IgG4-related Disease Research Articles

6797 Pituitary Apoplexy as initial Presentation of IgG4-Related hypophysitis

Abstract Disclosure: M. Alameri: None. A. Alnuaimi: None. Introduction: IgG4-related hypophysitis is a rare disease due to IgG4 lymphoplasmacytic infiltration of the pituitary gland. It can either be isolated or part of a multisystemic disease. We report a rare case of pituitary apoplexy as first manifestation of IgG4-RD. Case report: A 27-year-old previously healthy male presented to emergency department with severe headache, nausea, vomiting and visual impairment. CT brain showed a large sellar suprasellar mass of 3cm with thick rim enhancement. Blood test showed evidence of central adrenal insufficiency, central hypothyroidism and secondary hypogonadism. Patient was started on hormone replacement therapy for central adrenal insufficiency and central hypothyroidism. Pituitary magnetic resonance imaging (MRI) demonstrated a 3.1 x 2.4 x 2.4 cm well-defined large sellar suprasellar mass with thick rim enhancement with intrinsic heterogeneous T2 signal with hypointense T1 signal on fat-suppressed post contrast imaging consistent with necrotic haemorrhagic suggestive of pituitary apoplexy and background of hypophysitis. Upward displacement of optic chiasm was noted without involvement of cavernous sinus. The patient was initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, eventually, he underwent transsphenoidal surgery due to alternated level of consciousness. Pituitary histopathology showed that vast majority of the tissue is necrotic. A small fragment of viable anterior pituitary tissue is present, which measures up to 5.5 mm in greatest dimension which exhibited marked chronic inflammation, predominantly comprised of small lymphocytes. Plasma cells were present and staining with IgG/IgG4 revealed two high-power fields with clusters of approximately 25 and 50 IgG4 positive plasma cells, respectively. Blood test showed elevated blood IgG4 levels of >2.60 g/L (normal reference range 0.03-2.01 g/L). Case was discussed at Endocrine MDT meeting which agreed that blood tests result along with histopathology findings were in keeping with IgG4-Related hypophysitis as per the Mayo Clinic, Leporati and Japan-Korea proposed criteria. Because blood IgG4 levels were elevated, a systemic evaluation was performed. No evidence of other systemic disease found. High dose steroid therapy was initiated, which reduced remnant inflammatory sellar changes. Discussion and conclusion: IgG4-related pituitary disease should be considered as differential diagnosis in unusual presentations of pituitary apoplexy in the context of sellar suprasellar hypophysitis. Presentation: 6/2/2024

8043 IgG4-related disease with isolated involvement of the pituitary gland: case report

Abstract Disclosure: J.M. Ramos: None. Female patient, 36 years old, presented to our service complaining of a headache lasting five weeks, mainly in the frontal and left periorbital region, radiating to the occipital region. The pain was intense and intermittent, lasting about 40 minutes. No nausea or vomiting was reported, but the patient experienced dizziness and double vision. During the symptomatic interview, the patient mentioned increased thirst and urinary volume. In her medical history, she denied comorbidities, with only frequent episodes of tension-type headaches. She had no continuous medication use and no known drug allergies. The patient had undergone two cesarean sections, with the last one in December 2021. On physical examination, she had horizontal binocular double vision in all three gazes to the left, accompanied by pain during eye movement. Increased facial sensitivity on the left in branches V1 and V2 was observed. The rest of the physical examination showed no abnormalities. Initial general laboratory tests were normal. Evaluation of pituitary function was mostly normal, except for slightly elevated prolactin. A cranial MRI revealed an expansive lesion with sellar and suprasellar components measuring 1.2x1.1x1.2cm. Additional imaging of the sella turcica showed an intra- and suprasellar expansive lesion, predominantly isointense on T1, hyperintense on T2, with discreetly heterogeneous enhancement with gadolinium. In consultation with the neuroradiology team, a hypointensity on T2 at the left margin of the pituitary was noted, suggesting an inflammatory etiology. Based on this, laboratory tests were conducted, and treatment with methylprednisolone 1g per day for 7 days was initiated. After treatment completion, the IgG4 level was found to be 146.7 mg/dL (upper limit of reference: 86 mg/dL). A follow-up MRI, five days after the steroid pulse therapy, showed a reduction in lesion size to 0.8 cm in the cranio-caudal dimension, with a preserved appearance of the optic chiasm. The patient experienced considerable symptom improvement and was discharged with oral corticosteroids and a scheduled initiation of rituximab. The patient meets criteria confirming the diagnosis of IgG4-related hypophysitis, a rare condition representing 30% of hypophysitis cases. Isolated pituitary involvement is even rarer, and its association with diabetes insipidus has been described. Treatment involves corticosteroids, and rituximab can be considered, especially in recurrent cases. Presentation: 6/3/2024

