Journal of Clinical Medicine

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9 pages, 1037 KiB

Open AccessArticle

Cross-Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for Children and Adolescents with Juvenile Idiopathic Arthritis

by Ana Carolina Londe, Jaqueline Cristina de Amorim, Paulo Rogério Julio, Nico M. Wulffraat, Roberto Marini and Simone Appenzeller

J. Clin. Med. 2023, 12(3), 1116; https://doi.org/10.3390/jcm12031116 - 31 Jan 2023

Cited by 3 | Viewed by 1604

Abstract

The Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire has been developed to identify MTX adverse events in juvenile idiopathic arthritis (JIA). The objective of this study was to translate and validate MISS into Brazilian Portuguese for children and adolescents. The MISS was translated [...] Read more.

The Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire has been developed to identify MTX adverse events in juvenile idiopathic arthritis (JIA). The objective of this study was to translate and validate MISS into Brazilian Portuguese for children and adolescents. The MISS was translated into Portuguese following the standardized guidelines. We analyzed the following psychometric properties: acceptability, internal consistency, test–retest reproducibility, relative–child reliability, and external criterion and discriminant validity. We included 138 JIA patients (age: 8–18 years) and 108 relatives who took less than 5 min to answer MISS. Reproducibility tested after 15 days was good, with a kappa > 0.76. We observed good internal consistency (Cronbach’s coefficient 0.75–0.87 (patients) and 0.75–0.79 (relatives)). Reliability between patients and relatives was good except for stomachache and restlessness. Cut-off points of 5 and 6 had good sensitivity (84 and 71, respectively) and specificity (80 and 87, respectively). Using a cut-off value of 6, we observed 86 (62.3%) MTX-intolerant patients. In conclusion, MISS is a viable and practical tool for routine clinical care to identify MTX intolerance in JIA. Parents do not easily identify stomachache and restlessness as adverse MTX events. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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12 pages, 766 KiB

Open AccessArticle

Physical Activity Influences Health-Related Quality of Life in Adults with Juvenile Idiopathic Arthritis

by Rodrigo Joel de Oliveira, Ana Carolina Londe, Débora Pessoa de Souza, Roberto Marini, Paula Teixeira Fernandes and Simone Appenzeller

J. Clin. Med. 2023, 12(3), 771; https://doi.org/10.3390/jcm12030771 - 18 Jan 2023

Cited by 2 | Viewed by 1817

Abstract

This cross-sectional study aimed to evaluate the impact of physical activity and physical fitness on the health-related quality of life (HQoL) of adult patients with Juvenile Idiopathic Arthritis (JIA). Fifty-nine JIA patients and sixty healthy individuals participated in this study. All individuals had [...] Read more.

This cross-sectional study aimed to evaluate the impact of physical activity and physical fitness on the health-related quality of life (HQoL) of adult patients with Juvenile Idiopathic Arthritis (JIA). Fifty-nine JIA patients and sixty healthy individuals participated in this study. All individuals had the following evaluations performed: body composition (electrical bioimpedance), physical fitness (6 min walk test (6MWT)), physical activity level (International Physical Activity Questionnaire (IPAQ)), and HQoL (Quality of Life Questionnaire in relation to Health—Short Form (SF36)). Thirty-nine (66%) JIA patients were considered sedentary compared with 15 (25%) in the control group (p < 0.01). JIA patients had a lower HQoL compared with the control group in all variables studied (p < 0.05). JIA patients who were very physically active had better HQoL conditions in the categories of functional capacity (p = 0.001), limitations by physical aspects (p = 0.003), and emotional aspects (p = 0.002) compared with sedentary patients. JIA patients had more cardiovascular abnormalities and walked shorter distances compared with healthy controls in the 6MWT. In conclusion, we observed that HQoL was reduced in adults with JIA. A high percentage of JIA patients were sedentary with lower physical fitness, but physically active patients had a better HQoL than sedentary patients. The duration of physical activity, rather than intensity, influenced the mental aspects of HQoL. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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14 pages, 1089 KiB

Open AccessArticle

GAAGs, COMP, and YKL-40 as Potential Markers of Cartilage Turnover in Blood of Children with Juvenile Idiopathic Arthritis Treated with Etanercept—Relationship with ADAMTS4, ADAMTS5, and PDGF-BB

by Klaudia Dąbkowska, Magdalena Wojdas, Kornelia Kuźnik-Trocha, Grzegorz Wisowski, Anna Gruenpeter, Katarzyna Komosińska-Vassev, Krystyna Olczyk and Katarzyna Winsz-Szczotka

J. Clin. Med. 2022, 11(17), 5069; https://doi.org/10.3390/jcm11175069 - 29 Aug 2022

Cited by 2 | Viewed by 1535

Abstract

We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of [...] Read more.

