
Mikulicz’S Disease ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Biopsy Specimens ◽  
Organ Specific ◽  
Low Sensitivity

Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team) and the other from lymph proliferation (Umehara team) supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC) for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP), compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease) and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.

IgG4-related Diseases Including Mikulicz’s Disease and Sclerosing Pancreatitis: Diagnostic Insights

2010 ◽  
Vol 37 (7) ◽  
pp. 1380-1385 ◽  
Author(s):  
YASUFUMI MASAKI ◽  
SUSUMU SUGAI ◽  
HISANORI UMEHARA
Keyword(s):  
Differential Diagnosis ◽  
Plasma Cells ◽  
Elevated Serum ◽  
Treatment Strategies ◽  
Mikulicz’S Disease ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4 ◽  
Sclerosing Pancreatitis ◽  
Systemic Condition

Since the first report of serum IgG4 elevation in sclerosing pancreatitis in 2001, various systemic disorders have been reported to elevate IgG4, and many names have been proposed from the perspective of the systemic condition. Despite similarities in the organs damaged in IgG4-related Mikulicz’s disease and Sjögren’s syndrome, there are marked clinical and pathological differences between the 2 entities. The majority of cases diagnosed with autoimmune pancreatitis in Japan are IgG4-related sclerosing pancreatitis, and it should be recognized that this is distinct from the Western type. Diagnosis of IgG4-related disease is defined by both elevated serum IgG4 (> 1.35 g/l) and histopathological features, including lymphocyte and IgG4+ plasma cell infiltration (IgG4+ plasma cells/IgG+ plasma cells > 50% on a highly magnified slide checked at 5 points). Differential diagnosis from other distinct disorders is necessary: these include sarcoidosis, Castleman’s disease, Wegener’s granulomatosis, lymphoma, cancer, and other existing conditions. The Japanese IgG4 research group has begun multicenter prospective studies to improve diagnostic criteria and treatment strategies.

scholarly journals A Case Report of an Atypical Presentation of IgG4-Related Disease and Idiopathic CD4 Lymphocytopenia

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Francesco Rapisarda ◽  
Luca Zanoli ◽  
Grazia Portale ◽  
Salvo Scuto ◽  
Pietro Castellino
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Plasma Cells ◽  
Elevated Serum ◽  
Serum Levels ◽  
Temporal Association ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
First Case ◽  
Idiopathic Cd4 Lymphocytopenia

The IgG4-related disease is a fibroinflammatory disease characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum levels of IgG4. Idiopathic CD4 lymphocytopenia is a heterogenic and rare syndrome characterized by the detection of a persistent absolute CD4 T cells count <300 cells/mm3(or <20% of total T cells) in more than one occasion and no evidence of HIV infection in absence of immunodeficiency or therapy associated with depressed levels of CD4 T cells. We report the case of a 50-year-old man with a multiorgan IgG4-related disease presenting in a temporal association with a profound and symptomatic idiopathic CD4 lymphocytopenia. Both clinical pictures improved after steroid treatment. Idiopathic CD4 lymphocytopenia has been associated with a number of autoimmune conditions but, to the best of our knowledge, this is the first case in which an association with the IgG4-related disease is reported.

scholarly journals Orbital Pseudotumor: Uncommon Initial Presentation of IgG4-Related Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Teresa Carbone ◽  
Ricardo Azêdo Montes ◽  
Beatriz Andrade ◽  
Pedro Lanzieri ◽  
Luis Mocarzel
Keyword(s):  
Elderly Patient ◽  
Plasma Cells ◽  
Elevated Serum ◽  
Lymphocytic Infiltration ◽  
Serum Levels ◽  
High Serum ◽  
Orbital Pseudotumor ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Igg4

IgG4-related disease (IgG4-RD) encompasses a group of fibroinflammatory conditions recognized in recent times. The main clinical features include variable degrees of tissue fibrosis, tumorlike expansions, perivascular lymphocytic infiltration rich in IgG4-positive plasma cells, and elevated serum IgG4. A case has been reported of an elderly patient with an unexplained unilateral exophthalmia; biopsy was performed and revealed lymphocytic infiltration, suggesting IgG4-RD. High serum levels of IgG4, in association with a good response to steroid therapy and to the exclusion of other diagnoses, confirmed the hypothesis of orbital pseudotumor by IgG4-RD.

