Microbiology · Year 2 · from Microbiology
Case 2: Infectious Mononucleosis with Complications
Presentation
A 17-year-old high school student presents with 2 weeks of fatigue, sore throat, and fever. He was seen at an urgent care clinic a week ago and was prescribed amoxicillin for strep throat despite a negative rapid strep test. Two days later, he developed a widespread maculopapular rash. Examination reveals temperature 38.5°C, posterior cervical and axillary lymphadenopathy, pharyngeal erythema with tonsillar enlargement and exudates, a diffuse maculopapular rash, and a palpable spleen tip. Laboratory studies show WBC 14,000/μL with 60% lymphocytes (many atypical), AST 145 U/L, and ALT 168 U/L.
Clinical Image
Peripheral blood smear demonstrating atypical lymphocytes (reactive CD8+ T cells) with abundant blue cytoplasm, irregular nuclei, and cytoplasm molding around surrounding red blood cells, characteristic of infectious mononucleosis.
Image Source: Lecture image - EBV laboratory findings
Questions
- What is the diagnosis, and what caused the rash?
- What is the origin of the atypical lymphocytes seen on peripheral blood smear?
- What are the potential complications, and why is this patient's physical activity being restricted?
- How would you confirm the diagnosis serologically?
Answers
- Diagnosis and rash etiology: This is infectious mononucleosis caused by Epstein-Barr virus (EBV). The rash developed after administration of ampicillin/amoxicillin, which occurs in up to 90% of patients with infectious mononucleosis who receive these antibiotics. The mechanism is not a true allergy but rather an interaction between the viral infection and the drug, possibly related to altered drug metabolism or immune activation. This does not preclude future use of aminopenicillins.
- Atypical lymphocytes origin: The atypical lymphocytes are reactive CD8+ cytotoxic T cells responding to EBV-infected B lymphocytes, NOT the infected B cells themselves. EBV infects B cells via the CD21 (complement receptor 2) receptor. The immune system mounts a robust T cell response to control the infection, and these activated T cells have the characteristic morphology with abundant blue cytoplasm, irregular nuclei, and membrane molding around adjacent red blood cells.
- Complications and activity restriction:
- Splenomegaly (50% of cases) with risk of splenic rupture - the most serious acute complication. Patients should avoid contact sports for 3-4 weeks minimum (some recommend until spleen returns to normal size on imaging)
- Hepatitis (elevated transaminases in 80-90%; clinical jaundice rare)
- Airway obstruction from tonsillar enlargement (may require corticosteroids)
- Hemolytic anemia from cold agglutinins
- Thrombocytopenia
- Rare: encephalitis, Guillain-Barré syndrome, myocarditis
- Serologic confirmation:
- Heterophile antibody test (Monospot): Quick screening test detecting antibodies that agglutinate sheep/horse RBCs; may be falsely negative early in illness or in children <4 years
- EBV-specific serologies:
- VCA IgM: Present during acute infection (confirms acute EBV)
- VCA IgG: Present during acute and remains positive lifelong
- EBNA (Epstein-Barr nuclear antigen): Appears weeks to months after acute infection; if positive, rules OUT acute infection
- Pattern of VCA IgM+, VCA IgG+, EBNA- confirms acute infection