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A 77-year-old Lithuanian man presented to our institution with recurrent episodes of periorbital cellulitis, submandibular swelling and sialadenitis. Investigations revealed a positive QuantiFERON, raised inflammatory markers and normal autoimmune screen. Cross-sectional imaging showed no signs of occult malignancy, and work-up for mycobacterial infection including imaging and bronchoalveolar lavage did not show active tuberculosis. During hospitalisation, the patient developed fevers of unknown origin, which were investigated with a positron emission tomography (PET) scan and a bone marrow aspiration, without evidence of occult infection or malignancy. Serum IgG4 level was three times the upper limit of normal. The patient responded well to oral steroids but relapsed after completing a slow taper. Serum IgG4 level was three times the upper limit of normal. He had an American College of Rheumatology/European League Against Rheumatism score of 20, in conjunction with involvement of orbital and salivary tissue. Therefore, IgG4-related disease was considered the most likely diagnosis, despite prominent fevers, which are among the exclusion criteria for this diagnosis. After a multidisciplinary review including rheumatology and ophthalmology, the patient was commenced on maintenance methotrexate with remission of symptoms.

An 8-year-old normal weight boy with a medical history of obstructive sleep apnoea since 4 years of age using a continuous positive airway pressure machine at night and with bronchial asthma was in his usual state of health until 1 month prior to presentation, when his mother noticed significant

IgG4 related disease is a term used to describe a fibroinflammatory condition characterized by storiform fibrosis, inflammation with a dense lymphoplasmocytic infiltrate rich in plasma cells expressing IgG4, and often, if not always, raised serum levels of IgG4. We report a case of a patient with a past history of retroperitoneal fibrosis presenting with a swollen left testicle, who underwent an orchidectomy due to suspicion of malignancy. The surgical specimen revealed a paratesticular pseudotumor with histopathological and immunohistochemical characteristics of IgG4 related disease. To the best of our knowledge, just nine such cases have previously been reported, of which only three were manifestations of systemic disease, as in the present case. Whilst it is important to recognize the clinical and radiological features of this entity, histopathology is often essential in order to confirm the diagnosis.

Rosai-Dorfman-Destombes disease (RDD) is a non-Langerhans cell histiocytosis characterized by the accumulation of histiocytes inside the lymph nodes or extranodally. The association between RDD and IgG4-related disease (IgG4-RD) is discussed. We herein report a case of RDD manifesting as acute tubulointerstitial nephritis mimicking IgG4-RD. The first renal biopsy showed severe tubulointerstitial nephritis with infiltration of S100-positive histiocytes and IgG4-positive plasma cells; storiform fibrosis and obliterative phlebitis were not confirmed. After prednisolone therapy, IgG4-positive cells and S100-positive histiocytes were decreased, but the IgG4/IgG ratio increased despite clinical improvement. These findings indicated extranodal RDD in the kidney presenting as tubulointerstitial nephritis.

Tubarial glands (TGs) are recently refocused gland tissues localized near the tori tubarius in the nasopharynx and their clinical relevance is not clear yet. IgG4-related disease (IgG4-RD) is a progressive fibrosing condition and salivary glands are well-affected lesions. The aim of the present study is to examine [18F]fluorodeoxyglucose ([18F]FDG) accumulation to the tori tubarius in IgG4-related disease (IgG4-RD). 48 patients with IgG4-RD who underwent positron emission tomography (PET) scanning with [18F]FDG were included and semi-quantitative analysis of [18F]FDG accumulation to tori tubarius was performed along with the clinical features and histopathological analysis. Of the 48 patients, abnormal [18F]FDG accumulation (metabolic tumour volume ≥ 1) to tori tubarius was observed in 15 (31.3%), all of whom had lesions in other head and neck glands. IgG4-RD patients with abnormal [18F]FDG accumulation to tori tubarius showed swollen nasopharyngeal walls around tori tubarius and forceps biopsy of the lesion revealed acinar cells and IgG4-positive plasma cells histologically. Abnormal [18F]FDG accumulation (maximum standard uptake value, metabolic tumour volume and total lesion glycolysis) to tori tubarius correlated with higher IgG4 and lower IgA serum concentrations. Abnormal [18F]FDG accumulation to tori tubarius can be observed in patients with IgG4-RD and the abnormal [18F]FDG accumulation to tori tubarius can be a clue of TG involvement in IgG4-RD.

Background IgG4-related disease mainly manifests as organomegaly and is accompanied by tissue fibrosis (Mimori, Mod Rheumatol 29(2):213, 2019) which is frequently confused with tumour (Dawei et al., J Gastroenterol Hepatol 29(12):1375–8, 2020). There are few reports with of IgG4-related disease with the first clinical manifestation involving the stomach. Case presentation We present the case of 46-year-old male patient with a “stomach tumour” as the first manifestation of IgG4-related disease. Gastroscopy showed a mass in the stomach, however, the pathology result was chronic inflammation with IgG4 positivity. CT scans of abdomen showed that the stomach wall was thick, the head of the pancreas was swollen, and retroperitoneal fibrosis was severe.The serum IgG4 level was 75 g/L (normal range 0.03–2.01 g/L).After treatment with methylprednisolone for one month, the symptoms were greatly relieved. Conclusions To reduce the suffering of patients and relieve their financial burden, we should consider the possibility of IgG4-related disease when the initial manifestation is a stomach mass.

