Table 1
Source publication
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. The case: A 16-year-old, previously healthy girl presents with a several-day histo...
Similar publications
Infectious mononucleosis (glandular fever) is a viral disease that occurs with tonsillitis and lymph node syndrome, together with characteristic changes in the hemogram. Laboratory confirmation of the diagnosis is most frequently performed by serological analysis aimed to detect specific IgM antibodies to the EBV capsid antigen (anti EBV VCA IgM)....
Citations
... In some patients, however, acute complications can be severe or even life-threatening. These include hematological or neurological disorders in up to 50% and 5%, respectively, as well as splenic rupture or upper airway obstruction each in up to 1% of all IM patients [6]. Severe complications account for about 30 IM-associated deaths per year in the U.S. [7]. ...
... Moreover, EBV is a common trigger of hemophagocytic lymphohistiocytosis (EBV-HLH), a life-threatening manifestation of severe immune dysregulation [8,9]. After IM, protracted symptoms such as fatigue and post-exertional malaise (PEM) can last for months or even years [5][6][7][8], and EBV is a common trigger of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Post-infectious ME/CFS is a severe and complex neurological disease known to significantly compromise daily activities, including school attendance or working ability, as well as quality of life [10,11]. ...
Background
Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM).
Methods
We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset).
Results
All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (rs = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells.
Conclusions
All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.
... Te infected B lymphocytes become the major viral reservoirs and play important roles in viral life-long persistence in infected hosts. EBV infections not only lead to benign mononucleosis [30] but also cause malignancy, including the well-recognized nasopharyngeal carcinoma [31] and Burkitt lymphoma [32,33]. Strikingly, EBV DNA replication has been found to be signifcantly more active in ME/CFS patients than in healthy individuals [3], including the current patient. ...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem disabling disease with unclear etiology and pathophysiology, whose typical symptoms include prolonged debilitating recovery from fatigue or postexertional malaise (PEM). Disrupted production of adenosine triphosphate (ATP), the intracellular energy that fuels cellular activity, is a cause for fatigue. Here, we present a long-term case of ME/CFS: a 75-year-old Caucasian female patient, whose symptoms of ME/CFS were clearly triggered by an acute infection of the Epstein–Barr virus 24 years ago (mononucleosis). Before then, the patient was a healthy professional woman. A recent DNA sequence analysis identified missense variants of mitochondrial respiratory chain enzymes, including ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V). Protein subunits ATP6 and Cox1 are encoded by mitochondrial DNA outside of the nucleus: the Cox1 gene encodes subunit 1 of complex IV (CIV: cytochrome c oxidase) and the ATP6 gene encodes subunit A of complex V (CV: ATP synthase). CIV and CV are the last two of five essential enzymes that perform the mitochondrial electron transport respiratory chain reaction to generate ATP. Further analysis of the blood sample using transmission electron microscopy demonstrated abnormal, circulating, extracellular mitochondria. These results indicate that the patient had dysfunctional mitochondria, which may contribute directly to her major symptoms, including PEM and neurological and cognitive changes. Furthermore, the identified variants of ATP6 (ChrMT: 8981A > G; Q152R) and Cox1 (ChrMT: 6268C > T; A122V), functioning at a later stage of mitochondrial ATP production, may play a role in the abnormality of the patient’s mitochondria and the development of her ME/CFS symptoms.
... Infectious mononucleosis (IM) is usually a self-limited, benign lymphoproliferative disease caused by the Epstein-Barr virus (EBV). EBV is a gamma herpesvirus with a double-stranded DNA genome of about 172 kb [1]. In seroprevalence surveys, over 90% of adults worldwide are infected with this virus [1,2]. ...
... EBV is a gamma herpesvirus with a double-stranded DNA genome of about 172 kb [1]. In seroprevalence surveys, over 90% of adults worldwide are infected with this virus [1,2]. It most commonly affects the adolescent population, with a peak incidence in persons between 15 and 19 years (3.2-3.7 cases per 1000 persons) [1,3]. ...
... In seroprevalence surveys, over 90% of adults worldwide are infected with this virus [1,2]. It most commonly affects the adolescent population, with a peak incidence in persons between 15 and 19 years (3.2-3.7 cases per 1000 persons) [1,3]. EBV is transmitted predominantly through infected saliva during kissing and less commonly through sexual contact, blood transfusions, or organ transplantations [1,2,4]. ...
... Infectious mononucleosis (IM), caused by Epstein-Barr virus (EBV), is characterized by fever, sore throat, lymphadenopathy, and fatigue. While most cases of IM are self-limiting and resolve without complication, rare complications such as splenic rupture or infarction have been described in 0.1-0.5% of cases [1,2]. EBVassociated splenic infarction has been reported in 29 cases per our literature review, yet the mechanism by which it occurs remains unclear. ...
