IgG4-related Disease Research Articles

Are We Over-Diagnosing Tuberculosis? IgG4-Related Disease is Another “Great Imitator”: A Review

Tuberculosis (TB) has a notorious role as the “great imitator”–frequently mimicking a variety of infectious and non-infectious medical conditions- which often contributes to delays in care-seeking, diagnosis, and management. Probably, the vice versa also holds true. India, being a high endemic zone for tuberculosis, the threshold to label an unexplained illness of more than 2 weeks as TB by Indian clinicians is quite low, often leading to missed or delayed diagnosis of the underlying disease. Immunoglobulin G4-related disease (IgG4-RD) is another such “mimicker” often underdiagnosed due to its varied clinical presentation and is erroneously treated with anti-tubercular drugs. The overlapping biochemical and imaging features of IgG4-RD make prospective diagnosis difficult without a high index of suspicion. The incidence reported in literature is 0.78 to 1.39 per 100,000 person-years, which is likely an underestimation of the disease. Here, we present two cases where patients suffering from IgG4-RD were initially diagnosed and treated as tuberculosis and we review the literature associated with IgG4-RD.

A rare case of limited granulomatosis with polyangiitis presenting as bilateral parotitis

Background: Granulomatosis with polyangiitis (GPA) is a rare autoimmune vasculitis affecting small and medium-sized vessels, commonly involving the respiratory tract and kidneys. Salivary gland involvement, particularly bilateral parotitis, is an uncommon presentation of GPA. Case Report: We report the case of a 38-year-old Asian male who presented with left ear pain and parotid swelling after a water park visit. Initially treated with antibiotics for suspected otitis externa, his symptoms worsened, leading to bilateral parotitis, facial palsy, and otomastoiditis. Imaging revealed parotid abscesses and lab results showed elevated antineutrophil cytoplasmic antibodies (ANCA), specifically cytoplasmic ANCA directed against proteinase 3, confirming the diagnosis of GPA. Cultures and autoimmune workups for other causes, such as Sjogren’s syndrome and immunoglobulin G4-related disease, were negative. Treatment with high-dose corticosteroids and methotrexate resulted in significant clinical improvement. Conclusion: This case highlights the importance of considering GPA in atypical presentations such as parotitis, even in the absence of renal involvement. Early diagnosis and appropriate immunosuppressive therapy are critical to prevent further complications in multisystem involvement.

An Unusual Case of Overlapping Immunoglobulin G4-Related Disease and Systemic Lupus Erythematosus

An Unusual Case of Overlapping Immunoglobulin G4-Related Disease and Systemic Lupus Erythematosus

Epidemiology of systemic vasculitis.

Ongoing research contributes to our understanding of the epidemiology of vasculitis and its outcomes across the globe. This review aims to summarize important research studies published on this topic in the last 18 months. The implementation of rapid referral systems and use of large vessel imaging have improved the diagnosis of giant cell arteritis. A population-based study in immunoglobulin G4-related disease provides incidence and prevalence estimates for the United States for the first time. Recently published data supported viral infectious triggers for Kawasaki disease and immunoglobulin A vasculitis. Population studies in antineutrophil cytoplasmic antibody associated vasculitis report an increase in the incidence of eosinophilic granulomatosis with polyangiitis and have provided further insights into the burden of cardiovascular disease in these patients. Data on Behçet's disease continues to show increased all-cause mortality and need for better treatment strategies. Recent literature highlights the heterogeneity of the epidemiology of vasculitis in different parts of the world as well as associated outcomes, comorbidities, and potential triggers. Thought new classification criteria are being employed in some forms of vasculitis, standardization of case identification remains an unmet need in multiple other forms of vasculitis.

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.

Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers. This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125mg SC every 14days (q14d), 250mg SC q14d, 375mg SC q14d, 250mg IV q14d, and 125mg SC every 7days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses. A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations. Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases. NCT02867098.

Perifollicular concentric granulomas: A clue to IgG4-related lymphadenopathy.