IgG4-thyroid-related disease (TRD) represents an uncommon spectrum of diseases, with four subcategories established so far, IgG4-related Hashimoto’s thyroiditis, fibrosing variant of Hashimoto’s thyroiditis, Riedel’s thyroiditis and Graves disease with elevated IgG4 levels. We report the case of a 59-year-old woman presenting with painless cervical swelling and hypothyroidism. Thyroid gland was enlarged and distinctively very hard, with reduced mobility. Neck ultrasonography showed multiple nodularity and diffuse thyroid enlargement, which on CT scan conditioned slight deviation of the airway. Fine-needle aspiration of the biggest nodule was suggestive of lymphocytic thyroiditis. She developed compressive symptoms and was submitted to total thyroidectomy. Histology of the thyroid revealed extensive areas of fibrosis, oncocytic cells and lymphoplasmacytic infiltrates. Immunohistochemistry confirmed the predominance of IgG4-secreting plasma cells. IgG4-TRD is characterised by a rapidly progressive and destructive thyroiditis process. Typical presentation can often mimic malignancy; hence, an opportune recognition of IgG4-TRD may avoid unnecessary burdens.

Patients with plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) often show elevated serum IgG4 levels and IgG4-positive cell infiltration in tissues due to overproduction of interleukin-6, and may meet the diagnostic criteria for IgG4-related disease (IgG4-RD). Although PC-iMCD has been listed as a major exclusion disease for IgG4-RD, distinguishing between these diseases is challenging due to a lack of highly specific diagnostic biomarkers. In 2020, we proposed exclusion criteria of IgG4-RD mimickers. In this paper, we validated the accuracy of the criteria in excluding one of the mimickers, PC-iMCD, from IgG4-RD. Validation was performed on 57 PC-iMCD patients (39 presenting lymph node lesions and 19 with lung lesions) and 29 IgG4-RD patients (22 presenting lymph node lesions and seven with lung lesions). According to our results, 20.5% of the PC-iMCD patients with lymph node lesions and 42.1% of those with lung lesions met the diagnostic criteria for IgG4-RD. All these patients with PC-iMCD were excluded from a diagnosis of IgG4-RD by the proposed criteria. Additionally, 6.9% of IgG4-RD patients met the exclusion criteria. Thus, if the exclusion criteria are met, diagnosis should be made based on a combination of findings including organ distribution of disease, response to steroid therapy, and other pathological findings.

Follicular lymphoma is clinically classified as a common type of indolent non-Hodgkin's lymphoma, and its clinical diagnosis is difficult because B symptoms and elevated soluble interleukin-2 receptor (sIL-2R) levels are less frequent in follicular lymphoma than in other lymphomas. We report a case of follicular lymphoma masquerading immunoglobulin G4-related disease (IgG4-RD) with elevated IgG4 levels. A 67-year-old man presented to our hospital with a 1-year history of deep right supraclavicular and para-aortic lymph node lymphadenopathy on plain computed tomography (CT) findings along with elevated IgG4 levels, and the 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan showed heterogeneous diffuse FDG uptake in the liver, and FDG uptake was noted at multiple sites in the enlarged right supraclavicular and para-aortic lymph nodes. Excisional biopsy of the right supraclavicular lymph node, performed under general anesthesia, showed a tumor-like structure mimicking a normal germinal center in the lymphoid follicle; immunostaining was positive for B-cell lymphoma 2 and CD10 proteins with some plasma cells stained with IgG, only 30% of them were positive for IgG4, and no marked fibrosis characteristic of IgG4-RD was observed; therefore, follicular lymphoma was diagnosed, and all symptoms, including FDG uptake, improved with rituximab monotherapy. Differential diagnoses of slowly progressive generalized lymphadenopathy over the years with elevated serum IgG4 levels include IgG4-RD, Castleman's disease, and indolent lymphoma. Multiple accumulation in the liver on FDG-PET/CT, if found, may suggest indolent lymphoma among them.

AimTo retrospectively evaluate the characteristic clinicopathological spectrum in patients with suspicion of IgG4-related disease (IgG4RD).MethodsWinpath histology database from January 2011 to April 2018 identified all suspected IgG4RD cases wherein IgG4 immunohistochemistry was performed. The histology slides were reviewed to categorise cases into Boston criteria groups—highly suggestive of IgG4RD, probable IgG4RD and insufficient evidence. Information regarding clinical data, treatment received, follow-up and serum IgG4 levels was obtained from medical records and AllScripts Patient Administration System (APAS) clinical database.ResultsThe study included 204 patients and the most common sites of biopsy/resection were pancreas and duodenum. The most common clinical presentation was fibroinflammatory lesion or mass/lump. On histology, 54/204 (26.47%) cases showed typical storiform fibrosis, 65/204 (32.64%) had >10 IgG4+ plasma cells per high power field and only one case showed thrombophlebitis (0.49%). There were 14/204 (6.78%) cases categorised as highly suggestive of IgG4RD; 8 of these showed high serum IgG4 levels and were managed clinically as true IgG4RD.ConclusionHistological diagnosis of IgG4RD remains challenging, as not all characteristic features are always present especially in small biopsies. Due to the novelty of its experience, fear of over diagnosis in the context of malignancy and features overlapping with diseases of similar clinical scenario, diagnosis of IgG4RD has become more puzzling. Further multicentre clinical trials/studies are advisable.

