Juvenile Spondyloarthritis

Weiss, Pamela F.; Colbert, Robert A.

doi:10.1016/j.pcl.2018.03.006

Cited by 53 publications

(24 citation statements)

References 73 publications

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“…Furthermore, the shared HLA associations between adult and childhood RF-positive arthritis or in SpA provide a rationale for testing treatments in children that have efficacy in adults. The use of drugs targeting the IL-17 axis, currently in use in adults 209,210 will probably become part of the armamentarium for HLA-B27-associated SpA in children and adolescents 216 . Any therapeutic benefit from such an approach would support the notion of shared disease mechanisms in children and adults.…”

Section: [H2] Therapymentioning

confidence: 99%

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

2019

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Our understanding of the mechanisms underlying HLA associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HLA genotype with other genes and environmental risk factors in determining disease risk have been identified. This Review provides basic information on the genetics and molecular function of HLA molecules, as well as general features of HLA associations with disease. We summarise evidence for various peptidedependent and peptide-independent mechanisms by which HLA alleles might contribute to the pathogenesis of three types of inflammatory arthritis: rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HLA allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and pediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HLA associations in developing personalized strategies for the treatment and prevention of these diseases. [ED: Some general editorial comments are replied to in the marginal comments. For replies to reviewers, please see the accompanying file.]

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Section: [H2] Therapymentioning

confidence: 99%

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

2019

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“…In undetermined disease stage of jSpA, without well-defined and serological testing, genomic and/or imaging biomarkers become crucial because, despite biologic therapy, fewer than half of children achieve reach long-term and sustainable remission off medication 5 years after diagnosis (2,194). Similarly, treatment of the various bone pathology in SpA remains an unmet clinical need.…”

Section: Putting It All Togethermentioning

confidence: 99%

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

Harjaček

2021

Front. Med.

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Juvenile spondyloarthritis (jSpA) is a an umbrella term for heterogeneous group of related seronegative inflammatory disorders sharing common symptoms. Although it mainly affects children and adolescents, it often remains active during adulthood. Genetic and environmental factors are involved in its occurrence, although the exact underlying immunopathophysiology remains incompletely elucidated. Accumulated evidence suggests that, in affected patients, subclinical gut inflammation caused by intestinal dysbiosis, is pivotal to the future development of synovial–entheseal complex inflammation. While the predominant role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including jSpA, is firmly established, the role of the cytokine macrophage migration inhibitory factor (MIF) is generally overlooked. The purpose of this review is to discuss and emphasize the role of epigenetics, neuroendocrine pathways and the hypothalamic-pituitary (HPA) axis, and to propose a novel hypothesis of the role of decreased NLRP3 gene expression and possibly MIF in the early phases of jSpA development. The decreased NLRP3 gene expression in the latter, due to hypomethylation of promotor site, is (one of) the cause for inflammasome malfunction leading to gut dysbiosis observed in patients with early jSpA. In addition, we highlight the role of MIF in the complex innate, adaptive cellular and main effector cytokine network, Finally, since treatment of advanced bone pathology in SpA remains an unmet clinical need, I suggest possible new drug targets with the aim to ultimately improve treatment efficacy and long-term outcome of jSpA patients.

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“…Skin and nail involvement characterizes the PsA ILAR subgroup. Clinical manifestations for this subgroup have been reviewed extensively elsewhere and will not be described in detail here (57)(58)(59). Briefly, children with nail involvement may exhibit nail pitting and onycholysis.…”

Section: Extra-articular Manifestationsmentioning

confidence: 99%

Outcomes in Juvenile-Onset Spondyloarthritis

Smith

Burgos‐Vargas

2021

Front. Med.

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Some studies have suggested children with juvenile onset spondyloarthritis (JoSpA) have a relatively poor outcome compared to other juvenile idiopathic arthritis (JIA) categories, in regards to functional status and failure to attain remission. Thus, in the interest of earlier recognition and risk stratification, awareness of the unique characteristics of this group is critical. Herein, we review the clinical burden of disease, prognostic indicators and outcomes in JoSpA. Of note, although children exhibit less axial disease at onset compared to adults with spondyloarthritis (SpA), 34–62% have magnetic resonance imaging (MRI) evidence for active inflammation in the absence of reported back pain. Furthermore, some studies have reported that more than half of children with “enthesitis related arthritis” (ERA) develop axial disease within 5 years of diagnosis. Axial disease, and more specifically sacroiliitis, portends continued active disease. The advent of TNF inhibitors has promised to be a “game changer,” given their relatively high efficacy for enthesitis and axial disease. However, the real world experience in various cohorts since the introduction of more widespread TNF inhibitor usage, in which greater than a third still have persistently active disease, suggests there is still work to be done in developing new therapies and improving the outlook for JoSpA.

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Juvenile Spondyloarthritis

Cited by 53 publications

References 73 publications

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The “Out of the Box” View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF)

Outcomes in Juvenile-Onset Spondyloarthritis

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