RESUMEN
BACKGROUND: Cytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine assays are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited. OBJECTIVES: We aimed to analyze real-world single center usage of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and explore its utility in pediatric practice. METHODS: A multiplexed cytokine panel, able to return same-day results, was implemented in April 2020 at our institution and its performance was validated for clinical use. Coded patient data were collected using a REDCap database, and correlations between cytokine levels and outcomes of interest were analyzed retrospectively. RESULTS: Cytokine levels correlate with acuity of care, with patients admitted to the pediatric intensive care unit (PICU) having the highest cytokine values. Patients with familial HLH (fHLH) showed prominent peaks in IFNγ, IL-10, and TNF, while patients with sepsis exhibited high IL-6 and IL-8 with relatively modest IFNγ, and cytokine release syndrome (CRS) post-CAR T cell therapy often demonstrated pan-panel positivity at peak levels, with a similar pattern as that of fHLH. A ratio of [IFNγ]+[IL-10]/[IL-6]+[IL-8] levels was able to distinguish fHLH and CRS from severe sepsis. CONCLUSIONS: Cytokine levels correlate with severity of illness and can help differentiate between syndromes that present similarly, including fHLH and CRS compared to sepsis. Cytokine panels can be used as biomarkers to inform diagnosis and management decisions, but significant work remains to dissect complex clinical patterns of disease.
RESUMEN
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking. METHODS: We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018-2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed. RESULTS: All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified 2 clusters-1 related to strains implicated in 2016-2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain. CONCLUSIONS: It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.