Autoimmune Serology Research Articles

S2833 A Midlife Crisis - A Rare Case of Late Onset Eosinophilic Gastroenteritis in a Middle-Aged Male, Caused by a New Onset Dairy Allergy

INTRODUCTION: Eosinophilic gastroenteritis (EG) is a rare disease of the digestive tract characterized by gastrointestinal tract (GIT) eosinophilia, abnormal function of the GIT and exclusion of other causes of eosinophilia (Eos). It is seen in 28/100,000 persons with equal male to female distribution with the majority of cases seen in children. Majority of occurrences can be linked to a food hypersensitivity especially if atopy (asthma, eczema, hay fever) is co-expressed. CASE DESCRIPTION/METHODS: 54-year-old male with dyspepsia and atopy presented with abdominal pain, vomiting, diarrhea and weight loss. He was discharged with diagnosis of gastroenteritis and dyspepsia. On last admission CBC showed Eos 39% and CT scan with gastric, small bowel and colonic thickening. Stool enteric pathogens, C. diff, ova and parasites, ESR/CRP, autoimmune panel, IGE levels, EGD and colonoscopy with biopsies were obtained. Autoimmune serologies were negative, ESR and CRP were elevated. Duodenal biopsy was negative for celiac disease but gastric and colonic biopsies revealed 34 Eos per Hpf. Patient worked on a dairy farm and consumed 4 servings of dairy per day his entire life. During the hospitalization he was placed on a dairy-free diet and was started on oral steroids. His symptoms improved in 48 hours. As an outpatient he underwent allergen testing, revealing grass allergies as well as a severe dairy allergy. He was tapered off steroids, placed on a PPI and with diet modification has been asymptomatic for over a year. DISCUSSION: EG in adults is likely missed as it can be self limited in up to 50% of cases. Careful history, high level of suspicion and a meticulous diagnostic approach is imperative to decrease the need for hospitalizations, and improve quality of life in patients with EG. Overall, there is conflicting data in regards to long term management. Studies of antihistamines, mast-cell stabilizers, leukotriene receptor antagonists, even biologic monoclonal antibodies as an adjunct to dietary modification all have yielded equivocal results. Corticosteroids are considered as the gold standard of therapy, but their unfavorable long term effects limit their use. Over the last 16 years there has been an increase in prevalence of EG, and there is growing evidence linking functional dyspepsia (FD) with an increase in GIT Eos. Prevalence of food sensitivities in FD has not been adequately studied, however it can possibly identify a largely underdiagnosed population with EG.Figure 1.: CT with IV Contrast showing small bowel and gastric wall thickening, with mesenteric edema and small volume ascites.Figure 2.: Endoscopic view of the Gastric Body and Antrum (Upper Panels), and small bowel with mild erythema (Lower Panels).Figure 3.: Hematoxylin and Eosin stain of representative gastric mucosa with noted eosinophilic infiltrate (white arrow).

A MATTER OF FLUX: A CASE REPORT ON ARC WELDER'S LUNG

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Occupational diseases are a major cause of individual health deterioration We present a case of occupational exposure to metal fumes resulting in Arc Welder’s Lungs (AWL). CASE PRESENTATION: A 63-year old male presented with shortness of breath and productive cough for 8 days. He was a welder for 27 years. He never smoked and was not taking any medications. He was afebrile, hypoxic at 78% O2 saturation, respiratory rate was 31, pulse of 97 and blood pressure of 172/90 mmHg. He had diffuse rhonchi most prominent in the bibasilar lung fields. Labs revealed a leukocytosis of 14.2 K/uL, normal liver and chemistry panels and a procalcitonin of 0.1 ng/mL. Chest X Ray showed perihilar and basilar multifocal consolidation.(Image A) A chest CT angiography was negative for pulmonary embolism but showed extensive bilateral focal consolidation and diffuse ground glass opacities with an enlarged main pulmonary artery.(Image B) He was started on antibiotics, steroids and required 6L of nasal cannula. Transthoracic echocardiography showed severe left ventricular hypertrophy, an ejection fraction of 70% and an estimated pulmonary artery pressure of 91 mmHg. His symptoms progressively worsened and oxygen requirements escalated. Viral panels, autoimmune serologies, amyloid workup and cultures were all negative. A right heart catheterization showed right atrial pressure of 6 mmHg, right ventricular pressure of 75/5 mmHg, pulmonary capillary wedge pressure of 10 mmHg, a cardiac index of 3.9 L/min/m2 and pulmonary vascular resistance of 5.3 WU suggesting a potential arteriopathy component in the setting of acute pulmonary inflammation. A bronchoscopy with lavage showed numerous hemosiderin laden macrophage with positive iron staining and positive oil red O stain. A transbronchial biopsy was not pursued due to potential bleeding risk in setting of pulmonary hypertension. Serum ferritin level was 2163 ng/mL. Based on occupational history and bronchoscopy findings, the patient was diagnosed with AWL. Given the acute inflammatory parenchymal process, pulse dose steroids were initiated with subsequent clinical improvement. DISCUSSION: AWL can present in different forms of lung disease.[1] Cases are usually “benign” without residual effects, however there are reports of symptomatic presentations with underlying fibrosis.[2] We describe the first welder’s lung case with an acute inhalational pneumonitis responsive to pulse dose steroids. Three months interval CT scan showed significant improvement of ground glass component with residual areas of underlying reticular and fibrotic changes in the bases, possibly suggestive of desquamative interstitial pneumonia.(Image C) CONCLUSIONS: Our case highlights the implications of occupational diseases which can be preventable and the possible variability in presentations. Physicians should be aware of AWL and include it in their differential diagnosis Reference #1: Riccelli MG, Goldoni M, Poli D, Mozzoni P, Cavallo D, Corradi M. Welding Fumes, a Risk Factor for Lung Diseases. Int J Environ Res Public Health. 2020;17(7):2552. Published 2020 Apr 8. doi:10.3390/ijerph17072552 Reference #2: M. P. Cosgrove, Pulmonary fibrosis and exposure to steel welding fume, Occupational Medicine, Volume 65, Issue 9, December 2015, Pages 706–712, https://doi.org/10.1093/occmed/kqv093 DISCLOSURES: No relevant relationships by Youssef Abouleish, source=Web Response No relevant relationships by Mit Patel, source=Web Response No relevant relationships by Anthony Quaranta, source=Web Response

S2745 Thinking Outside the Box: Is This Really NASH?

