Epstein Barr virus (EBV) is a double-stranded DNA virus that infects B lymphocyte cells. It is in the herpesvirus family and was discovered in 1964. It can cause a variety of diseases and is spread mainly from saliva containing virus-infected epithelial cells. Close to 95% of adults throughout the world have been infected with EBV. It is a causative agent of infectious mononucleosis. Treatment is generally supportive care.
Epstein Barr virus is a herpesvirus with double-stranded DNA enclosed by proteins. The envelope of the virus has glycoproteins, which are important for attachment and entry into the host cells (B cells and epithelial cells). EBV targets B cells by utilizing their molecular machinery to replicate the viral genome. The virus causes B cells to differentiate into memory B cells, which then can move into the circulatory system, or become latent until a trigger causes reactivation.
The transmission of the Epstein Barr virus occurs in several ways, such as deep kissing or food-sharing. Increased levels of viral DNA are found in salivary secretions after the initial infection. Children can be infected after eating food that has already been chewed by an EBV infected individual. The transmission has occurred through stem cell and organ transplantation, as well as blood transfusion.
Nearly 95% of the world’s population of adults have been infected with the Epstein Barr virus. In the United States, children and adolescents between the ages of 6 to 19 years had an EBV prevalence of 66.5%. Children between 6-8 years of age had a prevalence of approximately 54%, while adolescents 18-19 years old had a prevalence of 82.9%. More females than males were infected, but the difference was minimal. Children and adolescents who identified as Mexican-American had a higher prevalence of Epstein Barr virus than non-Hispanic Blacks and Whites. There was a higher prevalence of Epstein Barr virus infection in children and adolescents who had larger households, lower household incomes, lower parental education, and who were born outside the U.S.
Worldwide prevalence rates of Epstein Barr virus vary. In England, the Epstein Barr virus prevalence rate for children ages 11 to 24 was 74.6%. Younger patients 11 to 14 years old had a lower prevalence rate of Epstein Barr virus when compared to older children. Young adults 22 to 24-year olds had 93% seropositivity. In a study population from Tehran, Iran, the seroprevalence of Epstein Barr virus IgG antibody was 81.4%. Almost 95% of the subjects over 40 years old were seropositive. The prevalence of seropositive subjects increased as age increased, except for in the infant population. Infants had elevated levels of Epstein Barr virus IgG antibodies that decreased as they aged, likely due to loss of maternal antibodies over time. In China, a study showed a prevalence rate of greater than 50% before 3 years of age, and over 90% by ages 8 to 9 years old.
One study found that the infection rates tend to increase between June and August, most likely due to increased human interaction during the summer months.
Determining if a patient has Epstein Barr virus requires a thorough history and physical. Infection with Epstein Barr virus can cause a variety of symptoms, ranging from asymptomatic to a spectrum of illnesses. In children, infection with Epstein Barr virus can often be asymptomatic or present with vague symptoms. Patients infected with Epstein Barr virus can have systemic manifestations including splenomegaly, lymphadenopathy, headache, malaise, fever, and sore throat. Patients may show symptoms for several months, with fatigue as the most common lingering complaint. In a study done by Rea et al., physical exam findings such as cervical lymphadenopathy and pharyngitis, were seen at six months after the initial infection in about one-quarter of the study group (n=140). Lab abnormalities such as lymphocytosis, with a presence of atypical lymphocytes, are most common. Liver function tests can also be abnormally elevated. In some patients, there was even a decline in functional and emotional status while they were sick that improved throughout the study period.
Determining if a patient has an infection due to Epstein Barr virus is usually most effective through serological testing. Atypical appearing lymphocytosis is most commonly present on peripheral smear. Heterophile antibody tests identify IgM antibodies against EBV. Heterophile antibody testing is a good initial test since it is inexpensive, fast, and has a sensitivity of 63-84% and specificity of 84 to 100%. The disadvantages of the heterophile antibody test include the possibility of a negative result in children, since they may not produce heterophile antibodies to EBV. Unfortunately, other disease processes can induce heterophile antibodies, or they may be present for over a year, causing a positive result unrelated to an acute EBV infection. Viral capsid antigen (VCA) IgM and IgG can be used to confirm the diagnosis. Elevated levels of VCA IgM antibodies detect an acute infection, while increased VCA IgG antibody levels indicate prior or chronic infection. Patients with EBV who were followed for 6 months showed VCA-IgM antibodies that subsided after a month and VCA-IgG that decreased over time.