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

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
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.

scholarly journals Hyper IgG4-Related Disease Presenting with Orbital Tumor and Immune Deficiency

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Caroline G. Olson ◽  
Nancy Y. Olson
Keyword(s):  
Plasma Cells ◽  
Elevated Serum ◽  
Pelvic Mass ◽  
Lymphocytic Infiltration ◽  
Orbital Mass ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
New Development ◽  
Initial Improvement ◽  
Functional Antibodies

We report a case of IgG4-RD in a patient with high IgG4 levels, low functional antibodies, and low IgM levels. He presented with bilateral orbital pseudotumors and, after initial improvement on corticosteroids, relapsed with recurrent pleural effusion and pelvic pseudotumor. He had a grossly elevated serum IgG (1905 mg/dl) with elevations in all IgG subclasses but marked elevation in IgG4 (412 mg/dl), low IgM, and low pneumococcal antibodies. Orbital mass biopsy showed polyclonal lymphocytic infiltration and increased IgG4 plasma cells. The patient was started on prednisone and tried several immunosuppressive medications including mycophenolate mofetil, methotrexate, hydroxychloroquine, and azathioprine with decrease in size of the orbital pseudotumor. During a period when the patient stopped his medications, the pseudotumor enlarged with new development of recurrent pleural effusions. He was also found to have a pelvic mass that was biopsy positive for IgG4 proliferation. This case with progression to multiorgan involvement highlights the importance of identifying patients with IgG4-related disease. In contrast to previous cases with normal-to-high IgM, the IgM was low with impaired functional antibodies.

scholarly journals Urologic manifestations of IgG4-related disease

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. 

scholarly journals Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Tobias Peikert ◽  
Bijayee Shrestha ◽  
Marie Christine Aubry ◽  
Thomas V. Colby ◽  
Jay H. Ryu ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Plasma Cells ◽  
Immunosuppressive Agents ◽  
Granulomatous Disease ◽  
Obliterative Phlebitis ◽  
Fibrosing Mediastinitis ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

Fibrosing mediastinitis (FM) and IgG4-related disease (IgG4-RD) are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases). We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted.

scholarly journals IgG4-Related Disease: A Multispecialty Condition

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.

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

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.

scholarly journals AB0760 HIGH SERUM IGA LEVELS HAVE LIMITED CLINICAL SIGNIFICANCE IN PATIENTS WITH IGG4-RELATED DISEASE DIAGNOSED BY EXPERTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1407.2-1407
Author(s):  
S. Tsuge ◽  
I. Mizushima ◽  
S. Shin ◽  
T. Yoshinobu ◽  
R. Hoshiba ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Clinical Course ◽  
Elevated Serum ◽  
High Serum ◽  
Classification Criteria ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Serum Iga ◽  
Organ Specific ◽  
Serum Crp

Background:While the diagnostic and classification criteria for IgG4-related disease (IgG4-RD) have been recently developed [1-3], it is known that, without appropriate exclusions, some non-IgG4-RDs may meet these criteria. In particular, hyper IL-6 syndromes, including Castleman disease, can be misdiagnosed as IgG4-RD. Some clinical findings, including elevated serum levels of C-reactive protein (CRP) or IgA, have been suggested to be useful for differentiating hyper IL-6 syndromes from IgG4-RD [4]. However, since few clinical studies have focused on IgG4-RD with high serum IgA levels, its clinical significance has not been well known.Objectives:This study aimed to clarify the clinical significance of high serum IgA levels in patients with IgG4-RD.Methods:We retrospectively investigated the clinical features of 170 patients with IgG4-RD on the basis of the presence or absence of elevated serum IgA levels (>410 mg/dL) at the time of diagnosis. The diagnosis of IgG4-RD was made by experts on the basis of the fulfillment of the comprehensive diagnostic criteria and/or each organ-specific diagnostic criteria.Results:Elevated serum IgA levels were observed in 18 patients (10.6%). In the patients with elevated serum IgA levels, serum CRP levels were higher (1.14 ± 1.18 vs. 0.31 ± 0.63 mg/dL, p=0.003) and the prevalence of relapse during the clinical course was lower (5.6% vs. 27.6%, p=0.046) than in those without elevated serum IgA levels. However, there were no significant differences in the other clinical features including the number of involved organs (2.4 ± 1.3 vs. 2.8 ± 1.6, p=0.443) and inclusion scores of the ACR/EULAR classification criteria (32 ± 14 vs. 36 ± 17, p=0.374). To evaluate the influence of serum IgA elevation on relapse, we performed Cox regression analysis, which showed that the elevated serum IgA levels had no significant association with lower incidence of relapse but a tendency of it (hazard ratio 0.997, 95% confidence interval 0.994-1.000, p=0.055) during the clinical course. In addition, a prompt improvement in the IgG4-RD responder index [5] during the clinical course was seen in the patients with serum IgA elevation, suggesting a similar good response to glucocorticoids as in those without it.Conclusion:The findings of the present study suggest that IgG4-RD patients with high serum IgA levels can be diagnosed and treated in the same way as those without it, although they may be characterized by mild serum CRP elevation.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;79:77-87.[2]Umehara H et al. The 2020 Revised Comprehensive Diagnostic (RCD) Criteria for IgG4-RD. Mod Rheumatol. 2020 Dec 4:1-14. doi: 10.1080/14397595.2020.1859710. Online ahead of print.[3]Umehara H et al. Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive diagnostic and organ - specific criteria. Mod Rheumatol. 2017;27:381-91.[4]Sato Y et al. Systemic IgG4-related lymphadenopathy: A clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol.2009;22:589-99.[5]Carruthers MN et al. Development of an IgG4-RD Responder Index. Int J Rheumatol. 2012;2012:259408.Disclosure of Interests:None declared

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