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Frontiers in Immunology 2021The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked... (Review)
Review
The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked to psoriasis and also the arthritis associated with inflammatory bowel disease. The argument supporting the role for IL-23 across the spectrum of SpA comes from 4 sources. First, genome wide associated studies (GWAS) have shown that all the aforementioned disorders exhibit IL-23R pathway SNPs, whereas HLA-B27 is not linked to all of these diseases-hence the IL-23 pathway represents the common genetic denominator. Secondly, experimental animal models have demonstrated a pivotal role for the IL-23/IL-17 axis in SpA related arthropathy that initially manifests as enthesitis, but also synovitis and axial inflammation and also associated aortic root and cutaneous inflammation. Thirdly, the emergent immunology of the human enthesis also supports the presence of IL-23 producing myeloid cells, not just at the enthesis but in other SpA associated sites including skin and gut. Finally, drugs that target the IL-23 pathway show excellent efficacy for skin disease, efficacy for IBD and also in peripheral arthropathy associated with SpA. The apparent failure of IL-23 blockade in the AS which is effectively a spinal polyenthesitis but evidence for efficacy of IL-23 inhibition for peripheral enthesitis in PsA and preliminary suggestions for benefit in axial PsA, raises many questions. Key amongst these is whether spinal inflammation may exhibit entheseal IL-17A production independent of IL-23 but peripheral enthesitis is largely dependent on IL-23 driven IL-17 production. Furthermore, IL-23 blocking strategies in animal models may prevent experimental SpA evolution but not prevent established disease, perhaps pointing towards a role for IL-23 in innate immune disease initiation whereas persistent disease is dependent on memory T-cell responses that drive IL-17A production independently of IL-23, but this needs further study. Furthermore, IL-12/23 posology in inflammatory bowel disease is substantially higher than that used in AS trials which merits consideration. Therefore, the IL-23 pathway is centrally involved in the SpA concept but the nuances and intricacies in axial inflammation that suggest non-response to IL-23 antagonism await formal definition. The absence of comparative immunology between the different skeletal sites renders explanations purely hypothetical at this juncture.
Topics: Animals; Biomarkers; Diagnosis, Differential; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Interleukin-17; Interleukin-23; Molecular Targeted Therapy; Signal Transduction; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 33815371
DOI: 10.3389/fimmu.2021.614255 -
European Journal of Rheumatology Jan 2022Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16, which is associated with peripheral joint...
Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16, which is associated with peripheral joint (especially large joints of the lower limbs) and axial skeletal (spine and sacroiliac joint) involvement, enthesitis, and human leukocyte antigen (HLA) B27 positivity. Juvenile spondyloarthropathies mainly cover juvenile ankylosing spondylitis (JAS), psoriatic arthritis, reactive arthritis, inflammatory bowel disease-associated arthritis, seronegative enthesopathy, arthropathy syndrome (SEA), and enthesitis-associated arthritis. Symptoms associated with spondyloarthropathies are enthesitis, inflammatory low back pain, dactylitis, nail changes, psoriasis, acute anterior uveitis, and inflammatory bowel disease-related symptoms. In JSpA, axial involvement is rarely seen in the early stages of the disease, in contrast to adult patients with ankylosing spondylitis (AS). The disease usually begins as asymmetric oligoarthritis of lower extremities in children, and axial skeletal involvement can occur in the course of the disease. Although the debate on the classification of juvenile spondyloarthropathies continues due to its initial nonspecific findings and the heterogeneity of the disease phenotype, the International League of Associations Rheumatology (ILAR) classification criteria are the most commonly used pediatric criteria. In that set of criteria, patients with JSpA are mainly classified under enthesitis-related arthritis or psoriatic arthritis group. Since juvenile spondyloarthropathies can cause severe loss of function and long-term sequelae, the main goal in treatment should be suppression of inflammation as early as possible and prevent sequelae.
