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Resumen: Objetivo: reporte de caso de enfermedad relacionada con IgG4 tratada exitosamente con azatioprina. Caso clínico: varón de 53 años con proptosis, cefalea y masa extraocular derecha visible por tomografía, el estudio anatomopatológico concluyó en enfermedad relacionada con IgG4. Se inició tratamiento con prednisona en dosis altas con descenso progresivo, añadiendo azatioprina a los 3 meses para inducción rápida de remisión. Resultados: se observó una mejoría significativa a los 6 meses de tratamiento mixto con prednisona y azatioprina, observándose ausencia de masa extraocular derecha en la resonancia magnética cerebral. Conclusiones: se puede optar por terapia doble con prednisona y azatioprina en un paciente con masa orbitaria debido a enfermedad relacionada con IgG4, ello con la intención de remisión rápida de la enfermedad. Abstract: Objective: case report of IgG4-related disease successfully treated with azathioprine. Clinical case: 53-year-old male with proptosis, headache and right extraocular mass visible by tomography, the pathological study concluded in IgG4-related disease. Treatment with high-dose prednisone was started with progressive reduction, adding azathioprine at 3 months for rapid induction of remission. Results: significant improvement was observed after 6 months of mixed treatment with prednisone and azathioprine, observing the absence of a right extraocular mass in the magnetic resonance imaging brain. Conclusions: dual therapy with prednisone and azathioprine can be chosen in a patient with an orbital mass due to IgG4-related disease, with the intention of rapid remission of the disease.

Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

IgG4-related disease (IgG4-RD) is an emerging disease concept that was first recognized in the 21st century. It has since then been attracting substantial attention in many fields of medicine as it tends to involve either synchronously or metachronously, various organs, including the pancreas, bile duct, lacrimal gland, salivary gland, and many others. This umbrella diagnosis now successfully explains a substantial number of disorders, which were previously regarded as “idiopathic.” Reports of the manifestations of IgG4-RD in the head and neck are extremely rare. Otologic manifestations have been reported, but only a handful of cases are available in literature that have been confirmed by immunohistopathology. We, herein, present a case of IgG4-RD of the middle ear, which manifested as a growth in the left mastoid and middle ear cavity, and became symptomatic with symptoms of chronic otitis media in the left ear, and was subsequently diagnosed to have IgG4-RD.

Background: IgG4-related disease (IgG4-RD) is a multi-organ immune-mediated disorder characterized by fibroinflammatory mass-forming lesions, mimicking malignancy or infection. While well-documented in salivary glands, orbit and thyroid in the head and neck, sinonasal IgG4-RD is rare. Methods: Cases of sinonasal IgG4-RD were retrieved, and clinicopathological features reviewed. Results: Seven cases of sinonasal IgG4-RD were identified over a 2-year period, including three males and four females, with an age range of 13–48 years (median: 32 years). Patients presented with cheek swelling, pain and visual disturbances. Serum IgG4 levels were mildly elevated. Storiform fibrosis, obliterative phlebitis and plasma cell infiltration were seen in varying proportions. Destruction of bone and subepithelial mucoserous glands was present. ALK-1 negativity distinguished from inflammatory myofibroblastic tumor. Conclusion: Sinonasal IgG4-RD expands the growing spectrum of IgG4-RD. A high degree of suspicion is required to include IgG4-RD in differential diagnosis of sinonasal masses, and perform detailed histological and immunohistochemical workup for accurate diagnosis. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is still an underestimated disorder which affects multiple organs, and its recognition as a distinct clinical disease has been only proved in the recent decades. The renal involvement has been documented in approximately 15% of patients with IgG4-RD, and the typical manifestation is a tubulo-interstitial nephritis. The main histological findings in IgG4-RD are typically a dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and frequently elevated IgG4 serum levels. Herein we report our atypical and peculiar clinical presentation of an IgG4-related nephropathy (IgG4-RN) and the remarkable response to rituximab (RTX) treatment at the renal imaging with computerized tomography assessment. The current nephrological evidences support the renal function recovery after steroids or steroids plus RTX therapy, even if the renal imaging data are not always shown. In a complex and enigmatic clinical scenario such as the IgG4-RN, both the renal biopsy and the renal imaging before and after the immunosuppressive therapy become mandatory tools to thoroughly define the diagnosis, the management and the response to the immunological therapy. [ABSTRACT FROM AUTHOR]

