Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive cytokine activation. Its treatment remains largely inadequate, with high mortality. Recent research into its pathogenesis has revealed a major role of cytokines such as Interferon-γ (IFN-γ), Tumour Necrosis Factor-α (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-18 (IL-18). These cytokines in the future may also help identify HLH in the early stage or predict HLH in high-risk patients. Both animal and human research provide evidence of the role of biochemical mediators in HLH. The interplay of cytokines and cells in the pathogenesis of HLH has also opened up new targeted therapeutics. These treatment options are being tried for primary and secondary forms of HLH, with promising results. Emapalumab, an anti-IFN-γ monoclonal antibody, has been widely studied in HLH with promising results. Anti-IL-1 receptor antibody (anakinra), anti-IL-18 neutralising molecule (tadekinig-α), and anti-CD-52 monoclonal antibody (alemtuzumab) are newer drugs in the pipeline for the treatment of HLH. Small molecule inhibition beyond receptor activation in cells has had immense success in the past in treating spondylarthritis and leukaemia. Ruxolitinib, a Janus kinase inhibitor, also showed positive outcomes in the treatment of HLH. With these emerging treatment options, the future outlook for HLH is moving toward a promising new horizon.