Clinical and laboratory features of hemophagocytic lymphohistiocytosis in people with disseminated histoplasmosis

Background 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. Methods 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. Results 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. Conclusion 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.