Figure 2.

Environmental and genetic factors can impair the ability of the child with MODS to resolve inflammation: 1) Immunoparalysis is a condition in which antigen presenting cells are unable to present and remove microbes and dead tissue, 2) Thrombocytopenia associated multiple organ failure (TAMOF) is a condition in which complement activation is unopposed by inhibitory complement and von Willebrand factor (vWF) microvascular thrombosis is unopposed by ADAMTS13 (vWF cleaving protease), and 3) Sequential MODS is a condition in which CTL and NK cells cannot induce virus, cancer, or activated immune cell death and sFasL-Fas interactions cause liver failure. The common end pathway of uncontrolled inflammation is macrophage activation syndrome which can be associated with one or more of these phenotypes, or an inability to remove the source of inflammation for other reasons, or the presence of other pediatric hyper-inflammatory syndromes including the CAPS (Cryopyrin Associated Autoinflammatory Periodic Syndromes) spectrum.

HLA - Human leukocyte antigen; TNF – Tumor necrosis factor; LPS – Lipopolysaccharide; TAMOF - Thrombocytopenia associated multiple organ failure; Plt Ct – Platelet count; AKI – Acute kidney injury; DIC – Disseminated intravascular coagulation; SMOF – Sequential multiple organ failure; EBV - Epstein Barr Virus; sFASL - Soluble Fas ligand; IL – Interleukin