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Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is implemented in selected rapidly progressive SSc with a high risk of organ failure. However, existing guidelines are based on clinical trials that do not represent the entire patient population and exclude critically ill patients with no therapeutic alternatives. Examples of AHSCT in IgG4-RD are absent. We report the case of a 44-year-old female patient with overlapping progressive diffuse SSc and sinonasal IgG4-RD. After 11 years of ineffective SSc treatment, AHSCT was performed. The 63-month follow-up showed a regression of SSc symptoms. AHSCT was not intended as treatment in the case of IgG4RD, although the first symptoms of the disease developed before transplantation. The sinus lesions progressed after AHSCT and remained indolent only after surgical treatment (bilateral ethmoidectomy, sphenoidotomy, intranasal buccal antrostomy), which allowed histopathological confirmation of IgG4-RD.

Abstract Objective To figure out the functions of thymic stromal lymphopoietin (TSLP) in IgG4-related disease (IgG4-RD). Methods Plasma TSLP levels were tested by Elisa, and its receptors were detected by flow cytometry. Expressions of TSLP and TSLPR in involved tissues were stained by immunohistochemistry and immunofluorescence. Proliferation, apoptosis, and B subsets of TSLP stimulated-B cells were analyzed by flow cytometry. TSLP-stimulated B cells were co-cultured with CD4+ Naïve T cells. Signaling pathway was identified by RNA-sequencing and western blot. Anti-TSLP therapy was adapted in LatY136F knock-in mice (Lat, IgG4-RD mouse model). Results Plasma TSLP level was increased in IgG4-RD patients and was positively correlated with serum IgG4 level and responder index (RI). TSLPR was co-localized with CD19+ B cells in the submandibular glands (SMGs) of IgG4-RD. TSLP promoted B cell proliferation, and TSLP-activated B cells polarized CD4+ naive T cells into follicular helper T (Tfh) cells through OX40L. RNA-sequencing identified JAK-STAT signaling pathway in TSLP-activated B cells and it was verified by western blot. Anti-TSLP therapy alleviated the inflammation of lung in Lat mice. Conclusion Elevated TSLP in IgG4-RD promoted B cells proliferation and polarized Tfh cells and might be served as a potential therapeutic target.

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. 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. [ABSTRACT FROM AUTHOR]

IgG4-related disease-associated hypertrophic pachymeningitis (IgG4RD-HP) is a fibroinflammatory autoimmune disorder in which diagnosis is difficult without biopsy. Guidance on management of disease refractory to glucocorticoids and intravenous rituximab is limited. We present the case of a 68-year-old woman with IgG4RD-HP who developed sensorineural hearing loss with associated bulky basilar pachymeningeal enhancement. Her cerebrospinal fluid was inflammatory and had an elevated IgG4 concentration, strongly suggestive of IgG4RD-HP. Biopsy of involved meninges was not possible due to surgical risk. Over years she developed bilateral optic neuropathies and hydrocephalus, requiring intravenous rituximab and ventriculoperitoneal shunt. Her disease was refractory to glucocorticoids. Despite maintenance intravenous rituximab, she developed slowly progressive symptoms of intracranial hypertension and hydrocephalus with persistently inflammatory spinal fluid. Switching to intrathecal rituximab therapy led to dramatic improvement in gait and headache and reduced pachymeningeal bulk and metabolic activity. In patients with IgG4RD-HP refractory to glucocorticoids and intravenous rituximab, intrathecal rituximab may be an efficacious therapy.

