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IgG4-related disease (lgG4-RD) is a chronic fibroinflammatory disorder with systemic involvement, predominantly affecting middle-aged and elderly males. Although the precise etiology and pathogenesis of the disease remain incompletely understood, its hallmark histopathological features include dense lymphoplasmacytic infiltration with IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and often increased numbers of eosinophils. While more than half of patients with IgG4-RD exhibit elevated serum IgG4 concentrations, this finding lacks specificity as it can also be observed in other conditions; furthermore, a subset of patients may present with normal serum IgG4 levels. Therefore, serum IgG4 elevation is not considered a definitive diagnostic criterion for this condition. The disease is characterized by its broad organ involvement frequently affecting the lymph nodes, salivary glands, lungs among others. The clinical and radiological manifestations of IgG4-RD exhibit a wide range of diversity, varying according to the specific organ involved. However, it generally demonstrates a favorable response to corticosteroid therapy while displaying a high propensity for relapse. Thoracic involvement in IgG4-RD presents an array of imaging findings encompassing abnormalities in the lungs, lymph nodes, pleura, chest wall, mediastinum, as well as large vessels such as the aorta and coronary arteries. Accurately differentiating IgG4-RD from malignancies, inflammatory conditions, and other autoimmune diseases poses a significant diagnostic challenge specifically for radiologists. This review aims to provide comprehensive insights into the pathophysiology, clinical characteristics, and thoracic imaging features of IgG4-RD with the ultimate goal of facilitating precise diagnosis and thorough evaluation of thoracic involvement. [ABSTRACT FROM AUTHOR]

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

IgG4-related disease (IgG4-RD) is a rare illness with inflammatory and fibrotic changes in affected organs such as pancreas, thyroid, salivary or lacrimal glands, and retroperitoneal space; rarely other organs may be involved. IgG4-related breast disease (IgG4-BD) is very rare and generally presents as a lump or mastitis. IgG4-BD as a presenting feature of IgG4-RD is extremely rare. Hence, this paper reviews the known (n=48) IgG-BD cases reported in the literature to date. The majority of cases were diagnosed on routine mammography or during assessment for other clinically significant features. The absence of a lump border, and especially the absence of calcifications on ultrasonography, mammography, or computed tomography, is typical for IgG4-BD. Characteristic IgG4-BD pathological findings were dense lymphoplasmacytic infiltration with stromal fibrosis, and more than 10% IgG4+ plasma cells/high-power field (HPF); the mean percentage of IgG4+/IgG+ plasma cells was 54.2%, and only one-third of the patients had all "classical" signs of IgG4-BD including storiform fibrosis and obliterative phlebitis. Most of the cases had a benign course and responded to surgical excision with or without steroid therapy. [ABSTRACT FROM AUTHOR]

Objectives: While autoimmune pancreatitis (AIP) responds well to steroid therapy, the high relapse rate in type 1 AIP remains a critical problem. The present study examined predictors of relapse of type 1 AIP following steroid therapy. Materials and methods: Nine factors potentially predictive of relapse were analyzed in 81 AIP patients receiving steroid therapy with follow-up ≥ 12 months. The rate of serum IgG4 decrease following steroid therapy was calculated by dividing the difference between serum IgG4 values before and at two months after the start of steroid by the IgG4 value before steroid. Results: A relapse occurred in 11 patients (13.5%) during a median of 38 months. Multivariate analysis revealed that the presence of IgG4-related retroperitoneal fibrosis (HR: 5.59; 95% CI: 1.42–22.0; p = 0.014) and the low rate of serum IgG4 decrease after steroid therapy (HR: 0.048; 95% CI: 0.005–0.46; p = 0.008) were significant, independent predictors of AIP relapse. The cut-off value based on receiver operating characteristic curve data for the rate of serum IgG4 decrease before and at two months after steroid therapy distinguishing patients with and without a relapse was 0.65. Using this cut-off value, the area under the curve, sensitivity, and specificity were found to be 0.63, 0.73, and 0.60, respectively. Conclusion: The low rate of serum IgG4 decrease after the start of steroid therapy and the presence of IgG4-related retroperitoneal fibrosis were predictive of type 1 AIP relapse. Cautious, gradual tapering of steroid dosage and longer maintenance therapy are recommended for patients with these factors. [ABSTRACT FROM AUTHOR]