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is a diagnosis of exclusion and an alternative diagnosis should always be sought. We present a patient with features of portal hypertension and possible sepsis, concerning for decompensated NASH cirrhosis. He was eventually diagnosed with a hemophagocytic syndrome-associated variant of intravascular large B-cell lymphoma on autopsy. CASE DESCRIPTION/METHODS: A 64-year-old Caucasian male with metabolic syndrome presented with a 2-month history of fatigue, fevers, and 20-pound weight loss. Initial work-up was notable for an elevated AST (65 IU/L) and high total bilirubin (2 mg/mL; direct 1.3 mg/mL). Albumin was 3.2 g/dL, INR was 1.0 and platelets were 48,000 cells/mL. CT imaging showed mild hepatosplenomegaly with no ascites. He had no known history of liver disease or alcohol use. He was referred to the liver clinic for possible chronic liver disease and portal hypertension, thought to be from NASH. At the time of presentation, he was febrile (101.8 °F), tachycardic (105 bpm), and hypotensive. Besides hepatosplenomegaly, there were no other stigmata of chronic liver disease on exam. Admission labs were unchanged except an increase in total bilirubin (4 mg/mL) and a high ferritin (2400 ng/ml). Work-up for infectious etiologies, autoimmune liver serologies and drug toxin screen were unrevealing. He met 5 out of 8 criteria to diagnose hemophagocytic lymphohistiocytosis (HLH) including fever, splenomegaly, cytopenia, increased ferritin, and absent NK cell function. A PET scan showed uptake in the bone marrow, liver, spleen and lymph nodes. The patient rapidly declined clinically and died from respiratory failure. Autopsy showed diffuse involvement of the liver, spleen, bone marrow, lymph nodes and several other organs by intravascular large B-cell lymphoma (IVBCL). DISCUSSION: Our case emphasizes the importance of considering a broad differential in patients with thrombocytopenia and hepatosplenomegaly, even if typical risk factors for liver cirrhosis are present. Hematological malignancies should be strongly considered in the differential especially if patients present with B symptoms. Hemophagocytic syndrome-associated variant of IVBCL, the so-called ‘Asian variant’, is a rare and aggressive form of diffuse large B cell lymphoma. A prompt diagnosis is crucial, given its life-threatening potential and possibility of recovery with institution of therapy early in the course of the disease.Figure 1.: The cut sections of the liver looked relatively normal and did not show any gross evidence of cirrhosis.Figure 2.: Histology of the liver, which shows intravascular infiltration of tumor cells.

Anti‐synthetase syndrome‐associated pulmonary veno‐occlusive disease

Pulmonary arterial hypertension has been reported with a prevalence of 7.9% in patients with anti-synthetase syndrome; however, anti-synthetase syndrome associated with pulmonary veno-occlusive disease (PVOD) has never before been described in the literature. We present a novel case of anti-synthetase syndrome-associated PVOD in a patient who presented with hypoxic respiratory failure associated with right heart failure and was diagnosed with anti-synthetase syndrome based on his autoimmune serology and pre-capillary pulmonary hypertension on right heart catheterization. He was initiated on pulmonary arterial hypertension therapy, but with escalating dose of parenteral epoprostenol, experienced acute clinical worsening with chest imaging concerning for PVOD that was confirmed on autopsy. Anti-synthetase syndrome can be associated with PVOD, and it should be suspected in patients who have evidence of pre-capillary pulmonary hypertension and who deteriorate with the initiation of pulmonary hypertension-specific therapy.

Autoimmune Hepatitis: Clinical Characteristics and Predictors of Biochemical Response to Treatment.

Background and ObjectivesAutoimmune hepatitis (AIH) is an important cause of chronic liver disease. Aim of this study was to evaluate the clinical characteristics and factors predicting response to treatment in patients with AIH.MethodsIn this prospective observational study, all patients diagnosed with AIH from 2017 to 2019 were included. Biochemical response to the treatment was checked three months after the start of the treatment. Response was considered good if transaminases normalized, or poor if either remained persistently elevated or improved partially.ResultsOf the total 56 patients, 41 (73.2%) were females. Mean age was 29.5 (±16.9) years. About half (53.6%; n = 30) the patients were aged < 25 years and majority [47 (83.9%)] were cirrhotic. Autoimmune serology was negative in 20 (35.7%). Seronegativity was associated with severe necroinflammation (P = 0.015) and esophageal varices (P = 0.021). Response to treatment was good in 34 (60.7%). Bivariate analysis showed that good response to treatment was associated with pre-treatment serum IgG level > 20 g/L (P = 0.024), presence of pseudorosettes on histopathology (P = 0.029) and three months post-immunosuppression serum total bilirubin < 2mg/dL (P < 0.001). Multivariate logistic regression analysis showed that only pre-treatment serum IgG >20 g/L (P = 0.038) and post-treatment serum total bilirubin <2 mg/dL (P = 0.004) were independent predictors of good response to treatment.ConclusionMajority of AIH patients in our study were young and cirrhotic. A negative autoimmune serology does not rule out AIH and liver biopsy may be required to confirm the diagnosis. Seronegative AIH rapidly progresses to advanced liver disease. Response to treatment is good with pre-treatment IgG > 20g/L and post-treatment total bilirubin < 2 mg/dL.

