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

IgG4-related 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.

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UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

BACKGROUND: The present study reviewed the clinicopathological features and outcomes of bilateral lacrimal gland lesions.
METHODS: The data of 113 patients who underwent lacrimal gland biopsy at the West China Hospital of Sichuan University, China, between January 1, 2010, and December 31, 2021, are presented in this case series. The patients all presented with bilateral lacrimal gland lesions. The collected data included patient demographics, clinical features, the results of laboratory examinations, imaging presentations, histopathological diagnoses, treatments, and outcomes.
RESULTS: The mean age of the 113 enrolled patients was 47.4 ± 14.9 years (range, 11-77 years) with a predominance of females (54.9%, n = 62). The lacrimal gland was the source of the majority of biopsy tissue (98.2%, n = 111). The most prevalent etiology was immunoglobulin G4-related ophthalmic disease (IgG4-ROD) (32.7%, n = 37), followed by idiopathic orbital inflammation (IOI) (28.3%, n = 32), mucosa-associated lymphoid tissue (MALT) lymphoma (17.7%, n = 20), reactive lymphoid hyperplasia (RLH) (10.6%, n = 12), and mantle cell lymphoma (4.4%, n = 5). Patients with IOI were significantly younger than those with IgG4-ROD and MALT lymphoma (t = 2.932, P = 0.005; t = 3.865, P<0.001, respectively). Systemic symptoms were more prevalent among patients with IgG4-ROD (χ2 = 7.916, P = 0.005). The majority of patients were treated with surgery (53.1%, n = 60), with surgery combined with corticosteroid therapy (21.2%, n = 24) being the second most common treatment. The majority of patients (91.2%, n = 103) attained complete resolution, stable disease, or significant improvement.
CONCLUSIONS: In conclusion, there are several aetiologies associated with bilateral lacrimal gland lesions, the most prevalent being IgG4-ROD, IOI, and MALT lymphoma. Systemic symptoms were more common in patients with IgG4-ROD. The majority of patients who presented with bilateral lesions of the lacrimal glands responded satisfactorily to treatment, with favorable results.

OBJECTIVE: Our study aimed to investigate the distinct clinical patterns of seronegative IgG4-related disease (IgG4-RD) patients.
METHODS: We retrospectively enrolled 698 treatment-naïve IgG4-RD patients in this study. Patients were divided into four different subgroups according to their baseline serum IgG4 levels. The distinct clinical patterns of seronegative IgG4-RD patients were revealed through the comparison of baseline clinical data and disease prognosis among the different subgroups. COX regression analyses were used to investigate the risk factors for disease relapse and to construct the nomogram model.
RESULTS: Seronegative IgG4-RD patients account for a minority of IgG4-RD patients (49/698, 7.02%). The proportions of seronegative IgG-RD patients in our study and several Asian cohorts were significantly lower than those of the European and American cohorts. Seronegative IgG4-RD patients got lower serum IgG levels (p < 0.0001), lower eosinophil count (p < 0.0001), lower serum IgE levels (p < 0.0001)), lower IgG4-RD responder index (RI) scores (p < 0.0001), and fewer affected organ numbers (p < 0.0001) compared with other subgroups, whereas they were more likely to manifest fibrotic type with some special organ involvement. Younger age at onset, GCs monotherapy, elevated C-reactive protein level, and elevated erythrocyte sedimentation rate level are the risk factors for the disease relapse of seronegative IgG4-RD patients. An effective nomogram model predicting disease relapse of seronegative IgG4-RD patients was constructed. Seronegative IgG4-RD patients with scores >84.65 at baseline were susceptible to suffering from disease relapse.
CONCLUSIONS: Distinct clinical features and multiple risk factors for disease relapse of seronegative IgG4-RD patients have been revealed in this study. A nomogram model was constructed to effectively predict disease relapse during the follow-up period.

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.

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.

BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
METHODS: 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.
CONCLUSIONS: 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: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.