Background: To investigate the potential utility of quantitative parameters obtained by 18F-fibroblast activation protein inhibitor positron emission tomography/computed tomography ([18F]AlF-NOTA-FAPI-04 PET/CT) in the assessment of organ involvement and disease activity in IgG4-related disease (IgG4-RD). Methods: This study enrolled patients who underwent [18F]AlF-NOTA-FAPI-04 PET/CT scans at the Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine from August 2021 to August 2022. The PET/CT images of the included patients were re-evaluated by PET center technicians, and the maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion FAPI (TL-FAPI) were used to evaluate the involved organs and tissues that abnormally accumulated [18F]AlF-NOTA-FAPI-04. The clinical and laboratory data of patients are also systematically collected and analyzed. Results: Among the patients included in this study, 12 patients met the IgG4-RD classification criteria established by the American College of Rheumatology in 2019. Among them, 8 were males and 4 were females, with an average age of 59.3 ± 11.5 years. 50% of IgG4-RD patients were found with more organ involvement on PET/CT than physical examination, ultrasonography, and computed tomography. IgG4 levels (Rho = 0.594, p = 0.042) and IgG4-RI (Rho = 0.647, p = 0.023) were significantly positively correlated with TL-FAPI. After linear regression analysis, only TL-FAPI showed a predictive value of RI (R2 = 0.356, B = 0.008, p = 0.041). Conclusions: [18F]AlF-NOTA-FAPI-04 PET/CT is a useful tool for identifying asymptomatic organ involvement and assessing disease activity. The TL-FAPI as an indicator was positively correlated with IgG4-RD disease activity. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4–related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory failure. This systematic literature review aims to summarise the pulmonary manifestations of IgG4-RD, including clinical outcomes and treatment. This review was registered on PROSPERO (CRD42023416410). Medline, Embase and Cochrane databases were searched for articles discussing IgG4-RD syndrome. Information was extracted on demographics, type and prevalence of pulmonary manifestations, treatment and clinical outcomes. Initially, after deduplication, 3123 articles were retrieved with 18 ultimately included. A pooled total of 724 patients with IgG4-RD were included, 68.6% male, mean age 59.4 years (SD 5.8) at disease onset. The most frequently described pulmonary manifestation was mediastinal lymphadenopathy (n = 186, 48.8%), followed by pulmonary nodules (n = 151, 39.6%) and broncho-vascular thickening (n = 85, 22.3%). Where treatment was reported, the majority of patients received glucocorticoids (n = 211, 93.4%). Other immunosuppressive therapy included cyclophosphamide (n = 31), azathioprine (n = 18), with mycophenolate mofetil (n = 6), rituximab (n = 6), methotrexate (n = 5) and other unspecified immunomodulators (50). Clinical outcomes were reported in 263 patients, where 196 patients had remission of their disease, 20 had relapse, 35 had stable disease, four had progression and eight patients died from complications of IgG4-RD. This systematic review summarises pulmonary manifestations, treatments and outcomes in patients with IgG4-RD. Pulmonary involvement in IgG4-RD is relatively common, leading to high levels of morbidity and mortality. Glucocorticoids remain the mainstay of treatment, but further work is required to explore the management of patients with pulmonary manifestations in association with IgG4-RD. [ABSTRACT FROM AUTHOR]

Background Although coronary artery involvement in patients with IgG4-related disease (IgG4-RD) is rare, emergency revascularization is recommended for managing acute coronary syndrome. However, coronary aneurysm formation and stent migration after sirolimus-eluting stent implantation have been reported for this disease. Thus, new treatment modalities are warranted for the management of coronary artery disease in this vasculitis. Case summary A 70-year-old male who experienced progressive chest discomfort for 1 month underwent cardiac examination. Coronary computed tomography angiography (CCTA) revealed right coronary artery hypoplasia, coronary artery aneurysm with severely calcified stenosis in the proximal left anterior descending artery (LAD), and subtotal obstruction in the mid-LAD. The left circumflex artery (LCX) also had stenosis and dilated lesions. Additionally, diffuse perivascular soft tissue thickening was observed in the mid-LCX. The percutaneous coronary intervention was performed for the proximal- and mid-LAD lesions. Rotational atherectomy with low-pressure drug-coated balloon (DCB) dilation was considered for these lesions owing to suspicion of vasculitis. The patient was later diagnosed with Sjögren's syndrome and IgG4-RD overlap syndrome. Oral steroids and immunosuppressive drugs were initiated. In a follow-up at 7 and 26 months, late lumen enlargement was observed in the treated area of the LAD, without enlargement of the adjacent aneurysm. CCTA performed after 26 months revealed resolution of the diffuse perivascular soft tissue thickening in the mid-LCX. Discussion To our knowledge, this is the first case report demonstrating favourable outcomes for treatment of a coronary artery lesion attributed to IgG4-RD with DCB, leaving nothing implanted in the coronary artery tree. [ABSTRACT FROM AUTHOR]