... Infectious mononucleosis (IM) is a self-limiting disease caused by acute infection with a variety of viruses, bacteria, and protozoa and typically presents with nonspecific systemic inflammatory symptoms, such as a fever, sore throat, lymphadenopathy, and malaise, often with liver damage and splenomegaly (1). This disease is also known as the "kissing disease," as the infection is transmitted primarily through contact with infected saliva (2). ...
... Epstein-Barr virus (EBV), also known as human herpesvirus-4, is a particularly common cause of IM and accounts for more than 90% of cases (3). Although more than 95% of the world population is reportedly infected with this virus (2,4), recent studies have demonstrated that the positivity rate tends to drop to nearly 50% in younger populations (5,6), raising concerns about the impact on the incidence of EBV-induced disorders (6). EBV is a doublestranded DNA virus belonging to the herpesvirus genus that primarily affects human lymphocyte B cells (2,4). ...
... Although more than 95% of the world population is reportedly infected with this virus (2,4), recent studies have demonstrated that the positivity rate tends to drop to nearly 50% in younger populations (5,6), raising concerns about the impact on the incidence of EBV-induced disorders (6). EBV is a doublestranded DNA virus belonging to the herpesvirus genus that primarily affects human lymphocyte B cells (2,4). In addition to causing IM as an acute manifestation, it has also been associated with malignancies, such as malignant lym-phoma and epithelial carcinoma, and autoimmune diseases, such as systemic lupus erythematosus and multiple sclerosis (4). ...
Sialadenitis has rarely been reported in patients with infectious mononucleosis (IM). Our patient was a 22-year-old man who presented with bilateral swelling of the parotid and submandibular glands, a fever, malaise, and splenomegaly. Laboratory tests revealed an increased percentage of atypical lymphocytes in the leukocyte fraction. Serological testing for antibodies against Epstein-Barr virus (EBV) revealed an acute infection pattern. The patient was diagnosed with sialadenitis associated with IM caused by EBV infection. With symptomatic treatment, the salivary gland swelling completely resolved within a week. This case suggests that EBV-induced IM should be included in the differential diagnosis of diffuse sialadenitis with elevated atypical lymphocyte counts.
... 9 About 50% of the population in industrialised nations acquire primary EBV infection at age 1-5 years when the probability of developing symptomatic disease is low. 10 Another large proportion of the population acquires primary infection during adolescence and early adulthood when symptomatic disease occurs in up to 70% of individuals. 11 A previous meta-analysis of cohort and case-control studies found that IM more than doubles the risk of MS (relative risk (RR) = 2.17, 95% confidence interval (CI) = 1.97-2.39; ...
Background
Epstein–Barr virus (EBV) is thought to be a necessary causative agent in the development of multiple sclerosis (MS). Infectious mononucleosis (IM), which occurs up to 70% of adolescents and young adults with primary EBV infection, appears to be a further risk factor but few studies have been highly powered enough to explore this association by time since IM diagnosis.
Objective
The objective was to quantify the risk of MS in individuals with IM compared with the general population, with particular focus on time since IM diagnosis.
Methods
In this retrospective cohort study using English national Hospital Episode Statistics from 2003 to 2023, patients with a hospital diagnosis of IM were compared with the general population for MS incidence.
Results
MS incidence in patients with IM was nearly three times higher than the general population after multivariable adjustment (adjusted hazard ratio = 2.8, 95% confidence interval (CI = 2.3–3.4), driven by strong associations at long time intervals (>5 years) between IM diagnosis and subsequent MS diagnosis.
Conclusion
While EBV infection may be a prerequisite for MS, the disease process of IM (i.e. the body’s defective immune response to primary EBV infection) seems to be, in addition, implicated over the long term.
... In pediatric populations, it often manifests as asymptomatic or presents with nonspecific symptoms. In contrast, adolescents and young adults frequently develop the clinical syndrome known as infectious mononucleosis (IM) [1,2]. Typically, IM starts with a sense of discomfort, headache, and a mild fever before progressing to more specific indications such as tonsillitis and/or pharyngitis, symmetrical swelling and sensitivity in the cervical lymph nodes, and moderate to high fever. ...
Primary Epstein-Barr virus (EBV) infection manifests with diverse clinical symptoms, occasionally resulting in severe complications. This scoping review investigates the rare occurrence of acute acalculous cholecystitis (AAC) in the context of primary EBV infection, with a focus on understanding its prevalence, clinical features, and underlying mechanisms. The study also explores EBV infection association with Gilbert syndrome, a condition that potentially exacerbates the clinical picture. Additionally, a case report of an 18-year-old female presenting with AAC and ascites secondary to EBV infection enhances the review. A comprehensive literature review was conducted, analyzing reported cases of AAC secondary to EBV infection. This involved examining patient demographics, clinical presentations, laboratory findings, and outcomes. The search yielded 44 cases, predominantly affecting young females. Common clinical features included fever, cervical lymphadenopathy, tonsillitis/pharyngitis, and splenomegaly. Laboratory findings highlighted significant hepatic involvement. The review also noted a potential link between AAC in EBV infection and Gilbert syndrome, particularly in cases with abnormal bilirubin levels. AAC is a rare but significant complication of primary EBV infection, primarily observed in young females, and may be associated with Gilbert syndrome. This comprehensive review underscores the need for heightened clinical awareness and timely diagnosis to manage this complication effectively.
