Epstein-Barr Virus Serology Research Articles

Use of Host Response to Refine the Diagnosis of Group A Streptococcal Pharyngitis.

Current diagnostic tests for pharyngitis do not distinguish between symptomatic group A Streptococcus (GAS) infection and asymptomatic colonization, resulting in over-diagnosis and unnecessary use of antibiotics. We assessed whether measures of host response could make this distinction. We enrolled 18 children with pharyngitis having Centor scores of 4 or 5 and 21 controls without pharyngitis or other acute infections. Both groups had throat cultures, molecular tests for GAS and respiratory viruses and IgM serology for Epstein-Barr virus. Host response was evaluated with white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and sequencing of RNA from peripheral blood leukocytes. Of 18 cases, 11 had GAS pharyngitis, 3 had adenovirus pharyngitis and 4 had other pharyngitis. Among asymptomatic controls, 5 were positive for GAS. WBC, CRP, and PCT were higher in subjects with pharyngitis compared to asymptomatic controls including those with GAS. Transcriptional profiles from children with symptomatic GAS were clearly distinct from those of children in all other groups. The levels of two genes, CD177 and TLR5 each individually accurately distinguished between symptomatic and asymptomatic GAS. Optimal diagnostic sensitivity and specificity were achieved by the combination of CRP and PCT, and by each of the two gene markers. In this exploratory study, we showed that traditional measures of inflammation and markers of host gene expression distinguish between symptomatic and asymptomatic GAS. These results point to future rapid molecular approaches for improving the diagnosis of GAS pharyngitis, that may help reduce unnecessary antibiotic use.

Combined assessment of Epstein-Barr virus viral capsid antigen and Epstein-Barr virus nuclear antigen-1 serology for post-transplant lymphoproliferative disorder risk stratification in adult solid organ transplant recipients.

Epstein-Barr virus (EBV) seronegative solid organ transplant recipients (SOTRs) are at increased risk for post-transplant lymphoproliferative disorder (PTLD). Assays for EBV serostatus assess antibody to both EBV viral capsid antigen (VCA) and Epstein-Barr nuclear antigen-1 (EBNA-1), but PTLD risk among SOT recipients with discordant VCA and EBNA-1 results is unknown. We performed a retrospective, single-center cohort study to determine the risk of PTLD among adult (≥ 18 years) SOTRs with discordant pre-transplant VCA and EBNA-1 IgG compared to that of SOTRs with concordantly negative or concordantly positive serology using univariable and multivariable Cox-proportional hazards models. Of 4106 SOTRs, the number (%) who were concordantly positive, concordantly negative, and discordant was 3787 (92.2%), 149 (3.6%), and 170 (4.2%), respectively. The adjusted hazard of PTLD was significantly higher among discordant SOTRs compared to concordantly positive SOTRs (aHR 2.6, 95% CI 1.04-6.6, p =.04) and lower compared to concordantly negative SOTRs (aHR 0.27, 95% CI 0.10-0.76, p <.001). The adjusted hazard of EBV+ PTLD among those with discordant serology was also significantly higher compared to the concordantly positive cohort (aHR 3.53, 95% CI 1.04-12.0, p =.04) and significantly lower compared to the concordantly negative cohort (aHR 0.23, 95% CI 0.06-0.82, p =.02). Risk of PTLD among SOTRs with discordant VCA and EBNA-1 may be intermediate between those with concordantly positive and negative serology. If confirmed in future studies, revision of national EBV serology reporting to include both VCA and EBNA results may be needed to optimize PTLD risk stratification.

Epstein-Barr virus-associated acute pancreatitis: a clinical report and review of literature

BackgroundAcute pancreatitis is a disorder of reversible inflammation of the pancreas. Only a few cases are related to infections and the most common pathogens are the viruses responsible for mumps, parotitis, and influenza. Epstein-Barr virus (EBV)-associated acute pancreatitis is a rare condition and it may occur in children and adults.Case presentationA 3-year-old female was admitted to the “G. Di Cristina” Children's Hospital in Palermo for vomiting and abdominal pain. Laboratory investigations revealed elevated amylase and lipase, with normal liver function tests. Abdominal ultrasound demonstrated an enlarged pancreas, with hypoechogenic areas; no biliary lithiasis was observed. Infectious disease serology was positive for the presence of EBV VCA IgM and IgG. A diagnosis of EBV-associated acute pancreatitis was made. The patient was treated conservatively and recovered.ConclusionsAcute pancreatitis is rarely associated with EBV infection; a review of the English literature revealed only 10 pediatric and 6 adult cases. Patients with pancreatitis should always be evaluated for EBV serology, even in the absence of the typical clinical and hematological features of infectious mononucleosis. For these patients, good prognosis is generally expected.

