Case Report: Periorbital Edema as an Overlooked Presentation of Epstein-Barr Virus

Primary Epstein-Barr virus hepatitis complicated by ascites with epstein-barr virus reactivation during primary cytomegalovirus infection.

Infectious mononucleosis (IM) is a viral disease most commonly caused by the Epstein–Barr virus (EBV). The triad of fever, pharyngitis, and cervical chain lymphadenopathy classically describe this benign condition. Ocular association is also possible, although less commonly reported, and manifests as bilateral periorbital oedema presenting early in the disease process. A case of a fit and well 18-year-old female patient who developed periorbital oedema before the classic triad is presented. Furthermore, her case describes a significantly longer duration of periorbital tissue involvement, contrary to what is described in the current literature. Clinicians should not only recognise periorbital oedema as an initial manifestation of IM but also be alerted of its possible protracted course.

BackgroundA teenager with periorbital edema can be a challenging diagnosis since there are numerous diseases that can have this sign, both infectious and non-infectiousCase-reportA 14-year-old female presents in the Emergency...

Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised. The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis. A search was conducted in October 2022 in PubMed Clinical Queries using the key terms "infectious mononucleosis" OR "Epstein-Barr virus" OR "EBV". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the aforementioned search was used in the compilation of the present article. Infectious mononucleosis, caused by Epstein-Barr virus, most commonly affects adolescents and adults aged 15 to 24 years. Epstein-Barr virus is transmitted primarily in saliva. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. Fatigue may be profound but tends to resolve within three months. Periorbital and/or palpebral edema, typically bilateral, occurs in one-third of patients. Splenomegaly and hepatomegaly occur in approximately 50% and 10% of cases, respectively. A skin rash, which is usually widely scattered, erythematous, and maculopapular, occurs in approximately 10 to 45% of cases. Peripheral blood leukocytosis is observed in most patients; lymphocytes make up at least 50% of the white blood cell differential count. Atypical lymphocytes constitute more than 10% of the total lymphocyte count. The classic test for infectious mononucleosis is the demonstration of heterophile antibodies. The monospot test is the most widely used method to detect the serum heterophile antibodies of infectious mononucleosis. When confirmation of the diagnosis of infectious mononucleosis is required in patients with mononucleosis-like illness and a negative mono-spot test, serologic testing for antibodies to viral capsid antigens is recommended. Infectious mononucleosis is a risk factor for chronic fatigue syndrome. Spontaneous splenic rupture occurs in 0.1 to 0.5% of patients with infectious mononucleosis and is potentially life-threatening. Treatment is mainly supportive. Reduction of activity and bed rest as tolerated are recommended. Patients should be advised to avoid contact sports or strenuous exercise for 8 weeks or while splenomegaly is still present. Most patients have an uneventful recovery. Infectious mononucleosis is generally a benign and self-limited disease. Prompt diagnosis is essential to avoid unnecessary investigations and treatments and to minimize complications. Splenic rupture is the most feared complication. As avoiding exposure to EBV is almost impossible, the most effective way to prevent EBV infection and infectious mononucleosis is the development of an effective, safe, and affordable EBV vaccine that can confer life-long immunity.

Hoagland Sign-A Common Diagnosis Preceded by an Uncommon Sign.

Meeting Abstracts1 May 1971Clinical and Immunologic Features of Primary EpsteinBarr Virus Infection and Infectious Mononucleosis.Daniel E. Lehane, M.D., Neil R. Newberg, M.D., Walter E. BeamDaniel E. Lehane, M.D.Search for more papers by this author, Neil R. Newberg, M.D.Search for more papers by this author, Walter E. BeamSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-828_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSeveral investigators have demonstrated rising Epstein Barr (EB) virus antibody titers in infectious mononucleosis. Since most EB virus infections go unrecognized and EB virus has been associated with several other conditions, the causal relationship of EB virus to infectious mononucleosis remains uncertain. We have attempted to clarify this relationship by describing primary EB virus infections in terms of serum and nasal secretory immunoglobin responses. The clinical manifestations of infectious mononucleosis have been determined by reviewing 66 documented cases, and a mild illness similar to mononucleosis has been demonstrated during typical EB virus infections.Serum and nasal secretion specimens collected biweekly... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: MSC USN Camp LeJeune, N.C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 828-828KeywordsClinical immunologyEpstein-Barr virus Issue Published: 1 May 1971 PDF downloadLoading ...

