Treatment Of IgG4-related Disease Research Articles

Recommendations for the diagnosis and treatment of IgG4-related disease in China

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multi-organs. It is a novel entity presented by variable manifestations. In recent years, there has been progress toward recognizing IgG4-RD. However, the diagnosis and treatment of IgG4-RD still present challenges due to insufficient experience. To address this, the Chinese Rheumatology Association has developed standardized guidelines for the diagnosis and treatment of IgG4-RD based on domestic and international experience. These guidelines aim to enhance the understanding and management of IgG4-RD, ultimately improving the prognosis for patients with IgG4-RD.

IgG4-Related Disease: A Concise Review

IgG4-related disease (IgG4-RD) is a multi-organ fibroinflammatory disorder that may result in organ dysfunction and complications. Glucocorticoids remain the primary treatment for inducing remission, while recently reported disease phenotypes might inform personalized therapeutic strategies. Progress in understanding the pathophysiology of IgG4-RD has led to the identification of novel treatment targets. Ongoing research will further refine the optimal treatment for IgG4-RD. This review offers an update on the latest evidence on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of IgG4-RD.

Frequency, clinical picture, diagnosis, and differential diagnosis of the pathology of the digestive tract (esophagus, stomach, and bowel) in IgG4-related disease (autoimmune pancreatitis)

Despite the publication of European guidelines for the diagnosis and treatment of IgG4-related disease (IgG4-RD), this problem is very complicated from a practical point of view. There are many publications about autoimmune pancreatitis and liver and biliary tract lesions in IgG4-RD, but the data on the digestive tract lesions are not sufficient. Gastrointestinal manifestations of IgG4-RD are considered to be rare or very rare.
 IgG4-RD presenting as esophageal lesions is rare condition. Only single clinical cases are available. I. Obiorah et al. reported the highest number of cases of IgG4-related esophagitis (8 cases). Interestingly, 7/8 cases reported by I. Obiorah et al. were males (age range: 18 to 79 years), and most patients had dysphagia as the most prominent symptom, with erosions and strictures at endoscopy. Histologically, all patients had a lymphoplasmacytic infiltrate and storiform fibrosis, while obliterative phlebitis was observed in 3/8 patients. Hence, 2 of the 3 major histological “Boston criteria” of IgG4-RD were fulfilled in all patients. Besides, all patients had at least 50 IgG4-positive cells per HPF (range: 50–110), and IgG4/IgG ratios of at least 50% (range: 50–90%). Of I. Obiorah’s patients, s-IgG4 had only been measured in three — all of whom had values in the normal range. Esophageal strictures were identified in three patients, two patients had achalasia.
 Based on K. Notohara’s series and the other published cases, it can be concluded that gastric IgG4-RD often (but not always) seems to be clinically asymptomatic, that s-IgG4 is elevated in a considerable number of cases, and histologically, that at least two of the Boston criteria often are found. The recommended cut-off of 50 IgG4-positive cells and IgG4/IgG ratios of >40% was often fulfilled in the reported cases of IgG4-RD.
 There are few reports of IgG4-RD involving the duodenum, duodenal papilla, ileum with small bowel obstruction caused by pseudotumor or sclerosing disease of the small bowel with luminal narrowing.
 There are case reports of IgG4-RD with lesion of ileocecal area with an obstructing ileocecal mass and appendix, mimicking Crohn’s disease, appendicitis or appendiceal tumor. IgG4-related inflammatory bowel disease may — rarely — also be one of manifestations of IgG4-RD.
 Treatment should be conducted in accordance with European guidelines.

Clinical characteristics of IgG4-related disease with lung involvement in 14 patients.

