Clinical Research Directory

Inclusion Criteria: * Adult patient * Confirmed diagnosis of HLH: * Hscore ≥ 169 * Diagnosis of HLH established by the multidisciplinary team caring for the patient(A 24/7 hotline will be available in case of diagnostic uncertainty: this will be the direct line to the on-call intensivist at Avicenne Hospital, who can contact the coordinating investigator as needed) * First episode of HLH * Admission to intensive care unit * Presence of one or more organ failures: * Circulatory: mBP \< 65 mmHg with lactate \> 2 mmol/L, or treatment with catecholamines * Respiratory: oxygen therapy \> 6 L/min or need for non-invasive ventilation, high-flow nasal cannula oxygen therapy, or invasive mechanical ventilation * Renal: stage 2 or higher according to KDIGO criteria, defined by a creatinine increase ≥ 2 times baseline, or urine output \< 0.5 mL/kg/h for ≥ 12 hours, or initiation of renal replacement therapy * Neurological: GCS ≤ 13 Exclusion Criteria: * Moribund patient with refractory distributive shock: multi-organ failure requiring noradrenaline \> 2.5 µg/kg/min and imminent risk of death. * Inability to administer etoposide within 12 hours. * Patient treated with etoposide prior to admission to the intensive care unit. * Hypersensitivity to etoposide or any of its excipients. * Hypersensitivity or contraindication to dexamethasone or any of its excipients, as described in the package insert for the dexamethasone specialty used in the trial and in the protocol. * Patient with a history of CAR-T cell therapy. * Patient developing HLH within 15 days following chemotherapy for cancer or hematologic malignancy. * Patient not covered by social security. * Patient under legal guardianship, tutelage, or curatorship. * Minor patient. * Pregnant women (positive βhCG), women for whom pregnancy has not been excluded (βhCG not performed in women of childbearing age), or lactating women. * Recent vaccination with a live attenuated vaccine. * Participation in another interventional research study.