Normal Serum IgG4 Levels Research Articles

IgG4-RD-Associated Mikulicz Syndrome Without Classic Systemic Involvement—A Case Report

Background: IgG4-related disease is a rare, chronic inflammatory disorder characterized by lymphoplasmacytic infiltration, ‘storiform’ fibrosis, and elevated IgG4 levels in affected tissues. This disease has a broad and heterogeneous clinical spectrum that includes four main phenotypes: pancreatic–hepatobiliary disease, retroperitoneal/aortic fibrosis, head and neck disease, and Mikulicz syndrome. Case Description: An 85-year-old male patient with a clinical presentation, which is unusual outside Asia, of IgG4-related disease phenotype Mikulicz syndrome, characterized by bilateral dacryoadenitis, orbital pseudotumor, and no evidence of significant systemic participation. Despite extensive involvement in the orbital and glandular region, the patient did not develop serious organ complications, a behavior rarely documented in the literature. Despite the serum IgG4 levels being normal (<135 mg/dL), the clinical and radiological picture suggested IgG4-RD, emphasizing the need for a biopsy for a definitive diagnosis. Histopathological examination revealed a dense lymphoplasmacytic infiltrate, storiform fibrosis, and more than 40% IgG4-positive cells, confirming the diagnosis. Results: Treatment with prednisone was initiated alongside azathioprine for long-term control. Calcium and vitamin D3 supplementation were added to prevent glucocorticoid-induced osteoporosis. Remarkable clinical improvement was observed within 24 h, with progressive orbital and glandular symptoms resolution. Over a year, the patient exhibited complete resolution of the orbital tumors, total recovery of vision, and no relapses. The only sequelae observed were dry eye. Conclusions: This case highlights the need to consider IgG4-RD with normal serum IgG4 levels, the importance of histopathology for diagnosis, and the efficacy of steroids as first-line treatment. A multidisciplinary approach is essential for timely treatment.

Identification of relapse predictors of IgG<sub>4</sub>-related sclerosing cholangitis

Introduction. Relapses occur in 30–50% of patients IgG4-related sclerosing cholangitis. Relapses may act an independent risk factor for malignancy development and the need in maintenance therapy for relapse prevention is still uncertain. Thus, studying relapse predictors and developing reliable preventive approaches is an important area of research for this condition.Aim. To determine relapse predictors of IgG4-related sclerosing cholangitis.Materials and methods. A single- center dynamic bidirectional observational study was conducted in patients aged 18 years and older with verified IgG4-related sclerosing cholangitis (n = 32). We searched for possible factors influencing the relapse of IgG4- related sclerosing cholangitis. The development of a prognostic model for the relapse probability was carried out using logistic regression. ROC analysis was used to assess the diagnostic performance of quantitative variables in predicting of relapse.Results. The median follow-up period was 33 (16–60) months. The majority of patients with IgG4-related sclerosing cholan- gitis were male (71.9%), median age was 59 ± 13 years. In most patients, delayed diagnosis (median 10.5 [4.8; 22.5] months) was associated with overdiagnosis of primary sclerosing cholangitis (41.2%) or bile duct malignancy (43.8%). Surgical interventions were performed in 50% of patients. Median serum IgG4 level was 2.70 g/L [1.92; 6.48], and 21.9% of patients had normal serum IgG4 level. Disease relapse developed in 34.4% (n = 11) of patients. Serum IgG4 level before glucocorticosteroid therapy ≥ 2.24 g/L and a delay in diagnosis by ≥ 17 months were associated with the relapse (p = 0.040 and p = 0.049 respectively). Multi-organ involvement, and extrahepatic localization of biliary strictures in the patients with the history of surgical interventions increased the risk of relapse 85 (p = 0.001) and 12 (p = 0.047) fold, respectively. The presence of biliary strictures below the confluence reduced the risk of relapse 7.5 fold (p = 0.032).Conclusions. Possible predictors of IgG4-related sclerosing cholangitis relapse may include multi- organ involvement, intrahepatic and proximal extrahepatic strictures, prior surgical interventions in patients with extrahepatic strictures, high serum IgG4 level, and delayed diagnosis.

