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Clinics in Laboratory Medicine Sep 2021Lymphadenitis in the pediatric population frequently is benign and self-limited, often caused by infections. In children with refractory symptoms, lymph node biopsy may... (Review)
Review
Lymphadenitis in the pediatric population frequently is benign and self-limited, often caused by infections. In children with refractory symptoms, lymph node biopsy may be indicated to rule out malignancy or obtain material for culture. Acute bacterial infections typically show a suppurative pattern of necrosis with abscess formation. Viral infections are associated with nonspecific follicular and/or paracortical hyperplasia. Granulomatous inflammation is associated with bacterial, mycobacterial, and fungal infections. Toxoplasma lymphadenitis displays follicular hyperplasia, monocytoid B-cell hyperplasia, and clusters of epithelioid histiocytes. Autoimmune and noninfectious inflammatory disorders are included in differential diagnosis of lymphadenitis. Infectious mononucleosis and Kikuchi-Fujimoto lymphadenitis may mimic Hodgkin and non-Hodgkin lymphomas.
Topics: B-Lymphocytes; Biopsy; Child; Diagnosis, Differential; Humans; Hyperplasia; Lymphadenopathy
PubMed: 34304774
DOI: 10.1016/j.cll.2021.04.001 -
American Family Physician Jan 2023Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and... (Review)
Review
Infectious mononucleosis is a viral syndrome characterized by fever, pharyngitis, and posterior cervical lymphadenopathy. It is usually caused by Epstein-Barr virus and most often affects adolescents and young adults 15 to 24 years of age. Primary transmission is through close personal contact with a person who is infected, particularly their saliva. Cost-effective, efficient initial laboratory testing for acute infectious mononucleosis includes complete blood count with differential (to assess for greater than 40% lymphocytes and greater than 10% atypical lymphocytes) and a rapid heterophile antibody test. The heterophile antibody test has a sensitivity of 87% and specificity of 91% but can have a false-negative result in children younger than five years and in adults during the first week of illness. The presence of elevated liver enzymes increases clinical suspicion for infectious mononucleosis in the setting of a negative heterophile antibody test result. Epstein-Barr viral capsid antigen-antibody testing is more sensitive and specific but more expensive and takes longer to process than the rapid heterophile antibody test. Treatment of infectious mononucleosis is supportive; routine use of antivirals and corticosteroids is not recommended. Current guidelines recommend that patients with infectious mononucleosis not participate in athletic activity for three weeks from onset of symptoms. Shared decision-making should be used to determine the timing of return to activity. Immunosuppressed populations are at higher risk of severe disease and significant morbidity. Epstein-Barr virus infection has been linked to nine types of cancer, including Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma, and some autoimmune diseases.
Topics: Adolescent; Child; Humans; Antibodies, Heterophile; Antibodies, Viral; Autoimmune Diseases; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Infectious Mononucleosis
PubMed: 36689975
DOI: No ID Found -
Current Pediatric Reviews 2024Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and... (Review)
Review
BACKGROUND
Infectious mononucleosis is common among adolescents and young adults. Although the majority of cases resolve spontaneously, life-threatening manifestations, and complications have been recognised.
OBJECTIVE
The purpose of this article is to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of infectious mononucleosis.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
Topics: Adolescent; Young Adult; Humans; Infectious Mononucleosis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Splenomegaly; Antibodies, Heterophile; Splenic Rupture
PubMed: 37526456
DOI: 10.2174/1573396320666230801091558 -
Frontiers in Immunology 2020Epstein-Barr Virus (EBV) is an extremely successful human herpes virus, which infects essentially all human beings at some time during their life span. EBV infection and... (Review)
Review
Epstein-Barr Virus (EBV) is an extremely successful human herpes virus, which infects essentially all human beings at some time during their life span. EBV infection and the associated immune response results in production of antibodies (seroconversion), which occurs mainly during the first years of life, but may also happen during adolescence or later in life. Infection of adolescents can result in infectious mononucleosis, an acute serious condition characterized by massive lymphocytosis. Transmission of EBV mainly occurs through saliva but can rarely be spread through semen or blood, e.g. through organ transplantations and blood transfusions. EBV transmission through oral secretions results in infection of epithelial cells of the oropharynx. From the epithelial cells EBV can infect B cells, which are the major reservoir for the virus, but other cell types may also become infected. As a result, EBV can shuttle between different cell types, mainly B cells and epithelial cells. Moreover, since the virus can switch between a latent and a lytic life cycle, EBV has the ability to cause chronic relapsing/reactivating infections. Chronic or recurrent EBV infection of epithelial cells has been linked to systemic lupus erythematosus and Sjögren's syndrome, whereas chronic/recurrent infection of B cells has been associated with rheumatoid arthritis, multiple sclerosis and other diseases. Accordingly, since EBV can shuttle between epithelial cells and B cells, the systemic autoimmune diseases often occur as overlapping syndromes with symptoms and characteristic autoantibodies (e.g. antinuclear antibodies and rheumatoid factors) reflecting epithelial and/or B cell infection.