Abstract Isolated external iliac artery aneurysm is a rare occurrence. These aneurysms have varied presentations depending on size and proximity. Both open surgical and endovascular modalities can be used for treatment depending upon presentation, aneurysmal anatomy, and patient condition. Preservation of at least one internal iliac artery is important to prevent post-repair hypogastric ischemia. There are no previous reports of IgG4-related disease (IgG4-RD) as etiology of these aneurysms. A 32-year-old male patient presented with a left lower abdominal lump and was found to have a left external iliac artery aneurysm on computed tomography angiography. The patient underwent iliofemoral bypass with an 8 mm polyester graft. Histopathological examination of the aneurysm wall suggested IgG4-RD. The patient fulfilled the 2020 Revised Comprehensive Diagnostic Criteria for IgG4-RD. An 18-Fluorodeoxyglucose-Positron Emission Tomography scan performed in the postoperative period showed no active disease, hence medical therapy was not instituted. The patient is doing well at 1 year.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by IgG4+ plasma cell infiltration of the skin and other organs. Cutaneous forms of the disease may be under recognized owing to poorly defined diagnostic criteria and relatively recent recognition in the literature. The aim of this review is to describe the clinical, histological, and serological presentations of cutaneous IgG4-RD, and to provide an overview of its systemic manifestations for dermatologists. Cases of cutaneous IgG4-RD identified in the literature review were compared to control cases. Clinically, plaque morphology and systemic involvement of the orbit, submandibular gland, lacrimal gland, and parotid gland were associated with a diagnosis of cutaneous IgG4-RD. Histologically, lymphoplasmacytic infiltrate and percentage of IgG4+ plasma cells/IgG+ plasma cells > 40% were associated with the diagnosis. Serologically, neither elevated serum IgG4 nor IgE concentrations were associated with the diagnosis. Dermatologists should consider IgG4-RD as part of the differential diagnosis for nodules, papules, and plaques with an IgG4+ plasma cell infiltrate, especially in middle-aged and elderly males with systemic manifestations of the disease. Diagnosis requires thorough investigation of both cutaneous and systemic clinical and histological presentations.

Abstract Background Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic disease that involves the infiltration of IgG4-positive plasma cells in multiple organs. Kimura disease (KD) presents as subcutaneous masses on the head and neck, frequently accompanied by eosinophilia and high immunoglobulin E (IgE) levels. Here, we report a rare case of concurrence of IgG4-RD and KD with manifestations of asthma, pulmonary embolism, and central diabetes insipidus accompanied by lung carcinoma. Case presentation A 65-year-old Chinese male with an eight-year history of KD was admitted to our hospital with complaints of dyspnea and expectoration for one month. Laboratory examination showed a considerable elevation in the serum eosinophil count and total IgE and IgG4 levels. Chest enhanced computed tomography showed filling defects in the right pulmonary artery and a nodule in the left inferior lobe. Pancreatic enhanced magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography showed a swollen pancreatic tail and local stricture of the pancreatic duct section of the common bile duct. Enhanced MRI of the pituitary gland showed thickening of the pituitary stalk. Additionally, immunohistochemistry of the specimens collected eight years prior revealed IgG4-positive cells. Following the diagnosis of IgG4-RD with KD, glucocorticoids with immunosuppressants were initiated; there was a prompt improvement in the patient’s condition. One-year post-discharge, the patient underwent wedge-shaped resection of the lung due to enlargement of the pulmonary nodule, and the pathology revealed lung squamous carcinoma. Conclusions This case presents a rare clinical condition in which the concurrence of IgG4-RD and KD causes various rare manifestations including asthma, pulmonary embolism, central diabetes insipidus, and complicated lung carcinoma. This highlights the importance of monitoring for malignancies in IgG4-RD patients during follow-up.

Introduction: Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. Methods: Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. Results: Fifteen patients (60% women), with a median age of 53 years (48.5 – 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 – 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. Conclusion: This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