Lymphoplasmacyte-Rich Meningioma or IgG4-Related Disease

Lymphoplasmacyte-rich meningioma (LP meningioma) is a rare form of grade 1 meningioma. It shows dense lymphoplasmacytic infiltrate, mimicking an inflammatory lesion. We present a case of Lymphoplasmacyte-rich (LP) meningioma in the left parasagittal region in a 47-year-old female. On histological examination, it showed dense lymphoplasmacytic infiltrate masking the meningothelial component. There was dense fibrosis and numerous IgG4-positive plasma cells (100-120/hpf), admixed with lymphocytes and few histiocytes. The meningothelial component was highlighted by epithelial membrane antigen (EMA) immunostain. The patient had normal serum IgG4 level. This case highlights the morphological overlap between LP meningioma and IgG4-related disease. The presence of fibrosis and increased IgG4-positive plasma cells as a major inflammatory component in LP meningioma, as demonstrated in the present case and some other previous studies raise suspicion of its association with IgG4-related disease. However, this hypothesis requires further detailed studies for confirmation.

LBMON134 Igg4 Related Hypophysitis And Skull Base Lesion: Retrospective Analysis Of 10 Years’ Experience Of A Tertiary Care Hospital Of Northern India.

Abstract Introduction 'IgG4-related' disease is a spectrum of autoimmune phenomenon that clinically manifests with multisystem disorder in nearly 50% of the cases. The nervous system involvement is noted only in 4% of cases. Hypophysitis is considered as rare inflammation of the pituitary gland and/or stalk that results in pituitary enlargement, that may or may not be associated with hypopituitarism. Design and setting: Retrospective study from a tertiary care hospital of North India. Methods and patients Biopsy proven IgG4-RD patients with various systemic manifestations registered in Postgraduate Institute of Medical Education and Research, Chandigarh between 2012 and 2022 were retrospectively analyzed. Results Among 3006 operated sellar and parasellar SOL since 2012, only 5 patients had IgG4 related hypophysitis and skull base lesion. After considering all organ systems, nearly 154 biopsy proven IgG4-RD had been reported from this institute. Three of those five patients were male and two were female. Mean age of presentation 32.2±9.49 years. Median duration of illness at presentation was 1 year. Two out of 5 cases reported with Headache, diminution of vision was the presenting complaints in rest of the three cases. Two of the 5 patients presented with some form of hypopituitarism. MRI showing Sellar space occupying lesion in 2 patients, although posterior pituitary bright-spot was absent in one case, none of them had diabetes insipidus at presentation. Three cases had stalk thickening on MRI. A female patient had retroperitoneal fibrosis leading to obstructive uropathy after four years of follow up of hypophysitis, one had associated craniopharyngioma, and one with testicular failure. Except one patient, all 3 patients had normal serum IgG4 level, data of one patient was missing. Methylprednisolone was the cornerstone of therapy for almost all the cases. Discussion Hypophysitis and inflammatory CNS lesions are not uncommon phenomena but relatively rare with IgG4-RD. IgG4-RD is diagnosed based on clinical and pathological criteria. The proposed diagnostic criteria include (1) characteristic diffuse or localized swelling or masses in single or multiple organs; (2) elevated serum IgG4 level; (3) histopathology demonstrating infiltration of lymphocytes and plasmacytes with the demonstration of IgG4 plasma cells (ratio of IgG4 to IgG cells > 40% and > 10 IgG4 plasma cells/high power field) and storiform fibrosis and /or obliterative phlebitis. The diagnosis is considered definite in the presence of all findings, probable if 1 and 3 are present, possible if 1 and 2 are present. Since they are inflammatory excellent steroid responsiveness has been documented in the literature. In this study we reported various presentation of hypophysial and skull base IgG4-RD which often confused as tumorous lesion, warrant high index of suspicion for diagnosis. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Treatment outcomes and their determinants of IgG4-related ophthalmic disease: a territory-wide cohort study

BackgroundOral corticosteroid remains the first-line treatment of IgG4-related ophthalmic disease, but steroid-dependence is common and serious. Factors associated with steroid dependence and relapse have to be further explored.Study populationA city-wide,...

