IgG4 Disease Research Articles

A Case of ALECT2 Renal Amyloidosis Associated with IgG4 Related Kidney Disease, Membranous Nephropathy and Early Diabetic Kidney Injury

Abstract Introduction/Objective ALECT-2 amyloidosis is a rare type of amyloidosis that mostly involves kidneys with other organs rarely affected. It has a high prevalence among patients of Hispanic descent. Membranous nephropathy is one of the most common causes of proteinuria in adults. IgG4-related disease is a systemic disease, which commonly involves the pancreas, but occasionally affects the kidney and manifests as chronic renal insufficiency. Here we describe a very unusual case of concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury. Methods/Case Report A 49-year-old Hispanic male patient with a history of diabetes and IgG4-related autoimmune pancreatitis and primary sclerosing cholangitis presented with abrupt onset of proteinuria and hypoalbuminemia. A kidney biopsy was performed and showed severe interstitial plasma cell-rich inflammatory infiltrates and interstitial fibrosis which had a storiform pattern. The glomerular basement membranes (GBM) showed focal pinpoint holes but no spikes by silver stain. Immunofluorescence microscopy (IF) showed diffuse and finely granular capillary loop staining for IgG, with Kappa and lambda light chains of equal intensity. IF for Anti-phospholipase A2 receptor (PLA2R) was negative. Immunohistochemical (IHC) stain showed IgG4 positivity in about 60% of IgG-positive plasma cells. Congo red was positive for birefringent deposits predominantly in the interstitium and arteriolar walls with focal deposits in the glomerular mesangium and capillary wall. IHC stain for Amyloid AA and DNAJB9 were negative. Electron microscopy showed scattered subepithelial immune complex-type electron dense deposits consistent with membranous nephropathy, randomly oriented fibrils in interstitium, mesangium and GBM, consistent with amyloidosis, and thickening of GBM (average 559 nm), consistent with early diabetic kidney change. The tissue was sent for mass spectrometry which showed a peptide profile consistent with ALECT-2 (Leukocyte chemotactic factor 2) type amyloidosis. Results (if a Case Study enter NA) NA Conclusion In up to a third of cases reported in the literature, a concomitant renal pathology was present. Diabetic nephropathy was the most common concurrent pathology, to be followed by IgA nephropathy and membranous nephropathy. However, the concurrence of membranous nephropathy, IgG4 disease involving the kidney, ALECT2 amyloidosis, and early diabetic kidney injury has never been described before.

Abstract 12428: An Unwelcome House Guest: Coronary Aneurysms and Evolving Stemi

Case Description: 54-year-old man presented to the Emergency Department (ED) three weeks after Covid-19 infection for progressively worsening dyspnea and hypoxemia. Dexamethasone and prophylactic apixaban (2.5mg twice a day) were initiated and he was discharged 48 hours later. A week after discharge he re-presented to the ED requiring 6L of oxygen (O 2 ) despite uninterrupted dexamethasone and apixaban therapy. His past medical history was significant for quiescent IgG4 disease on Rituximab and Type 1 Diabetes. He was afebrile, tachycardic and tachypneic with decreased right lower lobe breath sounds. He had an elevated erythrocyte sedimentation rate and C-reactive protein, no leukocytosis and no pulmonary embolism of CT. He was admitted and vancomycin and cefepime antibiotic therapy for a superimposed bacterial pneumonia was begun. On day 12 of the hospital stay, he experienced new onset chest pain. Evaluation showed an elevated troponin and submillimeter ST segment elevation concerning for an evolving STEMI. Coronary angiography demonstrated an 90% diffuse mid LAD stenosis and two large coronary aneurysms of the left circumflex artery (LCx). The mid-LAD was stented using a 3.0 x 38 mm and 2.75 x 26 mm Onyx drug eluting stents with resolution of his chest pain. IgG4 serum level was normal and imaging did not demonstrate active IgG4 disease. He was discharged on aspirin and clopidogrel. Due to concern for a hypercoagulable state in the setting of Covid 19 infection, IgG4 disease and the large coronary aneurysms for thrombus formation, warfarin anticoagulation was also initiated. On review of his coronary imaging, the largest LCx aneurysm was 9mm on admission and 12mm three weeks later with evidence of diffuse coronary inflammation. CT Fractional Flow Reserve (abnormal ≤ 0.80) demonstrated decreased flow at the distal aneurysm with no focal stenosis to account for flow reduction. Conclusion: 54-year-old man with IgG4 disease presenting with prolonged Covid-19 infection and acute NSTEMI. He was found to have large, flow limiting coronary aneurysms and inflamed coronary arteries all consistent with his IgG4 disease. Management of these aneurysms will be discussed.

Abstract 10781: An Unusual Case of Transient Inflammatory Constrictive Pericarditis: IgG4 Disease

