IgG4-related Disease Research Articles

A Rare Presentation of IgG4-Related Disease with Gastric Outlet Obstruction and Lymphadenopathy: A Case Report.

Background. IgG4-related disease (IgG4-RD) is a systemic immune-mediated condition characterized by fibro-inflammatory infiltration. It is a rare disease that can affect any organ, with the involvement of the stomach being particularly uncommon. The clinical manifestations of IgG4-RD are highly variable depending on the type and number of organs involved and mirror the symptoms of other conditions. Case presentation. We report a 61-year-old man who presented with symptoms of gastric outlet obstruction and was subsequently diagnosed with IgG4-RD. The patient experienced recurrent vomiting, early satiety, and substantial weight loss. Imaging studies revealed luminal narrowing in the pyloric region, prompting further endoscopic evaluation. Initial endoscopic biopsies were nondiagnostic. Because the patient's clinical symptoms and previous investigations were highly indicative of malignancy, he underwent distal gastrectomy with Roux en Y anastomosis. However, final histopathology revealed lymphoplasmacytic infiltration and dense fibrosis, confirming the diagnosis of IgG4-RD; no malignant cells were noted. The surgery resulted in symptom improvement. Conclusion. This presentation highlights the diagnostic challenges of IgG4-RD with gastric outlet obstruction, emphasizing the significance of a multidisciplinary approach involving clinical, radiological, and histopathological assessments to achieve an accurate diagnosis and develop tailored management strategies.

CT Coronary Angiogram in Diagnosing IgG4 of Coronary Arteries Presenting as Acute Coronary Syndrome: A Case Report with Literature Review

AbstractImmunoglobulin G4-related disease (IgG4 RD), first described in 2001, as a case of autoimmune pancreatitis, is a multisystemic condition, involving the salivary glands, bile ducts, pancreas, retroperitoneal organs, and mesentery and is associated with raised level of serum IgG4. Reports of coronary involvement by IgG4 RD are scarce and we could find only 16 case reports in the literature. Here, we present a case of a 61-year-old lady, with no known comorbidities, who presented with rapid progression of coronary artery stenosis. Initially, she presented with mild stenosis of left anterior descending which rapidly progressed to significant triple vessel disease in 3 months. Serological workup for antibodies was negative, except for raised serum IgG4 antibodies. She was managed effectively with steroids.

Clinical Presentation, Investigation Findings, and Outcomes of IgG4-Related Pachymeningitis

ImportanceImmunoglobulin G4 (IgG4)–related disease is an increasingly recognized fibroinflammatory condition that can involve multiple organs, including the pachymeninges. The understanding of IgG4-related pachymeningitis (IgG4-RP) remains limited because of its rarity and the predominance of knowledge derived from case reports and case series.ObjectiveTo systematically review and synthesize the clinical presentation, investigation findings, and prognosis of IgG4-RP to better understand its diagnosis and management.Evidence ReviewA comprehensive systematic review was conducted following guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed/MEDLINE, Embase, and Scopus were searched from their inception until May 30, 2023, using terms related to IgG4-related disease and pachymeningitis without language or publication restrictions. Case reports and series that met the 2020 Revised Comprehensive Diagnostic Criteria or the 2019 American College of Rheumatology/European League Against Rheumatism classification criteria were included. Data on clinical presentations, investigation findings, and treatment outcomes were extracted and summarized.FindingsA total of 148 case reports contributed data from 208 patients. Their median (IQR) age was 52 (39-62) years; 132 patients were male (63.5%) and 76 female (36.5%). Headache and cranial nerve dysfunctions were the most common neurological manifestations. Systemic involvement was identified in nearly half of the patients. Diagnostic imaging often showed preferential involvement of cavernous sinus and middle fossa. Laboratory results highlighted elevated serum IgG4 levels in 97 of 147 patients (65%) of patients and cerebrospinal fluid pleocytosis in 43 of 82 patients (52%). Storiform fibrosis or obliterating phlebitis were uncommon pathological findings. Mortality was below 1% (1/134; 0.7%), but only a third of patients presented complete clinical improvement, and the recurrence rate was 60 patients (40%) in a median (IQR) follow-up time of 9 (1-20) months. Glucocorticoids were the most commonly prescribed treatment, in 143 of 169 patients (85%); rituximab was prescribed as maintenance therapy in 53 of 169 patients (31%).Conclusions and RelevanceIgG4-RP commonly presents with headaches and cranial nerve dysfunction, posing diagnostic challenges due to the significant absence of systemic manifestations, low IgG4 serum levels, and atypical pathological findings. Current treatment outcomes are limited by incomplete recovery and frequent relapses underscoring the necessity for new treatment strategies.

