Immunoglobulin G4 (IgG4)-related disease (RD) is a newly recognized disease, and a few epidemiologic studies about this disorder have been published. This research aimed to demonstrate the clinical features and outcomes of IgG4-related kidney disease (RKD) and IgG4-related retroperitoneal fibrosis (RPF) compared to other organs' involvement. Patients who were diagnosed with IgG4-RD from January 2009 to July 2019 at three medical institutions in South Korea were included. They were classified into three groups: RKD, RPF, and Others groups. The differences in symptoms, laboratory, histological and radiological findings, treatment, and outcomes among the three groups were evaluated. Of 94 patients, 13 (13.8%) and 22 patients (23.4%) were classified into the RKD and RPF groups, respectively. There were older (p = 0.004) and more asymptomatic patients (p = 0.02) in the RKD and RPF groups. In the RKD group, hypocomplementemia (p = 0.003) and eosinophilia (p = 0.001) were more frequently identified. In logistic regression analysis, hypocomplementemia (odds ratio [OR], 14.04; 95% confidence interval [CI], 1.38-142.95) and decreased renal function at the time of diagnosis (OR, 0.95; 95% CI, 0.91-0.98) were associated with renal involvement. Older age (OR, 1.05; 95% CI, 1.00-1.11), male (OR, 6.11; 95% CI, 1.41-26.61), and higher serum IgG4 levels (OR, 1.00; 95% CI, 1.00-1.00) were associated with retroperitoneal involvement. The treatment duration was longer in the RKD and RPF groups (p = 0.01) with glucocorticoids. Renal and retroperitoneal involvement in IgG4-RD presented clinical features that distinguish it from other organs' involvement, such as incidental diagnosis, hypocomplementemia, eosinophilia, and the need for a longer duration of maintenance treatment.

IgG4-related disease (IgG4-RD) is a chronic, immune-mediated disorder characterized by widespread inflammation and fibrosis, leading to potential organ dysfunction if untreated. Often underdiagnosed due to subtle and varied symptoms, the disease can affect multiple organ systems. This case series highlights two patients who were diagnosed as cases of IgG4-related retroperitoneal fibrosis. A total of two patients were included in this prospective case series who presented to the gastroenterology department of a tertiary care hospital with the same signs and symptoms and were diagnosed with IgG4-related retroperitoneal fibrosis (IgG4-RPF). Two patients were included in our case series, aged 25 and 26 years. The chief complaints included dull, radiating epigastric pain, other symptoms include diffuse abdominal pain, intensified, accompanied by nausea, vomiting, and episodic diarrhea, and a history of B-cell lymphoproliferative disorder. Endoscopic ultrasound (EUS)-)-guided biopsies were performed, showing findings consistent with (IgG4-RPF). Both patients were started on a regimen of prednisolone, pantoprazole, and vitamin D, which they tolerated well without adverse effects. They were advised to follow up with a CT scan after one month. IgG4-related disease (IgG4-RD) is a rare, chronic condition often presenting as retroperitoneal fibrosis (RPF) and affecting multiple organs. Serum IgG4 levels can be normal in certain cases, histopathological and radiological investigations are necessary for the correct diagnosis. Early initiation of immunosuppressive drugs are necessary for the disease control.

IgG4-RD is an immune-mediated systemic fibroinflammatory condition with characteristic clinicopathological findings. The exact etiology is uncertain. A combination of environmental and genetic factors is considered to be involved. It can affect multiple organs often mimicking malignancy or infectious disorder. Because of myriad of clinical presentations, the clinical diagnosis is cumbersome and requires a detailed histopathological, radiological, and serological workup. IgG4-retroperitoneal fibrosis is usually seen as a component of systemic manifestation of the disease that presents as mass lesion causing pressure and pain symptoms. These clinical symptoms are usually of insidious onset with gradually progressive course. The early diagnosis and treatment is essential to prevent its long-term irreversible complications. Isolated retroperitoneal fibrosis due to IgG4-RD is rare, as is being reported in our elderly male patient. Our case report highlights the rare presentation of IgG4-related RPF mimicking renal cell carcinoma.