Case Presentation: A 54-year-old male with a past medical history of hypertension presented with chest tightness, shortness of breath, fatigue, and ankle edema. His vital signs were within normal limits but physical exam was significant for jugular venous distension and bilateral peripheral edema. Laboratory studies were unremarkable except for elevated inflammatory markers (C-reactive protein [23.6 mg/dl] and erythrocyte sedimentation rate [34 mm/hour]). Interferon assay, Influenza A/B antigens and anti-nuclear antibody were negative. The patient was diagnosed with constrictive pericarditis (CP). Although the patient was treated appropriately for pericarditis with a steroid taper, colchicine and ibuprofen, his symptoms recurred. Therefore, he underwent a radical pericardiectomy which resulted in a marked clinical improvement. The final pericardial pathology revealed fibrosis and plasma cell infiltrates with >30% of cells positive for IgG4. An echocardiogram revealed a small pericardial effusion with septal bounce, annulus reversus, and a plethoric inferior vena cava consistent with a diagnosis of CP. Cardiac magnetic resonance imaging showed a small circumferential pericardial effusion and respirophasic septal flattening during inspiration with marked pericardial delayed enhancement (DHE). Discussion: CP is commonly caused by viral or idiopathic etiologies, with infection (tuberculosis) being more prominent in developing countries. IgG4 disease is an uncommon cause of CP with only a few cases of IgG4-related CP have been reported. Pathological findings on histology include IgG4-positive lymphoplasmacytic cells and fibrosis. The disease is characterized by steroid-responsive condition but pericardiectomy is pursued with a suboptimal response. Cardiovascular manifestations of IgG4 disease are under explored and our case illustrates the importance of recognizing and treating the pericardial complications of IgG4 disease.

PSAT325 Unmasking the Effect of IgG4 Disease Surge on Thyroid Gland: A Case of Bilateral Sialadenitis in Patient with Past History of Graves.

Abstract Introduction Immunoglobulin G4-related disease is a fibrous-inflammatory disease characterized by lymphoplasmacytic tissue infiltration of IgG4 positive plasmablasts and small lymphocytes, that may be related to storiform fibrosis, obliterative phlebitis and modestly increased tissue eosinophils. This condition was recently recognized in 2013. It has unknown pathophysiology. The common characteristics shared by the different entities that make up the IgG4-related disease are: raised serum IgG4 levels, alterations in the imaging tests with neoplastic-like swelling of the affected organs, specific histopathological characteristics, and in immunostaining, as well as a good response to treatment with glucocorticoids. Clinical Case A 75-year-old male with a history of Grave's disease with ophthalmopathy, osteopenia, gastroesophageal reflux disease, obstructive sleep apnea, and benign prostatic hypertrophy presented to the clinic after a neck ultrasound and CT neck were ordered for investigation of bilateral "neck lumps". Neck ultrasound was evident for the heterogeneous appearance of submandibular glands and a hypoechoic nodule in the left neck with internal vascularity below the left jaw. CT neck with IV contrast showed evidence of possibly sialadenitis and lobular soft tissue thickening in the inferior aspect of the left submandibular gland measuring approximately 3.5 cm. Surgical pathology report of the left submandibular gland demonstrated a significant increase with IgG and IgG4 plasma cells and CD38 confirmed a dense plasmacytic infiltrate. IN the laboratory, IgG4 was elevated, 462 mg/dL (2-96 mg/dl) Conclusion As with many autoimmune diseases, it is unknown what triggers the Immunoglobulin G4-related disease. Given that the latter has just recently been diagnosed and recognized it is imperative to continue to record and develop data regarding it to better understand it. Multiple endocrine organs could be involved in the pathology of IgG4 related disease. The health care providers need to be cognizant of this condition and the wide variety of manifestations it could have. This disease can be first encountered by any medical field due to the broad spectrum of clinical findings that it could encompass. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

S3620 IgG4 Gastropathy: Hemorrhagic Gastropathy as the Culminating Presentation of Undiagnosed IgG4-Related Disease

Introduction: IgG4 related disease (IgG4-RD) is a newly recognized, immune-mediated disease with IgG4-positive plasma cell infiltration. Serum IgG4 levels are often elevated (although not required for diagnosis). IgG4-RD can affect a multitude of organs, including but not limited to the pancreatic-biliary system, salivary/lacrimal glands, retroperitoneum, liver, aorta, lymph nodes, and rarely, the gastrointestinal tract. This case highlights the rare GI tract presentation of a patient’s heretofore unrecognized IgG4 disease. Case Description/Methods: An 81-year-old woman with past medical history of Sjogren’s disease, myelodysplastic syndrome, and chronic myelomonocytic lymphoma presented to the emergency department for melena. Physical exam was unremarkable, but melena confirmed on digital rectal exam. Laboratory studies with hemoglobin nadir at 5.0 g/dL (baseline 8), hypergammaglobulinemia (without monoclonal peak) and elevated IgG4. Gastroenterology was consulted and performed esophagogastroduodenoscopy, showing hemorrhagic gastropathy and friable tissue. Biopsy showed gastric mucosa with patchy severe chronic gastritis and predominant plasma cell infiltration (without light chain restriction), thought to be isolated IgG4 gastropathy. Melena resolved with supportive care. Bone marrow biopsy obtained, appropriately decreased cellularity, no monocytes on flow cytometry. Abdominal computerized tomography with intravenous contrast showed diffusely atrophic pancreas, 4.8 cm infrarenal aneurysmal abdominal aorta (AAA), and post cholecystectomy changes. Reported history of pancreatitis (records unavailable), fine needle aspiration of pancreatic head and tail (ten years prior) showed predominantly acute inflammatory cells, necrotic tissue debris and benign ductal epithelial cells, respectively. Salivary gland biopsies (ten years prior) showed benign mucinous gland tissue and multiple reactive lymphoid follicles. The clinical picture was concerning for possible systemic IgG4 disease. Unfortunately, four months after initial evaluation, patient suffered from a cerebrovascular event and passed away a month later after progressive debilitation. Discussion: On initial evaluation, patient appeared to present with isolated IgG4 gastropathy. Given history of salivary gland disease, pancreatic disease, and AAA, high degree of suspicion exists for underlying IgG4- RD connecting previous diagnoses. Although rare, IgG4-RD may present in various ways, and clinicians must remain vigilant for appropriate diagnosis and treatment.