Topics: Animals; Autoimmune Diseases; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans
PubMed: 33488588
DOI: 10.3389/fimmu.2020.587380 -
World Journal of Clinical Cases Jun 2023Kikuchi-Fujimoto disease, a rare form of necrotizing lymphadenitis, is an uncommon, benign, self-limiting disorder of obscure etiology. It affects mostly young adults of... (Review)
Review
Kikuchi-Fujimoto disease, a rare form of necrotizing lymphadenitis, is an uncommon, benign, self-limiting disorder of obscure etiology. It affects mostly young adults of both genders. Clinically, it presents with fever and lymphadenopathy of a firm to rubbery consistency frequently involving cervical lymph nodes while weight loss, splenomegaly, leucopenia, and elevated erythrocyte sedimentation rate feature in severely affected patients. Cutaneous involvement occurs in about 30%-40% of cases as facial erythema and nonspecific erythematous papules, plaques, acneiform or morbilliform lesions of great histologic heterogeneity. Both Kikuchi-Fujimoto disease and systemic lupus erythematosus share an obscure and complex relationship as systemic lupus erythematosus may occasionally precede, develop subsequently, or sometimes be associated concurrently with Kikuchi-Fujimoto disease. It is often mistaken for non-Hodgkin lymphoma while lupus lymphadenitis, cat-scratch disease, Sweet's syndrome, Still's disease, drug eruptions, infectious mononucleosis, and viral or tubercular lymphadenitis are other common differentials. Fine needle aspiration cytology mostly has features of nonspecific reactive lymphadenitis and immunohistochemistry studies usually show variable features of uncertain diagnostic value Since its diagnosis is exclusively from histopathology, it needs to be evaluated more carefully; an early lymph node biopsy will obviate the need for unnecessary investigations and therapeutic trials. Its treatment with systemic corticosteroids, hydroxychloroquine, or antimicrobial agents mostly remains empirical. The article reviews clinicoepidemiological, diagnostic, and management aspects of KFD from the perspective of practicing clinicians.
PubMed: 37383134
DOI: 10.12998/wjcc.v11.i16.3664 -
British Journal of Biomedical Science Jul 2021EBV is the sole causative agent of the acute illness in humans described either as infectious mononucleosis (IM), or glandular fever. IM, when not clinically silent, can... (Review)
Review
EBV is the sole causative agent of the acute illness in humans described either as infectious mononucleosis (IM), or glandular fever. IM, when not clinically silent, can present in patients with at least two of the classic triad of symptoms of fever, pharyngitis, and lymphadenopathy. Challenges for the clinician arise when atypical cases present. Early, accurate and informed laboratory test results are vital for diagnosis, appropriate treatment, and management. A key challenge for the practitioner, particularly in cases where the illness can present atypically, is distinguishing bacterial tonsillitis infections from early acute IM. The ability to draw on timely, clear, and insightful laboratory results to distinguish viral from bacterial infection is vital. Correct and prompt diagnosis of IM can help prevent the unnecessary administration of antibiotics and mitigate the need for other expensive exploratory tests in cases of IM that present with splenomegaly, lymphadenopathy, or suspect haematological conditions. Good communication between the requesting clinician and those carrying out the investigative process, and between the different laboratory departments involved, is good practice and would ultimately benefit the patient. This communication will comprehensively review the aetiology, clinical presentation, and laboratory findings in IM with a view to promoting further research and so derive a standard diagnostic algorithm of the condition.