Inebilizumab for Treatment of IgG4-Related Disease.

IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease. In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission. A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo. Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.).

Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease

ObjectivesHypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.MethodsWe performed a...

A case of PLA2R-positive membranous nephropathy with subsequent development of IgG4-related disease.

Membranous nephropathy (MN) is a common cause of adult-onset nephrotic syndrome. It is also known as a minor but established renal manifestation of Immunoglobulin G4-related disease (IgG4-RD). Previous reports suggest that MN can also be an initial manifestation of IgG4-RD, all of which are phospholipase A2 receptor (PLA2R)-negative MN. We describe a case of PLA2R-positive MN that subsequently developed other manifestations of IgG4-RD. A 60-year-old male with nephrotic syndrome was diagnosed as primary MN with positive staining for PLA2R on the initial renal biopsy, which remained in partial remission with supportive therapy using angiotensin II receptor blocker (ARB) without steroid. About 1year later, a renal mass was detected during an annual checkup, and contrast-enhanced computed tomography revealed low-density masses in bilateral kidneys and the head of the pancreas. The findings of endoscopic biopsy of the pancreatic mass were consistent with autoimmune pancreatitis (AIP) and the second renal biopsy showed the findings of MN with tubulointerstitial nephritis, both of which led to a diagnosis of IgG4-RD. The second renal biopsy also showed positive PLA2R. The patient received oral glucocorticoid therapy for IgG4-RD, which improved IgG4-related AIP and renal masses and also resulted in complete remission of MN. To our knowledge, this is the first reported case of PLA2R-positive MN with subsequent development of IgG4-RD. It is sometimes difficult to determine whether PLA2R-positive MN occurring with IgG4-RD is primary MN or secondary MN associated with IgG4-RD. The possibility of developing IgG4-RD should be considered even when preceding MN is PLA2R-positive, suggesting of primary MN.

Hydroxychloroquine as a Promising Therapy for Systemic IgG4-Related Disease: A Case Report

Hydroxychloroquine as a Promising Therapy for Systemic IgG4-Related Disease: A Case Report

Exploring cardiovascular involvement in IgG4-related disease: a case series approach with cardiovascular magnetic resonance

BackgroundIgG4-related disease (IgG4-RD) is a relapsing–remitting, fibroinflammatory, multisystem disorder. Cardiovascular involvement from IgG4-RD has not been systematically characterised. In this study, we sought to evaluate consecutive patients with IgG4-RD using...

Clinicopathological features of lacrimal gland biopsy lesions in 582 Chinese patients