Immunoglobulin G4-related diseases (IgG4-RD) is a rare autoimmune disease, and there is no specific diagnostic test for patients with lung involvement yet. This study aims to summarize the clinical characteristics of IgG4-RD with lung involvement and improve the understanding and diagnosis of this disease. All patients diagnosed with IgG4-RD in the Second Xiangya Hospital from December 2014 to February 2022 were re-diagnosed according to the recommendations of Chinese Expert Consensus on the Diagnosis and Treatment of IGG4-Related Diseases in 2021. The clinical data of 14 IgG4-RD patients with pulmonary abnormalities were collected and analyzed. Among the 14 patients, 11 were males and 3 were females, and the median age of diagnosis was 66 (22-82) years old. Six cases had respiratory symptoms such as cough, sputum and short breath. Extrapulmonary involvement was the most common in the glands of head and neck (6/14), followed by pancreas and bile duct (4/14). Elevated serum IgG4 level was found in all patients, and most (11/14) were accompanied by abnormal inflammatory markers. Patients' pulmonary imaging findings were diverse, the most common performances were mediastinal/hilar lymphadenopathy (12/14), followed by multiple pulmonary nodules (9/14), patchy density enhancement (7/14) and the increased broncho vascular bundles (6/14). Lung biopsy was performed in 9 patients, their pathology results showed lymphoplasmic cell infiltration, 5 cases of them had interstitial fibrosis, 2 cases with phlebitis, and extrapulmonary biopsy was performed in 8 patients. Immunohistochemical results of all the patients showed that the number of IgG4+ plasma cells was more than 10 per high magnification, and the ratio of IgG4/IgG was more than 40%. For treatment, 12 patients received hormone therapy, and 5 patients combined immunosuppressive therapy with hormone. 10 patients were in remission after treatment, while 2 patients were progressed. IgG4-RD with lung involvement is rare and has no specific clinical manifestation. Its pulmonary imaging is diverse. Diagnosis for it should combine with serum IgG4 level and pathological examination. Glucocorticoid is the first line treatment, and combination with immunosuppressant can help prevent disease recurrence.

Abatacept in IgG4-related disease: a prospective, open-label, single-arm, single-centre, proof-of-concept study.

There is strong rationale for interference with T cell co-stimulation in IgG4-related disease (IgG4-RD), but the literature to evaluate this is limited to a single case report. We conducted a ten-subject proof-of-concept trial of abatacept in active IgG4-RD. All subjects met the ACR/EULAR Classification Criteria for IgG4-RD. Subjects received subcutaneous abatacept 125 mg weekly for 24 weeks. Concurrent glucocorticoid treatment was permitted but if used had to be discontinued by week four. The primary endpoint, complete remission at 24 weeks, was defined as an IgG4-RD Responder Index score of 0. Peripheral blood mononuclear cells were collected at baseline, four weeks, and 12 weeks. B and T cell subsets were quantified using a 25-parameter flow cytometry panel. The subjects' median age was 68 years; seven subjects were male and nine were Caucasian. Baseline organ involvement was diverse with a median of 5 organs affected at the time of enrollment. The median serum IgG4 concentration was 597 mg/dL (IQR 304-913 mg/dL). Three subjects received concomitant prednisone at baseline. Six subjects (60%) had a disease response by week 12, five of whom maintained this response at week 24. Abatacept was stopped in the remaining five subjects (50%) due to flare (N = 1) or lack of response by week 12 (N = 4). Three subjects (30%) achieved the primary endpoint.Baseline proportions of unswitched memory B cells predicted responsiveness to abatacept. Reductions in serum IgE, circulating plasmablasts, and activated type 2 T follicular helper (TFH2) cells correlated with response to treatment. One adverse event (grade two thrombocytopenia) was attributed to abatacept. Abatacept was associated with variable treatment responses in IgG4-RD. Half of the subjects achieved sustained treatment responses to abatacept alone, without glucocorticoids. Correlates of clinical response included reductions in serum IgE, circulating plasmablasts, and activated TFH2 cells. Response to abatacept was predicted by higher proportions of unswitched memory B cells at baseline.

Abatacept for IgG4-related disease: therapeutic prospects according to disease immunophenotype.

IgG4-related disease is a chronic, immune-mediated fibroinflammatory disease characterised by disorders of multifunctional immune cells (eg, plasmablasts and T follicular helper [Tfh] cells) in the peripheral blood and involved tissues.1,2 Currently, glucocorticoids are the first-line treatment for IgG4-related disease. Most patients respond well to the initial use of glucocorticoids, but 24–63% relapse and there can be severe adverse events with long-term administration.3 Furthermore, there is no relevant evidence that conventional steroid-sparing immunosuppressants (eg, azathioprine, mycophenolate mofetil, and cyclophosphamide) can replace glucocorticoids in the treatment of IgG4-related disease.