412.1: Lip Actinic Cheilitis and Its Relationship to Clinical Characteristics and Immunosuppression in Kidney Transplant Recipients

Introduction: Due to drug immunosuppression after kidney transplantation (KT), as well as factors such as chronic uremia and chronic sun exposure, Kidney Transplant Recipients (KTR) have a 46-fold increased incidence of Lip Cancer (LC). Because of the high prevalence of LC in KTR, there are concerns about its prevention, which can be accomplished by diagnosing Actinic Cheilitis (AQ) on lips, a potentially malignant oral lesion that can progress to LC. Aim: The purpose of this investigation was to see if there was a link between the clinical manifestations of AQ and the clinical profile of KTRs. Methods: Convenience sampling in a cross-sectional observational clinical study. An expert researcher completed the diagnosis and clinical staging of AQ in KTRs using Pointevin et al 2017 criteria and a clinical evaluation and photographic record of six different angulations of the lower lip were used to calibrate the researcher (Kappa intra-avaliador >0.8). Demographic data, time since KT, immunosuppressants, exposure to AQ risk factors such as alcoholism, smoking, chronic sun exposure, and exposure to volatile chemical agents, and history of positive serology for oncogenic viruses after KT were all obtained retrospectively from electronic medical records. For the association of variables, Chi-square and Macnemar tests were performed, with a significance value of (0.05). Results: The sample size was 48 (100%) KTR, with 29 people diagnosed with AQ (60.41 percent). Light-siknned KTR was linked with the most severe AQ staging in 9 subjects (18.75 percent; p=0.035). History of exposure to volatile chemical agents (16.33 percent; p=0.007), drunkenness (15.25 percent; p=0.008), and smoking (20.66 percent; p=0.05) were also risk factors for AQ. A history of prolonged sun exposure was linked to a higher severity of QA 22(45.83 percent; p<0.001). The prevalence of AQ was linked to the usage of tacrolimus 43 (89,58 percent; p<0.001) and azathioprine 11 (22,91 percent; p0.001). However, the use of Mycophenolate Mofetil was linked to the most severe cases of AQ in 7 patients (14.58 percent; p=0.05). Individuals who got sirolimus, on the other hand, showed less AQ expression, with 7 patients (14.58 percent; P=0.016) manifesting with lesser degrees. After TxR, positive Epstein-Barr Virus serology was linked to the existence of AQ 17 (35,41 percent; p=0.028). Conclusion: The presence and severity of AQ in KTR were linked to fair skin, chronic sun exposure, Epstein-Barr Virus infections, and the use of Mycophenolate Mofetil. Sirolimus appears to have a protective effect against the development of AQ. It is possible to select groups of patients at higher risk for AQ and, as a result, for LC using this clinical profile associated with the manifestation of AQ, allowing for prevention and early diagnosis. This study was approved by the Ethics and Research in Human Beings Committee under protocol CAAE12798019.3.0000.5417.

Epstein-Barr virus seroprevalence and viral load at disease onset in children with inflammatory bowel disease.

Background and AimPatients with inflammatory bowel disease (IBD) are at increased risk for life‐threatening complications of Epstein–Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection.MethodsWe included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2‐year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre‐treatment viral load of EBV.ResultsOne hundred twenty patients were included in the study. Fifty‐three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine.ConclusionEBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

Abstract 2799: Peripheral blood glycoproteomic biomarkers as a powerful new tool for the detection of nasopharyngeal carcinoma

