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.[2] Patients infected with Epstein Barr virus can have systemic manifestations including splenomegaly, lymphadenopathy, headache, malaise, fever, and sore throat.[8] 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.[9]

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.[1] 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%.[2][10] 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.[1][3] 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.[1] 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.[9]

Epstein Barr virus is treated symptomatically with medications that can reduce fever and pain.[1] 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.[2] Corticosteroids are not therapeutic, but they can be beneficial in patients who develop airway compromise or autoimmune complications caused by EBV infection.[1]

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.[11] 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.[12] 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.[13]

Infectious mononucleosis caused by Epstein Barr virus is a self-limiting disease with a relatively good prognosis, as most patients will improve over time.[9] However, there are complications from having EBV infection, which vary in frequency.[1]

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.[14] 

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.[2][15][16]

Acute acalculous cholecystitis is a complication that can be treated conservatively with pain medication and antiemetics.[17][18] In some cases, patients elected to have laparoscopic cholecystectomy due to unbearable abdominal pain.[18]

There are many other complications from Epstein Barr virus infection that can occur, such as myocarditis, encephalitis, hemophagocytic lymphohistiocytosis, pancreatitis, and autoimmune hemolytic anemia.[19][20][21][22] EBV has also been implicated in causing lymphomas and nasopharyngeal cancers.[1]

Infected patients should avoid sharing utensils, drinks, and kissing others since EBV is transmitted through saliva.[1]

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.[2]

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).[9] 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.[2]