Chinese expert consensus on the diagnosis and treatment of IgG4 related diseases

IgG4 related disease (IgG4-RD) is an immune medicated rare disease, characterized with chronic inflammation and fibrosis in the involved organs, it is a systemic disease affected nearly every anatomic site of the body, usually involvement of multiple organs, and with diverse clinical manifestations. Due to the the relative novelty of the disease and under-recognition, the overall level of diagnosis and treatment in China is uneven. Till now, there is no relevant expert consensus or guidance of IgG4-RD in China. In order to further improve the understanding and standardize the management of IgG4-RD, on the basis of summarizing domestic and international experience, the China Alliance For Rare Diseases, together with the Chinese Rheumatology Association, organized an expert group and established the Chinese expert consensus on the diagnosis and treatment of IgG4 related diseases.

Interpretation of Chinese expert consensus on the diagnosis and treatment of IgG4-related diseases

IgG4-related disease (IgG4-RD) is an immune-mediated disease characterized by chronic inflammation and fibrosis of affected organs. With a deeper understanding of this disease among Chinese scholars and the rich experience in diagnosis and treatment in recent years, an expert group was organized by China Alliance for Rare Diseases and Chinese Rheumatology Association in 2020 and developed the first Chinese expert consensus on the diagnosis and treatment of IgG4-related diseases. This consensus comprehensively summarizes the principles of the diagnosis and treatment of IgG4-RD and thus provides a basis for its diagnosis and treatment by clinicians.

Diagnosis and Treatment of 43 Patients with IgG4-related Disease

To summarize the clinicopathological characteristics, diagnosis and treatment of IgG4-related disease (IgG4-RD). The clinical data of 43 cases with IgG4-RD diagnosed from January 2013 to December 2017 were retrospectively analyzed. The clinical data of the patients including clinical characteristics, accessory examinations, diagnosis, and treatment were collected. Among the 43 patients with IgG4-RD, the ratio of male to female was 3∶1, the mean age was (51.3±15.9) years. Eleven patients had gastrointestinal symptoms, including 5 cases of IgG4-related cholangitis with the feature of dilation of the biliary system and narrowing of the lumen in the abdominal enhanced CT scans, and 6 cases of IgG4-related autoimmune pancreatitis with the feature of pancreatic enlargement or soft tissue density shadow in the abdominal enhanced CT scans. There were 10 cases (23.3%) with periorbital involvement, with the feature of intraorbital soft tissue nodule in the CT scan. Besides, 9 cases (20.9%) had lymphadenopathy, 6 cases (14.0%) had fever. The results of autoimmune antibody tests showed that 14 of 42 patients had increased antinuclear antibody (ANA). Among 40 patients who underwent immunoglobulin tests, 25 cases had elevated IgG, 12 cases had increased IgA, and 29 cases had increased IgE. Coombs test were performed for 6 cases and 4 patients were positive. Serum immunoglobulin G4 subtypes showed that the IgG4 levels of 35 patients were higher than 1 350 mg/L. The immunohistochemistry showed that IgG4 (+) cells (3->500/HPF) were infiltrated, with the CD20 (+), CD3ε (+) or CD138 (+). Among the 43 patients, 5 patients underwent operations due to misdiagnosis. All patients were treated with steroid and immunosuppressive agents after diagnosis, and their clinical symptoms were improved. The clinical symptoms of IgG4-RD are various, involving multiple organs. Therefore, the standardized diagnosis and treatment of IgG4-RD should be strengthened.

