Epstein-Barr Virus IgM Research Articles

Chronic active Epstein–Barr Virus infection in a teenage girl with suspect autoimmune Hepatitis

BackgroundThe pathogenesis of chronic active Epstein–Barr virus (EBV) disease (CAEBV) is complex, involving infection, inflammation, and in some cases malignancy. EBV reactivates in some patients, who develop a chronic disease with infectious mononucleosis-like symptoms. On occasion, it might be confused with autoimmune hepatitis (AIH), based on the similar symptoms and elevated liver enzymes. We aimed to describe a similar case to remind reader of this disease.Case Presentation: A 14-year-old girl was diagnosed with AIH based on biopsy and biomarker findings 1 year prior to admission and initially presented with elevated liver enzymes, portal hypertension, and parenchymal liver disease. Despite steroid administration, her condition fluctuated, and she was admitted to the hospital several times. She underwent a renal biopsy because of massive ascites, hypoalbuminemia, and increased renal echogenicity. An evaluation for impaired liver function showed positivity for EBV IgM, IgG, and early antigen (EBEA) antibodies. A PCR-based assay showed 5265 copies/mL of EBV DNA in peripheral blood. Epstein–Barr encoding region (EBER) in situ hybridization revealed abundant positive cells. Immunohistochemistry for CD56 also showed abundant positive cells, and CAEBV was diagnosed on this basis. Chemotherapy, hematopoietic stem cell transplantation (HSCT), and liver transplantation were proposed but her family refused.ConclusionsCAEBV should be considered when diagnosing AIH or in cases of treatment-refractory AIH.

Can the Epstein-Barr Virus Play a Role in the Development of Prostate Cancer?

Prostate cancer (PCa) is the fourth most frequently diagnosed cancer worldwide, accounting for 7.3% of all cancers. PCa mortality is the fifth most common cause of cancer death. Despite well-known factors influencing the development of PCa, such as age, race/ethnicity and family history, many researchers have raised the possibility of persistent infections with oncogenic viruses. Therefore, we aimed to assess the frequency of Epstein-Barr virus (EBV) DNA in tissue collected from PCa patients. Next, the frequency and the level of Epstein-Barr virus capsid antigen (EBVCA) and Epstein-Barr nuclear antigen 1 (EBNA1) antibodies in both IgA and IgG classes were measured. The antibody titer was also analyzed depending on the risk group, Gleason score (GS) and tumor, node, metastasis (TNM) classification. Serum samples were analyzed using the Microblot-Array EBV IgM, IgA and IgG test kits. The study group consisted of 115 patients diagnosed and histopathologically confirmed with PCa. In 49% of patients included in the study, EBV DNA was detected in the tumor tissue. The studies showed both higher seroprevalence and higher antibody titers in patients with EBV-positive PCa compared to patients with EBV-negative PCa. We also observed a dependence of antibody titer on pathological features, such as GS, risk group and T stage.

ВЕСТИБУЛЯРНЫЙ НЕЙРОНИТ: КЛИНИЧЕСКИЙ ПРИМЕР ТЕЧЕНИЯ ЗАБОЛЕВАНИЯ С ИСПОЛЬЗОВАНИЕМ БИОЛОГИЧЕСКИ ОБРАТНОЙ СВЯЗИ (БОС)

The examination was conducted with the consent of patient P., born in 1961, who was undergoing treatment in the neurological department of the Federal State Budgetary Health Care Institution "Clinical Hospital No. 8 of the Federal Medical and Biological Agency" (FGBUZ KB No. 8 FMBA of Russia). The patient was examined for viral and bacterial infections: Herpes simplex virus 1,2 IgM, herpes simplex virus 1,2 IgG, cytomegalovirus IgM, Epstein-Barr virus IgM to AG capsid, SARS-CoV-2 coronavirus, IgM antibodies, meningococcus, haemophilus bacillus, streptococcus (Neisseria meningitidis, heamophilus influenzae, streptococcus pneumoniae, PCR), influenza type B virus. It should be noted that all analyses were performed with quantitative evaluation in order to observe the course of the disease in dynamics. This list of analyses was determined not only to monitor the dynamics of the disease, but also to perform differential diagnosis (e.g. with labyrinthitis, as this disease has a similar clinical picture). In the course of the study, as a result of a rational evaluation, it was identified and decided to focus the study on herpes simplex virus 1, 2 IgG analyses in the dynamics - accordingly, the analyses were taken on day 5 of the disease, on day 14, and then on day 21. The patient underwent instrumental diagnostics: audiometry, SCT study, MRI study to exclude other similar pathological phenomena. In addition to laboratory tests, the patient underwent diagnostic and rehabilitation tests on a stabilisation platform with biofeedback based on StabMed 2-"Stabilan-01-2" software, both at the beginning of treatment and at the end (the main diagnostic test performed was a stabilography test. Various variants of the Romberg test are a standard tool in the arsenal of a modern doctor, for example, clinical recommendations on differential diagnosis of peripheral vertigo include it in the list of mandatory procedures during physical examination of a patient with complaints of dysfunction of the vestibular apparatus ).

