Factors Associated with in-Hospital Mortality in Patients with Hemophagocytic Lymphohistiocytosis: A 5-Year Analysis from the National Inpatient Sample

Background: Haemophagocytic lymphohistiocytosis (HLH) is an aggressive, life-threatening syndrome caused by a robust and excessive immune response leading to multi-organ failure. HLH can be due to a myriad of etiologies that range from primary disorders related to genetic defects or secondary to infections, autoimmune conditions, malignancies, etc. HLH has been broadly recognized in the pediatric population. Most of the clinical guidelines and evidence are based on this population; thus, more literature is needed amongst the adult population, especially on what factors increase mortality. Therefore, our study aims to evaluate factors associated with mortality in HLH Among Hospitalized Patients in the US using a Large Nation-wide Database.

Methods: We performed a retrospective survey analysis of the National Inpatient Sample (NIS) using ICD10-CM and PCS codes to identify adult patients hospitalized with a primary or secondary diagnosis of HLH between October 2015 and December 2019. We compared patients who survived the illness as a control group versus patients who died during the hospitalization. A comparison was done between demographic variables including age, race, sex, median income, among other factors. Data regarding past medical history was also included. The most common causes of HLH were queried and compared between the two groups. Lastly, we performed a final comparison between multiple inpatient complications and outcomes between the two groups. We used qui-square and fisher exact test for categorical variables and student t-test or Mann-Whitney U test for continuous variables. All analysis was done using R studio utilizing the survey package.

Results: Data from 8,660 admissions with HLH were included, of which 21% of patients died during the hospitalization. Patients with HLH who died tended to be males (61%), slightly older at age 53 years, and a higher percentage of white patients (55%), though not statistically significant than those who did not die. On the other hand, increased mortality was associated with hematological malignancies (37% vs 24%, p<0.05), baseline chronic kidney, heart, and liver disease. Additionally, these patients were also more likely to develop renal failure, non-septic shock, and pneumonia. Interestingly, patients with rheumatological disorders had statistically lower deaths (13% vs 17% p<0.05). Patients in the lowest percentile of income had the highest percentage of deaths at 30% and the highest percentile of income had a lower percentage of deaths at 22%. The length of inpatient stay was significantly longer in patients who died (18 vs 14 days, p<0.05). In terms of location, larger academic hospitals had higher mortality (77% vs 71%, p=0.02), with no difference between regions.

Conclusions: This nationwide data analysis demonstrates the high mortality rates that persist in patients with HLH. Our study contributes to the growing literature on HLH, an intricate and complex topic that is not yet fully understood. Increased attention should be placed on the older population with pre-existent co-morbidities as well as patients with hematological malignancies and low socioeconomic status who are at potentially higher risk of death, to elucidate the mechanisms leading to poor outcomes and potential treatments of this condition.

No relevant conflicts of interest to declare.