IGG4-related diseases in endocrinology

Immunoglobulin-G4-related disease (IgG4-RD) is a chronic immunomediated pathology of different organs of local or systemic nature, which has been established as a separate clinical entity in the early 2000s and is characterized by storiform fibroid inflammation of the affected tissues, their increase, and elevated serum immunoglobulin-G4 (IgG4) levels. The most common manifestations of the disease are major salivary and lacrimal gland enlargement, lymphadenopathy and type 1 autoimmune pancreatitis (AIP1), however, other organs may be also involved (the thyroid, eyes, meninges, heart, lungs, kidneys, aorta, upper airways, mesentery, etc.). The effectiveness of treatment of IgG4-RD, as well as other pathological conditions, is also determined by the timely diagnosis. However, the latter is complicated due to the variety of clinical manifestations and rather variable diagnostic criteria. It is necessary to constantly update the evidence-based knowledge and diagnostic algorithms within this pathology in order to overcome the difficulties, and involve immunologists, endocrinologists, pathologists and specialists in other spheres. This review provides information about the etiology, pathogenesis, and current methods of diagnosis and treatment of IgG4-related diseases, as well as examples of some manifestations of IgG4-RD that an endocrinologist may face in practice.

Clinical case of membranous nephropathy in a patient with IgG4-related disease

IgG4-related disease (IgG4-RD) currently is considered as a chronic fibroinflammatory immune-mediated multisystemic condition of unidentified etiology, which can imitate a wide range of malignant, infectious, rheumatologic, and other diseases. It can affect almost any organ system in the body synchronously or sequentially, but the most often affected are the pancreas, hepatobiliary tract, periorbital structures, salivary glands, kidneys, and lymph nodes. The most frequent renal manifestations of IgG4-RD is IgG4-related tubulointerstitial nephritis. Membranous nephropathy is the most common glomerular disease accompanied by IgG4-RD. Regardless of the organ localization, patients with IgG4-RD are characterized by elevated serum IgG4, but this laboratory abnormality is not specific and can be changed in other diseases. In all suspected cases of IgG4-RD the diagnosis should be confirmed by histological examination. Characteristic pathologic features include diffuse or focal lymphoplasmacytic infiltration with prominent IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. Patients with IgG4- RD usually have an excellent clinical response to glucocorticoids, but relapse rates after steroid withdrawal are high, which may require additional use of immunosuppressants or rituximab. Due to the low prevalence and multitude of clinical manifestations the disease often remains underdiagnosed on time. This case report describes middle-aged patients with a history of chronic recurrent pancreatitis complicated by the nephrotic syndrome. Kidney biopsy showed membranous nephropathy and diagnosis IgG4-RD with multiorgan involvement was made. Partial remission was achieved on corticosteroid therapy. The presented case clearly demonstrates the difficulties of diagnosis and treatment of IgG4-RD. IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with nephrotic syndrome accompanied by multiorgan dysfunction.

Thoracic paravertebral involvement in patients withIgG4-related disease: CT and MR imaging findings.

To retrospectively evaluate CT and magnetic resonance (MR) imaging thoracic paravertebral findings at baseline and follow-up in patients with IgG4-related disease. The study consisted of 36 patients with IgG4-related disease involving thoracic paravertebral regions (32 men and four women; mean age, 58 years; range, 25-78 years). A total of 36 patients underwent CT or MR imaging at baseline; 20 patients underwent follow-up. CT and MR images were reviewed and analysed in consensus by two radiologists for the various features of thoracic paravertebral lesions. All lesions were located around two or more thoracic vertebrae, particularly the lower thoracic vertebrae (n = 36). The right side of vertebrae was predominantly affected in all cases (n = 36). Radiologically, IgG4-related thoracic paravertebral lesions were categorized into three types: solitary or multiple saddle-like masses type (32 patients); multiple nodules type (three patients); and invasively irregular mass type (three patients). All the types showed soft-tissue density on CT images, isointense on T1- and T2-weighted images, and homogeneous enhancement with penetration of small arteries in the lesions on contrast-enhanced CT and MR images. Steroid therapy administered to 20 patients dramatically diminished the mean maximum thickness in 18 patients. One patient with T7-12 vertebrae involved improved after steroid therapy. IgG4-related paravertebral lesions occur mainly around the right side of the lower thoracic vertebrae and manifest as three major patterns of CT and MR imaging findings. Recognition of these diagnostic features will assist in the diagnosis and treatment of IgG4-related disease.

