Clinical And Laboratory Characteristics, Genetic Features Of Macrophage Activation Syndrome In Children With Systemic-Onset Juvenile Idiopathic Arthritis: A Single Center Experience

Background: Macrophage activation syndrome (MAS) is a life-threatening complication of systemic-onset juvenile idiopathic arthritis (sJIA) characterized by fever, hepatosplenomegaly, lymphadenopathy, coagulopathy, and rapid development of multiple organ failure. MAS is triggered by viral and bacterial infections, most often Epstein-Barr viruses, cytomegalovirus, influenza and parainfluenza viruses, parvavirus B19, yersiniosis, salmonellosis, sepsis. Despite modern diagnostic and treatment technologies, MAS still remains a formidable complication of sJIA, it is characterized by an aggressive course, a heterogeneous clinical presentation, especially in conditions of treatment with genetically engineered biological drugs, an ambiguous response to pathogenetic therapy and is accompanied by mortality in 5-10% of patients. Objectives: To analyze the clinical and laboratory features of MAS in children with sJIA and to study the genetic predisposition of this syndrome. Methods: The study included 24 patients with MAS who are being followed up in the rheumatology department of the National Medical Research Center of Children’s Health, Moscow. The clinical presentation and laboratory manifestations were assessed in 24, and genetic features were described in 7 patients using a new generation sequencing with further biostatistical processing of the obtained genetic data. Results: Of 24 patients, 23 (98%) had fever, 16 (68%) patients had rash, 17 (72%) - organomegaly, 4 (16%) - polyserositis, 2 (7%) - myalgia and myopathy. All 24 (100%) patients had an increase in ferritin level of more than 684 ng/ml, 98% of them had a high level of lactate dehydrogenase (LDH) and 97% - a high level of triglycerides. In CBC, cytopenia was found in 80% of children: in 54% - erythrocytopenia, in 74% - leukopenia, in 88% - thrombocytopenia, in 15% - sharp decrease in erythrocyte sedimentation rate. In a coagulogram of 24 patients, 90% had an increase in D-dimer, 85% had a decrease in fibrinogen. Hyponatremia presented in 95% of patients. Thus, 85% of patients met the diagnostic criteria of the HLH-2004 protocol, adapted for children with sJIA. Genetic characteristics were analyzed in 7 children out of 94 patients with MAS. They are presented in Table 1. These patients have rare and frequent variants, as well as genes polymorphisms that are associated with macrophage activation syndrome. Conclusion: The macrophage activation syndrome has a typical clinical presentation, there are clinical and laboratory manifestations: fever, hyperferritinemia, cytopenia, hyponatremia, increased levels of LDH and triglycerides, based on which, a diagnosis can be made. Patients with MAS at our center also had genetic characteristics that predisposed to the development of this condition. References: [1]Crayne CB, Albeituni S, Nichols KE, Cron RQ. The Immunology of Macrophage Activation Syndrome. Front Immunol. 2019 Feb 1;10:119. doi: 10.3389/fimmu.2019.00119. PMID: 30774631; PMCID: PMC6367262. [2]Henderson LA, Cron RQ. Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management. Paediatr Drugs. 2020 Feb;22(1):29-44. doi: 10.1007/s40272-019-00367-1. PMID: 31732958; PMCID: PMC7334831. [3]Ravelli A, Davi S, Minoia F, Martini A, Cron RQ. Macrophage Activation Syndrome. Hematol Oncol Clin North Am. 2015 Oct;29(5):927-41. doi: 10.1016/j.hoc.2015.06.010. Epub 2015 Aug 25. PMID: 26461152. Disclosure of Interests: None declared