Mononucleosis (Epstein–Barr)
B. Denise Hemby and Theresa M. Campo
Definition
A.Infectious mononucleosis is an acute, infectious viral disease caused by Epstein–Barr virus (EBV), with four classic symptoms: fever, pharyngitis, fatigue, and lymphadenopathy. The spread is via intimate contact between susceptible persons and asymptomatic EBV shedders through the passage of bodily fluids, primarily saliva.
B.Oral shedding may occur for 6 months after the onset of symptoms prior to its latency phase.
C.Epstein–Barr is not related to chronic fatigue syndrome (CFS); however, the fatigue related to EBV may last several months.
Incidence
A.Antibodies to EBV have been demonstrated in all population groups with a worldwide distribution. Approximately 90% to 95% of adults are EBV-seropositive.
Pathogenesis
A.EBV (human herpesvirus [HHV]-4) is the primary agent of infectious mononucleosis. EBV persists asymptomatically for life in nearly all adults and is associated with the development of B-cell lymphomas, T-cell lymphomas, and Hodgkin’s lymphoma in certain patients.
B.The incubation period is 1 to 2 months with an average of 11 days; it is communicable during the acute phase, which may be prolonged. Acute symptoms resolve in 1 to 2 weeks. Pharyngeal excretion may persist for up to 18 months following clinical recovery. It is estimated that once infected with EBV, the virus may be intermittently shed in the oropharynx for decades.
C.EBV has also been isolated both in the cervix and in male seminal fluid, suggesting the possibility of sexual transmission.
D.EBV has also been noted in breast milk.
Predisposing Factors
A.Exposure through oropharyngeal secretions (kiss, cough, shared food).
B.Roommates.
C.Intrafamilial transmission to siblings.
Common Complaints
A.Infectious mononucleosis is characterized by the following four symptoms:
1.Fever.
2.Tonsillar pharyngitis (with exudate may possibly have a white, gray-green, or necrotic appearance).
3.Fatigue: May be persistent and severe.
4.Lymphadenopathy (usually posterior cervical chains—typically symmetric).
Other Signs and Symptoms
A.Uvular edema—fairly specific finding.
B.Generalized aches.
C.Appetite loss.
D.Headache.
E.Hepatosplenomegaly: Mild hepatitis is encountered in approximately 90% of individuals; splenomegaly is noted in approximately 50%. Jaundice is uncommon.
F.Rash may be present in approximately one third of patients with cytomegalovirus (CMV) mononucleosis:
1.Macular.
2.Papular.
3.Maculopapular can be caused by a large variety of infections and noninfectious agents.
4.Rubelliform.
5.Morbilliform.
6.Scariantiniform.
Subjective Data
A.Review signs, symptoms, and course and duration of symptoms, specifically pharyngitis, fever, fatigue, and lymphadenopathy.
B.Assess the patient for recent upper respiratory infection (URI), and sore throat.
C.Inquire about any contact with persons known to have mononucleosis and other infections such as strep infections.
D.Review the patient’s history for other family members with similar symptoms.
E.Carefully review medications. A mononucleosis syndrome with atypical lymphocytosis can be induced by drugs, including the following:
1.Phenytoin.
2.Carbamazepine.
3.Antibiotics such as isoniazid and minocycline.
Physical Examination
A.Check temperature, pulse, respirations, and blood pressure:
B.Inspect:
1.Conduct ear, nose, and throat exam, especially tonsils and palate:
a.Pharynx shows lymphoid hyperplasia, erythema, and edema.
b.Tonsillar exudate is present in about 50% of cases.
c.Tonsillar pillars may touch kissing tonsils
and may lead to airway compromise.
d.Evaluate for petechiae at the junction of the hard and soft palate.
e.Evaluate for oral hairy leukoplakia (OHL) on the lateral portions of the tongue. OHL appears as white corrugated painless plaques that cannot be scraped from the surface. (EBV-related malignancies as well as HIV may present with OHL.)
C.Auscultate: Auscultate the heart and lungs.
D.Palpate:
1.Palpate the lymph nodes, especially anterior and posterior cervical chains, axilla, and groin. Firm, tender, and mobile lymph nodes are indicative of mononucleosis; lymphadenopathy is usually symmetric and presents in the posterior cervical chain more than the anterior chain.
2.Palpate the abdomen, especially the spleen. Splenomegaly is noted in 50% of cases. Hepatomegaly and tenderness are noted in 10% of cases.
