A 16-year-old boy comes to see his pediatrician because of a 7-day history of intense sore throat, fever, malaise, and abdominal pain. He also complains of bilateral neck swelling and tenderness. On examination, he has markedly enlarged tonsils with bilateral whitish exudates, and very large lymph nodes palpable in the posterior neck bilaterally (Figure 184-1). In addition, his spleen is palpable at 1 cm below the left costal margin. A heterophile antibody test (monospot) is positive and he is offered symptomatic treatment. His symptoms persist for about 10 days, after which he recovers completely.

Epstein Barr virus (EBV) is a DNA virus that belongs to the Herpes virus family. It is the most common etiological agent of infectious mononucleosis, a clinical syndrome characterized by fever, pharyngitis and cervical lymphadenopathy. Rarely, encephalitis, myocarditis, and hemolytic anemia can develop as a consequence of EBV infections.¹ In the immunocompromised host, this virus can cause life-threatening infections.²

EBV infection is synonymous with infectious mononucleosis although infectious mononucleosis can be caused by other viruses such as cytomegalovirus (CMV). Other terms associated with EBV are glandular syndrome and human herpes virus 4. It is referred to as “the kissing disease” in the popular vernacular.

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  Ubiquitous in the environment.

  
  
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  In developed countries, EBV infections are not common in infants and young children. In contrast, in developing nations, 90 percent of children less than 6 years of age have been exposed to the virus.^1,3,4

  
  
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  The majority of primary infections occur in adolescents and young adults.

  
  
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  By adulthood, greater than 90 percent have serological evidence of previous EBV exposure.

  
  
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  The virus has no defined seasonal variations and occurs year round with slightly higher incidence during summer months.^5–7

  
  
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  Oral secretions are the main source of transmission; that is, deep kissing, toddlers sharing toys.⁸

  
  
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  In childhood, EBV infections may be asymptomatic.

  
  
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  EBV infection results in infectious mononucleosis in 30 to 40 percent of adolescents.

  
  
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  Incubation 30 to 50 days.

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  The virus infects epithelial cells in the tonsillar crypts and B lymphocytes.²

  
  
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  The virus is disseminated throughout the reticuloendothelial system (tonsils, spleen, and lymph nodes) by the infected B cells.

  
  
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  CD4 and CD8 T cell responses are activated.

  
  
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  The virus establishes permanent latent infections in the host.

  
  
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  Disease severity may be related to high numbers of NK and CD8⁺ T cells and elevated blood viral loads.⁸

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  In developed countries, teenagers and college students are the highest risk group. Behaviors such as “deep kissing”⁸ and sexual activity are risk factors for primary EBV infections.

  
  
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  Immunocompromised hosts, including patients with diabetes, HIV, transplant patients, and patients on immunomodulators are at risk of developing severe manifestations of EBV infections.

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  Infectious Mononucleosis—The classical presentation consists of the triad of fever, exudative pharyngitis and lymphadenopathy.

  
  
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  Younger children may present with mild symptoms, or may present with fever as their only sign of infection.

  
  
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  Constitutional symptoms such as fever, myalgias, malaise, and headache may precede the lymphadenopathy and pharyngitis by 3 to 5 days.

  
  
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  Cervical lymphadenopathy can be significant and give the neck the appearance of “bull’s neck.” The posterior cervical chains are commonly involved. Epitrochlear nodes can also be enlarged (Figure 184-1).^9,10 Splenomegaly occurs in 80 percent of the patients and may lead to splenic rupture after mild trauma.^11,12

  
  
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  Hepatomegaly is less common.

  
  
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  Fatigue is a common feature and often persists throughout the course of illness.

Ocular Manifestations

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  Periorbital edema may be the presenting sign of infectious mononucleosis and can be confused with cellulitis.^13,14

  
  
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  Oculo-glandular syndromes (eyelid swelling with non-tender pre-auricular lymphadenopathy).^15,16

  
  
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  Less commonly keratitis, uveitis and acute retinal necrosis.^17,18

Dermatological Manifestations

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  A rash may be present in 10 percent of the patients. The rash is morbilliform and usually is present over the trunk and arms (Figure 184-2). Occasionally the rash may be urticarial or petechial.^19–21

  
  
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  Over 90 percent will develop a rash if exposed to ampicillin.²⁰

  
  
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  Papular acrodermatitis, also known as Gianotti-Crosti syndrome, has been associated with EBV.²¹ It tends to occur in infancy and early childhood (Figure 184-3).

  
  
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  Erythema nodosum (Figure 184-4).

  
  
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  Genital ulcerations in adolescent girls can be seen in conjunction with EBV infections (Ulcus Vulvae Acutum). They can be single or multiple and very painful.^22,23

Central Nervous System Manifestations

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  The virus may affect central and peripheral and nervous system and has been associated with encephalitis, meningitis, encephalomyelitis, and radiculitis.²⁴

  
  
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  Acute disseminated encephalomyelitis (ADEM; Figure 184-5).²⁵

  
  
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  Alice in Wonderland syndrome—Associated with EBV and consists of abnormal perceptions where patients experience distortions of forms, size, or colors. Children will say objects look long, or small or different. This condition usually transient and improves with the improvement of the infectious mononucleosis.²⁶