Clinical Characteristics and Potential Mechanisms in Patients with Abnormal Liver Function Indices and Elevated Serum IgG4.

We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21. Clinical data (age, sex, past history, clinical manifestations, laboratory tests, imaging, diagnosis, and treatment) and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients (n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment. Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease.

Antibody deficiencies with normal IgG in adults with Non-cystic fibrosis bronchiectasis or recurrent pneumonia: Cross-sectional study.

Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured. Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.

IgG4-related chronic sclerosing sialadenitis in a child with recurrent parotitis: a case report

BackgroundIgG4-related disease (IgG4-RD) includes a group of immune-mediated diseases histologically characterized by lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children.Here we report the case of IgG4-related sialadenitis in a six-year-old patient previously diagnosed as juvenile recurrent parotitis.Case presentationA six-year-old patient was referred to our Centre for left parotid swelling of 4 × 3 cm, that was tender, soft in consistency, with overlying red and warm skin. His general condition was good but he was subfebrile; general examination revealed mild enlargement of left cervical lymph nodes. In the last 2 years he had had five episodes of parotitis, diagnosed by another pediatric Center as juvenile recurrent parotitis.On ultrasound examination the left parotid gland appeared enlarged, inhomogeneous, with a colliquative intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests showed an increase of white blood cells and anti-VCA IgM and IgG positivity, with anti-EBNA e anti-EA I negativity.The patient was initially treated with oral antibiotics, but after 10 days the parotid became fluctuating, requiring surgical biopsy and drainage. Postoperative course was regular, with complete remission under oral antibiotic and steroid therapy. Microbiological tests, including cultures for aerobic and anaerobic bacteria, mycobacteria and Bartonella, were negative.Surprisingly, histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltrate with polyclonal plasma cells mostly expressing IgG4 immunoglobulins. Thus, the diagnosis of IgG4 related chronic sialadenitis in recurrent parotitis and recent EBV infection was made.ConclusionsIgG4-related sialadenitis is very unusual in children. Histology plays a key role in diagnosis, considering that up to 30% of patients have normal serum IgG4 levels, as shown in our case.The lack of previous histological data makes it impossible to attribute our patient’s previous episodes of parotitis to IgG4-RD, though it is a very consistent possibility.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

Mass-forming immunoglobulin G4-related disease shows indolent clinical course after surgical resection, clinicopathological analysis of a series of 15 cases.

The purpose of this study is to characterize the clinicopathological features of mass-forming immunoglobulin G4-related disease (IgG4-RD). A retrospective search for cases of mass-forming IgG4-RD diagnosed at Singapore General Hospital between 2008 and 2019 was performed. A total of 15 cases of mass-forming IgG4-RD were identified. The male-to-female ratio was 2.5:1, and the median age was 61years old. The majority of cases showed a solitary lesion (12/15) with a mean size of 35mm. IgG4-RD was considered as a clinical differential diagnosis only in one case (1/15) prior to the surgical resection. Diagnostic histopathological features, such as dense lymphoplasmacytic infiltrate positive for IgG4 plasma cells (15/15), storiform fibrosis (15/15), and obliterative phlebitis (9/15), were observed in most cases. These findings were distributed heterogeneously within the lesions. Cases with single organ involvement showed a low relapse rate (2/10) and normal serum IgG4 level after surgical resection. Mass-forming IgG4-RD has a male predilection and involves various organ systems. It may be initially misdiagnosed as malignancy and undergo surgical resection. The diagnostic histological features of IgG4-RD are readily identified in different organs. However, they may be distributed heterogeneously within a single lesion. Cases of single organ involvement show an indolent clinical course and normal serum IgG4 level after surgical resection.

