Systemic juvenile idiopathic arthritis and macrophage activation syndrome

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Target exams

Red flags

• A child with known or suspected systemic JIA who develops a new persistent fever with a falling platelet count and a rapidly rising ferritin has macrophage activation syndrome until proven otherwise; do not wait for the full syndrome before starting treatment
• A falling ESR in a child whose disease is worsening is paradoxical and points to macrophage activation syndrome, because the fibrinogen that drives the ESR is being consumed
• Macrophage activation syndrome can present silently under tocilizumab because the IL-6 blockade suppresses the fever and the CRP without controlling the underlying IFN-gamma cytokine storm
• Ferritin in macrophage activation syndrome often exceeds ten thousand nanograms per millilitre; a ferritin over ten thousand with a falling platelet count is an emergency
• Untreated macrophage activation syndrome progresses to multiorgan failure and death within days; the survival depends on the speed of recognition and the early anakinra and glucocorticoid therapy

Life stages

Care settings

Clinical exam formats

Board mappings

• Names systemic juvenile idiopathic arthritis as the autoinflammatory subtype of JIA defined by quotidian fever with an evanescent rash and arthritis by the ILAR criteria
• Recognises macrophage activation syndrome as the life-threatening complication of uncontrolled cytokine storm presenting with falling platelets, rising ferritin and falling fibrinogen
• States that a child with known systemic JIA who develops a new persistent fever with falling platelets and rising ferritin has macrophage activation syndrome until proven otherwise
• Explains how the innate-immune IL-1 and IL-6 cytokine axis drives the systemic features of sJIA and how the uncontrolled T-cell and macrophage activation with IFN-gamma produces the macrophage activation syndrome
• Applies the 2016 EULAR ACR PRINTO classification criteria for MAS in the febrile child with sJIA
• Coordinates the multidisciplinary management of the child with sJIA and MAS across paediatric rheumatology, intensive care, haematology and infectious diseases
• The 2016 EULAR ACR PRINTO MAS criteria require ferritin over six hundred and eighty-four nanograms per millilitre plus any two of platelet count under one hundred and eighty-one, AST over forty-eight, triglycerides over one hundred and fifty-six, and fibrinogen under three hundred and sixty
• IL-1 blockade with anakinra or canakinumab is first-line for the systemic features, with IL-6 blockade by tocilizumab for the under thirty kilograms child at twelve milligrams per kilogram every two weeks
• MAS is treated with intravenous methylprednisolone pulses, ciclosporin and anakinra, with the refractory case escalating to etoposide
• Synthesises the recognition, prevention and stepwise management of sJIA and its macrophage activation syndrome into a single bedside plan in the specialist centre
• Counsels the family of a child with sJIA on the risk of macrophage activation syndrome, the warning signs of persistent fever and falling platelets, and the rationale for IL-1 blockade
• Builds the disposition and retrieval plan for the child with established MAS, with the early escalation to intensive care
• Level 1: Recognition of the clinical features of sJIA and the warning signs of macrophage activation syndrome
• Level 2: Application of the 2016 MAS classification criteria and the IL-1 and IL-6 biologic treatment pathway
• Level 3: Coordination of the definitive management of refractory MAS with the multidisciplinary team
• The ILAR classification of juvenile idiopathic arthritis with the systemic subtype defined by quotidian fever, evanescent rash and arthritis
• The pathophysiology of the innate-immune cytokine storm of IL-1, IL-6 and IL-18 that drives sJIA and the uncontrolled IFN-gamma macrophage activation that produces MAS
• The management of sJIA with IL-1 and IL-6 blockade and the management of MAS with high-dose glucocorticoids, ciclosporin and anakinra
• Structured assessment of the child with suspected sJIA for the quotidian fever, the evanescent rash and the arthritis
• Recognition that a falling platelet count with a rising ferritin and a falling fibrinogen in the febrile child with sJIA is macrophage activation syndrome
• Communication of the plan for biologic therapy and the MAS warning signs to the child and family
• Systemic juvenile idiopathic arthritis as the autoinflammatory subtype of JIA driven by the innate-immune IL-1 and IL-6 axis
• The 2016 EULAR ACR PRINTO classification criteria for macrophage activation syndrome and the HScore
• The role of anakinra, canakinumab and tocilizumab in the treatment of sJIA and the escalation pathway for refractory MAS
• Recognition of the clinical features of sJIA and the warning signs of macrophage activation syndrome
• Application of the IL-1 blockade as first-line biologic therapy for the systemic features of sJIA
• Coordination of the diagnostic and therapeutic pathway and the transfer to the specialist centre
• Canadian approach to the recognition and treatment of sJIA with the IL-1 and IL-6 blockade
• The 2016 classification criteria for macrophage activation syndrome and the role of the HScore
• The management of refractory MAS with high-dose glucocorticoids, ciclosporin and the escalation to etoposide