Recent advances and evolving concepts in Still's disease. [Review]
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All Authors
Ruscitti, P.
Cantarini, L.
Nigrovic, PA.
McGonagle, D.
Giacomelli, R.
LTHT Author
McGonagle, Dennis
LTHT Department
NIHR Leeds Biomedical Research Centre
Non Medic
Publication Date
2024
Item Type
Journal Article
Review
Review
Language
Subject
Subject Headings
Abstract
Still's disease is a rare inflammatory syndrome that encompasses systemic juvenile idiopathic arthritis and adult-onset Still's disease, both of which can exhibit life-threatening complications, including macrophage activation syndrome (MAS), a secondary form of haemophagocytic lymphohistiocytosis. Genetic insights into Still's disease involve both HLA and non-HLA susceptibility genes, suggesting the involvement of adaptive immune cell-mediated immunity. At the same time, phenotypic evidence indicates the involvement of autoinflammatory processes. Evidence also implicates the type I interferon signature, mechanistic target of rapamycin complex 1 signalling and ferritin in the pathogenesis of Still's disease and MAS. Pathological entities associated with Still's disease include lung disease that could be associated with biologic DMARDs and with the occurrence of MAS. Historically, monophasic, recurrent and persistent Still's disease courses were recognized. Newer proposals of alternative Still's disease clusters could enable better dissection of clinical heterogeneity on the basis of immune cell profiles that could represent diverse endotypes or phases of disease activity. Therapeutically, data on IL-1 and IL-6 antagonism and Janus kinase inhibition suggest the importance of early administration in Still's disease. Furthermore, there is evidence that patients who develop MAS can be treated with IFNgamma antagonism. Despite these developments, unmet needs remain that can form the basis for the design of future studies leading to improvement of disease management.
Journal
Nature Reviews Rheumatology