Infectious Mononucleosis & Mono-Like Syndromes

EBV infection and presentation

Virology. Epstein–Barr virus (HHV-4) spreads through saliva, incubates for 4–6 weeks, and enters B cells through the CD21 receptor. Infection in early childhood is usually silent; primary infection in adolescents and young adults, peaking around ages 15–24, produces infectious mononucleosis. The virus then persists latently in memory B cells for life, which explains its links to Burkitt and Hodgkin lymphoma, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disorder.

Clinical picture. The classic triad is fever, pharyngitis (often exudative), and lymphadenopathy that favors the posterior cervical chain and may be generalized. Profound fatigue is typical and can last weeks to months. Splenomegaly occurs in about half of patients, and palatal petechiae and eyelid edema are useful clues. Group A streptococcal pharyngitis, by contrast, peaks at ages 5–15, causes tender anterior cervical nodes without splenomegaly, resolves quickly, and is treated with penicillin or amoxicillin to prevent rheumatic fever.

Laboratory findings. Lymphocytosis with more than 10% atypical lymphocytes is characteristic; these Downey cells are reactive CD8+ T cells attacking infected B cells. Most patients have mildly elevated aminotransferases, though jaundice is uncommon, and mild thrombocytopenia is frequent. Atypical lymphocytosis is not specific: CMV, acute HIV, toxoplasmosis, and drug reactions produce it too.

Diagnosis

Heterophile antibody test. The Monospot detects IgM heterophile antibodies that agglutinate animal red cells. It is the first-line test, but it is falsely negative in up to about a quarter of patients during the first week and often in children younger than 4. When suspicion remains high, repeat it in 5–7 days or send EBV-specific serology. Heterophile antibodies persist for months, so the test cannot be used to time recovery.

Many patients with mono who receive amoxicillin or ampicillin, often for presumed strep throat, develop a diffuse, pruritic maculopapular rash within about a week. It is a transient virus–drug immune interaction, not IgE-mediated allergy: stop the drug, test for EBV, and do not label the patient penicillin-allergic.

Management and complications

Supportive care. Rest as tolerated, fluids, and acetaminophen or NSAIDs for fever and throat pain are the treatment. Acyclovir and valacyclovir do not shorten the illness. Glucocorticoids are not given routinely; they are reserved for impending airway obstruction, severe autoimmune hemolytic anemia, and severe thrombocytopenia. Return to school or work is guided by energy level, not by laboratory values.

Splenic rupture. Rupture is rare (about 0.1–0.5%) but clusters in the first 3 weeks and can follow minor trauma or none at all. Sudden left upper quadrant pain, pain referred to the left shoulder (Kehr sign), and hypotension demand emergent imaging and surgical evaluation.

Avoid contact sports and heavy lifting for at least 3–4 weeks from symptom onset and until any splenomegaly has resolved.

Airway compromise. Massive tonsillar hypertrophy can cause drooling, stridor, inability to swallow saliva, and a muffled voice. Treat with glucocorticoids, airway monitoring, and ENT involvement, and exclude a peritonsillar abscess.

Other complications:

• hematologic: cold agglutinin (IgM anti-i) hemolytic anemia, immune thrombocytopenia, neutropenia
• hepatic: usually mild hepatitis; cholestatic jaundice is rare
• neurologic (rare): Guillain–Barré syndrome, Bell palsy, encephalitis, transverse myelitis
• cardiac and immune (rare): myocarditis, hemophagocytic lymphohistiocytosis (HLH); boys with X-linked lymphoproliferative disease (SH2D1A mutation) can develop fulminant, often fatal EBV infection

Heterophile-negative mono-like illness

When repeat heterophile testing and EBV serology are negative, consider other causes of fever, lymphadenopathy, and atypical lymphocytosis. Acute HIV must be excluded in anyone with possible exposure, and concurrent group A streptococcal pharyngitis should be sought when the throat findings are prominent.

In acute HIV, antibodies may still be undetectable. HIV-1 RNA turns positive first, before p24 antigen and antibodies, so it is sent together with the antigen/antibody test, and antiretroviral therapy is started promptly once infection is confirmed.