Background Paratesticular fibrous pseudotumour is a rare benign growth with unclear pathogenesis and clinical management. It has been linked to Serum IgG4-related disease. This mass can notoriously masquerade around as a malignancy; however, a conservative (testis sparing) approach is sufficient as surgical management. Case presentation We present the case of a 35-year-old gentleman who presented with a slow growing paratesticular mass, raising the suspicion of a malignancy. However, normal tumour markers and benign appearance on imaging modalities compelled us to give trial of local excision with intra-operative frozen section analysis. After confirmation of benign pathology of the mass, the incision was closed. Final histopathology confirmed the diagnosis of benign paratesticular fibrous pseudotumour, and serum IgG levels were noted to be elevated. Conclusion Thus, using tumour markers, radiological imaging and intraoperative frozen section, a potential radical resection can be avoided, testis sparing surgery, employed.

The 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown.To validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management.Four experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab.Among the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes.The ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.

IgG4-related disease (IgG4-RD) is a systemic, immune-mediated fibro-inflammatory disease that can affect virtually every organ system. It is usually insidious in onset and often mimics malignant or other inflammatory disorders. Diagnosis frequently requires a combination of clinical, serological, radiographic, and histopathological features, including increased serum-IgG4 levels and tissue infiltration of IgG4-positive plasma cells with associated fibrosis. Unlike more frequently affected sites, including the hepatobiliary system, salivary glands and retroperitoneum, pericardial involvement of IgG4-RD has only rarely been described. We report the case of a 76-year-old woman presenting with refractory pericarditis and imminent cardiac tamponade, successfully treated with therapeutic pericardiectomy. A diagnosis of IgG4-RD was made based on elevated serum-IgG4 levels and the presence of typical pericardial histopathological findings, meeting all 3 of the 2011 comprehensive diagnostic criteria for IgG4-RD. Following pericardiectomy, the patient remained in remission without a need for glucocorticoids or additional immunosuppressive therapy. Adding to this case, we reviewed the literature for previously described cases of IgG4-RD presenting with pericarditis and described their characteristics and the available treatment options. Our case-based literature review provides a clear overview of the diagnostic process for IgG4-RD and the need to apply classification criteria with the necessary caution, particularly in the case of rare disease manifestations, including pericarditis. ispartof: RHEUMATOLOGY INTERNATIONAL vol:42 issue:7 pages:1287-1295 ispartof: location:Germany status: published

IgG4-related disease is a rare, immune-mediated, systemic disease that is characterized by soft tissue lymphocyte infiltration and resultant fibrosis. The salivary glands are among the most commonly affected organs. Patients present with subacute submandibular and/or parotid swelling and sialadenitis. Diagnosis incorporates clinical, serologic, radiologic, and pathologic findings. Most cases respond quickly to systemic glucocorticoids. IgG4-related disease mimics many infectious, inflammatory, and neoplastic diseases. Therefore, IgG4-related disease is frequently misdiagnosed. A knowledge of the pathophysiology, diagnosis, and management of IgG4-related disease is important for providers who treat salivary gland diseases.

Background IgG4-related disease (IgG4-RD) is an immune-mediated disease that may present as a tumefactive lesion in nearly any organ. These mass lesions often resemble malignancy both clinically and radiologically, and some patients undergo surgical resection which could possibly be avoided with early recognition of IgG4-RD. We performed a retrospective single-center study examining how many patients with IgG4-RD were initially believed to have malignancy, with particular attention to those who underwent potentially avoidable surgical procedures. Methods Sixty-three patients with biopsy confirmed IgG4-related disease were included. Clinical, laboratory, radiological, and histological data were collected and analyzed. Results Over 60% of patients (38/63) were initially thought to have a malignancy when they initially presented with symptomatic IgG4-RD. The most common types of malignancy suspected were lymphoma (18/38) and pancreatic cancer (11/38). Of the 38 patients with suspected malignancy, 14 underwent an invasive intervention either to alleviate the severity of their symptoms or as treatment for their presumed malignancy. These included Whipple resection/attempted Whipple (3), nephrectomy (3), bile duct resection and reconstruction (1), removal of other abdominal/retroperitoneal masses (3), and stenting of obstructed organs (4). Conclusion IgG4-RD should be on the differential diagnosis of patients with mass lesions, in particular those with pancreatic masses and obstructive jaundice, extensive lymphadenopathy, or retroperitoneal masses. Oncologists and other physicians involved in cancer care should be aware of the various manifestations and diagnostic approach to IgG4-RD in order to provide accurate diagnosis and minimize unnecessary invasive procedures. While some procedures in this study, such as stenting of obstructed organs, were required regardless of diagnosis, others could have potentially been avoided or attenuated with early recognition of IgG4-RD. Patients with mass lesions suspicious for IgG4-RD should have serum protein electrophoresis, IgG subclass measurement, and, where possible, tissue biopsy before undergoing major surgical resection. Consultation with a physician experienced in IgG4-RD is recommended.

A 68-year-old man presented with a solid mass at the left renal pelvis and ureter with multiple systemic lymphadenopathies and a mass with a cavity in the right lower lobe of the lung. While a transbronchial lung biopsy revealed no malignancy, a biopsy of the renal pelvis showed marginal zone lymphoma with polyclonal IgG4-positive cells. The serum IgG4 level and presence of a bilateral orbital mass suggested Mikulicz disease. The lesions shrank following the administration of steroids. A rebiopsy confirmed lung adenocarcinoma, and its background showed IgG4-positive cells a year later. IgG4-related diseases require careful follow-up because they can be complicated by malignancy.