IgG4-related diseases (IgG-RDs) are a group of fibroinflammatory diseases that affect a variety of tissues, resulting in tumour-like effects and/or organ dysfunction. Monoclonal gammopathies (MGPs) are a group of disorders characterized by clonal proliferation of plasma cells or lymphoid cells resulting in the secretion of a monoclonal immunoglobulin. Cases of MGPs in IgG4-RDs coexisting with plasma cell dyscrasias and lymphoid neoplasms have been reported over the past few years. Therefore, the results of examinations of M protein in IgG4-RD patients should be interpreted with caution. Herein, we report the case of a 58-year-old male with a history of type 2 diabetes who presented with submandibular masses, anosmia, swollen lymph nodes, proteinuria, and renal impairment. Laboratory tests revealed hyperglobulinemia and elevated levels of IgG4 (124 g/L) and serum-free light chains (sFLCs). Serum protein electrophoresis (SPEP) revealed an M spike of 5.6 g/dL, and immunofixation electrophoresis (IPE) revealed biclonal IgG-κ and IgG-λ. The patient underwent bone marrow, lymph node, and kidney biopsy, which ruled out plasma cell disorders and lymphoma. He was finally diagnosed with an IgG4-RD comorbid with diabetic nephropathy. The findings in this case highlight that significant activation of B cells in IgG4-RD patients, especially those with multiorgan involvement can lead to significant hyperglobulinemia and high sFLC and IgG4 levels, which are more pronounced in the setting of renal impairment. Relatively high concentrations of polyclonal IgG4 can give rise to a focal band bridging the β and γ fractions, which may mimic the appearance of a monoclonal band on SPEP and monoclonal gammaglobulinemia in IFE. The patient experienced considerable improvement in his symptoms after rituximab combined with glucocorticoid therapy, and a monoclonal immunoglobulin was not detected. [ABSTRACT FROM AUTHOR]

• For IgG4-related disease, rituximab induction therapy has shown satisfactory efficacy and favorable safety profile. • Rituximab maintenance therapy further reduces the relapse rate and prolongs the free-relapse time of IgG4-related disease patients. • Further research, especially randomized control trials, encompassing larger sample sizes and long-term follow-up, is warranted to evaluate the efficacy and safety of rituximab induction and maintenance therapy in the treatment of IgG4-related disease. Previous studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. The protocol was registered in the PROSPERO (CRD42023427352). PubMed, Embase, the Cochrane database, Scopus, and the Web of Science were interrogated to identify studies that evaluated the impact of RTX on prognosis in IgG4-RD. We explored the impact of various subgroups of factors on relapse outcomes and focused on the possible role of maintenance therapy in reducing relapse rates. The pooled incidence of adverse events of RTX therapy and the influencing factors have also been evaluated. Eighteen studies comprising 374 patients (mean age 56.0 ± 8.7 years; male 73.7 %) with a mean follow-up duration of 23.4 ± 16.3 months were included. The pooled estimate of the response rate, complete remission rate, overall relapse rate, adverse event rate, and serious adverse event rate of RTX induction therapy were 97.3 % (95 % CI, 94.7 %–99.1 %), 55.8 % (95 % CI, 39.6 %–71.3 %), 16.9 % (95 % CI, 8.7 %–27.1 %), 31.6 % (95 % CI, 16.7 %–48.9 %) and 3.9 % (95 % CI, 0.8 %–8.9 %), respectively. In subgroup analysis, the pooled relapse rate was significantly lower in studies with maintenance than without maintenance (2.8% vs 21.5 %, p < 0.01). Pooled Kaplan-Meier relapse curves also demonstrated that RTX maintenance therapy provided a better prognosis. RTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the histological characteristics and treatment efficacy of non-immunoglobulin G4-related fibrosing mediastinitis and discuss differential diagnoses for this rare entity. Methods: We present a case study of non-immunoglobulin G4-related fibrosing mediastinitis diagnosed on core biopsy and treated with steroids. A total of four 18-gauge core needle biopsy specimens were obtained for surgical pathology. Analysis of the patient's medical history, radiological characteristics of fibrosing mediastinitis, histological features, immunohistochemistry results, the differential diagnosis and treatment efficacy of different types of fibrosing mediastinitis was performed. Results: This report describes a unique presentation of fibrosing mediastinitis (syncope and weight loss) that was concerning for malignancy. Histological, laboratory and radiographical studies confirmed the diagnosis of non-immunoglobulin G4-related fibrosing mediastinitis. The patient received corticosteroid treatment which showed marked improvement after 1 month of treatment. Conclusions: Fibrosing mediastinitis is an extremely uncommon entity with unknown pathogenesis, and it is more important to rule out malignancy and infection than to delineate between fibrosing mediastinitis and IgG4-related disease. In doing this, we may reasonably initiate a trial of corticosteroids which may prove beneficial, as in this patient. More studies on the pathogenesis of fibrosing mediastinitis are necessary to guide better directed treatments. [ABSTRACT FROM AUTHOR]

[Display omitted] Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function (GOF) IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. We studied 7 relatives with autoimmune/inflammatory and lymphoproliferative manifestations to identify the immunologic disturbances and the genetic cause of their disease. We analyzed biopsy results and performed whole-exome sequencing and immunologic studies. Disease onset occurred at a mean age of 25.2 years (range, 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, 4 had confirmed IG4-related disease (IgG4-RD), and 5 developed B-cell malignancies: lymphoma in 4 and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening coronavirus disease 2019 pneumonia, of whom 1 had autoantibodies neutralizing IFN-α. The recently described IKZF1 GOF p.R183H variant was found in the 5 affected relatives tested and in a 6-year-old asymptomatic girl. Immunologic analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, effector memory CD4 T cells that have regained surface expression of CD45RA and CD28−CD57+ CD4+ and CD8+ T cells, T H 2, and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in 3 patients. Heterozygosity for GOF IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD, and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunologic data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity. [ABSTRACT FROM AUTHOR]