Effect of monovalent COVID-19 vaccines on viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome

Epstein–Barr virus (EBV) reactivation may be involved in long-COVID symptoms, but reactivation of other viruses as a factor has received less attention. Here we evaluated the reactivation of parvovirus-B19 and several members of the Herpesviridae family (DNA viruses) in patients with long-COVID syndrome. We hypothesized that monovalent COVID-19 vaccines inhibit viral interference between SARS-CoV-2 and several DNA viruses in patients with long-COVID syndrome, thereby reducing clinical symptoms. Clinical and laboratory data for 252 consecutive patients with PCR-verified past SARS-CoV-2 infection and long-COVID syndrome (155 vaccinated and 97 non-vaccinated) were recorded during April 2021–May 2022 (median 243 days post-COVID-19 infection). DNA virus–related IgG and IgM titers were compared between vaccinated and non-vaccinated long-COVID patients and with age- and sex-matched non-infected, unvaccinated (pan-negative for spike-antibody) controls. Vaccination with monovalent COVID-19 vaccines was associated with significantly less frequent fatigue and multiorgan symptoms (p < 0.001), significantly less cumulative DNA virus–related IgM positivity, significantly lower levels of plasma IgG subfractions 2 and 4, and significantly lower quantitative cytomegalovirus IgG and IgM and EBV IgM titers. These results indicate that anti-SARS-CoV-2 vaccination may interrupt viral cross-talk in patients with long-COVID syndrome (ClinicalTrials.gov Identifier: NCT05398952).

Study about the immunological investigations done before Kidney transplant in Basrah during (2012-2017)

Kidney transplant considered as alternative treatment in end-stage renal disease. Human leukocyte antigens an important role in graft rejection, donor specific HLA antibodies that measured by panel reactive antibody, lead to increased sensitization. Cytomegalovirus, Epstein-Barr virus, Hepatitis-B, and -C viruses have an association with poor outcome of the transplant. Aim of the study the immunological investigations done before the transplant. The study have carried out in College of Medicine by analyzing the data records for 36 patients undergo kidney transplant in Al-Sadder Teaching Hospital, 5 patients excluded for incomplete data. Data recorded during (2012-2017). HLA matching between recipients and donors including HLA-A, -B, -DR and -DRB1. Presence of PRAs, Hepatitis B virus surface antigen, Hepatitis C virus antibody, Cytomegalovirus IgM and IgG, Epstein-Barr virus IgM and IgG screened in recipients. Out of 31 recipients, 83.9% of were males and 16.1% females. 77.4% of donors and recipients were relatives and 22.6% were not relatives. 22.6% of donors and 25.8% of recipients tested for HLA and only 57.14% showed partially matching within some HLA classes. 9.7% of recipients have PRA. No recipient showed positive results for the presence of HBV sAg and HCV Ab. 6.5% of recipients have CMV IgM, 67.7% have CMV IgG, 9.7% showed positive results for the presence of EBV IgM and 6.5% have EBV IgG. In a conclusion, recipients and donors showed partially matched HLA classes, not all recipients and donors tested for HLA matching. Some recipients have PRA, high percentage of recipients has CMV IgG, and some of them have CMV IgM antibodies. All these factors might effects on the fate of transplant. HLA-DQ have to be tested and screening for the presence of PRA, viral Ag or Abs specific to these viruses in both recipients and donors is recommended.

A case of Epstein-Barr virus presenting as spondyloarthritis

Viral arthritis can be caused by various viruses such as parvovirus, alphavirus, rubella, hepatitis B, C and flavivirus. High titre of antibodies to Epstein-Barr virus (EBV) is present in rheumatoid arthritis (RA) patients. EBV, a member of the herpes virus family, is one among the most common human viruses. Vitamin D deficiency can worsen the prognosis in such patients. Abnormalities in innate and adaptive immune reactions in response to EBV infection were one of the complications observed in RA patients. It was a self-limiting infection with a 90% lifetime prevalence. On the other hand, spondyloarthritis was rarely associated with viral infections. A 35 year old male patient who had a history of TB, admitted through OP, with complaints of intermittent fever, joint pain, pain radiating from back to lower limbs. On investigation, the patient was found to be vitamin D deficient. Differential diagnosis such as TB with reactive arthritis, lymphoma and CMV infection were ruled out. MRI of the spine and pelvis confirmed spondylarthritis. The serology for EBV showed that the EBV IgM levels had increased by two-fold. The on-going inflammatory status was well-managed with NSAIDS, as there was low evidence for antiviral therapy. EBV infection presenting as spondyloarthritis is a very rare presentation and here we are discussing a case of spondylarthritis in a patient with infectious mononucleosis. The patients with fever, polyarthritis, lymphadenopathy and spondylarthritis are to be investigated for EBV infection along with the other cause of polyarthritis.

