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International Journal of Rheumatic... Oct 2023
Topics: Humans; Arthritis, Juvenile; Rheumatology
PubMed: 37807617
DOI: 10.1111/1756-185X.14813 -
Genes & Diseases Mar 2024Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children, with onset before age 16 and lasting for more than 6... (Review)
Review
Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children, with onset before age 16 and lasting for more than 6 weeks. JIA is a highly heterogeneous condition with various consequences for health and quality of life. For some JIA patients, early detection and intervention remain challenging. As a result, further investigation of the complex and unknown mechanisms underlying JIA is required. Advances in technology now allow us to describe the biological heterogeneity and function of individual cell populations in JIA. Through this review, we hope to provide novel ideas and potential targets for the diagnosis and treatment of JIA by summarizing the current findings of single-cell RNA sequencing studies and understanding how the major cell subsets drive JIA pathogenesis.
PubMed: 37692495
DOI: 10.1016/j.gendis.2023.04.014 -
Children (Basel, Switzerland) Oct 2023Enthesitis-related arthritis (ERA) represents 5-30% of all cases of juvenile idiopathic arthritis (JIA) and belongs to the spectrum of the disorders included in the... (Review)
Review
Enthesitis-related arthritis (ERA) represents 5-30% of all cases of juvenile idiopathic arthritis (JIA) and belongs to the spectrum of the disorders included in the group of juvenile spondyloarthritis. In the last decade, there have been considerable advances in the classification, diagnosis, monitoring, and treatment of ERA. New provisional criteria for ERA have been recently proposed by the Paediatric Rheumatology INternational Trials Organisation, as part of a wider revision of the International League of Associations for Rheumatology criteria for JIA. The increased use of magnetic resonance imaging has shown that a high proportion of patients with ERA present a subclinical axial disease. Diverse instruments can be used to assess the disease activity of ERA. The therapeutic recommendations for ERA are comparable to those applied to other non-systemic JIA categories, unless axial disease and/or enthesitis are present. In such cases, the early use of a TNF-alpha inhibitor is recommended. Novel treatment agents are promising, including IL-17/IL-23 or JAK/STAT pathways blockers.
PubMed: 37892310
DOI: 10.3390/children10101647 -
Medicine Mar 2024Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active... (Review)
Review
Juvenile idiopathic arthritis (JIA) is a chronic clinical condition characterized by arthritic features in children under the age of 16, with at least 6 weeks of active symptoms. The etiology of JIA remains unknown, and it is associated with prolonged synovial inflammation and structural joint damage influenced by environmental and genetic factors. This review aims to enhance the understanding of JIA by comprehensively analyzing relevant literature. The focus lies on current diagnostic and therapeutic approaches and investigations into the pathoaetiologies using diverse research modalities, including in vivo animal models and large-scale genome-wide studies. We aim to elucidate the multifactorial nature of JIA with a strong focus towards genetic predilection, while proposing potential strategies to improve therapeutic outcomes and enhance diagnostic risk stratification in light of recent advancements. This review underscores the need for further research due to the idiopathic nature of JIA, its heterogeneous phenotype, and the challenges associated with biomarkers and diagnostic criteria. Ultimately, this contribution seeks to advance the knowledge and promote effective management strategies in JIA.
Topics: Child; Animals; Humans; Infant; Arthritis, Juvenile; Phenotype; Biomarkers
PubMed: 38552102
DOI: 10.1097/MD.0000000000037567 -
Paediatric Drugs Nov 2023Chronic lung disease in children with systemic juvenile idiopathic arthritis (SJIA-LD) is an emerging and potentially life-threatening disease complication. Despite... (Review)
Review
Chronic lung disease in children with systemic juvenile idiopathic arthritis (SJIA-LD) is an emerging and potentially life-threatening disease complication. Despite recent descriptions of its clinical spectrum, preliminary immunologic characterization, and proposed hypotheses regaarding etiology, optimal approaches to diagnosis and management remain unclear. Here, we review the current clinical understanding of SJIA-LD, including the potential role of biologic therapy in disease pathogenesis, as well as the possibility of drug reactions with eosinophilia and systemic symptoms (DRESS). We discuss approaches to evaluation of children with suspected SJIA-LD, including a proposed algorithm to risk-stratify all SJIA patients for screening to detect LD early. We review potential pharmacologic and non-pharmacologic treatment approaches that have been reported for SJIA-LD or utilized in interstitial lung diseases associated with other rheumatic diseases. This includes lymphocyte-targeting therapies, JAK inhibitors, and emerging therapies against IL-18 and IFNγ. Finally, we consider urgent unmet needs in this area including in basic discovery of disease mechanisms and clinical research to improve disease detection and patient outcomes.