Aim: To study the clinical presentation, radiological findings, and therapy responsiveness of patients with biopsy-proven immunoglobulin G4 (IgG4)-related neurological disease. Methods: The study was conducted between January 2016 and March 2018 from the Department of Neurology and Pathology of Nizam's Institute of Medical Sciences. Patients with neurological symptoms and biopsy suggestive of IgG4-related disease (IgG4-RD) were included. These patients were studied for their demographic pattern and clinical presentation. The presence of serological markers such as vasculitic profile and IgG4 levels was analyzed. Radiological findings were studied in detail. Therapeutic agents used and the response to therapy were assessed. Results: There were six cases with IgG4-related neurological disease which were all hypertrophic pachymeningitis. The age ranged from 35 to 64 (mean = 46) years. The clinical presentation was acute in one, subacute in two, and chronic in three patients. The most common presenting symptom was headache (4), followed by gait and/or urinary disturbances (2), paraparesis (1), and diplopia (1). IgG4 levels were elevated in 50% of them. Pseudotumor-like mass and sinovenous thrombosis, not described previously, were seen in one patient. All the patients were treated with oral or intravenous steroid. Rituximab was given in three patients; azathioprine was the steroid-sparing agent in one patient. Those with acute/subacute onset of presentation had an excellent response to steroids. All the patients with a chronic duration of their symptoms received empirical anti-tuberculous therapy before a definitive diagnosis of Ig G4-RD was made. Conclusions: The characterization of patients with IgG4-related neurological disease based on the understanding of the clinical spectrum increases the confidence in the clinician to resort to early immunosuppression, thereby having prognostic implications.

Hepatic inflammatory pseudotumor (IPT) is characterized by a well-circumscribed benign tumor mimicking or often mistaken for a malignant lesion. A 48-year-old male presented to the hospital with complaints of epigastric pain, with initial laboratory findings showing mildly elevated alkaline phosphatase (140 U/L) with normal AST, ALT, bilirubin, and lipase, a CD4 count of 384, and an HIV viral load of > 10 million copies. The total IgG level was elevated to 2,228 mg/dL (normal IgG4 level 114 mg/dL). Contrast-enhanced MRI of the abdomen showed heterogeneous mass-like infiltration in the right lobe of the liver measuring 9.6 cm. The liver mass was biopsied which showed dense collagenous fibrosis with abundant lymphoplasmacytic infiltrates with 18 IgG4-positive plasma cells per high-power field. The patient was not given any treatment for this IPT. For more than 1 year of follow-up triple-phase CT scan of the liver was repeated, which showed no liver mass. As radiological images of hepatic IPTs, including IgG4-related hepatic IPT, mimic liver malignancy, histological analysis of the biopsy remains the cornerstone for the diagnosis. Symptomatic patients with IgG4-related hepatic IPT have shown improvement with corticosteroid use; however, spontaneous resolution has also been reported like in the present case.

Copyright of Medical Journal of Ankara Training & Research Hospital is the property of Medical Journal of Ankara Training & Research Hospital and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

IgG4-related disease (IgG4-RD) is an emerging disease concept that was first recognized in the 21st century. It has since then been attracting substantial attention in many fields of medicine as it tends to involve either synchronously or metachronously, various organs, including the pancreas, bile duct, lacrimal gland, salivary gland, and many others. This umbrella diagnosis now successfully explains a substantial number of disorders, which were previously regarded as "idiopathic." Reports of the manifestations of IgG4-RD in the head and neck are extremely rare. Otologic manifestations have been reported, but only a handful of cases are available in literature that have been confirmed by immunohistopathology. We, herein, present a case of IgG4-RD of the middle ear, which manifested as a growth in the left mastoid and middle ear cavity, and became symptomatic with symptoms of chronic otitis media in the left ear, and was subsequently diagnosed to have IgG4-RD. [ABSTRACT FROM AUTHOR]