Presumed Choroidopathy of IgG4-Related Disease Discovered During 16-Year Follow-Up of a Patient With Polycystic Kidney Disease

Presumed Choroidopathy of IgG4-Related Disease Discovered During 16-Year Follow-Up of a Patient With Polycystic Kidney Disease

IgG4-Related Disease: A Case Report and Diagnostic Challenges

IgG4-Related Disease: A Case Report and Diagnostic Challenges

B-153 Improving Accuracy of IgG subclasses Quantitation in Serum Using Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) on SCIEX 7500

Abstract Background Serum IgG subclasses (IgGSC) are most often measured for identification of selective immunodeficiency disease and IgG4-related disease (IgG4RD). Traditional nephelometric (IN) assays suffer from errors related to antigen excess and cross-reactivity that can impact the accuracy of results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been the routine testing methodology for serum IgG subclasses at St. Paul’s Hospital since 2015 due to the simplicity and freedom from inter-subclass cross-reactivity problems. In brief, 20 μL of serum sample is denatured, reduced, alkylated and digested, processed semi-automatically on Hamilton Starlet liquid handler. This is followed by analysis on a SCIEX 5500 QTRAP LC-MS/MS. However, when the method was migrated to the SCIEX 7500, it suffered from calibration curve splitting and poor between-device comparability. It was hypothesized that this could be caused by detuning of some high concentration analytes, suboptimal internal standard (IS) concentrations and, suboptimal IS multiple reaction monitoring (MRM) transition choices, and matrix effects from artificial calibrators. Methods Several modifications were made to improve accuracy and robustness: 1) new in-house calibrators were prepared using patient sample pool instead of using Binding Site IgG Subclass Kit calibrators. 2) More IS MRM transitions were added to the method with each analyte MRM quantitated using its own IS MRM using the same fragment ion. The IS concentration was also increased 5-fold for IgG1 and Total IgG. 3) To avoid problems arising from selectively ion detuning, the injection volume was reduced from 10 μL to 1 μL which permitted collision energies (CEs) to be normalized for each analyte/IS MRM pair. Results The new SCIEX 7500 method compares well with the original method (N=168) with Passing Bablok regression slopes of 0.94, 1.1, 1.0, 0.98, and 0.98 for IgG1-4 and IgG total respectively with corresponding intercepts of 0.3, -0.1, 0.0, 0.0, and 0.41 g/L and R^2 of 0.96, 0.95, 0.99, 0.98, and 0.95. Median differences were -1.76%, 1.07%, 1.06%, 6.13% and 1.91%. In a typical batch of 90 patient samples and four sets of calibrators, the calibration curves overlap well. Use of patient-based calibrators allowed calibration values to be centered in the range of typical patient sample values, particularly for IgG4, where the calibration curve was extended to 3.46 g/L compared with the previous high calibrator value of 0.48 g/L. Conclusions The new IgG subclass quantitation method on SCEIX 7500 LC-MS/MS system is robust with excellent reproducibility and between-device comparability.

Identification of red flags for IgG4-related disease: an international European Reference Network for Rare Connective Tissue Diseases framework.

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4+ plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis.

