IgG4-related Disease Research Articles

Distinct features of ANCA-associated hypertrophic pachymeningitis compared to other etiologies: findings from a study of 74 patients.

We aimed to characterize the clinical and radiological features, and outcomes, of a large cohort of hypertrophic pachymeningitis (HP) patients from a single center. We conducted a retrospective study at a tertiary referral center, encompassing patients diagnosed with HP between 2003 and 2022. The diagnosis of HP relied on the identification of thickening of the dura mater via magnetic resonance imaging (MRI) of the brain or spine. We included 74 patients with a mean age of 43.6 ± 14.2 years, of whom 37 (50%) were male. Among them, 32 (43.2%) had an immune-mediated origin, including 21 with granulomatosis with polyangiitis (GPA) (predominantly PR3-ANCA positive), four with systemic lupus erythematosus, three with IgG4-related disease, three with idiopathic HP, and one with rheumatoid arthritis. Non-immune-mediated HP accounted for 45 cases (56.8%). Within this category, 21 (28.4%) were infectious cases, with 14 being Mycobacterium tuberculosis infection (TB-HP), and 21 (28.4%) were malignancy-associated HP. Clinical and MRI characteristics exhibited variations among the four etiological groups. Hypoglycorrhachia was primarily observed in infectious and malignancy-associated HP. Immune-mediated HP was associated with a peripheral pattern of contrast enhancement and the Eiffel-by-night sign. MRI features strongly indicative of TB-HP included leptomeningeal involvement, brain parenchymal lesions, and arterial stroke. MPO-ANCA GPA was associated with a higher prevalence of spinal HP. Within our cohort, GPA and Mycobacterium tuberculosis emerged as the predominant causes of HP. We identified significant disparities in clinical and radiological features among different etiologies, which could have implications for diagnosis.

Robot-assisted thoracoscopic resection of a posterior mediastinal tumor with immunoglobulin G4-related disease: a case report

BackgroundImmunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported.Case presentationA 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications.ConclusionThe clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.

A NEGLECTED RARE DISORDER: IGG4 RELATED DISEASE

Abstract IgG4–related disease (IgG4–RD) is an autoimmune disorder characterized by infiltration of plasma cells with IgG4. Almost any organ could be affected. Common presentations include lung manifestation, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. Cardiovascular involvement is less frequent. Corticosteroids are first line therapy, with or without anti–rheumatic drugs. Long–term prognosis of IgG4–RLD remains unknown. We present the case of a 65–years old woman, with a previuos diagnosis of IgG4–RD with mediastinal involvement. In the meantime she was recovered for pyelonephritis with high fever and positive blood coltures (S. hominis). We were called to perform a transthoracic echocardiogram to rule out infective endocarditis. The exam showed normal size of cardiac chambers, normal biventricular systolic function, absence of relevant valvular disease. In apical view we noticed a hyperechogenic ovalar imagine in the right atrium, not visible in all the projections. A first differential diagnosis included a mass with site of implantation at the top of the right atrium or something external but contiguous to heart structures. To clear this doubt the patient performed a thoracic CT with stunning results. The CT highlighted parietal encasement of chardiac structures and, particularly, of the superior vena cava at the confluence in right atrium, explaining the image we saw with transthoracic echo. The exam also showed encasement of ascending aorta, aortic arch and descending aorta with maximum thickness of 18 mm. CT also reported encasement of right pulmonary arthery. The CT highlighted a progression of the disease with indication to more aggressive therapy. In fact IgG4–RD of the cardiovascular system results in serious complications that need to be recognized and treated. Aortic involvement in IgG4–RD is extremely rare and tipically affects the infrarenal abdominal aorta. Cardiovascular IgG4–RD could also lead to aortitis, medium–vessel arteritis, pulmonary vascular disease, phlebitis, valvulopathy, pericarditis and myocardial disease. These forms of Igg4–RD are often underdiagnosed as clinical presentations is similar to cardiovascular disease due to more common aetiologies. Regarding our case the patient began methotrexate based on the results of the CT. This was a really interesting case for our working group to deepen this little–known disease. “The eyes see only what the mind is prepared to comprehend”.