A 62-year-old woman was admitted to our hospital because of fever, renal dysfunction, eosinophilia, and the presence of MPO-ANCA. Based on the renal pathological examination which showed granuloma lesion with eosinophils and crescentic glomerulonephritis, eosinophilic granulomatosis with polyangiitis (EGPA) was diagnosed. On the other hand, laboratory examination showed elevated serum IgG4 levels and renal pathological examination showed marked lymphoplasmacytic infiltration and fibrosis surrounding nest "Bird's eye pattern," which were characteristic of IgG4-related kidney disease (IgG4-RKD). Because there are cases when EGPA has clinical features of IgG4-RKD, we should be careful about diagnoses of IgG4-RKD in patients with EGPA. [ABSTRACT FROM AUTHOR]

A 39-year-old female came for evaluation for progressive lower costochondral pain and swelling with no associated systemic or constitutional symptoms and no evidence of the involvement of any other organ system. Diagnostic thoracotomy with excision of involved rib and costochondral junction showed plasma cell-rich chronic inflammation with foci of fibrosis with no definite storiform fibrosis or obliterative phlebitis. Immunohistochemistry showed 30%–40% immunoglobulin G4 (IgG4)-positive cells/hpf with an IgG:IgG4 ratio of 30% with sterile cultures and no elevation of serum IgG4 levels. With a presumptive diagnosis of IgG4-related disease, she was started on steroids with which she had complete symptom relief and resolution of the lesion. This case highlights the importance of considering the diagnosis of IgG4 disease even in the absence of typical histopathological findings and elevated serum IgG4 levels. The authors have not found any prior reports in the English literature of IgG4 disease of the ribs and costochondral junction.

Aim: To study the clinical presentation, radiological findings, and therapy responsiveness of patients with biopsy-proven immunoglobulin G4 (IgG4)-related neurological disease. Methods: The study was conducted between January 2016 and March 2018 from the Department of Neurology and Pathology of Nizam's Institute of Medical Sciences. Patients with neurological symptoms and biopsy suggestive of IgG4-related disease (IgG4-RD) were included. These patients were studied for their demographic pattern and clinical presentation. The presence of serological markers such as vasculitic profile and IgG4 levels was analyzed. Radiological findings were studied in detail. Therapeutic agents used and the response to therapy were assessed. Results: There were six cases with IgG4-related neurological disease which were all hypertrophic pachymeningitis. The age ranged from 35 to 64 (mean = 46) years. The clinical presentation was acute in one, subacute in two, and chronic in three patients. The most common presenting symptom was headache (4), followed by gait and/or urinary disturbances (2), paraparesis (1), and diplopia (1). IgG4 levels were elevated in 50% of them. Pseudotumor-like mass and sinovenous thrombosis, not described previously, were seen in one patient. All the patients were treated with oral or intravenous steroid. Rituximab was given in three patients; azathioprine was the steroid-sparing agent in one patient. Those with acute/subacute onset of presentation had an excellent response to steroids. All the patients with a chronic duration of their symptoms received empirical anti-tuberculous therapy before a definitive diagnosis of Ig G4-RD was made. Conclusions: The characterization of patients with IgG4-related neurological disease based on the understanding of the clinical spectrum increases the confidence in the clinician to resort to early immunosuppression, thereby having prognostic implications. [ABSTRACT FROM AUTHOR]