Abstract Introduction: Nasopharyngeal carcinoma (NPC) is a malignancy characterized by distinct geographic, ethnic, and genetic differences. It presents a major threat to human health, particularly in East Asia and Southeast Asia. NPC commonly invades adjacent tissues and organs, resulting in complex and difficult to treat clinical presentations. NPC commonly remains largely asymptomatic during early disease stages due to its small primary foci. Hence, NPC patients are diagnosed mostly at advanced stage. Currently, no accurate and effective methods are available for the early diagnosis, evaluation, or prognosis for NPC. While Epstein-Barr virus (EBV) DNA and EBV serology tests have been advocated for early diagnosis and screening for NPC, the sensitivities of these two tests vary. due to the fact that only a small proportion of individuals infected with EBV ultimately develop NPC. The ability to detect neoplasms at early stages provides useful information for early intervention. We have recently demonstrated that interrogating the serum glycoproteome, using a proprietary platform that couples artificial intelligence (AI) to targeted liquid chromatography-massspectrometry (LC-MS) yields highly informative biomarkers in a range of neoplastic diseases. Experimental procedures in this proof-of-principle study, a total of 106 plasma samples (1:1 ratio of histologically confirmed cases of NPC and cancer-free controls), which were matched for age (average 49 years) were used. All subjects were male, from a multi-ethnic patient population in Malaysia, including three ethnic minority groups (Bidayuh, Iban and Kadaza). To identify diagnostic glycoprotein profiles for NPC we applied an in-house developed targeted glycoproteomics workflow, whereby plasma proteins were first digested with trypsin/LysC, followed by targeted analysis using LC-MS. The LC-MS generated chromatographic peaks were integrated using an in-house AI-based software for high throughput analysis and further subjected to multivariate statistical analysis. Summary of new data among the 579 glycopeptides interrogated in this study we found 62 glycopeptides statistically significantly abundant in NPC cases compared to healthy controls (at FDR &amp;lt;0.1). From these, we built a predictive algorithm that differentiates NPC cases from controls with high sensitivity and selectivity (AUC of 0.955). Six glycopeptide markers were found as associated with ethnicity. Conclusions: In summary, our results indicate that LC-MS-based glycopeptide profiling provides a highly accurate means of for differentiating NPC cases from healthy controls. Follow-up studies with larger sample size are currently in progress. Citation Format: Klaus Lindpaintner, Thi Thin Aye, Gege Xu, Rachel Rice, Alan Mtchell, Daniel Serie, A Malek, LH Low, Lp Tan, Ct Low, Cy Wong, H Sawali, Yy Yapp, As Khoo. Peripheral blood glycoproteomic biomarkers as a powerful new tool for the detection of nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2799.

VORICONAZOLE-ASSOCIATED MUCOSAL ULCERATION AFTER LUNG TRANSPLANT

TYPE: Case Report TOPIC: Transplantation INTRODUCTION: Colonization and isolation of Aspergillus from bronchial specimens predisposes lung transplant (LTx) recipients to airway anastomotic complications and allograft rejection. Post-LTx antifungal prophylaxis with voriconazole has been associated with cutaneous malignancies. We report a case of voriconazole-associated mucosal ulceration in an LTx recipient that improved upon drug discontinuation. CASE PRESENTATION: A 56-year-old LTx recipient (November 2020) presented to the clinic in January 2021 for painful oral and anal ulcers. He was managed with reduced maintenance immunosuppression, filgrastim, lidocaine-diphenhydramine-corticosteroid oral rinse, and topical nitroglycerin-nystatin ointments without relief. He returned to the emergency department in February for worsening pain, facial swelling, inability to open mouth, and difficult defecation. Inpatient evaluation demonstrated neutropenia (0.8/μL), lymphopenia (0.5/μL), and elevated inflammatory markers [ESR: 119 mm/h; CRP: 123.2 mg/L; procalcitonin: 0.14 ng/mL]. However, blood culture, serology for Epstein-Barr virus, herpes simplex virus, cytomegalovirus, head-neck and chest imaging, esophagogastroduodenoscopy, perianal punch biopsy, and anal canal incisional biopsy were unremarkable. Importantly, serum voriconazole level was elevated (7.2 μg/mL). Discontinuation of voriconazole led to relief in symptoms and discharge. On clinic follow-up, he endorsed complete resolution of ulcers. Of note, his antifungal prophylaxis was temporarily switched from isavuconazole to voriconazole in January. DISCUSSION: Voriconazole-induced photosensitivity and elevated plasma retinol levels may progress to cutaneous malignancies. In our patient, temporality of onset (one week) and resolution (within days) of mucosal ulceration with voriconazole discontinuation suggest an association. No residual scarring or recurrence was observed. CONCLUSIONS: Physicians must be mindful of dermatologic adverse events of voriconazole in LTx recipients. DISCLOSURE: Nothing to declare. KEYWORD: Lung transplantation

