Management and outcomes in secondary diabetes among pediatric patients hospitalized with hemophagocytic lymphohistiocytosis

Abstract

Objectives: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder marked by massive cytokine release from macrophage and T-cell activation. Hallmarks include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogemia, and elevations in ferritin and soluble IL-2 receptor. Given the association of HLH with inflammation and glucocorticoid therapy, the development of hyperglycemia is not unexpected. Descriptions of the prevalence of secondary diabetes in youth diagnosed with HLH are lacking.

Methods: Retrospective review from 2010 through 2019 of hospitalized youth 0-21 years diagnosed with HLH. The primary outcome of interest was the development of secondary diabetes, defined as a serum glucose 200 mg/dL or higher necessitating insulin therapy.

Results: Of 28 patients with HLH, 36 % (n=10) developed secondary diabetes. The only risk factor associated with secondary diabetes was an infectious cause of HLH (60 % vs. 27.8 %, p 0.041). Intravenous regular insulin was used in 80 % of patients with a mean duration of 9.5 days (2-24 days). Most (70 %) needed insulin within 5 days of starting steroids. Stays in the ICU were longer (median 20 vs. 3 days, p 0.007) and intubation more likely (90 vs. 45 %, p 0.041) among those with secondary diabetes. Mortality was high (16-30 %) regardless of insulin use (p 0.634).

Conclusions: One-third of hospitalized pediatric patients with HLH developed secondary diabetes requiring insulin therapy. Insulin is typically started within 5 days of initiating steroids, limited to IV infusions, and often is not needed by discharge. Secondary diabetes was associated with longer ICU stays and heightened risk of intubation.

Keywords: diabetes mellitus; hemophagocytic lymphohistiocytosis; hyperglycemia; pediatrics.