S2919 Bile Duct Injury Due to Ketamine Use

Introduction: Ketamine is used routinely in the hospital for anesthesia, but is also used recreationally for its hallucinogenic and dissociative side effects. Chronic recreational use has been linked to bile duct damage and ulcerative cystitis. We report a case of ketamine induced sclerosing cholangiopathy. Case Description/Methods: A 42-year-old Cantonese woman with past medical history of bilateral hydronephrosis with stents leading to chronic kidney disease presented with abdominal pain associated with abnormal transaminases. Alkaline phosphatase was high at 1,017 IU/L with gamma glutamyl transferase of 2,310 IU/L with normal bilirubin. Abdominal imaging showed diffuse dilatation of the common bile duct. Viral serologies and anti-mitochondrial antibody were negative. She reported chronically elevated liver tests of unknown etiology. Social history was notable for prior alcohol abuse. She denied family history of liver diseases. Her pain resolved and plan was for outpatient follow-up, but she re-presented with sepsis with a rise in bilirubin to 2.9 mg/dL (Table 1). Given prior abnormal imaging, a magnetic resonance cholangiopancreatography was obtained, which showed increased intra- and extrahepatic bile duct dilation with irregular appearance of the central intrahepatic ducts with possible stricture. Differential diagnoses were recurrent pyogenic cholangitis, sclerosing cholangitis, and IgG4 disease. Her IgG level was high at 2,779 mg/dL with IgG4 elevated at 213 mg/dL. Liver biopsy showed chronic cholestatic liver injury consistent with sclerosing cholangitis (Image 1). IgG4 stain was negative. Upon further investigation, patient admitted to at least a decade of daily ketamine use, which was likely the culprit of both her kidney and liver diseases. Discussion: Due to her age, race, gender and rarity of ketamine induced cholangiopathy, she was not directly asked about ketamine use. Since the early 2000s, ketamine has emerged as the illicit drug of choice in Hong Kong and has seen increased use throughout Asia. The biliary damage from ketamine has been studied by a Chinese group that found 62% of the 257 chronic ketamine users had biliary tract anomalies. The greater the alkaline phosphatase, the higher the likelihood of finding biliary tract anomalies on imaging. Ketamine cessation has resulted in normalization of liver tests and imaging, however worsening cholangiopathy has been seen despite abstinence. In patients who present with unexplained cholangiopathy, chronic ketamine use should be considered.Figure 1.: Liver biopsy: A mild lymphoplasmacytic inflammation is noted in some triads with focal and mild interface activity. The bile ducts are injured (irregular contour, unevenly distributed nuclei, intracytoplasmic vacuoles) with focal periportal cholestasis. Immunohistochemical stain for keratin 7 confirms predominantly periportal cholestatic hepatocytes. Keratin 19 shows widespread loss of canals of Hering and focal bile duct loss. Rhodanine stain confirms periportal hepatocellular copper accumulation compatible with a chronic cholestatic process. Table 1. - Patient's hepatic function panels during initial encounter, subsequent encounter, and at least 6 months after subsequent encounter Liver Tests Reference Range & Units Initial Hospitalization Subsequent Hospitalization Most Recent Liver Tests Total bilirubin 0.2 – 1.2 mg/dL 0.8 2.9 4.5 Direct bilirubin 0 – 0.5 mg/dL 0.7 1.8 3.3 Aspartate aminotransferase 5 – 34 IU/L 75 104 88 Alanine transaminase 0 – 37 IU/L 74 129 91 Alkaline phosphatase 40 – 150 IU/L 1017 1106 845 Gamma glutamyl transferase 12 – 43 IU/L 2310 2516 1897

S1848 Testosterone Supplement-Induced Pancreatitis

Introduction: Common causes of acute pancreatitis (AP) in the United States are gallstone pancreatitis and alcohol use. However, about 2% of AP cases are attributed to Drug-induced pancreatitis (DIP). Though infrequent, the pathology is associated with substantial morbidity and mortality, which makes timely identification of the inflicting agent important. Supplements that enhance athletic performance and libido are commonplace in today’s community and remain largely unregulated. The lack of understanding and awareness of the detrimental adverse effects of such drugs can affect physical and mental health. Case Description/Methods: A 51-year-old gentleman with a history of chronic kidney disease Stage II, hyperlipidemia on statin, diverticulosis, and GERD on omeprazole presented to the ER with acute abdominal pain associated with nausea and vomiting for a day. The epigastric pain was described as 10/10 in intensity, sharp with radiation to the back and associated with 3 episodes of non-projectile, bilious, non-bloody vomiting. He is a non-smoker and drinks alcohol occasionally, his last drink being a can of beer 1 week prior. He denied recent infections, abdominal procedures, or trauma. On examination, his vitals were normal, and was in minimal distress. Tenderness was elicited in the epigastric region. Initial labs showed leukocytosis with left shift, elevated AST of 225, ALT of 202, LDH of 274, and a significant increase in levels of lipase >3000. A CT scan of the abdomen showed findings consistent with acute interstitial pancreatitis. Imaging and laboratory investigations were negative for biliary disease and IgG4 disease. On asking further history, he reported taking over the counter testosterone supplements to enhance his libido for 2 weeks. A diagnosis of DIP was made and was treated appropriately with aggressive hydration and pain management. Discussion: DIP is attributed to four classes of drugs (I to IV) and steroids like testosterone are placed under Class I. The possible mechanism for causing AP include pancreatic duct constriction, cytotoxic and metabolic effects, accumulation of a toxic metabolite or intermediary, and hypersensitivity reactions. Prevalent use of testosterone in the male community for bodybuilding and increasing libido warrant the need to create awareness. Additionally, these drugs are difficult to study due to the varied consumption patterns, unknown origin and ingestion of high doses.

