The nature of EBV disease depends on the pt's age and immune status: young children typically develop asymptomatic infections or mild pharyngitis, adolescents and adults develop an IM syndrome, and immunocompromised pts can develop lymphoproliferative disease.

• In IM, a prodrome of fatigue, malaise, and myalgia may last for 1-2 weeks before the onset of fever, exudative pharyngitis, and lymphadenopathy with tender, symmetric, and movable nodes; splenomegaly is more prominent in the second or third week.
  • - The incubation period is ~4-6 weeks.
  • - Most pts treated with ampicillin develop a rash that does not represent a true penicillin allergy.
  • - Illness lasts for 2-4 weeks, but ~10% of pts have fatigue that persists for ≥6 months. EBV is not, however, a cause of chronic fatigue syndrome.
  • - Lymphocytosis occurs in the second or third week, with >10% atypical lymphocytes (enlarged cells with abundant cytoplasm and vacuoles); abnormal liver function is common.
  • - Complications include CNS disease (e.g., meningitis, encephalitis), Coombs-positive autoimmune hemolytic anemia, splenic rupture, and upper airway obstruction due to hypertrophy of lymphoid tissue.
• Lymphoproliferative disease—i.e., infiltration of lymph nodes and multiple organs by proliferating EBV-infected B cells—occurs in pts with deficient cellular immunity (e.g., pts with AIDS, those with severe combined immunodeficiency, and those receiving immunosuppressive medications). Pts develop fever and lymphadenopathy or GI symptoms.
• Oral hairy leukoplakia—raised, white, corrugated, EBV DNA-containing lesions on the tongue—is an early manifestation of infection with HIV in adults.
• EBV-associated malignancies include Burkitt's lymphoma (~90% of cases in Africa and ~15% of cases in the United States), anaplastic nasopharyngeal carcinoma in southern China, gastric cancer (with ~9% of these tumors positive for EBV), Hodgkin's disease (especially the mixed-cellularity type), and CNS lymphoma (especially HIV-related).