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Peer-reviewedCC BY-NC-NDInternal Medicine

Development of a Simple Scoring System to Distinguish Epstein-Barr virus-related Infectious Mononucleosis (EBV-IM) from Non-EBV IM Using Routine Laboratory Parameters

Abstract

Objective Infectious mononucleosis (IM) is most commonly caused by Epstein-Barr virus (EBV). However, recent epidemiological shifts have increased the proportion of adult cases attributable to cytomegalovirus (CMV). Early distinction of EBV-related IM (EBV-IM) using routine laboratory parameters may reduce unnecessary testing and facilitate timely counseling regarding activity restriction. This study aimed to identify the laboratory features that distinguish EBV-IM from non-EBV IM and to develop a simple diagnostic scoring system. Methods We retrospectively analyzed 39 consecutive patients with IM (EBV-IM, n = 22; non-EBV IM, n = 17, including CMV-IM, n =8). The laboratory parameters and inflammatory indices were compared between the groups, and receiver operating characteristic curve analyses were used to determine the optimal cutoff values for score development. Results EBV-IM patients had higher alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels than non-EBV IM patients, whereas the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were lower in EBV-IM patients. Four variables were used for scoring: ALT ≥ 120 U/L, ALP ≥ 200 U/L, NLR ≤ 0.6, and CRP ≤ 2.0 mg/dL, collectively termed the EBV-IM Laboratory Score (EL-Score). A score ≥ 2 predicted EBV-IM with an area under the curve of 0.95 (95% confidence interval: 0.88-1.00), a sensitivity of 0.91, and a specificity of 0.94. Conclusions The EL-Score, based on routinely available laboratory parameters, may enable the early distinction between EBV-IM and non-EBV IM in internal medicine practice.

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BibTeX
@article{noguchi2026development,
  title = {{Development of a Simple Scoring System to Distinguish Epstein-Barr virus-related Infectious Mononucleosis (EBV-IM) from Non-EBV IM Using Routine Laboratory Parameters}},
  author = {Erina Noguchi and Takashi Ogasawara and Yuki Hiraoka and Koji Nagayama and Hiroaki Takatori and Kazuyuki Shigeno},
  journal = {Internal Medicine},
  year = {2026},
  month = jul,
  doi = {10.2169/internalmedicine.7450-26},
  url = {https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7450-26/_article},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Development of a Simple Scoring System to Distinguish Epstein-Barr virus-related Infectious Mononucleosis (EBV-IM) from Non-EBV IM Using Routine Laboratory Parameters
AU  - Erina Noguchi
AU  - Takashi Ogasawara
AU  - Yuki Hiraoka
AU  - Koji Nagayama
AU  - Hiroaki Takatori
AU  - Kazuyuki Shigeno
PY  - 2026
DA  - 2026/07/11
JO  - Internal Medicine
DO  - 10.2169/internalmedicine.7450-26
UR  - https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7450-26/_article
AB  - Objective Infectious mononucleosis (IM) is most commonly caused by Epstein-Barr virus (EBV). However, recent epidemiological shifts have increased the proportion of adult cases attributable to cytomegalovirus (CMV). Early distinction of EBV-related IM (EBV-IM) using routine laboratory parameters may reduce unnecessary testing and facilitate timely counseling regarding activity restriction. This study aimed to identify the laboratory features that distinguish EBV-IM from non-EBV IM and to develop a simple diagnostic scoring system. Methods We retrospectively analyzed 39 consecutive patients with IM (EBV-IM, n = 22; non-EBV IM, n = 17, including CMV-IM, n =8). The laboratory parameters and inflammatory indices were compared between the groups, and receiver operating characteristic curve analyses were used to determine the optimal cutoff values for score development. Results EBV-IM patients had higher alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels than non-EBV IM patients, whereas the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were lower in EBV-IM patients. Four variables were used for scoring: ALT ≥ 120 U/L, ALP ≥ 200 U/L, NLR ≤ 0.6, and CRP ≤ 2.0 mg/dL, collectively termed the EBV-IM Laboratory Score (EL-Score). A score ≥ 2 predicted EBV-IM with an area under the curve of 0.95 (95% confidence interval: 0.88-1.00), a sensitivity of 0.91, and a specificity of 0.94. Conclusions The EL-Score, based on routinely available laboratory parameters, may enable the early distinction between EBV-IM and non-EBV IM in internal medicine practice.
SN  - 1349-7235
SN  - 0918-2918
ER  -