Diagnostic approach of fibrosing interstitial lung diseases of unknown origin

Interstitial lung diseases encompass a broad range of numerous individual conditions, some of them characterized histologically by fibrosis, especially idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, chronic hypersensitivity pneumonia, interstitial lung disease associated with connective tissue diseases, and unclassifiable interstitial lung disease. The diagnostic approach relies mainly on the clinical evaluation, especially assessment of the patient's demographics, history, smoking habits, occupational or domestic exposures, use of drugs, and on interpretation of high-quality HRCT of the chest. Imaging is key to the initial diagnostic approach, and often can confirm a definite diagnosis, particularly a diagnosis of idiopathic pulmonary fibrosis when showing a pattern of usual interstitial pneumonia in the appropriate context. In other cases, chest HRCT may orientate toward an alternative diagnosis and appropriate investigations to confirm the suspected diagnosis. Autoimmune serology helps diagnosing connective disease. Indications for bronchoalveolar lavage and for lung biopsy progressively become more restrictive, with better considerations for their discriminate value, of the potential risk associated with the procedure, and of the anticipated impact on management. Innovative techniques and genetics are beginning to contribute to diagnosing interstitial lung disease and to be implemented routinely in the clinic. Multidisciplinary discussion, enabling interaction between pulmonologists, chest radiologists, pathologists and often other healthcare providers, allows integration of all information available. It increases the accuracy of diagnosis and prognosis prediction, proposes a first-choice diagnosis, may suggest additional investigations, and often informs the management. The concept of working diagnosis, which can be revised upon additional information being made available especially longitudinal disease behaviour, helps dealing with diagnostic uncertainty inherent to interstitial lung diseases and facilitates management decisions. Above all, the clinical approach and how thoroughly the patient's history and possible exposures are assessed determine the possibility of an accurate diagnosis.

Ocular myasthenia gravis: updates on an elusive target.

Ocular myasthenia gravis (OMG) is a complex condition with heterogenous phenotypes and ill-defined diagnostic criteria. Understanding concomitant risk factors and autoimmune serology can help inform prognosis for generalization and guide treatment. Although antibodies to acetylcholine receptors or muscle-specific kinase likely increase risk of generalization, they are less frequent in OMG. Patients without either antibody tend to have a milder disease process and often have variable antibodies to other end-plate proteins such as LRP4, agrin, or cortactin. The treatment of OMG begins with pyridostigmine and is supplemented by oral prednisone if treatment-resistant or high risk for generalization. Variable oral prednisone regimens have been used with success and further immunosuppression may be best achieved with mycophenolate mofetil and azathioprine. Checkpoint inhibitor-induced myasthenia gravis is increasingly recognized and likely has high rates of mortality associated with myocarditis. Our understanding of OMG and its variable phenotypes continues to evolve. Autoantibody testing increasingly provides valuable diagnostic and prognostic information. Despite these improvements, a lack of quality treatment trials creates significant challenges for evidence-based management guidelines.

Quantitative Mass Spectrometric Analysis of Autoantibodies as a Paradigm Shift in Autoimmune Serology.

Affecting ~7–9% of individuals worldwide (1), autoimmunity is a relatively common condition that can cause substantial morbidity and mortality (2). However, there are considerable challenges in finding robust and accurate biomarkers for this heterogeneous group of diseases. Serum autoantibodies have served as archetypal diagnostic biomarkers for autoimmune diseases over decades (3). As pathologic species, they can be used to monitor disease activity and treatment responses (4). Most diagnostic laboratory tests for autoantibodies utilize conventional assays such as the solid-phase enzyme immunoassay (EIA), enzyme-linked immunosorbent assay (ELISA), or radioimmunoassay (RIA). All of these assays quantitate amounts of autoantibodies in the bodily fluid but fail to delineate their molecular composition. Multiplex assays have emerged for autoantibody high-throughput screening that enable rapid identification of subsets of patients to facilitate diagnostic and predictive medicine (5). This is particularly important since multiple autoantibodies are often responsible for autoimmune disease (6). However, such conventional assays cannot unravel clonal evolution and dynamic autoimmune responses. Frustratingly, prediction of disease onset and flares with these biomarkers remains suboptimal. Mass spectrometry (MS) is an analytical technique which can identify proteins by determining the amino acid sequence of peptides derived from each protein. MS can also measure changes in relative abundance of specific proteins as a consequence of treatment, and with appropriate standards, quantify absolute abundance. MS has been used previously to analyze specific antibodies or the repertoire of antibodies in order to better understand the dynamics of humoral immune responses in vaccinated animals (7). This technology has been used to characterize autoantibodies in diseases such as systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS) by identifying their immunoglobulin variable region (IgV) subfamily usage and mutational profiles at a molecular level (8). Despite conventional immunoassays determining stability in autoantibody profiles, MS-based quantitative proteomics has been used to uncover the dynamic changes in molecular signatures and levels of autoantibodies as the disease progresses (9). Subtle nuances in the molecular profile of patient autoantibodies can be identified, paving the way for new diagnostic biomarkers that can anticipate the onset or severity of disease before conventional biomarkers or immunoassays (10). This exciting technology hence offers a unique opportunity to identify pathogenic “rogue” and/or protective clonotypes that characterize autoimmune diseases. By deconstructing these clonotypes by quantitative proteomics and establishing a database of clonotypes with their corresponding pathogenicity, this would possibly facilitate identification of at-risk patients for deterioration, or predict response to targeted therapy.

2331 Post-Infantile Giant Cell Hepatitis Leading to Severe Acute Liver Injury in Chronic Lymphocytic Leukemia (CLL): Progression of CLL vs. Drug Induced Liver Injury (DILI)

