|
Infectious
mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus
type 4), characterized by fatigue, fever, pharyngitis, and lymphadenopathy.
Fatigue may persist weeks or months. Severe complications, including splenic
rupture and neurologic syndromes, occasionally occur. Diagnosis
is clinical or with heterophil antibody testing. Treatment is supportive.
Etiology
and Pathophysiology
EBV is a herpesvirus that infects 50% of children before age 5. Its host is humans. After initial replication in the nasopharynx, the virus infects B cells, which are induced to secrete immunoglobulins, including heterophil antibodies. Morphologically abnormal (atypical) lymphocytes develop, mainly from CD8 + T cells.
After primary infection, EBV remains within the host, primarily in B cells, for life and undergoes intermittent asymptomatic shedding from the oropharynx. It is detectable in oropharyngeal secretions of 15 to 25% of healthy EBV-seropositive adults. Shedding increases in frequency and titer in immunocompromised patients (eg, organ allograft recipients, HIV-infected people).
EBV has not been recovered from environmental sources and is not very contagious. Transmission may occur by transfusion of blood products but much more frequently occurs by kissing between an uninfected and an EBV-seropositive person who is shedding the virus asymptomatically. Only about 5% of patients acquire EBV from someone who has acute infection. Early childhood transmission occurs more frequently among lower socioeconomic groups and in crowded conditions.
EBV is statistically associated with and likely has a causal role in Burkitt's lymphoma, certain B-cell tumors in immunocompromised patients, and nasopharyngeal carcinoma. EBV does not cause chronic fatigue syndrome. However, it may occasionally cause a syndrome of fever, interstitial pneumonitis, pancytopenia, and uveitis (ie, chronic active EBV).
Symptoms and Signs
In most young children, primary EBV infection is asymptomatic. Symptoms of infectious mononucleosis develop most often in older children and adults.
The incubation period is about 30 to 50 days. Usually, fatigue develops initially, lasting several days to a week or longer, followed by fever, pharyngitis, and adenopathy. However, some of these symptoms may not develop. Fatigue can last months, but is usually maximal in the first 2 to 3 wk. Fever usually peaks in the afternoon or early evening, with a temperature around 39.5° C, although it may reach 40.5° C. When fatigue and fever predominate (the so-called typhoidal form), onset and resolution may be much slower. Pharyngitis may be severe, painful, and exudative and may resemble streptococcal pharyngitis. Adenopathy is usually symmetric and may involve any group of nodes, particularly the anterior and posterior cervical chains. Adenopathy may be the only manifestation.
Splenomegaly, which occurs in about 50% of cases, is maximal during the 2nd and 3rd wk and usually produces only a barely palpable splenic tip. Mild hepatomegaly and hepatic percussion tenderness may occur. Less frequent findings include maculopapular eruptions, jaundice, periorbital edema, and palatal enanthema.
Complications:
Although recovery is usually complete, complications may be dramatic.
Neurologic complications include encephalitis, seizures, Guillain-Barré syndrome, peripheral neuropathy, aseptic meningitis, myelitis, cranial nerve palsies, and psychosis. Encephalitis may present with cerebellar dysfunction or it may be global and rapidly progressive, similar to herpes simplex encephalitis, but usually is self-limited.
Hematologic complications are usually self-limited. They include granulocytopenia, thrombocytopenia, and hemolytic anemia. Transient mild granulocytopenia or thrombocytopenia occurs in about 50% of patients; severe cases, associated with bacterial infection or bleeding, occur less frequently. Hemolytic anemia is often due to anti-i–specific antibodies.
Splenic rupture can cause severe consequences. It can result from splenic enlargement and capsular swelling, which are maximal 10 to 21 days after presentation. A history of trauma is present only about half of the time. Rupture is usually painful but occasionally causes painless hypotension. Treatment is discussed in Spleen Disorders: Splenic Injury.
