006 Macrophage activation syndrome as a complication of adult onset Still's disease: a case series

Abstract

Background: Adult onset Still's disease (AOSD) is a rare autoimmune inflammatory condition associated with a variable prognosis ranging from limited benign disease to life-threatening complications. One such potentially fatal complication is macrophage activation syndrome (MAS) which occurs due to an impairment in cytotoxic function. It is characterised by pyrexia, pancytopenia, hepatosplenomegaly, lymphadenopathy, encephalopathy, coagulopathy, hypofibrinogenemia, hyperferritinemia, increased triglycerides and deranged liver function tests (LFTs). Methods: We describe a case series of three patients with newly diagnosed AOSD complicated by MAS. These cases highlight the aggressive nature of MAS and the diagnostic difficulty they present. We report good response to anakinra in two of these cases. Results: Case 1: A 27-year-old female presented with symptoms of pyrexia, malaise, rash, arthralgia and abdominal pain. A failure to detect a source of infection or malignancy prompted a diagnosis of AOSD based on clinical features and serological markers. A good response to steroids facilitated discharge. She was soon readmitted with signs and symptoms of severe shock. A failed response to antibiotics with concomitant deranged blood tests led to a diagnosis of MAS. A repeat regime of pulsed methylprednisolone proved inadequate, prompting a decision to add anakinra. Unfortunately, the patient rapidly deteriorated prior to anakinra commencement and passed away. Case 2: A 32-year-old female presented with pyrexia, fatigue, myalgia, night sweats, hepatosplenomegaly, lymphadenopathy, arthralgia and a rash. Blood tests revealed anaemia, thrombocytopenia, deranged LFTs and raised ferritin. Immunology, septic screen and CT thorax abdomen and pelvis was negative. Subsequently, a diagnosis of AOSD complicated by MAS was made which was supported by bone marrow aspirate. Triple therapy with high dose steroids, cyclosporine and anakinra led to clinical improvement and discharge. Case 3: A 29-year-old male presented with pyrexia, malaise, polyarthralgia, sore throat and an intermittent rash following recent travel to USA. He rapidly developed respiratory failure requiring ICU support. Investigations revealed raised inflammatory markers, hyperferritinemia, splenomegaly and pleural effusions. He was initially treated for chest sepsis causing ARDS. However, a detailed infection screen was negative and he deteriorated despite antibiotics. Initial bone marrow aspirate was non diagnostic. He was intermittently treated with IVIG and low dose IV methylprednisolone. A repeat bone marrow biopsy was supportive of MAS complicating AOSD. Triple therapy with cyclosporine, hydrocortisone and anakinra facilitated clinical improvement and successful discharge. Conclusion: MAS carries a high mortality rate and early detection with aggressive management has shown to improve patient survival. Distinguishing between the clinical manifestations and serological markers for AOSD and MAS remains a challenge due to overlap in clinical features and the lack of a validated classification criteria for MAS. We recommend the use of anakinra in MAS as a complication of AOSD and that clinicians should be vigilant of MAS in such cases.