We quantified galactosaminoglycans (GAAGs), oligomeric cartilage matrix protein (COMP), and human cartilage glycoprotein 39 (YKL-40) in blood obtained from juvenile idiopathic arthritis (JIA) before and during 2-year treatment with etanercept (ETA), as potential biomarkers of cartilage extracellular matrix (ECM) dysfunction and indicators of efficacy of biologic therapy. We also evaluated the relationship of the mentioned markers with the factors that regulate their metabolism, disintegrin and thrombospondin motif metalloproteinases 4 (ADAMTS4), ADAMTS5, and platelet-derived growth factor BB (PDGF-BB). Methods: We studied 38 children diagnosed with JIA and 45 healthy children. We quantified GAAGs by assessing the concentration of unsaturated disaccharide units formed by digestion of isolated glycosaminoglycans with chondroitinase ABC, while COMP, YKL-40, and PDGF-BB were quantified using immunoenzymatic methods. Results: Compared to the control group, GAAGs and COMP levels were significantly lower, while YKL-40 levels were higher in the blood of patients with aggressive JIA, qualified for ETA treatment. ETA therapy leading to clinical improvement simultaneously promoted normalization of COMP and YKL-40 levels, but not GAAGs. After 24 months of taking ETA, glycan levels were still significantly lower, relative to controls. GAAGs, COMP, and YKL-40 levels were significantly influenced by ADAMTS4, ADAMTS5, and PDGF-BB levels both before and during ETA treatment. Conclusions: The dynamics of changes in marker concentrations during treatment seem to indicate that measurement of COMP and YKL-40 levels can be used to assess the chondroprotective biological efficacy of therapy. In contrast, changes in GAAGs concentrations reflect systemic extracellular matrix transformations in the course of JIA. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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11 pages, 255 KiB

Open AccessArticle

Programmed Cell Death Protein-1 Upregulation in Response to SARS-CoV-2 in Juvenile Idiopathic Arthritis: A Case-Control Study

by Violetta Opoka-Winiarska, Ewelina Grywalska, Izabela Korona-Głowniak, Izabela Morawska, Krzysztof Gosik, Anna Malm and Jacek Roliński

J. Clin. Med. 2022, 11(14), 4060; https://doi.org/10.3390/jcm11144060 - 13 Jul 2022

Cited by 3 | Viewed by 1580

Abstract

Currently, data regarding the impact of COVID-19 disease (caused by SARS-CoV-2) on patients with childhood rheumatic diseases are significantly limited. To assess the possible connection, we measured levels of IgA and IgG anti-SARS-CoV-2 antibodies in children with juvenile idiopathic arthritis (JIA) and a [...] Read more.

Currently, data regarding the impact of COVID-19 disease (caused by SARS-CoV-2) on patients with childhood rheumatic diseases are significantly limited. To assess the possible connection, we measured levels of IgA and IgG anti-SARS-CoV-2 antibodies in children with juvenile idiopathic arthritis (JIA) and a control group during the pandemic, prior to the introduction of anti-COVID-19 vaccination. We assessed levels of PD-1 suppressive molecule and inflammatory markers in patients and correlated those results with serological response to SARS-CoV-2. In JIA patients, the activity of the disease was assessed using the Juvenile Arthritis Disease Activity Score 71 (JADAS 71) scale. The study consisted of 96 children, 65 diagnosed with JIA, treated with antirheumatic drugs, and 31 healthy volunteers. In patients with JIA, significantly higher levels of SARS-CoV-2 antibodies in the IgA and IgG were demonstrated compared to the control group. We also found significantly higher serum PD-1 levels in JIA patients and control volunteers who were seropositive for SARS-CoV-2 IgA or IgG antibodies compared to those who were seronegative. The humoral immune response to SARS-CoV-2 infection is associated with the persistent upregulation of PD-1 expression in both JIA patients and healthy children. The clinical significance of the detected disorder requires further careful observation. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

