Doctor123.org

Epstein-Barr Virus (Infectious Mononucleosis), Pediatric

Basics

Description

- Rare illnesses of the nervous system have been reported, including the following: - Guillain-Barr пїЅ syndrome - Bell palsy - Aseptic meningitis - Meningoencephalitis - Peripheral and/or optic neuritis

- Hematologic complications have been reported in association with EBV. - Aplastic anemia - Hemolytic anemia - Agranulocytosis - Hemophagocytic syndrome

- Lymphoproliferative disorders - Burkitt lymphoma - Nasopharyngeal carcinoma - Lymphoma and non-Hodgkin lymphoma (in immunocompromised children) - Lymphomatoid granulomatosis - Posttransplant lymphoproliferative disorders (PTLD) - X-linked lymphoproliferative disease (Duncan disease)

- A prodrome may occur. - Most often, lasts 3-5 days - Malaise, fatigue, with or without fever

- In the acute phase, the following features are common: - Fever: begins abruptly, lasts 1-2 weeks - Fatigue - Malaise - Anorexia - Sore throat - "Swollen glands"пїЅ - Rash; more common with ampicillin administration

- Lymphadenopathy - Occurs in 90% - Most prominent in cervical chains - May be diffuse - Usually nontender, nonerythematous, and discrete

- Hepatosplenomegaly - Splenomegaly occurs in more than half the cases. - Even if not palpable, splenomegaly may be demonstrated on ultrasound. - Most prominent in 2nd-4th week of illness - Hepatomegaly is less common.

- EBV serology - Usually reserved for heterophile-negative patients or children <4 years of age when strong clinical suspicion persists - Antibodies are detected by indirect immunofluorescence or enzyme-linked immunosorbent assay techniques. - Acute or past infection can usually be detected and differentiated. - EBV IgM is consistent with acute infection, whereas EBV nuclear antibody (EBNA) is indicative of past infection.

- Other technology - Tissue culture of EBV is difficult and, therefore, not clinically useful. - Polymerase chain reaction (PCR) may detect EBV genetic material. - Real-time PCR may quantify the amount of EBV genome present, which is useful in patients with PTLD.

- Acetaminophen or ibuprofen reduces fever and provides analgesia. - Corticosteroids (prednisone 1 mg/kg/24 h PO, maximum of 20 mg/24 h) may reduce swelling of lymphoid tissues (see "FAQ"пїЅ) - 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 central nervous system dysfunction - 7-day treatment followed by tapering

- 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

A double-stranded DNA virus implicated as a causative agent for infectious mononucleosis by an infected laboratory worker in 1968 пїЅ

General Prevention

  • No vaccine is clinically available.
  • Standard precautions should be used in the hospitalized patient.
  • Restriction of intimate contact with immunosuppressed individuals may be advisable.
  • Patients with recent Epstein-Barr virus (EBV) infection, either proven or suspected, should not donate blood or solid organs.

Epidemiology

  • Worldwide distribution
  • Humans are the only known reservoir.
  • Transmission occurs through saliva and, occasionally, via blood transfusions and solid organ transplant (SOT).
  • Incubation period is 4-7 weeks.
  • Antibodies to EBV are almost universally present in adult populations.
  • Areas with a high population density or low socioeconomic status usually become primarily infected within the first 3 years of life.

Incidence

In developed countries, acquisition of EBV is biphasic. пїЅ

  • Initial peak in incidence occurs before the age of 5 years.
  • Second peak occurs during adolescence, coinciding with an increased frequency of intimate oral contacts.

Prevalence

90-95% of adults have demonstrable EBV titers. пїЅ

Pathophysiology

  • 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 heterophile 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 may be reactivated during periods of immunosuppression.