This systematic review aims to clarify and comprehensively detail the sometimes variable published imaging features as well as the pathogenesis, clinical diagnostic criteria, and treatment options of IgG4-Related Diseases (IgG4-RD) in the head and neck to aid the radiologist in diagnosing relapse and new sites of disease. A literature search in PubMed and EMBASE for reported cases of IgG4-RD was performed in December 2019. Case reports or series of IgG4-RD in the head and neck in adults that included sufficient imaging and pathology findings were included. This yielded 50 reports. IgG4-RD locations included the orbits, thyroid, pituitary gland, paranasal sinuses, salivary and parotid glands, larynx, pharynx, cervical lymph nodes, meninges, and skull base. Most lesions demonstrated non-specific homogenous CT attenuation, diffuse enhancement, isointense/low T2 signal intensity, and low T1 signal intensity. 6 cases from our institution followed previously reported imaging patterns.

Küttner tumor is an uncommon cause of salivary gland enlargement that most frequently affects the submandibular gland. More recently it has been considered a manifestation of IgG4-related disease (IgG4-RD) and synonymous with chronic sclerosing sialadenitis (CSS). We present a series of cases to emphasize this clinical entity as a disease pattern and presentation that is separate from IgG4-RD. Retrospective case series of 3 patients with unilateral salivary gland enlargement, or “Küttner tumor,” histologically classified as “chronic sclerosing sialadenitis,” The clinical history, radiology reports, laboratory studies, and pathology slides were reviewed for each case. Radiology showed discrete unilateral mass-like lesions in all three cases. Immunohistochemistry showed reduced tissue IgG4-positive plasma cells in two cases and increased numbers in one case, but insufficient to diagnose IgG4-RD. Storiform fibrosis was not seen in all cases and did not coincide with increased IgG4-positive plasma cells. A systemic workup, including serum IgG4 levels in two cases, was normal. A brief review of the literature on the spectrum of salivary gland involvement by IgG4-RD is presented. Küttner tumor is not necessarily the same as chronic sclerosing sialadenitis and is not always associated with IgG4-related disease. This report includes the second documented case of Küttner tumor of the sublingual gland.

The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

Immunoglobin-G4 related disease (IgG4-RD) is an auto-immune inflammatory condition where patients present with a tumour-like mass that shows infiltration by plasma cell and subsequent fibrosis. It is a systemic condition that primarily involves the salivary glands, pancreas, kidneys, aorta, and retroperitoneum amongst other organs. Testicular involvement is a rare occurrence in this disease entity. A 55-year old male patient presented with the complaints of pain and swelling in the right scrotal region. Right-sided orchidectomy was carried out which on histopathology showed features suggestive of IgG4-RD which was later confirmed on immunohistochemistry. Whole body MRI revealed that no other organ was involved in the disease process in this patient. IgG4-RD has a variable clinical course and considerable overlap with its differentials. Imaging studies and serum IgG4 levels are neither confirmatory nor customarily diagnostic in every case. The only confirmatory diagnostic investigation is histopathological examination, which shows infiltration of IgG4+ plasma cells and fibrosis in the involved tissue. Whenever a mass-forming lesion with typical histomorphological features is encountered with involvement of multiple organs/anatomic sites, IgG4-related disease should be considered among the differentials, and clinicians of all disciplines should be familiar with this disease entity.

IgG4-related disease (IgG4-RD) is an immune-mediated disease condition that can affect almost any organ, including the head and neck. It is a chronic, systemic inflammation of unknown etiology. Tumor formation is the most common clinical symptom. Any tumor in the head and neck area is always a concern for an otorhinolaryngologist, head and neck surgeon, that we are dealing with malignant neoplastic growth. Ultrasound imaging, computer tomography, magnetic resonance imaging and even fine needle aspiration biopsy usually do not exclude neoplastic hyperplasia. Only open biopsy or excision biopsy followed by histopathological examination suggest the diagnosis of IgG4-RD, which requires further diagnosis, mainly serological. The authors present the most common IgG4-RD in the head and neck area, diagnostic criteria and their differentiation from apparently similar diseases.

Background Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4+ plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements. Methods Serum samples were collected from untreated 59 patients with IgG4-RD, 13 patients with rheumatoid arthritis, and 37 healthy controls (HCs). HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within 7 days. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical phenotypes of IgG4-RD. Results In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between the serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements, although both Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy. Conclusion Serum levels of Gal-9 and sTIM-3 were significantly elevated in untreated patients with IgG4-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs. IgG4-RD may show a variety of initial symptoms. In the oral mucosa, lesions present as inflammatory fibrosis with a large number of IgG4-positive plasma cells. Evaluating treatment is a well-known problem in IgG4-RD due to the absence of an established assessment system. There are difficulties in defining the severity of the disease, which is why treatment is primarily based on its clinical manifestations. We present a case report of localized IgG4-RD with ulcerative and proliferative manifestations on the tongue, which clinically mimicked oral squamous cell carcinoma. A tumor-like lesion on the tongue can indicate something else other than the malignant or reactive changes commonly found in the oral mucosa. Multiple differential diagnoses of these atypical oral lesions, including localized IgG4-RD, should be considered.

We report a 5.8 cm left renal artery aneurysm in a 71-year-old male with IgG4-related disease. To our knowledge, this is the first reported renal artery aneurysm associated with this condition. After being considered for nephrectomy, the patient underwent ex vivo left renal artery aneurysm repair to preserve renal function and remains dialysis-free at 2 years of follow-up.