S2168 The Use of Rituximab for IgG4–Related Sclerosing Mesenteritis

Introduction: Sclerosing mesenteritis (SM) is an uncommon fibro-inflammatory disease affecting the abdominal mesentery. Although some patients are asymptomatic or have minimal symptoms, SM can present with complications such as bowel obstruction, chylous ascites, and mesenteric ischemia. First-line therapy includes glucocorticoids in combination with tamoxifen in those who are symptomatic. Case Description/Methods: An 82-year-old man with a history of prostate cancer and melanoma in remission and lymphocytic colitis presented with 4-months of poor appetite and 40-pound unintentional weight loss. Computed tomography (CT) abdomen showed an irregular 8.6 cm mesenteric mass with surrounding misty mesentery (Figure, Panel 1). CT-guided biopsy demonstrated fibro-adipose tissue with increased IgG4-positive plasma cells, supporting a diagnosis of IgG4-related SM. Follow-up CT abdomen 6 months later demonstrated enlargement of the mass with new encasement of the jejunal and ileal branches of the superior mesenteric artery and vein. Given impending mesenteric ischemia, he was treated with rituximab, a monoclonal anti-CD20 antibody, with 2 infusions 2 weeks apart without side-effects. He had contraindications to first-line therapy with glucocorticoids given prior suicidal ideation while on budesonide for microscopic colitis. Three months following treatment, his erythrocyte sedimentation rate improved from 52 to 25 (reference range, 3-28 mm/h) and IgG4 level from 851 to 267 (2.4-121 mg/dL). CT abdomen demonstrated a 50% decrease in the volume of the mesenteric mass without significant vascular involvement (Figure, Panel 2) and he had regained 30 pounds. Discussion: Although rituximab has been studied for IgG4-related disease in general, the use of rituximab specifically for IgG4-related SM is not well-known. We report a case of a patient with IgG4-related SM treated effectively with rituximab, suggesting this may be a suitable medication for those who have contraindications or do not respond to current first-line therapy, especially if IgG4-related. Whether this drug would also work in patients with SM not related to IgG4 disease is unknown. Patients treated with rituximab should be closely monitored for infections, as well as allergic and infusion-related reactions.Figure 1.: CT abdomen pelvis of sclerosing mesenteritis before (1) and after (2) rituximab treatment.

P20 Treatment resistant psoriatic arthritis: a case report

Introduction/BackgroundAlthough the era of targeted drugs has transformed the treatment of psoriatic arthritis (PsA), treatment resistant PsA still occurs. We present a rare case of a patient (renamed Ms Smith) with severe treatment resistant PsA.Ms Smith, a previously healthy 25-year-old, was diagnosed with arthritis in July 2018. She presented at that time with severe monoarthritis of right ankle starting in September 2017. It was initially thought to be possible sarcoma, but biopsy confirmed inflammation. She had no psoriasis and was HLA-B27 positive. She was diagnosed seronegative peripheral spondyloarthritis (psoriatic type).Description/MethodShe was treated with sulfasalazine and methotrexate in September 2018 but had side effects and no response. Her arthritis spread to multiple joints (tender joint count (TJC) 8, swollen joint count (SJC) 5, patient/physician global 4) and treatment was escalated to adalimumab biosimilar, but with minimal improvement (6 TJC, 5 SJC, patient/physican global 4). Despite additional prednisolone and subcutaneous methotrexate, she did not make a significant response.Given her poor response, she was switched to secukinumab in March 2019 along with short course prednisolone. At 12 weeks she had partial response from physician assessment, but she did not feel much better. To maximise response, she was also given leflunomide but experienced side effects and no benefit. She also developed bloody diarrhoea, raising concern about inflammatory bowel disease (a recognised complication of IL-17), but investigations were negative. Given the side-effects and non-response, secukinumab and leflunomide were stopped after 6 months.In January 2020, she presented with TJC 24, SJC 6 and patient/physician global of 5. She was switched to tofacitinib and restarted on leflunomide with subcutaneous methotrexate. Again, she stopped leflunomide but continued tofacitinib plus methotrexate until August 2020. At that time, she had presented with left hip pain; MRI confirmed sacroiliitis and left hip synovitis. She also had multiple swollen joints. Given worsening disease and spinal involvement, she was switched to etanercept as fourth biologic but did not respond to this either.Discussion/ResultsShe saw a second rheumatologist who agreed with diagnosis/treatments. Bloods tests, illustrated in Table 1, showed increase in her CRP. X-rays reviewed by radiology specialist interestingly showed significant erosive disease as well as unexpectedly some subluxation that appeared more like RA than PsA. Following an IFR, she was started on tocilizumab (subcutaneously initially and then one intravenously) but developed a non-allergic reaction to it (so only given half the infusion) and unusually her CRP increased to 325.P20 Table 1:Blood test resultsBlood testsResultsC-reactive protein127 (previously consistently around 80-90)Rheumatoid factorNegativeAnti-cyclic citrullinated peptides (anti-CCP) NegativeAnti-nuclear antibodiesNegativeProteinase 3 (PR3)Normal (2.5)Myeloperoxidase (MPO)Borderline positive (4.3)IgG4Very raised (no antibodies identified)TriglyceridesNormalFerritin300A PET-CT scan showed FDG avid nodes in the axillae, abdominal retroperitoneum, pelvis, and inguinal regions. A lymph node biopsy found IgG4 cells and reactive changes to a tattoo. Discussion in regional IgG4 meeting felt IgG4 disease was unlikely. Echocardiogram and blood cultures were negative.She was recently started on rituximab, alongside methotrexate. If no response to this - what next? Cyclophosphamide? She has recently been diagnosed with Human Papillomavirus and had Cervical Intraepithelial Neoplasia 1 on colposcopy.Key learning points/ConclusionMs Smith has one of the most resistant forms of arthritis that did not respond to any treatment to date.