Background This study was conducted to assess the clinicopathological characteristics of biopsy lesions in the lacrimal gland, in response to evolving pathological technologies and the emergence of new diseases. A retrospective review of case notes was conducted for 582 patients with biopsied lacrimal gland lesions at West China Hospital of Sichuan University in China. This study, spanning from January 1, 2010, to December 31, 2021, recorded demographics, clinical features, imaging findings, histopathological diagnoses, and recurrence rates. In a cohort of 582 patients, the mean age was 47.5 years, with 318 being female. Bilateral disease was present in 127 patients. Common signs and symptoms included a palpable mass, lid swelling, proptosis, and decreased ocular movements or diplopia. The predominant pathologies identified were inflammation, epithelial tumors, and lymphoproliferative lesions. Patients with inflammation (mean 32.8 months) experienced symptoms for a longer period compared to those with lymphoproliferative lesions (mean 22.2 months) (95% confidence interval [CI] 1.53–19.27, P = 0.022). Younger patients tended to have structural lesions (mean 42.5 years) (95%CI 4.74–21.59, P = 0.003), inflammation (mean 42.9 years) (95%CI 0.46–6.57, P<0.001), or epithelial tumors (mean 46.4 years) (95%CI 6.21–12.38, P<0.001), while older patients more frequently had lymphoproliferative lesions (mean 55.7 years). The period from 2016 to 2021 saw a higher diagnosis rate of biopsied lacrimal gland lesions than from 2010 to 2015. During this later period, there was an increase in cases of immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and malignant epithelial tumors, while lymphoid hyperplasia cases declined. Adenoid cystic carcinoma showed the highest recurrence rate, with lesion extent and Ki-67 index identified as independent risk factors in our study. Inflammation, epithelial tumors, and lymphoproliferative lesions were the three primary causes of lacrimal gland lesions in our study group. Among the inflammatory conditions, IgG4-ROD was the most specific. The incidence of lacrimal gland lesions has risen, particularly for IgG4-ROD. Adenoid cystic carcinoma among the lacrimal gland lesions was prone to recurrence, with the extent of the lesion and Ki-67 index serving as independent risk factors.

IgG4-related disease presented with a neck nodule; a case report

Introduction and importance: Immunoglobulin G4 (IgG4)-related disease is an infrequent systemic condition that affects males more than females. Fatigue, arthralgia, salivary and lacrimal gland enlargement, symptoms of pancreatitis, tubulointerstitial nephritis, and retroperitoneal fibrosis are the frequent manifestations. The spectrum of IgG4-related thyroid disease includes Hashimoto thyroiditis, Graves’ disease, and Riedel thyroiditis. Case presentation: We presented a 49‐year‐old male presented with progressive painless swallowing of the neck for a year without any accompanying symptoms. Conclusion: Expanding goiter is common, but its severity leads to the rare diagnosis of IgG4-related thyroiditis.

Idiopatické střevní záněty a autoimunitní pankreatitida

Autoimmune pancreatitis is a subtype of chronic pancreatitis. Currently, type 1 is known (LPSP – lymphoplasmacytic sclerosing pancreatitis), which is classified among the clinical forms of a group of diseases designated as IgG4-related disease. This form occurs in younger individuals and IgG4 levels are normal with a few exceptions. This type is accompanied in 20–30% via findings of inflammatory bowel diseases, mainly ulcerative colitis. Type 3 autoimmune pancreatitis has been described, but it is still debated. The number of persons with inflammatory bowel diseases and the finding of type 2 autoimmune pancreatitis is highest in persons with ulcerative colitis – up to 2/3 of all patients. In the Mayo Clinic study, 19 persons with inflammatory bowel disease were found in a group of 43 patients with type 2 AIP; similarly, a Japanese study found AIP in 11 cases in a group of 52 patients with inflammatory bowel disease. Other studies have shown similar results. Inflammatory bowel disease with autoimmune pancreatitis is diagnosed in 20% of cases and steroid therapy is usually successful.

