Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report.

BACKGROUND: Immunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly manifests as a tubulointerstitial nephritis and is associated with glomerular disease in a proportion of cases. Membranous nephropathy is the most frequent glomerular lesion. Herein, we report the first documented case of immunoglobulin G4-related disease presenting with nephrotic syndrome owing to minimal change disease. CASE PRESENTATION: A 67-year-old South Asian male presented to our service with systemic upset and leg swelling. He had heavy proteinuria (urine protein:creatinine ratio 1042 mg/mmol) and was hypoalbuminemic (17 g/L) and hypercholersterolemic (9.3 mmol/L), consistent with the nephrotic syndrome. His serum creatinine was 140 µmol/L, and he was hypocomplementemic (C3 0.59 g/L, C4 < 0.02 g/L) with raised immunoglobulin G4 subclass levels (5.29 g/L). Kidney biopsy demonstrated minimal change disease alongside a plasma-cell-rich tubulointerstitial nephritis with strong positive staining for immunoglobulin G4. A diagnosis of minimal change disease in the setting of immunoglobulin G4-related disease was made. He was commenced on oral prednisolone at 60 mg daily but suffered infectious complications, including necrotizing fasciitis within 3 weeks of starting treatment, ultimately resulting in his death 52 days after initial presentation. CONCLUSION: This case highlights the potential for immunoglobulin G4-related disease to be associated with a spectrum of glomerular pathologies including minimal change disease. It adds to the differential diagnosis of secondary causes of minimal change disease, and moreover, aids as an important reminder of the potential complications of high-dose steroids used in its treatment.

[Salivary gland disorder: consider IgG4-related disease]. / Speekselklierafwijking: denk aan IgG4-gerelateerde ziekte.

A 73-year-old man was presented with painless, bilateral swelling of the submandibular salivary glands and unilateral swelling of the parotid gland on the right side, and complaints of dry mouth. A parotid biopsy was taken and a serologic exam was carried out, resulting in the diagnosis of IgG4-related disease. IgG4-related disease is a rare systemic disorder that can cause symptoms in the head and neck region. Usually there are complaints of bilateral, painless swelling of the submandibular, parotid and/or lacrimal glands, with or without complaints of dryness of the mouth and eyes.

Case of IgG4-related Disease with Crescentic Glomerulonephritis: An Unusual Presentation of the Disease.

IgG4-related disease (IgG4-RD) is a chronic systemic inflammatory  disease, characterized by tissue infiltration of lymphocytes and  IgG4-secreting plasma cells, presenting by fibrosis of different  tissues, which is usually responsive only to oral steroids therapy.  Kidneys are the most commonly involved organs, exhibiting renal  insufficiency, tubulointerstitial nephritis, and glomerulonephritis.  Here, we describe a patient with acute renal insufficiency who  was presented with edema, weakness, anemia and multiple  lymphadenopathies. Kidney and lymph node biopsy showed  crescentic glomerulonephritis in kidneys and lymphoplasmacytic  infiltration in lymph nodes. After a course of treatment with an  intravenous pulse of corticosteroid and cyclophosphamide, the  patient's symptoms subsided, and kidney function improved. DOI: 10.52547/ijkd.7788.

Adult ocular adnexal xanthogranulomatous disease associated with immunoglobulin G4-related disease: an unusual association.

Adult-onset xanthogranuloma (AOX) and immunoglobulin G4-related disease (IgG4-RD) are uncommon fibrosing conditions that may exhibit localized ocular manifestations and occasionally systemic symptoms. These conditions exhibit overlapping clinical and histological features, suggesting a potential correlation between them, although their exact relationship remains unclear. This paper presents the case of a black male patient exhibiting typical histological indications of both AOX and IgG4-RD. The patient responded positively to corticosteroid treatment.

A case with multiple nodules and mucosal oedema of the trachea and both bronchi induced by IgG4-related disease.

BACKGROUND: IgG4-related disease is a systemic fibroinflammatory disease that is mainly seen in older men, and involves multiple organs, such as the pancreas and lungs. However, 75% of patients with IgG4-related lung disease are asymptomatic (if they are symptomatic, they mainly complain of nasal congestion, rhinorrhoea, chest pain, and cough) and are incidentally diagnosed through chest computed tomograph. Although, nodules in the airway and bronchial wall thickening are criteria for diagnosis, it is important that nodules have been reported in peripheral airways in several cases and rarely in the central airway. CASE PRESENTATION: A 74-year-old woman previously diagnosed with Mikulicz's disease presented with swelling of the eyelid margin on both sides and visual disturbances. Computed tomography revealed extensive multiple nodules and mucosal oedema of the trachea and both bronchi. On flexible bronchoscopy under local anaesthesia, extensive lesions were observed from the middle of the trachea to the carina, extending into both segmental bronchi. The nodules were continuous with the normal respiratory tract mucosa, and the surfaces were smooth with minimal neovascularisation. Due to the solid nature of the lesion, obtaining an adequate amount of specimen was challenging. Therefore, we used a 1.9 mm cryoprobe under intubation, resulting in minimal bleeding. Subsequently, the patient was diagnosed with IgG4-related lung disease. CONCLUSIONS: The present case is very rare because of the presence of multiple nodules, severe mucosal edema of the central airway and the absence of mediastinal lymphadenopathy, ground glass nodules, and lung masses. Therefore, it is important to consider differential diagnoses. Thus, we emphasise the importance of endobronchial cryobiopsy for obtaining an adequate number of tissue specimens in such cases to establish a definitive pathological diagnosis.

