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A Epstein-Barr Virus Infectious MononucleosisA  A more recent article on this topic is available.
Infectious mononucleosis is a clinical syndrome caused by Epstein-Barr virus (EBV) that is particularly common in adolescents and children. An atypical lymphocytosis of at least 20 percent or atypical lymphocytosis of at least 10 percent plus lymphocytosis of at least 50 percent strongly supports the diagnosis, as does a positive heterophile antibody test.
Typical features of infectious mononucleosis include fever, pharyngitis, adenopathy, malaise, and an atypical lymphocytosis. In an acute infection, heterophile antibodies that agglutinate sheep erythrocytes are produced. HSV-1 often causes sores (lesions) inside the mouth, such as cold sores (fever blisters), or infection of the eye (especially the conjunctiva and cornea).
False-negative results of heterophile antibody tests are relatively common early in the course of infection.
Given the lack of evidence for bed rest in many other conditions, it seems sensible to recommend that patients base their return to usual activities on their energy levels.A meta-analysis22 of five randomized controlled trials involving 339 patients found that patients who took acyclovir (Zovirax) had less oropharyngeal shedding at the end of therapy, but this treatment provided no significant or consistent clinical benefit and is therefore not recommended.
Patients with negative results may have another infection, such as toxoplasmosis, streptococcal infection, cytomegalovirus infection, or another viral infection. Another trial found no significant benefit from the use of ranitidine (Zantac) in patients with infectious mononucleosis.23Corticosteroids have been advocated for the treatment of patients with infectious mononucleosis,8 and some early studies24,25 seemed to show a benefit from these agents with regard to normalization of temperature and laboratory values. Symptomatic treatment, the mainstay of care, includes adequate hydration, analgesics, antipyretics, and adequate rest. However, diagnostic testing is warranted in pregnant women because toxoplasmosis and acute human immuno-deficiency virus (HIV) and CMV infections are associated with significant pregnancy complications.Symptoms of acute HIV infection can resemble those of infectious mononucleosis.
Bed rest should not be enforced, and the patient’s energy level should guide activity. If acute HIV infection is suspected, a quantitative polymerase chain reaction test should be performed. A more recent and better-designed study26 found no benefit from a combination of acyclovir and prednisone. The likelihood of childhood infection is higher among those with lower socioeconomic status. Herpes simplex virus 2 (HSV-2) is usually, but not always, sexually transmitted.


Corticosteroids, acyclovir, and antihistamines are not recommended for routine treatment of infectious mononucleosis, although corticosteroids may benefit patients with respiratory compromise or severe pharyngeal edema. In a small, double-blind, randomized trial27 of 40 children with suspected infectious mononucleosis (33 of whom had confirmed infectious mononucleosis), those who were given oral dexamethasone (0.3 mg per kg) had less pain at 12 hours but not at 24, 48, and 72 hours. Patients with infectious mononucleosis should be withdrawn from contact or collision sports for at least four weeks after the onset of symptoms. Fatigue, myalgias, and need for sleep may persist for several months after the acute infection has resolved. Two other studies29,30 reported GABHS pharyngitis rates of only 3 to 4 percent in studies of more than 100 patients.
The true rate of concomitant infectious mononucleosis and GABHS pharyngitis probably lies between these extremes and may depend on the time of year.
It seems prudent to obtain a rapid strep test in patients with infectious mononucleosis and to treat them with antibiotics only if the strep test result is positive. Amoxicillin and ampicillin should not be used because they may cause a morbilliform rash in patients with infectious mononucleosis.Patients with infectious mononucleosis are likely to have splenomegaly. Although most patients do not have a palpable spleen on physical examination, a study31 of 29 patients who were hospitalized with infectious mononucleosis (and who therefore may have had more severe disease) found that all patients had splenomegaly on ultrasound examination and that one half of them had hepatomegaly. Sometimes, young children also can get the disease. HSV can infect a fetus and cause abnormalities.
A mother who is infected with HSV may transmit the virus to her newborn during vaginal delivery, especially if the mother has an active infection at the time of delivery.
These data suggest that patients should be kept out of athletics for at least three to four weeks and until they are asymptomatic.
However, 60 - 80% of HSV infections acquired by newborns occur in women who do NOT have symptoms of HSV infection or a history of genital HSV infection. It's possible for the virus to be transmitted even when there are no symptoms or visible sores.
Some experts suggest a longer duration of restricted activity of five to six weeks35 or even six months,36 although data from natural history studies do not necessarily support these recommendations. Although they are relatively specific, heterophile antibody tests are somewhat insensitive, particularly in the first weeks of illness.
Because the physical examination is so insensitive, ultrasound imaging to assess the size of the spleen at three weeks may be a better guide for determining whether a patient should return to athletics.37 The cost to prevent one traumatic rupture probably is well over $1 million when this strategy is used, given that the risk of rupture overall is one in 1,000, the risk of rupture beyond four weeks is considerably less, about one half of ruptures are atraumatic, and the cost of an ultrasound scan is several hundred dollars.


Between 9 and 22 percent of patients reported persistent fatigue or hypersomnia six months after clinical infectious mononucleosis, compared with zero to 6 percent of patients following uncomplicated upper respiratory infection.5 The best study13 of the natural history of infectious mononucleosis followed 150 patients for six months.
The infection may be more severe and last longer in people who have a condition that weakens the immune system. Once an infection occurs, the virus spreads to nerve cells and stays in the body for the rest of a person's life.
Antibody to Epstein-Barr nuclear antigen (EBNA), while typically not detectable until six to eight weeks after the onset of symptoms, can help distinguish between acute and previous infections. In this study, sore throat, fever, headache, rash, cough, and nausea largely had resolved one month after the onset of symptoms. If EBNA is positive in a patient with acute symptoms and suspected infectious mononucleosis, previous infection is suggested. Fatigue resolved more slowly (77 percent initially, 28 percent at one month, 21 percent at two months, and 13 percent at six months), as did sleeping too much (45 percent initially, 18 percent at one month, 14 percent at two months, and 9 percent at six months) and sore joints (23 percent initially, 15 percent at one month, 6 percent at two months, and 9 percent at six months).13 This study also followed functional status over the same six-month period and found that patients required about two months to achieve a stable level of recovery. The association between EBV infection and chronic fatigue syndrome remains uncertain, and a positive IgG test for EBV does not imply a causal relationship.
Patients between 10 and 30 years of age with sore throat, fever, and significant anterior cervical adenopathy, fatigue, posterior cervical adenopathy, inguinal adenopathy, palatal petechiae, or splenomegaly are at high risk for infectious mononucleosis. A positive result of a heterophile antibody test also is strong evidence in favor of a diagnosis of infectious mononucleosis. A negative result of an antibody test, particularly during the first week of illness, may indicate that the patient does not have infectious mononucleosis. However, it also could be a false-negative result or could indicate that the patient has an infectious mononucleosis–like syndrome caused by CMV or toxo-plasmosis. The patient should be treated symptomatically, and if the patient does not clinically improve within five to seven days, a second heterophile antibody test should be performed. If an accurate diagnosis is urgently required (for example, in a competitive athlete who wants to return to competition as soon as possible), a VCA-IgM test may be selected.



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