A 69-year-old with well-controlled HIV was evaluated for persistentcough, in the context of years of fatigue and influenza A infection 6months prior. Chest CT and PET scans were notable for adenopathyconcerning for a lymphoproliferative disorder. Radiologic studies alsoshowed diffuse FDG uptake in the prostate, consistent with prostatitis.Axillary lymph node biopsy showed follicular and paracorticalhyperplasia, and few germinal centers showed perifollicular non-necrotizing granulomas. Immunohistochemical staining demonstrated apredominance of IgG4 positive plasma cells. Serum proteinelectrophoresis (SPEP) and immunosubtraction showed a board-domedpeak pattern suggestive of possible monoclonality. Serum IgG4 levelswere elevated, and the patient was diagnosed with IgG4-relateddisease (IgG4-RD). This case highlights morphologic and SPEP patternsthat can aid in supporting a diagnosis of IgG4-RD.

Interdigitating dendritic cell sarcoma presenting as retroperitoneal mass and obstructive jaundice. An uncommon entity of complex diagnosis.

A 60-year-old male was admitted for obstructive jaundice secondary to a 2 cm retroperitoneal lesion. Ultrasound endoscopy (UES) with fine needle biopsy (FNB) was performed, as well as endoscopic retrograde cholangiopancreatography (ERCP) with placement of a metal stent for bile duct drainage. Initially IgG4-related disease was suspected from FNB. After 8 months of treatment the patient attended with a progression evidenced in computed tomography (CT) with retroperitoneal adenopathies and liver metastasis, with involvement of duodenum and fistulation towards hepatic angle of colon. Upper endoscopy and colonoscopy was performed. The patient underwent a cephalic duodenopancreatectomy with antrectomy and right hemicolectomy. The histological study of the specimen revealed cells of fascicular distribution, fusiform aspect, with ovoid nuclei, accompanied by a polymorphic inflammatory infiltrate with mononuclear cells. Immunohistochemistry (IHQ) was positive for S100, CD21, CD23, D2-40 and Bcl-2 and negative for CD1a, CD2, CD3, CD4, CD5, CD8, CD20, CD79a, PD1, desmine, langherin, c-kit, PDGFR. These findings were suggestive of interdigitating dendritic cell sarcoma (IDCS). Systemic chemotherapy with R-CHOP was initiated and after the first 4 cycles of treatment, retroperitoneal adenopathies regressed, with stability of metastatic liver disease.

Recurrent Submandibular Mass and Bilateral Periorbital Edema in IgG4-Related Disease: A Case Report

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated systemic disorder characterized by inflammatory, proliferative, and fibrotic lesions that can affect any body organ. The severity and extent of organ involvement vary significantly among individuals. Diagnosis of IgG4-RD necessitates a comprehensive assessment, including clinical presentation, radiological findings, laboratory tests, and histopathological examination. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria offer a valuable framework for diagnosing IgG4-RD. Although glucocorticoids and rituximab are the primary treatment options, the optimal long-term management strategy for IgG4-RD remains undetermined.

IgG4 in the gut: Gastrointestinal IgG4-related disease or a new subtype of inflammatory bowel disease.

IgG4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. While primarily affecting the pancreas, bile ducts, and salivary glands, IgG4-RD can also involve the gastrointestinal tract, raising questions about its relationship with inflammatory bowel disease (IBD). Recent studies suggest that patients with IBD may exhibit histological and serological features consistent with IgG4-RD, such as a dense lymphoplasmacytic infiltration, a storiform-type of fibrosis and a prominent IgG4 immune response. This overlap represents a diagnostic challenge, as differentiating between primary IBD and IgG4-RD involving the gut is crucial for appropriate treatment. Further research is essential to delineate the prevalence of tissue and serum IgG4 expression in patients with IBD. This approach could classify subtypes of IBD, enabling advancements in non-invasive diagnosis and monitoring as well as personalized therapies. The purpose of this review is to summarize the available evidence regarding intestinal involvement in IgG4-RD and the role of both serum and tissue IgG4 in inflammatory bowel diseases IBD.

Bronchial Obstruction in IgG4-Related Disease

Bronchial Obstruction in IgG4-Related Disease

Research progress in IgG4-related disease over the recent decade

Research progress in IgG4-related disease over the recent decade

Image and Videos - Clinical Gastroenterology and Hepatology IgG4-related gastrointestinal disease diagnosed by underwater endoscopic mucosal resection.