Abstract Objectives In IgG4-related disease, the relationship between pathological findings and relapse has not been well established. This study aimed to identify the clinical and pathological predictors of disease relapse in IgG4-RD. Methods Patients with newly diagnosed IgG4-RD (n = 71) were enrolled between January 2011 and April 2020; all cases were pathologically confirmed. The clinical and pathological features were recorded in a database at baseline and each follow-up visit. Patients were followed up at least once a month via outpatient clinic examinations and telephone calls. Univariate and multivariate Cox regression analyses and receiver operating curve (ROC) analysis were used to identify the predictors of disease relapse and to assess their predictive value. Results Over a median follow-up of 26 (range, 6–123) months, 3/71 (4.2%) patients died. Of the remaining 68 patients, 47 (69.1%) patients had achieved clinical remission and 21 (30.9%) had suffered relapse at the last follow-up. The independent predictors of relapse were IgG4 ≥ 6.5 g/L (HR = 2.84, 95% CI: 1.11–7.23), IgG ≥ 20.8 g/L (HR = 4.11, 95% CI: 1.53–11.06), IgG4-RD responder index (RI) ≥ 9 (HR = 3.82, 95% CI: 1.28–11.37), and severe IgG4+ plasma cell infiltration (HR = 6.32, 95% CI: 1.79–22.41). A prognostic score developed using three of the identified predictors (IgG ≥ 20.8 g/L, IgG4-RD RI ≥ 9, and severe IgG4+ plasma cell infiltration) showed good value for predicting impending relapse (AUC, 0.806). Conclusions In patients with IgG4-RD, IgG4 ≥ 6.5 g/L, IgG ≥ 20.8 g/L, IgG4-RD responder index (RI) ≥ 9, and severe IgG4+ plasma cell infiltration are predictors of relapse.

A 56-year-old male subject with bilateral eyelid swelling was diagnosed with an immunoglobulin G4–related disease. After whole-body surveillance, concomitant coronary arteritis with a mural thrombus and myocardial involvement were observed. In this case, multimodal diagnostic imaging assessment led to the diagnosis of both coronary arteritis and myocardial fibrosis associated with immunoglobulin G4–related disease. (Level of Difficulty: Advanced.)

Immunoglobulin G4-related disease (IgG4-RD) is a chronic multi-organic immune fibrosing disease. It affects preferentially men around middle age and almost any organs can be involved; however, lymph nodes, submandibular and lacrimal glands, pancreas, and retroperitoneum are the most affected. The mainstay treatment is corticosteroids, sometimes adjuncts with DMARDs or rituximab as steroid sparing agents. Th2 inflammation is implicated in the pathophysiology of the disease. Several reports indicate that allergy and/or atopy often affect patients with IgG4-RD. The frequency varies greatly between studies with allergies/allergic diseases reported in 18–76% while atopy is reported in 14–46%. In studies including both, they affect 42 and 62% of patients. Rhinitis and asthma are the most frequent allergic diseases. IgE and blood eosinophiles are often elevated and few studies report that basophils and mast cells could participate in the disease pathogenesis; however, the implication of allergy and atopy remain unclear. No common allergen has been identified and IgG4 production seems to be polyclonal. Although a direct causal effect is unlikely, they could potentially shape the clinical phenotype. Allergies/allergic diseases and/or atopy are reported to be more frequent in IgG4-RD patients presenting head, neck, and thoracic involvement, with higher IgE and eosinophils and less frequent in retroperitoneal fibrosis; however, studies regarding allergy and atopy in IgG4-RD are highly heterogenous. The aim of this article is to review what is currently known about the allergy and atopy in the context of Ig4-RD.

Abstract Background Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. Case presentation Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. Conclusion Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

Purpose: IgG4-related disease is an immune-mediated fibroinflammatory condition that can affect almost every major organ system. Orbital and adnexal involvement in IgG4-related disease though not uncommon can be varied depending on the site of the lymphoplasmacytic infiltration. This case of profound bilateral orbital inflammation is presented to demonstrate the significant clinical manifestations of IgG4-related ophthalmic disease. Observations: A 52-year-old man with a remote and seemingly unrelated history of lymphadenopathy presented to the Oculoplastics clinic with massive bilateral upper and lower lid swelling and induration. Hematologic testing demonstrated an elevation in serum IgG4 - a non-specific finding seen in various infectious, inflammatory, and malignant processes. Imaging demonstrated diffuse enlargement of orbital structures, including the lacrimal glands and extraocular muscles, as well as inflammatory changes of the adnexal and retrobulbar soft tissue. Orbital biopsy was required to confirm the diagnosis of IgG4-related ophthalmic disease. Conclusions and Importance: IgG4-related ophthalmic disease presents with various non-specific clinical signs and symptoms. The most common presentations include dacryoadenitis, enlarged orbital nerves, and orbital fat involvement; however, the extent of involvement both locally and systemically varies greatly. Clinical findings and imaging are helpful in narrowing the differential diagnosis; however, biopsy for histopathologic examination is essential to confirm IgG4-related disease. Physicians must maintain a high level of suspicion for the disease for proper management.

