Macrophage activation syndrome in systemic juvenile idiopathic arthritis

Abstract

Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of systemic juvenile idiopathic arthritis (s-JIA). An immunological feature is the excessive activation and proliferation of T lymphocytes and macrophages. Massive hypercytokinemia is strongly associated with its pathogenesis, particularly the overproduction of interleukin (IL)-1, IL-6 and IL-18; interferon (IFN)-c; and tumor necrosis factor (TNF)-a. Furthermore, heterozygous mutations in causative genes for primary hemophagocytic lymphohistiocytosis and in vivo exposure to highly elevated levels of IL-6 and IL-18 might induce natural killer cell dysfunction and decrease their numbers, respectively. A proper diagnosis is important to begin appropriate therapeutic interventions and change an unfavorable prognosis. The 2016 ACR/EULAR classification criteria for MAS have a high diagnostic performance; however, the diagnostic sensitivity for onset is relatively low. Therefore, careful monitoring of laboratory values during the course of MAS is necessary to diagnose it early in s-JIA. Further studies on the diagnosis and monitoring of disease activity using serum cytokine profile and a targeted cytokine strategy are required.

Systemic juvenile idiopathic arthritis in French Afro-Caribbean children, a retrospective cohort study

“…Our patients had few autoantibodies, which clearly differentiates this entity from other JIA or systemic disease [ 13 ]. Although we chose an international definition of MAS associated with sJIA [ 7 ] to avoid it simply reflecting the perception of the clinicians, we found a high percentage of MAS in our cohort, higher than previously described [ 14 ], which was not related to an increase in mortality. However, in our cohort most of the children who had MAS at some point during the course of their diseases required biotherapy for disease control.…”

Clinical Course and Cytokine Profile of Systemic Juvenile Idiopathic Arthritis in a Patient with Trisomy 21

“…After the first mPSL pulse therapy, laboratory values such as CRP levels showed improvement but inflammatory cytokines such as IL-6 and IL-18 did not. These findings suggest a risk of MAS recurrence or progression 14,16 . The serum IL-18 was observed to be re-elevated on 22 days after admission and the value of on 22 days was higher than on admission.…”

Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases

“…IL-18/IL-18BP imbalance is highly linked to immunologically mediated diseases, especially diseases that have a pathological role of IFNγ, such as macrophage activated syndrome (MAS) [ 2 , 32 , 90 , 91 , 92 , 93 , 94 ]. MAS is a life-threatening condition that is not mainly a syndrome on its own, but is also found to be associated with other infectious and autoinflammatory diseases [ 2 , 32 , 93 , 95 , 96 , 97 , 98 , 99 , 100 ].…”

“…Various infections developed MAS, including Epstein–Barr virus, cytomegalovirus, and herpes virus, and infections with other pathogens, such as intracellular bacteria and parasites, as well as numerous lymphomas [ 32 , 90 , 91 , 92 , 93 ]. Moreover, MAS could be present as a form of secondary hemophagocytic lymphohistiocytosis (HLH), in addition to the rare and serious rheumatic diseases, such as adult-onset Still’s disease (AOSD) and its counterpart in children and systemic juvenile idiopathic arthritis (sJIA) [ 94 , 101 , 102 , 103 , 104 , 105 ]. In both conditions, secondary HLH and AOSD/sJIA, a significant elevation of IL-18 was validated and found to be correlated to disease activity and severity [ 94 , 104 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 ].…”

“…Moreover, MAS could be present as a form of secondary hemophagocytic lymphohistiocytosis (HLH), in addition to the rare and serious rheumatic diseases, such as adult-onset Still’s disease (AOSD) and its counterpart in children and systemic juvenile idiopathic arthritis (sJIA) [ 94 , 101 , 102 , 103 , 104 , 105 ]. In both conditions, secondary HLH and AOSD/sJIA, a significant elevation of IL-18 was validated and found to be correlated to disease activity and severity [ 94 , 104 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 ]. MAS and IL-18 serum levels both represent the shared pathogenic features between these two different disease conditions.…”