Introduction: Lymphocyte-rich inflammation of the esophageal mucosa has gained increased awareness among pathologists and clinicians recently. Patients usually present with symptoms of esophageal dysfunction, including dysphagia and food bolus impaction. Endoscopy may show changes similar to eosinophilic esophagitis but may also be entirely normal ('microscopic esophagitis'). Three morphological subtypes or variant forms have been described which include lymphocytic, lichenoid and lymphocyte-predominant esophagitis. These need to be discriminated against other distinct causes of esophageal lymphocytosis, such as gastro-esophageal reflux disease and Candida infection. Areas covered: This review provides an overview of diagnostic criteria and clinical associations of the disorder and presents an algorithmic approach to diagnosis. A comprehensive literature review was conducted using PubMed, Medline and Google Scholar databases to identify articles related to lymphocyte-rich esophageal inflammation, published up to March 2024. Expert opinion: Lymphocyte-rich inflammation needs to be included in the differential diagnosis and clinical work-up of patients with esophageal dysfunction. There is currently considerable morphological overlap among published subtypes or variant forms. Follow-up studies of affected individuals are needed to formalize diagnostic parameters and identify the clinical course of disease in order to optimize treatment modalities. [ABSTRACT FROM AUTHOR]

A 60-year-old female with a BRCA2 mutation and a history of breast cancer presented with diffuse abdominal pain and elevated liver enzymes. Imaging revealed a porta-hepatis mass, prompting consideration of hilar cholangiocarcinoma or breast cancer metastasis. Further investigation including biopsy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings were inconsistent with malignancy, leading to investigation of non-neoplastic causes. Elevated IgG4 levels suggested IgG4-related disease, a mass-forming fibroinflammatory condition. This case demonstrates IgG4-related disease exclusively impacting the portal vein and underscores the importance of considering IgG4-related disease in the differential diagnosis of hepatic masses.

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

Abstract Background Elevated serum immunoglobulin G4 (IgG4) concentrations are one of the characteristic findings in IgG4-related disease (IgG4-RD). This study investigated the frequency of elevated serum IgG4 levels and associated factors in a general Japanese population. Methods Serum IgG4 concentrations were measured in 1,201 residents of Ishikawa prefecture who underwent general medical examinations. Factors associated with elevated serum IgG4 concentrations were assessed by logistic regression analysis. Participants with elevated serum IgG4 were subjected to secondary examinations. Results The mean serum IgG4 concentration was 44 mg/dL, with 42 (3.5%) participants having elevated serum IgG4 levels. Age- and sex-adjusted logistic regression analyses showed that male sex, older age, and lower intake of lipids and polyunsaturated fatty acids and higher intake of carbohydrates in daily diet were associated with elevated serum IgG4 concentration. Subgroup analyses in men showed that older age, lower estimated glomerular filtration rates based on serum cystatin C (eGFR-cysC) levels, and higher hemoglobin A1c (HbA1c) levels were associated with elevated serum IgG4 concentration. Analyses in women showed that lower intake of lipids and fatty acids and higher intake of carbohydrates were significantly associated with elevated serum IgG4 concentration. One of the 15 participants who underwent secondary examinations was diagnosed with possible IgG4-related retroperitoneal fibrosis. Conclusions Elevated serum IgG4 levels in a Japanese general population were significantly associated with older age, male gender, and dietary intake of nutrients, with some of these factors identical to the epidemiological features of IgG4-RD.

A paraganglioma is a neuroendocrine tumor that may secrete catecholamines and present with symptoms of sympathetic overload such as hypertension and diaphoresis. It is important that paragangliomas are identified, as they must often be treated by surgical excision. IgG4-related retroperitoneal fibrosis (IgG4-RPF) is a systemic inflammatory disease that results in the infiltration of IgG4-positive plasma cells in the retroperitoneum. Such fibrosis may adversely affect nearby organs and tissues. Here, we describe a case of combined paraganglioma and IgG4-RPF in a 47-year-old female patient. This case demonstrates the deleterious effect of these two conditions when they occur simultaneously.

