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Background/Objective: IgG4-related disease (IgG4-RD) is an immune-mediated condition that affects multiple organs, including the pituitary gland. Here we present a patient with isolated pituitary involvement of IgG4-RD mimicking pituitary apoplexy. Case Report: A 49-year-old woman presented to the emergency department with abdominal pain, nausea, vomiting, and weight loss. Her blood pressure was low, and she appeared euvolemic with the rest of physical examination being noncontributory. Her electrolytes showed low serum sodium of 118 mmol/L (normal 135-145). Further investigations were significant for low morning cortisol of 20 nmol/L (N:100-500) and low adrenocorticotropic hormone. Magnetic resonant imaging of the pituitary fossa showed a pituitary macroadenoma with hemorrhagic transformation. She was started on glucocorticoids and levothyroxine before undergoing surgical removal of the pituitary tumor. The pathology was positive for IgG-4-related hypophysitis (IgG4-RH) with no evidence of pituitary tumor. Discussion: IgG4-RD is an immune-mediated condition that can affect many organs including the pituitary gland, in the form of hypophysitis. IgG4-RH can affect anterior, posterior, or both pituitary lobes. In 2011, Leporati et al developed a diagnostic criteria for IgG4-RH which includes the following: imaging, serology, histopathology, and response t glucocorticoids. The mainstay of treatment is glucocorticoids and hormone replacement therapy. Conclusion: IgG4-RH might be underestimated and should be suspected in those with hypophysitis or unknown cause of hypopituitarism. Moreover, pituitary macroadenoma with hemorrhagic transformation and panhypopituitarism should be considered as rare and unusual presentations of IgG4-RD.

Abstract Background The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. Methods We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. Results IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. Conclusions Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4-RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype.

Abstract Background IgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement. Case presentation This paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment. Conclusions This case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management.

IgG4-related tubulointerstitial nephritis (IgG4-related TIN) is the prevalent clinical manifestation of IgG4-related diseases (IgG4-RD). However, there are limited cases of IgG4-RD occurring with membranous nephropathy (MN) in the absence of phospholipase A2 receptor (PLA2R). There have been no indications of treatment using Tripterygium wilfordii. This study reported a rare case of IgG4-RD with PLA2R-associated MN without any of the distinct IgG4-related TIN. The patient was treated effectively with T. wilfordii. A 71-year-old patient was admitted to the medical facility after presenting with a 1 month history of edema and 8 months of albuminuria. The renal biopsy tissue examination confirmed the presence of MN (phase II) in the absence of pathological manifestations of IgG4-related TIN. Immunohistochemistry identified PLA2R++ (granular capillaries). The serum PLA2R antibody titer was 1:180 (1:20). The patient met the diagnosis with IgG4-RD. Over 8 years of follow-up, the patient was effectively treated with low-dose hormones and T. wilfordii, without any adverse effects. This MN is considered a unique form of IgG4-RD, regardless of whether PLA2R antibodies are present or not. Research suggests that T. wilfordii could be a promising option for elderly people with IgG4-related MN, as it has been found to have fewer adverse effects.

Introduction IgG4-related disease (IgG4-RD) is a progressive and potentially life-threatening condition characterized by immune system activation and tissue fibrosis, affecting various organs such as the pancreas, kidneys, and lungs. Initially recognized in 2003, it often presents as mass-like lesions, which can mimic tumors. Despite advancements in understanding its pathology, epidemiological data are limited, and many patients remain undiagnosed due to unfamiliarity with the disease. Aim of the study The aim of this article wast to summarize the latest knowledge on the diagnosis and clinical manifestations of IgG4-related disease. Materiał and methods This review is based on articles from the PubMed and Google Scholar databases, covering the years 2007-2024, using the keywords: IgG4-related disease; autoimmune pancreatitis; retroperitoneal fibrosis; classification criteria. Results The disease's complex pathogenesis involves B and T cell activity, with genetic and environmental factors contributing. While effective treatments, like B cell depletion, exist, the disease's broad clinical manifestations and multi-organ involvement require a multidisciplinary approach for proper diagnosis and management. Conclusion Diagnosing IgG4-RD is challenging due to its varied symptoms, often mimicking other diseases. Key findings include high IgG4 levels and specific histopathological features. Further research is needed to understand its genetic factors, pathogenesis, and epidemiology.

This report describes a unique case of IgG4-related disease in a 36-year-old woman who presented with a pelvic mass. Although CT and MR imaging initially suggested a malignant process, further work-up including sigmoidoscopy and surgical exploration revealed no evidence of malignancy. The final pathology indicated an inflammatory process, leading to the diagnosis of IgG4-related disease. After receiving appropriate systemic treatment, the patient's symptoms significantly improved. This case underscores the limitations of current imaging studies and emphasizes the importance of considering a wide range of potential diagnoses when dealing with pelvic masses of uncertain etiology.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases.

Abstract 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.

Abstract 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.

Abstract Objectives IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single/multiple organ(s). Pathological findings include the infiltration of IgG4-producing plasma cells, obliterative phlebitis, and storiform fibrosis. Although immunological studies have shed light on the dysregulation of lymphocytes in IgG4-RD pathogenesis, the role of non-immune cells remains unclear. This study aimed to investigate the demographics and characteristics of non-immune cells in IgG4-RD and explore potential biomarkers derived from non-immune cells in the sera. Methods We conducted single-cell RNA sequence (scRNA-seq) on non-immune cells isolated from submandibular glands of IgG4-RD patients. We focused on fibroblasts expressing collagen type XV and confirmed the presence of those fibroblasts using immunohistochemistry. Additionally, we measured the levels of collagen type XV in the sera of IgG4-RD patients. Results The scRNA-seq analysis revealed several distinct clusters consisting of fibroblasts, endothelial cells, ductal cells, and muscle cells. Differential gene expression analysis showed upregulation of COL15A1 in IgG4-RD fibroblasts compared to control subjects. Notably, COL15A1-positive fibroblasts exhibited a distinct transcriptome compared to COL15A1-negative counterparts. Immunohistochemical analysis confirmed a significant presence of collagen type XV-positive fibroblasts in IgG4-RD patients. Furthermore, immune-suppressive therapy in active IgG4-RD patients resulted in decreased serum levels of collagen type XV. Conclusions Our findings suggest that collagen type XV-producing fibroblasts may represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.

Key Clinical Message IgG4‐related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract IgG4‐related disease (IgG4‐RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4‐positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45‐year‐old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4‐related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second‐line therapy with rituximab was initiated. Over the 6 years of follow‐up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow‐up by reumathology, infectious diseases, and family medicine specialists.