Image and Videos - Clinical Gastroenterology and Hepatology IgG4-related gastrointestinal disease diagnosed by underwater endoscopic mucosal resection.

A Rare Presentation of IgG4-Related Sinusitis With Chronic Nasal Obstruction and Headache: A Case Report and Literature Review

IgG4-related disease (IgG4-RD) is a systemic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells and a tendency to form mass-like lesions in various organs. IgG4-related sinusitis, although a relatively rare manifestation of IgG4- RD, significantly impacts the paranasal sinuses. A 52-year-old man presented with persistent rhinorrhea, nasal obstruction, and headaches. He was diagnosed with IgG4-RD involving the bilateral nasal cavity, paranasal sinuses, submandibular glands, lacrimal glands, and parotid glands. We recently managed a case of IgG4-related sinusitis, which was successfully diagnosed and treated. This condition represents a distinct subset of chronic rhinosinusitis, with unique pathophysiological and clinical features. Accurate diagnosis and effective management of IgG4-related sinusitis require a high index of suspicion and a multidisciplinary approach.

IgG4-related disease: A systematic review of a rare pediatric condition

IgG4-related disease: A systematic review of a rare pediatric condition

Clinical profile of IgG4-related disease in Japan based on the rare disease data registry

We started a registry for cases of immunoglobulin (Ig)G4-related disease (IgG4-RD) in December 2019 to clarify the clinical profile of IgG4-RD. In this study, clinical information from 854 cases registered by February 16, 2024 was analyzed from multiple perspectives. Diagnosis of IgG4-RD was made in 808 cases, comprising 638 definite, 38 probable, and 132 possible. The mean ± SD age at time of enrollment of the 808 cases was 67.9 ± 11.3 years, with 68.8% being male. The pancreas was the most frequently affected organ (49.8%), followed by the submandibular glands (46.2%) and lacrimal glands (30.6%). This study reconfirmed the pancreas and head-and-neck region as major affected areas in IgG4-RD. Clinically, submandibular adenitis and autoimmune pancreatitis often occur together in the same patient, but no association between the two organs was observed in our analysis. Regarding diagnosis, the comprehensive diagnostic criteria were most commonly used (63.6%). Storiform fibrosis and phlebitis obliterans were detected at different frequencies in different organs. In summary, this registry study identified clinical, imaging, hematologic, and pathologic findings in 808 Japanese patients with IgG4-RD. The frequency of affected organs and their characteristic pathological findings will be particularly useful for future practice.

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.

Plasma cell type Castleman's disease of lacrimal gland: a case report and literature review

BackgroundOrbital Castleman's disease is a rare benign lymphoproliferative disorder of extranodal origin.Case presentationA 72-year-old man presented with bilateral upper eyelid swelling. Radiology revealed enlarged lacrimal glands in both eyes. Castleman's disease (plasma cell type) was confirmed by histo-immunochemical examinations after excision of the left orbital mass. No extraorbital involvement was found in systemic evaluation. Postoperatively, corticosteroid therapy was given. After 1 year of follow-up, there was no recurrence in the left orbit, and the swelling of the right eyelid was improved.ConclusionsHere, we report a case of orbital Castleman's disease involving the lacrimal gland bilaterally and summarize previously reported cases. For bilateral orbital masses, the possibility of Castleman's disease should be considered. Before the diagnosis, it is necessary to fully distinguish from other diseases such as IgG4-related eye diseases.

Autoimmune Pancreatitis Type 1: A Rare Cause of Epigastric Pain, About a Case

Type 1 autoimmune pancreatitis is a rare autoimmune disorder, part of a systemic disease known as IgG4 related disease. Its diagnosis is based on a group of criteria defined according to an international consensus on the disease (ICDC criteria). This diagnosis is challenging, as the clinical, biological and radiological signs of the disease can be similar to those of pancreatic cancer. We report a case of type 1 AIP diagnosed after a suspicion of pancreatic cancer.

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.