The HLH-2004 protocol provides a framework for diagnosing HLH, outlining clinical, laboratory, and pathological criteria, including fever, splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis in hematopoietic or lymphoid organs, low or absent NK cell activity, hyperferritinemia, elevated soluble CD25, and elevated chemokine (C-X-C motif) ligand 9 (CXCL9) [12]. This evidence concerns the gene CXCL9 and hemophagocytic syndrome.