CORONARY ARTERY ANEURYSM IN IGG4–RELATED DISEASE

Abstract Introduction Coronary artery ectasia is a rare disease defined as a local or diffuse dilatation of the coronary artery more than 1.5 times the diameter of the adiacent normal segment. The etiology is diverse and can be rarely associated with immunoglobulin G4 (IgG4)–related disease. The high levels of serum IgG4 may promote the development of low–density plaques, intimal thickening due to pericoronitis and subsequent coronary ectasia. Case Report We present the case of a 72–year–old male patient with arterial hypertension, dyslipidemia, chronic renal insufficiency, and a family history of cardiovascular diseases. In the previous year, he suffered a cerebral hemorrhage attributed to an unspecified cerebral vascular malformation, which was managed with an endovascular approach. The patient was admitted for Non–ST–segment Elevation Myocardial Infarction (NSTEMI). Coronary angiography revealed widespread ectasia of the coronary vessels, a chronically occluded marginal branch, and an aneurysmatic proximal right coronary artery with the presence of a thrombus on the aneurysmal segment, dissolved following administration of intracoronaric heparin. Furthermore a critical stenosis at the crux involving the posterior interventricular branch was detected and angioplasty with drug–eluting stent implantation was performed on the affected vessel. Given the coronary artery ectasia, aortic ectasia revealed by echocardiography, renal insufficiency and persistently elevated amylase and lipase levels, further diagnostic investigation was conducted suspecting IgG4–related disease. Hematological tests revealed elevated IgG and IgG4 subclass levels (882 mg/dL and 1438 mg/L, respectively), C3 117 mg/dL, C4 30 mg/dL, and total IgE 130 KU/L. The diagnosis of IgG4–related disease was confirmed and the patient was advised to continue cardiological and rheumatological follow–up. Conclusion When the coronary arteries are involved in the IgG4–related disease, risk of acute events such as heart attack may increase and the prognosis is poor. Coronary thickening and ectasia, typical imaging features, other aortic involvement and inflammation indicators, like elevated serum IgG4, should be considered as red flags for an early investigation and subsequent early intervention.

Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. Males predominated (10:7), with an average lesion size of 3.9cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Clinical manifestations of chronic pancreatitis in English cocker spaniels.

Chronic pancreatitis (CP) is common in English cocker spaniels (ECS). It is histologically similar to IgG4-related disease (IgG4-RD) in humans and is characterized by duct destruction, interlobular fibrosis, and dense periductular and perivenous lymphocytic aggregates. However, the clinical manifestations of CP in ECS have not been previously described. Characterize the clinical manifestations of CP in a group of ECS, including similarities and differences to IgG4-RD in humans. One-hundred four ECS with CP and 44 client owned control ECS without CP (both healthy and diseased controls). Affected dogs were divided into 2 groups according to the methods used to diagnose CP. Case records were searched for signalment, clinical, and clinicopathological findings, and evidence of keratoconjunctivitis sicca (KCS), proteinuria, other immune-mediated diseases, and anal sacculitis. Involvement of other organs was common. Affected ECS presented with a high frequency of KCS (n = 49), proteinuria (n = 47), anal gland disease (n = 36), atopy (n = 21), and other immune-mediated diseases (n = 16). Those with parti-color hair coats, particularly blue roan, had a strong association with CP, suggesting a link between coat color and autoimmune conditions in this breed. English cocker spaniels with CP show clinical similarities to humans with IgG4-RD and common involvement of other organs. Clinicians should evaluate affected Cocker Spaniels for proteinuria, keratoconjunctivitis sicca, and other potential immune-mediated diseases.

Artificial intelligence-based differential diagnosis of orbital MALT lymphoma and IgG4 related ophthalmic disease using hematoxylin-eosin images.

To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.

Increased prevalence of malignancies in patients with IgG4-related disease: implications for clinical care.