IgG4-related disease (IgG4-RD) is an immune-mediated multi-organ inflammatory disorder caused by tissue infiltration of lymphocytes with IgG4-secreting plasma cells. Herein, we discuss a case of a patient with IgG4-RD who had involvement of multiple organs: the kidneys, lymph nodes, bone marrow (biopsy performed), lungs, liver, and small intestine (imaging abnormalities). Although several case reports and series of IgG4-RD involving different organ involvement are in the literature, our patient has extensive simultaneous multi-organ involvement. We utilized the four domains (serologic, pathologic, radiologic, and pathologic) as discussed in the new 2019 ACR/EULAR classification criteria to provide a useful framework in considering an alternative tool for IgG4-RD in multi-organ involvement, where biopsy is more invasive and not always accessible. We highlight the findings of each organ involved that increase the likelihood that the patient has IgG4-RD. In our patient, the IgG4-RD classification criteria was fulfilled with total points adding up to 48. Our case meets the classification criteria for IgG4-RD, since at least one organ is involved to meet entry criteria (biopsy proven), no exclusion criteria are present, and the total points are ≥ 20. When such extensive involvement of IgG4-RD occurs, early diagnosis and treatment are recommended to avoid irreversible organ damage and better outcomes.

Background Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic, immune-mediated, and fibro-inflammatory disease. Hypocomplementemia was found in part of IgG4-RD patients especially in the setting of active disease. Objectives This study aimed to clarify the clinical features, treatment efficacy, and outcome in IgG4-RD patients with hypocomplementemia. Methods 312 IgG4-RD patients were recruited in our prospective cohort conducted in Peking Union Medical College Hospital. Patients were divided into hypocomplementemia group and normal complement group according to serum C3 and C4 levels measured at baseline before treatment. Low serum C3 levels ( Results Hypocomplementemia was identified in 65 (20.8%) cases of untreated IgG4-RD patients at baseline. The average age of hypocomplementemia group was 55.85 ± 10.89 years, with male predominance (72.3%). Compared with normal complement group, patients with hypocomplementemia were likely to have more involved organs, higher IgG4-RD responder index (IgG4-RD RI), and higher laboratory parameters such as counts of eosinophils, inflammatory markers, immunoglobulin G (IgG), IgG1, IgG3, IgG4, and IgE. In addition, lymph nodes, lacrimal gland, submandibular gland, parotid gland, paranasal sinus, bile ducts, and prostate gland were more commonly affected (p P = 0.401). Conclusions Clinical characteristics of IgG4-related disease with hypocomplementemia differ from normal complement group. Serum C3 and C4 at baseline before treatment could be biological markers for disease activity. IgG4-RD with hypocomplementemia responded well to treatment and had no significant difference of relapse rate in IgG4-RD with normal complement.

Aim To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease (IgG4-MALT lymphoma), a rare but clinically important complication of ocular adnexal IgG4-related disease. Methods We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three tertiary and one secondary referral centers, between February 2003 and December 2016. Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified. CT and MR images were analyzed by consensus of two experienced head and neck radiologists. Results Lacrimal glands were the main site of involvement in all seven patients. The lesions typically showed well-demarcated margins, iso- to hyperattenuation on precontrast CT, T2 hypo- to isointensity, T1 isointensity, and homogenous internal architecture with homogenous enhancement pattern. Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images, respectively. Conclusion Unlike in typical ocular adnexal IgG4-related disease, T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases. Although the findings may be nonspecific, the possibility of accompanying MALT lymphoma may need to be considered, when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients. However, this is a case series of a very rare complication of ocular adnexal IgG4-related disease, and thus caution is warranted to generalize the conclusion.

IgG4-related disease (ER-IgG4) is a recognised systemic disease. It was described after patients diagnosed with autoimmune pancreatitis showed signs of extra-pancreatic disease. The clinical manifestation of these patients is subacute and is manifested by the appearance of pseudotumoral lesions, or inflammatory or fibrous tumours. Sometimes it can be serious as in the case of patients with cholangitis or large vessel vasculitis. Diagnostic criteria include, among others, serum IgG4 elevation and/or histological parameters. The 18F-FDG-PET/CT is useful in the initial diagnosis, biopsy guidance as well as in the assessment of response to therapy. It usually responds to steroid therapy.

IgG4-related disease is a systemic disorder characterised by diffuse or tumoural inflammatory lesions. It can mimic pancreatic cancer, leading to errors in diagnosis and treatment increasing rates of morbidity and mortality in patients. The aim of this review is to take a differential diagnostic approach to these two entities using epidemiology, clinical and laboratory findings, imaging and histopathology.

The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren’s syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.

Background We report a case of atypical presentation of IgG4-related disease (IgG4-RD) with recurrent scleritis and optic nerve involvement. Case presentation A 61-year-old male presented with ocular pain and injection in his left eye for 2 months. Ocular examination together with ancillary testing led to the diagnosis of scleritis, which relapsed in spite of several courses of steroid treatment. After cessation of steroid, the patient complained of severe retro-orbital pain and blurred vision. His best corrected vision was count finger, the pupil was mid-dilated and a relative afferent pupillary defect was found. Funduscopic examination demonstrated disc swelling. Magnetic resonance imaging (MRI) showed enhancing soft tissue encasing the left globe, medial rectus muscle and optic nerve. Systemic work-up revealed multiple nodules in right lower lung and a biopsy showed histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms with no recurrence for 2 years. Conclusions This case highlights the significance of IgG4-RD in the differential diagnosis of recurrent scleritis. IgG4-RD may cause optic neuropathy resulting in visual loss. Early diagnosis and proper treatment can prevent irreversible organ damage and devastating visual morbidity.

A 71-year-old Japanese man with progressive kidney failure was referred to our hospital. Laboratory tests showed elevated IgG4 levels. Contrast-enhanced computed tomography (CT) revealed soft tissue surrounding the left kidney and right atrophic kidney. A histopathological examination revealed inflammation and fibrosis with rich IgG4-positive cells in the thickened kidney capsule, but not in the kidney parenchyma. Poor enhancement in the left kidney on contrast-enhanced CT and wrinkling of glomerular capillaries in pathological tissues were also observed. These findings indicated IgG4-related perirenal lesions leading to low renal perfusion and kidney failure. The perirenal lesions and kidney failure were improved by corticosteroid therapy.

Immunoglobulin G4-related sclerosing disease (IgG4RD) is an emerging immune-mediated fibro-inflammatory disorder which can involve any organ. We describe the first IgG4-RD spondylitis treated with total en-bloc spondylectomy (TES). A 55-year-old man presented with back pain. Magnetic resonance imaging (MRI) of the thoracic spine revealed a pathologic compression fracture on T11 vertebral body and both pedicles suggestive of primary bone tumor or bone metastasis. We conducted TES of T11, because we could not exclude the possibility of primary bone tumor including giant cell tumor. Immunohistochemical examination of the pathology specimens from pleura around the pedicle demonstrated diffuse infiltration of IgG4-bearing plasma cells. Six weeks later from the surgery, a delayed serologic test was done and his serum IgG4 concentration was 45 mg/dL. The final diagnosis was probable IgG4RD on the basis of serological, imaging, histopathological findings. After 6 weeks of oral prednisolone treatment, patient's back pain improved dramatically. IgG4RD is very rare systemic disease and its paraspinal soft tissue like pleura involvement with vertebra body invasion was absent until now. Our experience indicated that surrounding soft tissue biopsy would be helpful when a percutaneous vertebra bone biopsy mismatched with the image studies, even though vertebra body was main pathological lesion considering the possibility of IgG4RD.

The features and treatment of 98 Chinese patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) referred to a single tertiary referring centre were reviewed. Patients diagnosed with IgG4-RD according to the comprehensive diagnostic criteria (CDC) were included in the retrospective study from May 2012 to March 2019. We collected data on clinical, laboratory, imaging, histological features and treatment. Totally, 98 patients with IgG4-RD were enrolled. The common clinical manifestations included abdominal pain, salivary gland swelling and lymphadenopathy. 51% of the patients had multiple organs involvement. Lymph nodes, pancreas and salivary glands were most commonly involved. Four rare sites including ulna, cerebellum, scalp, and mammary gland were found. The serum IgG4 level was increased by 85.7%. The serum IgG4 level was positively correlated with the number of involved organs, IgG and IgG4/IgG. Low C3 and C4 levels were observed in 37.5% and 12.2% patients respectively, and all patients with kidney involvement had hypocomplementemia. A total of 54 patients underwent tissue biopsies, and 55.6%, 31.5% and 11.1% cases were diagnosed as definite, probable and possible IgG4-RD, respectively. Eighty-eight patients received glucocorticoids (GCs) therapy. Five patients underwent radical surgery to remove the lesion. 73% of them presented a complete or partial remission. IgG4-RD is a systemic fibroinflammatory disease with involvement of multiple organs throughout the body including some rare sites. Most IgG4-RD patients had increased serum IgG4 levels and patients with kidney involvement showed hypocomplementemia. GCs therapy is effective. More research is needed to provide a more reliable basis for the diagnosis and treatment of patients.

IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

This paper considers the new 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease, discusses essential differences with IgG4-RD comprehensive diagnostic criteria (Umehara H., 2011) and comments their potential use in clinical practice.

OBJECTIVE. IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and fibrosis in various organs. The objective of this study is to investigate CT findings of IgG4-related lesions involving the upper urinary tract and compare them with those of urothelial carcinomas. MATERIALS AND METHODS. This study reviewed pretreatment CT images of 13 consecutive patients with IgG4-related disease with upper urinary tract lesions and 80 consecutive patients with urothelial carcinomas. The findings assessed were laterality, location, growth pattern, margins, internal structure, presence of calcification and lipid component, enhancement pattern, and extraurinary findings. RESULTS. Bilaterality (p < 0.0001), an extramural growth pattern (p < 0.0001), a greater number of affected segments (p = 0.04), and a gradual dynamic enhancement pattern (p < 0.001) were significantly more frequent in patients with IgG4-related disease. With regard to extraurinary findings, paraaortic fat stranding (p = 0.03), presacral fat stranding (p < 0.001), fat stranding of the pelvic walls (p < 0.001), and aortic involvement (p < 0.001) were seen more frequently in patients with IgG4-related disease; on the other hand, there was no statistically significant difference in terms of frequency of pancreatic involvement. Hydronephrosis and renal involvement were seen more frequently in patients with urothelial carcinoma, although the difference was not statistically significant. CONCLUSION. CT findings suggestive of IgG4-related upper urinary tract lesions in comparison with urothelial carcinoma are bilateral and have a longer urinary tract involvement and exhibit an extramural growth pattern, ill-defined margins, a gradual enhancement pattern, aortic involvement, and fat stranding in the paraaortic, presacral, or pelvic wall areas.

