Do you recommend the use of dexamethasone and anakinra as upfront treatment in a pediatric patient with secondary HLH (nonrheumatic) who is too ill to tolerate etoposide?

If there is no concern for new malignancy or systemic infection, then glucocorticoids are reasonable. I use methylprednisolone up to 30 mg/kg/day (max. one gram). Anakinra is a safe and often effective therapy for secondary HLH. It is quick acting and has a short half-life so I use it early. I generally start adults at 100 mg IV/SC every 6 hrs (children 10 mg/kg/day divided q 6 hrs or q 12 hrs if under 20 kg).

Eloseily et al., PMID 31513353.