Commonly Associated Conditions

  • Subclinical infectionMost 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"пїЅ): most commonly observed with late primary acquisition of EBV. The classically defined illness is characterized by the following:FatigueMalaiseFeverTonsillopharyngitis (often exudative)LymphadenopathySplenomegalyUsually associated with increased atypical lymphocytes in the peripheral blood
  • Rare illnesses of the nervous system have been reported, including the following:Guillain-Barr пїЅ syndromeBell palsyAseptic meningitisMeningoencephalitisPeripheral and/or optic neuritis
  • Hematologic complications have been reported in association with EBV.Aplastic anemiaHemolytic anemiaAgranulocytosisHemophagocytic syndrome
  • Other illnesses associated with EBV in case reports include the following:Hemolytic uremic syndromeHepatitisPancreatitisMyocarditisMesenteric adenitisOrchitisGenital ulcerative disease
  • Lymphoproliferative disordersBurkitt lymphomaNasopharyngeal carcinomaLymphoma and non-Hodgkin lymphoma (in immunocompromised children)Lymphomatoid granulomatosisPosttransplant lymphoproliferative disorders (PTLD)X-linked lymphoproliferative disease (Duncan disease)

Diagnosis

History

  • A prodrome may occur.Most often, lasts 3-5 daysMalaise, fatigue, with or without fever
  • In the acute phase, the following features are common:Fever: begins abruptly, lasts 1-2 weeksFatigueMalaiseAnorexiaSore throat"Swollen glands"пїЅRash; more common with ampicillin administration
  • Young children are more likely to have rash or abdominal pain.

Physical Exam

  • TonsillopharyngitisMay be exudative and mimic streptococcal pharyngitisOften accompanied by palatal petechiae
  • LymphadenopathyOccurs in 90%Most prominent in cervical chainsMay be diffuseUsually nontender, nonerythematous, and discrete
  • HepatosplenomegalySplenomegaly occurs in more than half the cases.Even if not palpable, splenomegaly may be demonstrated on ultrasound.Most prominent in 2nd-4th week of illnessHepatomegaly is less common.

Diagnostic Tests & Interpretation

Lab

  • Complete blood count with differentialLeukocyte count up to 20,000/mm3LymphocytosisAtypical lymphocytes often constitute >10% of total leukocyte count.Thrombocytopenia may occur.False positives: Atypical lymphocyte counts >10% of the total leukocyte count also occur with cytomegalovirus and toxoplasmosis infections.
  • Liver enzymesMild hepatitis is often found.Jaundice is rare.
  • "Monospot"пїЅ (mononucleosis rapid slide agglutination test for heterophile antibodies)Detects heterophile antibodies (nonspecific IgM antibodies to unrelated antigens)Appears in first 2 weeks of illness, usually slow decline over 6 monthsDetects 85% of cases in adolescents/adultsFalse positives: infrequent; heterophile antibodies are also produced in serum sickness and neoplastic processes; heterophile antibodies may persist for months after acute infection and be indicative of past illness.
  • EBV serologyUsually reserved for heterophile-negative patients or children <4 years of age when strong clinical suspicion persistsAntibodies are detected by indirect immunofluorescence or enzyme-linked immunosorbent assay techniques.Acute or past infection can usually be detected and differentiated.EBV IgM is consistent with acute infection, whereas EBV nuclear antibody (EBNA) is indicative of past infection.
  • Other technologyTissue culture of EBV is difficult and, therefore, not clinically useful.Polymerase chain reaction (PCR) may detect EBV genetic material.Real-time PCR may quantify the amount of EBV genome present, which is useful in patients with PTLD.

Alert

  • Heterophile antibodies may not appear early in the illness.
  • Up to 10% of patients with acute EBV infection may have no heterophile response 3 weeks into the illness.
  • The heterophile response is less common in infants and children and should not be used in children <4 years of age.

Differential Diagnosis

  • InfectiousGroup A StreptococcusAdenovirusCytomegalovirusToxoplasma gondiiHuman herpesvirus-6Mycoplasma pneumoniaeHuman immunodeficiency virusRubellaDiphtheriaViral hepatitis (A, B, C)
  • Noninfectious

Treatment

Medication

  • Acetaminophen or ibuprofen reduces fever and provides analgesia.
  • Corticosteroids (prednisone 1 mg/kg/24 h PO, maximum of 20 mg/24 h) may reduce swelling of lymphoid tissues (see "FAQ"пїЅ)Indicated for patients with impending airway obstructionMay be considered for patients with severe tonsillopharyngitis requiring IV hydrationMay be considered for patients with rare, life-threatening manifestations of EBV infection, such as hepatitis, aplastic anemia, and central nervous system dysfunction7-day treatment followed by tapering
  • Acyclovir has not been shown to provide clinical benefit; sometimes, used in cases of active replicating EBV in posttransplant situations
  • Patients with PTLD should have immunosuppression reduced.
  • Advise avoidance of contact sports until resolution of symptoms and no further splenomegaly.

