Spinal cord compression by cystic IgG4-related spinal pachymeningitis mimicking neurocysticercosis: a case report.

BACKGROUND: To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. CASE PRESENTATION: A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. CONCLUSIONS: This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.

Factors related to elevated serum immunoglobulin G4 (IgG4) levels in a Japanese general population.

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

Idiopathic hyalinizing fibrosclerosis: A systemic steroid-resistant condition distinct from IgG4-related disease.

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of 'idiopathic hyalinizing fibrosclerosis' for this under-recognized, rare, systemic condition.

Classical autoimmune hepatitis and the IgG4-associated autoimmune hepatitis in paediatric patients.

The IgG4-associated autoimmune hepatitis (IgG4-AIH) is a newly proposed disease entity characterised by the accumulation of the IgG4-expressing plasma cells in the liver. Its pathophysiology and clinical significance remain unclear and have poor evidence in the paediatric population. Thus, our study aims at comparing the group of paediatric patients with classical AIH and the IgG4-AIH. We carried out a retrospective analysis of 23 children (median age 8.5 years) diagnosed with AIH, who were compared according to the presence of IgG4-positive plasma cells in the liver biopsy. IgG4-AIH was defined if 10 or more IgG4 positive plasma cells/high-power field were found in the biopsy. The presence of the IgG4 component seems to be clinically insignificant. That is why, the conventional immunosuppressive protocol should be considered the standard treatment in the case of the IgG4-associated AIH.

IgG4-related disease presenting with gastric outlet obstruction.

A woman in her 20s presented with 6 weeks of fever, persistent vomiting and 28% loss of body weight. Symptoms were refractory to treatment with antiemetics and broad spectrum antibiotics.Further investigation via oesophageogastroduedenoscopy revealed a large gastric ulcer and pyloric stricture, causing gastric outlet obstruction (GOO). Biopsies of the stomach and duodenum showed plasma cell infiltration with a large proportion being IgG4 positive.Treatment with methylprednisolone, and later prednisolone, quickly improved inflammatory markers and symptoms. Balloon dilatation of the pyloric stricture also improved vomiting, allowing eventual re-establishment of oral nutrition. The patient made a full recovery with maintenance treatment on mycophenolate mofetil.IgG4-related disease (IgG4-RD) is a multisystem disorder with unpredictable presentation. The case highlights diagnostic challenges in IgG4-RD and identifies it as a rare differential in upper gastrointestinal symptoms. To our knowledge this is the first published case of IgG4-RD in the duodenum causing GOO.

Malignancy and mass-forming phenotypes of IgG4-related disease: a challenging diagnosis.

Mass-forming phenotypes of IgG4-related disease (IgG4-RD) mimic malignancy and histological confirmation can be challenging. A woman in her 70s with HIV infection presented with painless obstructive jaundice and weight loss. Magnetic resonance imaging was suggestive of unresectable cholangiocarcinoma. Tumour markers and serum IgG4 were normal. Percutaneous liver biopsy was consistent with IgG4-RD inflammatory pseudotumour, with complete response to glucocorticoid therapy. Two years later, a new episode of obstructive jaundice occurred, with CT showing a solid lesion in the head of the pancreas with double duct sign and encasement of the portal vein. Re-induction therapy was tried without response. Fine-needle biopsy was consistent with pancreatic cancer. Supportive care was offered and the patient died 8 months later, with no signs of disease progression on subsequent imaging. We discuss the challenges of IgG4-RD diagnosis and treatment and the differential diagnosis between mass-forming phenotypes and malignancy, highlighting the difficulties in managing such patients.

Rare mandibular condition presenting as trismus: an exploration of IgG4-related disease.

A woman in her 30s presented with a 12-month history of reduced mouth opening and swelling on the right side of her mandible. The swelling was non-tender and firm on palpation. The swelling began to increase in size after the extraction of her carious wisdom tooth. Histopathological and serological examinations confirmed the diagnosis of IgG4-related disease, manifested as a mass in the mandible. The patient was prescribed oral corticosteroids at a tapering dosage over 8 weeks. After 3 months, there was an improvement in the patient's mouth opening and a reduction in the size of the swelling. The patient remains in follow-up care. Including IgG4-related disease in the list of potential diagnoses for oral soft tissue masses is crucial, given their positive response to medical treatment, highlighting the significance of an accurate diagnosis to prevent unnecessary surgery, with oral lesions potentially serving as early indicators before multiorgan complications arise.

IgG4-related disease with nasopharyngeal malignancy-like manifestations.

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

Elevated polyclonal IgG4 mimicking a monoclonal gammopathy in IgG4-related disease-a case-based review.

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 ß 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.

The 2023 revised diagnostic criteria for IgG4-related ophthalmic disease.

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

IgG4-associated disease with systemic lupus erythematosus: A case report and review.

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

Clinicopathological features of immunoglobulin G4-related constrictive pericarditis.

AIM: Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. METHODS: Among 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. RESULTS: Compared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. CONCLUSIONS: Pericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.

Sinonasal immunoglobulin G4-related disease: a case report of an atypical and rare entity.

BACKGROUND: Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 105 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain. CASE PRESENTATION: This report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments. CONCLUSIONS: The main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.

A Case of IgG4 Related Lung Disease.

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

IgG4-related disease: Effectiveness evaluation through Umehara-Okazaki 2011 and ACR/EULAR 2019 diagnostic criteria.

BACKGROUND: IgG4-related disease (IgG4-RD) is a rare, systemic immune-mediated fibro-inflammatory condition with an unclear etiology and pathophysiology, potentially affecting multiple organs. It presents with common clinical, radiological, and serological characteristics. This study aims to compare the latest two IgG4-RD classification and diagnostic criteria: Umehara-Okazaki 2011 and ACR/EULAR 2019. MATERIAL AND METHODS: In a retrospective cross-sectional study conducted across two centers from January 2010 to July 2023, we included patients suspected of having IgG4-RD from various hospital departments. Patients finally diagnosed with other pathologies were excluded. The remaining suspected IgG4-RD cases were evaluated using both Umehara-Okazaki 2011 and ACR/EULAR 2019 criteria. RESULTS: Out of 34 patients with a clinical diagnosis of IgG4-RD, the Umehara-Okazaki 2011 classified 20 patients: 5 as definitive, 7 as probable, and 8 as possible cases. Applying the ACR/EULAR 2019 criteria to the same cohort resulted in the diagnosis of 9 patients. Notably, retroperitoneal fibrosis and aortitis were the most prevalent form of presentation, accounting for 25% and 22.2% of cases classified under the 2011 and 2019 criteria, respectively. DISCUSSION: The more recent and stringent ACR/EULAR 2019 criteria focus on histopathology, various forms of presentation, and analytical data, allow for a more accurate classification of patients.