... Disparities exist in the populations susceptible to EBV infection, with notable variations observed between industrialized and developing nations. The prevalence of EBV infection is higher among infants and young children in underdeveloped countries, whereas the prevalence is higher among older children and teenagers in industrialized countries [30]. IMN should be included in the differential diagnosis of KD and MIS-C due to elevated inflammatory marker levels and similar presentations, including high fever [31]. ...
This study examined the distinctions between multisystem inflammatory syndrome associated with coronavirus disease 2019, Kawasaki disease, and infectious mononucleosis. These three inflammatory disorders have commonalities according to clinical and laboratory results, particularly in relation to eosinophil levels. In this retrospective, single-center study, we documented the examination records (acute phase reactants and complete blood count) and clinical and cardiological findings of 130 patients diagnosed with multisystem inflammatory syndrome, Kawasaki disease, and infectious mononucleosis. These patients were treated and received follow-up care in our hospital from March 12, 2020, to September 13, 2022, as per the hospital records. Statistical analyses were performed using NCSS 2007, version 1 software. Eosinopenia was more prevalent in children with multisystem inflammatory syndrome than in those with Kawasaki disease, who showed normal or elevated eosinophil counts. The eosinophil counts in patients with infectious mononucleosis typically fell within the normal range. Our study found no correlation between the eosinophil counts and cardiac involvement in pediatric patients with either condition. These findings indicate a higher prevalence of eosinopenia in patients with multisystem inflammatory syndrome, irrespective of cardiac involvement, than in those with Kawasaki disease. Despite similarities in clinical findings, Kawasaki disease and multisystem inflammatory syndrome in children necessitate further studies for distinct characteristic elucidation.
... It has been reported in the literature that there are cases of fulminant hepatitis due to acute EBV infection. [2][3][4][5][6][7] Herein, a case of acute cholestatic hepatitis due to EBV is described to remind EBV infection in the differential diagnosis of cholestatic hepatitis. ...
... Studies on EBV show that 90-95% of adults have encountered the virus at some point in their lifetime. 2,3 It is known that the virus, which remains in the B lymphocytes and tonsil crypt epithelial cells of seropositive individuals for life, is transmitted to seronegative people through the infected person's secretions. 4,5 The most common symptoms in patients are nonspecific complaints such as fatigue, loss of appetite, muscle pain and headache. ...
... [16][17][18][19] As in our patient, anaemia and thrombocytopenia can be seen in complete blood count in infectious mononucleosis cases; however, lymphocytosis and monocytosis are frequently seen in the blood picture. 3 In addition, lymphocytes known as "Downey cells" can be seen in the peripheral blood smear, with blue cytoplasms, large, and adhered around the erythrocytes. ...
Cholestatic hepatitis is a rare complication of acute Epstein-Barr virus (EBV) infection. Here, we presented a case of acute cholestatic hepatitis secondary to acute infectious mononucleosis, who presented with complaints of abdominal pain, yellowing of the eyes and body, itching, widespread body pain, fever, nausea and vomiting. It was emphasized that EBV infection should also be considered in the differential diagnosis of cholestatic hepatitis etiology.
... While there have been a few reports of primary EBV infection presenting with neurological signs in children, this is uncommon [6,12]. Although some cases of EBV encephalitis have been reported in adults, these have occurred during coinfections with other central nervous system infections, superimposed on an underlying neurocognitive disorder, or in immunocompromised states [13][14][15][16][17]. Acyclovir treatment for patients diagnosed with EBV encephalitis is not recommended [18]. ...
Epstein-Barr virus (EBV) encephalitis is a rare complication of EBV infection, with most cases described in children. Although some cases of EBV encephalitis have been reported in adults, they have occurred in the presence of other central nervous system infections, superimposed on an underlying neurocognitive disorder, or in immunocompromised states. We present herein a rare case of rapidly progressive EBV encephalitis in an adult male with HIV infection on highly active antiretroviral therapy (HAART) with no pre-existing neurocognitive symptoms. A 52-year-old African American man with HIV infection on HAART presented with acute altered mental status and weakness. On admission, he had normal muscle tone and reflexes, with no signs of meningism. Head CT without contrast showed no acute intracranial pathology. Blood and urine cultures were negative. CSF analysis was suggestive of a viral infection. Viral studies were positive only for EBV DNA by PCR in CSF. The patient received IV acyclovir for two weeks, followed by four weeks of oral valacyclovir with full recovery. Clinicians should consider a diagnosis of EBV encephalitis in HIV-positive patients on HAART who present with acute altered mental status. Treatment with antiviral therapy should be considered in patients with EBV encephalitis.