IGG4-RELATED DISEASE: A CHALLENGING DIAGNOSIS

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: IgG4-Related Disease (IgG4-RD) is a recently recognized chronic fibroinflammatory disease that can be difficult to diagnose. We present a case of a fifty-one-year-old female diagnosed with IgG4-RD despite normal serum IgG4 levels. CASE PRESENTATION: A fifty-one-year-old female with history of chronic kidney disease stage 2, membranous glomerulonephropathy (MGN), Type 2 Diabetes Mellitus, Hypertension, and Rheumatoid Arthritis was referred to pulmonology for evaluation of abnormal findings on CT. She was diagnosed with MGN three years prior to presentation and her renal function improved with cyclophosphamide 50mg and prednisone 60mg daily. Two years later she was admitted to an outside hospital for acute hypoxic respiratory failure secondary to presumed PNA, resulting in intubation. She recovered and the decision was made to discontinue her cyclophosphamide due to concerns of pneumonia. Six months later her kidney function began to worsen resulting in a repeat kidney biopsy. Pathology showed glomeruli positive for IgG4 and negative for PLA2-R. During this time, she lost 20 pounds within 3 months and had CT C/A/P done to rule out malignancy. The CT showed diffuse ground glass infiltrates, for which she was referred to pulmonology. Repeat high resolution CT showed thickening of the interstitium mainly in the subpleural areas of the bilateral lungs with lower lung predominance, consistent with ILD. Of note, serum IgG4 levels returned normal. DISCUSSION: IgG4-Related disease (IgG4-RD) is a rare immune-mediated disease that can affect multiple organs. Clinical presentation may include any of the following: autoimmune pancreatitis, head/neck gland tumors, retroperitoneal fibrosis, glomerulonephropathy, and ILD. Diagnosis of IgG4-RD should not be solely based on serum IgG4 levels since the levels can be normal in up to 30% of cases. Diagnosis can be established with clinical suspicion and histopathological analysis of tissue biopsy. IgG4-RD has no established incidence or prevalence as there are no reliable studies likely due to disease being recently recognized or under diagnosed. CONCLUSIONS: IgG4-RD should be considered as a differential diagnosis in patients with ILD and nephropathy, despite a normal serum IgG4 level. Delay of diagnosis and treatment could be life-threatening as in our patient with multiple episodes of acute hypoxic respiratory failure requiring intubation. REFERENCE #1: Opriţă R, Opriţă B, Berceanu D, Diaconescu IB. Overview of IgG4 - Related Disease. J Med Life. 2017;10(4):203-207. REFERENCE #2: Legatowicz-Koprowska M. IgG4-related disease: why is it so important?. Central European Journal of Immunology. 2018;43(2):204-208. doi:10.5114/ceji.2018.77391. DISCLOSURES: No relevant relationships by Prangthip Charoenpong, source=Web Response No relevant relationships by Cesar Davila-Chapa, source=Web Response No relevant relationships by Diana Song, source=Web Response

Molecular basis of immunoglobulin heavy constant G4 gene (IGHG4)-related low serum IgG4 subclasses in Down syndrome.