CASE REPORT OF EPSTEIN–BARR VIRUS-INDUCED AUTOIMMUNE VITILIGO IN NIGERIA

Vitiligo is an acquired skin depigmenting disorder resulting from melanocytes loss in the epidermis, associated with an autoimmune aetiopathophysiology. However, there are limited data about the association between vitiligo and Epstein–Barr virus (EBV). Hence, the authors present a case of a 43-year-old male who had progressive symmetrical hypopigmented macules, sometimes coalescing to patches that were generalised but predominantly on the face and torso, with scanty involvement of proximal and distal extremities of the body. The diagnosis of vitiligo was made clinically, and seborrhoeic dermatitis was considered as a differential. Since the patient had been offered treatment for seborrhoeic dermatitis using antifungal with no relief and extensive depigmentation, the authors’ working diagnosis was vitiligo and was confirmed with histology. To establish the likely cause of the condition, viral serology for HIV, Cytomegalovirus, herpes, and EBV were completed, but only EBV serology was abnormal. Therefore, the authors report this case to encourage clinicians to consider EBV infection in the aetiology and predisposition for vitiligo to help explore other pathology that the virus may cause.

An Unusual Presentation of Glandular Fever

Epstein-Barr virus (EBV) is an ubiquitous DNA herpesvirus with >90% of adults >40 years of age showing a serological response. While in their youth, primary EBV infection may pass unnoticed, young adults have a high incidence of infectious mononucleosis (IM). This is characterized by a triad of pharyngitis, cervical lymphadenopathy, and fever because of a self-limiting lymphoproliferative disease. Common complications include but are not limited to hepatitis, splenomegaly, encephalitis, and haemophagocytic lymphohistiocytosis (HLH) with evidence that Caucasian males and smokers are more likely to suffer severe disease. Here we present a 21-year-old male who presented with a 2-week history of fever, dry cough, and a 4-week history of pharyngitis. He had no exposure to unwell contacts and denied any new sexual partners. Examination revealed general pallor with tender bilateral cervical lymphadenopathy and pharyngeal erythema. Admission bloods revealed pancytopenia (WCC 1.5 × 109/L, Plt 84 × 109/L, and Hb 82 g/L) with normal reticulocyte count and raised mean corpuscular volume (114 fL). Serum vitamin B12 and folate were low with serum ferritin raised (1027 µg/L) suggesting a proinflammatory state. Admission liver function tests, coeliac serology, autoimmune panel (ANA, ANCA, and anti-dsDNA), hepatitic (hepatitis A, B, and E), human immunodeficiency virus (HIV), toxoplasmosis, parvovirus, and CMV serology were normal. The monospot test on day 1 of the presentation was negative. Ultrasound (US) of the abdomen on day 3 of the presentation revealed isolated splenomegaly (16.8 cm). Day 4 EBV serology (VCA IgM, VCA IgG, and EBNA IgG) was negative as such haematological investigations including JAK2, serum free light chains, and BCR-ABL were undertaken alongside cervical lymph node core biopsy. Repeat Monospot testing on day 7 came back positive. Repeat EBV serology now showed equivocal EBV VCA IgG (0.77 OD) and positive VCA IgM (9.04 OD) with concurrent new hepatitis. Histopathology of the core biopsy revealed Sternberg-reed cells and a mixed immunoblastic reaction in keeping with resolving IM. This case highlights the need for physicians to have a strong clinical suspicion of IM and understand the multiple ways in which IM may be present as well as the time lag to positivity in serological testing.

COVID-19 associated EBV reactivation and effects of ganciclovir treatment.