INTRODUCTION: Post-infantile giant cell hepatitis (PIGCH) is a form of hepatocyte degeneration, triggered by noxious injury. Underlying etiologies are autoimmune, drug-induced, virus mediated and miscellaneous e.g. sickle cell, CLL, post-transplant. While only occurring in 5 per 100,000 adults, when present, rapid progression to liver failure can result in a 50% mortality rate. CASE DESCRIPTION/METHODS: A 76 yo lady with a history of anemia, remote breast cancer in remission, and CLL (not on treatment), presented with a 3-week history of fatigue, nausea and jaundice following a 5-day course of azithromycin and prednisone (20 mg OD), and one dose of ceftriaxone, for acute bronchitis. Exam revealed jaundice and abdominal distension. Admission labs: AST 4233U/L, ALT 3175U/L, ALP 187IU/L, total bilirubin 9.4 (7.1 direct) mg/dl, sodium 131mEq/L, BUN 27, Cr 0.7 mg/dl. INR 1.4. WBC 68.3/µL, hemoglobin 8.2 g/dl, platelets 233/µL. CT Abd/Pelvis without contrast: mild periportal edema, with enlarged liver, otherwise normal. Workup for viral hepatitis, other viruses and autoimmune serologies was negative, other than ANA titer of 1:640. Tox screen and mass spectrometry were negative. Given worsening liver injury, liver biopsy was obtained, which had active hepatitis with giant cell transformation, patchy necrosis, and CLL in portal areas (Figure 1). The patient was recommended high-dose prednisone, but she deferred therapy. Labs were followed closely, with remarkable improvement within a few days. She was discharged on ursodiol. On follow-up 2 months later, a mild transaminitis was persistent, so prednisone therapy was started with subsequent resolution of her hepatitis. However, subsequent imaging revealed development of cirrhosis. DISCUSSION: Treatment of PIGCH is dependent on underlying etiology, with autoimmune pathology having the best prognosis described in the literature versus variable courses for drug induced PIGCH, once the offending agent is stopped. In our patient, the trigger for giant cell transformation was suspected to be drug induced liver injury, from treatment with azithromycin/ceftriaxone. Interestingly, CLL itself can spontaneously transform to PIGCH as well, with treatment of CLL improving prognosis. Our patient did not want immunosuppressive therapy initially. Although her acute liver injury spontaneously improved, she did develop cirrhosis as a long-term complication. PIGCH must be aggressively treated/monitored to prevent life-threatening fulminant hepatic failure, or subsequent cirrhosis.

3028 Glycogenic Hepatopathy Masquerading as Acute Relapsing Hepatitis: A Diagnostic Pitfall

INTRODUCTION: Glycogenic hepatopathy (GH) is a rare conditioned characterized by elevated liver enzymes, hepatomegaly with or without right upper quadrant pain, typically seen in poorly controlled diabetes type 1, rarely in type II. It is related to glycogen accumulation during periods of high blood glucose, and tends to resolve with improvement of glycemic control. The course of liver enzyme abnormalities is transient. We present a case of glycogenic hepatopathy masquerading as biliary stones. CASE DESCRIPTION/METHODS: A 54 year old female with no known liver, history of HTN, CVA and poorly controlled type 2 diabetes mellitus (T2DM), complicated by multiple episodes of DKA and hyperosmolar hyperglycemic state, presented to the hospital with abdominal pain, nausea, constipation and high liver enzyme abnormalities. This was preceded by an admission 2 months prior with hyperglycemia above 600, ketones, and similar liver enzyme abnormalities. Work up was initiated including liver US, CT scan, MRCP, viral and autoimmune serologies which were normal or negative (Graph 1). Liver biopsy in progress. DISCUSSION: The patient in this case report has risk factors for metabolic syndrome with HTN, BMI of 26, T2DM with poor control, with episodes of hyperglycemia, associated with peaks of liver enzymes that mimic hepatocellular or mixed injury, which resolved slowly with control of hyperglycemia, being completely normal between spikes. This pattern of presentation is typical for GH, a metabolic entity that was linked to poorly controlled diabetes, and is caused by transient accumulation of glycogen within hepatocytes that follows passive influx of glucose into hepatocytes utilizing hepatic glucose transporter-2. Long-term prognosis is unclear and may in recurrent cases progress to fibrosis and cirrhosis, similar to NAFLD. Clinical suspicion for GH is based on correlation between peaks of blood sugar and acute rise in LFTs as well as periods of normalization of LFTs corresponding to resolution of acute hyperglycemia. Recognition of this entity is highly significant, as not only direct the effort to correct the underlying metabolic abnormalities, it also avoids unnecessary and costly work up knowing its transient and self-limited course. Liver biopsy if confirmatory. Glycogenic hepatopathy is an underdiagnosed metabolic hepatopathy in the setting poorly controlled diabetes, completely reversible, and should be considered in patients with T1 or T2DM with risk factors for NAFLD who present with acute and relapsing hepatitis.

2368 A Rare Case of Segmental Arterial Mediolysis in a Patient With Alpha-1 Antitrypsin Deficiency and Alcoholic Cirrhosis

INTRODUCTION: Alpha-1 antitrypsin deficiency (AAT deficiency) is a systemic disease characterized by lack of the protease inhibitor, alpha-1 antitrypsin and typically manifests as severe emphysema and/or liver disease. There are several case reports describing vascular compromise in patients with AAT deficiency, however mostly in the context of systemic vasculitis and connective tissue disease. Segemental arterial medioloysis (SAM) is a rare non-vasculitis, non-atherosclerotic arteriopathy of middle and small arteries that can lead to aneurysmal dilation or arterial stenosis. We report the first case of a patient with cirrhosis secondary to AAT deficiency noted to have arteriopathy due to SAM. CASE DESCRIPTION/METHODS: A 30 year old patient with end stage renal disease (ESRD) on hemodialysis, alcoholic cirrhosis and underlying AAT deficiency presented to our tertiary care center for liver transplant evaluation with a presenting MELD score of 39. Evaluation for other causes of cirrhosis revealed AAT deficiency with a homozygous ZZ phenotype and undetectable serum levels. As part of his pre-transplantation workup at our institution, he underwent computed tomography angiography (CTA) of the abdomen and pelvis which revealed severe irregular narrowing of the celiac axis. Similar narrowing was noted of the renal arteries and splenic artery and focal aneurysmal dilation of the hepatic and gastroduodenal arteries was additionally seen (Image 1). Autoimmune serologies were negative. Patient proceeded to orthotropic liver transplantation during his hospitalization. Intraoperatively, hepatic artery appeared visually vasculitic but histopathologic report was consistent with diagnosis of SAM. Due to concern for potential graft compromise that could result from the recipient hepatic artery aneurysm, an aortic conduit was performed using the donor vessels with anastomosis to the recipient supraceliac aorta. DISCUSSION: To our knowledge, there is only one other published report describing SAM in a patient with co-existing AAT deficiency. SAM in this case resulted in hepatic aneurysm which complicated liver transplantation, necessitating alternative graft revascularization via an aortic conduit. Although doppler evaluation 3 days after transplantation showed hepatic artery anastomosis was still patent, the rate of complications related to aorto-hepatic bypass grafts is high, and close follow up remains prudent.

