What are the Presentations of Epstein Barr Virus Infections?

Patient Presentation
A 19-year-old female came to clinic with a two week history of becoming progressively more tired and sleeping more.
That day, one of her college professors, pulled her aside after class and asked if something was wrong because the professor felt that she was not acting right.
She said that she had just been more tired, but had been going to school. She said that she has been eating and drinking but not as much. She also said that she has had some problems concentrating and it had been taking her much longer to finish her homework.
With further questioning, she related taking an examination 2 days prior, after which she walked out of the room, and when she looked back at the door she couldn’t remember what she had been doing in the room.
She also stated that sometimes things seem ‘strange’ to her. She said that everyday items would appear distorted such that they are much larger or much smaller than they should be.
The past medical history and family history was negative including psychiatric disease.
The review of systems was negative for fever, chills, cough, pain, sore throat, weight loss, urinary symptoms or rashes.
The pertinent physical exam showed a tired appearing female with normal weight. She had minimal pharyngeal redness. She hadhas 3 posterior cervical lymph nodes bilaterally that were 1 – 1.5 centimeters in size . She has had shoddy anterior cervical and inguinal lymph nodes.
She had no supraclavicular, axillary or popliteal lymph nodes. There was no hepatomegaly, but a spleen tip was palpable laterally. She had no rash. Her mental status examination was normal, but she stated that she felt like it was taking a great deal of effort to remember the items asked or to do the mathematical problems.
The laboratory evaluation included a complete blood count which showed a white blood cell count of 17,000/mm2 with a predominance of lymphocytes. Her erythrocyte sedimentation rate was 25 mm/hr. Her liver enzymes and a rapid strep test were normal. Her heterophil monospot was positive.
The diagnosis of infectious mononucleosis or Epstein Barr virus infection (EBV infection) was made. She was counseled as to the natural history of the viral infection and was treated with supportive care and her activity was restricted because of the splenomegaly.
She slowly improved over the next 6 weeks.

Epstein Barr virus infection (EBV infection) is viral infection spread mainly through saliva. It is only found in humans.The incubation period is 30-50 days and usually has a 3-5 day prodrome of malaise, fatigue, headache, nausea or abdominal pain. Primary infection occurs in the 0-3 years age group for those with low socioeconomic status or in high population densities. In developed countries, it has two peaks for presentation: before age 5 and in adolescents.

Heterophil antibodies (detected by monospot test) may not appear for up to 3 weeks after the prodrome making the monospot test falsely negative often . False positive heterophil tests can be caused by serum sickness or neoplastic processes.
EBV serology is usually done for patients whose heterophil test is negative but there is a strong clinical suspicion.

Patients with EBV should be warned to avoid contact with immunocompromised persons and to not share saliva with other persons through intimate contact, toothbrushes, glasses, etc. They should also not donate blood.

Most patient recover within a few weeks. Fatigue may take months to recover from though. splenomegaly may persist for weeks after primary infection.

Learning Point
Clinical presentations of EBV infections include:

  • Subclinical – may have minor symptoms of rhinorrhea, diarrhea and/or fever.
  • Infectious Mononucleosis – also called glandular fever. This is classically seen with fatigue, fever, lymphadenopathy, malaise, exudative pharyngitis, and splenomegaly. The triad of fever, sore throat and posterior cervical adenopathy occurs in more than 80% of patients.
  • Airway obstruction – secondary to lymphoid hyperplasia
  • Rash – morbilliform usually seen after ampicillin or amoxicillin but also urticaria, hemorrhagic, bullous or scarletinoform rashes.
  • Chronic fatigue syndrome – is not specifically related to EBV infection but a small group of patients with persistent symptoms have abnormal serologic tests for EBV and other viruses.
  • Dehydration
  • Hematologic problems – aplastic anemia, hemolytic anemia, hemolytic-uremic syndrome
  • Inflammatory problems – hepatitis, genital ulcerative disease, mesenteric adenitis, myocarditis, orchitis, pancreatitis, periorbital edema
  • Nervous system infection – aseptic meningitis, Bell’s palsy, Guillian-Barre syndrome, meningoencephalitis, peripheral or optic neuritis
  • Oncologic/lymphoproliferative problems – Burkitt’s lymphoma, lymphoma and Hodgkin’s lymphoma, nasopharyngeal carcinoma, x-linked lymphoproliferative syndrome
  • Psychiatric symptoms – sometimes called the “Alice in Wonderland” effect after the similar descriptions in the Lewis Carroll’s book. People have distorted space, time and body image as presented in this case.
  • Splenic rupture – occurs in 1/1000 patients with 50% of these being spontaneous rupture
  • Streptococcal pharyngitis – 5-25% of patients have a concomitant infection

Questions for Further Discussion
1. When can a patient with splenomegaly be returned to normal activity?
2. What are the indications for corticosteroids for patients with EBV infection?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MEDLINEplus for this topic: Infectious Mononucleosis
and at Pediatric Common Questions, Quick Answers for this topic: Mononucleosis.

To view current news articles on this topic check Google News.

Cooperman SM. “Alice in Wonderland” syndrome as a presenting symptom of infectious mononucleosis in children: a description of three affected young people. Clin Pediatr. 1977 Feb;16(2):143-6.

Ousterhoudt KC. Epstein Barr Infections, In M. William Schwartz (ed.) 5 Minute Pediatric Consult. Lippincott Williams & Wilkins; 3rd edition. 2000:356-57.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1035-1039.

American Academy of Pediatrics. Epstein-Barr Virus Infections, In Pickering LD, ed. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2003;271-275.

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effecively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competency performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Donna M. D’Alessandro, MD
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    April 10, 2006