Epidemiological risk factors associated with primary infection by Epstein–Barr virus in HIV-1-positive subjects in the Brazilian Amazon region

To identify the prevalence and risk factors for primary Epstein–Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51–15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01–2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12–2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79–1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22–3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1–10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.

Prevalence of viral co-infection among COVID-19 cases in association disease severity and oral hygiene

Background: In December 2019, an episode of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2) was reported in Wuhan, China and has spread around the world, increasing the number of contagions. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common herpesviruses that can cause persistent latent infections and affect the developing immune system.The study was conducted to explore the prevalence and reactivation of CMV and EBV antibodies in COVID-19 patients group in comparison to healthy group and to investigate the association between the presence of these viruses with each of severity of disease and oral hygiene. Materials and Methods: Eighty Five subjects were participated in this case control study (50 patients with COVID-19 and 35 healthy controls), their age range from 18 to 77 years. Oral health status was established by oral hygiene index. Serum obtained from patients and controls was analyzed using ELISA to assess levels of anti- CMV and anti- EBV antibodies. Results: The study revealed that the mean of anti-EBV IgG in patients was significantly elevated (p&lt;0.01) than that in controls. Otherwise, there was no significant difference (p&gt;0.05) in levels of anti- EBV IgM, anti- CMV IgG and IgM between two groups (P&gt;0.05). In addition there were no significant differences between patients and controls (p&gt;0.05) in the number and percentage of anti-EBV and anti-CMV antibodies. Interestingly, there was a significant increase in the level of anti-CMV IgM in severe cases as compared to mild cases, (P&lt;0.01). Furthermore, these results revealed that there were no significant differences (P&gt;0.05) in levels of anti-viral antibodies in patients with good oral hygiene compared to patients with poor oral hygiene. Conclusions: Higher frequency of anti-EBV IgG among patients indicates that latent infection is more common in COVID-19 patients. While an increased percentage of anti-CMV IgM indicated reactivation of latent infection and is related to disease severity suggesting that COVID-19 can cause cellular immune impairment.

Painful Plantar Rash with Systemic Symptoms

Painful Plantar Rash with Systemic Symptoms

S2462 A Patient Presenting With Acute Hepatitis and Retroperitoneal Lymphadenopathy Due to Cytomegalovirus and Epstein-Barr Virus Co-Infection: A Rare Complication in an Immunocompetent Patient

INTRODUCTION: Acute hepatitis refers to an acute inflammation of a liver and hepatic cell necrosis. Viral infection accounts for 95% of cases. Acute viral hepatitis due to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infection in an immunocompetent individual is very rare. We report a patient who presented with fatigue, fever, and retroperitoneal lymphadenopathy due to EBV and CMV infection. CASE DESCRIPTION/METHODS: A 26-year-old man presented with intermittent high-grade fever, nausea, fatigue and generalized body weakness of 1-week duration. The patient noticed a pinkish rash on his abdomen and legs while he was febrile. Otherwise patient denied vomiting, hematemesis, melena, jaundice, or contact with a patient with similar illness. He was not immunocompromised and had no personal history of hematological disorders or autoimmune disease. On examination, the patient was sick looking; blood pressure was 120/68 mmHg, heart rate 110 beats/min, temperature 102 F. He had pink conjunctiva and non-icteric sclera. No palpable lymphadenopathy was felt in accessible areas. The abdomen was nontender, no organomegaly, and no sign of ascites. Laboratory tests revealed a white blood cell count 7.6K, hemoglobin 13.8gm/dl, platelet 163K. Peripheral blood smear revealed lymphocytosis (59%). Alanine transferase 279units/L, aspartate transaminases 217units/L, alkaline phosphatase 121units/L, and total bilirubin of 0.4 mg/dl. Both CMV IgM and IgG were positive, both EBV IgM and IgG were positive. Hepatitis viral panel A, B, C, human immunodeficiency virus, ANA and rheumatoid factor were all negative. Computed tomography of chest/abdomen/pelvis revealed multiple enlarged axillary and retroperitoneal lymph nodes, normal liver and spleen size. DISCUSSION: CMV and EBV are a family of herpes virus commonly encountered during childhood. CMV transmission is either congenital or contact with body secretions or blood transfusion. EBV is transmitted by close contact during child hood or by kissing in adults. Hepatitis as a manifestation of CMV/EBV is rare in an immune-competent patient, but both can present with infectious mononucleosis. Although acute hepatitis can happen in both cases, it is more likely due to CMV. This patient did not have typical symptoms of infectious mononucleosis on presentation, and lymphoma and other causes were considered. A high degree of suspicion helped us to do serology that confirmed the diagnosis. Treatment is supportive in an immune-competent patient.