Respiratory complications include, rarely, upper airway obstruction due to pharyngeal or paratracheal lymphadenopathy; respiratory complications may respond to corticosteroids. Clinically silent interstitial pulmonary infiltrates occur mostly in children and are usually visible on x-rays.
Hepatic complications include elevated aminotransferase levels (about 2 to 3 times normal, returning to baseline over 3 to 4 wk), which occur in about 95% of cases. If jaundice or more severe enzyme elevations occur, other causes of hepatitis should be investigated.
Overwhelming infection with EBV occurs sporadically but may cluster in families, particularly those with X-linked lymphoproliferative syndrome (see also Immunodeficiency Disorders: X-linked Lymphoproliferative Syndrome). These survivors of primary EBV infection are at risk for developing agammaglobulinemia or lymphoma.
Diagnosis
Infectious mononucleosis should be suspected in patients with typical symptoms and signs. Exudative pharyngitis, anterior cervical lymphadenopathy, and fever may be clinically indistinguishable from those caused by group A β-hemolytic streptococci; however, posterior cervical or generalized adenopathy or hepatosplenomegaly suggest infectious mononucleosis. Moreover, detection of streptococci in the oropharynx does not exclude infectious mononucleosis. Cytomegalovirus (CMV) may produce a syndrome similar to infectious mononucleosis, with atypical lymphocytosis as well as hepatosplenomegaly and hepatitis but usually not with severe pharyngitis. Toxoplasmosis, hepatitis B, rubella, primary HIV infection, or atypical lymphocytes associated with adverse drug reactions can also produce infectious mononucleosis–like syndromes, but these can usually be distinguished by other clinical features.
Laboratory diagnosis usually involves a CBC and a heterophil antibody test. Lymphocytes that are morphologically atypical account for up to 80% of the WBCs. Although individual lymphocytes may resemble leukemic lymphocytes, lymphocytes are heterogeneous, which is unlikely with leukemia.
Heterophil antibodies are measured using various card-agglutination (monospot) tests. The antibodies are present in only 50% of patients < 5 yr but are present in 90% of adolescents and adults with primary EBV infection. The titer and prevalence of heterophil antibodies rise during the 2nd and 3rd wk of illness. Thus, if the diagnosis is strongly suspected but the heterophil antibody test is negative, repeating the test after 7 to 10 days of symptoms is reasonable. If the test remains negative, then antibodies to EBV should be measured. If EBV antibody titers do not reveal acute EBV infection, then a heterophil antibody-negative infectious mononucleosis–like syndrome such as CMV should be considered. Heterophil antibodies may persist 6 to 12 mo after recovery.
In children ≤ 4 yr, in whom heterophil antibodies may never be detectable, IgM antibodies to the EBV viral capsid antigen (VCA) indicate primary EBV infection. These antibodies disappear within 3 mo after infection. Only some laboratories have the capability to measure them. IgG EBV-VCA antibodies persist for life in high titers and do not discriminate between acute and past infection.
Prognosis
and Treatment
Infectious mononucleosis is usually self-limited. Duration of illness varies; the acute phase lasts about 2 wk. Generally, 20% of patients can return to school or work within 1 wk and 50% within 2 wk. Fatigue may persist for several more weeks, or, in 1 to 2% of cases, for months. Death occurs in < 1%, mostly due to complications (eg, encephalitis, splenic rupture, airway obstruction).
Treatment is supportive. Patients are encouraged to rest during the acute phase but should quickly resume activity when fever, pharyngitis, and malaise abate. To prevent splenic rupture, heavy lifting and contact sports should be avoided for 1 mo after presentation and until splenomegaly (which can be monitored by ultrasound) resolves.
Although corticosteroids hasten defervescence and relieve pharyngitis, they should not generally be used in uncomplicated disease. Corticosteroids can be helpful for complications such as impending airway obstruction, severe thrombocytopenia, and hemolytic anemia. Although oral or IV acyclovir decreases oropharyngeal shedding of EBV, there is no convincing evidence to warrant its clinical use.
Last full review/revision November 2005
Content last modified November 2005
| 