13 pages, 607 KiB

Open AccessArticle

The Effects of TNF-α Inhibition on the Metabolism of Cartilage: Relationship between KS, HA, HAPLN1 and ADAMTS4, ADAMTS5, TOS and TGF-β1 Plasma Concentrations in Patients with Juvenile Idiopathic Arthritis

by Kornelia Kuźnik-Trocha, Katarzyna Winsz-Szczotka, Iwona Lachór-Motyka, Klaudia Dąbkowska, Magdalena Wojdas, Krystyna Olczyk and Katarzyna Komosińska-Vassev

J. Clin. Med. 2022, 11(7), 2013; https://doi.org/10.3390/jcm11072013 - 4 Apr 2022

Cited by 5 | Viewed by 2132

Abstract

We assessed the effect of 24-month anti-tumor necrosis factor alpha (TNF-α) treatment on the remodeling of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: Quantitative evaluation of keratan sulfate (KS), hyaluronic acid (HA), hyaluronan and proteoglycan link protein [...] Read more.

We assessed the effect of 24-month anti-tumor necrosis factor alpha (TNF-α) treatment on the remodeling of the cartilage extracellular matrix (ECM) in patients with juvenile idiopathic arthritis (JIA). Methods: Quantitative evaluation of keratan sulfate (KS), hyaluronic acid (HA), hyaluronan and proteoglycan link protein 1 (HAPLN1), as potential biomarkers of joint dysfunction, and the levels of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5, total oxidative status (TOS) and transforming growth factor (TGF-β1) was performed (using immunoenzymatic methods) in blood obtained from patients before and after 24 months of etanercept (ETA) treatment. Results: When compared to the controls, KS, HA and HAPLN1 levels were significantly higher in patients with an aggressive course of JIA qualified for ETA treatment. An anti-cytokine therapy leading to clinical improvement promotes the normalization only of the HA level. Proteolytic and pro-oxidative factors, present in high concentrations in patients before the treatment, correlated with HAPLN1, but not with KS and HA levels. In these patients, negative correlations were found between the levels of TGF-β1 and KS, HA and HAPLN1. Conclusion: The anti-TNF-α therapy used in patients with JIA has a beneficial effect on ECM cartilage metabolism, but it does not completely regenerate it. The changes in the plasma HA level during the anti-cytokine therapy suggest its potential diagnostic utility in monitoring of disease activity and may be used to assess the efficacy of ETA treatment. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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Review

Jump to: Research, Other

17 pages, 960 KiB

Open AccessReview

JAK Inhibition in Juvenile Idiopathic Arthritis (JIA): Better Understanding of a Promising Therapy for Refractory Cases

by Isabelle Melki and Marie-Louise Frémond

J. Clin. Med. 2023, 12(14), 4695; https://doi.org/10.3390/jcm12144695 - 14 Jul 2023

Cited by 4 | Viewed by 2709

Abstract

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases with probably differential underlying physiopathology. Despite the revolutionary era of biologics, some patients remain difficult to treat because of disease severity, drug adverse events, drug allergy or association with severe comorbidities, i.e., uveitis, [...] Read more.

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases with probably differential underlying physiopathology. Despite the revolutionary era of biologics, some patients remain difficult to treat because of disease severity, drug adverse events, drug allergy or association with severe comorbidities, i.e., uveitis, interstitial lung disease and macrophagic activation syndrome. Janus Kinase (JAK) inhibitors are small molecules that target JAK/Signal Transducers and Activators of Transcription (STAT) pathways, which could then prevent the activity of several proinflammatory cytokines. They may provide a useful alternative in these cases of JIA or in patients actually affected by Mendelian disorders mimicking JIA, such as type I interferonopathies with joint involvement, and might be the bridge for haematopoietic stem cell transplantation in these disabling conditions. As these treatments may have side effects that should not be ignored, ongoing and further controlled studies are still needed to provide data underlying long-term safety considerations in children and delineate subsets of JIA patients that will benefit from these promising treatments. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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14 pages, 987 KiB

Open AccessReview

Juvenile Psoriatic Arthritis: Myth or Reality? An Unending Debate

by Roberta Naddei, Ana Rebollo-Giménez, Marco Burrone, Valentina Natoli, Silvia Rosina, Alessandro Consolaro and Angelo Ravelli

J. Clin. Med. 2023, 12(1), 367; https://doi.org/10.3390/jcm12010367 - 3 Jan 2023

Cited by 4 | Viewed by 11983

Abstract

Juvenile psoriatic arthritis (JPsA) accounts for 1–7% of all cases of juvenile idiopathic arthritis (JIA) and its definition has been a matter of controversy among pediatric rheumatologists for many years. The traditional attribution of JPsA to the spondyloarthropathy group was challenged in the [...] Read more.

