EBV

**Virology:** Human herpesvirus 4 (HHV-4), enveloped, linear dsDNA, gammaherpesvirus. Transmitted via saliva ("kissing disease"). Infects B cells and oropharyngeal epithelial cells. Enters B cells by binding CD21 (complement receptor 2, CR2). Establishes lifelong latency in memory B cells.

**Infectious mononucleosis:** - Classic triad: fever, exudative pharyngitis/tonsillitis, posterior cervical lymphadenopathy. Also fatigue, splenomegaly, and sometimes hepatitis (elevated transaminases). - Peak in adolescents and young adults. - Blood: lymphocytosis with atypical lymphocytes (Downey cells). These are reactive CD8+ cytotoxic T cells, not infected B cells. - Diagnosis: positive heterophile antibody test (Monospot), which agglutinates sheep or horse RBCs. The test can be falsely negative early in the illness and in young children. If it is negative and suspicion remains, check EBV-specific serology (VCA-IgM, VCA-IgG, EBNA). - Complications: splenic rupture (avoid contact sports for about 3–4 weeks), airway obstruction from tonsillar hypertrophy (treat with steroids), autoimmune hemolytic anemia (cold agglutinins, IgM, anti-i), and thrombocytopenia. - Amoxicillin or ampicillin given for presumed strep pharyngitis causes a diffuse maculopapular rash. - Treatment is supportive. Antivirals are not routinely indicated. - Differential diagnosis: CMV mononucleosis (heterophile-negative, with less pharyngitis), acute HIV, toxoplasmosis, and group A strep.

**Associated malignancies and diseases:** - Burkitt lymphoma: t(8;14) c-myc translocation, "starry sky" histology. The endemic (African) form involves the jaw and is EBV-associated. - Nasopharyngeal carcinoma: especially in Southern China and North Africa. - Hodgkin lymphoma: Reed-Sternberg cells (CD15+, CD30+) are often EBV-positive. - Primary CNS lymphoma in AIDS: ring-enhancing lesions. EBV PCR in CSF helps distinguish it from toxoplasmosis. - Post-transplant lymphoproliferative disorder (PTLD): occurs with T-cell immunosuppression. - Oral hairy leukoplakia: in HIV, a white, non-scrapable lesion on the lateral tongue. - X-linked lymphoproliferative disorder (SH2D1A/SAP mutation): severe, often fatal EBV infection.

**Serology:** - VCA-IgM: acute infection. - VCA-IgG: persists for life. - EBNA: appears weeks to months after infection, so it indicates past infection. Its absence with positive VCA-IgM suggests acute infection.

**Pathophysiology and immunity:** Cytotoxic CD8+ T cells control the infection. This explains the lymphocytosis and why T-cell deficiency leads to EBV-driven lymphoproliferation. EBV also has links to multiple sclerosis risk.

**High-yield pearls:** Monospot is positive in the first weeks of illness but can miss early disease. Atypical lymphocytes are T cells. EBV is the most common cause of heterophile-positive mononucleosis.