Clinical characteristics and treatment of IgG4-related diseases: a report of 48 cases

Forty eight patients with IgG-related disease (IgG-RD) were treated in Beijing Luhe Hospital, Capital Medical University between January 2014 and January 2017. The clinical features, organ involvement, laboratory findings and treatment of patients were analyzed. The median age of patients was 59 (29-78) years old. The most common symptoms were submandibular gland enlargement (20.8%), abdominal pain (18.8%), eyelid mass or edema (18.8%) and jaundice (16.7%). The involved organs mainly were submandibular glands (62.5%), lymph nodes (54.2%), lacrimal glands (45.8%), parotid glands (41.7%) and pancreas (31.3%). PET/CT was performed in 9 cases (18.8%), the SUVmax value was not correlated with the number of affected organs (r=0.511, P=0.160) and IgG4 (r=0.385, P=0.306). Histopathology showed increased lymphocytes and plasma cells in 46 cases (95.8%), eosinophilia in 15 cases (31.3%), and fibrous hyperplasia in 26 cases (54.2%). Twenty-three patients (47.9%) were treated with single glucocorticoid, 20 patients (41.6%) were treated with glucocorticoid combined immunosuppressants, 3 patients (6.3%) received surgical treatment, and 2 (4.2%) were observed with watch and wait regimen. Forty (97.9%) patients responded well to the initial treatment. Ten out of 23 cases (43.5%) in corticosteroid monotherapy group relapsed, while 6 out of 20 cases (30.0%) in corticosteroids plus immunosuppressive group relapsed, for whom the full dose of corticosteroid and immunosuppressive agents were still effective. IgG4-RD is a chronic inflammatory and fibrous sclerotic disease with multiple organ involvement, increase serum IgG4 level and tissue infiltration with large number of IgG4+cells. Hormone and immunosuppressive therapy is effective, and the overall prognosis is good. Key words: Immunoglobulin G; IgG4-related disease; Clinical characteristics; Treatment outcome

IgG4-related disease: rare presentation as a soft-tissue mass in the thigh of an adolescent.

We report a case of a 16-year-old boy who presented a soft-tissue mass in the anterior compartment of the right thigh discovered by positron emission tomography/computed tomography within the work-up of unexplained prolonged inflammatory syndrome. The mass has no calcification. Subsequently, magnetic resonance imaging of the femoral triangle was carried out. Axial short tau inversion recovery images showed a 3.5-cm ill-defined mass in the femoral triangle with focal areas of hypointensity, which suggests that there might be fibrosis or hemosiderin within the tumor. Axial T1-weighted images showed a slight hyperintense mass involving the iliopsoas muscle. Contrast-enhanced fat-suppressed T1-weighted imaging showed a heterogeneous solid enhancement. Adjacent thick fascia enhancement of the vastus intermedius and the vastus lateralis muscles extending from the mass as a tail-like margin suggested the infiltrative spread of the tumor along the fascial plane. The mass and the lymphadenopathy were excised. Immunohistochemically, tumor cells were staining for muscle actin and desmin. Many plasma cells were IgG4+ (175per high-power field) with a ratio IgG4+/IgG+ of 50%. The diagnosis of IgG4-related disease (IgG4-RD) was made. Although a diffuse array of musculoskeletal symptoms has been observed in IgG4-related disease, reports of biopsy-proven musculoskeletal involvement of the limb are rare. We showed the radiological features of IgG4-RD presenting as a soft-tissue mass of the thigh. Musculoskeletal involvement, clinical significance, and treatment of IgG4-RD are also discussed.

Combined membranous nephropathy and tubulointerstitial nephritis as a rare renal manifestation of IgG4-related disease: a case-based literature review.

IgG4-related disease (IgG4-RD) is a newly recognized immune-mediated multisystemic disease characterized by a fibro-inflammatory condition with tissue infiltration of IgG4-positive plasma cells and often associated with elevated serum IgG4 levels. Typical renal involvement of IgG4-RD presents as tubulointerstitial nephritis (TIN), membranous or membranoproliferative nephropathy. We are presenting a case with combined IgG4 membranous nephropathy and TIN, as well as a literature review on pathophysiology, diagnosis and treatment of IgG4-RD. A 62-year-old man presented with weight loss and fatigue. Labs showed significant proteinuria and hematuria with elevated serum creatinine (2.5mg/dL). CT/PET scan found scattered lymphadenopathy without increased FDG uptake. Kidney biopsy showed glomerular lesions as well as severe interstitial fibrosis and tubular atrophy. Immunohistochemistry study was negative for anti-phospholipase A2 receptor antibodies and showed interstitial lymphocytic infiltration with IgG4 positive plasma cells. Patient also had elevated serum IgG4 level and IgG4 to total IgG ratio. Prednisone treatment was initiated soon after the diagnosis was made, patient responded well with proteinuria and hematuria both resolved. IgG4-related disease (IgG4-RD) is a newly increasingly recognized immune-mediated multisystemic disease; IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with proteinuria.