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

Abstract Background Chronic pancreatitis (CP) is common in English cocker spaniels (ECS). It is histologically similar to IgG4‐related disease (IgG4‐RD) in humans and is characterized by duct destruction, interlobular fibrosis, and dense periductular and perivenous lymphocytic aggregates. However, the clinical manifestations of CP in ECS have not been previously described. Objectives Characterize the clinical manifestations of CP in a group of ECS, including similarities and differences to IgG4‐RD in humans. Animals One‐hundred four ECS with CP and 44 client owned control ECS without CP (both healthy and diseased controls). Methods Affected dogs were divided into 2 groups according to the methods used to diagnose CP. Case records were searched for signalment, clinical, and clinicopathological findings, and evidence of keratoconjunctivitis sicca (KCS), proteinuria, other immune‐mediated diseases, and anal sacculitis. Results Involvement of other organs was common. Affected ECS presented with a high frequency of KCS (n = 49), proteinuria (n = 47), anal gland disease (n = 36), atopy (n = 21), and other immune‐mediated diseases (n = 16). Those with parti‐color hair coats, particularly blue roan, had a strong association with CP, suggesting a link between coat color and autoimmune conditions in this breed. Conclusions and Clinical Importance English cocker spaniels with CP show clinical similarities to humans with IgG4‐RD and common involvement of other organs. Clinicians should evaluate affected Cocker Spaniels for proteinuria, keratoconjunctivitis sicca, and other potential immune‐mediated diseases.

Abstract Background IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. Case presentation : A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz’s disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. Conclusion Mikulicz’s disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

Background: To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. Methods: Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. Results: Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96–1.00), body mass index (1.10, 1.03–1.18), and tofacitinib (0.34, 0.14–0.79). Further analysis indicated that age (1.10, 1.03–1.16), coronary heart disease (24.38, 3.33–178.33), COVID-19-related dyspnea (7.11, 1.85–27.34), pulmonary infection (73.63, 16.22–4615.34), and methotrexate (17.15, 1.93–157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89–0.98), male sex (0.16, 0.03–0.80), ever/current smoking (19.23, 3.78–97.80), COVID-19-related headache (2.98, 1.09–8.17) and psychiatric symptoms (3.12, 1.07–9.10), disease activity before COVID-19 (1.89, 1.02–3.51), number of involved organs (1.38, 1.08–1.76), glucocorticoid dosage (1.08, 1.03–1.13), and methotrexate (5.56, 1.40–22.08) were strong factors for COVID-19-related IgG4-RD relapse. Conclusions: Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages. [ABSTRACT FROM AUTHOR]

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

Immunoglobulin G4 (IgG4)-related disease is a clinical entity characterized by elevated serum IgG4 concentrations and infiltration of IgG4-immunopositive plasmacytes in various organs, including ophthalmic lesions. Diagnostic criteria for IgG4-related ophthalmic disease (IgG4-ROD) were established in 2014 and describe the most affected ocular adnexal tissues such as lacrimal glands, trigeminal nerves and extraocular muscles, but do not mention optic neuropathy, the most severe indication of ophthalmic lesions. We reviewed published case reports of optic neuropathy in IgG4-related disease (n = 44), and in many cases, decreased visual acuities recovered well following treatment such as systemic corticosteroids, rituximab, and orbital surgery. However, some patients did not recover, especially when pretreatment visual acuities were as low as light perception or less. Herein, we propose a 2023 revised diagnostic criteria for IgG4-ROD, which include a reminder not to overlook optic neuropathy. The 2014 diagnostic criteria specify mucosa-associated lymphoid tissue (MALT) lymphoma as an important differential diagnosis for the relationship between IgG4-ROD and orbital lymphoma. The 2023 revision directs physicians' attention toward lymphomas other than MALT lymphoma, considering that the 2014 criteria might have placed too much emphasis on MALT lymphoma. [ABSTRACT FROM AUTHOR]

This article discusses the rare occurrence of urinary bladder involvement in IgG4-related disease (IgG4-RD). It presents a case study of a 39-year-old male who initially presented with urinary symptoms and was suspected to have bladder carcinoma. However, further investigations confirmed the diagnosis of IgG4-RD. The patient was treated with glucocorticoids and showed improvement after one year of follow-up. The article emphasizes the importance of considering IgG4-RD in the differential diagnosis of urinary bladder masses and the need for prompt treatment to minimize damage. [Extracted from the article]

This article presents a case study of a 39-year-old man with ulcerative colitis and IgG4-related disease who experienced a relapse despite treatment with tacrolimus and 6-mercaptopurine. The patient was then treated with tofacitinib, a Janus-associated kinase inhibitor, which successfully maintained remission of both diseases while allowing for a reduction in glucocorticoid dose. The case suggests that Janus-associated kinase inhibitors may be a promising treatment option for complex cases of IgG4-related disease, particularly when there are concurrent conditions such as ulcerative colitis. Further research is needed in this area. [Extracted from the article]

Autoimmune pancreatitis (AIP) is an immune - mediated, special type of chronic pancreatitis, which can involve multiple organs. The clinical manifestation of AIP is complex and varied, making the diagnosis and treatment challenging. With reference to the latest guidelines and studies from both domestic and international sources, this guideline comprises 20 recommendations regarding the diagnosis, treatment, follow-up, and prognosis of AIP. The aim of this guideline is to promote the care capability and improve the outcome of patients with AIP in China. [ABSTRACT FROM AUTHOR]