BackgroundSystemic reactivation of Epstein–Barr virus (EBV) may occur in novel coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). However, the clinical consequences of EBV reactivation remain uncertain.MethodsIn this retrospective study, we screened 1314 patients with confirmed COVID‐19 who died or were discharged between January 1, 2020 and March 12, 2020, in Wuhan Infectious Disease Hospital, Wuhan, China. Patients who had complete data for EBV serology and cytomegalovirus (CMV) serology were eligible. Serum levels of viral capsid antigen (VCA)‐immunoglobulin G (IgG), Epstein–Barr nuclear antigen‐IgG, VCA‐IgM, early antigen (EA)‐IgG, CMV‐IgG, and CMV‐IgM were compared between survivors and nonsurvivors. Dynamic changes of laboratory tests and outcomes were compared in patients with and without ganciclovir treatment. We used 1:1 matching based on age, gender, and illness severity to balance baseline characteristics.ResultsEBV reactivation was present in 55 of 217 patients. EBV reactivation was associated with age (57.91 [13.19] vs. 50.28 [12.66] years, p < .001), female gender (31 [56%] vs. 60 [37%], p = .02). Patients with EBV reactivation have statistically nonsignificant higher mortality rate (12 [22%] vs. 18 [11%], p = .08). EA‐IgG levels were significantly higher in nonsurvivors than in survivors (median difference: −0.00005, 95% confidence interval, CI [−3.10, 0.00], p = .05). As compared to patients with COVID‐19 who did not receive ganciclovir therapy, ganciclovir‐treated patients had improved survival rate (0.98, 95% CI [0.95, 1.00] vs. 0.88, 95% CI [0.81, 0.95], p = .01). Hemoglobin (p < .001) and prealbumin (p = .02) levels were significantly higher in ganciclovir‐treated patients.ConclusionA high proportion of COVID‐19 patients had EBV reactivation that may be associated with an increased risk of death. Whether treatment with ganciclovir may decrease the mortality of COVID‐19 patients complicated with EBV reactivation warrants to be addressed in a placebo‐controlled randomized trial in the future.

Acute posterior multifocal placoid pigment epitheliopathy associated with infectious mononucleosis: A rare presentation

This case report describes the association between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and Epstein-Barr virus (EBV) infection. A 26-year-old female presented with acute bilateral blurred vision and paracentral scotoma. The patient also had prodromal flu-like symptoms. Funduscopic examination showed bilateral yellow-white placoid lesions at the level of retinal pigment epithelium (RPE). Fluorescein Angiography showed characteristic early hypofluorescence and late hyperfluorescence of the lesions. The diagnosis of APMPPE was made based on these findings. Laboratory investigation showed a positive result for EBV serology test. Severe dry eye symptoms were presented at the end of 6-month follow-up. APMPPE may be associated with acute systemic EBV infection.

Characterization of the humoral immune response to the EBV proteome in extranodal NK/T-cell lymphoma

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that has been etiologically linked to Epstein-Barr virus (EBV) infection, with EBV gene transcripts identified in almost all cases. However, the humoral immune response to EBV in NKTCL patients has not been well characterized. We examined the antibody response to EBV in plasma samples from 51 NKTCL cases and 154 controls from Hong Kong and Taiwan who were part of the multi-center, hospital-based AsiaLymph case–control study. The EBV-directed serological response was characterized using a protein microarray that measured IgG and IgA antibodies against 202 protein sequences representing the entire EBV proteome. We analyzed 157 IgG antibodies and 127 IgA antibodies that fulfilled quality control requirements. Associations between EBV serology and NKTCL status were disproportionately observed for IgG rather than IgA antibodies. Nine anti-EBV IgG responses were significantly elevated in NKTCL cases compared with controls and had ORshighest vs. lowest tertile > 6.0 (Bonferroni-corrected P-values < 0.05). Among these nine elevated IgG responses in NKTCL patients, three IgG antibodies (all targeting EBNA3A) are novel and have not been observed for other EBV-associated tumors of B-cell or epithelial origin. IgG antibodies against EBNA1, which have consistently been elevated in other EBV-associated tumors, were not elevated in NKTCL cases. We characterize the antibody response against EBV for patients with NKTCL and identify IgG antibody responses against six distinct EBV proteins. Our findings suggest distinct serologic patterns of this NK/T-cell lymphoma compared with other EBV-associated tumors of B-cell or epithelial origin.

Epstein-Barr Virus Prevalence at Diagnosis and Seroconversion during Follow-Up in Pediatric Inflammatory Bowel Disease.

