To analyze the clinical characteristics of infectious mononucleosis (IM) and Epstein-Barr virus associated hemophagocytic syndrome (EBV-HLH), and to investigate the risk factors for IM progressing to EBV-HLH.

Data of 217 patients with EBV infection who were treated in the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2020 were collected, and then divided into IM group and EBV-HLH group according to whether complicated with hemophagocytic syndrome or not. The general data, clinical manifestations, laboratory examination, treatment and prognosis of the two groups were collected and analyzed, retrospectively. The clinical risk factors of IM progressing to EBV-HLH were analyzed by multivariate Logistic regression.

The median age of patients in EBV-HLH group was elder than IM group [25 (21, 56) years old vs. 21 (18, 25) years old; Z =-2.658, P = 0.008]. Compared with patients in IM group, patients in EBV-HLH group had higher peaks [40.3 (39.8, 40.9) ℃ vs. 38.9 (38.4, 39.3) ℃; Z =-5.723, P < 0.001] and longer duration of fever [30 (18, 44) d vs. 7 (4, 12) d; Z =-5.469, P < 0.001]. The incidences of hepatomegaly, diarrhea, jaundice, pneumonia, bleeding (χ² = 18.341, χ² = 13.444, χ² = 27.344, χ² = 68.405, χ² = 32.967; all P < 0.001) and heart failure (Fisher’s exact test: P = 0.005) in EBV-HLH group were significantly higher than those of IM group, while the incidence of tonsillitis of patients in EBV-HLH group was significantly lower than that of IM group [83.1% (167/201) vs. 25.0% (4/16); χ² = 26.556, P < 0.001]. Compared with patients in IM group, the leukocytes [2.2 (1.4, 3.0) × 10⁹/L vs. 11.2 (7.7, 14.4) × 10⁹/L ; Z =-5.883, P < 0.001], hemoglobin [(87.8 ± 17.1) g/L vs. (134.4 ± 16.5) g/L; t =-10.806, P < 0.001], platelet [45.5 (27.0, 74.5) × 10⁹/L vs. 165.0 (133.0, 205.5) × 10⁹/L; Z =-6.316, P < 0.001] of patients in EBV-HLH group were significantly higher. The liver function showed that total bilirubin [58.2 (13.9, 108.3) μmol/L vs. 12.3 (9.1, 16.7) μmol/L; Z =-4.119, P < 0.001], lactate dehydrogenase [3 000.0 (953.8, 6 665.8) U/L vs. 1 459.5 (991.0, 2 023.6) U/L; Z =-3.206, P = 0.001] of patients in EBV-HLH group were higher than those of IM group, while albumin of patients in EBV-HLH group was lower than that of IM group [(26.9 ± 4.6) g/L vs. (40.1 ± 4.6) g/L; t =-11.054, P < 0.001]. The coagulation function showed D-D dimer significantly increased [4.8 (0.8, 10.4) mg/L vs. 1.0 (0.7, 1.7) mg/L, Z =-3.063, P = 0.002], and fibrinogen decreased [0.9(0.7, 2.9) g/L vs. 2.7 (2.2, 3.1) g/L; Z =-3.395, P = 0.001] of EBV-HLH patients. C-reactive protein [51.7 (31.6, 90.0) mg/L vs. 17.2 (7.1, 23.0) mg/L; Z =-3.206, P < 0.001], ferritin [7 835.0 (2 101.5, 23 481.5) ng/ml vs. 563.3 (213.9, 1215.5) ng/ml; Z =-4.859, P = 0.001] and triglyceride [2.5 (1.8, 2.9) mmol/L vs. 1.6 (1.1, 2.2) mmol/L; Z =-2.809, P = 0.005] of patients in EBV-HLH group were significantly higher than those of IM group. There were significant differences between patients with EBV-HLH and IM in the percentage of CD4⁺ T cell [36.28 (28.90, 46.02)% vs. 13.07 (9.49, 18.16)%; Z =-4.698, P < 0.001], the percentage of B cell [6.50 (1.36, 9.74)% vs. 1.89 (1.06, 4.05)%; Z =-2.217, P = 0.027], the percentage of CD3⁺ T cell [80.14 (70.17, 87.59)% vs. 91.71 (89.02, 94.40)%; Z =-3.750, P < 0.001], the percentage of CD8⁺ T cell [35.60 (23.58, 50.98)% vs. 72.98 (65.02, 80.00)%; Z =-4.938, P < 0.001], while all lymphocyte subsets in patients with EBV-HLH were lower than those of patients with IM. Multivariate Logistic regression analysis showed that the duration of fever (OR = 1.171, 95%CI: 1.010-1.357, P = 0.036) was the risk factors for patients with IM progressing to EBV-HLH.

The duration of fever was the risk factor for patients with IM progressing to EBV-HLH. Patients with infectious mononucleosis who have persistent fever, accompanied by multiple blood cell decline and multiple organ dysfunction, screening for hemophagocytic syndrome should be performed and timely treatment should be taken to improve the prognosis.