Expert consensus on the diagnosis and treatment of immunoglobulin-G4 related ophthalmic disease (2024 edition)

Immunoglobulin-G4 related ophthalmic disease (IgG4-ROD) is an immune-mediated fibroin flammatory condition characterized by ocular mass lesions and elevated plasma IgG4 level. Since all the ocular tissues can be involved, and it can be accompanied by multiple organ and systemic diseases, the diagnosis and treatment require multidisciplinary collaboration. The Oculoplastic and Orbital Disease Group of Chinese Ophthalmological Society of Chinese Medical Association and the Chinese Rheumatology Association convened experts in ophthalmology, and rheumatology and immunology, and formulated "Expert consensus on the diagnosis and treatment of immunoglobulin-G4 related ophthalmic disease (2024 edition)" for the diagnosis and treatment of IgG4-ROD based on domestic and international studies and experience. The consensus mainly standardized the diagnostic criteria of IgG4-ROD from the aspects of ocular imaging, serum IgG4 level and ocular histopathology, and recommended the methods and indications of drug therapy (glucocorticoids, immunosuppressants and biologics) and surgical treatment.

IgG4-related Breast Disease: Review of the Literature.

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.

Omics in IgG4-related disease.

Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition - and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.

IgG4-Related Disease Involving the Ear: A Case Report.

IgG4-related disease is a chronic inflammatory disease with widespread clinical presentation. It mimics various malignant, infectious, and inflammatory conditions, leading to confusion in diagnosis and management. Otological manifestations, though relatively rare, can lead to significant complications. A 45-year-old male with a recent history of ventilation tube placement in the right ear presented with a sensation of imbalance associated with profound hearing loss. He was managed in line of acute otitis media with labyrinthitis with steroids and antibiotics and removal of the ventilation tube. He returned in one week and presented with right-sided lower motor neuron-type facial paresis. Computed tomography images of the temporal bone showed a soft tissue density lesion in the right middle ear cavity extending to the mastoid antrum. He underwent a right cortical mastoidectomy with decompression of the facial nerve. Histopathology and immunohistochemistry of granulation tissues from the middle ear and the mastoid revealed evidence suggestive of probable IgG4 disease. IgG4-related disease is a relatively new entity, and its pathogenesis has not been properly understood. IgG4 subclass has been involved in this disease resulting in fibro-inflammatory conditions leading to tumor-like masses or fibrosis of the affected organs. Treatment includes glucocorticoids and immunosuppressant medications.

Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: case report and literature review.

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.

Clinical characteristics and prognosis analysis of patients with IgG4-related hepatobiliary-pancreatic disease

Objective: To explore and analyze the clinical features of patients with immunoglobulin (Ig)G4-related hepatobiliary-pancreatic disease and the independent factors affecting the prognosis of IgG4-related sclerosing cholangitis (IgG4-SC). Methods: The clinical data of 179 adult cases diagnosed with IgG4-related hepato-pancreato-biliary disease in the Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2011 to December 2022 were retrospectively analyzed. Patients were divided into three groups: isolated IgG4-SC, IgG4-SC/type 1 autoimmune pancreatitis(type 1 AIP), and isolated AIP according to the clinical manifestations. Demographic characteristics, baseline biochemical immunological indexes, and imaging manifestations were analyzed. The treatment response rate and survival rate were compared. The COX proportional hazards model was used to analyze the independent factors related to prognosis. Results: The mean age of diagnosis of patients with IgG4-related hepatobiliary-pancreatic disease was 60.3±12.0 years. Males accounted for 74.9%, and the median follow-up time was 38 months. The 1-year clinical response rate of patients with isolated IgG4-SC was lower than that of IgG4-SC/AIP (67.9% vs. 91.7%, P=0.019), and the primary endpoint-free 5-year survival rate was significantly reduced (64.9% vs. 95.9%, P<0.001). COX regression analysis showed that having cirrhosis before treatment (HR=6.708, P=0.004) and poor response after half a year of treatment (HR=11.488, P=0.002) were independent risk factors associated with the occurrence of adverse events in hepatobiliary diseases among patients with IgG4-SC. Conclusions: The clinical response rate and survival rate of patients with isolated IgG4-SC are lower than those of patients with IgG4-SC/AIP. Patients with IgG4-SC who do not respond well at six months of treatment and who have progressed to cirrhosis before treatment are at significantly increased risk of adverse events.