A pilot study on pediatric mononucleosis presenting with abscess

To describe this new clinical entity, diagnosis, and potential management of pediatric intratonsillar/peritonsillar abscesses in children affected by infectious mononucleosis. After institutional review board approval, a retrospective chart review of patients who underwent testing for infectious mononucleosis and also had a computed tomography scan of the head and neck was completed. Those who did not have imaging showing the palatine tonsils and those with insufficient testing to diagnose infectious mononucleosis were excluded. One hundred patients were included in the study; 15 had a peritonsillar abscess and 29 had an intratonsillar abscess. Four of the patients with a peritonsillar abscess (26.7%) had a positive Monospot or Epstein-Barr virus IgM result, and two of 15 (13.3%) had positive rapid strep or culture results. Of the 29 patients with an intratonsillar abscess, eight (27.6%) had a positive Monospot or Epstein-Barr virus IgM result while two (6.9%) had a positive rapid strep or culture result. Of those with bilateral intratonsillar abscess, five of 12 (41.7%) patients showed laboratory markers for infectious mononucleosis compared with three of 17 (17.6%) with unilateral intratonsillar abscess. This difference was not statistically significant (Fischer's, p=0.218). In our cohort of patients undergoing computed tomography scan and acute infectious mononucleosis testing, patients with intratonsillar and peritonsillar abscess tested positive for mononucleosis markers more commonly than for streptococcus markers. Recognizing uncomplicated intratonsillar and peritonsillar abscess in the setting of infectious mononucleosis in these pediatric patients may help tailor management in this population.

An Absence of Epstein-Barr Virus Reactivation and Associations with Disease Activity in People with Multiple Sclerosis Undergoing Therapeutic Hookworm Vaccination.

Background: Epstein–Barr virus (EBV) infection is strongly associated with multiple sclerosis (MS). Helminth infection can downregulate antiviral immune responses, potentially protecting against MS, but with a theoretical risk for reactivating latent EBV infection. Objective: To investigate parameters of EBV infection and their relationship with disease activity in people with MS (PwMS) therapeutically vaccinated with Necator americanus (hookworm). Methods: Sequential serum samples from 51 PwMS; 26 therapeutically infected (25 larvae) with N. americanus and 25 controls were tested for EBV virus capsid antigen (VCA) IgG and IgM, EBV nuclear antigen-1 (EBNA-1) IgG, and EBV early antigen (EA) IgG. Disease activity was assessed by periodic MRI. Significance was set at p < 0.05. Results: All PwMS were EBV VCA IgG and EBNA-1 IgG positive, and 35.2% were EBV EA IgG positive. EBV antibody levels were generally stable, and EBV reactivation in PwMS was not demonstrated by significant increases in IgG titre over 12 months. Disease activity was most frequent in PwMS possessing high levels of EBV VCA IgG (>600 units/mL) or EBNA-1 IgG (>150 units/mL); however, there was no association with hookworm treatment. Interpretation: Therapeutic hookworm vaccination was not associated with EBV reactivation. Multiple sclerosis disease activity was associated with high levels of EBV VCA IgG or EBNA-1 IgG.

Acute Epstein-Barr virus hepatitis presenting clinically as ascending cholangitis in an immunocompetent patient

Symptomatic acute Epstein-Barr virus (EBV) hepatitis, without associated infectious mononucleosis syndrome, is exceptionally rare. A 30-year-old female presented to hospital with jaundice, fevers, and right upper quadrant abdominal pain. Her blood tests demonstrated marked hyperbilirubinemia and mild global liver function test abnormalities consistent with obstructive jaundice. Preliminary imaging with ultrasound showed gallbladder wall thickening and cholelithiasis, suggestive of potential cholecystitis. Authors were concerned for potential ascending cholangitis in the setting of her hyperbilirubinemia. The diagnosis was refuted after magnetic resonance cholangiopancreatography demonstrated no choledocholithiasis. A hepatic panel was performed which revealed positive EBV IgM serology. This case highlights the importance of considering EBV hepatitis as a potential differential diagnosis in patients with right upper quadrant pain, fevers and jaundice in the absence of an obstructing cause.