Objective To investigate the risk factors for pneumonia in children with Epstein-Barr virus (EBV) infectious mononucleosis(IM). Methods The clinical data of children with EBV-IM from March 2015 to February 2018 in Children′s Hospital of Chongqing Medical University were retrospectively analyzed.The patients were divided into a pneumonia group and a non-pneumonia group.The difference between 2 groups was analyzed, including gender, age, duration of fever, the maximum temperature in disease duration, the size of liver, the size of spleen, tonsillopharyngitis, cervical lymphadenopathy, edema of the eyelids, white blood cell (WBC), lymphocyte, atypical-lymphocytes, C-reactive protein (CRP), procalcitonin (PCT), alanine transaminase (ALT), glutamic oxalacetic transaminas (AST), lactic dehydrogenase (LDH), cytomegalovirus (CMV) antibody, the titer of mycoplasma (MP) antibody, EBV DNA, length of stay, and hospitalization expenses.The single factor analysis was performed to analyze the above data between 2 groups, and the data with statistical significance were analyzed by the multifactor Logistic regression.The recei-ver operator characteristic (ROC) curve was drawn to evaluate the predicting ability of the indicators for IM combined with pneumonia. Results Among 923 cases, 133 cases(14.4%) EBV-IM patients were complicated with pneumonia.The findings of single factor analysis indicated that the risk factors were the duration of fever, the size of liver, the size of spleen, and the titer of MP antibody (all P<0.05). The multifactor Logistic regression showed that the duration of fever, the size of liver, the titer of MP antibody were the risk factors for EBV-IM children with pneumonia (P=0.013, 0.028, 0.014). The area under curve (AUC) of the duration of fever was 0.624, and the critical value was 7.5 d (P=0.000); the AUC of the size of liver was 0.590, and the critical value was 2.65 cm (P=0.003). Conclusions The incidence rate of EBV-IM children combined with pneumonia was high.With the presence of the titer of MP antibody ≥1∶160, the duration of fever≥7.5 days, and the size of liver>2.65 cm, it may be independent risk factors for pneumonia in IM children with EBV infection, which requires special attention clinically and earlier chest imageological examination are needed. Key words: Epstein-Barr virus; Infectious mononucleosis; Pneumonia; Risk factor; Child

Epstein-Barr virus (EBV) infectious mononucleosis is often diagnosed based on characteristic clinical features and either a positive heterophil antibody test or serology, both of which can be unreliable in young children. Real time quantitative PCR assays that measure EBV DNA load in serum or plasma are highly sensitive in young children, but serum and plasma contain inhibitors of PCR which must be removed by DNA extraction techniques. A real time TaqMan PCR assay was designed and evaluated for simultaneously measuring EBV DNA load and validating the removal of PCR inhibitors from serum samples. A serum sample was available from patients classified serologically as primary EBV infection (n = 28), EBV-seronegative (n = 25) and EBV-seropositive (n = 26). Patients were classified as having EBV infectious mononucleosis if they had specified clinical findings and > or =10% atypical lymphocytes in peripheral blood or had a positive Monospot test result. DNA was purified by a spin column method and tested in PCR reactions with primers for EBV DNA polymerase gene and internal control targets. Amplification of the two PCR products was measured in real time with separate TaqMan DNA probes labeled with various fluorescent reporters. The mean age of study patients was 9 years, 4 months. Twenty-one (75%) of the patients in the primary EBV infection group, one (4%) of the seronegatives and none of the seropositives had detectable EBV DNA. Within the primary infection group, those with detectable virus were more likely than those without detectable virus to have evidence of lymphadenopathy (14 of 16 vs.1 of 5; P = 0.011), higher mean atypical (11.7 vs.0.9%; P = 0.002) and absolute atypical (1.5 vs.0.1 x 109/l; P = 0.004) lymphocyte count, higher mean absolute lymphocyte count (4.7 vs.2.3 x 109/l; P = 0.026) and higher mean aspartate aminotransferase value (119.8 vs.37.3 IU/l; P = 0.036). Ten patients, all in the primary infection group, had EBV infectious mononucleosis, and all had positive PCR results. No sample contained PCR inhibitors. A real time TaqMan PCR assay allows rapid identification of patients with primary EBV infection and those with EBV infectious mononucleosis.