E.Percuss: Percuss the abdomen, especially the spleen area.
F.Neurologic exam: Evaluate for facial nerve palsy or symptoms of meningitis.
Diagnostic Tests
A.White blood cell (WBC) count with differential and a heterophile test.
B.Throat swab for rapid strep; if negative, send for culture.
C.Monospot test—heterophile antibody test—may be negative early in course. Positivity increases during the first 6 weeks.
D.EBV immunoglobulin M (IgM) and immunoglobulin G (IgG):
1.Viral capsid antigen (VCA).
2.VCA IgM—early infection and disappears within 4 to 6 weeks.
3.VCA IgG—acute phase, peaks 2 to 4 weeks after onset, decreases slightly then persists rest of life.
4.Early antigen (EA)—EA IgG in acute phase, peaks 3 to 4 weeks after onset, falls to undetectable levels after 3 to 6 months.
5.EBV nuclear antigen (EBNA) IgG—not seen in acute infection, appears 2 to 4 months after onset of symptoms and persists through life.
E.Liver function tests: Abnormal liver function tests in a patient with pharyngitis strongly suggest the diagnosis of infectious mononucleosis. Mild elevation is constant in early EBV, high elevation should suggest viral hepatitis.
F.Abdominal ultrasound if indicated for splenomegaly.
Differential Diagnoses
A.Mononucleosis.
B.Streptococcal pharyngitis (GAS).
C.Viral syndrome.
D.Hodgkin’s disease.
E.Hepatitis.
F.CMV.
G.Secondary syphilis.
H.CFS.
I.Acute HIV.
J.Toxoplasmosis.
K.Adenovirus.
L.Rubella.
M.Acute HIV.
N.HHV-6 (Roseola).
O.HHV-7 (Herpesvirus).
Plan
A.General interventions:
1.Make certain that the patient does not have an upper airway obstruction from enlarged tonsils and lymphoid tissue.
2.Treat concurrent infections.
3.Isolation is not required with good handwashing and prevention of the spread of pharyngeal secretions.
4.Bed rest is unnecessary.
5.There is no commercially available vaccine to prevent EBV infection.
6.Splenic rupture is rare but potentially life-threatening, occurring in one to two cases per thousand. It occurs between the 4th and 21st day of symptomatic illness, but it can be the presenting symptom. The typical manifestations are abdominal pain and/or a falling hematocrit.
B. 
See Section III: Patient Teaching Guide Mononucleosis
:
1.Prolonged communicability may persist for up to 1 year.
C.Pharmaceutical therapy:
1.Antibiotic therapy is reserved for concurrent infections such as streptococcal pharyngitis.
2.Administer analgesics, such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) for fever, body aches, and malaise.
3.Corticosteroids may be considered in the presence of significant inflammation and swelling of the throat.
Follow-Up
A.Examine patient every 1 to 2 weeks.
B.Initial monospot test may be negative; repeat in 7 to 10 days.
C.If splenomegaly is present, schedule an appointment to reevaluate the patient prior to the release for contact sports. Splenomegaly puts patients at risk for rupture secondary to blunt trauma (i.e., sports and motor vehicle accidents).
D.Patients with the classic four symptoms of mononucleosis should also have a diagnostic test for strep because the presenting symptoms are so similar.
Emergent Issues/Instructions
A.Severe pain in the upper left abdomen is considered a medical emergency to evaluate a ruptured spleen.
Consultation/Referral
A.Consult a physician for marked tonsil enlargement and difficulty swallowing or symptoms lasting longer than 2 weeks. An emergent consultation with an otolaryngologist may be required.
Individual Considerations
A.Pregnancy: Intrauterine infection with EBV is rare.
B.Geriatrics:
1.Typically, geriatrics do not always present with of symptoms of sore throat, tender adenopathy, or leukocytosis.
2.The sexually active older adult population have an increased risk of exposure to EBV. However, common complaints from this population include tired, right-sided tenderness, myalgias, and occasionally slightly jaundice. Consider an EBV workup to rule out mononucleosis.
3.Studies revealed that patients receiving immunosuppressive therapy/medications for rheumatic conditions were susceptible to EBV inducing lymphoid proliferations (B-cell lymphoma, Hodgkin’s lymphoma, and other variants). Recommendations are to evaluate geriatrics taking immunosuppressive agents for EBV and further explore other diagnostic measures specific to clinical manifestations.