Juvenile psoriatic arthritis (JPsA) accounts for 1–7% of all cases of juvenile idiopathic arthritis (JIA) and its definition has been a matter of controversy among pediatric rheumatologists for many years. The traditional attribution of JPsA to the spondyloarthropathy group was challenged in the early 1990s, whereas the recent demonstrations of its heterogenous nature have led to questions about its identification as a distinct category in JIA classification. It has been shown that children with the phenotype of JPsA can be divided in two subgroups, one presenting with the features of early-onset ANA-positive JIA, and another that belongs to the spectrum of spondyloarthropathies. The few studies that have compared the clinical characteristics and genetic determinants of JPsA with those of the other JIA categories have obtained contrasting findings. The debate on the categorization of JPsA as a distinct entity within JIA classification is still ongoing and has prompted the revision of its current classification. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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14 pages, 6157 KiB

Open AccessReview

Contribution of Ultrasound in Current Practice for Managing Juvenile Idiopathic Arthritis

by Charlotte Borocco, Federica Anselmi and Linda Rossi-Semerano

J. Clin. Med. 2023, 12(1), 91; https://doi.org/10.3390/jcm12010091 - 22 Dec 2022

Cited by 5 | Viewed by 2420

Abstract

The interest and application of musculoskeletal ultrasound (MSUS) in juvenile idiopathic arthritis (JIA) are increasing. Numerous studies have shown that MSUS is more sensitive than clinical examination for detecting subclinical synovitis. MSUS is a well-accepted tool, easily accessible and non-irradiating. Therefore, it is [...] Read more.

The interest and application of musculoskeletal ultrasound (MSUS) in juvenile idiopathic arthritis (JIA) are increasing. Numerous studies have shown that MSUS is more sensitive than clinical examination for detecting subclinical synovitis. MSUS is a well-accepted tool, easily accessible and non-irradiating. Therefore, it is a useful technique throughout JIA management. In the diagnostic work-up, MSUS allows for better characterizing the inflammatory involvement. It helps to define the disease extension, improving the classification of patients into JIA subtypes. Moreover, it is an essential tool for guiding intra-articular and peritendinous procedures. Finally, during the follow-up, in detecting subclinical disease activity, MSUS can be helpful in therapeutic decision-making. Because of several peculiarities related to the growing skeleton, the MSUS standards defined for adults do not apply to children. During the last decade, many teams have made large efforts to define normal and pathological US features in children in different age groups, which should be considered during the US examination. This review describes the specificities of MSUS in children, its applications in clinical practice, and its integration into the new JIA treat-to-target therapeutic approach. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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10 pages, 733 KiB

Open AccessReview

Hypersensitivity to Biological Treatments in Juvenile Idiopathic Arthritis: How Should It Be Managed?

by Muserref Kasap Cuceoglu, Ozge Basaran, Ozge Soyer and Seza Ozen

J. Clin. Med. 2022, 11(24), 7291; https://doi.org/10.3390/jcm11247291 - 8 Dec 2022

Cited by 1 | Viewed by 1561

Abstract

Juvenile idiopathic arthritis (JIA) is one of the most frequent diseases in the practice of pediatric rheumatology. JIA treatments have been modified and improved with the use of biological drugs along with technological innovations. However, different types of hypersensitivity reactions to biological drugs [...] Read more.