Background. IgG4-related disease is a new disease entity, but little attention was drawn to urinary system involvement besides nephritis or nephropathy. Here, we described clinical, radiological, and pathological manifestations of IgG4-related urinary disease (IgG4-RUD) and assess its treatment responses. Methods. We conducted a retrospective study enrolling 65 IgG4-RUD patients from an IgG4-related disease (IgG4-RD) cohort of the Peking Union Medical College Hospital. Clinical, laboratory, radiological, pathological data were collected, and treatment response to immunosuppressants were analysed. Results. IgG4-related interstitial nephritis (TIN, 32.3%), glomerular nephritis (GN, 7.7%), renal pelvis and ureter involvement (21.5%), abnormal radiology with quiescent clinical presentation (13.8%), and renal parenchymal lesion plus retroperitoneal fibrosis (RPF, 18.5%) were major lesion types of IgG4-RUD. All patients had elevated serum IgG4, 76.9% had hyperglobulinemia, and 92.3% had elevated serum IgE at diagnosis. IgG4-TIN patients presented with renal dysfunction, and 94.3% had low serum complement C3 and IgG4-GN presented with nephrotic syndrome, while renal pelvis and ureter involvement had normal renal function and urinalysis. IgG4-RPF with renal parenchymal involvement presented with acute renal dysfunction and required emergency medical intervention. Renal cortex low-density areas, parenchyma or pelvis nodular mass, bilateral enlargement of the kidney, and renal pelvis and ureter mass/wall thickening were specific image patterns of IgG4-RUD. Infiltration of plasma lymphocytes and storiform fibrosis were histopathological features of IgG4-RUD. Patients showed satisfactory responses to immunosuppressive treatment, but complete recovery of renal function was difficult to achieve in IgG4-TIN. Four patients (6.2%) experienced clinical relapses during the maintenance period. Conclusion. IgG4-RUD had diverse lesion types and distinctive manifestations. Radiological examinations were helpful for diagnosis and treatment evaluation. Patients showed good initial response to immunosuppressive treatment but relapses could occur at the maintenance period.

IgG4-related disease (IgG4-RD) is a condition that was first described recently, and is capable of affecting any organ of the body. Diagnosis is based on the correlation of clinical findings with histopathological findings and elevated serum IgG4. Treatment involves corticosteroids and rituximab for the most severe cases. We report the case of a symptomatic patient diagnosed of IgG4-RD whose diagnosed was guided by elevated serum IgG4 levels.

Background: Serum IgG4 is typically measured to investigate for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. However, increased IgG4 can also be monoclonal, and little is known about IgG4 myeloma. Methods: We describe two cases of IgG4 myeloma without clinical, radiologic, or laboratory features of IgG4-related disease. Results: An 84 year old man presented with anemia and compression fractures and a 77 year old man presented with anemia, hypercalcemia and renal failure. Both had markedly elevated monoclonal serum IgG4, 34 g/L and 48 g/L in the beta region, and increased IgG positive bone marrow plasma cells, 50% and 80%, respectively. Neither had clinical or radiological manifestations of IgG4-related disease (IgG4-RD) such as salivary or lacrimal gland swelling, autoimmune pancreatitis , or retroperitoneal fibrosis. Both cases responded well to standard myeloma therapy. The IgG4 paraprotein caused spuriously elevated beta-2 microglobulin of 45.2 mg/L in case two due to interference with the assay. Conclusion: These cases illustrate the importance of performing serum protein electrophoresis in tandem with IgG subclasses to distinguish between polyclonal and monoclonal increases in serum IgG4. The lack of typical IgG4-RD features in these two patients suggests that monoclonal elevation in serum IgG4 alone is insufficient to cause the organ damage characteristic of IgG4-RD. Larger studies of IgG myeloma subtypes are warranted to explore whether IgG1, IgG2, IgG3 and IgG4 myeloma differ in natural history and whether the interference with beta-2 microglobulin is specific to IgG4 monoclonal proteins.

Objective We believe that IgG4 may have a role in the pathogenesis of Peyronie's disease (PD), and this role could be particularly beneficial for developing new strategies; therefore, we aimed to investigate the role of IgG4 in PD. Methods This study included 3 groups with a total of 139 subjects: (I) PD group (n=61), (II) control group (n=48), and (III) benign prostatic hyperplasia (BPH) group (n=30). IgG4 measurement was performed using the enzyme-linked immunosorbent assay. Plaque size, penile curvature, and the presence of concomitant impotence were evaluated in the PD group. Impotence was assessed based on the International Index of Erectile Function (IIEF). Results A significant difference was observed between the PD and control groups and between the PD and BPH groups with regard to IgG4 levels, while no significant difference was found between the BPH and control groups (p=0.0001, p=0.002, and p=0.07, respectively). The IgG4 levels were significantly higher in the PD than in the other groups. The cutoff value determined between the groups was 87.5, 82, and 31.5, respectively. Mean plaque size was 2.0±1.01 cm, and a significant relationship was found between plaque size and IgG4 concentration (p=0.02). Mean penile curvature was 35.6±25.1°, and a significant relationship was found between penile curvature of >60° and IgG4 concentration (p=0.001). Mean IIEF score was 19 (range, 7-25). Moreover, no significant relationship was found between erectile dysfunction and IgG4 concentration. Penile pain was present in 24 (39.3%) patients with PD. Conclusion The IgG4 levels were significantly increased in patients with PD, which implies that IgG4 may have a role in the pathogenesis of PD. This finding could be particularly beneficial for developing new strategies. Future studies with larger patient series are needed to substantiate our findings.

