Systemic juvenile idiopathic arthritis (sJIA) is a heterogeneous category of arthritis that frequently leads to disability and severe complications. The clinical cause of sJIA is very variable, which results in difficulties of disease recognition. In this literature review based on case series we outline the main challenges in diagnostic of sJIA and macrophage activation syndrome (MAS). Using the 2016 criteria for MAS diagnostic allowed to consider MAS in the diagnostically challenging cases, that confirms their sensitivity in pediatric patients. The reviewed literature showed last updates for the improvement of classification, diagnostic of sJIA and its complication. The modification of JIA criteria, initiated by Paediatric Rheumatology International Trials Organisation, will allow to improve detection and treatment of JIA. The presentation of this clinical cases and the discussion may be useful for understanding the disease cause and will help to differentiate sJIA and MAS from other disorders, and to improve treatment outcomes.