Purpose: To investigate a possible link between acute Epstein-Barr virus infection and Lemierre syndrome, a rare yet life-threatening infection.

Methods: A systematic review was conducted adhering to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnosis criteria for Lemierre syndrome were established, and data extraction encompassed demographic data, clinical, and laboratory information.

Results: Out of 985 initially identified papers, 132 articles were selected for the final analysis. They reported on 151 cases of Lemierre syndrome (76 female and 75 male patients with a median of 18 years) alongside interpretable results for Epstein-Barr virus serology. Among these, 38 cases (25%) tested positive for acute Epstein-Barr virus serology. There were no differences in terms of age, sex, or Fusobacterium presence between the serologically positive and negative groups. Conversely, instances of cervical thrombophlebitis and pulmonary complications were significantly higher (P = 0.0001) among those testing negative. The disease course was lethal in one case for each of the two groups.

Conclusions: This analysis provides evidence of an association between acute Epstein-Barr virus infection and Lemierre syndrome. Raising awareness of this link within the medical community is desirable.