Topics: Child; Humans; Arthritis, Juvenile; Lung Diseases
PubMed: 37787872
DOI: 10.1007/s40272-023-00593-8 -
Clinical and Experimental Immunology Oct 2023Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and comprises of multiple subtypes. The most relevant disease subtypes,...
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and comprises of multiple subtypes. The most relevant disease subtypes, grouped upon current insight in disease mechanisms, are nonsystemic (oligo- and polyarticular) JIA and systemic JIA (sJIA). In this review, we summarize some of the main proposed mechanisms of disease in both nonsystemic and sJIA and discuss how current therapeutic modalities target some of the pathogenic immune pathways. Chronic inflammation in nonsystemic JIA is the result of a complex interplay between effector and regulatory immune cell subsets, with adaptive immune cells, specifically T-cell subsets and antigen-presenting cells, in a central role. There is, however, also innate immune cell contribution. SJIA is nowadays recognized as an acquired chronic inflammatory disorder with striking autoinflammatory features in the first phase of the disease. Some sJIA patients develop a refractory disease course, with indications for involvement of adaptive immune pathways as well. Currently, therapeutic strategies are directed at suppressing effector mechanisms in both non-systemic and sJIA. These strategies are often not yet optimally tuned nor timed to the known active mechanisms of disease in individual patients in both non-systemic and sJIA. We discuss current treatment strategies in JIA, specifically the 'Step-up' and 'Treat to Target approach' and explore how increased insight into the biology of disease may translate into future more targeted strategies for this chronic inflammatory disease at relevant time points: preclinical disease, active disease, and clinically inactive disease.
PubMed: 37074076
DOI: 10.1093/cei/uxad045 -
Pediatrics Oct 2023Juvenile idiopathic arthritis is a common chronic childhood disease, with a prevalence of ∼1 per 1000 children. Arthritis can also be a manifestation of other...
Juvenile idiopathic arthritis is a common chronic childhood disease, with a prevalence of ∼1 per 1000 children. Arthritis can also be a manifestation of other inflammatory conditions, such as inflammatory bowel disease (IBD). Studies suggest a genetic influence in IBD, including mutations in CARD8. CARD8 is a negative regulator of the NLRP3 inflammasome, and mutations in this gene are hypothesized to induce gastrointestinal inflammation. However, few studies have evaluated this association and most have included a limited number of patients. We present a case of a pediatric patient with IBD-associated arthritis and a CARD8 mutation. Our patient is a 7-year-old female who was initially evaluated by rheumatology for right leg pain and an intermittent rash. She had clinically active arthritis on exam and was started on methotrexate with only slight improvement. Additional workup revealed sacroiliitis by imaging, elevated inflammatory markers, no anemia, and a variant of unknown significance in CARD8. Adalimumab was recommended but before medication initiation, our patient's symptoms progressed to worsening joint pain, fatigue, fevers, nausea, vomiting, diarrhea, and hematochezia. Infectious testing was negative. Fecal calprotectin was >8000 µg/g. A colonoscopy revealed IBD most consistent with Crohn's disease. Adalimumab was ultimately added, and she has responded well to combination therapy. This case report highlights the association between CARD8 mutations and IBD, especially in the setting of IBD-associated arthritis.
Topics: Female; Humans; Child; Arthritis, Juvenile; Adalimumab; Inflammatory Bowel Diseases; Crohn Disease; Chronic Disease; Mutation; Neoplasm Proteins; CARD Signaling Adaptor Proteins
PubMed: 37724393
DOI: 10.1542/peds.2022-058964 -
Biology Jul 2023Juvenile Idiopathic Arthritis (JIA) represents the most common chronic pediatric arthritis in Western countries and a leading cause of disability in children. Despite... (Review)
Review
Juvenile Idiopathic Arthritis (JIA) represents the most common chronic pediatric arthritis in Western countries and a leading cause of disability in children. Despite recent clinical achievements, patient management is still hindered by a lack of diagnostic/prognostic biomarkers and targeted treatment protocols. MicroRNAs (miRNAs) are short non-coding RNAs playing a key role in gene regulation, and their involvement in many pathologies has been widely reported in the literature. In recent decades, miRNA's contribution to the regulation of the immune system and the pathogenesis of autoimmune diseases has been demonstrated. Furthermore, miRNAs isolated from patients' biological samples are currently under investigation for their potential as novel biomarkers. This review aims to provide an overview of the state of the art on miRNA investigation in JIA. The literature addressing the expression of miRNAs in different types of biological samples isolated from JIA patients was reviewed, focusing in particular on their potential application as diagnostic/prognostic biomarkers. The role of miRNAs in the regulation of immune responses in affected joints will also be discussed along with their potential utility as markers of patients' responses to therapeutic approaches. This information will be of value to investigators in the field of pediatric rheumatology, encouraging further research to increase our knowledge of miRNAs' potential for future clinical applications in JIA.
