Epstein-Barr Virus Complications

Clinical meaning

Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is a member of the Herpesviridae family and is one of the most common human viruses worldwide, infecting approximately 95 percent of the adult population globally. EBV has a particular tropism for B lymphocytes and oropharyngeal epithelial cells. Primary infection typically occurs during childhood (often subclinical) or adolescence/young adulthood, when it commonly manifests as infectious mononucleosis (IM), colloquially known as the 'kissing disease.' The virus is transmitted primarily through saliva (oral secretions), making kissing, sharing utensils, and sharing drinking containers the most common modes of transmission. After primary infection, EBV establishes lifelong latency in memory B lymphocytes, with periodic reactivation and asymptomatic viral shedding in saliva. The pathophysiology of infectious mononucleosis involves EBV infection of B lymphocytes in the oropharyngeal lymphoid tissue (Waldeyer ring). The virus stimulates polyclonal B cell proliferation, which triggers a robust cytotoxic T lymphocyte (CD8+) response. These activated T lymphocytes are the 'atypical lymphocytes' (Downey cells) seen on the peripheral blood smear, which is a hallmark laboratory finding of infectious mononucleosis. The intense immune response causes lymph node enlargement (lymphadenopathy), pharyngitis with tonsillar exudates, fever, and profound fatigue. The spleen is involved in over 50 percent of cases, with splenomegaly resulting from lymphocyte infiltration and congestion of the splenic red pulp. Splenic rupture is the most feared acute complication of infectious mononucleosis, occurring in approximately 0.1 to 0.5 percent of cases. Rupture typically occurs between days 4 and 21 of illness and may be spontaneous or triggered by abdominal trauma, including contact sports. This is why activity restriction, particularly avoidance of contact sports, is a critical component of patient management. Long-term oncologic associations of EBV include Burkitt lymphoma (endemic African form), nasopharyngeal carcinoma, Hodgkin lymphoma (30-40 percent of cases are EBV-associated), and post-transplant lymphoproliferative disorder (PTLD) in immunosuppressed organ transplant recipients.

Exam relevance

Risk factors: - Adolescents and young adults (15 to 25 years) experiencing primary EBV infection, which is more likely to manifest as symptomatic infectious mononucleosis compared to childhood infection - Immunocompromised patients (organ transplant recipients on immunosuppressive therapy, HIV/AIDS patients, chemotherapy patients) at increased risk for EBV reactivation and post-transplant lymphoproliferative disorder - Close contact with saliva of infected individuals through kissing, sharing utensils, sharing drinking containers, or exposure to respiratory droplets in crowded environments - Collegiate athletes and military recruits in communal living environments where close contact facilitates transmission - Patients with active mononucleosis who participate in contact sports or heavy physical activity, increasing risk of traumatic splenic rupture - Individuals with X-linked lymphoproliferative disease (Duncan syndrome), a rare genetic condition causing severe, potentially fatal immune response to EBV infection - Patients receiving ampicillin or amoxicillin during acute EBV infection, at high risk (70 to 100 percent) for developing a diffuse maculopapular rash

Diagnostics: - Complete blood count with differential: lymphocytosis (greater than 50 percent lymphocytes) with atypical lymphocytes (greater than 10 percent) on peripheral blood smear; total WBC typically 10,000 to 20,000 cells/mcL; mild thrombocytopenia may be present - Monospot test (heterophile antibody test): rapid screening test detecting heterophile antibodies produced during EBV infection; sensitivity 70 to 92 percent in adults but may be negative in children under 4 and in the first week of illness (false-negative period) - EBV-specific serology: VCA-IgM (viral capsid antigen IgM, positive in acute infection), VCA-IgG (positive in acute and past infection), EA-D (early antigen, positive in acute infection), EBNA (Epstein-Barr nuclear antigen, positive 6 to 8 weeks after onset, indicates past infection); this panel differentiates acute from past infection - Liver function tests (AST, ALT, ALP, bilirubin): elevated transaminases occur in up to 80 percent of mononucleosis cases; significant elevation (greater than 3 times upper normal) suggests EBV hepatitis - Abdominal ultrasound: evaluates spleen size to guide activity restriction decisions; splenomegaly is present in over 50 percent of mononucleosis cases; serial measurements may be needed to confirm resolution before return to contact sports - Throat culture or rapid strep test: performed to rule out concurrent Group A Streptococcus pharyngitis (coinfection occurs in approximately 5 to 30 percent of mononucleosis cases)

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