2212 Hemophagocytic Lymphohistiocytosis Disguised as Acute Liver Injury

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder with unregulated immune activation and inflammation. Primary HLH occurs in infants or young children with or without family history whereas secondary HLH manifests in older children or adults without a family history or gene mutation. Concurrent infection, malignancy or rheumatological disorder usually trigger an uncontrolled immune response in the older age group. Our aim is to raise is awareness among physicians to recognize the early signs and symptoms of this life-threatening condition. CASE DESCRIPTION/METHODS: A 33-year-old female with a history of multiple sclerosis and rheumatoid arthritis presents with elevated LFTs, cholestatic jaundice and intermittent high-grade fever. Imaging studies showed no significant abnormality in the hepatobiliary system. Viral and autoimmune serologies were negative. Lab works revealed low fibrinogen and elevated ferritin and IL-2 receptor levels. Bone marrow biopsy was unremarkable; however, liver biopsy showed features suggestive of HLH. Steroid and etoposide therapy was started but treatment was complicated by pancytopenia and hemodynamic instability despite multiple transfusions and filgrastim administration. With worsening clinical pictures, emapalumab (Interferon gamma blocker) was started. However, the patient developed multiorgan failure with overwhelming sepsis and died within days of emapalumab administration. DISCUSSION: HLH has a wide spectrum of clinical manifestation often masquerading as sepsis or SIRS. Some studies have found that cholestasis and high AST levels are associated with poor outcomes in adult HLH patients. The goal of therapy is to suppress hyper inflammation with agents such as corticosteroids, calcineurin inhibitors, and immunoglobulins. When a patient presents with prolonged fever and liver dysfunction of unknown etiology, HLH should be considered in the differential diagnosis as early recognition and treatment can prevent mortality, which can be high up to 75 % in the adult age group.

2338 Drug-Induced Liver Injury From Prolonged Kava Kava and Kratom Use

INTRODUCTION: Several herbal supplements carry the risk of drug-induced liver injury (DILI).Kava Kava is a herbal compound derived from the root of the Piper methysticum plant that is indigenous to the South and Western Pacific. Kratom is a herbal extract derived from the leaves of Mitragyna speciosa, a evergreen tree indigenous to Southeast Asia. Here we report a case of Kava and Kratom induced hepatocellular hepatitis in a male with complex regional pain syndrome (CRPS). CASE DESCRIPTION/METHODS: A 48-year-old male with history of CRPS and rheumatoid arthritis presented with a 7-day history of nausea, vomiting, dark urine, and jaundice. He denied alcohol, tobacco, or IV drug abuse. Denied use of medications. On exam, he was jaundiced. His labs on admission were- WBC 10.8, HGB 17.2, INR 1.4, creatinine 0.97, Total Bilirubin 21.8, Conjugated Bilirubin 16.7, ALP 293, ALT 1805, AST 1539. Viral hepatitis, HIV, HSV, EBV, and CMV were ruled out. Autoimmune serologies and ceruloplasmin were negative. Abdominal ultrasound showed a dilated common bile duct measuring 9.6mm. MRCP ruled out biliary ductal abnormality. Patient refused liver biopsy. Further questioning revealed prior use of opioids for pain, but in the last 9 months he had been substituting with a combination of Kava Kava and Kratom tea. DISCUSSION: Herbal supplementation use is increasing, and often, not discussed with medical providers. Kava Kava is comprised of kavalactones, which have similar effects to alcohol with regards to relaxation, sociability and euphoria. Kratom is used for its opioid-like ability to increase stamina and treat chronic pain. Its highly potent agonist activity on the mu, kappa and delta opioid-receptors have led to its popularity as a recreational drug. Formulations of Kava Kava and Kratom can be found for sale in herbal supplement stores and on the internet. Although a few case reports exist of these supplements leading to hepatocellular damage, the exact mechanism of injury is still not well understood and more research is necessary. Health care professionals should be aware of the hepatotoxic potential associated with Kratom and Kava Kava use and should be vigilant in identifying patients who would benefit from education regarding supplement use and discontinuation. Although these herbal supplements can cause hepatotoxicity, it’s important to exclude other possible causes of hepatic injury, including infection, vascular, autoimmune, and biliary etiologies.

2389 Nivolumab-Induced Hepatitis: A Rare Side Effect of Programmed Cell Death-1 (PD-1) Inhibitor

INTRODUCTION: Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that blocks the function of programmed cell death (PD-1) activity by binding to the PD-1 receptor. This prevents suppression of T-cell activity, which can lead to T-cells targeting cancer cells. Unfortunately, these medications induce various types of immune related adverse events including colitis, pneumonitis, endocrinopathies and hepatitis. We report rare case of of nivolumab-induced hepatitis. CASE DESCRIPTION/METHODS: An 86-year-old female with history of metastatic melanoma and was started on nivolumab 3 mg/kg every 3 weeks. Patient noted to have abnormal liver chemistries, nausea and yellowing of skin after 6 months of nivolumab. On presentation she was found to have a total bilirubin of 7.79 mg/dL, INR 1.3, AST 885 IU/L and ALT 999 IU/L. Physical examination was significant for mild scleral icterus only. An ultrasound of liver was notable prominent left lobe of liver but no focal hepatic masses and s/p cholecystectomy with no bile duct dilation. Infectious etiologies were unrevealing for viral hepatitis and acute EBV. Her autoimmune serologies were negative for anti-smooth muscle antibody and anti-mitochondrial antibody. Work up was negative for herbal supplements, illicit substance or other medications. The most likely culprit for her hepatitis was due to nivolumab. Patient was started on prednisone at 1 mg/kg daily for a total of 100 mg prednisone daily and her nivolumab dose was held. On discharge her total bilirubin was 2.45, INR 1.2, AST 62, ALT 249 and Alk Phos 252. Patient continued prednisone taper over 30-day period and by end of the month her liver chemistries had normalized and patient was asymptomatic. DISCUSSION: Nivolumab-induced hepatoxicity is rare and accounts for 3-6% of all immune-related adverse effects. The median time of onset was 3.3 months (range: 6 days to 9 months). In addition to systemic corticosteroid, alternative immunosuppressive therapies may be employed if symptoms continue after 3-5 days. Etiologies of liver dysfunction such as viral infection, obstruction and other forms of autoimmune hepatitis must be excluded. In such an event, oral mycophenolate mofetil 500 mg every 12 hours can be used for treatment. Our patient showed rapid improvement in liver chemistries and had minimal physical side effects. Healthcare provides managing patients with liver injury should be able to recognize and treat prior to development of fulminant hepatitis.

