IgG4-related Disease Research Articles

Multiple lymphadenopathies in eosinophilic granulomatosis with polyangiitis: Differentiating from IgG4-related lymphadenopathy.

We report a case of eosinophilic granulomatosis with polyangiitis in a 75-year-old man who developed mononeuritis multiplex and purpura in the lower legs concomitantly presenting with lymphadenopathies. Biopsied lymph node tissue pathologically demonstrated fibrinoid necrotising vasculitis with perivascular eosinophil infiltration, resulting in eosinophilic granulomatosis with polyangiitis diagnosis. Additionally, abundant immunoglobulin (Ig) G4-positive plasma cell infiltration exhibiting >70% IgG4/IgG ratio, without storiform pattern fibrosis and obliterative phlebitis, was observed in the biopsied lymph node. Clinical improvement was observed after corticosteroid therapy. IgG4-related lymphadenopathy has been defined as a distinct clinical category regardless of fulfilling IgG4-related disease classification criteria. However, some autoimmune diseases, including eosinophilic granulomatosis with polyangiitis, can develop lymphadenopathy pathologically similar to IgG4-related lymphadenopathy.

IgG4-related disease involving the cervical spinal cord

IgG4-related disease involving the cervical spinal cord

P181 Clinical assessment of radiologically defined clinically isolated aortitis in a single centre study

Abstract Background/Aims Aortitis may occur in the absence of systemic vasculitis and is termed clinically isolated aortitis (CIA). Our purpose was to describe a cohort of patients with CIA and compare their characteristics with aortitis patients associated with rheumatic diseases. Methods We conducted a retrospective analysis of 32 patients with non-infectious aortitis evaluated in our centre. Online records were analysed. We included demographic variables, symptoms, laboratory data, imaging, treatment, outcomes, and mortality. The description of quantitative variables was made using percentages and medians with interquartile range (IQR). Results Out of 32 patients, 10 were classified as CIA and 22 had other inflammatory diseases (approx. 1:2 ratio) - fourteen had giant cell arteritis, 4 had Takayasu's arteritis, 2 with granulomatosis with polyangiitis, 1 each with IgG4 related disease and ankylosing spondylitis, classified according to the ACR/EULAR criteria for each disease. All patients underwent PET-CT imaging confirming isolated aortitis; none had an artery biopsy. Table 1 shows the main clinical characteristics. Among the CIA patients, the median duration of follow-up was 65 months (IQR 42-72). Three patients were asymptomatic and seven had constitutional symptoms (fever, weight loss, sweats, fatigue). Only one patient reported abdominal, back pain. The diagnosis was incidental in two cases. All patients had negative infection screen and serological markers for other rheumatologic conditions. Six (60%) patients had involvement only of the abdominal aorta, 2 had only thoracic aorta, and 2 had abdominal and thoracic aortitis. Six patients (60%) were treated with glucocorticoids (GCs) and methotrexate, 2 with GCs alone, 1 with GCs and mycophenolate mofetil, and 1 patient had resistant disease requiring tocilizumab. Four patients had follow-up PET-CT imaging: 2 showed reduction in FDG avidity, 1 had a stable tracer uptake, and 1 had no evidence of persistent aortitis. All the CIA patients demonstrated clinical and biochemical (ESR/CRP) improvement and at follow-up. Conclusion Our CIA patients had a male predominance, between the sixth and seventh decades, consistent with the previous literature. Aneurysms are more common in CIA patients than in those with GCA or TAK. There is no fixed protocol for CIA but conventional DMARDs and glucocorticoids are helpful. Disclosure S. Jain: None. M. Muñoz-Urbano: None. A. Khormi: None. S. Sangle: Other; Principle Investigator for HAVEN Trial. D. D'Cruz: Consultancies; GlaxoSmithKline, CSL Vifor. Grants/research support; Medical Research Council, National Institute for Health and Care Research. Other; Principal Investigator Clinical trials with Pfizer. Eli Lilly, AbbVie, Syneos, Idorsia.

