# Clinical and Laboratory Features of Hemophagocytic Lymphohistiocytosis in People With Disseminated Histoplasmosis

## TL;DR

This study found that nearly a quarter of hospitalized patients with disseminated histoplasmosis also had hemophagocytic lymphohistiocytosis, a severe immune condition.

## Contribution

The study reports the first prevalence of HLH in DH at a single center and identifies specific biomarkers associated with HLH in this population.

## Key findings

- 20% of participants with disseminated histoplasmosis met criteria for hemophagocytic lymphohistiocytosis.
- Elevated serum ferritin, urine Histoplasma antigen, and serum beta-D-glucan were strongly associated with HLH.
- HLH patients were more likely to require intensive care, though mortality was not significantly higher.

## Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome involving pathologic excitation of the immune system. Disseminated histoplasmosis (DH) is a known trigger of HLH. However, the prevalence of HLH in DH is unknown. Limited data exist on risk factors and outcomes. The goals of this study are to determine the prevalence of HLH among participants with DH at a single center, identify risk factors for HLH in this population, and describe the treatment and outcomes of people with DH and HLH.

We retrospectively identified cases of DH at our institution from 2014 to 2022 and reviewed electronic medical records. We used HLH-2004 criteria to identify those with HLH.

Among 110 participants with DH, 22 (20%) met criteria for HLH. In the subset who were hospitalized, 24% (22/93) had HLH. Compared to participants without HLH, the HLH cohort was more likely to have serum ferritin above the limit of quantification (LOQ) (>15 000 ng/ml), urine Histoplasma antigen above the LOQ (>19 ng/mL), serum 1,3 beta-D-glucan (BDG) above the LOQ (>500 pg/mL), and more likely to require intensive care. There was no significant difference in HIV/AIDS status, race, or sex. Mortality was numerically higher in the HLH cohort (18% vs 7%), but the difference was not statistically significant.

Nearly a quarter of participants with DH admitted to our hospital had HLH. Extreme levels of serum ferritin, urine Histoplasma antigen, and serum BDG should prompt investigation for HLH. Further studies are needed to assess optimal treatment strategies.

Hemophagocytic lymphohistiocytosis occurred in 20% of people with disseminated histoplasmosis at our institution in Arkansas. Very elevated serum ferritin, beta-D-glucan, and urine Histoplasma antigen correlated with HLH and should prompt further investigation for HLH.