Peritoneal effusion as a marker of disease severity in secondary hemophagocytic lymphohistiocytosis: Clinical and immunological insights

Abstract

Objective Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome with cytokine storm-mediated multiorgan damage. Although serous effusions are frequent complications, the prognostic significance of peritoneal effusion in secondary HLH (sHLH) remains undefined. This study aimed to determine the incidence, clinical and immunological correlates, and prognostic value of peritoneal effusion in sHLH patients. Methods We retrospectively analyzed 107 adult patients diagnosed with sHLH at the Second Affiliated Hospital of Anhui Medical University between March 2013 and March 2023. Peritoneal effusion was diagnosed based on abdominal ultrasound, computed tomography, or positron emission tomography–computed tomography at initial presentation. Clinical characteristics, laboratory parameters, and lymphocyte subset profiles were compared between patients with and without peritoneal effusion. Logistic regression was used to identify risk factors for peritoneal effusion. Overall survival (OS) was estimated using the Kaplan–Meier method, and independent prognostic factors were assessed using multivariate Cox regression analysis. Results Peritoneal effusion was found in 24/107 (22.4%) sHLH patients and was associated with lower white blood cell, lymphocyte, monocyte, and platelet counts. Lower monocyte counts, higher direct bilirubin, and distinct immune dysregulation (reduced CD4+ T cells, higher NK cell percentages) were identified as risk factors for peritoneal effusion. Peritoneal effusion correlated with concurrent serous effusions (p < 0.05) and markedly shorter median survival (19 vs. 103 days, p = 0.002). Multivariate analysis identified peritoneal effusion as an independent mortality predictor (HR=1.88; 95% CI 1.09-3.24, p = 0.023). Conclusions Peritoneal effusion is an independent predictor of mortality in sHLH patients and is associated with a distinct immune profile. Its presence should alert clinicians to a higher risk of death and prompt early, aggressive therapeutic intervention.