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Pediatric Rheumatology Online Journal Aug 2021Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations... (Review)
Review
Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatological disorder and is classified by subtype according to International League of Associations for Rheumatology criteria. Depending on the number of joints affected, presence of extra-articular manifestations, systemic symptoms, serology and genetic factors, JIA is divided into oligoarticular, polyarticular, systemic, psoriatic, enthesitis-related and undifferentiated arthritis. This review provides an overview of advances in understanding of JIA pathogenesis focusing on aetiology, histopathology, immunological changes associated with disease activity, and best treatment options. Greater understanding of JIA as a collective of complex inflammatory diseases is discussed within the context of therapeutic interventions, including traditional non-biologic and up-to-date biologic disease-modifying anti-rheumatic drugs. Whilst the advent of advanced therapeutics has improved clinical outcomes, a considerable number of patients remain unresponsive to treatment, emphasising the need for further understanding of disease progression and remission to support stratification of patients to treatment pathways.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Child; Disease Progression; Humans; Medication Therapy Management; Risk Assessment
PubMed: 34425842
DOI: 10.1186/s12969-021-00629-8 -
Nature Reviews. Disease Primers Jan 2022Juvenile idiopathic arthritis (JIA) is an umbrella term for arthritis of unknown origin, lasting for >6 weeks with onset before 16 years of age. JIA is the most common... (Review)
Review
Juvenile idiopathic arthritis (JIA) is an umbrella term for arthritis of unknown origin, lasting for >6 weeks with onset before 16 years of age. JIA is the most common chronic inflammatory rheumatic condition of childhood. According to the International League Against Rheumatism (ILAR) classification, seven mutually exclusive categories of JIA exist based on disease manifestations during the first 6 months of disease. Although the ILAR classification has been useful to foster research, it has been criticized mainly as it does not distinguish those forms of chronic arthritis observed in adults and in children from those that may be unique to childhood. Hence, efforts to provide a new evidence-based classification are ongoing. Similar to arthritis observed in adults, pathogenesis involves autoimmune and autoinflammatory mechanisms. The field has witnessed a remarkable improvement in therapeutic possibilities of JIA owing to the availability of new potent drugs and the possibility to perform controlled trials with support from legislative interventions and large networks availability. The goal of drug therapy in JIA is to rapidly reduce disease activity to inactive disease or clinical remission, minimize drug side effects and achieve a quality of life comparable to that of healthy peers. As JIA can influence all aspects of a child's and their family's life, researchers increasingly recognize improvement of health-related quality of life as a key treatment goal.
Topics: Adult; Arthritis, Juvenile; Child; Humans; Quality of Life
PubMed: 35087087
DOI: 10.1038/s41572-021-00332-8 -
The Journal of Allergy and Clinical... Jan 2023The understanding of immune dysregulation in many different diseases continues to grow. There is increasing evidence that altered microbiome and gut barrier dysfunction... (Review)
Review
The understanding of immune dysregulation in many different diseases continues to grow. There is increasing evidence that altered microbiome and gut barrier dysfunction contribute to systemic inflammation in patients with primary immunodeficiency and in patients with rheumatic disease. Recent research provides insight into the process of induction and maturation of pathogenic age-associated B cells and highlights the role of age-associated B cells in creating tissue inflammation. T follicular regulatory cells are shown to help maintain B-cell tolerance, and therapeutic approaches to increase or promote T follicular regulatory cells may help prevent or decrease immune dysregulation. Meanwhile, novel studies of systemic-onset juvenile idiopathic arthritis reveal a strong HLA association with interstitial lung disease and identify key aspects of the pathogenesis of macrophage activation syndrome. Studies of hyperinflammatory syndromes, including the recently described multisystem inflammatory syndrome of children, characterize similarities and differences in cytokine profiles and T-cell activation. This review focuses on recent advances in the understanding of immune dysregulation and describes potential key factors that may function as biomarkers for disease or targets for therapeutic interventions. Future trials are necessary to address the many remaining questions with regards to pathogenesis, diagnosis, and treatment of autoimmune, inflammatory, and immunodeficiency syndromes.