Evaluation of the Serological Point-of-Care Testing of Infectious Mononucleosis by Data of External Quality Control Samples.

Timely and reliable laboratory diagnostics is a necessity for patient safety and good patient management. Success in external quality assessment (EQA) reflects on the everyday work in a clinical laboratory. This study evaluated the reliability of serological point-of-care (POC) testing for the Epstein-Barr virus (EBV) that causes infectious mononucleosis (IM). Data from the results of 95 external quality control (EQC) samples, altogether 18 885 results during an eight-year period (2010-2017) were collected from 273 Finnish testing sites. Diagnosing acute infectious mononucleosis (EBV IM) is based on clinical, haematological and serological findings. Heterophile antibody tests are used for this purpose because they can be carried out at POC and are cheap and robust to perform. In this study, the data showed that the testing sites used 3 test methods and 17 different test kits; of the kits, 4 were used during the whole study period. The most commonly used test methods were immunochromatographic assays (12 test kits, 17 959 EQC results). Latex agglutination (4 test kits, 504 results) and immunofiltration test methods (one kit, 422 results) were also used. The overall success rate was 99.3% (for positive samples 99.6%, for negative samples 99.1%). The success rates of the different test methods varied from 94.3% for the immunofiltration method to 99.6% for the latex agglutination method. The lowest success rates were found for negative samples: 82.0% (QuickVue, Quidel [immunochromatographic method]), 91.3% (RDT EBV IgM Assay, Bio-Rad [immunofiltration method]). The results of the negative samples that represented old EBV immunity were the most difficult to interpret with a success rate of 98.9% compared to success rates of clearly positive (99.6%) and negative (99.5%) samples (P < .001). Especially the immunofiltration method (RDT EBV IgM Assay) produced 13.7% false positive results for samples of old immunity. The data showed that 42 of the studied 95 EBV IM EQA rounds were reported as expected (true positive or true negative) by all testing sites.

Immunological and epidemiological evaluation of EBV infections among HIV-1 infected individuals in Abakaliki, Nigeria supports the potential use of neutrophils as a marker of EBV in HIV disease progression and as useful markers of immune activation

ABSTRACTHuman herpesvirus 4 which is commonly known as Epstein-Barr virus (EBV) is one of the opportunistic pathogens that affect human immunodeficiency virus (HIV) infected individuals and it is the leading cause of death and cancer in humans. The study was designed to evaluate the prevalence of EBV among HIV-1 infected individuals in Abakaliki metropolis, Ebonyi State, Nigeria. A total of 91 HIV-1 infected individuals were collected from Mile 4 Hospital, Abakaliki, Ebonyi State, Nigeria. ELISA was used to determine the Epstein-Barr Nuclear Antigen (EBNA) IgG and IgM antibodies. Full blood count (FBC), white cell count (WBC) and differential counts were also determined using standard hematological methods. Of the 91 serum samples obtained from HIV-1 infected individuals, 87(95.6%) and 20(22.0%) samples were found to be positive for EBVNA IgG and IgM antibody respectively. All the age groups had significant IgG prevalence, but age groups ≤ 20 years, and ≥ 41 had the highest prevalence while age group 21–30 years was found to have a less rate of prevalence. Also, the highest seropositivity for IgM antibodies was observed in the age group 31–40 years (32.4%) while the age groups ≤20 years (0.0%) is the lowest. However, these differences were not statistically associated with PVL and EBVNA IgG (p = .4311) and IgM antibodies (p = .4861).Higher seropositivity of EBVNA IgG occurred among those with PVL 41–10,000 copies/mL (100.0%) and PVL 10,001 copies/mL and above (100.0%) compared to those with PVL less than or equal to 40 copies/mL (95.0%). While regarding EBVNA IgM antibodies, higher seropositivity of EBVNA IgM occurred among those with PVL less than or equal to 40 copies/mL (25.0%) compared to those with PVL 41–10,000 copies/mL (20.0%) and PVL 10,001 copies/mL and above (8.3%). There was a significant difference in Neutrophils p < .026 between the mean of females and males (40.9 ± 11.7 and 36 ± 31.1) infected with EBV IgM in HIV individuals. There was also a significant positive correlation between CD4 counts and the WBC, Lymphocytes, Eosinophils and the neutrophil among the HIV-1 individuals used for this study. The correlations observed between both CD4+ count and neutrophil support the potential use of neutrophils as a marker of EBV in HIV disease progression and as useful markers of immune activation.