The association between cancer and IgG4-related disease (IgG4-RD) is evolving. The primary aim of this study was to investigate the prevalence of malignancies in IgG4-RD. The secondary aim was to describe the epidemiological and clinical characteristics of IgG4-RD patients with a history of cancer. Two hundred and ten patients with IgG4-RD were included in this retrospective study. IgG4-RD phenotypes, clinical and serological variables were analyzed. The prevalence of cancer in IgG4-RD was compared with that in the Italian population using the registry of the Global Cancer Observatory (GCO) of the World Health Organization. The Standardized Incidence Ratio (SIR) for cancer in IgG4-RD was obtained based on the 5-years Limited Duration Prevalence (2015-2020) of tumors in the Italian population. Thirty-seven/210 patients (18%) developed cancer before or after the diagnosis of IgG4-RD. Solid and hematologic tumors were more frequently observed in pancreato-biliary IgG4-RD. The SIR for malignancy in IgG4-RD patients was 2.54 higher than the general Italian population (p= 0.007). The SIR was 2.78 higher for males (p= 0.005) and 1.15 higher for females (p> 0.05). Thirty-two malignancies were diagnosed before and 16 after IgG4-RD diagnosis. Interval "from IgG4-RD to cancer" was shorter than that "from cancer to IgG4-RD". Most tumors occurring after IgG4-RD developed within 36 months from diagnosis of IgG4-RD. The prevalence of cancer in patients with IgG4-RD is increased compared with the Italian population and mechanistically suggests a possible paraneoplastic association. Close surveillance is warranted for the first 36 months after IgG4-RD diagnosis.

Clinicopathologic Features of IgG4-Related Kidney Disease

IntroductionIgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that can involve nearly any organ. IgG4-RD can affect the kidney in different disease patterns, collectively referred to as IgG4-related kidney disease (IgG4-RKD). MethodsWe conducted a tissue-based cohort study with clinicopathological correlation in 125 patients with IgG4-RKD. ResultsThe mean age at biopsy (n=120) or nephrectomy (n=5) was 63 years; 80% were male. 118 patients (94%) had IgG4-related tubulointerstitial nephritis (IgG4-TIN); 20 patients (16%) had IgG4-related membranous glomerulonephritis (IgG4-MGN; 13 with concurrent IgG4-TIN). The primary clinical indication for biopsy/nephrectomy was acute or chronic renal failure in 78%, proteinuria in 17%, and mass lesion(s) in 15% (with overlap in primary indication). 52% (41/79) had abnormal radiographic findings, including mass(es) in 30% (24/79). All patients with IgG4-MGN had proteinuria. Extra-renal involvement by IgG4-RD was present in 79%. Median serum creatinine at presentation was 2.5 mg/dL (range 0.7-12). Serum IgG and/or IgG4 was increased in 91% (53/58); hypocomplementemia was present in 56% (43/77). Light microscopy showed plasma cell-rich interstitial nephritis in all cases of IgG4-TIN. 92% showed increased IgG4+ plasma cells. 7% showed an acute interstitial nephritis (AIN) pattern, and 5% showed non-necrotizing arteritis. Tubular basement membrane immune deposits were present in 83% of IgG4-TIN. Treatment information was available for 71 patients; 62 were treated with immunosuppression. Of those with elevated creatinine, 72% (41/57) showed a treatment response. ConclusionThis largest tissue-based series more clearly defines the disease phenotype of IgG4-RKD.

18F]FDG PET/CT in Benign and Malignant Diseases Involving the Biliary Tract.

Role of FDG PET/CT in evaluation of biliary tract diseases remains relatively unexplored. PET/CT with FDG helps in evaluation of both infective / inflammatory as well as neoplastic diseases as increased glucose utilization is observed in both the conditions. In this article, we describe the spectrum of FDG PET/CT findings in various diseases affecting the biliary tract. Role of FDG PET/CT in neoplastic diseases involving the biliary duct has been described at the time of staging and response evaluation; in characterization of the intrahepatic mass (abscess v/s cholangiocarcinoma). In addition, we have discussed about the false positive FDG uptake along the biliary duct stent, which interfere with scan interpretation. Few of the benign conditions described are Langerhans cell histiocytosis and IgG4 related disease involving the biliary duct and adenomyomatosis and Xanthogranulomatous cholecystitis involving the gall bladder.

Infraorbital nerve involvement as a pathognomonic sign of IgG4-related ophthalmic disease

Infraorbital nerve involvement as a pathognomonic sign of IgG4-related ophthalmic disease

Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

IgG4-related autoimmune pancreatitis and sclerosing cholangitis: A case report and literature review.