Topics: Child; Humans; Arthritis, Juvenile; Macrophage Activation Syndrome; Inflammation; Rheumatic Diseases; Immunologic Deficiency Syndromes
PubMed: 36608984
DOI: 10.1016/j.jaci.2022.11.001 -
Rheumatic Diseases Clinics of North... Nov 2021Juvenile idiopathic arthritis is a group of heterogeneous chronic inflammatory arthropathies occurring in childhood without a known cause. This article discusses the key... (Review)
Review
Juvenile idiopathic arthritis is a group of heterogeneous chronic inflammatory arthropathies occurring in childhood without a known cause. This article discusses the key clinical features of juvenile idiopathic arthritis and treatment updates for oligoarthritis, polyarthritis, enthesitis-related arthritis, psoriatic arthritis, and systemic arthritis. Paradigm changes in management include the earlier use of biologic agents and the introduction of biosimilars and targeted synthetic disease modifying agents like tofacitinib. This review summarizes recent developments while considering potential areas for improvement and study.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Biosimilar Pharmaceuticals; Humans
PubMed: 34635291
DOI: 10.1016/j.rdc.2021.07.009 -
Clinical Immunology (Orlando, Fla.) Feb 2020Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in children and JIA-associated uveitis its most frequent extra-articular manifestation. The... (Review)
Review
Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in children and JIA-associated uveitis its most frequent extra-articular manifestation. The uveitis is potentially sight-threatening and so carries a considerable risk of morbidity. The commonest form of uveitis seen in JIA is chronic anterior uveitis which is almost always asymptomatic in the initial stages. Therefore, screening for JIA-associated uveitis in at-risk patients is essential. The aim of early detection and treatment is to minimise intra-ocular inflammation and avoid complications leading to visual loss, resulting from both disease activity and medications. There is increasing evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. Two randomised controlled trials of adalimumab in JIA-associated uveitis provide convincing evidence for the use of this biologic in patients who fail to respond adequately to methotrexate. Tocilizumab and baricitinib are being investigated as alternatives to anti-tumour necrosis factor drugs.
Topics: Arthritis, Juvenile; Humans; Prognosis; Uveitis
PubMed: 31830532
DOI: 10.1016/j.clim.2019.108322 -
Rheumatic Diseases Clinics of North... Nov 2021Childhood noninfectious uveitis leads to sight-threatening complications. Idiopathic chronic anterior uveitis and juvenile idiopathic arthritis-associated uveitis are... (Review)
Review
Childhood noninfectious uveitis leads to sight-threatening complications. Idiopathic chronic anterior uveitis and juvenile idiopathic arthritis-associated uveitis are most common. Inflammation arises from an immune response against antigens within the eye. Ophthalmic work-up evaluates anatomic involvement, disease activity, ocular complications, and disease course. Local and/or systemic glucocorticoids are initial treatment, but not as long-term sole therapy to avoid glucocorticoids-induced toxicity or persistent ocular inflammation. Children with recurrent, refractory, or severe disease require systemic immunosuppression with methotrexate and/or anti-tumor necrosis factor monoclonal antibody medications (adalimumab, infliximab). Goals of early detection and treatment are to optimize vision in childhood uveitis.
Topics: Adalimumab; Adolescent; Arthritis, Juvenile; Child; Humans; Infliximab; Methotrexate; Uveitis
PubMed: 34635295
DOI: 10.1016/j.rdc.2021.07.005 -
Refractory systemic onset juvenile idiopathic arthritis: current challenges and future perspectives.Annals of Medicine Dec 2022Systemic juvenile idiopathic arthritis (SJIA) is a rare disease with distinct features not seen in other categories of juvenile idiopathic arthritis. In recent years,... (Review)
Review
Systemic juvenile idiopathic arthritis (SJIA) is a rare disease with distinct features not seen in other categories of juvenile idiopathic arthritis. In recent years, advances in the understanding of disease immunopathogenesis have led to improved targeted therapies with significant improvement in patient outcomes. Despite these advances, there remain subsets of SJIA with refractory disease and severe disease-associated complications. This review highlights existing options for treatment of refractory SJIA and explores potential future therapeutics for refractory disease.Key Points:Despite targeted Interleukin IL-1 and IL-6 inhibitors a subset of SJIA remains refractory to therapy. About 1 in 7 SJIA patients will be refractory to targeted IL-1 or IL-6 therapy.There is no current agreed upon definition for refractory SJIA and we propose in this review that refractory SJIA is presence of active systemic or arthritic features despite treatment with anti-IL-1 or anti-IL-6 therapy or disease requiring glucocorticoids for control beyond 6 months.SJIA disease associated complications include presence of associated macrophage activation syndrome (MAS), interstitial lung disease (ILD) or amyloidosis and management of each differs.Refractory SJIA treatment options currently include additional conventional synthetic disease modifying anti-rheumatic drugs (csDMARDS), biologic (bDMARDS), combination biologic therapy, targeted synthetic (tsDMARDS) or other immunomodulatory therapies.