Awareness of the uncommon associated clinical manifestations of immunoglobulin G4 (IgG4)-related kidney disease is essential for the early diagnosis and effective treatment of patients. To the best of our knowledge, there have been few reports of patients with IgG4-related kidney disease associated with autoimmune hemolytic anemia. We here report a rare case of IgG4-related kidney disease associated with autoimmune hemolytic anemia. A 70-year-old man with kidney dysfunction and severe anemia had been diagnosed with chronic kidney disease and treated without any improvement. On admission, he had a high serum creatinine level, low hemoglobin level, positive direct Coombs test, and mild proteinuria. Serum IgG and IgG4 were elevated. Kidney biopsy showed marked infiltration of IgG4-positive plasma cells and storiform fibrosis in the interstitial compartment, which confirmed the diagnosis of IgG4-related kidney disease. Corticosteroid therapy was initiated, and subsequently, the kidney dysfunction and anemia dramatically improved. [ABSTRACT FROM AUTHOR]

A 62-year-old woman presented with a one month history of a hard, nonmobile subcutaneous mass along the right nasojugal fold. Hematological studies showed elevated serum immunoglobulin G4 levels. Histopathological examination of the biopsy sample disclosed immunoglobulin G4-positive lymphoplasmacytic infiltration with a storiform fibrosis, vein occlusion, and epithelioid granulomas with necrosis. Systemic review corresponded to a sarcoidosis. Without treatment, the eyelid mass did not recur six months after the excisional biopsy. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) includes a wide spectrum of inflammatory and fibrous procedures that affect a variety of issues and organs and are accompanied by elevated serum IgG4 levels. The clinical presentation is quite heterogeneous as almost every organ can be influenced. Clinical, laboratory and histopathological features and criteria must be taken into account and both malignancies (solid tumors and lymphomas) and benign disorders be excluded for the diagnosis to be established. Intrathoracic involvement in IgG4-RD varies and includes the lung parenchyma causing nodules, masses, ground-glass opacities, infiltrates resembling consolidation and thickened bronchovascular bundles, the central airways resulting in stenosis, obstruction and bronchiectasis as well as the pleura with effusion and nodular lesions and the mediastinum. Hilar and mediastinal lymphadenopathy are the most common intrathoracic manifestation while fibroid mediastinitis is much more rare. Corticosteroids are the cornerstone of therapy and most of cases present complete or partial response. However, rates of recurrence after treatment termination are high. In addition, patients may develop IgG4-related extrathoracic disease during the next months or even years after the initial diagnosis. [ABSTRACT FROM AUTHOR]

An 81-year-old woman was referred to nephrology for a follow-up on progressive chronic kidney disease. She has a past medical history of hypertension, T2DM, breast cancer, and secondary hyperparathyroidism related to renal disease. A renal biopsy showed patchy interstitial fibrosis and tubular atrophy with an increased number of IgG4-positive plasma cells. A diagnosis of IgG4-related kidney disease was made based on clinical presentation and pathology. The patient ultimately required the initiation of hemodialysis, despite the administration of steroids and rituximab., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nguyen et al.)

Immunoglobulin G4-related disease (IgG4-RD) is characterized by extensive infiltration of IgG4+ plasma cells and fibrosis in various organs. However, the involvement of the ovary in IgG4-RD has never been reported. A 59-year-old woman presented with urinary retention. Magnetic resonance imaging and computed tomography revealed a huge multinodular pelvic mass and common iliac/para-aortic lymph node swelling. A laparotomy was performed under the suspicion of advanced ovarian cancer, and the pelvic mass was identified as ovary in origin. Histopathology of the excised tumor revealed massive lymphoplasmacytic infiltration (>90% were IgG4+ plasma cells), storiform fibrosis, and obliterative phlebitis; thus leading to a diagnosis of IgG4-RD. We conclude that IgG4-RD can present as a bilateral ovarian mass along with lymphadenopathy, therefore mimicking ovarian cancer. [ABSTRACT FROM AUTHOR]