P133 Post-COVID-19 recurrent fungal urinary tract infections: A case series

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMBackgroundCOVID-19 has opened a pandora's box of opportunistic infections and immune alteration. We hereby present a series of patients with recurrent fungal urinary tract infections triggered by an episode of COVID-19.DescriptionCase 1: A 66-year-old male, diabetic, known chronic kidney disease, had moderate COVID-19 in September 2020 needing remdesivir and steroids; 2 months later, he was treated for a fungal UTI elsewhere. In May 2021, he presented with right-sided pyelonephritis, hydroureter, and pyonephrosis. DJ stenting was done and cultures grew C. tropicalis. Record of anti-fungal susceptibility from the fluconazole resistance and was hence treated with 21 days of micafungin with significant improvement. Despite 3 weeks of directed anti-fungal treatment, he had recurrent episodes of candiduria with azotemia. Cystoscopy and selective sampling yielded C. tropicalis from the right pelvi-calyceal system, but as he was unwilling for nephrostomy and local antibiotic instillation he was started on anidulafungin and long-term 5-flucytosine suppression.Case 2: A 61-year-old male, diabetic, with uncontrolled sugars, had severe COVID-19 in September 2020 needing oxygen, remdesivir, and steroids; 1 month later, presented with right-sided flank pain and four episodes of painless passage of fleshy tissue per urethra in the last 1 year (Fig. 2). He had multiple episodes of bacterial UTIs which were treated, with complete resolution. The fleshy mass showed septate fungal elements and culture grew Aspergillus flavus sensitive to voriconazole, itraconazole, and posaconazole. He received multiple prolonged courses of voriconazole and caspofungin prior to presenting to us. CT revealed right-sided pyelonephritis with dilated pelvi-calyceal system. The patient was started on 2 weeks of micafungin followed by a prolonged course of voriconazole and 5-flucytosine with close clinical and therapeutic drug monitoring.Case 3: A 68-year-old female, diabetic, had moderate COVID-19 in April 2021, and was given remdesivir and steroids. She was admitted 1 month later with UTI (Pyelonephritis with early forming renal abscess) with urine culture growing CR Klebsiella p. (OXA-48) and C. glabrata for which she was given ceftazidime-A, vibactam, and voriconazole and underwent bilateral DJ stenting followed by stent removal after 1 month along with switching to micafungin in view of repeated candiduria on treatment. She has developed multiple UTIs in the subsequent months with C. auris being isolated twice and bacterial UTIs, treated with antibiotics and micafungin. Subsequent CT revealed retroperitoneal fibrosis encasing the ureters causing obstruction, a biopsy was inconclusive but was empirically started on methotrexate for IgG4 disease.DiscussionThe proposed immune alteration mechanism of COVID-19 of decreased phagocytic function, uncontrolled sugars, and steroid-related neutrophil dysfunction predisposes to several opportunistic infections including fungal infections. It is intriguing that these patients with refractory funguria never underwent any instrumentation The challenges associated with the management of these cases included deranged renal functions precluding the use of intravenous contrast for imaging and several anti-fungal drugs; inadequate urinary penetration of antifungals especially with deranged renal functions and hesitancy with local instillation of antibiotics, and the need for repeated surgical intervention including insertion of stents in an infected urinary tract.

Atypical Optic Neuritis: The Potential Red Flags.

Many potential causes of optic nerve inflammation exist, including typical and atypical causes, which require different management strategies. The objective of this study is to identify red flags that help differentiate typical from atypical optic neuritis (ON). This prospective study included 66 patients (100 eyes) with immune-mediated ON from January 2016 to June 2019, carefully excluding the nonimmune causes. The clinico-radiological features, investigations, therapy, and outcome were analyzed. We evaluated 33 cases each of typical and atypical ON. The typical group included 29 idiopathic ON and four associated with multiple sclerosis. Atypical ON included 19 neuromyelitis optica (NMO), seven MOG-associated ON (MOG-ON), and others due to Sjogren's syndrome, granulomatous polyangiitis, sarcoidosis, and IgG4 disease. Atypical ON occurred significantly and more frequently with extremes of ages (<10 or >70 years), bilateral simultaneous or severe vision loss with early disc pallor, multiple attacks, symptoms/neuro-imaging indicating non-MS disease e.g., long segment ON/myelitis, large confluent lesions, the involvement of optic tract, chiasma, area postrema or diencephalon, and (pachy) meningitis. Systemic involvement and poor outcomes despite steroids and second-line immunosuppression were observed more often in the atypical ON. The red flags indicating atypical ON are onset at extremes of age, multiple attacks, bilateral simultaneous or severe to very severe vision loss, early disc pallor, neurological symptoms, or imaging abnormalities suggesting non-MS disease, systemic involvement, and poor steroid responsiveness. The awareness might help the clinician promptly identify and escalate therapy to ensure a better outcome.

