How is the diagnosis made?
It can be very difficult to differentiate HLH from overwhelming sepsis and so the condition requires a high degree of suspicion. Secondary HLH should be suspected in any unwell patient with an unexplained fever, cytopenias (especially thrombocytopenia) and organ dysfunction. A serum ferritin should be checked in these cases, and if >4000 mg/L should trigger further investigations as the likelihood of HLH is increased. Ferritin levels of >10,000 mg/L are highly concerning and may indicate the need for immediate treatment. There is no universally accepted diagnostic criteria however there are scoring systems in use including HLH-2004 and Hscore.3
The following easy to use mnenomic uses some of the parameters from the scoring systems (reproduced with thanks to Dr Gui Tran, Cons Rheumatologist, Harrogate and District Foundation Trust):
|CONSIDER A DIAGNOSIS OF HLH IF:|
|BONE MARROW ASPIRATE||Haemohagocytosis|
|CYTOPENIA||2 of Hb <9g/dL, platelet count <100×109/L, neutrophil count <1×109/L|
|ELEVATED TEMPERATURE||Pyrexia with no focus of infection|
|HEPATOSPLENOMEGALY||Evidence on physical or radiological exam|
Other markers include
- Elevated LDH
- Elevated D-dimer
- Elevated CRP
Further imaging including PET scans, additional tissue sampling and bone marrow aspiration may aid in the diagnosis, however ultimately the final diagnosis of HLH is a clinical one and requires support from rheumatology and haematology experts.