PubMed: 34101576
DOI: 10.5152/eurjrheum.2021.20235 -
Frontiers in Pediatrics 2022Spondyloarthritides (SpA) are a family of interrelated rheumatic disorders with a typical disease onset ranging from childhood to middle age. If left untreated, they... (Review)
Review
Spondyloarthritides (SpA) are a family of interrelated rheumatic disorders with a typical disease onset ranging from childhood to middle age. If left untreated, they lead to a severe decrease in patients' quality of life. A succesfull treatment strategy starts with an accurate diagnosis which is achieved through careful analysis of medical symptoms. Classification criterias are used to this process and are updated on a regular basis. Although there is a lack of definite knowledge on the disease etiology of SpA, several studies have paved the way for understanding plausible risk factors and developing treatment strategies. The significant increase of HLA-B27 positivity in SpA patients makes it a strong candidate as a predisposing factor and several theories have been proposed to explain HLA-B27 driven disease progression. However, the presence of HLA-B27 negative patients underlines the presence of additional risk factors. The current treatment options for SpAs are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), TNF inhibitors (TNFis), Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and physiotherapy yet there are ongoing clinical trials. Anti IL17 drugs and targeted synthetic DMARDs such as JAK inhibitors are also emerging as treatment alternatives. This review discusses the current diagnosis criteria, treatment options and gives an overview of the previous findings and theories to clarify the possible contributors to SpA pathogenesis with a focus on Ankylosing Spondylitis (AS) and enthesitis-related arthritis (ERA).
PubMed: 36619518
DOI: 10.3389/fped.2022.1074239 -
Open Access Rheumatology : Research and... 2019In this narrative review, we overview the recent literature on enthesitis-related arthritis (ERA). For the purpose of our review, we searched Scopus for recent articles... (Review)
Review
In this narrative review, we overview the recent literature on enthesitis-related arthritis (ERA). For the purpose of our review, we searched Scopus for recent articles on this subject from 2013 onward, including some classic older articles for perspective. ERA is a juvenile idiopathic arthritis (JIA) subtype more common in males, associated in a majority with human leucocyte antigen B27. Such children generally present with asymmetric oligoarthritis or polyarthritis, predominantly of lower limb joints, associated with enthesitis or sacroiliitis. While diagnosis remains clinical, ultrasound is being increasingly used to detect subclinical enthesitis and for guiding entheseal site injections. Spine MRI can help detect sacroiliitis, inflammatory spinal changes, and pelvic sites of enthesitis in such patients. The recent juvenile spondyloarthropathy disease activity index recognizes the key clinical features of ERA, viz enthesitis and inflammatory back pain, which other disease activity indices used in JIA did not include. Management includes NSAIDs with physical therapy. Conventional disease-modifying agents like sulfasalazine and methotrexate may be used to minimize duration of NSAID use and in those with high inflammatory burden. In patients refractory to these drugs, biologics such as antitumor necrosis factor alpha agents have proven useful, based on evidences from randomized controlled trials and retrospective registry analyses. Factors predicting a poorer outcome in such children include hip or ankle involvement or restricted spinal mobility. Considering that children with ERA have overall poorer long-term outcomes than other subtypes of JIA, there is a need to further optimize therapeutic strategies for such patients.
PubMed: 30774484
DOI: 10.2147/OARRR.S163677 -
Jornal de Pediatria 2022In this article, the authors aimed to review the different tools used in the monitoring of enthesitis-related arthritis. (Review)
Review
OBJECTIVES
In this article, the authors aimed to review the different tools used in the monitoring of enthesitis-related arthritis.
SOURCES
The authors performed a literature review on PubMed, Google Scholar, and Scopus databases. The dataset included the original research and the reviews including patients with enthesitis-related arthritis or juvenile spondylarthritis up to October 2020.
SUMMARY OF FINDING
Enthesitis-related arthritis is a category of juvenile idiopathic arthritis. It is characterized by the presence of enthesitis, peripheral arthritis, as well as axial involvement. The only validated tool for disease activity measurement in juvenile idiopathic arthritis is the Disease Activity Score: It has proven its reliability and sensitivity. Nevertheless, due to an absence of validated evaluation tools, the extent of functional impairment, as well as the children and parents' perception of the disease, could not be objectively perceived. Despite the great progress in the field of imaging modalities, the role they play in the evaluation of disease activity is still controversial. This is partially due to the lack of validated scoring systems.