2464 A Case of Acute Icteric Hepatitis Caused by Epstein Barr Virus in an Immunocompetent Adult

INTRODUCTION: Epstein Barr Virus (EBV) is a viral infection that can often remain asymptomatic but is also a major cause of infectious mononucleosis. Patients often present with sore throat, fever, lymphadenopathy and can develop splenomegaly. EBV-associated hepatitis is uncommon and cases with clinical jaundice are rare. CASE DESCRIPTION/METHODS: A 23-year old male without significant past medical history presented with one week of flu-like symptoms and acute onset of a generalized pruritic rash, right upper quadrant (RUQ) abdominal pain and dizziness. He denied any recent alcohol consumption, IV drug use or new medication initiation. On arrival to the emergency department the patient was afebrile with a blood pressure 130/84. Physical exam revealed scleral icterus and cutaneous jaundice, a diffuse macular rash was across his face, chest and arms and he had tender hepatomegaly. He was alert and oriented without confusion. Laboratory examination revealed a leukocytosis of 11.8, a total bilirubin of 15.8, direct bilirubin of 13.3, an INR of 1.2, ammonia of 26, an alkaline phosphatase of 499, and an ALT of 615 with AST of 405 signifying acute hepatitis. A urine drug screen was negative. A RUQ ultrasound with doppler showed no evidence of Budd-Chiari or portal vein thrombus; fatty infiltration of the liver was seen with no evidence of cholelithiasis or common bile duct obstruction. Hepatitis A, B and C viral screen was negative, acetaminophen level was within normal limits, HIV antibody test was negative, herpes virus IgM negative, CMV IgM negative, anti-smooth muscle antibody negative for autoimmune hepatitis. Ceruloplasmin and alpha-1 antitrypsin levels were not suggestive of Wilson's disease or alpha-1 antitrypsin deficiency. A peripheral smear showed reactive lymphocytosis. There was significant elevation in EBV IgM and heterophile antibody suggesting systemic Epstein Barr viral infection as the cause of acute hepatitis. Over the next 3 days, his liver enzymes began trending down slowly with symptomatic management and he was determined stable for discharge with plans for 2 and 4 week follow ups to monitor for resolving acute EBV hepatitis. DISCUSSION: It is important to remember that, although rare, EBV can cause hepatitis with diffuse jaundice and significant hyperbilirubinemia along with AST and ALT levels over 10 times the upper limit of normal. Such presentation could easily be misconstrued as an alternative diagnosis and patient safety compromised with unnecessary treatment.

2372 Atypical Infectious Mononucleosis From EBV in a Splenectomized Sickle Cell Disease Patient

INTRODUCTION: Infectious mononucleosis (IM) is a clinical entity usually presenting with fever, pharyngitis and lymphadenopathy. However, atypical features of IM in Sickle cell disease (SCD) patients post splenectomy have been rarely reported. Here, we present a case of an atypical IM from Epstein Barr Virus (EBV) in a SCD patient post splenectomy with concurrent sickle cell hepatopathy (SCH). CASE DESCRIPTION/METHODS: This is a 22-year-old young man with history of SCD post splenectomy, who presented with severe dull pain in his right knee and persistent fevers up to 38.3oC along with watery diarrhea for 2-3 days. The patient denied any sore throat, sick contacts or recent blood transfusions. Besides a history of transient hemochromatosis from blood transfusions, the patient denied any history of liver disease or immunosuppression. Clinical examination was significant for non-tender hepatomegaly and a small palpable lymph node in the left posterior cervical chain. Initial workup was significant for lymphocytosis, mild transaminitis with raised AST, ALT, ALP, total bilirubin and direct bilirubin. Blood and urine cultures, parasitic screen, hepatitis and autoimmune hepatic panel were all unremarkable. Imaging studies were only significant for hepatomegaly on Abdominal Ultrasound. Despite initial management with broad spectrum antibiotics, the patient continued to have high fevers and rising liver transaminitis. Subsequent investigations revealed a positive EBV IgM and a viral load of 6119 along with 19% atypical lymphocytes. The patient was diagnosed with atypical EBV infection with mild SCH and managed supportively with IV fluids, hydroxyurea and analgesics. DISCUSSION: IM often presents as a clinical triad of fever, pharyngitis and lymphadenopathy with EBV being the most common pathogen implicated. EBV has often been associated with a mild transaminitis in healthy adults. A similar pattern is also seen in SCD patients with SCH resulting in tender hepatomegaly secondary to vaso-occlusive hepatic ischemia. Hence, it can be difficult to distinguish an atypical presentation of EBV-IM from SCH. In our patient, although his liver transaminitis partially resolved post exchange transfusion, he continued to have rising fever and atypical lymphocytosis along with high EBV viral load indicating an active atypical EBV-IM with a concurrent mild SCH. Therefore, any mild transaminitis with cholestasis in SCD patients post splenectomy, should prompt an evaluation for atypical EBV-IM.

