Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis

Correll, Colleen K.; Binstadt, Bryce A

doi:10.1038/pr.2013.187

Cited by 48 publications

(31 citation statements)

References 58 publications

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“…The shortened survival of erythrocytes in AI has been attributed to macrophage activation by inflammatory cytokines that causes the macrophages to ingest and destroy erythrocytes prematurely. Anemia and excessive erythrophagocytosis are prominent features of macrophage activation syndromes, especially those associated with systemic juvenile rheumatoid arthritis 22 . Here, treatment targeting IL-1 or IL-6 is proving effective, suggesting an important (although possibly indirect) role of these cytokines in the pathogenesis of excessive erythrophagocytosis.…”

Section: Pathophysiologymentioning

confidence: 99%

Anemia of Inflammation

Nemeth

Ganz

2014

Hematology/Oncology Clinics of North America

348

261

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Synopsis Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic normochromic anemia that is caused by an underlying inflammatory disease. It is diagnosed when serum iron concentrations are low despite adequate iron stores, as evidenced by serum ferritin that is not low. In the setting of inflammation, AI may be difficult to differentiate from iron deficiency anemia, and the two conditions may coexist. In AI, erythropoiesis is iron-restricted by hepcidin-mediated hypoferremia and erythrocyte production is suppressed by cytokines acting on erythroid progenitors. Decreased erythropoiesis is unable to compensate for shortened erythrocyte lifespan caused by enhanced erythrophagocytosis by cytokine-activated macrophages. Treatment should focus on the underlying disease. If this is not feasible and the anemia limits the quality of life or the performance of daily activities, a combination of erythropoiesis-stimulating agents and intravenous iron may be effective but should be attempted only after careful consideration of risk and benefit. Recent advances in molecular understanding of AI are stimulating the development of new pathophysiologically targeted experimental therapies.

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Section: Pathophysiologymentioning

confidence: 99%

Anemia of Inflammation

Nemeth

Ganz

2014

Hematology/Oncology Clinics of North America

348

261

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“…While serum levels of TNFα are increased in patients with SJIA, levels are comparable to those seen in patients with other systemic inflammatory disease such as Kawasaki disease [67]. Similarly, while there are reports of good clinical response in SJIA patients with TNF-blocking agents, the results have been inconsistent [68], and these agents are not included in the consensus treatment plans for new-onset SJIA [69]. …”

Section: Pathophysiologymentioning

confidence: 99%

Macrophage activation syndrome and cytokine-directed therapies

Schulert

Grom

2014

Best Practice & Research Clinical Rheumatology

145

112

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Macrophage activation syndrome (MAS) is an episode of overwhelming inflammation that occurs most commonly in children with systemic juvenile idiopathic arthritis. It is characterized by expansion and activation of T lymphocytes and hemophagocytic macrophages, and bears great similarity to hemophagocytic lymphohistiocytosis (HLH). This disorder has substantial morbidity and mortality, and there is frequently a delay in recognition and initiation of treatment. Here, we will review what is known about the pathogenesis of MAS and in particular its similarities to HLH. The development of MAS is characterized by a cytokine storm, with the elaboration of numerous proinflammatory cytokines. We will examine the evidence for various cytokines in the initiation and pathogenesis of MAS, and discuss how new biologic therapies may alter the risk of MAS. Finally we will review current treatment options for MAS, and examine how cytokine-directed therapy could serve as novel treatment modalities.

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“…50 %) [25]. A feared acute complication in sJIA is macrophage activation syndrome (MAS) that affects around 10 % of patients and goes along with high fever, cytopenia, impaired liver function, coagulopathy and considerable mortality [26]. Long-term complications also include AA amyloidosis [27,28].…”

Section: Systemic Juvenile Idiopathic Arthritismentioning

confidence: 99%