IgG4 cholangiopathy is a recently described distinctive type of hepatobiliary manifestation of IgG4-related disease. This is often misdiagnosed as a malignancy of the hepatobiliary system on clinical presentation and imaging. Accurate diagnosis is crucial for appropriate management. Histopathology provides crucial information and is characterized by IgG4-positive lymphoplasmacytic infiltration with storiform fibrosis and obliterative phlebitis. We present the clinicopathological spectrum of a retrospective series of 6 cases of IgG4 cholangiopathy that clinically masqueraded as hepatobiliary malignancies. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 - related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder. Although patients have been described more then 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. IgG4-RD can affect any organ such as salivary glands, orbits, retroperi-toneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative flebitis, are found in IgG4-RD biopsies. Elevated serum IgG4 levels are found in many but not all patiens. Treatment is based on clinical experience. Glucocorticoids are the mainstay of therapy, although adjunctive immu-nosuppressive agents are used in relapsing patient. [ABSTRACT FROM AUTHOR]

Objectives. Our study aimed to clarify the immunological characteristics and the mechanism of interstitial fibrosis in immunoglobulin G4-related kidney disease (IgG4-RKD) by the immunohistological analysis. Methods. Immunohistological study was performed in the biopsied renal tissues of 16 IgG4-RKD, 16 Sjögren syndrome (SJS), and 17 idiopathic tubulointerstitial nephritis (ITIN) patients using antibodies against IgG; IgG1; IgG4; CD38; CD3; C-X-C chemokine receptor type 3 (CXCR3); chemokine (C-C motif) receptor 4 (CCR4); forkhead box 3 (Foxp3); Type I, Type III, Type IV, and Type VI collagens; and transforming growth factor (TGF)-β1. Results. Interstitial lymphoplasmacytic and eosinophilic infiltration and the severity of interstitial fibrosis were greater in IgG4-RKD than SJS and ITIN. The ratio of CXCR3+/CD3 + cells was greater in SJS as compared with that in IgG4-RKD and ITIN. The ratio of CCR4+/CD3 + cells was not different among the three diseases. The ratio of interstitial IgG4+/IgG+ plasma cells, Foxp3+/CD3 + cells, and TGF-β1 + cells/total infiltrating cells was higher in IgG4-RKD than SJS and ITIN. There was a positive correlation between the ratio of Foxp3+/CD3 + cells and that of IgG4+/IgG+ plasma cells in IgG4-RKD. Significant correlation was found between the ratio of Foxp3+/CD3 + cells and that of TGF-β1 + cells/total infiltrating cells in IgG4-RKD. Foxp3 + cells and TGF-β1 + cells were colocalized in the interstitium in IgG4-RKD. The significant correlation between the ratio of TGF-β1 + cells/total infiltrating cells and the severity of fibrosis was noticed in IgG4-RKD. The interstitial distribution of type III collagen and type IV collagen was higher in IgG4-RKD than in SJS. Conclusions. Our results suggest that regulatory T-cells (Tregs) may play a central role in IgG4 production in the interstitium and TGF-β1 induced by Tregs may play a pivotal role in the interstitial fibrosis including type III and type IV collagens in IgG4-RKD. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is defined as a multi-organ systemic disorder with typical pathological findings affecting a wide range of organ systems and elevated IgG4 levels. The disease unifies a large number of clinical diagnoses previously considered as being confined to single organ systems. In recent years under the leadership of Japanese researchers a new nomenclature as 'IgG4-related disease' was endorsed uniting the different organ involvements and diagnostic criteria have been defined. Typical histopathologic manifestations are lymphoplasmacytic infiltrate composed of IgG4+ plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The pathophysiology of the disease still remains controversial, including the natural history of the disease, the pathogenic role of IgG4, and its use as a biomarker. Although elevated autoreactive IgG4 antibodies are observed, there is no evidence that they are directly pathogenic. Glucocorticoids constitute the primary treatment option and the response is generally good. Treatment with steroids often decreases serum levels of IgG4 and tissue levels of IgG4+ plasma cells. In cases either refractory to steroids or resistant to dose reduction of steroids immunosuppressive therapy such as azathioprine or mycophenolate mophetil may be considered. In patients with recurrent or refractory disease, rituximab or bortezomib treatment is also recommended. [ABSTRACT FROM AUTHOR]

