Performance of Current Guidelines for Diagnosis of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis
Authors: Davì Sergio , Minoia Francesca , Pistorio Angela , Horne AnnaCarin , Consolaro Alessandro , Rosina Silvia , Bovis Francesca , Cimaz Rolando , Gamir Maria Luz , Ilowite Norman T. , Kone‐Paut Isabelle , Feitosa de Oliveira Sheila Knupp , McCurdy Deborah , Silva Clovis Artur , Sztajnbok Flavio , Tsitsami Elena , Unsal Erbil , Weiss Jennifer E. , Wulffraat Nico , Abinun Mario , Aggarwal Amita , Apaz Maria Teresa , Astigarraga Itziar , Corona Fabrizia , Cuttica Ruben , D'Angelo Gianfranco , Eisenstein Eli M. , Hashad Soad , Lepore Loredana , Mulaosmanovic Velma , Nielsen Susan , Prahalad Sampath , Rigante Donato , Stanevicha Valda , Sterba Gary , Susic Gordana , Takei Syuji , Trauzeddel Ralf , Zletni Mabruka , Ruperto Nicolino , Martini Alberto , Cron Randy Q. , Ravelli Angelo ,   on behalf of the Paediatric Rheumatology International Trials Organisation, the Childhood Arthritis and Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group, and the Histiocyte Society
Published: July 2014

ObjectiveTo compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH‐2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)–associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection.MethodsInternational pediatric rheumatologists and hemato‐oncologists were asked to retrospectively collect clinical information from patients with systemic JIA–associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH‐2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5‐adapted) or 4 of 5 of the remaining items (4/5‐adapted) were present.ResultsThe study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5‐adapted HLH‐2004 guidelines performed better than the 4/5‐adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5‐adapted HLH‐2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections.ConclusionThe preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH‐2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.