Understanding the complexity of secondary HLH and its relationship to genetic predisposition

The concept of secondary HLH is complex and involves a spectrum of inflammation responses in patients, making it challenging to define primary and secondary HLH. Secondary HLH may have a genetic predisposition, while historically primary HLH was attributed to genetic abnormalities. However, the understanding has shifted to a gradient, with some patients having a strong genetic predisposition while others may have minor genetic tweaks that increase their risk of developing HLH when exposed to triggers. This challenges the previous notion that HLH is solely a genetic, congenital disease and is crucial in the adult population. Ultimately, many patients with secondary HLH may have genetic abnormalities, even if they are not readily identifiable.