2366 Acute Liver Failure Caused by Hemophagocytic Lymphohistiocytosis Secondary to Aggressive Natural Killer Cell Leukemia and Epstein-Barr Virus Reactivation

INTRODUCTION: Acute liver injury is a common presentation of many systemic illnesses, including hematologic malignancies. The present case was an unusual presentation of acute liver failure (ALF) caused by hemophagocytic lymphohistiocytosis (HLH) secondary to aggressive natural killer cell leukemia(ANKL) associated with Epstein-Barr virus(EBV) infection reactivation. CASE DESCRIPTION/METHODS: A 24-year-old female presented with fever and altered mental status. Her physical examination revealed massive hepatosplenomegaly. Complete blood count showed pancytopenia with WBC 460/µL, microcytic anemia Hgb 7.8g/dL with MCV 79, thrombocytes 45,000/µL, AST 170IU/L, ALT 162IU/L, INR 1.5, albumin 1.3g/dl and total bilirubin 11.08mg/dL, triglycerides 1164mg/dL, ferritin 1792ng/ml. CT abdomen showed hepatosplenomegaly with hepatic steatosis. Her liver biopsy showed hepatic necrosis with moderate steatohepatitis and perisinusoidal fibrosis with normal liver copper level. She was initially treated with steroids and N-acetylcysteine. Flow cytometry and bone marrow biopsy revealed CD56+ and CD3+ positive cells with high serum soluble IL-2 receptor consistent with ANKL and HLH. EBV markers were found positive for EBV IgG antibody and EBV nuclear antigen with high EBV PCR and negative for EBV IgM antibody, which is consistent with EBV reactivation. A modified SMILE chemotherapy regimen with rituximab was initiated. Unfortunately, her clinical status continued to decline progressively with worsening acute encephalopathy, acute hypoxic respiratory failure and Pseudomonas septic shock which required vasopressors and IV antibiotics. The patient died on day-30 of hospitalization due to her hematologic malignancy, septic shock, and ALF. DISCUSSION: HLH is a consequence of abnormal immune activation which could be secondary to infections, malignancies, or autoimmune diseases; leading to life-threatening multi-organ inflammatory response, especially in the liver. Natural killer (NK) cells are types of lymphocytes that play an important role as part of innate immune system in fighting tumors and viral cells; NK cells are abundant in the liver. It was shown that NK cells might be involved in the intense immune response causing severe liver damage. ANKL is a rare malignant lymphoproliferative disorder of mature NK cells closely associated with EBV. EBV reactivation can occur in this disease setting. Careful evaluation of patients with ALF and abnormal hematologic profile is essential for early detection and therapy of the primary culprit.

2219 Chronic Active Epstein-Barr Virus Presenting Primarily With Abnormal Liver Enzymes

INTRODUCTION: Epstein-Barr virus (EBV) usually causes asymptomatic infections in adults. In rare cases, infected individuals develop Chronic Active EBV (CAEBV), a systemic disorder characterized by elevated EBV DNA in blood and lymphocytes in tissues. We present a rare case of CAEBV in a 24-year-old woman with serology suggestive of autoimmune hepatitis (AIH). CASE DESCRIPTION/METHODS: A 24-year-old Guatemalan woman presented with RUQ abdominal pain, nausea, vomiting and subjective chills for two weeks. Labs were significant for AST 1,167 U/L, ALT 1,049 U/L, total bilirubin 2.8 mg/dL, INR 1.2, ALP 1,118 U/L, GGT 123 U/L, EBV PCR &gt; 1,000,000 copies, EBV IgM positive, positive ANA, serum IgG 3,690 mg/dL (normal 700 – 1,600), weakly positive smooth muscle antibody (SMA) titers 1:40 (negative &lt; 1:20), and F-actin antibodies 42 units (positive ≥ 31 units). Mild scleral icterus and RUQ abdominal tenderness noted on physical exam. CT abdomen &amp; pelvis showed hepatosplenomegaly. Liver biopsy (LB) showed panlobular hepatitis with focal parenchymal necrosis and a prominent sinusoidal T-lymphocyte dominant infiltrate, many of which were positive for EBV-encoded small RNAs (EBER) on in situ hybridization (Figure 1). Bone marrow biopsy (BMB) showed mildly hypocellular bone marrow without evidence of lymphoproliferative disorder. She left against medical advice (AMA) 6 days later and did not follow up in clinic. Five months later, she returned with similar complaints with pancytopenia and febrile neutropenia. A repeat BMB showed a hypercellular bone marrow with findings suggestive of CAEBV of T-cell type. She left AMA shortly after initiating steroids. A referral to the National Institute of Health for stem cell transplant (SCT) was unsuccessful as she was lost to follow up. DISCUSSION: Hepatic manifestations of CAEBV include acute hepatitis in 47% of patients in the United States with a mixed hepatocellular-cholestatic pattern and hepatomegaly. Her labs were suggestive of AIH such as elevated IgG, positive ANA, weakly positive SMA titers &amp; elevated F-actin antibodies. Several cases report false positive serology suggestive of AIH in patients with active EBV. Inappropriate and possibly dangerous treatment could result if one is unaware of this association. Allogenic hematopoietic SCT is the only known curative therapy to date and without treatment, the average time to death after disease onset is 6.2 years. Given the high mortality associated with delay in treatment, prompt recognition and diagnosis of CAEBV is imperative.

