Validation of the HScore and the HLH-2004 diagnostic criteria for the diagnosis of hemophagocytic lymphohistiocytosis in a multicenter cohort.

UNLABELLED

Timely diagnosis of hemophagocytic lymphohistiocytosis (HLH) is critical and relies on clinical judgment. The HLH-2004 criteria are commonly used diagnostic criteria, whereas HScore was recently developed for reactive HLH.

OBJECTIVE

In this external validation study, we sought to compare the diagnostic accuracy of the HLH-2004 criteria and HScore and identify optimal cutoffs stratified by underlying etiology.

METHODS

In this retrospective cohort of all hospitalized adults in Alberta, Canada, (1999-2019) who had ferritin >500 ng/ml and underwent either biopsies or soluble CD25 testing, we calculated the diagnostic accuracy of HLH-2004 and HScore for the overall population and different etiologies.

RESULTS

Of 916 patients, 98 (11%) had HLH. HLH-2004 criteria ≥5 predicted HLH with a sensitivity of 91%, specificity of 93%, positive predictive value of 90%, and negative predictive value of 94% (c-statistic 92%). HScore ≥169 predicted HLH with better sensitivity (96%) but reduced specificity (71%), whereas the optimal cutoff ≥200 performed comparably to HLH-2004. HLH-2004 criteria outperformed HScore in most etiologies, whereas HScore improved sensitivity in inflammatory/autoimmune-HLH. The optimal cutoff of HScore was higher in hematopoietic cell transplant due to higher prevalence of fevers and cytopenias.

CONCLUSION

HLH-2004 criteria and HScore demonstrated excellent discriminatory power in identifying HLH. HScore may improve diagnostic accuracy in autoimmune-HLH.