Immunoglobulin G4-related pancreatitis presenting as an obstructive pancreatic mass in a Latino male

Immunoglobulin G4-related disease (IgG4-RD) is a localized or diffuse autoimmune fibro-inflammatory condition that can affect any organ. The literature is sparse on IgG4-RD in the Latino population. This is a case report of a Latino male diagnosed with IgG4-related pancreatitis presenting as a mass. Our 40-year-old Latino male patient presented with diarrhea and epigastric discomfort progressing to jaundice and pruritus. He had associated elevations in liver enzymes, antinuclear antibody, and IgG4. Magnetic resonance cholangiopancreatography revealed a lobulated pancreatic head mass with common bile duct (CBD) narrowing. Endoscopic ultrasound-guided biopsy of the pancreas revealed no malignancy, and the patient underwent CBD stenting through endoscopic retrograde cholangiopancreatography. The patient demonstrated a favorable response to systemic glucocorticoid therapy with resolution of his symptoms and normalization of his liver function tests. Coronavirus disease-2019 infection during treatment had no impact on the outcomes.

S1776 Demographics and Serologic Data of a Group of IgG4-related hepatobiliary Disease Patients

S1776 Demographics and Serologic Data of a Group of IgG4-related hepatobiliary Disease Patients

S2502 Development of IgG4-Related Disease and Autoimmune Pancreatitis-Like Changes on Cross-Sectional Imaging After GLP-1 Agonist

S2502 Development of IgG4-Related Disease and Autoimmune Pancreatitis-Like Changes on Cross-Sectional Imaging After GLP-1 Agonist

S2702 Küttner’s Tumor and Autoimmune Pancreatitis as Metachronous Manifestations of IgG4-Related Disease

S2702 Küttner’s Tumor and Autoimmune Pancreatitis as Metachronous Manifestations of IgG4-Related Disease

Central Retinal Artery Occlusion Following Intralesional Triamcinolone Injection for IgG4-related Orbital Disease.

The risk of blindness associated with periocular and facial injections is well documented. Previous cases describing vision loss following a recent periocular or facial injection have emphasized the importance of facial "danger zones." To date, the literature suggests that nearly half of all cases of central retinal artery occlusion in the setting of a recent periocular or facial injection involve an injection in or around the nose. Here, the authors report the second known case of central retinal artery occlusion following a triamcinolone injection to the lacrimal gland. A 30-year-old female with a diagnosis of IgG4-related disease underwent lacrimal gland debulking with an intralesional steroid injection. She noted OD vision loss immediately after surgery, with posterior segment examination demonstrating retinal whitening with a cherry-red spot and intra-arterial yellow-white plaques. This case serves as a reminder to clinicians regarding the risk of iatrogenic embolism following triamcinolone injections around the face with special attention drawn to the lacrimal gland.

Research Progress in the Treatment of IgG4-related Diseases in Chinese and Western Medicine

IgG4-related diseases (IgG4-RD) is a group of diseases characterized by abnormally elevated levels of IgG4 antibodies and infiltration of IgG4+ plasma cells. Currently, Western medicine mainly uses hormones, immunosuppressants, and biologically targeted therapies for treatment. Traditional Chinese medicine mainly uses dialectic therapy to treat the disease. The syndrome types are mostly Yin deficiency of the liver and kidney, phlegm and blood stasis, Yang deficiency of the spleen and kidney, and damp-heat of the liver and gallbladder. This article provides a review of the research progress in epidemiology, clinical manifestations, diagnosis, and treatment of IgG4-related diseases in Chinese and Western medicine.

A case of immunoglobulin G4-related disease with a urethral lesion diagnosed by radiological imaging before biopsy.

A case of immunoglobulin G4-related disease with a urethral lesion diagnosed by radiological imaging before biopsy.

Efficacy of Rituximab in Autoimmune-Mediated IgG4 Pancreaticobiliary Disease: A Systematic Review and Meta-Analysis.