Background: Chronic pancreatitis (CP) is common in English cocker spaniels (ECS). It is histologically similar to IgG4‐related disease (IgG4‐RD) in humans and is characterized by duct destruction, interlobular fibrosis, and dense periductular and perivenous lymphocytic aggregates. However, the clinical manifestations of CP in ECS have not been previously described. Objectives: Characterize the clinical manifestations of CP in a group of ECS, including similarities and differences to IgG4‐RD in humans. Animals: One‐hundred four ECS with CP and 44 client owned control ECS without CP (both healthy and diseased controls). Methods: Affected dogs were divided into 2 groups according to the methods used to diagnose CP. Case records were searched for signalment, clinical, and clinicopathological findings, and evidence of keratoconjunctivitis sicca (KCS), proteinuria, other immune‐mediated diseases, and anal sacculitis. Results: Involvement of other organs was common. Affected ECS presented with a high frequency of KCS (n = 49), proteinuria (n = 47), anal gland disease (n = 36), atopy (n = 21), and other immune‐mediated diseases (n = 16). Those with parti‐color hair coats, particularly blue roan, had a strong association with CP, suggesting a link between coat color and autoimmune conditions in this breed. Conclusions and Clinical Importance: English cocker spaniels with CP show clinical similarities to humans with IgG4‐RD and common involvement of other organs. Clinicians should evaluate affected Cocker Spaniels for proteinuria, keratoconjunctivitis sicca, and other potential immune‐mediated diseases. [ABSTRACT FROM AUTHOR]

Orbital inflammatory disease (OID) is a heterogeneous group of immunologic disorders whose etiology is often non-specific despite routine investigation. In this proof-of-concept study, metagenomic deep sequencing (MDS) is applied to examine host gene expression in two subtypes of OID. Prospectively collected lacrimal gland tissue from patients with OID was processed for MDS. Differential gene expression analysis was performed to evaluate for host transcriptome signatures. Proof-of-concept comparison was made between histologically confirmed samples of idiopathic dacryoadenitis and IgG4-related disease (IgG4-RD). Twelve genes were identified to be differentially expressed between idiopathic dacryoadenitis and IgG4-RD. Differences in innate humoral immunity gene expression were observed. Several additional genes of interests were also found to be upregulated in idiopathic dacryoadenitis. A unique transcriptome signature was found when comparing idiopathic dacryoadenitis to IgG4-RD. This suggests that MDS can identify differentially expressed genes in OID. Such insight could potentially provide a better understanding of host gene expression and the inflammatory pathways involved in OID. [ABSTRACT FROM AUTHOR]

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases. [ABSTRACT FROM AUTHOR]

Purpose: Within the large umbrella of histiocytosis are a few similar yet heterogenous entities involving the orbit and periocular tissues with or without systemic infiltration, termed adult onset xanthogranuloma or orbital xanthogranuloma. Due to rarity of these conditions, different classifications in use, diverse clinical presentations and still unknown etiology, the aim of this paper was to provide an up-to-date literature review of the actual understanding of histiocytosis and its subgroups involving the orbit and periocular area, diagnostic strategies and therapeutic modalities. Methods: We present a review of literature and small case series comprising four patients diagnosed and treated in the period from 2001 until 2023 in our hospital. Clinical files of 4 patients with adult-onset xanthogranulomatous disease of the orbit and ocular adnexa (AOXGD) were reviewed retrospectively. Clinical, laboratory, radiological, histopathological, and immunohistochemical findings were reexamined. Results: Reviewing medical records of our patients with AOXGD, we found significant overlap between histiocytosis and different immune disorders. A broad workup should be considered in these patients as they can harbour severe immune disfunctions and hematologic disorders. Preferred treatment modality depends on a histopathologic type of AOXGD, clinical presentation and systemic involvement and should be conducted multidisciplinary. Conclusion: The diagnosis is often delayed because of its rarity and diverse clinical findings. Development of molecular genetic tests, detection of BRAF V600E mutation and different types of kinase mutations, mutations in transcriptional regulatory genes as well as tyrosine kinase receptors have shed a new light on the etiopathogenesis and potential targeted treatment of histiocytosis. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4+ plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention. [ABSTRACT FROM AUTHOR]

Background: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. Case presentation: : A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. Conclusion: Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly. [ABSTRACT FROM AUTHOR]

Constrictive pericarditis (CP) presents as a pathophysiological state where the pericardium becomes inelastic due to fibrotic changes, most commonly secondary to a protracted inflammatory process. The disease is characterized by compromised diastolic cardiac function due to loss of pericardial compliance. Immunoglobulin G4 (IgG4)-related disease, an entity marked by the insidious proliferation of IgG4-positive plasma cells and subsequent fibrosis within various organs, is an infrequent but recognized cause of CP. A case of a 55-year-old male patient with clinical manifestations of dyspnea and edema in the lower extremities elucidates the diagnostic complexity inherent to CP. Echocardiography revealed a constellation of signs, including annulus reversus, septal bounce, and a congested inferior vena cava; cardiac magnetic resonance imaging (MRI) demonstrated diffuse pericardial thickening with delayed gadolinium enhancement, suggestive of a long-term inflammatory state; and right heart catheterization confirmed the hemodynamic hallmark of CP—equalization of diastolic pressures across the cardiac chambers. The serological analysis elicited elevated serum levels of IgG4 and IgE, pointing to the differential diagnosis of IgG4-related disease. Given the nonspecific clinical presentation of IgG4-related CP, a heightened index of suspicion combined with a systematic approach to imaging and serological evaluation is paramount. [ABSTRACT FROM AUTHOR]