Topics: Algorithms; Decision Support Techniques; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Infectious Mononucleosis; Predictive Value of Tests; Prognosis; Virology
PubMed: 33721513
DOI: 10.1080/09674845.2021.1903683 -
Frontiers in Immunology 2021Epstein-Barr virus (EBV) is the first human tumor virus discovered and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. Each year EBV... (Review)
Review
Epstein-Barr virus (EBV) is the first human tumor virus discovered and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. Each year EBV associated cancers account for over 200,000 new cases of cancer and cause 150,000 deaths world-wide. EBV is also the primary cause of infectious mononucleosis, and up to 70% of adolescents and young adults in developed countries suffer from infectious mononucleosis. In addition, EBV has been shown to play a critical role in the pathogenesis of multiple sclerosis. An EBV prophylactic vaccine that induces neutralizing antibodies holds great promise for prevention of EBV associated diseases. EBV envelope proteins including gH/gL, gB and gp350 play key roles in EBV entry and infection of target cells, and neutralizing antibodies elicited by each of these proteins have shown to prevent EBV infection of target cells and markedly decrease EBV titers in the peripheral blood of humanized mice challenged with lethal dose EBV. Recent studies demonstrated that immunization with the combination of gH/gL, gB and/or gp350 induced markedly increased synergistic EBV neutralizing activity compared to immunization with individual proteins. As previous clinical trials focused on gp350 alone were partially successful, the inclusion of gH/gL and gB in a vaccine formulation with gp350 represents a promising approach of EBV prophylactic vaccine development. Therapeutic EBV vaccines have also been tested clinically with encouraging results. Immunization with various vaccine platforms expressing the EBV latent proteins EBNA1, LMP1, and/or LMP2 promoted specific CD4+ and CD8+ cytotoxic responses with anti-tumor activity. The addition of EBV envelope proteins gH/gL, gB and gp350 has the potential to increase the efficacy of a therapeutic EBV vaccine. The immune system plays a critical role in the control of tumors, and immune cell therapy has emerged as a promising treatment of cancers. Adoptive T-cell therapy has been successfully used in the prevention and treatment of post-transplant lymphoproliferative disorder. Chimeric antigen receptor T cell therapy and T cell receptor engineered T cell therapy targeting EBV latent proteins LMP1, LMP2 and/or EBNA1 have been in development, with the goal to increase the specificity and efficacy of treatment of EBV associated cancers.
Topics: Animals; Epitopes; Epstein-Barr Virus Infections; Genetic Therapy; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; T-Lymphocytes; Vaccination; Vaccine Development; Viral Proteins; Viral Vaccines
PubMed: 34691042
DOI: 10.3389/fimmu.2021.734471 -
Nature Reviews. Neurology Mar 2023Epidemiological studies have provided compelling evidence that multiple sclerosis (MS) is a rare complication of infection with the Epstein-Barr virus (EBV), a... (Review)
Review
Epidemiological studies have provided compelling evidence that multiple sclerosis (MS) is a rare complication of infection with the Epstein-Barr virus (EBV), a herpesvirus that infects more than 90% of the global population. This link was long suspected because the risk of MS increases markedly after infectious mononucleosis (symptomatic primary EBV infection) and with high titres of antibodies to specific EBV antigens. However, it was not until 2022 that a longitudinal study demonstrated that MS risk is minimal in individuals who are not infected with EBV and that it increases over 30-fold following EBV infection. Over the past few years, a number of studies have provided clues on the underlying mechanisms, which might help us to develop more targeted treatments for MS. In this Review, we discuss the evidence linking EBV to the development of MS and the mechanisms by which the virus is thought to cause the disease. Furthermore, we discuss implications for the treatment and prevention of MS, including the use of antivirals and vaccines.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Multiple Sclerosis; Longitudinal Studies; Antibodies, Viral
PubMed: 36759741
DOI: 10.1038/s41582-023-00775-5