Immunoglobulin G4 (IgG4) related disease is a systemic disease that causes fibrosis, tumor-like nodules, and lymphoid hyperplasia with infiltration of IgG4 positive plasma cells. It can manifest in many organ systems; however, there are few cases that report gynecologic organ involvement. It is crucial to correctly diagnose IgG4-related disease versus malignancy because the former is treated with glucocorticoids or rituximab. In this case report, we describe two patients in which IgG4-related disease mimics gynecologic cancer. In the first case, an 85 year old woman presented with diffuse lymphadenopathy and a uterine mass concerning for malignancy. Biopsies were negative for carcinoma. Inguinal lymph node biopsy demonstrated IgG4 positive plasma cells and the patient was treated with rituximab therapy given concurrent severe rheumatoid arthritis. In the second case, a 35 year old woman under surveillance for Stage IB2 squamous cell carcinoma of the cervix (status post definitive chemoradiation therapy) presented with fluorodeoxyglucose (FDG) avid paraaortic lymph nodes on positron emission tomography (PET) imaging with subsequent negative paraaortic lymph node biopsies. Serial imaging and biopsies remained inconclusive despite ongoing diffuse lymphadenopathy and clinical concern for recurrence. Supraclavicular lymph node excision was performed which demonstrated lymphoid hyperplasia with increased IgG4 plasma cells and no evidence of carcinoma, supporting the diagnosis of IgG4-related disease. The patient was treated with high dose steroids with clinical improvement and resolution of abnormal imaging findings. We demonstrate that IgG4-related disease can present with FDG-avid lesions on PET imaging and lymphadenopathy that mimics primary or recurrent gynecologic malignancy. While rare, we conclude the IgG4-related disease is an important differential diagnosis to consider in the workup of primary or recurrent gynecologic malignancy and highlights the value of PET imaging to identify unusual patterns of lymphadenopathy and guide histologic confirmation of disease.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder of obscure etiology characterized by significant infiltration of IgG4-positive plasma cells toward several organs. Coronary artery involvement is rarely seen in IgG4-RD patients; thereby, we aim to outline the noninvasive imaging findings of this rare case. Cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) from a 15-year-old female diagnosed with IgG4-RD via histopathological assessment of orbital biopsy, were analyzed. CMR showed a severely reduced left ventricular ejection fraction and akinesia of the basal to mid-lateral, anterior, and septal walls. Inflammation of the basal to apical lateral wall and subendocardial infarction of the basal to apical lateral and mid inferoseptal walls were also evident. CCTA findings showed stenosis in branches of the left main artery (LM), left anterior descending artery (LAD), and right coronary artery (RCA), aortitis, and aortic wall thickening. After courses of proper treatment with prednisolone, Cellcept, and adalimumab, follow-up CMR showed significant improvement in LV systolic function and resolution of inflammation. Although IgG4-RD is an uncommon cause of coronary artery disease, it can cause lethal complications such as myocardial infarction. Hence, clinicians should be aware of cardiac complications in these patients.

Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.

IgG4-related disease (IgG4-RD) is an immune-mediated disorder marked by fibro-inflammatory masses that can infiltrate multiple organ systems. Due to its relatively recent discovery and limited understanding of its pathophysiology, IgG4-related disease may be difficult to recognize and is consequently potentially underdiagnosed. Renal involvement is becoming regarded as one of the key features of this disease. To date, the most well-recognized renal complication of IgG4-related disease is tubulointerstitial nephritis, but membranous glomerulonephritis, renal masses, and retroperitoneal fibrosis have also been reported. This concise review has two objectives. First, it will briefly encapsulate the history, epidemiology, and presentation of IgG4-related disease. Second, it will examine the reported renal manifestations of IgG4-related disease, exploring the relevant histology, imaging, clinical features, and treatment considerations. This synthesis will be highly relevant for nephrologists, rheumatologists, general internists, and renal pathologists to raise awareness and help improve early recognition of IgG4-related kidney disease (IgG4-RKD).

