Abstract
INTRODUCTION: Macrophage activation syndrome (MAS) is a potentially fatal clinical syndrome due to a cytokine storm secondary to immune dysregulation which can complicate infection, malignancy, autoimmune or autoinflammatory conditions. Recognising the difference between a protective inflammatory response and a pathological one early in the course is imperative. Identifying it can be challenging as it can masquerade as other common presentations including sepsis. We must consider MAS when there is clinical deterioration despite appropriate treatment particularly with autoimmune conditions. CASE DESCRIPTION: 7-year-old girl presented to her local hospital with fever, arthralgia and urticarial rash of 5 days. She had previously had similar episodes which were self-limiting in the previous 3 years. She had an extensive infection screen and antibiotics before being transferred to our hospital in view of persistent symptoms, persistently raised inflammatory markers including ferritin of 50,000, thrombocytopenia, anaemia, stage 3 AKI and hypotensive episodes. Her clinical and laboratory picture was in keeping with systemic JIA developing MAS. Her investigations at this point showed normal white cell count, thrombocytopenia (81) and anaemia (Hb 97g/l), CRP of 248 mg/l and ferritin of 75,050mcg/l with drop in ESR to 2mm/hr. She was treated with IV methylprednisolone 30 mg/kg IV and anakinra 2 mg/kg SC. Despite initial improvement she deteriorated quicky, needing fluid boluses and transfer to PICU. She was resuscitated with fluid boluses and inotropes, developed multiorgan dysfunction, needing ventilatory support and hemofiltration. She was treated with IV methylprednisolone pulse 30 mg/kg, IVIg, increasing dose of subcutaneous anakinra followed by continuous infusion up to a maximum of 12 mg/kg. She developed DIC which was managed with blood products, tranexamic acid and vitamin K. DISCUSSION: Despite appropriate treatment escalation, she deteriorated quickly, developing multiorgan dysfunction with worsening thrombocytopenia, static CRP >200 and ferritin rising to 75,000. She was discussed with haematology and trialled on ciclosporin and etoposide. Our dilemma with her being in a life-threatening situation was how long to wait for the medications used to take effect and when to jump in with the next agent. Her bone marrow biopsy showed no evidence of malignancy. Her extensive investigations included abnormal perforin tests, and whole genome sequencing that was awaited to differentiate primary HLH. In view of life-threatening MAS despite a multipronged approach, we decided to try emapalumab as a last resort. This helped the child turn the corner on day 6. She briefly went on to HLH protocol 2004 until genetic tests came back unsupportive of primary HLH, primary immunodeficiency and systemic autoinflammatory diseases, after which she went onto maintenance treatment with anakinra and methotrexate and is doing well. KEY LEARNING POINTS: • Important to recognise MAS in a timely manner with falling ESR, high CRP, coagulopathy in a sick child • Multidisciplinary approach is crucial to manage these complex patients to including haematology, rheumatology, critical care, immunology, genetics and national forums where possible. • Timely use of medications specifically IL1 blockade and newer drugs like interferon gamma inhibitor emapalumab • The dilemma of a multipronged approach versus a stepwise approach – time is crucial faced with life-threatening MAS