Lymphadenopathy is a common clinical finding and diagnostic challenge within general medicine and rheumatology practice. It may represent a primary manifestation of an underlying immune-mediated disease or indicate an infectious or neoplastic complication requiring differing management. Evaluating lymphadenopathy is of particular relevance in rheumatology, given that lymph node enlargement is a common finding within the clinical spectrum of several well-known rheumatologic disorders including RA, SLE and SS. In addition, lymphadenopathy represents a hallmark manifestation of rare immunological diseases such as Castleman disease and IgG4-related disease that must be considered in the differential diagnosis because effective targeted treatments can now impact the prognosis of these conditions. In this review we present an overview of the clinical significance of lymphadenopathy in common and rare rheumatologic diseases and propose a practical approach to lymphadenopathy in the rheumatology practice. Differential diagnosis of Castleman disease and therapeutic options for this condition of increasing rheumatologic interest will be discussed in detail. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic hypertrophic pachymeningitis (IHP) is a rare disorder presenting with headache, cranial and spinal neuropathy. This study is to explore the clinical, laboratory and imaging changes; treatment; and clinical outcomes of idiopathic hypertrophic pachymeningitis (IHP). Methods: This was a retrospective evaluation of 9 patients (5 men and 4 women; mean age: 53.6 years), their clinical features, laboratory tests, cerebral spinal fluid (CSF) analysis, MRI results, pathological features, treatment and clinical outcomes from a tertiary centre in Qingdao, North East China. The serum IgG4 was negative for all the cases. Results: Headache was the most common symptom (7/9), followed by oculomotor, trigeminal, abducens and facial nerve neuropathies, and limb numbness in one case. Two cases showed increased ESR and CRP, and four were positive for ANA or anti-SSA antibodies. On CSF analysis, 2/7 had increased pressure, and 4/7 showed lymphocytosis and high protein levels. MRI revealed a thickening and enhancement of the dura, mainly involving bilateral tentorium (85%), falx cerebri (57%), and cerebellar hemisphere (57%). The tissue biopsy of dura mater in three cases showed thickened collagen fibers, lymphocytosis and focal necrosis, with similar but not identical features to IgG4-related sclerosing disease. Most patients were treated with corticosteroids, and 79% showed improvement. The abnormal thickness and enhancement of the dura mater disappeared in one case. Conclusion: Gadolinium-enhanced MRI serves as the key preliminary investigation for the diagnosis and evaluation of the clinical course for IHP. Majority of patients have good respond to steroid. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case highlights the importance of a definite diagnosis of an IgG4‐related chronic sclerosing duodenitis based on histological and radiological findings to rule out any malignancy in the mass. While dealing with patients having concentric duodenal thickening resulting in stricture formation, one should think of inflammatory etiology as well. IgG4‐related disease is one of these inflammatory disorders where we see soft tissue thickening without a large mass or any associated lymphadenopathy as in our case. Immunoglobulin G4‐related disease (IgG4‐RD) is distinguished as an infiltration of IgG‐4‐positive plasmacytes involving inflammatory lesions across multiple organs which is accompanied by raised IgG4 levels in the serum. Several inflammatory disorders are recognized as part of the IgG4‐RD family based on shared histopathological features, which include Mikulicz's disease, chronic sclerosing sialadenitis, or Riedel's thyroiditis. Our case highlights a distinctive presentation of IgG4‐related diseases; a 58‐year‐old man presenting with duodenal stricture highly suspicious of a duodenal mass/ampullary mass later found to be due to IgG4‐related sclerosing duodenitis with negative malignancy on biopsy. We present the diagnostic challenges faced and relevant findings noted. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We should consider IgG4‐related disease (IGRD) as one of the potential causes of constrictive pericarditis. In patients with constrictive pericarditis due to IGRD, the combination of surgical treatment and immunosuppressive therapy may be an effective strategy. [ABSTRACT FROM AUTHOR]

This study aimed to review the lesser‐known intraoral manifestations of immunoglobulin G4‐related disease (IgG4‐RD). In this paper we report an unprecedented case of oral IgG4‐RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4‐RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow‐up duration. Fifty‐one cases of oral IgG4‐RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4‐RD should report clear adherence to the recognized international diagnostic criteria of the disease. [ABSTRACT FROM AUTHOR]