Background: IgG4-related disease with multiorgan involvement predicts higher disease activity, thus, it is necessary to identify whether IgG4-related disease involves multiple organs at the early stage. To further clarify the clinical characteristics and risk factors for IgG4-related disease with multiorgan involvement, we conducted an observational study. Methods: We retrospectively analysed the clinical data of 160 patients who were primarily diagnosed with IgG4-related disease at the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2021. According to the number of involved organs, patients were divided into two groups: multiorgan involvement and nonmultiorgan involvement. Patients were divided into a multiorgan group and a nonmultiorgan group according to multiple organ involvement. Results: There were 82 cases identified with multiorgan involvement and 78 cases diagnosed with no multiorgan involvement in this series. Most cases were elderly and male (p > 0.05). The most frequently affected organs in IgG4-RD were the lymph nodes (50.6 %), pancreas (38.7 %) and salivary glands (35.6 %). Multivariate analysis showed that eosinophilia, IgG4>2*ULN, lymph node involvement, salivary gland involvement and lung involvement were independent risk factors for multiorgan involvement (p

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maslinska and Kostyra-Grabczak.)

Objectives: We aimed to report the characteristics of pediatric IgG4-related disease (IgG4-RD) through a multicentre registry, to assess disease clusters, and to evaluate the performances of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria in this cohort., Methods: Data of IgG4-RD patients in 13 pediatric rheumatology centers were recorded to a web-based registration system. The diagnosis of IgG4-RD was made according to the 2011 comprehensive diagnostic criteria., Results: Thirty-five children (19 females and 16 males) with IgG4-RD were enrolled. The median age at diagnosis was 13.3 (25p-75p; 9.9-15.2) years. The most common organ involvement was the eye (n = 21, 60%), followed by lymph nodes (n = 12, 34.3%), musculoskeletal system (n = 12, 34.3%), and neurological system (n = 9, 25.7%). We identified three clusters in our study cohort: those with eye involvement (n = 11, 31.4%), those with eye involvement and neurological findings (n = 15, 42.9%), and those with pancreato-hepatobiliary disease and lymph node involvement (n = 9, 25.7%). Serum IgG4 levels were high in 19 out of 28 patients (67.8%). All patients except one received corticosteroid treatment, and azathioprine was the most preferred drug as a steroid-sparing agent. The sensitivities of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were 5.7% and 88.5%, respectively., Conclusion: IgG4-RD has a wide variety of clinical manifestations, however in children the most common presentation was orbital involvement. The 2020 RCD criteria had a better performance whereas the 2019 ACR/EULAR classification criteria performed poorly in pediatric patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Declaration of competing interests The authors declare they have no conflict of interest.

IgG4-related disease is a fibroinflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells affecting multiple organs. Though the most common renal manifestation of IgG4-related disease is tubulointerstitial nephritis, it can rarely present as secondary membranous nephropathy. We present a case of a 75-year-old male with phospholipase A2 receptor-negative membranous nephropathy as an atypical manifestation of IgG4-related disease. The patient presented with nephrotic syndrome and was found to have elevated serum IgG4 levels and IgG4-positive plasma cells in the kidney biopsy. He was successfully treated with corticosteroids and rituximab, resulting in significant improvement in proteinuria and normalization of IgG4 levels. This case highlights the importance of considering IgG4-related disease in patients with phospholipase A2 receptor-negative membranous nephropathy, especially in those with a history of other organ involvement. Early recognition and treatment of IgG4-related disease are crucial to prevent progressive kidney damage and improve patient outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)