I90. MACROPHAGE ACTIVATION SYNDROME: A REVIEW OF THE LITERATURE AND PRACTICAL APPROACH TO CLINICAL CASES

Abstract

The cytokine storm syndrome-Haemophagocytic Lymphohistiocytosis (HLH)/Macrophage activation syndrome (MAS) - is an underrecognized, hyperinflammatory state causing significant morbidity and mortality in children and adults. It can be subdivided into a primary genetic form and a secondary acquired form. Primary HLH presents in infants and requires definitive treatment with bone marrow transplant. Secondary acquired HLH/MAS complicates diverse infections, malignancies and autoimmune or autoinflammatory disorders. Both subtypes present with a similar spectrum of non-specific symptoms, making accurate diagnosis and rapid treatment initiation challenging. Early recognition and prompt, rational treatment saves lives. In rheumatology, secondary HLH (often termed MAS) is classically seen as a consequence of uncontrolled systemic juvenile idiopathic arthritis (SJIA) but may also complicate other active autoimmune conditions such as systemic lupus erythematosus (SLE). Recent research has provided evidence-based guidelines for diagnosis and treatment of MAS resulting from SJIA. Secondary HLH/MAS is being increasingly recognized in nonrheumatological patients as a result of infection (especially Epstein- Barr Virus and cytomegalovirus), malignancy (particularly haematological), post-bone marrow transplant and as a late presentation of the primary genetic form. Patients either present in crisis or have had an indolent illness, usually with multiple speciality opinions and tests that do not yield a diagnosis while becoming more and more unwell. Treatment in this group is less well standardized and evidence-based but is based on the treatment principles of HLH in the primary and rheumatological forms. Rheumatologists from both paediatric and adult rheumatology backgrounds may well be asked for an opinion about the possibility of MAS from colleagues in infectious diseases, haematology or critical care and need to maintain vigilance for MAS in their patient population. Diagnosis of HLH/MAS is challenging requiring a high index of suspicion and interpretation of patterns in blood tests rather than absolute values. Treatment involves heavily immune suppressing already very ill patients but prompt recognition and early treatment to down-regulate the acquired cytokine storm syndromes can save lives. This session will cover the pathophysiology of HLH/MAS and review the literature about diagnosis and treatment of acquired HLH/MAS using several clinical cases to illustrate learning points.