P023 A case of ANCA-associated vasculitis with possible IgG4-related disease

Abstract Background/Aims IgG4-related disease (IgG4-RD) and granulomatous polyangiitis (GPA) have apparent different pathology. There are infrequent reports of the two conditions occurring simultaneously. We add to the literature by describing a patient who appears to have both conditions. Methods A 65-year-old male presented with low back pain radiating to the perineum. His past history included T2DM, CABG and ablation for AF. Initial investigations showed a CRP of 102mg/ml and an eGFR of > 90ml/hr. A CT urogram revealed possible aortitis. A dedicated aortogram showed a cuff of added tissue around the infrarenal aorta and iliac arteries. A whole aortogram showed an increase in the abnormal tissue and detected a left upper lobe cavitating lesion. A PET-CT scan showed activity in the infrarenal aortic tissue, with focal uptake in the aortic arch and right superficial femoral artery. Several pleural based and parenchymal lesions showing moderate increased FDG activity were seen. A CT scan of the sinuses showed multifocal sinonasal mucosal thickening without bony erosions. C-ANCA was positive at 1/40, with raised PR3 of 32U/ml and IgG4 of 2.2g/L. Other immunoglobulin levels were normal and IGRA was negative. A biopsy of the lung lesion showed necrotising granulomatous inflammation and surrounding palisading histocytes, withno vasculitic element. Treatment with prednisolone 40mg daily and methotrexate 15mg weekly was started. A quick symptomatic improvement followed. CRP fell to 14mg/ml within two months. It was discussed in the national IgG4-RD MDT, and the consensus was that he had features of both GPA and IgG4-RD. A follow-up CT scan showed reduction in the volume of para-aortic tissue, with regression of some lesions in the chest, while others increased. However, he remains well with a normal CRP, stable renal function and normal urinalysis. His latest IgG4 level dropped to 0.67 g/L. Results The ANCA positivity and lung biopsy findings satisfy classification criteria of GPA. While aortic involvement is not commonly seen in GPA; it is typical of IgG4-RD; however, its diagnostic criteria require a confirmatory biopsy. This is challenging due to the risk of sampling around the aorta and ureters. Our case fulfils criteria for ‘possible’ IgG4-RD. In retrospect, an earlier PET CT scan may have spared the patient several CT scans. Conclusion The co-existence of IgG4-RD and ANCA-associated vasculitis may be more common than might be expected. Our case highlights the usefulness of early PET-CT scanning in rheumatic conditions. It is important to check ANCA in suspected IgG4-RD cases. It is possible that future AI programmes may help clinicians better judge the timing of investigations that may be more expensive, invasive or have increased radiation exposure in such complex cases. Finally, the usefulness of a national MDT for IgG4-RD is highlighted. Fortunately, treatment modalities are similar for both conditions. Disclosure H. Eltahir: None. M. Lloyd: None.

Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review.