IgG4-related Orbital Disease Presenting as an Orbital Apex Lesion.

IgG4-related disease is an uncommon multisystem inflammatory disease characterized by tissue infiltration by IgG4 plasma cells, extensive fibrosis, and sclerosing inflammation. Diffuse orbital involvement extending to the orbital apex and cavernous sinus has been reported, but a solitary well-circumscribed lesion at the apex has not been previously reported. Herein, we report a unique case of IgG4-related orbital disease presenting as a solitary well-circumscribed orbital apex lesion causing subacute visual decline in a 45-year-old male. MRI demonstrated bilateral lacrimal gland and infraorbital nerve enlargement and an 18 × 7 mm left orbital apex lesion demonstrating homogeneous contrast enhancement and isointense signal on T2. He was initially treated with tapering systemic corticosteroid therapy with improvement in his vision; however, he experienced visual deterioration 3 months later with recurrent inflammation. He subsequently commenced high-dose systemic corticosteroid therapy and rituximab infusions with improvement of left visual acuity to 6/7.5 + 2.

IgG4 disease with multiorgan involvement: a case report.

BACKGROUND: IgG4-related disease (IgG4RD) is a rare fibroinflammatory disease with multiorgan involvement. It presents insidiously over several years and can be a diagnostic enigma. Delays in diagnosis occur due to failure to consider IgG4 as a differential diagnosis, atypical presentations, and an insidious clinical course. CASE PRESENTATION: We report the case of a 70-year-old Sri Lankan man with pulmonary, renal, and neurological involvement of IgG4-related disease. Clinical manifestations evolved over a 4-year period and included exertional shortness of breath and dysesthesia of extremities. The diagnosis was established with clinical, radiological, and pathological criteria laid down by The American College of Rheumatology/European League Against Rheumatism in 2019. Following diagnosis, the patient was started on oral steroids, with rapid improvement of his respiratory and neurological symptoms. He is currently under follow-up and will be monitored with clinical and radiological parameters, complement levels, and lung function tests. CONCLUSION: This case outlines the presentation of a patient with IgG4-related disease with concurrent involvement of three uncommon sites. It highlights methods of diagnostic deduction by considering the clinical course of illness, imaging, and histopathology. It also describes evolving associations of IgG4-related disease with tuberculosis and lymphomas, which bear important diagnostic and therapeutic considerations.

PLA2R-positive membranous nephropathy in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases. CASE PRESENTATION: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy. CONCLUSIONS: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Immunoglobulin G4-Related Disease Complicating Ruptured Isolated Iliac Artery Aneurysm: A Complex Management Dilemma.

BACKGROUND Managing IgG4-related disease (IgG4-RD) in the context of vascular complications, such as aneurysms, poses significant challenges, particularly when considering surgical intervention options. The risk of rupture and infection in patients on long-term glucocorticoid therapy complicates treatment decisions. CASE REPORT A 63-year-old woman with a history of IgG4-RD presented with a ruptured right iliac artery aneurysm. She was on long-term oral glucocorticoid therapy. Initial emergency endovascular stent graft implantation was followed by embolization for suspected arterial bleeding and subsequent Salmonella bacteremia. Repeated hospitalizations involved stent graft removal and surgical repair due to persistent infection. Over 2 years, the patient required multiple pelvic drainages and long-term antibiotic and prednisolone therapy, yet her quality of life remained compromised. CONCLUSIONS Our case highlights the unique challenges and considerations in the treatment of IgG4-related aneurysms. Patients with IgG4-RD who are on long-term oral glucocorticoids have an inherent risk of aneurysm rupture. We believe regular follow-ups to monitor the progression of the aorta and iliac arteries into aneurysms are essential. For patients who have developed aneurysms, it is advisable to reduce the dosage of glucocorticoids or even consider surgical treatment as soon as possible. As for the choice of surgical method, there is no consensus yet. While endovascular treatment is less invasive and quicker, it can increase the risk of rupture and bleeding. Open surgery might be a better option. More data are needed to make a definitive judgment.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.

IgG4-related disease presenting as severely symptomatic hypercalcemia: A case report and review of literature.

