eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Mononucleosis and Epstein-Barr Virus Infection: Follow-up

Author: Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Coauthor(s): Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Contributor Information and Disclosures

Updated: Oct 20, 2009

Follow-up

Further Inpatient Care

  • Patients with uncomplicated infectious mononucleosis rarely require inpatient therapy.
  • Hospitalization is warranted in the presence of splenic rupture, airway compromise, dehydration, significant thrombocytopenia or hemolytic anemia, and neurologic or other major complications.

Further Outpatient Care

  • If diagnosis is firmly established, only supportive care is required in the absence of significant complications.

Inpatient & Outpatient Medications

  • Nonspecific treatment includes saline gargles and acetaminophen or ibuprofen for sore throat, fever, and myalgia. Constipation may be treated with a laxative.
  • Corticosteroids decrease the duration of febrile illness and constitutional symptoms, but their routine use for treatment of a virus known to be related to tumor development is discouraged.
  • Acyclovir has no demonstrable benefit for treatment of uncomplicated infectious mononucleosis in placebo-controlled trials.
  • Various therapies are used for complications of Epstein-Barr virus (EBV) infection, although only a few have been studied in controlled trials.
    • Corticosteroids are used for treatment of severe airway obstruction due to tonsillar enlargement, hemolytic anemia, and severe thrombocytopenia.
    • Interferon-alfa decreases shedding of Epstein-Barr virus in renal transplant recipients.
    • Acyclovir and desciclovir can reverse Epstein-Barr virus–associated hairy leukoplakia in patients with HIV. Acyclovir has been used to treat interstitial pneumonitis, X-linked lymphoproliferative syndrome, and lymphoproliferative disorders. Posttransplant lymphoproliferative disorder (PTLD) has been treated with ganciclovir and CMV intravenous immunoglobulin (CytoGam).
    • Immune thrombocytopenia has been treated with intravenous immunoglobulin.
    • Whether corticosteroids are beneficial or harmful in patients with encephalitis, pericarditis, and myocarditis is unclear.
    • Combination therapy with corticosteroids and acyclovir has been reported, with varying outcomes.

Transfer

  • Transfer to a tertiary care center may be necessary for the treatment of significant complications.

Deterrence/Prevention

  • Isolation is not required. Epstein-Barr virus has low transmissibility and cannot be acquired from environmental surfaces or fomites.
  • Avoid contact with saliva.
    • Epstein-Barr virus is present in throat washings of individuals with acute infectious mononucleosis. Virus can be cultured from the oropharynx for up to 18 months. It can be recovered from the oropharynx of 10-20% of healthy adults.
    • Epstein-Barr virus infection is usually acquired through contact between a susceptible individual and the saliva of an asymptomatic individual who is shedding Epstein-Barr virus. In young children, saliva is spread by drooling and hand-to-mouth behaviors. In adolescents, infected saliva may be transferred by kissing, hence the label "kissing disease."
  • Do not kiss children on the mouth.
  • Maintain clean conditions, especially when young children are present (eg, in daycare), and avoid having children share toys.
  • Epstein-Barr virus can be transmitted by blood transfusion and by bone marrow transplantation. However, because the organism is so common, no procedures are in place to prevent this.
  • Vaccine development is proceeding, although the role of a vaccine is unclear. Animal studies suggest the antigenicity of a vaccinia-based vector.13

