Laboratory markers of central nervous system disease activity in children with hemophagocytic lymphohistiocytosis

Abstract

Background Central nervous system (CNS) disease among patients with hemophagocytic lymphohistiocytosis (HLH) has not been standardized, which complicates the study of CNS-HLH and its management. Aims To investigate cerebrospinal fluid (CSF) ferritin, triglycerides (TG), and lactate dehydrogenase (LDH) levels as laboratory markers of CNS-HLH. Settings and design A study was conducted on available frozen pretreatment CSF samples of children treated for HLH. Inclusion criteria were children younger than 18 years, fulfilled at least five of the HLH-2004 diagnostic criteria, their frozen initial CSF sample was available, and all necessary clinical, radiological, and laboratory data were available. Patients and methods TG, ferritin, and LDH were measured in the CSF samples. CNS disease was positive if abnormal neurologic symptom/sign, abnormal CSF analysis (pleocytosis and/or elevated protein), or abnormal neuroimaging. Results Of 101 children with HLH, 33 met the inclusion criteria. Their age ranged from 1.1 to 196 months at diagnosis with a median of 13.5 months. The majority were females (69.7%). Seven patients were negative for CNS-HLH (19.4%) and 29 (80.6%) patients were positive according to the classical CNS-HLH criteria. At the end of the follow-up, 45% of patients had died. Significant correlations were found between CSF TG and both CSF protein and leukocytes (P=0.036 for both), and between CSF TG and serum ferritin (P=0.037). Only ferritin showed a significant correlation between its serum and CSF levels (P<0.0001). CSF ferritin and LDH were higher in nonsurvivors. Conclusions CSF TG may have a diagnostic value as a marker of CNS-HLH, whereas CSF ferritin and LDH may have a prognostic value. Further larger prospective studies are needed to verify these preliminary findings.