Objectives:To investigate the molecular mechanism of low serum IgG4 at the level of the immunoglobulin heavy constant G4 gene (IGHG4). Patients with Down syndrome (DS) are more likely to exhibit immunological abnormalities that predispose them to infection. Among other anomalies, individuals with DS have altered serum concentrations of some subclasses of immunoglobulin G (IgG), particularly the IgG4 subclasses.Methods:In this prospective study, quantitative real-time polymerase chain reaction (qPCR) was carried out from December 2017 to June 2019 in the University Hospital of Saint-Etienne, Saint-Etienne, France to measure the number of IGHG4 copies and to compare those outcomes with a reference gene (36B4). An IGHG4/36B4 ratio was considered normal when between 0.8 and 1.2. Forty-four DS patients, comprising 23 DS patients carrying severe low serum IgG4 and 21 DS patients with normal serum IgG4 (level >0.1 g/L). The patient group was compared with 38 healthy donors (controls) without DS.Results:The heavy chain gene IGHG4 heterozygous deletion was found in 16 (69.57%) DS patients with low serum IgG4 versus in 2 (9.52%) DS with normal serum IgG4 (p=0.0001). In the control group, deletion was found in 5.26% (2/38) of the sample.Conclusion:The heavy chain gene IGHG4 haploinsufficiency is highly correlated with low serum IgG4 in our population with DS, but other relevant factors must be assessed in future work.

Idiopathic retroperitoneal fibrosis: clinical features, treatment modalities, relapse rate in Greek patients and a review of the literature.

Retroperitoneal fibrosis (RPF) is mostly idiopathic (iRPF); however, it can be secondary to drugs, malignancies, infections, or, as recently recognised, can be part of the IgG4-related diseases. The aim of our study was i) to describe the presenting clinical/laboratory/imaging features and treatment modalities used in patients with iRPF and ii) to evaluate factors potentially associated with disease relapse. The medical records of patients diagnosed with iRPF and followed in four tertiary medical units in Athens, Greece from 2000 to 2018 were retrospectively evaluated. Sixty-seven patients with iRPF were included in the study. Seventy-three per cent were males, with a mean age at diagnosis 56.0±9.2 years. Low-back pain (63%) and constitutional symptoms (57%) were the commonest presenting symptoms. Elevated acute-phase reactants (78%), anaemia (43%) and impaired renal function (41%) were the most common laboratory findings. Serum IgG4 at diagnosis was evaluated in 36/67 patients and 36% of them had elevated levels (mean 297.7±166.3mg/dL). Diagnosis was mainly based on abdominal CT and/or MRI. Clinical/laboratory/radiological presentation did not differ between patients with elevated and normal serum IgG4 levels. Steroids were used as first-line treatment in 98%. Relapse occurred in 28.6% after a mean of 43.1±31.8 months. Relapse did not associate to initial clinical/imaging findings or to any treatment used, however patients with increased serum IgG4 had a significantly higher relapse rate (75% vs. 25%, p=0.005). Relapse occurred in one-fifth of patients independently of the initial clinical/radiographic presentation or treatment used. iRPF patients with baseline elevated serum IgG4 levels have a higher relapse rate.

A Rare Case of Recurrent Lymphocytic Hypophysitis Spanning 8 Years

Background: Lymphocytic Hypophysitis (LH) is predominantly a self-limiting condition. Reports of recurrent LH have been limited to case series, predominantly within first two years of initial presentation (1). There is paucity of data on long term follow up of these cases and late recurrence of LH is considered very rare (2). Clinical Case: We describe the clinical course of a 47-year female, who first presented to us, 8 years back, with headache, visual disturbance and secondary amenorrhea. Her MRI pituitary was suggestive of a pituitary mass, which was removed by trans-sphenoidal surgery. Histopathology of the mass was suggestive of LH. Patient had symptomatic improvement, and remained well on out-patient follow-up, on hormone replacement therapy. She took replacement dose of glucocorticoid for 4 years after the initial surgery and then it was discontinued. However, she re-presented to us with headache and visual disturbance this time associated with xerostomia and xerophthalmia. In this presentation, due to presence of sicca symptoms a suspicion of autoimmune aetiology was kept. Her lab parameters were consistent with pan hypopituitarism along with new appearance of anti-TPO antibodies. She underwent two consecutive trans-sphenoidal surgeries for relief of pressure symptoms, and has been started immunosuppressive doses of glucocorticoids along with methotrexate. Other causes of recurrent hyophysitis, as IgG4 related Hypophysitis, were excluded by immunohistochemistry and normal serum IgG4 level (0.72g/l). She has since been discharged, and remains well on outpatient follow-up with no mass effect. MRI pituitary done at 2 months follow up is not suggestive of residual regrowth or mass effect. Conclusion: This case highlights the importance of long term follow up of LH patients. Other autoimmune aetiology maybe considered in cases unresponsive to standard treatment, necessitating titration of additional immunosuppressive therapy.

