Although reviews show disseminated histoplasmosis (DH) is commonly complicated with haemophagocytic lymphohistiocytosis (HLH), few studies haves described the clinical and laboratory features associated with HLH in patients with DH. Mandrell et al retrospectively analysed 110 participants with DH in the USA and reported an HLH prevalence of 20%. The HLH cohort had higher levels of serum ferritin, urine Histoplasma antigen, and serum 1,3 beta-D-glucan (BDG) compared with DH without HLH.
Besides the markedly elevated levels of ferritin observed in 100% of participants complicated with HLH, other factors listed in the HLH-2004 criteria, including bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, fever > 38.5 °C, splenomegaly, and hemophagocytosis were also assessed and present in 100%, 95.4%, 95.5%, 63.6% and 54.5% of the HLH cases, respectively.
Mandrell et al, however, noted that the prevalence of HLH in the index study was somewhat lower compared with a previous study from Mexico by Cruz-Quezada et al, which reported a prevalence of 36.1%. The authors speculated that the disparity may be because their US study population was not restricted to participants with DH living with HIV. Corroboratively, in the index study, HLH were more common in cases of DH living with HIV (68%) compared with DH without HIV infection (32%), although not statistically significant. In contrast, in a review of pancytopenia in DH, Ekeng and colleagues highlighted that cases of DH complicated with HLH were more in participants living without HIV (62.2%) compared with those living with HIV (37.8%). Thus, while infections are known risk factors for HLH, it is seemingly unclear whether HIV infection increases the likelihood of HLH occurrence in patients with DH.
A more predictive tool of HLH occurrence in DH should rather entail an assay for biochemical parameters such as ferritin, triglycerides, and fibrinogen. In addition, laboratory features such as markedly elevated urine Histoplasma antigen and serum BDG levels were seen to be significantly associated with HLH in DH. Cytopenias may also suggest HLH coexisting with DH. Ekeng et al affirmed this in a review, which reported a much higher HLH prevalence of 62.5% in DH with pancytopenia.
