Flow diagram of clinical decision making when confronted with a patient who has signs and symptoms of HLH. aSome patients with genetic predisposition to HLH may develop atypical disease presentations; bIf safe to obtain; cIf not previously performed; dFor example, consider HSV, VZV, HHV6, HIV, Parvovirus, leishmaniasis, tick-borne illnesses, mosquito-borne illnesses, histoplasmosis and TB, amongst others.