A245 IGG4- RELATED DISEASE AS A RARE CAUSE OF GASTRIC OUTLET OBSTRUCTION: A CASE REPORT AND LITERATURE REVIEW

Abstract Background IgG4- related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition that can affect a wide range of organs, including the pancreas, biliary system, retroperitoneum, lymph nodes and salivary glands. However, gastrointestinal luminal involvement is very rare, and the presentation with isolated gastrointestinal obstruction is extremely unusual. Aims We present a case of IgG4-RD presenting with gastric outlet obstruction secondary to severe duodenal stricture. Methods A 59-year-old female presented with 6 months history of abdominal pain, postprandial nausea and vomiting associated with significant weight loss. CT showed circumferential wall thickening of the 2ndand 3rd parts of the duodenum with gastroscopy showing severe ulcerated duodenal stricture that could not be passed through. Biopsies from the ulcerated area did not reveal a specific etiology, but malignancy could not be excluded, and the decision was made to pursue surgical management with Whipple’s procedure. Surgical pathology revealed IgG4 related disease in the form of an ulcerated gastric mass invading the duodenum and the pancreas with normal serum IgG4 level. Postoperatively, the patient developed anastomotic leak that was managed conservatively with antibiotics and drainage resulting in significant improvement in her symptoms. MRCP did not show any pancreatic or biliary abnormalities. Results A few weeks later, she represented with abdominal pain as well as nausea and vomiting. CT scan revealed severe inflammatory changes at the anastomosis site with mucosal thickening concerning for persistent leak. However, as she was optimally treated before, it was concluded that these changes are likely related to recurrent IgG4-RD. To induce remission, prednisone was started with remarkable improvement in her symptoms within two weeks, and complete resolution of the previous inflammatory changes around the anastomosis on repeat imaging. Subsequently, she was started on mycophenolate mofetil (MMF) with a slow prednisone taper. Conclusions IgG4-RD involving the gastrointestinal tract is rare with rare cases reported in the literature presenting in variable ways. Our case demonstrates the possibility of IgG4-RD presenting as gastric outlet obstruction; IgG4-RD should be considered in the differential diagnosis of unexplained duodenal stricture or gastric outlet obstruction. IgG4-RD usually responds to steroids but long-term response rates to steroid-sparing agents, especially in the subset of patients with luminal IgG4-RD, remains to be seen. Funding Agencies None

Treatment Response to Idiopathic Retroperitoneal Fibrosis-associated Hydronephrosis With a Focus on IgG4/IgG3 Serum Concentration Ratio.

Hydronephrosis, a common complication of idiopathic retroperitoneal fibrosis (iRPF), may lead to poor renal outcomes unless resolved in a timely manner IgG4-related diseases characterized by elevated serum IgG4 levels are responsible for a few iRPF cases However, the underlying immunologic features of most iRPF cases have not been clearly defined, and these cases exhibit varied responses to medical treatment Thus, we investigated the predictive factors for hydronephrosis-associated outcomes among iRPF patients. We retrospectively included 18 iRPF patients with hydronephrosis in a tertiary referral hospital from 2012 to 2019 Hydronephrosis improvement was assessed on images taken 6 months after diagnosis Categorical variables were compared using chi-square or Fisher's exact test Continuous variables were compared using Mann-Whitney U-test. On follow-up images, 8 patients (444%) showed an improvement in hydronephrosis Patients with improvement more frequently had reverse serum IgG4/IgG3 ratio (875% vs 30%, p=0025), abdominal aorta involvement (875% vs 30%, p=0025) and glucocorticoid treatment administration (875% vs 30%, p=0025) than those without improvement The proportion of elevated serum IgG4 level did not differ between the two groups Even in the 14 cases with normal serum IgG4 levels, reverse serum IgG4/IgG3 ratio was more frequently observed in patients with improvement than in those without improvement (833% vs 125%, p=0026). The reverse serum IgG4/IgG3 ratio was associated with hydronephrosis improvement in iRPF patients, suggesting it to be a suitable serologic marker for predicting favourable responses to glucocorticoid treatment.