IgG4 pancreaticobilliary disease (IgG4-PBD) typically shows a rapid improvement with glucocorticoid treatment, yet most patients experience a recurrence. Rituximab (RTX) has emerged as a hopeful approach to prevent relapses in IgG4-PBD. Nevertheless, there is a lack of data on the efficacy and safety of RTX in IgG4-PBD. In this study, we aim to perform a systematic review and meta-analysis to study the pooled efficacy of RTX in this patient population. Multiple databases, including MEDLINE, SCOPUS, and Embase, were searched (in March 2024) using specific terms for studies evaluating the efficacy and safety of RTX in IgG4 pancreatic biliary disease. Outcomes of interest were relapse, remission, partial remission rates, and adverse events. Standard meta-analysis methods were used using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. Twelve studies were included in the study (257 patients). The pooled rate of complete remission was 68% (54% to 80%), I2 =53%, respectively. The pooled relapse rate was 23% (13% to 36%), I2=64%. The pooled rate of total adverse events was 21% (12% to 35%), I2=52%. The pooled partial remission rate is 16% (7% to 32%), I2=25%. The pooled rate of complete and partial remission was 81% (66% to 90%), I2=75%. The pooled infusion reaction and infection were 12% (7% to 18%), I2=0% and 14% (8% to 22%), I2=16%, respectively. RTX therapy appears effective in inducing and maintaining remission of pancreaticobiliary disease with a low rate of side effects. RTX presents as a promising treatment option for patients grappling with recurrent or unresponsive IgG4-related ailments. In addition, RTX emerges as an attractive alternative for individuals intolerant to steroids or experiencing IgG4-related disease relapses. Future studies comparing RTX with other immunomodulators will offer deeper insights into relapse factors and elucidate the appropriateness of utilizing this maintenance treatment following the initial flare.

Validation of the Diagnostic Criteria for IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis (IgG4PA/RPF) 2018, and Proposal of a Revised 2023 Version for IgG4-Related Cardiovascular/Retroperitoneal Disease.

In 2018, diagnostic criteria were introduced for IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis (PA/RPF). This study assessed the existing criteria and formulated an improved version. Between August 2022 and January 2023, we retrospectively analyzed 110 Japanese patients diagnosed with IgG4-related disease (IgG4-RD) involving cardiovascular and/or retroperitoneal manifestations, along with 73 non-IgG4-RD patients ("mimickers") identified by experts. Patients were stratified into derivation (n=88) and validation (n=95) groups. Classification as IgG4-RD or non-IgG4-RD was based on the 2018 diagnostic criteria and various revised versions. Sensitivity and specificity were calculated using experts' diagnosis as the gold standard for the diagnosis of true IgG4-RD and mimickers. In the derivation group, the 2018 criteria showed 58.5% sensitivity and 100% specificity. The revised version, incorporating "radiologic findings of pericarditis", "eosinophilic infiltration or lymphoid follicles", and "probable diagnosis of extra-PA/-RPF lesions", improved sensitivity to 69.8% while maintaining 100% specificity. In the validation group, the original and revised criteria had sensitivities of 68.4% and 77.2%, respectively, and specificities of 97.4% and 94.7%, respectively. Proposed 2023 revised IgG4-related cardiovascular/retroperitoneal disease criteria show significantly enhanced sensitivity while preserving high specificity, achieved through the inclusion of new items in radiologic, pathological, and extra-cardiovascular/retroperitoneal organ categories.

Evaluation of the specificity of trigeminal nerve enlargement in the diagnosis of IgG4-related ophthalmic disease

Evaluation of the specificity of trigeminal nerve enlargement in the diagnosis of IgG4-related ophthalmic disease

Steroid-resistant immunoglobulin G4-related coronary arteritis: A case report

Abstract Background Immunoglobulin G4 (IgG4)-related diseases are systemic fibroinflammatory disease characterized by extensive infiltration of IgG4-positive plasma cells in the affected tissue(s), with high plasma levels of IgG4. However, coronary involvement is rare. Case Summary A 70-year-old man was diagnosed with IgG4-related coronary arteritis, pancreatitis, and cholangitis during full-body contrast computed tomography (CT) examination prior to surgery for an iliac artery aneurysm. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT showed increased uptake of 18F-FDG in the pancreas, extrahepatic bile ducts, and proximal right coronary artery (RCA). Despite the patient being asymptomatic, the RCA showed severe stenosis. The patient was administered a conservative treatment with prednisolone, 30 mg/day, gradually tapered to 5 mg/day, for 6 months. Two years later, contrast CT showed improvement of the pancreatic and bile duct lesions; however, the steroid therapy had not improved the coronary artery lesions, and gradual progression of the lesions was observed. Percutaneous coronary intervention was performed with a cutting balloon in the RCA, and good patency was maintained for 1 year after the procedure. Discussion Steroid therapy is the first-line treatment for IgG4-related diseases; however, there may be some refractory cases. The stenotic and aneurysmal type IgG4-related coronary arteritis are life-threatening; therefore, we performed revascularization using balloon angioplasty. Determining the optimal revascularization technique for drug-refractory cases requires further investigation.