Primary Epstein–Barr virus infection in pediatric patients with inflammatory bowel disease during immunomodulation with thiopurines has been associated with increased risk for malignancies or hemophagocytic lymphohistiocytosis. We determined Epstein–Barr virus (EBV) seroprevalence at inflammatory bowel disease (IBD) diagnosis and seroconversion during follow-up in a large single center cohort of children with IBD. EBV serology results and patient characteristics were retrospectively retrieved from the hospital documentation system. EBV seronegative patients at IBD diagnosis were prospectively retested. We report on IBD patients with symptomatic active EBV infection and a complicated disease course, and those diagnosed with malignancy with respect to EBV status and drug exposure. Of 402 patients, 194 (48%) had available EBV serology results at time of IBD diagnosis at a median of 12 years (IQR 9–14 years). Thereof, 102 (53%) were EBV-positive. Of 92 EBV-negative patients, 66 were retested and 17% showed a seroconversion at a mean follow-up time of 4.3 years (SD 3 years). Three children treated with azathioprine experienced acute clinically relevant EBV infection 2, 2.5, and 4 years after IBD diagnosis, two developed signs of hemophagocytic lymphohistiocytosis. Three cases of malignancy occurred in the cohort, though none seemed to be triggered by EBV. In conclusion, almost 50% of pediatric IBD patients were EBV-naïve following diagnosis and may be at increased risk to develop severe EBV infection during immunosuppressive therapy, potentially associated with complications such as hemophagocytic lymphohistiocytosis or malignancy.

S2703 A Rare Case of EBV Reactivation in an Immunocompetent Patient

Introduction: Hepatic involvement during an active primary Epstein-Barr virus (EBV) infection often results in mild, self-resolving elevation of transaminases and is associated with infectious mononucleosis (IM). EBV rarely reactivates, and most cases occur in immunocompromised individuals. We present a rare case of EBV reactivation in an immunocompetent patient only presenting with cholestatic liver injury. Case Description/Methods: A 19-year-old female with a history of resolved EBV IM one year prior presented with dark urine and jaundice. She had no fever, abdominal pain, nausea, vomiting, weight changes or night sweats. She had no history of illicit drug, tobacco or alcohol use, recent travel, or sick contacts. Her medications were loratadine and an OCP;she denied use of acetaminophen or herbal supplements. Family history was unrevealing. On exam she was jaundiced but otherwise normal. Initial laboratory tests showed AST 97 U/L, ALT 75 U/L, ALP 165 U/L, T-BILI 8.1 mg/dL, D-BILI 5.7 mg/dL. CT abdomen revealed splenomegaly. Work up revealed ASMA titer (1:40), but otherwise negative/ normal ANA, IgG, AMA, HCV Ab, HBV serologies, HAV IgM, CMV PCR, iron studies, tick borne serologies, SARS CoV-2 PCR, A1AT and ceruloplasmin. On the second day, the T-BILI peaked to 12.4 mg/dL, AST 151 U/L, ALT 131 U/L, ALP 237 U/L. (Fig.1) EBV serologies were positive (EBV VCA IgG >750.0 U/ml, EBV VCA IgM >160.0 U/ml), EBV viral load of 23,500 copy/ ml and negative monospot test. On day four, the LFTs improved and she was discharged. One month later LFTs had normalized, and she was asymptomatic. Discussion: EBV reactivation causing cholestatic liver injury is extremely rare in immunocompetent individuals. Furthermore, EBV-induced hepatitis is usually associated with IM but our patient's sole complaint was jaundice and dark urine. Interestingly, she had mononucleosis due to EBV one year prior with unremarkable LFTs. The fact that the hepatitis was caused by the reactivation of the virus instead of a primary infection may be the reason for lack of other symptoms. It is unclear whether EBV reactivation increases the risk of hepatitis. The diagnosis can be made without a liver biopsy if thorough work up for hepatitis is negative and the EBV serologies are positive. The disease is often self-limited and the use of antivirals is controversial and thus there is no clear indication. Our case demonstrates that EBV reactivation presenting without the 'classic' IM symptoms may be under-recognized as a cause of cholestatic liver injury. (Figure Presented).

