HLH-2004 diagnostic criteria. Diagnosis of HLH is based on HLH-2004 clinical and laboratory diagnostic criteria along with clinical judgement and patient’s history. In 1991, the Histiocyte Society proposed a standardized set of 5 diagnostic criteria for HLH, which were used for the prospective HLH-94 clinical trial. These criteria were revised for HLH-2004. The five criteria in the 1991 guidelines were kept: 1) fever, 2) splenomegaly, 3) cytopenias affecting at least two of three lineages in the peripheral blood, 4) hypertriglyceridemia and/or hypofibrinogenemia, and 5) hemophagocytosis in bone marrow, spleen, or lymph nodes. In addition, three additional criteria were introduced: 6) low or absent NK-cell activity, 7) hyperferritinemia, and 8) high levels of sIL-2r. Individuals need to meet 5 or more of of 8 diagnostic criteria, though patients with a molecular diagnosis consistent with HLH do not necessarily need to fulfill the diagnostic criteria. The score was developed for children, and has not been validated in adults. Another score, called the HScore (not shown) generates a score indicating the likelihood of secondary HLH based on graded clinical and laboratory parameters and may be helpful in distinguishing HLH from infection and for patient monitoring.