Epstein Barr virus is treated symptomatically with medications that can reduce fever and pain. Some studies using antiviral medications for EBV treatment did show a decrease in the amount of virus shed in the oral cavity, but there was no improvement in overall symptoms. Corticosteroids are not therapeutic, but they can be beneficial in patients who develop airway compromise or autoimmune complications caused by EBV infection.
Several other diseases need to be considered as part of the differential diagnosis. Bacterial pharyngitis presents with a sore throat, cervical lymphadenopathy, pharyngeal swelling, and tonsillar exudates. Viral pharyngitis usually includes fatigue, fever, rhinorrhea, or conjunctivitis. Cytomegalovirus (CMV) is another virus in the Herpesviridae family that presents similarly to EBV with a sore throat, fevers, chills, elevated liver function tests, and fatigue. Splenomegaly and lymphadenopathy are less common CMV symptoms. Acute HIV infection is also on the differential. These patients present with fevers, muscle and joint pain, fatigue, headaches, and sometimes with lymphadenopathy and pharyngitis.
Epstein Barr virus has several associated complications. One dangerous complication is splenic rupture due to infectious mononucleosis. In one case study, splenic rupture occurred 6 days after symptoms of infection. It can be treated conservatively or surgically. Pain control and close monitoring are appropriate conservative management strategies reserved for hemodynamically stable patients. Another non-surgical management option is splenic artery embolization. The surgical option is splenectomy which requires post-operative immunizations, antibiotics, and close follow-up.
Another complication of infectious mononucleosis from EBV is airway obstruction from tonsillar edema of the pharyngeal tissues. Treatment of airway obstruction includes steroids, tracheotomy, or intubation. Airway obstruction is a rare (1-3.5% of cases) but an important complication of infectious mononucleosis that occurs mostly in children.
Acute acalculous cholecystitis is a complication that can be treated conservatively with pain medication and antiemetics. In some cases, patients elected to have laparoscopic cholecystectomy due to unbearable abdominal pain.
There are many other complications from Epstein Barr virus infection that can occur, such as myocarditis, encephalitis, hemophagocytic lymphohistiocytosis, pancreatitis, and autoimmune hemolytic anemia. EBV has also been implicated in causing lymphomas and nasopharyngeal cancers.
Infected patients should avoid sharing utensils, drinks, and kissing others since EBV is transmitted through saliva.
Patients in sports should be cleared by a clinician before resuming activities. A minimum of three weeks and full resolution of splenomegaly is standard to decrease the risk of splenic rupture.
Patients with EBV infection should be under the care of an interprofessional team including primary clinicians, nurses, and pharmacists to improve outcomes. As shown in a prospective study done by Rea et al., symptoms can last for several months (Level 5). Patients should be instructed on what symptoms to expect and for how long to expect them to last. They should be aware of possible complications and when to seek help. Patients who participate in sports need medical clearance and a minimum of three weeks before returning to activities to reduce the risk of splenic rupture.
