Table 1.

The spectrum of hyperferritinemic syndromes: suspected aetiologies, clinical features and therapeutic strategies

Hyperferritinemic syndromes
Name	Aetiology	Clinical features	Therapeutic strategy
Secondary haemophagocytic lymphohistiocytosis	Infections • Viruses • Bacteria • Parasites • Fungi Malignancies • Mainly malignant lymphoma Autoinflammatory or autoimmune disorders Other causes • Transplantation • Metabolic • Traumatic • Iatrogenic (immunosuppression, vaccination, surgery, haemodialysis) • Pregnancy	Fever, rash, hepatosplenomegaly, lymph node enlargement, bleeding diathesis, sepsis-like syndrome, variable degrees of neurologic symptoms, possibly rapidly unexpected progress to multiple organ failure	HLH-94 protocol: • Glucocorticoids • Cyclosporine A • Intrathecal therapy • Etoposide Treatment of the specific trigger/underlying disease: • Glucocorticoids • Anti-viral drugs • Anti-CD20 (rituximab) • Intravenous immunoglobulins • Chemotherapy • IL-1 inhibitors (anakinra, canakinumab) • IL6 inhibitors (tocilizumab) Currently being tested: • JAK1/2 inhibitors (ruxolitinib) • anti–IFN-γ (alemtuzumab, emapalumab)
Catastrophic antiphospholipid syndrome	Trigger supposed to be infections in the presence of antiphospholipid antibodies	Microvascular thrombosis: renal insufficiency, acute respiratory distress syndrome/pulmonary embolism, encephalopathy, stroke, seizures, headache and coma, heart failure, myocardial infarction, valvular defects, livedo reticularis, skin necrosis and digital ischemia; spleen, adrenal glands, pancreas, retina and bone marrow infarction	Intravenous heparin Glucocorticoids Intravenous immunoglobulins Cyclophosphamide Anti-CD20 (rituximab) Plasmapheresis Eculizumab
Adult onset Still’s disease	Not clearly defined • Viruses • Bacteria • Solid cancers • Haematological malignancies	Fever, arthritis, skin rash, myalgias, splenomegaly, lymphadenopathy, sore throat, liver involvement, pleurisy or pericarditis, abdominal pain, aseptic meningitis, disseminated intravascular coagulation, haemolysis	Glucocorticoids Hydroxychloroquine Intravenous immunoglobulins Methotrexate Cyclosporine IL-1 inhibitors (anakinra, canakinumab, rilonacept) IL-6 inhibitors (tocilizumab) TNF-inhibitors (infliximab, etanercept and adalimumab)
Septic shock	Infections • Viruses • Bacteria • Parasites • Fungi	Fever, rash, disseminated intravascular coagulation, variable degrees of neurologic symptoms, possibly rapidly unexpected progress to multiple organ failure	Broad spectrum antibiotic therapy Fluid resuscitation Vasopressors