Eosinophils have widespread procoagulant effects. In daily practice, eosinophil-related cardiovascular toxicity consists of endomyocardial damage, eosinophilic vasculitis and arterial or venous thrombosis. Here we aim to report on the clinical features and treatment outcomes of patients with unexplained ophthalmic vascular manifestations and eosinophilia. We conducted a retrospective, multicenter, observational study and a literature review of patients with eosinophilia (≥0.5 x109/L) and concomitant ophthalmic vascular manifestations independent of the underlying eosinophilic disease but with no alternative cause for ophthalmic manifestations. Fifty-seven patients were included (20 from the observational study and 37 from the literature review). Ophthalmic vascular features were the initial manifestation of eosinophil-related disease in 34 (59%) patients and consisted of 29 central retinal artery occlusions, six branch retinal artery occlusions, five central retinal vein occlusions, two branch retinal vein occlusions, seven retinal vasculitides, two retinal vasospasms, 12 Purtscher's retinopathies, 13 anterior ischemic optic neuropathies and two posterior ischemic optic neuropathies. The median [IQR] absolute eosinophil count at onset of ophthalmic vascular manifestations was 3.5 [1.7-7.8] x109/L. Underlying eosinophil-related diseases included eosinophilic granulomatosis with polyangiitis (n=32), clonal hypereosinophilic syndrome (HES) (n=1), idiopathic HES (n=13), lymphocytic HES (n=2), adverse drug reactions (n=3), parasitosis (n=2), polyarteritis nodosa (n=1), IgG4-related disease (n=1), eosinophilic fasciitis (n=1) and primary sclerosing cholangitis (n=1). Other extra-ophthalmologic arterial or venous thromboses related to eosinophilia were reported in four (7%) and nine (16%) patients, respectively. Visual prognosis was poor: only eight (10%) patients achieved full recovery of ophthalmologic symptoms. After a median follow-up of 10.5 [1-18] months, one patient (3%) had a recurrence of an ophthalmic vascular manifestation, and three patients (10%) had a recurrence of other vascular symptoms (deep vein thrombosis in two and pulmonary embolism in one patient). At the time of recurrence, absolute eosinophil counts were above 0.5 x109/L in all cases (n=4). This study broadens the spectrum of vascular manifestations associated with hypereosinophilia by adding ophthalmic vascular manifestations. In patients with ophthalmological vascular manifestations and hypereosinophilia, aggressive treatment of the underlying pathology (and normalization of blood count) should be implemented.

Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report

BackgroundImmunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly manifests as a tubulointerstitial nephritis and is associated with glomerular disease in a proportion of cases. Membranous nephropathy is the most frequent glomerular lesion. Herein, we report the first documented case of immunoglobulin G4-related disease presenting with nephrotic syndrome owing to minimal change disease.Case presentationA 67-year-old South Asian male presented to our service with systemic upset and leg swelling. He had heavy proteinuria (urine protein:creatinine ratio 1042 mg/mmol) and was hypoalbuminemic (17 g/L) and hypercholersterolemic (9.3 mmol/L), consistent with the nephrotic syndrome. His serum creatinine was 140 μmol/L, and he was hypocomplementemic (C3 0.59 g/L, C4 < 0.02 g/L) with raised immunoglobulin G4 subclass levels (5.29 g/L). Kidney biopsy demonstrated minimal change disease alongside a plasma-cell-rich tubulointerstitial nephritis with strong positive staining for immunoglobulin G4. A diagnosis of minimal change disease in the setting of immunoglobulin G4-related disease was made. He was commenced on oral prednisolone at 60 mg daily but suffered infectious complications, including necrotizing fasciitis within 3 weeks of starting treatment, ultimately resulting in his death 52 days after initial presentation.ConclusionThis case highlights the potential for immunoglobulin G4-related disease to be associated with a spectrum of glomerular pathologies including minimal change disease. It adds to the differential diagnosis of secondary causes of minimal change disease, and moreover, aids as an important reminder of the potential complications of high-dose steroids used in its treatment.

Rapid progression of a coronary artery aneurysm caused by IgG4-related disease

BackgroundIgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder that can affect almost any organ. IgG4-RD has also been reported in coronary arteries as periarteritis. IgG4-related coronary periarteritis may cause coronary artery aneurysms, and IgG4-related coronary artery aneurysms (IGCAs) are life-threatening. We describe a case of a patient with IGCA that highlights the usefulness and limitations of various IGCA evaluation modalities and provides insight into disease pathophysiology. Case summaryA 60-year-old man with IgG4-RD diagnosed 2 years before and with IGCA at the proximal right coronary artery (RCA) on coronary angiography (CAG) 9 months prior to admission to the hospital presented with acute coronary syndrome. Emergent CAG revealed the rapid progression of IGCA at the RCA, an obstruction of the diagonal branch, and stenosis of the left anterior descending artery (LAD) and the high lateral branch (HL). The patient underwent percutaneous coronary intervention for the diagonal branch. The RCA aneurysm was resected and bypassed with a saphenous vein graft (SVG); coronary bypass grafting (left internal mammary artery to LAD and SVG to HL) was performed. Pathological findings showed inflammatory cell infiltration and disruption of the elastic plate. ConclusionIGCAs require careful follow-up with computed tomography scans for early detection of aneurysmal enlargement.