A CASE OF EPSTEIN-BARR VIRUS MYOCARDITIS

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Numerous viruses can cause myocarditis with Enteroviruses being a common cause and Epstein-Barr Virus (EBV) being a rare cause. This virus has also been described in the pathophysiology of hepatitis and cholangiopathy. CASE PRESENTATION: A 22-year-old woman with no significant past medical history presented with a 3-day history of generalized abdominal pain, diarrhea, vomiting, fever, and chest pain. She also endorsed 1 week of myalgias, sore throat, and fatigue. Physical examination showed fever, abdominal tenderness, and scleral icterus. Initial laboratory data demonstrated mildly elevated transaminases, alkaline phosphatase, and bilirubin. ERCP demonstrated mild intrahepatic ductal dilation, 1 cm narrowing of the common bile duct, and non-obstructing gall stones necessitating cholecystectomy and biliary duct stent placement. However, her symptoms persisted, and she became more tachycardic and dyspneic, with worsening chest pain. Laboratory data showed an elevated N-terminal pro-brain natriuretic peptide > 6500 pg/ml with leukocytosis up to 35,000 WBC/microliter. She was transferred to the intensive care unit and clinical evaluation commenced. Empiric antimicrobial therapy was instituted and computed tomography angiography (CTA) was performed which was negative for pulmonary embolus but did demonstrate bilateral large pleural effusions and diffuse airspace infiltrates. Impending respiratory failure was averted with Bi-PAP and transthoracic echocardiogram revealed ejection fraction of 35% confirming suspected cardiomyopathy. Infectious diseases evaluation was extensive and negative except for Epstein-Barr Virus (EBV) polymerase chain reaction (PCR) 472 copies/mL, markedly elevated EBV IgM and IgG to viral capsid antigen, EBV D antigen IgG, and EBV antibody to nuclear antigen. Other etiologies were excluded by PCRs, serologies, cultures, autoimmune evaluation, bone marrow biopsy, imaging, and bronchoscopy. Antimicrobial agents were discontinued, and glucocorticoids were initiated resulting in gradual improvement of symptoms and laboratory abnormalities. The patient was diagnosed with EBV myocarditis with associated hepatitis/cholangiopathy. DISCUSSION: The differential diagnosis of patients with dyspnea, fever, abdominal pain, chest pain and leukocytosis can be broad. This case demonstrates that unusual symptoms of a relatively common viral infection (infectious mononucleosis) must be considered in order to not delay diagnosis and proper treatment. Myocarditis can be the first symptom of EBV infection with manifestations ranging from asymptomatic electrocardiographic changes to fulminant heart failure, cardiac arrhythmias, or even sudden death. CONCLUSIONS: Manifestations of EBV infection can cross multiple organ systems and must be considered by clinicians in the differential diagnosis of acute cardiomyopathy with fever, leukocytosis and signs of hepatitis/cholangiopathy. Reference #1: Muneuchi, J., Ohga, S., Ishimura, M. et al. Cardiovascular Complications Associated with Chronic Active Epstein–Barr Virus Infection. Pediatr Cardiol (2009) 30: 274. Reference #2: Lawee D. Mild infectious mononucleosis presenting with transient mixed liver disease: case report with a literature review. Can Fam Physician. 2007;53(8):1314-6. Reference #3: Fauci, A., Hauser, S., Jameson, J., Kasper, D., Longo, D. and Loscalzo, J. (2016). Harrison's Manual of Medicine, 19e. New York, N.Y.: McGraw-Hill Education LLC. DISCLOSURES: No relevant relationships by Christopher Farmakis, source=Web Response No relevant relationships by Leigh Hunter, source=Web Response