Challenges in the diagnosis of mandible metastasis

Aim: To report the clinical course of a patient with long-lasting pain and swelling of mandible who was subsequently diagnosed with large cell neuroendocrine carcinoma (LCNEC) of the lung and to point out the importance of expanding the diagnostic approach. Case report: A 61-year-old female patient was referred to the Department of maxillofacial surgery due to severe pain in the area of temporomandibular joint (TMJ) spreading to the upper and lower jaw. Physical examination revealed tenderness, swelling and pain of the preauricular area. MR imaging showed anterior disc displacement with degenerative signs on the left side which indicated arthrocentesis. It resulted with clinical improvement that lasted for 1.6 years. Newly made orthopantomogram revealed unclear changes of the left mandibular corpus. Due to the unclear diagnosis patient underwent biopsy on two occasions, which excluded IgG4 disease, other rheumatology and hematology diseases as well as the tumor. Five years after the initial admission, the patient stated the occasional dyspnea and cough leading to administration of the chest RTG, showing visible round mass in the upper left lobe of the lung. PET/ CT showed accumulation of radiopharmaceutical substance in the corresponded area, affected regional and distant lymph nodes and accumulation within mandible. Somatostatin receptor scintigraphy confirmed the diagnosis, which may indicate the possibility of distant malignancies. Wedge resection of the lung mass was performed and pathohistological examination confirmed the large-cell neuroendocrine carcinoma (LCNEC) stage 3. Chemotherapy was administrated. Patient referred to an emergency medical tract due to the threatening cardiac tamponade and died 11 days after. Conclusions: Mandibular metastases are often presented by atypical signs and symptoms and often present the first sign of the malignant disease. Broad spectrum of examinations must be performed in order to prove or exclude distant malignancies so the best therapy option can be provided.

P148 Clinical &amp; radiological profile of 24 cases of retroperitoneal fibrosis diagnosed between 2008 and 2018 in England

Abstract Background/Aims Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disorder, with only a few international case series described. Urinary obstruction is the most common complication, requiring ureteric stenting or nephrostomy. Ureterolysis with omental wrap allows long-term ureteric patency after initial bypass stenting - this is a procedure offered by the Department of Urology at our centre since 2008. We describe the clinical and radiological profile, including medical and surgical treatment outcomes of RPF cases referred to the departments of Urology and Rheumatology of a tertiary centre in north England. Methods Electronic notes of RPF patients referred to Urology or Rheumatology, were reviewed for clinical data, radiological findings, monitoring and treatment outcomes. Results 24 RPF patients were referred to the departments of Urology and Rheumatology between 2008 and 2019. Six were under joint care between Urology and Rheumatology of our centre. The remaining 18 patients were managed by Urology of our centre and the local rheumatology, nephrology, vascular surgery, colorectal, gynaecology or urology services. 15 (62.5%) patients were male, while 9 (37.5%) were female. Median age at diagnosis was 54.5 years. Acute kidney injury was the most frequent presentation, in 91.7% of patients. Vascular involvement at presentation includes involvement of aorta (66.6%) and bowel (12.5%), accelerated hypertensive crises (8.3%) and incident deep vein thrombosis (DVT) (8.3%). Three (12.5%) cases were due to IgG4 disease. No secondary cause of malignancy was detected. CT detected RPF in all 24 patients. MAGs scans assessed individual kidney viability before ureterolysis. Five of eight PET scans detected activity metabolic activity. All 24 patients needed either double J-stenting or nephrostomy. Following nephrostomy, two cases had extra-anatomical stent instead of ureterolysis. 17 patients had ureterolysis. At follow up, 14 of these 17 (82.4%) patients remained free of stents or nephrostomy. Small treatment size suggested corticosteroid monotherapy and methotrexate to be poorly effective. Azathioprine was poorly tolerated, effective in four of seven patients. Rituximab was effective in a case of IgG4-related RPF. Long-term complications showed 70.8% of patients remained in GFR category G3a CKD, or worse, during follow up, and a total of five patients had DVT (20.8%). Aorto-arterial complications had also resulted in complex surgeries such as aneurysm repair, arterial bypass, mesenteric stenting and bowel resection. Five (20.8%) patients required nephrectomies. 41.7% of patients suffered from chronic pain. Conclusion RPF is associated with renal and aorto-venous complications, a variety of surgical morbidities and chronic pain. Multi-disciplinary care is necessary to address the multi-faceted complications and treatment strategy. In view of the varied organ complications and morbidities in this rare disease, a central registry data collection on investigation and treatment outcome is likely to be helpful to guide future management directions to reduce renal morbidity and aorto-venous complications. Disclosure E.P. Chua: None. R. Napier-Hemy: None. E.M. McCarthy: None. P. Ho: None.