Immunoglobulin G4-related disease (IgG4-RD) can involve various organs throughout the body, primarily manifesting as endocrine dysfunction, visual impairment, jaundice, and limited sexual function. IgG4-related autoimmune pancreatitis is triggered by autoimmune reactions and characterized by structural changes in the pancreas and pancreatic ducts. The disease mainly affects middle-aged and elderly males, typically presenting as progressive painless jaundice and misdiagnosed as cholangiocarcinoma or pancreatic cancer. This study reports a 54-year-old male who consulted with different institutions multiple times due to diabetes, pancreatitis, elevated liver enzymes, and jaundice. Magnetic resonance imaging revealed swollen head of the pancreas and atrophic tail. Liver and pancreatic tissue pathology showed IgG4 plasma cell infiltration, while liver biopsy indicated interface hepatitis, liver fibrosis, and pseudolobule formation, with no evidence of bile duct damage. Following hormone therapy, the patient's serum IgG4 levels and liver enzyme levels returned to normal. The disease relapsed 2 years after maintaining hormone therapy, and the patient underwent additional hormone-induced remission therapy combined with azathioprine. The purpose of this research report is to enhance the awareness and understanding of IgG4-RD, emphasizing the necessity for personalized treatment strategies that take into account its recurrence, associations, and imaging features. This report provides valuable insights and guidance for clinicians in managing and diagnosing patients with IgG4-RD.

Viral DNA in submandibular gland tissue with an inflammatory disorder

ABSTRACT Background The etiology behind different types of chronic sialadenitis (CS), some of which exhibit IgG4 overexpression, is unknown. Further, IgG4-related disease (IgG4-RD) commonly affects the submandibular gland, but its relationship to IgG4-overexpressing CS, and the antigen triggering IgG4 overexpression, remain unknown. Materials and Methods By qPCR, we assessed the presence of 21 DNA-viruses causing IgG4 overexpression in submandibular gland tissue from patients with IgG4-positive and IgG4-negative CS. Healthy submandibular glands and glands with sialolithiasis without CS were used as controls. We examined the distribution of HHV-7, HHV-6B and B19V DNA, within virus PCR-positive tissues with RNAscope in-situ hybridization (RISH). Results We detected DNA from seven viruses in 48/61 samples. EBV DNA was more prevalent within the IgG4-positive samples (6/29; 21%) than the IgG4-negative ones (1/19; 5.3%). B19V DNA was more prevalent within the IgG4-negative samples (5/19; 26%) than the IgG4-positive ones (4/29; 14%). The differences in virus prevalence were not statistically significant. Of the IgG4-RD samples (n = 3) one contained HHV-6B DNA. RISH only showed signals of HHV-7. Conclusions None of the studied viruses are implicated as triggering IgG4-overexpression in CS. Although our results do not confirm viral etiology in the examined conditions, they provide valuable information on the prevalence of viruses in both diseased and healthy submandibular gland tissue.

Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study

Plain Language SummaryImmunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

Positive association of serum IgG4 levels with modified marsh classification system in children with gluten enteropathy: a single centre experience

Background: Celiac disease or gluten enteropathy is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and is characterized by the presence of gluten enteropathy, celiac disease-specific antibodies, HLA-DQ2/DQ8 haplotypes. IgG4-related diseases is an increasingly recognized immune-mediated condition in autoimmune disorders such as primary sclerosing cholangitis, autoimmune hepatitis, and autoimmune thyroiditis, characterized by tissue fibrosclerosis and infiltration by IgG4-positive plasma cells and increased serum IgG4 concentrations. Methods: A total of 33 children with newly diagnosed celiac disease and 31 control subjects were included in this study. All suspected celiac disease children underwent duodenal biopsy and were diagnosed based on Marsh grading. Serum IgG4 level estimations were performed using an enzyme-linked immune sorbet assay method with a cut-off of 135 mg/dl for diagnosis. Results: A significant positive association between serum IgG4 levels and Marsh classification was found, the higher the levels of IgG4 in serum, the higher the grade on Marsh staging. Mean serum IgG4 levels in Marsh 3a was 126.32 mg/dl, in 3b was 171.35 mg/dl and in 3c was 209.24 mg/dl (p value=0.004) Conclusions: With increasing serum IgG4 levels, increased severity of damage was seen on biopsy specimens based on higher Marsh grade. To the best of found knowledge, this is the first study to establish the relation between IgG4 and mucosal damage in children with celiac disease.

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.