PubMed: 37508421
DOI: 10.3390/biology12070991 -
Cureus Aug 2023Autoimmune thyroid disease seems to occur more often in children with juvenile idiopathic arthritis (JIA) than in the general pediatric population. We investigated the...
PURPOSE
Autoimmune thyroid disease seems to occur more often in children with juvenile idiopathic arthritis (JIA) than in the general pediatric population. We investigated the prevalence of autoimmune thyroiditis (Hashimoto's thyroiditis) in young patients with JIA in Greece, which has not been evaluated previously.
METHODS
This descriptive study included patients with JIA followed up at the Pediatric Rheumatology Unit of the Second Department of Pediatrics of a tertiary general hospital in Thessaloniki, Greece. All patients were diagnosed and sorted according to the classification criteria of the International League of Associations for Rheumatology. The presence of thyroid autoantibodies was considered for determining autoimmune thyroiditis. Basic demographic, clinical, and laboratory data were collected from patients' records. Results: The analyzed sample comprised 130 patients with JIA (mean age 12.22 years; 69.2% female). Most patients (70%) had a family history of at least one autoimmune disease and 30.8% of Hashimoto's thyroiditis. More than half (53.8%) had enthesitis-related arthritis (ERA), 22.3% had oligoarthritis, and 15.4% had psoriatic arthritis. Thyroid autoantibodies were detected in 22/130 patients (16.9%) suggesting autoimmune thyroiditis; most of these patients were euthyroid, whereas 3/22 (13.6%) had overt hypothyroidism determined by elevated levels of thyroid-stimulating hormone, decreased levels of free thyroxine, and typical ultrasound findings for Hashimoto's thyroiditis. The prevalence of clinical cases of Hashimoto's disease was 2.3%.
CONCLUSIONS
The prevalence of autoimmune thyroiditis in our JIA cohort is higher compared to the general population and consistent with the previously reported range. Hence, investigation for thyroid autoimmunity should be included in the workup of patients with JIA.
PubMed: 37654906
DOI: 10.7759/cureus.44384 -
Cureus Nov 2023Polyarticular course juvenile idiopathic arthritis (pcJIA) is a form of arthritis that affects at least five joints at a time and presents before the age of 16. Its most... (Review)
Review
Polyarticular course juvenile idiopathic arthritis (pcJIA) is a form of arthritis that affects at least five joints at a time and presents before the age of 16. Its most common symptoms are pain, swelling, redness, and a limited range of motion, making it incredibly difficult for patients diagnosed to function in daily life. Historically, the leading treatment options have consisted of non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) such as methotrexate. However, these drugs have serious toxic side effects associated with long-term use in addition to being ineffective in refractory cases. Recently, small molecule biologics have emerged as an alternate treatment to pcJIA. Tofacitinib is a small molecule JAK inhibitor that blocks the JAK/STAT cascade and decreases the transcription of genes responsible for immune function. We conducted a risk-benefit analysis to determine the viability of tofacitinib as a treatment for pcJIA. In our review, we found the side effect profile of tofacitinib to be relatively mild, with many of the serious adverse side effects occurring in those immunocompromised and those with impaired renal and hepatic metabolism. Overall, we have determined that tofacitinib has the potential to be effective in reducing flare-ups and lowering erythrocyte sedimentation rate (ESR) in immunocompetent patients with pcJIA. Additionally, our review has found that tofacitinib has the potential to be effective in patients who are refractory to traditional treatment. However, large-scale clinical trials are needed to determine if this effect holds true in younger pediatric populations, as limited data surrounds this demographic.
PubMed: 38054155
DOI: 10.7759/cureus.48258