IgG4-related disease is a chronic fibroinflammatory disorder that is becoming increasingly recognized in the pediatric population. The orbit is one of the most commonly affected sites. We present the youngest case of IgG4-related ophthalmic disease in the literature, with an immunodeficiency phenotype associated with a homozygous IRAK-4 variant gene. We also review the clinical and histological features in children with IgG4-related ophthalmic disease. In addition to the young age of presentation, the case is unique for absence of lacrimal gland involvement, dural enhancement on magnetic resonance imaging, and an association with an IRAK-4 deficiency phenotype. Management required a multidisciplinary approach, with judicious use of immunosuppression. IgG4-related ophthalmic disease should be considered as a differential diagnosis in infants and children presenting with an orbital mass. Further, a particularly young age of onset may indicate an overarching immune dysregulation syndrome.

Immunoglobulin G4 (IgG4)–related disease was first identified as a systemic condition in 2003 when extrapancreatic manifestations were identified in patients with autoimmune pancreatitis. Its peak incidence occurs in the fifth or sixth decades of life. Isolated extraaortic mediastinal involvement is extremely rare. This report describes a case of isolated extraaortic mediastinal IgG4-related disease encasing the superior vena cava (SVC) and manifesting as SVC syndrome in a 25-year-old man with no personal or family history of autoimmune disease. Resection with SVC reconstruction was performed.

Prostate involvement by IgG4-related disease (IgG4-RD) is a rarely described organ manifestation and knowledge regarding its frequency and clinical features is limited.From a single-center cohort, 168 male patients were examined who satisfied the 2019 ACR/EULAR classification criteria or 2012 consensus histopathologic criteria for IgG4-RD.Prostate involvement were identified in 25 (15%) of these cases. The majority of patients with IgG4-RD involving the prostate gland (80%) were symptomatic at presentation with incomplete voiding (64%), urinary frequency (52%), and urinary hesitancy (48%) being the most common complaints. The radiologic presentation of prostate disease is most often a focal abnormality suggesting inflammation rather than a mass lesion. While most patients with IgG4-related prostate disease (89%) experienced recurrence after or during glucocorticoid tapering, patients treated with B cell targeted therapy in this series experienced clinical improvement and were tapered off of glucocorticoids. Additionally, patients with IgG4-RD involving the pancreas (p = 0.001) were more likely to have prostate involvement than were those with other types of organ involvement.This report provides the first comprehensive clinical description of IgG4-RD involving the prostate gland and links this manifestation with pancreatic involvement.

Objectives To evaluate the efficacy and safety of leflunomide (LEF) and glucocorticoids (GCs) combination therapy compared with GCs monotherapy in preventing relapse of IgG4-related disease (IgG4-RD). Methods A 12-month, randomized, open-label, controlled trial was conducted at a large academic medical center (ClinicalTrials.gov: NCT02703194). Enrolled patients with active IgG4-RD were randomly allocated to the GCs + LEF (20 mg/day) combination therapy or GCs monotherapy group. All patients received GCs with a predefined taper regimen starting from a dosage of 0.5–0.8 mg/kg/d. The primary outcome was the time to relapse. The secondary outcomes included complete response, remission, GCs dosage, and serum IgG4 level. Results Sixty-six patients with active IgG4-RD were enrolled (33 patients in each group). The demographic and disease characteristics showed no statistically significant differences between groups. Additionally, the initial GCs dosages were similar (50.00 vs. 50.00 mg/day, P = 0.295). Disease relapses occurred in 6 (18.2%) and 14 (42.4%) patients in the combination therapy group and GCs monotherapy group, respectively (P = 0.032). The combination therapy was significantly superior to GCs monotherapy regarding the primary outcome, the time to relapse (HR, 0.35; 95% confidence interval [CI], 0.13–0.90; P = 0.023), as well as the secondary outcome, the time to complete response (HR, 1.75; 95% CI, 1.01–3.02; P = 0.034). A longer duration of remission was observed in the combination therapy group (7.00 vs. 3.00 months, P = 0.002) and less cumulative dosage of GCs was used (5103.13 vs. 5637.50 mg, P = 0.031). Additionally, a higher proportion of patients in the combination therapy group (54.5%) were able to reach a daily GCs dose of ≤5 mg/day compared with the GCs monotherapy group (18.2%) (P = 0.006). The incidences of adverse events were similar in the 2 groups (P = 0.325). Conclusion LEF in combination with GCs therapy is well-tolerated and significantly superior to GCs monotherapy in preventing the relapse of IgG4-RD. LEF can be used as a steroid-sparing agent in the management of IgG4-RD.

Objective To clarify relevant proteins and clinical characteristics of a phenotype of IgG4-related disease (IgG4-RD) with lymphadenopathy. Methods We enrolled patients newly diagnosed with IgG4-RD in our department between January 2000 and June 2018 and performed proteomic analysis to measure serum concentrations of 1305 proteins. We extracted proteins overexpressed in patients with IgG4-RD with lymphadenopathy by comparing between those with lymphadenopathy, those without lymphadenopathy and healthy controls. We further reviewed all the patients with IgG4-RD in our institution and investigated the characteristics and prognosis of the patients with IgG4-RD with lymphadenopathy. Results Eighty-five patients with IgG4-RD were enrolled, of which, 55% had lymphadenopathy. Proteomic analysis in 31 patients with IgG4-RD and 6 healthy controls revealed that eotaxin-3 was a potential serum biomarker in the patients with lymphadenopathy versus those without lymphadenopathy and healthy controls. A cohort of 85 patients with IgG4-RD demonstrated that patients with lymphadenopathy showed a significantly higher serum IgG4, IgG4:IgG ratio, IgG4-RD responder index and eosinophilia (P Conclusion Lymphadenopathy in IgG4-RD represents a phenotype associated with high disease activities, eosinophilia and relapsing disease. Eotaxin-3 is a novel biomarker related to IgG4-RD with lymphadenopathy.