Unexpected Presentations of Histiocytic Disorders as Mass Lesions in the Central Nervous System and Spine

Abstract Introduction/Objective A number of neoplastic and non-neoplastic hematolymphoid lesions can involve the CNS and spine. The majority are lymphomas, but some are rare lesions that mimic primary neoplasms clinically, radiologically, and even pathologically. Here, we present our experience of such cases. Methods/Case Report Pathology archives were searched, and five cases representing different challenges were identified to review clinical, radiological, and pathologic features. Case 1. 31-year-old female presented with vision changes and hearing loss and numerous supratentorial extra-axial masses, suspicious for meningiomatosis. Extensive lymphoplasmacytic infiltrate was seen at Intraoperative consult (IOC). Final diagnosis was Rosai-Dorfman disease with features of IgG4 related disease. Case 2. 31-year-old female with Chronic myeloid leukemia (CML), which progressed to AML presented with a right frontal brain mass. IOC displayed atypical hematolymphoid infiltrate. Final diagnosis was myeloid sarcoma. Case 3. 29-year-old male presented with a T10 vertebral lesion. IOC showed hypercellular tissue with atypia and was deferred. Subsequently, histiocytic sarcoma was diagnosed. Case 4. 22-year- old male presented with a T3-T4 intradural, extramedullary mass radiologically thought to be a meningioma. No IOC was requested. Final diagnosis was juvenile xanthogranuloma. Case 5. 36-year-old male presented with a C7-T1 dura-based mass. IOC revealed granulomatous inflammation, eventually resulting in a diagnosis of non-necrotizing granulomatous inflammation, suggesting sarcoidosis. Results (if a Case Study enter NA) NA Conclusion These cases highlight the importance of incorporating all clinical and radiological findings into pathologic evaluation, while being alert for mimickers and pitfalls. Both practicing general surgical pathologists and neuropathologists should remain alert to such unexpected and unusual cases especially at the time of IOC and initiate appropriate work-up with expedited diagnostic protocols such as intraoperative cultures, flow cytometry, and cytogenetics, as the differential diagnosis is broad with inflammatory, infectious, and neoplastic possibilities, presenting a variety of challenges.

Multisystem diseases in the abdomen and pelvis: imaging manifestations and diagnostic roles of cross-sectional imaging.

Systemic diseases, such as IgG4-related disease, sarcoidosis, and amyloidosis, usually involve multiple systems or organs simultaneously or sequentially. The gastrointestinal tract, hepatobiliary system, and genitourinary tract are commonly involved in many multisystem diseases and can also be the first sites with disease involvement. Cross-sectional imaging, such as CT and MR, plays an important role in the diagnosis and management of multisystem diseases by aiding in the evaluation of multiorgan involvement. Here, common imaging features of frequently affected organs are reviewed in multisystem diseases that we often encounter in the abdomen and pelvis, and the diagnostic roles of cross-sectional imaging for these diseases are also discussed.

Aortic Valve Replacement Surgery Caused by IgG4-Related Aortic Regurgitation

While IgG4-related disease affects different organs, it is uncommon to associate it with the aortic valve. The clinical manifestations and prognosis of an uncommon IgG4-related aortic valve disease were examined by reporting it. After common activity, a 50-year-old man experienced shortness of breath and chest tightness. IgG4+ was expressed at a level of 4.23 g/L. The aortic valve had severe reflux, and the ascending aorta and aortic sinus were dilated, as evidenced by transesophageal echocardiography. Pathological results suggested that the ratio of IgG4+ cells to IgG+ cells was over 40%. Thus, the patient was diagnosed with aortic valve disease caused by IgG4+. Surgical treatment was executed. In clinical practice, IgG4-associated aortic regurgitation is uncommon and has the same clinical manifestations as general aortic valve disease. Nevertheless, there was a significant increase in serum IgG4+ levels. There was an association between the two. The pathology of valves can be proven.