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Emergency And Acute Medicine – Infectious Mononucleosis
Infectious mononucleosis most commonly results from infection with the Epstein–Barr virus, a herpesvirus transmitted primarily through close or intimate contact with saliva, giving rise to the term “kissing disease.” Viral shedding may persist intermittently for life, even in asymptomatic individuals, and transmission may also occur through blood transfusions or organ transplantation. The incubation period is typically 4–6 weeks. More than 90% of adults demonstrate serologic evidence of prior EBV infection, although most do not recall a classic illness. Non-EBV causes of a mononucleosis-like syndrome include cytomegalovirus, adenovirus, hepatitis A, HIV, rubella, toxoplasmosis, herpesvirus 6, and group A β-hemolytic streptococci.
The clinical manifestations of infectious mononucleosis are largely driven by the host immune response. T-cell activation, particularly cytotoxic CD8 cells, leads to an elevated absolute lymphocyte count and the appearance of atypical lymphocytes on peripheral smear. EBV infects B-cells, transforming them into plasmacytoid cells that secrete immunoglobulins, including IgM heterophile antibodies detected by the Monospot test. Mortality is rare but may occur due to complications such as airway edema, splenic rupture, hepatic failure, myocarditis, neurologic involvement, or secondary bacterial infection. EBV infection is also associated with certain malignancies, including African Burkitt lymphoma and nasopharyngeal carcinoma.
Presentation is often insidious, developing over days to weeks, though abrupt onset may occur. Patients typically report profound fatigue, malaise, fever, and severe sore throat, often described as the worst they have experienced. Cervical lymphadenopathy is prominent, and headache is common. Significant abdominal pain is uncommon and should prompt concern for splenic enlargement or rupture. Rashes may occur, particularly in children and adolescents, and administration of ampicillin or amoxicillin frequently results in a morbilliform rash that should not be mistaken for a penicillin allergy.
Physical examination commonly reveals fatigue, pharyngitis with tonsillar enlargement, fever, and symmetric tender lymphadenopathy. Splenomegaly is present in approximately half of cases, and hepatomegaly occurs less frequently. Eyelid edema and palatal petechiae may be seen. Complications identified on examination include airway compromise from pharyngeal edema, jaundice from hepatitis, signs of splenic rupture such as severe abdominal tenderness or referred left shoulder pain, neurologic deficits, and evidence of hematologic abnormalities such as pallor from anemia.
Laboratory evaluation typically shows a modest leukocytosis with lymphocyte predominance, often exceeding 50% lymphocytes, and more than 10% atypical lymphocytes. Liver transaminases are elevated in the majority of patients during the first two weeks of illness, and mild hyperbilirubinemia may occur. The heterophile antibody test is highly specific but moderately sensitive and may be negative early in the disease course or in children younger than four years. EBV-specific serologic testing can confirm the diagnosis when needed, particularly in atypical or severe cases. Abdominal ultrasound or CT imaging is reserved for patients with significant abdominal pain or concern for splenic rupture.
Management in the emergency and acute care setting is primarily supportive. Attention should be given to airway assessment, hydration, fever control, and analgesia. Corticosteroids may be considered in cases of significant tonsillar or pharyngeal edema with concern for airway obstruction, as well as in select severe complications such as massive splenomegaly, hemolytic anemia, myocarditis, or hemophagocytic lymphohistiocytosis, though their use remains controversial. Antibiotics are reserved for suspected bacterial superinfection, and ampicillin should be avoided due to the high likelihood of rash development.
Hospital admission is indicated for patients with airway compromise, severe neurologic, hepatic, or hematologic complications, or inability to tolerate oral intake. Most patients may be safely discharged once hydration and pain are controlled and there is no evidence of serious complications. Patients should be counseled to avoid contact sports and strenuous activity for at least three weeks due to the risk of splenic rupture, with reassessment prior to return to full activity. While infectious mononucleosis is generally self-limited, clinicians must remain vigilant for potentially life-threatening complications and ensure appropriate follow-up.
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