Compromiso gástrico por enfermedad relacionada con IgG4

Introduction: IgG4-related disease (IgG4-RD) is a recently described entity, characterized by IgG4+ infiltration of plasma cells and storiform pattern sclerosis mediated by CD4+ lymphocytes and follicular helper T-cells (Tfhs). Most patients present with adenopathy and weight loss. Among the most affected sites are the pancreas, salivary and lacrimal glands, aorta, and retroperitoneum. Gastric involvement is rare. Diagnosis is based on histopathological examination of the involved organ, clinical manifestations, and serological results. Glucocorticoid therapy is the first line management. Case report: a 38-year-old male patient with symptoms suggestive of upper gastrointestinal (GI) bleeding, upper GI endoscopy revealed a gastric corpus ulcer, suspicious of an ulcerated gastric subepithelial lesion, possibly a gastrointestinal stromal tumor (GIST). Consequently, laparoscopic subtotal gastrectomy was performed. Histology was compatible with an ulcerated IgG4-related fibrosclerosing tumor. Glucocorticoid therapy was started with patient´s favorable response. Conclusion: in this paper, we will review the cases of IgG4-RD with gastric involvement reported in the literature to describe the most important features of this condition.

Immunoglobulin G4 in primary Sjögren's syndrome and IgG4-related disease - connections and dissimilarities.

Primary Sjögren's syndrome (pSS) is an autoimmune disease, with B cell hyperactivation and autoantibody production as its immunological hallmarks. Although the distinction between immunoglobulin G4-related disease (IgG4-RD) and pSS, based on the presence or absence of certain autoantibodies, seems easy to make, possibility of elevated serum IgG4 concentration and often similar organ involvement may lead to a misdiagnosis. The increased serum concentration of IgG4 in IgG4-RD is not clearly linked to the pathogenesis of IgG-RD and it has been suggested that it may constitute just an epiphenomenon. The aim of this article is to discuss the presence of IgG4 in pSS and IgG4-RD and its potential significance for these two diseases.

A rare disease with many faces: A multicenter registry of IgG4-related disease in children

Abstract Objectives We aimed to report the characteristics of pediatric IgG4-related disease (IgG4-RD) through a multicentre registry, to assess disease clusters, and to evaluate the performances of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria in this cohort. Methods Data of IgG4-RD patients in 13 pediatric rheumatology centers were recorded to a web-based registration system. The diagnosis of IgG4-RD was made according to the 2011 comprehensive diagnostic criteria. Results Thirty-five children (19 females and 16 males) with IgG4-RD were enrolled. The median age at diagnosis was 13.3 (25p-75p; 9.9–15.2) years. The most common organ involvement was the eye (n = 21, 60%), followed by lymph nodes (n = 12, 34.3%), musculoskeletal system (n = 12, 34.3%), and neurological system (n = 9, 25.7%). We identified three clusters in our study cohort: those with eye involvement (n = 11, 31.4%), those with eye involvement and neurological findings (n = 15, 42.9%), and those with pancreato-hepatobiliary disease and lymph node involvement (n = 9, 25.7%). Serum IgG4 levels were high in 19 out of 28 patients (67.8%). All patients except one received corticosteroid treatment, and azathioprine was the most preferred drug as a steroid-sparing agent. The sensitivities of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were 5.7% and 88.5%, respectively. Conclusion IgG4-RD has a wide variety of clinical manifestations, however in children the most common presentation was orbital involvement. The 2020 RCD criteria had a better performance whereas the 2019 ACR/EULAR classification criteria performed poorly in pediatric patients.