Clinical differentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan

INTRODUCTION: Infectious mononucleosis (IM) is a common viral infection that typically causes fever, pharyngitis, and lymphadenopathy in young patients. The Epstein-Barr virus (EBV) is the most common cause of IM, followed by cytomegalovirus (CMV). Given that serological testing is associated with limitations regarding its accuracy, availability, and time to receive results, clinical differentiation based on symptoms, signs, and basic tests would be useful. We evaluated whether clinical findings could be used to differentiate EBV-IM from CMV-IM. METHODS: In this single-center retrospective case-control study, we evaluated >14-year-old patients with serologically confirmed EBV-IM or CMV-IM during 2006–2017. We compared the patients’ symptoms, physical findings, blood counts, and serum biomarkers to create three regression models: model 1 (symptoms and signs), model 2 (model 1 plus sonographic hepatosplenomegaly and blood counts), and model 3 (model 2 plus hepatobiliary biomarkers). RESULTS: Among the 122 patients (72.6%) with EBV-IM and 46 patients (27.4%) with CMV-IM, the median age was 25 years and 82 patients (48.8%) were male. The median age was 10 years older in the CMV-IM group (p < 0.001) and the median interval from onset to visit was 5 days longer in the CMV-IM group (p < 0.001). Logistic regression revealed that EBV-IM was predicted by younger age, short onset-to-visit interval, lymphadenopathy, tonsillar white coat, hepatosplenomegaly, atypical lymphocytosis, and elevations of lactate dehydrogenase and gamma-glutamyl transferase. All regression models had areas under the curve of >0.9. CONCLUSION: History and physical findings, especially when used with atypical lymphocytosis and sonographic hepatosplenomegaly, can help physicians differentiate EBV-IM from CMV-IM.