2337 Secondary Sclerosing Cholangitis and Nodular Regenerative Hyperplasia Caused by Hereditary Spherocytosis

INTRODUCTION: Hereditary spherocytosis is a hemolytic anemia that leads to premature cell destruction due to red cell membrane defect. It causes release of unconjugated bilirubin, and subsequent bilirubin gallstone formation occurs. Chronic recurrent choledocholithiasis can cause secondary sclerosing cholangitis (SSC). Hemolysis can lead to chronic vascular injury and portal vein thrombosis, resulting in Nodular Regenerative Hyperplasia (NRH). Here, we report a case of HS causing SSC with concurrent NRH. CASE DESCRIPTION/METHODS: A 37-year-old female with a history of hereditary spherocytosis with thrombocytosis presented to the office for abnormal liver function tests (LFTs). History of splenectomy and cholecystectomy in 2002. Patient was noted to have abnormal LFTs in 2009 (Figure 1). Her LFTs were routinely monitored until 2016 when she presented with epigastric pain, jaundice, and abnormal LFTs. Viral and autoimmune hepatitis serologies were negative. Iron studies were normal. Right upper quadrant (RUQ) ultrasound (US) showed mildly dilated intrahepatic ducts. Magnetic resonance cholangiopancreatography(MRCP) was performed which showed a questionable stricture in the proximal CBD and mild dilatation of the central intrahepatic duct. ERCP showed normal caliber CBD with multiple filling defects. A biliary sphincterotomy was performed and the stone was removed. ERCP performed in 2016 and 2018 revealed multiple stones in the biliary ductal system, which were removed and the CBD was dilated. Liver biopsy showed mild portal and lobular inflammation with mild portal fibrosis and changes suggestive of NRH. DISCUSSION: HS caused the patient's recurrent choledocholithiasis and contributed to SSC. Pathologically, SSC causes inflammation, obliterative fibrosis, stricture formation, and destruction of the biliary tree, which leads to biliary cirrhosis. Although often reversible, outcomes may not be as favorable if it is not recognized quickly, particularly in critical illness induced SSC. NRH is a liver disease characterized by many hyperplastic nodules without separation by fibrotic tissue. It is associated with any systemic disease that causes vascular injury, in this case our patient’s HS. Pathology in our case revealed only “mild” changes suggestive of NRH, so the patient hasn’t yet developed portal hypertension. There are no cases in literature that document HS as a factor contributing to either of these disease states. Early suspicion and liver biopsy are necessary for prompt diagnosis and improved outcomes.

PULMONARY TUMOR THROMBOTIC MICROANGIOPATHY: A RARE CAUSE OF PULMONARY HYPERTENSION

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: We present a case of a 64 year old male who was admitted to the hospital for rapidly progressive dyspnea. Imaging revealed bilateral mosaic attenuation, septal thickening and ground glass opacities. After an extensive work-up, the patient was diagnosed with pulmonary hypertension related to pulmonary tumor emboli mircoangiopathy(PTTM). CASE PRESENTATION: A 64-year-old male with a history of atrial fibrillation and OSA presented with dyspnea on exertion associated with hemoptysis and hematuria. The patient was in his usual state of health until the summer when he was diagnosed with atrial fibrillation as a part of his work physical. After of which he was referred to a cardiologist who attempted multiple unsuccessful cardioversions while on different anti-arrhythmic agents. During this time, he was also continued on rivaroxaban for anticoagulation. After his last cardioversion he was maintained in normal sinus rhythm but this unfortunately did little to help resolve his profound dyspnea on exertion. He then underwent a right heart catheterization as an outpatient and had a right atrial pressure of 3 mmHg, pulmonary artery pressure of 67/19 and a pulmonary capillary wedge pressure of 3 mmHg. As he was quickly worsening from a respiratory stand point, he was then referred to the emergency department for admission and pulmonary was consulted. Physical exam demonstrated clear lungs bilaterally with no palpable lymphadenopathy. Chest x-ray on admission showed clear lung fields with no infiltrate, effusions, or masses. CT chest revealed multiple ground glass opacities, mosaic attenuation and septal thickening. Differential diagnosis at the time included inflammatory, vasculitis, autoimmune, and malignant etiologies. Extensive lab work that included auto-immune serologies were all negative. Given radiologic findings and right heart catheterization report there was concern of an occlusive disease and the patient underwent a VATS wedge resection. Pathology showed metastatic poorly differentiated carcinoma involving pulmonary arteries and vein with immunohistochemical findings suggest urothelial carcinoma. DISCUSSION: Pulmonary hypertension in PTTM presents with rapidly progressive dyspnea and develops due to progressive vascular fibrointimal stenosis and occlusion. A unique abnormality that can be found on lab work in patients with PTTM is a ‘compensated DIC’ in which there is a slow consumption of clotting factors and platelets. This along with progressive RV dysfunction can clue a diagnostician to preform a RHC with a pulmonary artery wedge aspiration for cytology. This has a reported sensitivity of 80-88% and 82-94% specificity respectively. CONCLUSIONS: In patients where the severity of pulmonary hypertension is otherwise not explained by the severity of heart or lung disease, PH due to pulmonary artery obstruction needs to be considered in the differential diagnosis. Reference #1: Uruga, Hironori, et al. "Pulmonary tumor thrombotic microangiopathy: a clinical analysis of 30 autopsy cases.” Internal Medicine 52.12 (2013): 1317-1323. Reference #2: Roberts, Kari E., et al. "Pulmonary tumor embolism: a review of the literature.” The American journal of medicine 115.3 (2003): 228-232. Reference #3: Price, Laura C., Athol U. Wells, and Stephen J. Wort. "Pulmonary tumour thrombotic microangiopathy.” Current opinion in pulmonary medicine 22.5 (2016): 421-428. DISCLOSURES: no disclosure on file for Eliot Friedman; No relevant relationships by Kriti Pathak, source=Web Response No relevant relationships by Noor Salam, source=Web Response