Background: IgG4-related disease (IgG4-RD) is an immune-mediated systemic inflammatory fibrotic disease, which is a relatively rare and novel disease that can involve multiple organs or tissues, with variable clinical manifestations, and for which pulmonary involvement has been reported relatively infrequently. Methods: Here we report a case of pulmonary infection that was initially suspected and received anti-inflammatory treatment, but the symptoms did not improve. CT examination indicated progression of the pulmonary lesion, and the nature of the lesion could not be determined by tracheoscopy and bronchoalveolar lavage. The diagnosis of IgG4 related lung disease (IgG4-RLD) was confirmed by percutaneous lung biopsy. A joint literature analysis was conducted to improve clinicians' understanding of this disease. Results: The patient's history, symptoms, signs and relevant examination results were analyzed. The final diagnosis was IgG4-RLD. Conclusions: When the clinical symptoms and imaging manifestations of the patients are consistent with IgG4-RLD, pathological examination can be appropriately performed to clarify the nature of the lesions. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and proper treatment should be given at an early stage. [ABSTRACT FROM AUTHOR]

Introduction: IgG4-related disease (IgG4-RD) is a rare disease entity in India. We aimed at studying the clinical profile of IgG4-RD of gastrointestinal tract (GIT) from our centre, while systematically reviewing data from India. Methods: Retrospective review of IgG4-RD of GIT was done using electronic medical records between January 2013 and July 2022. Literature search was done for studies of IgG4-RD of the GIT reported from India from 2000 till January 2023. Case series, case reports of IgG4-RD of GIT and case reports describing GIT with multi-organ involvement were included in the review. Primary outcome measure was response to treatment. Secondary outcome measure was relapse after remission. Results: Thirty-one patients were included with 71% (22/31) having autoimmune pancreatitis. The diagnosis was achieved on surgical specimen in 35% (11/31) patients. Steroid was given to 64% (20/31) patients with remission achieved in 70% (14/20) patients. Four patients exhibitted response to prolonged course of steroids with maintenance azathioprine. Relapse was seen in four (20%) patients who achieved remission. Of 731 articles screened, 48 studies (four case series and 44 case reports) were included in the literature review. Of 95 patients described, steroids were given to 65.2% (62/95), while surgery was done in 33.6% (32/95). Remission was seen in 96.6% (85/88) with relapse occurring in 11.4% (10/88) patients on follow-up. Conclusion: One-third patients of IgG4-RD of GIT are diagnosed after surgery. Response to steroids is good with relapse occurring in up to 12% patients. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is a rare illness with inflammatory and fibrotic changes in affected organs such as pancreas, thyroid, salivary or lacrimal glands, and retroperitoneal space; rarely other organs may be involved. IgG4-related breast disease (IgG4-BD) is very rare and generally presents as a lump or mastitis. IgG4-BD as a presenting feature of IgG4-RD is extremely rare. Hence, this paper reviews the known (n=48) IgG-BD cases reported in the literature to date. The majority of cases were diagnosed on routine mammography or during assessment for other clinically significant features. The absence of a lump border, and especially the absence of calcifications on ultrasonography, mammography, or computed tomography, is typical for IgG4-BD. Characteristic IgG4-BD pathological findings were dense lymphoplasmacytic infiltration with stromal fibrosis, and more than 10% IgG4+ plasma cells/high-power field (HPF); the mean percentage of IgG4+/IgG+ plasma cells was 54.2%, and only one-third of the patients had all “classical” signs of IgG4-BD including storiform fibrosis and obliterative phlebitis. Most of the cases had a benign course and responded to surgical excision with or without steroid therapy.

Hidradenitis suppurativa (HS) is a chronic cutaneous and systemic inflammatory condition. Increasingly, reports have found that immunoglobulins play a role in the exaggerated immune response occurring in severe HS. It is important to recognize these implications as HS patients may present with laboratory abnormalities relating to chronic inflammation and immune activation. If these laboratory abnormalities are mistakenly associated with another disease process, it could lead to invasive workup and treatment, causing harm to patients. We describe the case of a 23-year-old woman with Hurley stage III HS who was hospitalized and found to have persistent immunoglobulin-G4 (IgG4) elevation. Upon discharge, the patient was diagnosed with IgG4-related disease (IgG4-RD) and started treatment with azathioprine. However, the biopsy ultimately was negative for IgG4-RD, and she presented to our clinic several months later with worsening HS disease during an active flare. Physical examination revealed actively draining nodules and sinus tracts in the bilateral axillae, inguinal folds, and mons pubis region. A confusing laboratory marker with HS was observed in this case. IgG4 has the potential to inhibit or activate inflammation depending on the context, and so IgG4 elevation has been noted in varying disease states. IgG4 elevation is observed in chronic inflammatory states and may represent a compensatory response by the body. While no other cases have reported the association between HS and IgG4 elevation, IgG levels have been found to reflect HS disease severity. Therefore, IgG4 could play a potential role in HS disease monitoring, and awareness of this association is important for providers when managing patients with HS.

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.

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

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