|||Odumade OA,Hogquist KA,Balfour HH Jr, Progress and problems in understanding and managing primary Epstein-Barr virus infections. Clinical microbiology reviews. 2011 Jan; [PubMed PMID: 21233512]|
|||Womack J,Jimenez M, Common questions about infectious mononucleosis. American family physician. 2015 Mar 15; [PubMed PMID: 25822555]|
|||Dunmire SK,Verghese PS,Balfour HH Jr, Primary Epstein-Barr virus infection. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2018 May; [PubMed PMID: 29525635]|
|||Dowd JB,Palermo T,Brite J,McDade TW,Aiello A, Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6-19, 2003-2010. PloS one. 2013; [PubMed PMID: 23717674]|
|||Winter JR,Taylor GS,Thomas OG,Jackson C,Lewis JEA,Stagg HR, Predictors of Epstein-Barr virus serostatus in young people in England. BMC infectious diseases. 2019 Nov 28; [PubMed PMID: 31779585]|
|||Sharifipour S,Davoodi Rad K, Seroprevalence of Epstein-Barr virus among children and adults in Tehran, Iran. New microbes and new infections. 2020 Mar; [PubMed PMID: 32025310]|
|||Xiong G,Zhang B,Huang MY,Zhou H,Chen LZ,Feng QS,Luo X,Lin HJ,Zeng YX, Epstein-Barr virus (EBV) infection in Chinese children: a retrospective study of age-specific prevalence. PloS one. 2014; [PubMed PMID: 24914816]|
|||Grotto I,Mimouni D,Huerta M,Mimouni M,Cohen D,Robin G,Pitlik S,Green MS, Clinical and laboratory presentation of EBV positive infectious mononucleosis in young adults. Epidemiology and infection. 2003 Aug; [PubMed PMID: 12948368]|
|||Rea TD,Russo JE,Katon W,Ashley RL,Buchwald DS, Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. The Journal of the American Board of Family Practice. 2001 Jul-Aug; [PubMed PMID: 11458965]|
|||Fugl A,Andersen CL, Epstein-Barr virus and its association with disease - a review of relevance to general practice. BMC family practice. 2019 May 14; [PubMed PMID: 31088382]|
|||Vincent MT,Celestin N,Hussain AN, Pharyngitis. American family physician. 2004 Mar 15; [PubMed PMID: 15053411]|
|||Taylor GH, Cytomegalovirus. American family physician. 2003 Feb 1; [PubMed PMID: 12588074]|
|||Chu C,Selwyn PA, Diagnosis and initial management of acute HIV infection. American family physician. 2010 May 15; [PubMed PMID: 20507048]|
|||Barnwell J,Deol PS, Atraumatic splenic rupture secondary to Epstein-Barr virus infection. BMJ case reports. 2017 Jan 24; [PubMed PMID: 28119438]|
|||Glynn FJ,Mackle T,Kinsella J, Upper airway obstruction in infectious mononucleosis. European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 2007 Feb; [PubMed PMID: 17198326]|
|||Kakani S, Airway compromise in infectious mononucleosis: a case report. Cases journal. 2009 Aug 13; [PubMed PMID: 19918540]|
|||Young C,Lampe R, Primary Epstein-Barr Virus Infection in an Adolescent Female Complicated by Acute Acalculous Cholecystitis. Cureus. 2019 Jun 30; [PubMed PMID: 31501735]|
|||Rezkallah KN,Barakat K,Farrah A,Rao S,Sharma M,Chalise S,Zdunek T, Acute Acalculous Cholecystitis due to primary acute Epstein-Barr virus infection treated with laparoscopic cholecystectomy; a case report. Annals of medicine and surgery (2012). 2018 Nov; [PubMed PMID: 30364603]|
|||Watanabe M,Panetta GL,Piccirillo F,Spoto S,Myers J,Serino FM,Costantino S,Di Sciascio G, Acute Epstein-Barr related myocarditis: An unusual but life-threatening disease in an immunocompetent patient. Journal of cardiology cases. 2020 Apr; [PubMed PMID: 32256861]|
|||Akkoc G,Kadayifci EK,Karaaslan A,Atici S,Yakut N,Ocal Demir S,Soysal A,Bakir M, Epstein-Barr Virus Encephalitis in an Immunocompetent Child: A Case Report and Management of Epstein-Barr Virus Encephalitis. Case reports in infectious diseases. 2016; [PubMed PMID: 27213062]|
|||Mărginean MO,Molnar E,Chinceşan MI, Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in a small child: A case report. Medicine. 2020 Jan; [PubMed PMID: 32011461]|
|||Singh S,Khosla P, A rare case of acute pancreatitis and life-threatening hemolytic anemia associated with Epstein-Barr virus infection in a young healthy adult. Journal of infection and public health. 2016 Jan-Feb; [PubMed PMID: 26190854]|