The diagnosis of HLH can be difficult due to the overlap with other hyperinflammatory syndromes (SIRS, sepsis, severe infection). The actual diagnostic criteria for HLH (Henter et al. 2007) are validated only for pediatric patients with genetic HLH. Therefore, for the diagnosis of HLH in adults always the dynamics of individual parameters (e.g. increase of ferritin) and the experience of the physician crucial. The detection of hemophagocytosis does not prove the existence of HLH and is not mandatory for the diagnosis. In case of critically ill patients and unclear diagnosis one of the HLH centers in Jena and Hamburg should be contacted.
The currently used diagnostic criteria are listed in Table 2 ( HLH Study Group of the Histiocyte Society, Henter et al 2007). A diagnostic path, which is taken from the current German Onkopedia guideline is shown in Figure 2.
- • Familial disease/knowngenetic defect
or
- Clinical and laboratory criteria(5/8 criteria should be fulfilled):
| Fever |
| Splenomegaly |
| Cytopenia(≥2 cell lines; Hemoglobin <9 g/dl; Platelets<100/nl; Neutrophils<1/nl) |
| Hypertriglyceridemia (≥3 mmol/l) and/or Hypofibrinogenemia (<1.5g/l) |
| Ferritin ≥500 μg/l |
| sCD25 ≥2,400 U/ml (sCD25 = löslicher IL-2-Rezeptor) |
| Decreased or absent NK cell activity |
| Hemophagocytosis (Bone Marrow, CSF, or lymph nodes) |
- Supporting clinical symptoms and laboratory anomalies for HLH diagnosis:
cerebral symptoms with moderate pleocytosis and/or elevated protein, elevated transaminases, bilirubin, and lactate dehydrogenase.
Table 2: Diagnostic criteria for HLH (sCD25 indicates soluble interleukin-2 receptor)
Abbildung 2: Diagnosepfad bei Verdacht auf HLH (aus: Onkopedia Leitlinie zur HLH, Onkopedia)
Legende: 1FUO – Fieber unklarer Genese (Fever of Unknown Origin); 2SIRS – Systemisches Inflammatorisches Response-Syndrom; 3MODS – multiples Organversagen (Multiple Organ Dysfunction Syndrome); 4MAS – Macrophase Activation Syndrome; 5Referenzzentrum Pädiatrie: http://www.uke.de/kliniken/haematologie/index_39115.php; Referenzzentrum Erwachsene Patienten: http://www.hlh-registry.org; 6MDS – Myelodysplastisches Syndrom; 7LED – Lupus Erythematodes Disseminatus