S1782 IgG4 Colitis and Infliximab Therapy

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition. It is characterized by increased serum levels of IgG4 and tissue infiltration by IgG4 cells. It can involve multiple organs and if untreated the disease can lead to fibrosis and irreversible organ damage. IgG4-RD has mostly been described in adults and it's exact prevalence in pediatrics is unknown. We report a pediatric case of IgG4-positive sclerosing colitis who had dramatic response to Infliximab therapy. CASE DESCRIPTION/METHODS: 6 year old adopted male who was previously healthy presented to ER with acute onset of severe abdominal pain and fever. He was febrile with severe RLQ tenderness, guarding and minimal bowel sounds. Labs showed elevated WBC and CRP. US abdomen study did not visualize appendix. Subsequent MRI abdomen showed descending colitis with no evidence of obstruction, abscess or acute appendicitis. He soon developed abdominal distension and multiple episodes of bilious emesis. AXR obtained showed dilated loops of small bowel concerning for partial SBO, requiring NGT decompression. Stool studies including C. Diff returned negative. As he developed a SIRS picture with worsening abdominal distension, stat CT abdomen obtained showed bowel dilation without an obvious transition zone or pneumatosis but thickening of terminal ileum and left colon. Due to patient's worsening clinical picture, there was concern for possible compromised bowel or distal bowel obstruction not diagnosed by imaging, hence he underwent diagnostic ex-laparoscopy which showed thickening and inflammation of the left colon leading to segmental left colon resection and descending colostomy. Biopsies were taken and immunostaining was concerning for an IgG4 sclerosis colitis. Serum IgG4 level was elevated at 202. Patient was started on steroids followed by Infliximab as maintenance therapy. Repeat EGD/Colonoscopy prior to colostomy reversal showed normal biopsies and immunostaining. He responded well to Infliximab therapy with subsequent normal serum IgG4 levels. DISCUSSION: The pathogenesis of IgG4-RD remains incompletely understood. Study shows that small subset of patients with IBD can be characterized by high levels of serum and mucosal IgG4. These patients are generally prone to more severe and extensive lesions suggesting that high level of IgG4 may be a biomarker for a new subtype of IBD. The current literature in this area is sparse. Our case showed positive response to Infliximab therapy in IgG4 positive colitis.

