Clinical Research Directory

Inclusion Criteria * Patient aged 0 to 22 years * Patient with HLH syndrome confirmed by at least one of the two criteria: 1. Confirmed genetic diagnosis of a condition predisposing to primary HLH (see table 1 and table 2) or abnormal expression of perforin, MUNC13-4, SAP or XIAP in FACS and/or positive family history OR 2. Presence of at least 5 of the 8 following HLH diagnostic criteria: * Fever * Splenomegaly * Cytopenia (affecting at least two cell lineages) * Haemoglobin \< 9 g/dl (\<10 g/dL in neonates) * Platelets \< 100,000/µL * Absolute neutrophil count (ANC) \< 1,000/µL * Hypertriglyceridemia and/or hypofibrinogenemia * Fasting triglycerides ≥ 3 mmol/l * Fibrinogen \<1.5 g/L * Haemophagocytosis found in a histological sample (without evidence of a malignant process or an underlying rheumatic disorder) * Decreased or absent NK function * Ferritin ≥ 500 µg/l * Presence of activated T cells in the immune phenotyping as evidenced by expression of the activation marker DR (superior to the normal value of the laboratory) OR CD25 soluble (sIL-2 receptor) ≥ 2,400 U/mL. * Patient with no previous specific treatment for HLH syndrome * For patients of childbearing age : using an effective method of contraception during the trial, and through to 90 days after EOS for male participants and 30 days after EOS for female participants * Freely given, informed and written consent of legal representative of the participant or consent of the adult participant * Affiliation to Social Security. Exclusion Criteria * Previous treatment with ATG, Alemtuzumab, Etoposide, JAK-inhibitors, rifampicin and/or anti-Interferon gamma antibodies. St. John's Wort, or any other strong CYP3A4 inducers. * Previous treatment with corticosteroids and/or cyclosporine A for more than 14 days * Isolated CNS disease. * Contraindication to receive Ruxolitinib: * History of hypersensitivity to the active substance or to any of the excipients * Pregnant or lactating female patient * Contraindication to receive methylprednisolone or prednisolone * History of hypersensitivity to the active substance or to any of the excipients * Any infectious condition with the exception of infections, which are the trigger for lymphohistiocytic activation. * Patient with acute very severe renal impairment (Creatinine Clearance \<15 mL/min/1.73m²) who are NOT receiving dialysis. * Patient with Grade 4 hepatic failure according to the CTCAE v5.0 of 27 November 2017 (Life-threatening consequences; moderate to severe encephalopathy; coma) * Past or know active tuberculosis * Known rheumatologic disorder. * Known active malignancy. * Patient who is taking another investigational agent or is enrolled in another treatment protocol. * Patient who cannot tolerate administration of drugs PO or through NG