2361 A Rare Presentation of Acute Hepatitis in the Setting of Wilson’s Disease

INTRODUCTION: Wilson’s disease is a genetic disorder that leads to impairment in the transportation of cellular copper. The worldwide incidence of Wilson’s disease is estimated at one per 30,000 live births. Autoimmune hepatitis (AIH) has a varying degree of prevalence, anywhere from 0.9-25 cases per 100,000 globally. We describe a rare case of a patient presenting with acute hepatitis in the setting of known Wilson’s disease with nonadherence to therapy who was diagnosed with concomitant autoimmune hepatitis. CASE DESCRIPTION/METHODS: A 19-year-old woman with a history of biopsy-proven Wilson’s disease diagnosed at age 17, non-adherent to trientine chelation therapy, presented to her primary care physician with nausea and abdominal pain. Physical exam was benign and workup revealed an elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 1500. She was referred for hospital admission. Acute viral hepatitis was ruled out and trientine was resumed as it was felt the presentation may be due to untreated Wilson’s Disease. Evaluation for drug-induced liver injury, human immunodeficiency virus, and thrombosis was negative. Despite therapy with trientine, transaminases continued to rise. Autoimmune serologies revealed a positive anti-smooth muscle antibody. A liver biopsy showed copper granules in hepatocytes consistent with Wilson’s disease, in addition to moderately active hepatitis with frequent plasma cells supporting the diagnosis of AIH. Prednisone was initiated for treatment of AIH and her hepatitis rapidly improved. One week follow up showed further improvement in her liver chemistries. She was transitioned to azathioprine for AIH. Trientine was continued for treatment of Wilson’s disease. DISCUSSION: Given the multiple causes of acute hepatitis and targeted therapies available, determining the etiology remains the cornerstone of management. This is an unusual case of biopsy-proven Wilson’s disease who presented with acute hepatitis. She was found to have serology and biopsy consistent with both Wilson’s disease and AIH. She responded rapidly to steroid therapy for AIH followed by treatment with an immunomodulator. This combination of a rare inherited disease coupled with an uncommon autoimmune phenomenon highlights the need for diagnostic precision in the patient with acute hepatitis, even when pre-existing liver disease is known. Ultimately liver biopsy findings directed specific therapy.

4. A paraneoplastic case of dermatomyositis

4. A paraneoplastic case of dermatomyositis

14. Digital ischemia and interstitial lung disease in antisynthetase syndrome with PL-12 antibody

IntroductionAntisynthetase syndrome (ASS) is a rare idiopathic inflammatory myopathy with nearly 89% showing interstitial lung disease (ILD). The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases that include Jo-1 (most commonly detected), PL-7, PL-12, OJ, EJ, KS, Wa, YRS and Zo. However, in a small subpopulation without evidence of myositis, the diagnosis may be critically delayed, hindering management of this rapidly progressive disease.We report an interesting case of anti-PL-12/anti-SSA 52kD ASS presenting as acute digital ischemia, an association rarely described previously. In cases with ILD, the severity of lung condition generally determines the prognosis.Case descriptionA 77-year-old Caucasian female presented with sudden onset of painful, blue discolouration in her bilateral fingertips two-weeks after mild lower respiratory tract infection and occasional pyrexia. She was a non-smoker, otherwise independent lady who had background history of ischemic heart disease, diverticulosis and hypertension. Her physical examination revealed dusky blue digits and dry ulceration. She had extensive investigations that showed raised CRP (61mg/L), eGFR 39ml/min/1.73m2 , weak positive rheumatoid factor and cold agglutinins, equivocal Lupus anticoagulant, negative ANCA, clear urinalysis, bilateral chronic inflammatory change on chest xray and thrombi of digital arteries on Doppler ultrasound of hands.She was initially treated for infection due to ongoing temperatures and had multiple scans with no definite source. An inflammatory aetiology was then thought likely due to lack of response to antibiotics and steroid therapy was commenced with settling of fevers and inflammatory markers. Autoimmune screens initially were negative but became more prominent over time with a positive Ro antibody and ultimately a positive Anti PL12 antibody, keeping with anti-synthetase syndrome.She subsequently developed florid interstitial lung disease, further ischemia and ultimately necrosis of her fingertips. Due to the onset of lung disease she was treated with IV steroids, Cyclophosphamide and Prostaglandins with some initial benefit. She received 3 cycles of cyclophosphamide and managed to come off supplemental oxygen. However, she had issues with recurrent chest infections due to immunosuppressive therapy which resulted in delays in her cyclophosphamide pulses and need for antibiotics. She later developed clostridium-difficile gastroenteritis and subsequent ileus of her bowel which was managed conservatively and found it difficult to overcome. As time went on, the progress that she had made with her hands started to deteriorate again. There were also further issues with intestinal obstruction, and sadly ultimately passed away with aspiration pneumonia.DiscussionASS is recognized as a rare autoimmune inflammatory myopathy of unknown etiology, 2–3 times more prevalent in women than in men. The clinical manifestations include myositis, polyarthritis, ILD, mechanic’s hands, and Raynaud phenomenon. The hallmark of ASS is the presence of serum autoantibodies directed against aminoacyl-tRNA synthetases that include Jo-1, PL-7, PL-12, OJ, EJ, KS, Wa, YRS and Zo. Anti-jo1 is the most commonly detected antibody. These autoantibodies may arise after viral infections, or patients may have a genetic predisposition.Our case was interesting as the autoimmune profile was positive for Anti-Ro/SSA and anti-PL-12. Anti-Ro/SSA and anti-La/SSB are traditionally associated with Sjögren’s disease and Sjögren’s-related ILD, however, anti-Ro/SSA has been independently associated with ASS and more severe and fibrotic ILD. It has been described that patients with anti-PL-12-ASS are most often clinically diagnosed with amyopathic dermatomyositis or ILD alone and there is higher prevalence and increased severity of ILD than PM/DM. Moreover, the prevalence of muscle symptoms (weakness and myalgia) is significantly lower in patients with anti-PL7/PL12 as compared to those with anti-Jo1 and less associated with malignancy as compared to DM. Interestingly, anti-PL-12 is also associated with higher rates of Raynaud phenomenon.Our case also reports that not all patients with antisynthetase antibodies or even those classified as ASS have all manifestations of this syndrome. Diagnostic criteria refers to presence of antisynthetase antibody plus two major criteria or one major criterion and two minor criteria (Solomon et all. 2011) or one or more of clinical features (Connors et all.2010). When the lungs are affected, the severity and extent of lung damage generally determines the prognosis because respiratory failure is the leading cause of death. Clinical presentation guides towards therapeutic management that mostly includes corticosteroids, immunosuppressive medications, and/or physical therapyKey learning pointsDigital ischemia could be a rare presentation of ASS. Clinical features of antisynthetase syndrome (ASS) include interstitial lung disease, ‘mechanic’ hands, myositis, polyarthritis and Raynaud’s phenomenon. Extensive myositis specific antibody testing is strongly recommended even if screening autoimmune serologies are unrevealing. Anti- PL-12 ASS has significantly lower prevalence of muscle symptoms (weakness and myalgia) and more association with Raynaud’s phenomenon as compared to those with anti-Jo1. It is imperative to recognize lesser-known manifestations of ASS in the absence of clinical myositis as delay in diagnosis and treatment worsens the prognosis.Conflicts of interestThe authors have declared no conflicts of interest.