Inpatient Considerations

Admission Criteria

  • Respiratory distress secondary to airway obstruction
  • Dehydration secondary to severe pharyngitis and poor oral intake

Discharge Criteria

  • Resolved airway obstruction
  • Good oral intake

Issues for Referral

  • PTLD
  • EBV in immunocompromised host
  • EBV-associated lymphoproliferative disorders
  • Considering steroid use as treatment

Ongoing Care

Follow-up Recommendations

Patient Monitoring

  • Immunocompetent individuals usually recover uneventfully in 1-4 weeks.
  • Recovery is often biphasic, with a worsening of symptoms after a period of improvement.
  • Splenomegaly may persist for weeks after primary infection (see "FAQ"пїЅ).
  • Fatigue may persist months after recovery.

Prognosis

  • Most patients with primary EBV infection will recover uneventfully in 1-4 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.

Complications

  • DehydrationSevere pharyngitis often limits fluid intake.Most common problem requiring hospitalization
  • Antibiotic-induced rashMorbilliform in appearanceMost common after administration of ampicillin or amoxicillinRare association with penicillinUsually benign; resolves with discontinuation of the aminopenicillin
  • Splenic ruptureIncidence of ~1 in 1,000 patientsMore common in males50% of the cases of splenic rupture are spontaneous; 50% follow blunt trauma.
  • Airway obstruction: may result from massive lymphoid hyperplasia and mucosal edema

Additional Reading

  • Bravender пїЅT. Epstein-Barr virus, cytomegalovirus, and infectious mononucleosis. Adolesc Med State Art Rev. 2010;21(2):251-264. пїЅ[View Abstract]
  • Hurt пїЅC, Tammaro пїЅD. Diagnostic evaluation of mononucleosis-like illness. Am J Med. 2007;20(10):911. e1-911. e8. пїЅ[View Abstract]
  • Macsween пїЅKF, Crawford пїЅDH. Epstein-Barr virus-recent advances. Lancet Infect Dis. 2003;3(3):131-140. пїЅ[View Abstract]
  • Okano пїЅM. Overview and problematic standpoints of severe chronic active Epstein-Barr virus infection syndrome. Crit Rev Oncol Hematol. 2002;44(3):273-282. пїЅ[View Abstract]
  • Putukian пїЅM, O'Connor пїЅFG, Stricker пїЅP, et al. Mononucleosis and athletic participation: an evidence-based subject review. Clin J Sport Med. 2008;18(4):309-315. пїЅ[View Abstract]

Codes

ICD09

  • 075 Infectious mononucleosis

ICD10

  • B27.90 Infectious mononucleosis, unspecified without complication
  • B27.99 Infectious mononucleosis, unsp with other complication
  • B27.91 Infectious mononucleosis, unspecified with polyneuropathy
  • B27.92 Infectious mononucleosis, unspecified with meningitis

SNOMED

  • 402121009 Epstein-Barr virus infection (disorder)
  • 271558008 Infectious mononucleosis (disorder)

FAQ

  • Q: Should all patients with infectious mononucleosis be given corticosteroids?
  • A: No. Symptomatic EBV infection is most often self-limited. EBV has been linked to certain lymphoproliferative disorders, and theoretic 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: More than half of patients with "mono"пїЅ will have a boggy, enlarged spleen, which is prone to rupture even if it is not palpable. Athletic activity should be restricted until no evidence exists for a clinically enlarged spleen. Return to contact sports is not advised until 4-6 weeks after resolution of illness. Some experts recommend ultrasound of the spleen before a return to heavy contact sports such as rugby, football, lacrosse, and hockey.