Immunoglobulin G4-related disease (IgG4-RD)-associated hypercalcemia has rarely been reported. We report a case of IgG4-RD that presented as severe symptomatic hypercalcemia. A 50-year-old woman with a history of sustained bilateral periorbital swelling and proptosis for more than 5 years presented to our hospital complaining of a 3-day history of significant and progressive nausea, vomiting, loss of appetite, fatigue, and pruritus. She denied a long history of medication. On admission, laboratory tests showed severe hypercalcemia with serum adjusted calcium elevated to 4.34 mmol/L and renal dysfunction with serum creatinine elevated to 206 µmol/L. Urinary calcium excretion was increased. The serum IgG4 subclass was markedly elevated to 22.4 g/L with polyclonal hypergammaglobulinemia. Tests of autoantibodies were all negative. Bone metabolism markers that reflect the activity of osteoblasts and osteoclasts were all significantly elevated. However, the levels of intact parathyroid hormone and 25(OH) vitamin D3 were decreased. B-ultrasonography showed chronic inflammation of bilateral submandibular glands. Neither bone marrow biopsy nor positron emission tomography - computed tomography examination showed evidence of neoplastic diseases. The patient was treated with intravenous saline infusion, loop diuretics, salmon calcitonin, glucocorticoids, and hemodialysis with a good response.

Nivolumab Therapy in Lung Cancer Associated with IgG4-related Disease.

A 75-year-old man with severe bilateral pleural thickening and dense soft tissue masses surrounding the abdominal aorta on computed tomography was diagnosed with IgG4-related disease (IgG4-RD) as a complication of lung cancer. He was started on nivolumab as second-line therapy along with low-dose prednisolone. Nivolumab was administered for 15 months until disease progression, during which time IgG4-RD did not relapse, and no problematic immune-related adverse events occurred. These results suggest that anti-programmed cell death protein-1 antibody may be used safely in lung cancer associated with IgG4-RD concomitantly with low-dose steroids.

IgG4-related uveitis. A French cohort and literature review.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature review. METHODS: Patients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature review and selected cases of definite IgG4-RD with uveitis. RESULTS: We reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab). DISCUSSION AND CONCLUSIONS: Uveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.

Coexistence of IgG4-related disease and ANCA-associated vasculitis: case report and review of the literature.

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that is characterized by storiform fibrosis, infiltration of IgG4-positive lymphocytes, obliterative phlebitis, and high IgG4 levels. Since IgG4-RD affects a wide variety of organs, a differential diagnosis must include multiple conditions. IgG4-RD is also believed to coexist with certain diseases. In recent years, case reports and case series describing the co-occurrence of IgG4-RD and ANCA-associated vasculitis (AAV) have been published. We intended to evaluate patients with IgG4-RD and AAV overlap in the literature using a case similar to one that was diagnosed and monitored in our department. We searched the databases of Web of Science, Scopus, and Google Scholar as well as PubMed with the keywords ANCA, IgG4, IgG4-RD, granulomatosis with polyangiitis, Wegener's granulomatosis, microscopic polyangiitis, Eosinophilic granulomatosis with polyangiitis, and Churg-Strauss syndrome. Cases and Case series addressing the coexistence of IgG4-RD and AAV have been selected. Comprehensive diagnostic criteria are used to diagnose IgG4-RD. The Chapel Hill Consensus Conference nomenclature criteria were used for the inclusion of AAV. Out of a total of 910 publications, 20 articles, including 65 cases, were found to be eligible. Forty-seven cases with IgG4-RD were evaluated as definitive (71.2%), 10 cases as probable (15.1%), and 9 cases as possible IgG4-RD (13.6%). 26 patients were diagnosed with GPA, 1 patient with localized GPA, 23 patients with MPA, and 4 patients with EGPA. The aorta, lacrimal tissue, pancreas, and retroperitoneum are the sites of IgG4-RD rather than AAV. AAV and IgG4-RD might coexist in the same patient. IgG4-RD is mainly associated with GPA.

Autoimmune Polyglandular Syndrome Type 3 Complicated with IgG4-related Disease.

A 52-year-old Japanese woman developed type 1 diabetes mellitus (type 1 DM) at 41 years old. She became complicated with Hashimoto's disease and showed swelling of both submandibular glands, which was diagnosed as IgG4-related disease (IgG4-RD). This is a rare case of a Japanese patient with autoimmune polyglandular syndrome type 3A (APS-3A) coexisting with autoimmune thyroid disease (AITD) and type 1 DM complicated by IgG4-RD. Bilateral submandibular gland resection was successfully performed without steroid therapy. We discuss the possibility that the immunological pathogenic mechanisms of APS-3A and IgG4-RD are related.

Cardiac Tamponade as an Initial Manifestation of Diffuse Large B-cell Lymphoma One Year after IgG4-related Disease in Remission.

A 65-year-old man with multiple lymphadenopathies was diagnosed with IgG4-related disease (IgG4-RD) based on findings of a cervical lymph node biopsy and an elevated serum IgG4 level. Treatment was initiated after the onset of autoimmune pancreatitis, and he achieved remission. He developed diffuse large B-cell lymphoma one year later. Pericardial involvement of lymphoma resulted in cardiac tamponade, and he died before histopathological confirmation of lymphoma was made due to a lethal arrhythmia caused by massive involvement of lymphoma into the myocardium. Because patients with IgG4-RD might have an increased risk of malignant diseases, including lymphoma, histopathological examinations should be considered at any time during the course of IgG4-RD.