Another link between adult orbital xanthogranulomatous disease and IgG4-related disease

Another link between adult orbital xanthogranulomatous disease and IgG4-related disease

Primary intraorbital inflammatory lumpy lesion: A rare case report.

Eosinophilic angiocentric fibrosis (EAF) is considered to be a kind of benign IgG4-related disease, and it is more often found in the nasal cavity. We present a pretty rare case of orbital EAF that is unlike any other reported case for this case is an IgG4 negative orbital EAF and successfully treated by the fronto orbitozygomatic approach surgery. This is a 68-year-old man from a rural area of Inner Mongolia Autonomous Region, went to our hospital for a 2-month history of vision loss with a local hospital orbital computer tomography which showed that there was a lesion in his left orbit. The inspection of the patient revealed that the patient left eye was protruding outward and the left eyelid unable to complete open or close. And his left eyeball movement had difficulty in all directions. Postoperative pathology diagnosed that this was a case of IgG4-negative EAF case. Orbital EAF. Surgical radical resection and postoperative glucocorticoid therapy. After surgery, the left eye vision of this patient increased to 0.6 tested in the standard logarithmic visual acuity chart. And his left eyeball movement dysfunction and eyeball outward protruding get a partially relief. EAF occurring in the orbit is a very rare disease and immunohistochemical results of EAF can be IgG4 negative.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

Bessel's disease-the first report of an IgG4-related disorder.

Many aspects of IgG4-related diseases were initially described during the late 19th and early 20th century. Avariety of clinical presentations caused by this common pathology have been named after the researchers who first described the disorders, such as Mikulicz, Küttner, Riedel or Ormond. However, the initial description of retroperitoneal fibrosis dates back to even 50years earlier, when in 1846, the Prussian private practitioner Raphael Jakob Kosch described ahitherto unknown constellation of symptoms and pathological findings in afamous patient. This celebrity was the mathematician and astronomer Friedrich Wilhelm Bessel, aclose friend of Alexander von Humboldt and Carl Friedrich Gauss.

ALECT2 amyloidosis with concurrent IgG4-related interstitial nephritis, membranous nephropathy and diabetic kidney disease: a case report and literature review

ALECT2 amyloidosis with concurrent IgG4-related interstitial nephritis, membranous nephropathy and diabetic kidney disease: a case report and literature review

Retroperitoneal space tumour misinterpreted as a renal colic attack in a patient with urolithiasis, a suspected IgG4-related disease

Retroperitoneal space tumour misinterpreted as a renal colic attack in a patient with urolithiasis, a suspected IgG4-related disease

Are Gender Differences Important for Autoimmune Liver Diseases?

Gender Medicine has had an enormous expansion over the last ten years. Autoimmune liver diseases include several conditions, i.e., autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and conditions involving the liver or biliary tree overlapping with AIH, as well as IgG4-related disease. However, little is known about the impact of sex in the pathogenesis and natural history of these conditions. The purpose of this review is to provide an update of the gender disparities among the autoimmune liver diseases by reviewing the data published from 1999 to 2023. The epidemiology of these diseases has been changing over the last years, due to the amelioration of knowledge in their diagnosis, pathogenesis, and treatment. The clinical data collected so far support the existence of sex differences in the natural history of autoimmune liver diseases. Notably, their history could be longer than that which is now known, with problems being initiated even at a pediatric age. Moreover, gender disparity has been observed during the onset of complications related to end-stage liver disease, including cancer incidence. However, there is still an important debate among researchers about the impact of sex and the pathogenesis of these conditions. With this review, we would like to emphasize the urgency of basic science and clinical research to increase our understanding of the sex differences in autoimmune liver diseases.