Topics: Arthritis, Juvenile; Combined Modality Therapy; Glucocorticoids; Humans; Macrophage Activation Syndrome
PubMed: 35786149
DOI: 10.1080/07853890.2022.2095431 -
Advances in Pediatrics Aug 2021
Review
Topics: Antirheumatic Agents; Arthritis, Juvenile; Biological Products; Humans
PubMed: 34243850
DOI: 10.1016/j.yapd.2021.05.014 -
Nature Reviews. Rheumatology Dec 2023Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory disease with hallmarks of severe systemic inflammation, which can be accompanied by arthritis.... (Review)
Review
Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory disease with hallmarks of severe systemic inflammation, which can be accompanied by arthritis. Contemporary scientific insights set this paediatric disorder on a continuum with its counterpart, adult-onset Still disease (AOSD). Patients with sJIA are prone to complications, including life-threatening hyperinflammation (macrophage activation syndrome (sJIA-MAS)) and sJIA-associated lung disease (sJIA-LD). Meanwhile, the treatment arsenal in sJIA has expanded markedly. State-of-the-art therapeutic approaches include biologic agents that target the IL-1 and IL-6 pathways. Beyond these, a range of novel agents are on the horizon, some of them already being used on a compassionate use basis, including JAK inhibitors and biologic agents that target IL-18, IFNγ, or IL-1β and IL-18 simultaneously. However, sJIA, sJIA-MAS and sJIA-LD still pose challenging conundrums to rheumatologists treating paediatric and adult patients worldwide. Although national and international consensus treatment plans exist for the treatment of 'classic' sJIA, the treatment approaches for early sJIA without arthritis, and for refractory or complicated sJIA, are not well defined. Therefore, in this Review we outline current approaches for the treatment of sJIA and provide an outlook on knowledge gaps.
Topics: Adult; Child; Humans; Arthritis, Juvenile; Biological Factors; Interleukin-18; Lung Diseases; Macrophage Activation Syndrome
PubMed: 37923864
DOI: 10.1038/s41584-023-01042-z -
Journal of the American Academy of... Jan 2021Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced... (Review)
Review
Psoriasis is a chronic, immune-mediated, systemic, inflammatory disorder characterized by skin plaques and, often, nail disease and arthritis that contribute to reduced quality of life. Psoriatic arthritis-a heterogeneous, inflammatory, musculoskeletal disease that can cause permanent damage to both peripheral and axial joints-is the most common comorbidity of psoriasis. Axial disease occurs in 25% to 70% of patients with PsA, with some patients exclusively experiencing axial joint involvement. Early therapeutic intervention is important for preventing permanent joint and spine damage and loss of functionality in these patients. Because skin symptoms associated with psoriasis often precede psoriatic arthritis, dermatologists are uniquely positioned to play an important role in identifying and treating patients with psoriatic arthritis. Proactive screening of patients with all severities of psoriasis for the signs and symptoms of psoriatic arthritis is key to early diagnosis and intervention. In this review, we discuss the clinical presentation, risk factors, and treatment options for psoriatic arthritis with axial involvement, with the aim of helping dermatologists understand the disease and identify patients who might benefit from further assessment, treatment, and/or referral to a rheumatology practice.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Arthritis, Psoriatic; Early Diagnosis; Humans; Quality of Life; Risk Factors
PubMed: 32747079
DOI: 10.1016/j.jaad.2020.05.089