Ruxolitinib as First Line Treatment in Primary Haemophagocytic Lymphohistiocytosis (R-HLH) (R-HLH)

Inclusion Criteria Patient aged 0 to 22 years Patient with HLH syndrome confirmed by at least one of the two criteria: 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 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