S2731 Isolated EBV-Induced Acute Hepatitis in the Absence of Infectious Mononucleosis

Introduction: Epstein-Barr virus (EBV) is a globally prevalent herpesvirus with an estimated 90-95% seropositivity rate worldwide. It is most known for causing infectious mononucleosis characterized by the classic triad of fever, pharyngitis, and lymphadenopathy. Hepatitis is a common manifestation seen in 90% of cases;however, isolated acute hepatitis in the absence of infectious mononucleosis is a rare clinical presentation. Case Description/Methods: An 18-year-old female with no medical history presented with fevers, fatigue, myalgia, and headache ongoing for one week. She had been evaluated previously with recommendations for supportive care for an unspecified viral illness. Workup at the time had been negative for urine hCG, COVID-19, heterophile antibody, Lyme disease, and bacteremia. However, symptoms worsened with the development of nausea, vomiting, and darkening of her urine. Prior to this, patient had been in her normal state of health without sick contacts, travel history, animal exposures, risky sexual practices, or substance use. Exam revealed cervical lymphadenopathy and hepatosplenomegaly. Labs showed normal leukocyte count 8.4 thou/cmm with differential significant for reactive lymphocytosis 19% and bandemia 8%. Liver function tests were abnormal with elevated total bilirubin 3.8 mg/dL, AST 366 U/L, ALT 460 U/L, ALP 562 U/L. Synthetic function was intact. Hepatic ultrasound was unrevealing. Extensive infectious workup revealed acute EBV infection with serologies showing positive VCA IgM Ab 74.3 U/mL, negative VCA IgG Ab 11.9 U/mL, negative EA Ab < 5 U/mL, negative EBNA Ab < 3 U/mL. Patient was managed supportively with improved symptoms. She was instructed to avoid physical contact sports for one month upon discharge. Discussion: Clinically significant EBV induced hepatitis is a rare entity seen in < 5% of cases. Nevertheless, it is important to consider EBV as a causative pathogen of acute hepatitis. Heterophile antibody or Monospot test is the diagnostic test of choice with a sensitivity of 85% and a specificity of 100%;however, false negatives can occur especially early in the disease course. EBV serology has an improved sensitivity of 97% with a comparable specificity of 94%. As such, follow-up serology is necessary especially if clinical suspicion is high. While no specific EBV targeted therapies exist, it is important to identify it given the potential complications, including splenic rupture, airway obstruction, malignancies, lymphoproliferative disorders, among others.

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.

Mediastinal Mass with Unusual Etiology.

Mediastinal Mass with Unusual Etiology.

A comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma

Using Epstein-Barr virus (EBV)-based markers to screen populations at high risk for nasopharyngeal carcinoma (NPC) is an attractive preventive approach. Here, we develop a comprehensive risk score (CRS) that combines risk effects of EBV and human genetics for NPC risk stratification and validate this CRS within an independent, population-based dataset. Comparing the top decile with the bottom quintile of CRSs, the odds ratio of developing NPC is 21 (95% confidence interval: 12–37) in the validation dataset. When combining the top quintile of CRS with EBV serology tests currently used for NPC screening in southern China, the positive prediction value of screening increases from 4.70% (serology test alone) to 43.24% (CRS plus serology test). By identifying individuals at a monogenic level of NPC risk, this CRS approach provides opportunities for personalized risk prediction and population screening in endemic areas for the early diagnosis and secondary prevention of NPC.

Donor EBV-Positive Serostatus Increases the Risk of Chronic GVHD in Patients with Myeloid and Lymphoid Malignancies Other Than Acute Leukemia: Infectious Diseases Working Party EBMT Study