Background: Infectious mononucleosis (IM) is typically caused by Epstein-Barr virus (EBV), but can also be caused by drugs and other pathogens, such as cytomegalovirus (CMV) and hepatitis B virus. It shows a wide range of clinical and laboratory characteristics, which are presumed to be dependent on the patient age during the primary infection. This report describes the clinical features of hospitalized adults who developed EBV- or CMV-induced IM. Methods: The medical records of adult patients, diagnosed as EBV- or CMV-induced IM at the Hallym Medical Center and Dankook University Hospital, between January 1999 and July 2004, were retros- pectively reviewed. Results: The analysis included 23 patients, consisting of 16 with EBV-induced IM and 7 with CMV- induced IM. Many of these patients were hospitalized under the impressions of either acute pharyngitis, acute hepatitis, fever of unknown origin or a malignant lymphoma. The vast majority of patients initially demonstrated lymphocytosis, with atypical lymphocytes. While patients younger than 20 years of age, usually presented with the classic triad of symptoms; IM-fever, pharyngitis and lymphadenopathy; those over the age of 20 often presented without pharyngitis or lymphadenopathy. There were no significant differences in the laboratory findings between EBV- and CMI-ind uced IM. Compared with patients with EBV-induced IM, however, those with CMV-induced IM were more likely to have abdominal pain (12.5% vs. 57%, P=0.04) and nausea or vomiting (25% vs. 75%, P=0.07), but less likely to have pharyngitis (69% vs. 14%, P=0.03) and cervical lymphadenopathy (75% vs. 14%, P=0.01). Conclusion: IM in adults, especially in those above 20 years of age or if induced by CMV, are charac- terized by the atypical clinical manifestations. A higher index of suspicion and more attention must be paid to reduce unnecessary diagnostic work-ups and management. (Korean J Hematol 2005;40:1-7.)

A rare case of microblading-induced preseptal cellulitis

Primary infection with Epstein-Barr virus (EBV) is asymptomatic in children with immature immune systems but may manifest as infectious mononucleosis, a vigorous immune activation, in adolescents or adults with mature immune systems. Infectious mononucleosis and chronic immune activation are linked to increased risk for EBV-associated lymphoma. Here we show that EBV initiates progressive lytic infection by expression of BZLF-1 and the late lytic genes gp85 and gp350/220 in cord blood mononuclear cells (CBMC) but not in peripheral blood mononuclear cells (PBMC) from EBV-naive adults after EBV infection ex vivo. Lower levels of proinflammatory cytokines in CBMC, used to model a state of minimal immune activation and immature immunity, than in PBMC were associated with lytic EBV infection. Triggering the innate immunity specifically via Toll-like receptor-9 of B cells substantially suppressed BZLF-1 mRNA expression in acute EBV infection ex vivo and in anti-IgG-stimulated chronically latently EBV-infected Akata Burkitt lymphoma cells. This was mediated in part by IL-12 and IFN-gamma. These results identify immune activation as critical factor for the suppression of initiation of lytic EBV infection. We hypothesize that immune activation contributes to EBV-associated lymphomagenesis by suppressing lytic EBV and in turn promotes latent EBV with transformation potential.

Periorbital complex regional pain syndrome

Validation of Roche LightCycler Epstein-Barr Virus Quantification Reagents in a Clinical Laboratory Setting