CONCLUSIONS
Further work is still required to standardize the monitoring strategy and validate the outcome measures in enthesitis-related arthritis.
Topics: Arthritis, Juvenile; Child; Humans; Reproducibility of Results; Spondylarthritis
PubMed: 34597529
DOI: 10.1016/j.jped.2021.08.002 -
Rheumatic Diseases Clinics of North... Nov 2021Spondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint... (Review)
Review
Spondyloarthritis represents a group of disorders characterized by enthesitis and axial skeletal involvement. Juvenile spondyloarthritis begins before age 16. Joint involvement is usually asymmetric. Bone marrow edema on noncontrast MRI of the sacroiliac joints can facilitate diagnosis. The most significant risk factor for axial disease is HLA-B27. Most patients have active disease into adulthood. Enthesitis and sacroiliitis correlate with greater pain intensity and poor quality-of-life measures. Tumor necrosis factor inhibitors are the mainstay of biologic therapy. Although other biologics such as IL-17 blockers have shown benefit in adult spondyloarthritis, none are approved by the US Food and Drug Administration.
Topics: Adolescent; Adult; Arthritis, Juvenile; Humans; Magnetic Resonance Imaging; Sacroiliac Joint; Sacroiliitis; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 34635292
DOI: 10.1016/j.rdc.2021.07.001 -
Frontiers in Medicine 2021Some studies have suggested children with juvenile onset spondyloarthritis (JoSpA) have a relatively poor outcome compared to other juvenile idiopathic arthritis (JIA)... (Review)
Review
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.
PubMed: 34124112
DOI: 10.3389/fmed.2021.680916 -
The Quarterly Journal of Nuclear... Sep 2017Despite major progress in the imaging diagnosis of spondyloarthritis (SpA), the relative advantages of various available imaging techniques remain unclear. The aim of... (Review)
Review
INTRODUCTION
Despite major progress in the imaging diagnosis of spondyloarthritis (SpA), the relative advantages of various available imaging techniques remain unclear. The aim of this study is to assess the current use of imaging in the diagnosis of SpA and to provide suitable recommendations for the use of imaging as an outcome measure as defined in the Assessment in SpondyloArthritis international Society (ASAS) criteria.
EVIDENCE ACQUISITION
A systematic literature search regarding imaging in SpA was performed. Articles were assessed by two reviewers to identify and summarized key information pertaining to imaging in SpA.
EVIDENCE SYNTHESIS
The search identified 180 relevant articles. Conventional radiography (CR) (17 articles), ultrasound (US) (26 articles), conventional computed tomography (CT) (13 articles), spectral computed tomography (spectral CT) (2 articles), bone scintigraphy (24 articles), and magnetic resonance imaging (MRI) were assessed (98 articles). Sacroiliitis and enthesitis were the major imaging findings in SpA. Multiple studies assessed the feasibility, validity, or differences among imaging modalities for the diagnosis of SpA; however, comprehensive assessments were not available due to a paucity of prospective imaging studies. CR is a widely available, inexpensive initial approach to evaluate patients with suspected SpA. CT enables assessment of structural changes from chronic sacroiliitis including bony erosions, subchondral sclerosis, joint space narrowing, and ankyloses; however, both CR and CT modalities are insensitive for demonstrating early enthesitis and sacroiliitis in SpA. US mainly identifies appendicular enthesitis but is more limited with respect to the sacroiliac joints. Bone scintigraphy can identify sacroiliac joint lesions and semi-quantitatively assess active sacroiliitis. MRI optimally evaluates not only early enthesitis and sacroiliitis of SpA but also chronic structural changes to the sacroiliac joints.
CONCLUSIONS
More than one modality may be required for diagnostic and assessment of SpA depending upon disease characteristics and evolution. CR is a suitable initial examination while MRI is able to detect both early and late changes of SpA. A combination of CR and MRI is recommended for the diagnosis and assessment of SpA.
Topics: Diagnostic Imaging; Humans; Image Processing, Computer-Assisted; Spondylarthritis
PubMed: 28497939
DOI: 10.23736/S1824-4785.17.02981-8