Juvenile idiopathic arthritis (JIA) is one of the most frequent diseases in the practice of pediatric rheumatology. JIA treatments have been modified and improved with the use of biological drugs along with technological innovations. However, different types of hypersensitivity reactions to biological drugs have also been reported. Anaphylaxis and infusion reactions occurring during the intravenous infusion require a critical approach in the acute period. On the other hand, the detection of drug-related late-type reactions and the development of antibodies to the agent highlight the need for an understanding of the drug-induced etiology to prevent the patient from continuing the treatment with the culprit drug. The chronic disease process, concomitant immune dysregulation, and multiple drug use may result in these hypersensitivity reactions. In this review, the hypersensitivity reactions to the biological treatments used in patients with juvenile idiopathic arthritis and the management of these conditions are discussed. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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8 pages, 236 KiB

Open AccessReview

Treat to Target (Drug-Free) Inactive Disease in JIA: To What Extent Is This Possible?

by Athimalaipet V. Ramanan and Anne M. Sage

J. Clin. Med. 2022, 11(19), 5674; https://doi.org/10.3390/jcm11195674 - 26 Sep 2022

Cited by 6 | Viewed by 1598

Abstract

Background: Treat to target (T2T) is a strategy that has been increasingly employed in the management of several chronic diseases, with demonstrated improved outcomes. The use of T2T in juvenile idiopathic arthritis (JIA), a common rheumatic disease of childhood, is still in [...] Read more.

Background: Treat to target (T2T) is a strategy that has been increasingly employed in the management of several chronic diseases, with demonstrated improved outcomes. The use of T2T in juvenile idiopathic arthritis (JIA), a common rheumatic disease of childhood, is still in its infancy, and the feasibility of its use in attaining drug-free clinical remission is unclear. Aims: We aim to explore the current literature of the use of T2T in JIA, and to review the potential benefits and limitations of this approach in regard to this chronic disease. Sources: A comprehensive PubMed search was conducted using relevant keywords, with full text articles in English included in the review. Content: T2T is an appealing strategy for improving outcomes of pediatric rheumatic diseases given the limited availability of therapeutics and potential cumulative effects of long-term immunosuppression. The application in a cohort of children, however, is limited by heterogeneity of disease, availability of high-quality evidence, and patient and parental preferences. Unlike adult rheumatoid arthritis, the ‘window of opportunity’ has not been definitively demonstrated in large scale trials, and although early studies of T2T in JIA have been favorable, the timing and means of escalation (especially with regard to biologics) need clarification. Implications: This review outlines several issues of implementing T2T in JIA, including the important extra-articular manifestations of disease and non-pharmacological management, that should be considered in future consensus guidelines. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

Other

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11 pages, 1106 KiB

Open AccessBrief Report

Rescue of Pap-Mas in Systemic JIA Using Janus Kinase Inhibitors, Case Report and Systematic Review

by Franck Zekre, Anita Duncan, Audrey Laurent, Maud Tusseau, Rémi Pescarmona, Sophie Collardeau-Frachon, Camille Ohlmann, Sébastien Viel, Philippe Reix, Sarah Benezech and Alexandre Belot

J. Clin. Med. 2023, 12(7), 2702; https://doi.org/10.3390/jcm12072702 - 4 Apr 2023

Cited by 8 | Viewed by 2384

Abstract

Introduction: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as [...] Read more.

Introduction: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity. Methods: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment. Results: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis. Conclusions: JAKi represent a promising option in the treatment of lung disease associated with sJIA. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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15 pages, 2410 KiB

Open AccessOpinion

Chronic Recurrent Multifocal Osteomyelitis (CRMO) and Juvenile Spondyloarthritis (JSpA): To What Extent Are They Related?

by Isabelle Koné-Paut, Inès Mannes and Perrine Dusser

J. Clin. Med. 2023, 12(2), 453; https://doi.org/10.3390/jcm12020453 - 5 Jan 2023

Cited by 7 | Viewed by 4317

Abstract

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and [...] Read more.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and falls into the spectrum of spondyloarthritis (SpA). The fact that a patient can progress from one disease to another raises the question of whether CRMO, like SAPHO, could fall within the spectrum of SpA, ranging from a predominantly osteoarticular form to an enthesitic form with more or less marked skin involvement. In this review, we set out to discuss this hypothesis by highlighting the differences and similarities between CRMO and juvenile SpA in clinical, radiological and pathophysiological aspects. A common hypothesis could potentially consider intestinal dysbiosis as the origin of these different inflammatory diseases. Interindividual factors such as gender, environment, genetics and/or epigenetic background could act as combined disease modifiers. This is why we suggest that pathophysiology, rather than clinical phenotype, be used to reclassify these diseases. Full article

(This article belongs to the Special Issue New Advances in Juvenile Idiopathic Arthritis (JIA))

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