S1477 A Spy Took a Bite to Get the Dx Right - A Case of Idiopathic Pancreatitis

INTRODUCTION: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that is infrequently recognized and is characterized clinically by frequent presentations with obstructive jaundice. Serum IgG4 testing as a means to “rule out” IgG4 related disease may not be as helpful as initially thought and may lead to inappropriate lack of diagnosis if suspicion is low. CASE DESCRIPTION/METHODS: A 40-year-old white male with GERD, chronic portal vein thrombosis, history of alcoholism, and chronic pancreatitis (since 2015) presents with nausea, vomiting, chills, and epigastric pain radiating to the back. He has had 8 episodes in the last year and required biliary stenting for multiple biliary strictures. He denied fever, dyspnea, chest pain, hematemesis, melena, alcohol use, scorpion sting, and trauma. Labs were significant for TRG 172, Ca 8.6, Lipase 239, AST 34, ALT 37. CT of the abdomen showed acute on chronic pancreatitis with a stable biliary stent. Previous workup for pancreatitis included normal TRG and calcium levels, lack of cholelithiasis, no inciting medications or infection, and serum IgG4 level of 7.3 (normal: 2-120). After admission, lipase increased to 1321 with worsening AST/ALT and bilirubin concerning for obstruction prompting Magnetic Resonance Cholangiopancreatography (MRCP). MRCP demonstrated extensive retroperitoneal inflammation and obstruction of the biliary stent. Endoscopic retrograde cholangiopancreatography (ERCP) with SpyGlass direct visualization revealed an occluded biliary stent, multiple strictures, and exophytic tissue in the lower common bile duct which was biopsied with SpyBite. The strictures were dilated, the stent was exchanged, and the biopsies were sent for pathology. Pathology returned negative for malignancy but stained positive for IgG4 and the patient was initiated on systemic steroid therapy. DISCUSSION: With recurrent pancreatitis, classic histological findings, biliary strictures, cholangitis, and improvement with steroids in the setting of normal serum IgG4 levels; this complex patient represents a challenging case of type 1 AIP. A 2016 meta-analysis found that serum IgG4 had 87% sensitivity 83% specificity for IgG4-RD (1). Other studies suggest that many (as much as 33%) patients with biopsy-proven IgG4-RD have normal serum IgG4 (2). With these findings, we believe it is imperative that others give further consideration to tissue sampling in similar patients with difficult to define pancreatitis.Figure 1.: MRI Abd w CBD stent mass and pneumobilia.Figure 2.: Mass in CBD.Figure 3.: IgG4 stain positive tissue from CBD mass.

Identification of serum IFN-\u03b1 and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

P119 Characteristics and treatment of fibrosclerosing orbital inflammatory disease

Abstract Background Orbital inflammatory disease (OID) encompasses a group of disorders which affect the orbit and neighbouring areas. Several multi-system inflammatory diseases including small vessel vascuilitides, Sarcoidosis and IgG4 disease can manifest as an OID. Treatment generally includes steroid therapy in combination with conventional immunosuppressant’s, cyclophosphamide or rituximab. Herewith we describe a series of non-vasculitic, fibroinflammatory OID. Methods We retrospectively reviewed records of 5 patients referred to rheumatology with inflammatory OID after malignancy, infection and Graves’ ophthalmopathy were excluded. General demographics, histology, MRI and treatment responses were reviewed. Results Patients were generally female (4:1) and of a young age (range 33-54). Proptosis and diplopia were the key symptoms with occasional sino-nasal symptoms. Inflammatory markers on presentation were marginally raised (CRP mean 11, ESR mean 37). All patients were negative for autoantibodies and had normal serum IgG4 levels. MRI showed fibrotic mass lesions in all cases with bone erosion/ destruction in 2 cases. Biopsy showed fibrosclerosis mixed with chronic inflammatory cells. 3 cases stained positive for IgG4 cells but only one of them achieved diagnostic levels (case 3). All patients were initially treated with high dose steroids (prednisolone 1mg/kg or IV methylprednisolone (MP)) with either methotrexate or cyclophosphamide (1g EUVAS protocol). Highly resistant cases were treated with rituximab (total 2g). There was a good clinical response to treatment in all cases but in 4 patients residual fibrosis persisted on follow-up MRI (Table 1). Conclusion We describe a series of fibrosclerosing OID with histology like IgG4 disease, but with normal serum IgG4 levels and negative tissue immunofluorescence (IF) in some cases. Most cases will respond well to steroids and second-line therapy, but residual fibrosis may persist with mild clinical sequelae. Early recognition and intensive therapy may minimise fibrotic complications. Disclosures V. Thanopoulou None. A. Weller None. E. Nigar None. J. Marais None. V. Lee None. B. Marjanovic None. A. Ahmed None. I. Balasundaram None. S. Hamdulay None.