BACKGROUND: In patients with acute leukemia (AL), donor EBV (Epstein-Barr Virus) seropositive status significantly increases the risk of development of acute and chronic GVHD after allo-HSCT, while it has no influence on other transplant outcomes (OS, RFS, RI, NRM) (Styczynski et al , J Clin Oncol, 2016). No data are available on the impact of EBV serostatus on transplant outcomes in patients with other hematological malignancies.OBJECTIVE: We analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival, OS; relapse-free survival, RFS; relapse incidence, RI; non-relapse mortality, NRM; acute graft-versus-host disease, aGVHD; chronic graft-versus-host disease, cGVHD) in patients with myeloid and lymphoid malignancies other than AL undergoing allo-HSCT.PATIENTS AND METHODS: 12,931 allo-HSCTs performed between 1997 and 2016 for myeloid (58.1%) or lymphoid malignancies (41.9%), other than AL, with PB (76%) or BM±PB (24%) as a stem cell source were included in this retrospective Registry megafile IDWP EBMT study.RESULTS:DEMOGRAPHICS : 48% had HSCT from a matched family donor, 4.2% from a mismatched family donor, and 47.8 from an unrelated donor. T-cell depletion was performed in vivo in 58.4%, and ex vivo in 7.9% patients. Conditioning regimen was myeloablative in 41.3%, RIC in 58.7%. Median follow-up was 4.7 years. TRANSPLANT OUTCOMES : EBV-seropositive patients receiving grafts from EBV-seropositive donors (EBV R+/D+ transplants) had worse transplant outcomes in comparison to EBV-seronegative patients receiving grafts from EBV-seronegative donors (EBV R-/D-): lower OS (59.6% vs 65.9%), lower RFS (51.1% vs 57.5%), higher incidence of chronic GVHD (49.5% vs 41.8%), and higher incidence of de novo chronic GVHD (30.5% vs 24.0%). No significant differences were found for: RI, NRM, and acute GVHD (Table 1). MULTIVARIATE ANALYSIS : Allo-HSCT from EBV-seropositive donors had higher risk of development of cGVHD (HR=1.13; p=0.0096). When 4 subgroups (R-/D-, R-/D+, R+/D-, R+/D+ EBV serology) were analyzed, the risk of cGVHD was higher for EBV R-/D+ (HR=1.22; p=0.0395), R+/D- (HR=1.21; p=0.0375), and for R+/D+ (HR=1.28; p=0.0013) when compared to R-/D- transplants. On the other hand, R/D EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of acute GVHD. Finally, since the R-/D- combination patients were more likely to be children than R+/D+, this could explain the effect in univariate analysis on OS and RFS while the chronic GVHD effect was independent of age.CONCLUSIONS: Allo-HSCT from EBV-seropositive donors are at 13% higher risk of chronic GVHD in patients with myeloid and lymphoid malignancies other than AL. [Display omitted] DisclosuresPetersen:Sanofi: Membership on an entity's Board of Directors or advisory committees. Leblond:SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees; GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ABBVIE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria; NOVARTIS: Honoraria, Membership on an entity's Board of Directors or advisory committees. Michallet:medac GmbH, Wedel, Germany: Honoraria, Other: Travel grants. Kröger:Janssen Global Services, LLC: Speakers Bureau; Amgen Inc.: Speakers Bureau; Novartis AG: Research Funding; RIEMSER Pharma: Research Funding; Neovii Pharmaceuticals AG: Speakers Bureau; Novartis AG: Speakers Bureau; Sanofi: Speakers Bureau.

Author Response: Teaching Video NeuroImages: Pathologic Yawning: A Sign of Brainstem Involvement in Acute Disseminated Encephalomyelitis?

We thank Drs. Fujimori and Nakashima for their comment on our article.1 Their previously published report is certainly an interesting case as well.2 We agree that anti-myelin oligodendrocyte glycoprotein antibody testing is appropriate to include in cases of suspected acute disseminated encephalomyelitis (ADEM). We ordered a broad inflammatory and infectious workup for our patient on both serum and CSF, with the latter being repeated 5 days after initial presentation. Oligoclonal bands were noted in the CSF on 1 of 2 tests. The CSF IgG index was elevated (0.80 initially and 0.68 on follow-up; reference range 0.34–0.66). Anti-AQP4 antibodies were negative. Infectious workup showed negative serology for Epstein-Barr virus and cytomegalovirus. Viral PCR (including enterovirus) was negative, as was CSF mycobacterial culture. Mycoplasma pneumoniae IgM was positive in serum. Bartonella henselae serum IgG was also positive (1:640), but this was not believed to be clinically relevant. We ordered anti-MOG antibodies at the time of initial presentation, but unfortunately these were canceled by the laboratory because of a registration error; we have not reordered the test because the patient has completely recovered and the lesions seen on brain MRI have resolved. At this point, M. pneumoniae infection is the most likely trigger for the ADEM.