Retroperitoneal fibrosis (RPF) is a rare condition marked by inflammation and fibrosis affecting the peritoneal and retroperitoneal soft tissues. In recent years, the identification of IgG4-related diseases has brought to light a significant association with fibrous disorders, including RPF, which were once considered independent. In this comprehensive cohort study, we performed a comparative analysis of the demographic, clinical, laboratory, histopathological, and therapeutic characteristics between patients with IgG4-related RPF and those with idiopathic retroperitoneal fibrosis (iRPF). We performed a retrospective analysis of 117 patients diagnosed with RPF at the First Affiliated Hospital of Naval Medical University between July 2007 and July 2023. Demographic, clinical, laboratory, histopathological, and therapeutic characteristics of 70 iRPF patients and 47 IgG4-related patients were systematically compared. The IgG4-related group exhibited an older age of onset, with a predominant occurrence among adult males. Significantly elevated levels of eosinophilia and IgE were observed in the IgG4-related group. Most patients across both groups displayed elevated CRP and ESR levels. Furthermore, at the time of diagnosis, the IgG4-related group had higher serum creatinine and lower levels of complement. The most prevalent clinical manifestation in both groups was flank pain. The proportion of lymphoplasmic infiltration and storiform fibrosis in IgG4-related RPF group was significantly higher. The IgG4-related RPF group had significantly higher IgG4-positive plasma cell count, IgG4/total IgG ratio, and eosinophils count than that in iRPF group. We conducted a comparative analysis of demographic, clinical, laboratory, histopathological, and therapeutic differences between the iRPF patients and the IgG4-related patients. Clarifying the distinctive characteristics of these two groups will contribute to a better understanding of the condition and facilitate the development of specific treatment strategies tailored to each group. Key Points • Identification of distinct clinical features and outcomes between IgG4-related and iRPF patients in a large retrospective study.

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect multiple organs throughout the body, predominantly in middle-aged and elderly males, with a male-to-female ratio of 2꞉1 to 3꞉1. IgG4-related retroperitoneal fibrosis (IgG4-RPF), a rare subtype of IgG4-RD, has an unclear etiology, and its comorbidity with type 2 diabetes mellitus is also uncommon. A lack of awareness of this condition in clinical practice can easily lead to misdiagnosis. On July 14, 2016, the Third Xiangya Hospital of Central South University admitted a patient with type 2 diabetes mellitus complicated by IgG4-RPF. Following comprehensive treatment, including blood glucose and blood pressure control, kidney protection, circulation improvement, and the use of prednisone, the patient's condition significantly improved. The retroperitoneal fibrotic mass decreased in size, renal function improved, and serum IgG4 levels decreased. After 8 years of follow-up, the condition did not recur. Analyzing this case in conjunction with a literature review suggests that the development of IgG4-RPF in diabetic patients may be related to chronic inflammation from metabolic syndrome and atherosclerotic plaques associated with long-standing diabetes. This provides valuable clinical ideas for clinicians in diagnosing and treating this rare comorbidity. IgG4相关性疾病(IgG4-related disease，IgG4-RD)是一种由免疫介导的纤维炎性反应性疾病，可以累及全身多器官，且好发于中老年男性，男女比例2꞉1~3꞉1。IgG4相关性腹膜后纤维化(IgG4-related retroperitoneal fibrosis，IgG4-RPF)作为IgG4-RD中的一种罕见类型，病因尚不明确，其与2型糖尿病的共病现象也较为罕见。临床上对该病的认识不足，易造成误诊。中南大学湘雅三医院于2016年7月14日收治1例2型糖尿病并发IgG4-RPF的患者，经降糖、降压、护肾、改善循环、应用激素等综合治疗后，病情较前明显好转，腹膜后纤维化包块较前明显缩小，肾功能好转，IgG4水平下降，且随访8年未再复发。对该病例进行深入分析并结合文献复习发现糖尿病合并IgG4-RPF的发生可能与代谢综合征产生的慢性炎症和长病程糖尿病的动脉粥样硬化斑块有关，这为临床医生提供了诊治思路。. IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can affect multiple organs throughout the body, predominantly in middle-aged and elderly males, with a male-to-female ratio of (2-3)꞉1. The disease has only been recognized relatively recently, and its prevalence is not well established in various countries. IgG4-related retroperitoneal fibrosis (IgG4-RPF), a rare subtype of IgG4-RD, has an unclear etiology, and its comorbidity with type 2 diabetes mellitus is also uncommon in clinical practice. A lack of awareness of this condition can easily lead to misdiagnosis. On July 14, 2016, the Third Xiangya Hospital of Central South University admitted a patient with type 2 diabetes mellitus complicated by IgG4-RPF. Following comprehensive treatment, including blood glucose and blood pressure control, kidney protection, circulation improvement, and the use of prednisone, the patient’s condition significantly improved. The retroperitoneal fibrotic mass decreased in size, renal function improved, and serum IgG4 levels decreased. After 8 years of follow-up, the condition did not recur. Analyzing this case in conjunction with a literature review suggests that the development of IgG4-RPF in diabetic patients may be related to chronic inflammation from metabolic syndrome and atherosclerotic plaques associated with long-standing diabetes. This provides valuable clinical ideas for clinicians in diagnosing and treating this rare comorbidity.