Abstract
Introduction Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome characterized by excessive activation of macrophages and T cells. Early identification and treatment are critical to patient survival, yet significant variability exists in clinical presentation. There is limited data on HLH in underserved patient populations. More information is needed on identifying associated risk factors and demographic data that could contribute to the understanding of HLH presentation, especially in an urban setting. We present a retrospective study on cases of diagnosed and potentially undiagnosed HLH at a single Academic Medical Center between 2019 and 2025.
Methods After obtaining IRB approval, retrospective data was collected from electronic medical records (EMR) at a single tertiary care hospital for patients at risk for HLH between 2019 and 2025. Data was extracted for all patients with an ICD-10 diagnosis code of HLH (D76.1 or D76.2) and all patients with an elevated ferritin level > 6,000 in the given time frame. H-scores and HLH-94 diagnostic criteria were manually calculated for all patients, and patients who were considered high risk (H-score > 169 or HLH-94 > 5) were identified. Finally, high risk patients were further analyzed by secondary chart review.
Patients were placed into three cohorts. Cohort 1: Patients who were diagnosed with HLH while inpatient at the hospital and had an associated ICD-10 diagnosis code, Cohort 2: Patients who were considered for HLH while in the hospital but who did not have a diagnosis code Cohort 3: Patients who were not considered for HLH while in the hospital, but met criteria for high risk HLH retrospectively (H-score > 169 or HLH-94 > 5). Demographic data, mortality rates, and comorbid conditions were extracted and analyzed.
Results 273 patients met initial inclusion criteria based on either a diagnosis code or ferritin > 6,000. Notably, 23 patients (8.4%) had incomplete data on fibrinogen or triglycerides levels that, if obtained, could have increased their risk from low or moderate risk to high risk.
68 patients were identified as high risk for HLH (H score > 169, H-94 criteria > 5). After thorough secondary chart review, 26 patients were excluded due low clinical suspicion for HLH based on other conditions (e.g. fulminant liver failure) contributing to abnormal laboratory findings.
The remaining 42 patients were considered high risk for HLH based on comorbid conditions, clinical presentation, and laboratory findings. Cohorts 1, 2, and 3 consisted of 14 patients each. Of these 42 patients, 55% were Black or African American, 26% were Hispanic, 7% were White, 12% were Other/Unknown. 8 patients had HIV (19%), and 6 patients had sickle cell (14%). All patients in Cohort 1 were tested for EBV viremia and 71% of patients had a positive viral load. The majority of patients in Cohort 2 and 3 were not tested for EBV. Cohort 1 had a mortality rate of 35%, compared to a 71% mortality rate in cohort 2 and a 50% mortality rate in cohort 3.
Conclusions HLH is poorly described in an underserved, urban setting. Identifying risk factors is crucial to rapid diagnosis and treatment of HLH, and these risk factors may vary by demographics. Our study highlights a unique subset of patients at a single urban Academic Medical Center. Sickle cell disease, HIV, and EBV viremia were identified as important risk factors impacting a significant number of HLH cases.
The cohort of patients with a high probability of HLH who were not considered for HLH represent an area for improved screening and diagnosis. Furthermore, there were 23 patients who may have been considered high risk for HLH if fibrinogen and triglyceride levels were drawn. Given the high mortality rate of HLH, an increased awareness of lab tests required for risk stratification is needed. We plan to implement focused education to hospitalist and critical care teams to bridge this knowledge gap and to improve diagnostic assessment and awareness of potential HLH cases.
There are limitations to the study. This is a retrospective single-center study and may include biases or not be representative of the patterns at every hospital system. More data is needed on this topic to generate broader insights into HLH in minority populations, reduce diagnostic delays, and improve patient outcomes.