IgG4-related disease of the thyroid gland requiring emergent total thyroidectomy: A case report

IgG4-related disease of the thyroid gland is a recently recognised subtype of thyroiditis, often with rapid progression requiring surgical treatment. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over three years, with subclinical hypothyroidism. CT scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed limited well-visualised follicular epithelial cells with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of ‘atypia of undetermined significance’. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate with fibrosis and focal obliterative phlebitis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids on treatment of IgG4-related disease.

Soluble Interleukin-2 Receptor: A Potential Marker for Monitoring Disease Activity in IgG4-Related Disease.

Background IgG4-related disease (IgG4-RD) is a fibroinflammatory condition. T-cells play a crucial role in the pathogenesis, and therefore, serum soluble interleukin-2 receptor (sIL-2R) may be a potential biomarker. Method We studied the levels of sIL-2R in 26 histologically proven IgG4-RD patients with available serum sIL-2R and compared them to those in newly diagnosed and untreated sarcoidosis patients (n = 78) and controls (n = 101) and the serum sIL-2R levels in patients after treatment of IgG4-RD (n = 15). The disease activity was measured using the IgG4-Related Disease Responder Index (IgG4-RD RI). Results Median serum sIL-2R in IgG4-RD patients was 4667 pg/ml compared to 1515 pg/ml in controls (P < 0.001) and 6050 pg/ml in sarcoidosis patients (P = 0.004 compared to IgG4-RD). All IgG4-RD patients had elevated serum sIL-2R levels compared to the reference value of <2500 pg/ml in controls and 85% elevated serum IgG4; however, these did not correlate with each other. Both serum sIL-2R and IgG4 levels declined significantly after treatment (P = 0.001 and P = 0.01, resp.). Before treatment, serum sIL-2R level and IgG4-RD RI did not correlate with each other. However, the decrease in serum sIL-2R upon treatment did correlate significantly (P = 0.04) with the decrease in disease activity assessed by IgG-RD RI. Conclusion Serum sIL-2R is elevated in IgG4-RD reflecting the inflammatory process with enhanced T-cell activation. Furthermore, serum sIL-2R might serve as a potential marker of response to treatment in IgG4-RD.

P23-3 - Two Cases of Complete Atrioventricular Block Suspected of Involvement of IgG4 Related Disease

Background: IgG4-related disease is a group of diseases reported from Japan that shows high level of serum IgG4 and tissue infiltration of IgG4 positive plasma cells, such as organ swelling and nodular lesions. Lesions are known to affect multiple organs of the whole body. However, cardiovascular disorder report is rare. The involvement of autoimmune mechanism is considered, PSL therapy is the first choice. We report two cases of complete AV block during the treatment of IgG4-related diseases. Case 1: 67-year-old male. He had undergone CABG and PCI. At about 2 months from the start of the PSL treatment, complete AV block was presented. Because coronary angiography did not change from before, permanent pacemaker implantation was done. Case 2: 67-year-old female. We diagnosed her with this disease due to pancreatic enlargement and high level of serum IgG4. After PSL treatment started, a complete AV block was recognized. Since she was asymptomatic and low in activity, we decided not to implant a pacemaker. Pancreatic enlargement shrank due to continuation of treatment, complete AV block also has disappeared. Conclusion: The clinical course of the two cases suggested a link between IgG4 related diseases and AV block. Because of one case improved the AV block with administration of PSL, it may be reversible by disease control.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report

BackgroundIgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis.Case presentationThe patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis.Discussion and conclusionThe diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease.

IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease.