Epstein-Barr Virus
The 5 Minute Pediatric Consult
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Epstein-Barr Virus (Infectious Mononucleosis) |
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Kevin C. Osterhoudt
DEFINITION
Epstein-Barr virus (EBV) is a double-stranded DNA virus, and was implicated as the causative agent for infectious mononucleosis by 1968.
PATHOPHYSIOLOGY
- EBV replicates initially in the oropharyngeal epithelium.
- Selective infection of B-lymphocytes occurs.
- The clinical syndrome of infectious mononucleosis results from proliferation of cells in the tonsils, lymph nodes, and spleen.
- Nonspecific humoral immune responses include the formation of heterophil antibodies and autoantibodies.
- Specific antibodies to EBV antigens are produced.
- Despite humoral responses, cellular immunity is responsible for controlling EBV infection.
- Latent, lifelong infection of B-lymphocytes occurs.
- Latent virus can be reactivated during periods of immunosuppression.
EPIDEMIOLOGY
- Worldwide distribution
- Humans are the only known reservoir.
- EBV spreads between individuals in saliva, and occasionally via blood transfusions.
- The incubation period is 30 to 50 days.
- Antibodies to EBV are almost universally present in adult populations.
- Populations with a high population density or low socioeconomic status usually become primarily affected within the first 3 years of life.
- In developed countries, acquisition of EBV is biphasic:
- The initial peak in incidence occurs before the age of 5 years.
- The second peak occurs during adolescence, coinciding with an increased frequency of intimate oral contacts.
COMPLICATIONS
- Dehydration
- Severe pharyngitis often limits fluid intake.
- Is the most common problem requiring hospitalization
- Streptococcal pharyngitis
- Between 5% and 25% of patients with acute EBV infection may have concomitant group A streptococcal pharyngitis.
- Antibiotic-induced rash
- Morbilliform in appearance
- Most common after administration of ampicillin or amoxicillin
- Rare association with penicillin
- Usually benign, resolves with discontinuation of the aminopenicillin
- Splenic rupture
- Incidence of approximately 1 in 1,000 patients
- More common in males
- Half of the cases of splenic rupture are spontaneous; half follow blunt trauma.
- Airway obstruction
- May result from massive lymphoid hyperplasia and mucosal edema
PROGNOSIS
- Most patients with primary EBV infection will recover uneventfully in 1 to 4 weeks.
- Long-lasting immunity generally ensues.
- Prognosis of patients with unusual manifestations of EBV infection depends on the severity of the illness and the organ system involved.
- Patients with inherited or acquired immunodeficiency are at higher risk of complications and neoplasms.
ASSOCIATED ILLNESSES
- Subclinical infection
- The majority of EBV infections in children, and even in adolescents, are clinically inapparent.
- Mild, nonspecific symptoms may include coryza, diarrhea, and/or fever.
- Immunologic seroconversion does occur.
- Infectious mononucleosis (“glandular fever”)
- Most commonly observed with late primary acquisition of EBV
- The classically defined illness is characterized by:
- Fatigue
- Malaise
- Fever
- Tonsillopharyngitis (often exudative)
- Lymphadenopathy
- Splenomegaly
- Usually associated with increased numbers of atypical lymphocytes in the peripheral blood
- Rare illnesses of the nervous system have been reported:
- Guillain-Barré syndrome
- Bell palsy
- Aseptic meningitis
- Meningoencephalitis
- Peripheral and/or optic neuritis
- Hematologic disorders have been reported in rare association with EBV:
- Aplastic anemia
- Hemolytic anemia
- Hemolytic-uremic syndrome
- Other illnesses associated with EBV in case reports:
- Hepatitis
- Pancreatitis
- Myocarditis
- Mesenteric adenitis
- Orchitis
- Genital ulcerative disease
- Congenital infection
- Primary EBV infection during pregnancy is uncommon.
- Although rare, TORCH-like congenital defects may conceivably be linked to EBV.
- Lymphoproliferative disorders
- EBV is suspected of occasionally playing a role in the etiology of the lymphoproliferative disorders:
- Burkitt lymphoma
- Nasopharyngeal carcinoma
- Lymphoma and non-Hodgkin lymphoma (in immunocompromised children)
- Virus-associated hemophagocytic syndrome
- Lymphomatoid granulomatosis
- Chronic fatigue syndrome
- EBV, as well as many other infectious and environmental agents, have been proposed to contribute to this vague clinical syndrome.
- Infectious mononucleosis is an illness with characteristic clinical features caused by EBV.Other causes of the infectious mononucleosis syndrome include:
- Adenovirus
- Cytomegalovirus
- Toxoplasma gondii
- Human herpes virus-6
- Human immunodeficiency virus
- Rubella
HISTORY
- A prodrome may occur:
- Commonly lasts 2 to 5 days
- Malaise, fatigue, 6 ± fever
- The following features are common:
- Fatigue
- Malaise
- Anorexia
- Fever
- Sore throat
- “Swollen glands”
- Young children are more likely to have a rash or abdominal pain.
- Tonsillopharyngitis
- May be exudative and mimic streptococcal pharyngitis
- Often accompanied by palatal petechiae
- Lymphadenopathy
- Most prominent in cervical chains
- May be diffuse
- Usually nontender
- Hepatosplenomegaly
- Splenomegaly occurs in over half of cases.
- Even if not palpable, splenomegaly may be demonstrated on ultrasound.
- Most prominent in second to fourth week of illness
- Hepatomegaly is less common.
TESTS
- CBC with differential
- Leukocyte count up to 20,000/mm3
- Lymphocytosis
- Atypical lymphocytes often comprise more than 10% of total leukocyte count.
- Thrombocytopenia may occur.
- Liver enzymes
- Mild hepatitis often is found.
- Jaundice is rare.
- “Monospot” (mononucleosis rapid slide agglutination test for heterophil antibodies)
- Detects heterophil antibodies (nonspecific IgM antibodies to unrelated antigens)
- Often negative in children under 6 years of age
- Detects 90% of cases in adolescents and adults
- EBV serology
- Usually reserved for heterophil-negative patients where strong clinical suspicion persists
- Antibodies detected by indirect immunofluorescence or ELISA techniques
- Acute or past infection can usually be detected and differentiated.
- Other technology
- Tissue culture of EBV is difficult and therefore not clinically useful.
- Polymerase chain reaction may detect EBV genetic material.
False Positives
- CBC
- Atypical lymphocyte counts greater than 10% of the total leukocyte count also occur with cytomegalovirus and toxoplasmosis infections.
- Monospot
- False-positive tests are infrequent.
- Heterophil antibodies are also produced in serum sickness and neoplastic processes.
- Heterophil antibodies may persist for months after acute infection and be indicative of past illness.
PITFALLS
- Heterophil antibodies may not appear early in the illness.
- Up to 10% of patients with acute EBV infection may have no heterophil response 3 weeks into the illness.
- The heterophil response is less common in infants and children.
- Supportive care and symptomatic treatment will be sufficient for most cases of primary EBV infection.
- Acetaminophen or ibuprofen will reduce fever and provide analgesia.
- Oral, and sometimes IV, rehydration is often indicated.
- Corticosteroids (prednisone, 1 mg/kg/d divided into two doses) may reduce swelling of lymphoid tissues (see section, Common Questions and Answers)
- Indicated for patients with impending airway obstruction
- May be considered for patients with severe tonsillopharyngitis requiring IV hydration
- May be considered for patients with rare, life-threatening manifestations of EBV infection, such as hepatitis, aplastic anemia, and CNS dysfunction
- Acyclovir has not been shown to provide clinical benefit.
PREVENTION
- No vaccine is clinically available.
- Hospitalized patients need not be isolated when rigorous handwashing is employed.
- Restriction of intimate contact with immunosuppressed individuals may be advisable.
- Patients with recent EBV infection, either proven or suspected, should not donate blood.
- Immunocompetent individuals usually recover uneventfully in 1 to 4 weeks.
- Recovery is often biphasic, with a worsening of symptoms after a period of improvement.
- Splenomegaly may persist for weeks after primary infection (see section, Common Questions and Answers).
- Fatigue may persist months after recovery.
| COMMON QUESTIONS AND ANSWERS |
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Q: Should all patients with infectious mononucleosis be given corticosteroids?
A: Even though children may feel tired, weak, and ill, symptomatic EBV infection is most often self-limited with only symptomatic care. Long-term effects from the use of steroids to treat EBV are not known. EBV has been linked to certain lymphoproliferative disorders, and theoretical risks to modulating the host immune response with corticosteroids have been proposed.
Q: How long after infectious mononucleosis may a patient return to athletic activity?
A: Over half of patients with “mono” will have a boggy, enlarged spleen. This enlarged spleen is prone to rupture even if it is not palpable. All athletic activity should be restricted until no evidence exists for a clinically enlarged or tender spleen. If this criterion is met, and the patient feels subjectively better, light (noncontact) activities may be resumed. Return to contact sports is not advised until at least 4 to 6 weeks after resolution of all signs and symptoms of illness. Some experts recommend ultrasound study of the spleen before a return to heavy contact sports such as rugby, football, lacrosse, and hockey.
ICD-9-CM 075
Chetham MM, Roberts KB. Infectious mononucleosis in adolescents. Pediatr Ann 1991;20:206–213.
Durbin WA, Sullivan JL. Epstein-Barr virus infection. Pediatr Rev 1994;15:63–68.
Hickey SM, Strasburger VC. What every pediatrician should know about infectious mononucleosis in adolescents. Pediatr Clin North Am 1997;44:1541–1556.
Peter J, Ray CG. Infectious mononucleosis. Pediatr Rev 1998;19:276–279.
Sumaya CV. Epstein-Barr virus infections in children. Curr Probl Pediatr 1987;Dec:682–722.
Copyright © 2000 Lippincott Williams & Wilkins
M. William Schwartz, Louis M. Bell, Jr., Peter M. Bingham, Esther K. Chung, David F. Friedman and Andrew E. Mulberg, The 5 Minute Pediatric Consult