P147 Venous fibrosis and stenosis in IgG4-related disease

Abstract Background/Aims IgG4-related disease (IgG4-RD) is a multi-system fibro-inflammatory disease. Common presentations involve salivary and lacrimal glands, orbital disease, autoimmune pancreatitis, retroperitoneal fibrosis and tubulointerstitial nephritis. The main histopathological features are a dense, polyclonal, lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, storiform fibrosis and obliterative phlebitis. Cases of retroperitoneal fibrosis resulting in venous compression with DVT are well described, however to our knowledge venous fibrosis and stenosis confirmed with IVUS in IgG4-RD RPF has never been described. Methods An 82-year-old lady presented with bilateral lower leg oedema. She had a past diagnosis of IgG4 disease made on the basis of retroperitoneal fibrosis (confirmed on PET-CT), raised serum IgG4 levels (IgG4 2.38; normal 0.04-0.86 g/l) a supportive tissue biopsy (fibro-lymphocytic tissue with non-diagnostic IgG4 plasma cells) and raised inflammatory markers (CRP 104, ESR 120). Disease responded well to prednisolone and azathioprine, resulting in regression of RPF. She presented with left leg pitting oedema 4 months after presentation which progressed to chronic leg venous ulceration. D-dimer testing, albumin, liver function, and renal function tests were normal. There were no signs of lymphoedema. Venous Doppler studies of the left lower leg showed a patent and compressible left common femoral, superficial femoral and popliteal vein excluding a DVT and Baker’s cyst. A repeat CT pelvis showed no compressive mass. An intravascular ultrasound showed that the wall of the IVC was stiff and of dampened amplitude with respiratory motion. There was also increased echogenicity of the left common and external iliac vein wall with significant stenosis of the distal left common iliac vein and the external iliac veins. On the right side, there was increased echogenicity of the right common iliac vein, but the lumen was well preserved. Results These findings indicated fibrosis of the IVC wall and left common iliac vein with resulting venous stenosis. The patient underwent bilateral iliac vein stenting with improvement of leg swelling and eventual healing of the venous ulcer. Conclusion This case demonstrates that venous fibrosis and stenosis may occur in the absence of compressive lesions leading to leg swelling. Further diagnostic information may be identified by IVUS and radiological intervention with venous stents may be required. Disclosure R. Baslas: None. D. Condurache: None. D. Greenstein: None. L. Patrone: None. S. Hamdulay: None.

Drug-induced acute pancreatitis in a bodybuilder: a case report

BackgroundUnregulated use of a variety of drugs and supplements by bodybuilders and athletes is common and can lead to severe adverse complications. Only a small proportion of acute pancreatitis cases are drug induced, and case reports are essential for identifying potential drug-related risks for pancreatitis. Here we present the first case report published of acute pancreatitis linked to recreational use of anabolic–androgenic steroids, subcutaneous growth hormone, and clenbuterol in a previously healthy male after excluding all other causes of pancreatitis.Case presentationA 31-year-old Arab male bodybuilder presented with acute abdominal pain associated with nausea and sharp pain radiating to the back. The patient was not using tobacco or alcohol but was using multiple drugs related to bodybuilding, including anabolic–androgenic steroids, subcutaneous growth hormone, clenbuterol, and multiple vitamin supplements. Laboratory studies revealed a normal white blood cell count, elevated C-reactive protein, minimally elevated aspartate aminotransferase and total bilirubin with normal remaining liver tests, and elevated amylase and lipase. The patient had no hypertriglyceridemia or hypercalcemia, and had had no recent infections, abdominal procedures, trauma, or scorpion exposure. Imaging and laboratory investigations were negative for biliary disease and IgG4 disease. Abdominal computed tomography revealed hepatomegaly and diffuse thickening and edema of the body and tail of the pancreas with peripancreatic fat stranding. An abdominal ultrasound showed slight hepatomegaly with no evidence of cholelithiasis. Genetic testing for hereditary pancreatitis-related mutations was negative. A diagnosis of drug-induced acute pancreatitis was made, and he was treated with aggressive intravenous hydration and pain management. The patient has avoided further use of these drugs and supplements and had no further episodes of pancreatitis during 1 year of follow-up.ConclusionsThis case describes a patient with drug-induced acute pancreatitis after the intake of anabolic–androgenic steroids, subcutaneous growth hormone, and clenbuterol, where all other common causes of acute pancreatitis were excluded. Clinicians should be alert to the possibility of drug-induced acute pancreatitis occurring in bodybuilders and athletes using similar drug combinations.

Respiratory Failure With Aspergillus submaranianii and Lymphoplasmacystic Vasculitis.

Aspergillus subramanianii is a very rare form of Aspergillus in section Circumdati. Aspergillus subramanianii has been rarely reported or ever published. IgG4 disease is an emerging disease entity that can be a diagnostic challenge. We report a critically ill patient who had invasive A subramanianii pulmonary aspergillosis and posthumous diagnosis of IgG subclass 4 interstitial lung disease.

Lacrimal Gland Lesions Biopsied in a Tertiary Eye Center in Saudi Arabia: A Clinical, Radiological, Surgical, and Histological Review.

PurposeTo study the demographics and clinical presentation of biopsied lacrimal gland lesions in a tertiary eye center and determine the accuracy of radiological imaging and blood investigations in reaching the diagnosis. We also studied the histopathological outcome of different lacrimal gland biopsy approaches.Materials and MethodsA retrospective review of patients’ charts from 2014 to 2021 who underwent lacrimal gland biopsy. The data collected included demographics, clinical presentations, surgical approaches used, blood workup done, and histopathological and radiological diagnoses. The accuracy of radiological imaging in diagnosing lacrimal gland pathologies was evaluated by comparing radiological interpretation to the final pathological report.ResultsIn a total of 48 cases, the most common lacrimal gland lesion was nonspecific inflammation of the lacrimal gland (34%, n=17) followed by lymphoproliferative lesions (25%, n=12). Females (62.5%, n=30) were more affected than males (37.5%, n=18). Other lesions included pleomorphic adenoma, angiolymphoid hyperplasia with eosinophilia, and IgG4 disease. Complete blood investigations were performed in 45.8% of patients and a systemic disease was found in only 18.2%. The initial assumptive diagnosis based on MRI and CT scan images was congruous with the histopathological diagnosis in 42% and 12%, respectively. Three surgical approaches were used for incisional biopsy in this study, including sub-periosteal, trans-septal, and palpebral lobe biopsy. Lateral orbitotomy was done in all excisional biopsy cases. We found no statistical difference in the histopathological outcome between the different surgical approaches used.ConclusionNonspecific inflammation and lymphoproliferative disorders are the most common causes of lacrimal gland lesions. Blood work-up should not be used to waive off the need for lacrimal gland biopsy, and the diagnosis should preferably be based on histopathology results. The MRI is a useful tool to diagnose lacrimal gland lesions; however, histopathology remains the gold standard method.