IgG4 related disease is a fibro‑inflammatory condition with involvement of renal and extra renal organs, characterized by lymphoplasmacytic infiltration with organ dysfunction. We describe three cases of IgG4 related renal disease from a tertiary care hospital in south India. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder (ORPHA284264). Although patients have been described more than 100 years ago, the systemic nature of this disease has been recognized in the 21st century only. Type 1 autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD. Typically, lymphoplasmacellular inflammation, storiform fibrosis and obliterative phlebitis are found in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Consequently, diagnostic criteria for IgG4-RD have been proposed recently. Treatment is largely based on clinical experience and retrospective case series. Glucocorticoids are the mainstay of therapy, although adjunctive immunosuppressive agents are used in relapsing patients. This review summarizes current knowledge on clinical manifestations, pathophysiology and treatment of IgG4-RD. [ABSTRACT FROM AUTHOR]

IgG4 interstitial nephritis is a recently described entity. A middle-aged gentleman with bilateral parotid enlargement, hepatosplenomegaly and generalized lymphadenopathy was referred to us for evaluation of renal failure. He had trace proteinuria and large kidneys. Kidney biopsy revealed interstitial nephritis with characteristic storiform fibrosis. Immunohistochemistry demonstrated intense staining for IgG4-secreting plasma cells in the interstitium. [ABSTRACT FROM AUTHOR]

Background IgG4-related disease is a multi-organ disorder characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive cells into affected organs. In routine studies, however, IgG subclasses are not estimated. In the present study, we attempted to clarify the light-microscopic characteristics of IgG4-related tubulointerstitial nephritis (TIN) to facilitate distinction from non-IgG4-related TIN in specimens obtained by renal biopsy using routine staining. Methods In specimens from 34 cases of TIN (13 IgG4-related and 21 non-IgG4-related), 9 nephrologists independently reviewed the following histological features of interstitial lesions: (i) cell infiltration extending into the renal capsule, (ii) cell infiltration into the renal medulla, (iii) regional lesion distribution, (iv) lymphoid follicles, (v) granulomatous lesions, (vi) necrotizing angiitis, (vii) eosinophil infiltration, (viii) neutrophil infiltration, (ix) tubulitis, (x) peritubular capillaritis, (xi) storiform fibrosis and (xii) the stage of interstitial fibrosis. The modified nominal group technique was applied to obtain a consensus in the pathological interpretation. Results Consensus was successfully attained among the diagnosticians for all but one pathological feature (regional lesion distribution). Storiform fibrosis was demonstrated in 12 of 13 (92.3%) cases of IgG4-related TIN but in none of the cases of other types of TIN. Cell infiltration extending into the renal capsule was also observed only in IgG4-related TIN. Conversely, neutrophil infiltration, severe tubulitis, severe peritubular capillaritis, granulomatous lesions and necrotizing angiitis were evident only in non-IgG4-related TIN. Conclusions This study revealed some useful and characteristic features for distinguishing IgG4-related from non-IgG4-related TIN on the basis of light-microscopic observation. [ABSTRACT FROM PUBLISHER]

The rapidly emerging disorder now known as IgG-related disease (IgG-RD) includes a variety of clinical entities once regarded as being entirely separate diseases. Manifestations of IgG-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-positive plasma cells, modest tissue eosinophilia, and extensive fibrosis. Tumorous swelling and obliterative phlebitis are other frequently observed features. Polyclonal elevations of serum IgG 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-RD. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition that may involve any organ in the body, including the kidneys. However, renal parenchymal lesions are not seen frequently and the treatment strategy remains unclear. We describe a case of IgG4-related renal mass, which resolved spontaneously. The patient presented with right loin pain, constitutional symptoms and raised inflammatory markers. Magnetic resonance imaging (MRI) showed a large infiltrative mass centered on the right renal hilum and biopsy demonstrated histological changes in keeping with IgG4-RD. A careful 'watch-and-wait' approach was taken and at six months following initial presentation, the patient's symptoms had fully resolved and inflammatory markers had normalised. Repeat MRI showed almost complete resolution of the mass. We propose that a careful 'watch- and-wait' approach could be considered as an alternative to immune suppression for IgG4-related renal masses, especially if they are not causing symptoms or organ compromise. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease (IgG4-RD) is a rare immune-mediated disease affecting multiple organs and tissues. There is often the presence of elevated serum Ig4 subtype with histological evidence of lymphoplasmacytic infiltration, fibrosis, and phlebitis. The mainstay of treatment is steroids therapy. We report the case of a 66-year-old man presenting with acute on chronic renal failure and pulmonary nodules seen on PET-CT scan. He also had elevated serum IgG4 subclass and histological features in keeping with IgG4-RD. He failed steroid therapy but responded subsequently to rituximab with complete resolution of his symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Osuorji et al.)