Objective To investigate the relationship between Epstein-Barr virus (EBV) DNA and EBV serology markers and evaluate the clinical application values in different diseases. Methods Plasma samples from 397 diagnosed EBV infection-associated patients and 120 health donors from May 2014 to November 2015 in Wuhan Tongji Hospital were collected. Real-time fluorescent quantitative PCR was performed to detect the levels of EBV-DNA in peripheral blood mononuclear cell and plasma. ELISA was used to detect VCA IgA, VCA IgM, VCA IgG, EA(D) IgG and EBNA IgG antibodies in plasma. The positive rate of EBV-DNA and EBV antibodies were counted in each group according to the detection threshold.Kappa statistic and Spearman sank correlation test were used to analysis the correlation and uniformity between EBV-DNA and EBV serology indicators. Results The positive rate of VCA IgG in patient and health control was 94.2% (374/397) and 93.3% (112/120) respectively (χ2=0.125, P=0.67); The positive rate of EBNA IgG in patient and health control was 95.4% (379/397) and 95.0% (114/120) respectively (χ2=0.045, P=0.807); but the positive rate of VCA IgM was 5.5% (22/397) and 0% (0/120) respectively (χ2=6.9, P<0.01); The positive rate of VCA IgA was 43.3% (172/397) and 9.2% (10/120) respectively (χ2=49.5, P<0.01); The positive rate of EA(D) IgG was 42.0% (167/397) and 7.5% (9/120) respectively (χ2=49, P<0.01). The positive rate of EBV-DNA was 65.5% (260/397) and 16.7% (20/120) respectively (χ2=88.5, P<0.01); The positive rate of EBV-DNA in plasma was 45.8% (182/397) and 5.0% (6/120) respectively (χ2=66.4, P<0.01). Furthermore, the uniformity and Spearman correlation analysis showed that there was no significant correlation between EBV-DNA and EBV serology indicators. The correlation analysis between PBMC EBV-DNA and VCA IgM, VCA IgA, EA(D) IgG showed the Kappa was 0.073, 0.147, 0.073, respectively; the correlation analysis between plasma EBV-DNA and VCA IgM, VCA IgA, EA(D) IgG showed the Kappa was 0.144, 0.369, 0.288, respectively. Thus, the patients were divided into different groups according to the discharge diagnosis, it was observed that the positive rates of EBV-DNA is more than 90% in extra-nodal NK/T cells lymphoma, EBV-associated hemophagocytic lymphoid tissue hyperplasia, chronic active EBV infection and infectious mononucleosis. In nasopharyngeal carcinoma patients, the positive rate of EBV antibodies (VCA IgA and EA(D) IgG) were higher than the detection of EBV-DNA. Conclusions There was no significant correlation between EBV-DNA and EBV serology markers for the same sample. The clinical application values of EBV DNA and EBV serology markers were not identical in nasopharyngeal carcinoma, extra-nodal NK/T cells lymphoma, infectious mononucleosis and EBV-associated hemophagocytic lymphoid tissue hyperplasia. (Chin J Lab Med, 2017, 40: 195-200) Key words: Herpesvirus 4, human; DNA, viral; Serologic tests; Nasopharyngeal neoplasms; Lymphoma

Correspondence: A Martin Lerner 32804 Pierce Road, Beverly Hills, MI, 48025, USA Tel +1 248 540 9866 Fax +1 248 540 0139 Email amartinlerner@yahoo.com Abstract: A systematic 2001–2007 review of 142 chronic fatigue syndrome (CFS) patients identified 106 CFS patients with elevated serum IgG antibodies to the herpesviruses Epstein– Barr virus (EBV), cytomegalovirus, or human herpesvirus (HHV) 6 in single or multiple infections, with no other co-infections detected. We named these 106 patients group-A CFS. Eighty-six of these 106 group-A CFS patients (81%) had elevated EBV early antibody, early antigen (diffuse), serum titers. A small group of six patients in the group-A EBV subset of CFS, additionally, had repetitive elevated-serum titers of antibody to the early lytic replicationencoded proteins, EBV dUTPase, and EBV DNA polymerase. The presence of these serum antibodies to EBV dUTPase and EBV DNA polymerase indicated EBV abortive lytic replication in these 6 CFS patients. None of 20 random control people (ageand sex-matched, with blood drawn at a commercial laboratory) had elevated serum titers of antibody to EBV dUTPase or EBV DNA polymerase (P , 0.01). This finding needs verification in a larger group of EBV CFS subset patients, but if corroborated, it may represent a molecular marker for diagnosing the EBV subset of CFS. We review evidence that EBV abortive lytic replication with unassembled viral proteins in the blood may be the same in infectious mononucleosis (IM) and a subset of CFS. EBV-abortive lytic replication in tonsil plasma cells is dominant in IM. No complete lytic virion is in the blood of IM or CFS patients. Complications of CFS and IM include cardiomyopathy and encephalopathy. Circulating abortive lytic-encoded EBV proteins (eg, EBV dUTPase, EBV DNA polymerase, and others) may be common to IM and CFS. The intensity and duration of the circulating EBV-encoded proteins might differentiate the IM and EBV subsets of CFS. Abortive lytic replication may be a pathogenic mechanism for EBV disease. EBV (HHV4) is a gamma herpesvirus composed of dsDNA about 170 Kb in length. For this discussion, there are early genes (including expressions of encoded proteins EBV dUTPase, DNA polymerase, and nuclear proteins) and late genes (including expressions of capsid and membrane proteins). Abortive infection infers incomplete virion expressions of either early or late proteins, but the virion is incomplete. The lytic virus infers a complete virion. The pathologic consequences of EBV abortive replication are currently being investigated by authors.