The role of infective trigger for macrophage activation syndrome in rheumatic diseases. A retrospective analysis in a tertiary pediatric care centre and review of the literature

Background: The role of infection in Macrophage Activation Syndrome (MAS) is controversial. In order to evaluate the prevalence of infections preceding the onset of MAS, we retrospectively analysed the cases of MAS complicating rheumatic diseases recorded in our tertiary hospital between 2005 and 2015. Methods: The clinical records of patients diagnosed with MAS and hospitalised between January 2005 and December 2015 were reviewed in order to identify their demographic characteristics, underlying rheumatological diseases, clinical and laboratory data, treatments, and complications. There was considered if an infection was documented during the 15 days preceding the onset of MAS. The presence of specific immunoglobulin M was considered separately as a possible indirect sign of recent infection Findings: Twelve children (eight females and four males) with underlying rheumatic disorders developed MAS during the study period: six were affected by systemic-onset juvenile idiopathic arthritis, three by systemic lupus erythematosus, two by dermatomyositis, and one by undifferentiated arthritis. There were 14 MAS-related events (one patient experienced three episodes). MAS occurred within 30 days of the onset of rheumatic disease in five cases, and during disease relapses in nine. In two cases, it followed the start of treatment with a new drug. Twelve of the 14 MAS episodes were suspected to be preceded by infections due to various pathogens, including Clostridium difficile, group A Streptococcus, Staphylococcus hominis, Escherichia coli, Entamoeba histolytica, Endolimax nana, Pseudomonas aeruginosa, Borrelia burgdorferi, Adenovirus, Coxsackie virus, Epstein-Barr virus, and Cytomegalovirus. Conclusions: The prevalence of infections in patients developing MAS may be underestimated, and their pathogenetic role should be considered also in patients with underlining rheumatic diseases.