Complications

  • Hepatitis develops in more than 90% of patients with infectious mononucleosis.
    • Liver function test results are mildly elevated but are usually no more than 2-3 times the reference range. Bilirubin levels are elevated in approximately 45% of patients, but jaundice occurs in only 5%.
    • Liver abnormalities are most pronounced in the second and third weeks of illness.
  • Approximately 50% of patients with infectious mononucleosis develop mild thrombocytopenia.
    • The platelet count is usually 100,000-140,000/mL. The platelet count usually reaches its nadir approximately 1 week after symptom onset and then gradually improves over the next 3-4 weeks.
    • Thrombocytopenia may be caused by the production of antiplatelet antibodies and peripheral destruction, especially in the enlarged spleen.
  • Hemolytic anemia occurs in 0.5-3% of patients with infectious mononucleosis.
    • Hemolytic anemia has been associated with cold-reactive antibodies, with anti-I antibodies, and with autoantibodies to triphosphate isomerase.
    • Hemolysis is usually mild and is most significant during the second and third weeks of symptoms.
  • Upper airway obstruction due to hypertrophy of tonsils and other lymph nodes in the Waldeyer ring occurs in 0.1-1% of patients.
    • Treatment with corticosteroids may be beneficial.
    • Patients with severe tonsillar and lymph node enlargement with impending airway obstruction may require intubation or tracheostomy.
    • Patients who require hospitalization may have concurrent streptococcal pharyngitis. Two thirds of patients admitted with infectious mononucleosis with upper airway obstruction and dehydration have alpha-hemolytic Streptococcus infection, usually due to group C streptococci.
  • Splenic rupture occurs in 0.1-0.2% of patients with infectious mononucleosis.
    • Rupture may be spontaneous, although the patient often has a history of some antecedent trauma.
    • Rupture is most likely during the second and third weeks of clinical symptoms.
    • Patients can present with mild-to-severe abdominal pain below the left costal margin, sometimes with radiation to the left shoulder and supraclavicular area. Massive bleeding may be accompanied by peritoneal irritation and shifting dullness. Shock may be the only presenting symptom.
    • Because bradycardia is common in infectious mononucleosis, tachycardia with pulse of faster than 100 beats per minute is an important sign.
    • Neutrophilia (instead of lymphocytosis) can occur.
    • Surgical intervention is usually required.
  • Hematologic complications are as follows:
    • Epstein-Barr virus has been implicated in hemophagocytic syndrome.
    • Immune thrombocytopenic purpura occurs and may evolve to aplastic anemia. Aplastic anemia and neutropenia are sometimes associated with antineutrophil antibodies.
    • Epstein-Barr virus infection may accelerate hemolytic anemia in individuals with congenital spherocytosis or hereditary elliptocytosis.
    • Disseminated intravascular coagulation associated with hepatic necrosis has occurred.
  • Neurologic complications are as follows:
    • Neurologic complications occur in less than 1% of patients with Epstein-Barr virus infections and usually develop during the first 2 weeks. In some patients, especially children, the neurologic symptoms are the only clinical manifestation of infectious mononucleosis. Patients are often negative for the heterophile antibody. However, these complications are often severe. Complete recovery is the rule, but fatalities do occur.
    • Primary Epstein-Barr virus infection has been associated with aseptic meningitis, acute viral encephalitis, coma, meningitis, and meningoencephalopathy. Hypoglossal nerve palsy, Bell palsy, hearing loss, brachial plexus neuropathy, and multiple cranial nerve palsies have been described. Guillain-Barré syndrome, autonomic neuropathy, GI dysfunction secondary to selective cholinergic dysautonomia, acute cerebellar ataxia, and transverse myelitis have been reported. Metamorphopsia (ie, Alice in Wonderland syndrome) has been described.
  • Cardiac and pulmonary complications are as follows:
    • Pulmonary complications are extremely rare, although upper airway obstruction due to lymphoid hypertrophy is relatively common. Chronic interstitial pneumonitis and pleural effusion have been associated with Epstein-Barr virus infection.
    • Cardiac abnormalities that can occur with Epstein-Barr virus infection include myocarditis and pericarditis.
  • Autoimmune complications are as follows:
    • Autoimmune diseases and Reye syndrome have been associated with Epstein-Barr virus infection.
    • Infectious mononucleosis stimulates production of many antibodies not directed against Epstein-Barr virus. These include autoantibodies, anti-I antibodies, cold hemolysins, antinuclear antibodies, rheumatoid factors, cryoglobulins, and circulating immune complexes. These antibodies may precipitate autoimmune syndromes.
  • Miscellaneous complications are as follows:
    • Renal disorders associated with Epstein-Barr virus infection include immune deposit nephritis, renal failure, and paroxysmal nocturnal hemoglobinuria.
    • After cardiac bypass or transfusion, an infectious mononucleosis–like syndrome has been described. Epstein-Barr virus may cause this, but it is more commonly associated with primary CMV infection.
    • A syndrome of chronic fatigue, myalgias, sore throat, and mild cognitive dysfunction that primarily occurs in young adult females was initially attributed to Epstein-Barr virus. Current data suggest that Epstein-Barr virus is not the etiologic agent.

Prognosis

  • Immunocompetent individuals with acute infectious mononucleosis have a good prognosis, with full recovery expected within several months.
  • The common hematologic and hepatic complications resolve in 2-3 months.
  • Neurologic complications usually resolve quickly in children. Adults are more likely to be left with neurologic deficits.
  • All individuals develop latent infection, which usually remains asymptomatic.
  • Long-term fatigue can occur, is more common in females, and can last 1-2 years or longer. This is separate from the chronic fatigue syndrome mentioned above (although post–Epstein-Barr virus fatigue can occur, chronic fatigue syndrome has not been causally linked to Epstein-Barr virus).

Patient Education

  • Educate patient and family about risk of splenic rupture and the need to refrain from contact sports for 2 months.
  • Inform patient and family about usual course of symptoms with acute mononucleosis.
  • For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center. Also, see eMedicine's patient education article Mononucleosis.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize splenic rupture is a concern.
  • Failure to recognize impending airway obstruction is another pitfall.
  • Acute mononucleosis has been known to cause false-positive enzyme-linked immunoassay (ELISA) findings for HIV. Because the syndrome of mononucleosis is similar to the seroconversion illness of HIV, and because Epstein-Barr virus may be acquired through intimate contact (kissing), care should be taken not to label a patient as HIV positive without confirmatory testing, especially in the absence of a high-risk exposure.
 
Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Glenna B Winnie, MD, to the original writing of this article.



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References
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Further Reading

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Keywords

mononucleosis, Epstein-Barr virus infection, EBV, acute infectious mononucleosis, infectious mononucleosis, mono, human herpesvirus 4, HHV-4, kissing disease, gamma-herpesvirus, human tumor virus, lymphoproliferative disorders, nasopharyngeal carcinoma, Burkitt lymphoma, endemic Burkitt lymphoma, acute glandular fever, non-Hodgkin lymphomas, Hodgkin lymphoma, Duncan syndrome, X-linked lymphoproliferative syndrome, fatal massive hepatitis, disseminated lymphoproliferative disorder, B-cell lymphoma, hypogammaglobulinemia, EBV-associated lymphoproliferative disorders, EBV-associated lymphomas, ataxia-telangiectasia, Chédiak-Higashi syndrome, Wiskott-Aldrich syndrome, posttransplant lymphoproliferative disorder, PTLD, lymphoproliferative syndrome, hairy leukoplakia, leiomyosarcoma, CNS lymphoma, lymphoid interstitial pneumonitis, infectious mononucleosis syndrome, sore throat, splenic rupture, pharyngitis, hepatosplenomegaly, petechiae, tonsillar enlargement, enlarged epitrochlear nodes, hepatomegaly, splenomegaly, maculopapular rash

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Contributor Information and Disclosures

Author

Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Nicholas John Bennett, MB, BCh, PhD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Rosemary Johann-Liang, MD, Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration
Rosemary Johann-Liang, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota Medical School
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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