13. Idiopathic inflammatory myopathy, everything it should not be: asymmetrical, normal CK, high fever

IntroductionMyositis can be infective, metabolic or immune-mediated. Idiopathic inflammatory myopathy, which is immune-mediated, tends to be subacute, with symmetrical symptoms, overlap clinical features and positive autoimmune serology. We present a case of acute onset lower limb seronegative inflammatory myopathy with a normal creatinine kinase (CK), a marked acute phase response that responded promptly to immunomodulatory therapy.Case descriptionA 68-year-old man presented with a 2-week history of lower limb pain with subjective weakness, on a background of well-controlled type 2 diabetes mellitus and hypertension. He was admitted with worsening symptoms of marked left thigh pain, night sweats, and fevers.On admission, he had swinging pyrexia (above >39 °C) while remaining haemodynamically stable. He had focal tenderness over the left anterolateral thigh, with a good range of movement, normal power and no signs of focal collection or cellulitis. There were no extra-muscular features to suggest systemic infection or overlap connective tissue disease.Bloods showed C-reactive protein (CRP) 225, normal CK 212 and negative blood cultures. X-rays knee, femur and pelvis were normal. Magnetic resonance imaging (MRI) on T2, fat-suppressed STIR sequences demonstrated increased signal/oedema both thighs throughout the anterior muscle compartment and along the fascial plane, notably most severe in the left vastus lateralis. He was treated empirically for infective myositis. Despite 14 days of broad-spectrum antibiotics, he remained febrile with persistently elevated CRP. There was no focal collection, lymphadenopathy or occult malignancy on CT abdomen and pelvis. Trans-oesophageal echocardiogram showed no evidence of infective endocarditis but revealed incidental moderate aortic stenosis.The patient described persistent now bilateral thigh pain with continued normal CK and high CRP. Full autoimmune screen (ANA, ANCA, ACE and complement studies) was negative. Despite negative nuclear and cytoplasmic HEp-2 immunofluorence, extended myositis immunoblot was negative. Muscle biopsy from the left vastus lateralis demonstrated inflammation within the perimysium and perivasculature. In view of biopsy findings and no response to anti-microbial therapy, prednisolone (0.5mg/kg) with significant clinical response (resolution of fever and pain) with concurrent normalisation in CRP. The patient remains in remission following steroid reduction with no additional immunomodulatory therapy required.DiscussionWe report a case of idiopathic inflammatory myopathy presenting with predominantly asymmetrical symptoms, normal CK, marked inflammatory response and negative myositis autoantibodies. Diagnosis was confirmed on MRI and muscle biopsy. The normal CK can be explained by the histology demonstrating inflammation in perivascular regions and around muscle fibres, rather than inflammation or necrosis in the muscle fascicles and fibres themselves. Idiopathic inflammatory myopathy including sporadic inclusion-body myositis, dermatomyositis, overlap CTD myositis and polymyositis/necrotising myopathy subsets are distinguishable based on clinical features, autoantibodies, MRI and biopsy features. The table below summarises the atypical aspects of this case. Differential diagnoses for this case include atypical infection, sarcoid myopathy and amyloid myonecrosis secondary to diabetes. Table: Features of typical idiopathic inflammatory myopathy compared with this atypical case.Idiopathic inflammatory myopathiesOur patient- typical featuresOur patient- atypical featuresSymptomsPain, fever, weakness.Pain and fever.Normal power.Clinical distributionSymmetrical, proximal muscle groups.Predominantly asymmetrical (worse on left), only in thighs.AntibodiesMyositis associated autoantibodiesSeronegativeMuscle enzymesElevated CKNormal CK.Inflammatory markersNormal to slightly elevated CRPMarkedly raised CRP and WCC.MR imaging resultsFocal muscle oedema in affected musclesDiffuse and speckled muscle oedemaKey learning pointsEarly idiopathic inflammatory myopathy can have inflammation around the muscle fascicles in the perimysium. Normal CK does not rule out a diagnosis of idiopathic inflammatory myopathy.Idiopathic inflammatory myopathies can present atypically with fevers >39 °C, significantly raised inflammatory markers, and asymmetrical symptoms and MRI findings.In the absence of overlap features, normal CK and negative serology, MRI and biopsy can delineate the type of myositis and direct management.Conflicts of interestThe authors have declared no conflicts of interest.