Case Report: Type 2 IgG4 Sclerosing Cholangitis with Autoimmune Pancreatitis

Introduction: IgG4 disease is relatively uncommon in clinical practice and often difficult to arrive at diagnosis. The clinical spectra is wide and pancreas/ biliary involvement is often involved in GI tract. Differentiating this entity with PSC remains challenging as some features overlap. We present a case which was diagnosed combining Imaging, IgG4 levels, other organ involvement and histopathology

A Pancreatic Head Mass and Extreme Elevation of CA 19-9; a Benign Masquerade of Cholangiocarcinoma

Background: Carbohydrate antigen 19-9 (CA 19-9) is a specific tumour marker for pancreatic and biliary malignancy. Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition in which IgG4 infiltrates are found in various organs, including the biliary tract and can present as pseudotumours. Method: This case report describes of an extreme elevation of CA 19-9 level of 3295 kU/L, in an 83-year-old woman presenting with severe obstructive jaundice and weight loss. An MRCP revealed a mass at the head of pancreas, amputating the biliary tree. Liver function tests revealed a significant cholestatic pattern and severe hyperbilirubinaemia (289umol/L). IgG4 level was found to be elevated 7.97g/L (normal titres 0.04-0.86g/L). Treatment high dose corticosteroids were commenced. Two months later a repeat MRCP revealed complete disappearance of the pancreatic head mass. There was also normalisation of the bilirubin and a dramatic decrease of CA 19-9 to 154 kU/L. Results: This case reports the highest published benign elevation of Ca19.9 level in the setting of IgG4 disease. In IgG4-RD, IgG4 histopathologic infiltrates are found in various organs. Immunoglobulin G4 sclerosing cholangitis and associated pseudotumours, biliary manifestations of IgG4-RD, are a recently described disease processes. Complicating diagnosis of IgG4-RD is the potential for dual pathology in patients; that being the presence of both cholangiocarcinoma as well as IgG4-RD. Conclusion: Differentiation between cholangiocarcinoma and IgG4-RD is extremely important, as the treatment is vastly different. This case illustrates that extreme elevation of Ca19.9 cannot be equated with malignant diagnosis in the setting of IgG4 disease.

The Spectrum of Autoimmune Liver Disorders, Clinical Presentation, and Autoantibodies in Patients From a Tertiary Care Center in Pakistan.

BackgroundThe autoimmune illnesses that affect the liver include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and overlap syndrome. In our patients, we aimed to address the complete spectrum of autoimmune liver disorders, clinical presentation, and autoantibodies.MethodsThe study included all the patients diagnosed with autoimmune liver disorder irrespective of age, gender, and ethnic background presented at the liver clinic of the hospital in the last two years. The diagnosis was based on characteristic clinical and laboratory findings, the presence of one or more characteristic autoantibodies, and/or histological abnormalities. The diagnosis of AIH was further validated by revised International AIH Group criteria using a scoring calculator. The diagnostic criteria for PBC required the presence of chronic elevation of alkaline phosphatase (ALP) with positive antimitochondrial antibody (AMA) or positive PBC-specific anti-nuclear antibodies (ANA) (sp-100, gp-210) tests and/or compatible histology. The patients of AIH-PBC overlap syndrome fulfilled the criteria for AIH in the setting of PBC. Patients having liver involvement in other autoimmune disorders were included in the study.ResultsThe total number of patients was 124; 83 (67%) were females; mean age ± standard error of mean (SEM) was 44.97 ± 1.47 years with a range of 09-84 years. Type-1 AIH was seen in 68 (54.8%) patients, type-2 AIH in 10 (8.1%) patients, PBC in 22 (17.7%) patients, overlap of PBC with AIH in 10 (8.1%) patients, IgG4 disease in four (3.2%) patients, psoriasis-specific immune hepatitis in four (3.2%) patients, celiac disease-related hepatitis in three (2.4%) patients, sarcoidosis in two (1.6%) patients, and ichthyosis-associated hepatitis in one (0.8%) patient. There was a high prevalence of cirrhosis (50%) at the time of presentation; 19% of patients had decompensated liver disease. ANA was positive in 52/68 cases of AIH type-1, but anti-smooth muscle antibody (ASMA) was reactive only in nine cases and anti-soluble liver antigen (SLA) in five cases. There was no female preponderance in type-2 AIH (M:F = 6:4). AMA was reactive in 25 (78%) cases of PBC and overlap syndrome. Antibodies prevalent in PBC (AMA-M2, AMA-M2-3E, sp-100, gp-210, anti-Ro52) were also seen in some cases of AIH, though they did not fulfill the criteria of the overlap syndrome.ConclusionThere is an unmet need for the early diagnosis of autoimmune liver diseases and the initiation of appropriate management to prevent complications.