ОСОБЕННОСТИ ТЕЧЕНИЯ IgG4-АССОЦИИРОВАННОГО ЗАБОЛЕВАНИЯ У ДЕТЕЙ

Purpose of this research was to summarize data on the features of the course of IgG4-related disease (IgG4-RD) in children in a series of clinical observations. Materials and methods used: a single-center observational study included four pediatric patients with both clinically and morphologically confirmed IgG4-RD. Age of onset, duration of the disease prior to diagnosis, clinical, instrumental, laboratory and morphological studies were analyzed at the time of onset and during follow-up. The duration of follow-up ranged from 6 months to 7 years. The disease manifested with orbital pseudotumor in two patients, with diabetes insipidus in a single patient and with fever, signs of high inflammatory and immunological activity in another patient. The period for diagnosis was 3 to 12 months. The diagnosis was based on a biopsy of orbital tissue with detection of signs of fibrosis, obliterating phlebitis, and subsequent immunohistochemical testing for the presence of IgG4. Three children received basic therapy with steroids and cytostatics, a single child had received cytostatics solely. A clinical effect was achieved during therapy: no progression of the disease was recorded in all patients according to instrumental observation.

IgG4-Related disease with diffuse myopericardial involvement- value of CMR: a case report and literature review of cardiac involvement

BackgroundIgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement.Case presentationThis paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment.ConclusionsThis case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management.

IgG4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant

BackgroundMonoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. MethodsWe studied seven relatives with autoimmune/inflammatory diseases and lymphoproliferative diseases. We analysed biopsy results and performed whole-exome sequencing and immunological studies. ResultsDisease onset occurred at a mean age of 25.2 years (range: 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, four had confirmed immunoglobulin G4-related disease (IgG4-RD), and five developed B-cell malignancies: lymphoma in four and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening COVID-19 pneumonia, one of whom had autoantibodies neutralizing interferon (IFN)-α. The recently described IKZF1 gain-of-function p.R183H variant was found in the five affected relatives tested and in a six-year-old asymptomatic girl. Immunological analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, TEMRA and CD28-CD57+ CD4+ and CD8+ T cells, Th2 and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in three patients. ConclusionHeterozygosity for gain-of-function IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunological data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

The "great imitator": IgG4-related disease of the oral cavity. Two case reports and scoping review.

This study aimed to review the lesser-known intraoral manifestations of immunoglobulin G4-related disease (IgG4-RD). In this paper we report an unprecedented case of oral IgG4-RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4-RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow-up duration. Fifty-one cases of oral IgG4-RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4-RD should report clear adherence to the recognized international diagnostic criteria of the disease.

Sino-Orbital IgG4 Related Disease- An Uncommon Entity.

IgG4 related disease (IgG4-RD) is an auto immune fibro-inflammatory condition, characterised by presence of IgG4 positive lymphoplasmacytic infiltrates and extensive fibrosis of the involved organ. It commonly affects pancreas, biliary tract and salivary glands. Sino-orbital involvement is a relatively rare presentation. There is extensive fibrosis of the involved organ. Biopsy is often diagnostic and it shows extensive necrosis and lymphoplasmocytic infiltrates. They show dramatic response to steroid therapy. Here we present three cases of IgG4-RD disease involving orbit and para nasal sinuses who were evaluated and treated in a tertiary care teaching hospital over a period of 2 years.

Imaging of Common and Uncommon Manifestations of Immunoglobulin G4‐Related Disease in the Head and Neck

Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic immune-mediated disease, encompassing several conditions previously thought to be unrelated, which can mimic malignant, infectious, and inflammatory disorders. Head and neck IgG4-RD most frequently affects the salivary glands and orbit; however, it can involve virtually any subsite. Diagnosis is challenging and relies on the clinical presentation, serum immunoglobulin G4 levels, and histopathology. Although imaging is nonspecific, growing knowledge of IgG4-RD allows characterization of imaging patterns and description of novel findings. This review focuses on cross-sectional imaging findings of extracranial IgG4-RD in the head and neck, presenting cases in frequent and unusual subsites, with some cases with few descriptions in the radiological literature, such as the pharynx and larynx, temporal bone, paranasal sinuses, and perivascular areas.Learning Objective: To describe the imaging findings of IgG4-RD in the head and neck to suggest the diagnosis and identify the involvement of common and uncommon subsites.