Macrophage activation syndrome (MAS) is a rare life-threatening complication of rheumatic diseases (RD) that requires early recognition and adequate immediate treatment. Objective of the study: to identify the features of onset of RD in patients who developed MAS, the clinical and laboratory characteristics of the MAS, possible trigger factors and the timing of development. Materials and methods of research: 57 patients (20 boys and 37 girls) with RD who developed MAS were included in a retrospective continuous non-randomized study: 36 (63%) with systemic juvenile idiopathic arthritis (sJIA), 19 (33%) with Systemic lupus erythematosus (SLE), 1 (2%) – with juvenile dermatomyositis (JDM), one (2%) – with overlapping syndrome. Results: in the structure of patients with sJIA, patients with a history of MAS accounted for 28%, among patients with SLE – 7,6%. The median age at the time of sJIA debut in the study group was 2,6 years [1,5; 5,75], patients with SLE – 11,8 years [8,6; 13,95]. The ratio of boys and girls in the study group was 1:1,85. 70 MAS episodes were recorded: 48 – with sJIA, 20 – with SLE, one episode each for JDM and crossover syndrome. A single episode of MAS at the onset had 22% of patients with sJIA, 47% – with SLE, MAS during the course of the disease – 55% and 47%, repeated episodes of MAS – 25% and 5% of patients, respectively. Clinical manifestations of MAS included fever in 91% of children, hepatomegaly in 54%, pericarditis in 51%, skin lesions in 68%, CNS damage in 44%, lung damage in 33%, hyperferritinemia in 96%, thrombocytopenia – in 79%, increased aminotransferases – in 89%, hypertriglyceridemia – in 53%. Patients with sJIA and MAS had statistically significantly earlier onset (p=0,047), a greater number of systemic manifestations (p=0,012), a typical exanthema (p<0,0001), and a smaller number of active joints (p=0,041). 83% of them had episodes of MAS before the initiation of therapy with biological disease-modifying antirheumatic drugs (bDMARDs). There was no statistically significant relationship between the development of MAS with the use of bDMARDs with a clear positive relationship with the violation of the therapy regimen. 19% of patients with sJIA and MAS had a history of infusion reaction to tocilizumab, 8% later had interstitial lung damage. Patients with SLE and MAS at the onset were statistically significantly more likely to have serositis (p=0,0028), ulcers of the oral mucosa (p<0,0001), neuropsychiatric disorders (p=0,0024), positive Coombs' test (p=0,026). All patients received glucocorticoid therapy; experience with the use of GIBP in the study group was limited. Conclusion: MAS in children develops more often with sJIA; the dominant provoking factor is the activity of the underlying disease. The overwhelming majority of patients developed MAS during the course of the disease, less often at the onset. Patients with a history of MAS with sJIA are characterized by an earlier age of onset, a predominance of systemic manifestations, the need for early administration of bDMARDs therapy, and a tendency to infusion reaction to tocilizumab. Against the background of bDMARDs, a subclinical course of MAS with the absence of fever is possible. The risk of developing MAS along with SLE is higher in patients with onset of serositis, ulcers of the oral mucosa, neuropsychiatric disorders, and a positive Coombs' test. MAS cases were detected with high SLE activity at the onset, violation of the treatment protocol.
Risk of significant cytopenias after treatment with tocilizumab in systemic juvenile arthritis patients with a history of macrophage activation syndrome