IgG4 related disease (igG4-RD) is a pathological process which integrates a large number of diseases of unknown pathogenesis, considered as being exclusive to many different organs. Diagnosis is established through histological, radiological and serological criteria. Treatment is based on long term corticosteroids; rituximab being used only in refractory cases. It is unusual for this entity to be found exclusively in the head and neck, without systemic involvement; there are only a few reported cases to date. We present a case of a nasosinusal IgG4-RD orbital tumor with paranasal sinus involvement. The accurate diagnosis made early onset corticosteroid treatment possible and the patient is currently asymptomatic., (Copyright © 2018 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Hypocomplementemia has been frequently reported in immunoglobulin G4-related kidney disease (IgG4-RKD). However, studies on the role of complement system in IgG4-RKD are lacking. A total of 40 429 renal biopsies from January 2010 to January 2018 were reexamined in the present study, and 17 patients were confirmed to meet the criteria of IgG4-RKD. According to the serum C3 levels, they were divided into 2 groups: the low-C3 group (C3 <0.8 g/L, n = 7) and the normal-C3 group (C3 ≥0.8 g/L, n = 10). Compared with the normal-C3-level group, the patients in the low-C3-level group had lower serum C4 concentrations (P = .025), higher serum IgG4 concentrations (P = .003), higher positive rates in rheumatoid factor (P = .033), more severe storiform fibrosis (P = .007) at diagnosis, and higher blood urea nitrogen levels at the latest test (P = .04). The serum levels of C3 were in negative correlation with the serum levels of IgG4 (P = .003), the levels of rheumatoid factor (P = .002), renal deposition of C1q (P = .028), storiform fibrosis (P < .001), scores of interstitial fibrosis (P = .015), the amount of renal IgG4-positive (IgG4 + ) plasma cells (P = .020), the ratios of IgG4 + plasma cells/CD138 + cells (P = .018), and the blood urea nitrogen concentrations at the last test (P = .023). Our study shows that IgG4-RKD is a relatively rare entity. Complement system may participate in the development of IgG4-RKD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This review will encompass definition, pathogenesis, renal clinical manifestations and treatment of immunoglobulin G4-related diseases (IgG4-RDs). IgG4-RD is a recently recognized clinical entity that often involves multiple organs and is characterized by high levels of serum immunoglobulins G4, dense infiltration of IgG4 + cells and storiform fibrosis. Cellular immunity, particularly T-cell mediated immunity, has been implicated in the pathogenesis of IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulopathy and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining, typical radiological findings and an appropriate clinical context. The first line treatment is the steroids with two warnings: Steroid resistance and relapse after discontinuation. In the case of steroid resistance, B cell depleting agents as rituximab represent the second-line treatment. In the case of relapse after discontinuation, steroid treatment may be associated with steroid sparing agents. Since the disease has been only recently identified, more prospective, long-term studies are needed to an improved understanding and a more correct and safe treatment., Competing Interests: Conflict-of-interest statement: The authors do not have any conflict of interest in relation to the manuscript, as in the attached form.

IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and III), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, α-smooth muscle actin-positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, "interstitial fibrosclerosis" would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)