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Advances in Pediatric Rheumatology: Focus on Juvenile Idiopathic Arthritis
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Advances in Pediatric Rheumatology: Focus on Juvenile Idiopathic Arthritis

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Allergy and Immunology".

Deadline for manuscript submissions: 15 November 2025 | Viewed by 1360

Special Issue Editor

Dr. Tamas Constantin

E-Mail Website
Guest Editor
2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary
Interests: pediatric rheumatology; juvenile idiopathic arthritis; juvenile systemic sclerosis

Special Issue Information

Dear Colleagues,

Recent developments in pediatric rheumatology have significantly advanced the understanding and treatment of juvenile idiopathic arthritis (JIA), and biomarkers are crucial in guiding diagnosis and therapeutic decisions. Notable biomarkers such as MRP8/14 (S100A8/A9) have emerged as valuable tools to monitor disease activity, particularly in systemic JIA (sJIA). Elevated levels of MRP8/14 can predict flares and are closely related to inflammation in active disease. Similarly, interleukin-18 (IL-18) has shown promise as a biomarker, especially in systemic JIA, where high levels of IL-18 correlate with disease severity and macrophage activation syndrome (MAS), a life-threatening complication of JIA.

In terms of complications, uveitis, a common extra-articular manifestation in JIA, has seen improved management through early biologic interventions. Adalimumab, a TNF inhibitor, has been particularly effective in controlling JIA-associated uveitis resistant to conventional treatments such as methotrexate. Early and aggressive use of these biologics, often in combination with methotrexate, has dramatically reduced the risk of long-term ocular complications such as cataracts and glaucoma. Second-line biologics, such as abatacept and tocilizumab, have provided additional options for patients with refractory uveitis, improving overall visual outcomes.

Early biologic therapies, including TNF inhibitors (etanercept, adalimumab), IL-1 blockers (anakinra, canakinumab), and IL-6 inhibitors (tocilizumab), continue to be transformative, mainly when initiated early in disease progression. This approach has led to better disease control, reduced long-term joint damage, and improved quality of life for patients. The introduction of JAK inhibitors, such as tofacitinib, has provided additional therapeutic options for patients who do not respond to traditional biologics, offering more personalized treatment strategies.

Furthermore, newer therapies, such as IL-17 inhibitors (secukinumab), have improved the treatment of juvenile spondyloarthropathies (JSPA). These drugs specifically target the inflammatory pathways involved in arthritis related to enthesitis, improving disease outcomes for patients with more resistant forms of JIA.

In general, advances in biomarkers such as MRP8/14 and IL-18, combined with early interventions and novel treatments, have significantly changed the landscape of JIA management. These developments enable precise disease monitoring, personalized therapies, and better long-term outcomes for pediatric patients.

Dr. Tamas Constantin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Children is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • juvenile idiopathic arthritis
  • pediatric rheumatology
  • Uveitis
  • MRP8/14 (S100A8/A9)
  • interleukin-18 (IL-18)
  • TNF inhibitors (etanercept, adalimumab)
  • IL-1 blockers (anakinra, canakinumab)
  • IL-6 inhibitors (tocilizumab)
  • JAK inhibitors
  • IL-17 inhibitors (secukinumab)

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Published Papers (3 papers)

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Research

14 pages, 9863 KiB  
Article
Examination of Behavioral and Neuropsychological Characteristics of Hungarian Patients with Juvenile Idiopathic Arthritis: A Cross-Sectional Analysis
by Diána Garan, Lilla Lengvári, Andrea Ponyi, Márton Szabados, Gyurgyinka Gergev, Imre Bozi, Wouter Wijker and Tamás Constantin
Children 2025, 12(8), 1057; https://doi.org/10.3390/children12081057 - 12 Aug 2025
Viewed by 148
Abstract
Background: Children with juvenile idiopathic arthritis (JIA) may experience chronic pain, contributing to psychological distress. Objective: The objective was to assess neuropsychological functions and behavioral skills in patients with JIA and identify demographic and disease-related factors influencing these outcomes. Methods: This cross-sectional study [...] Read more.
Background: Children with juvenile idiopathic arthritis (JIA) may experience chronic pain, contributing to psychological distress. Objective: The objective was to assess neuropsychological functions and behavioral skills in patients with JIA and identify demographic and disease-related factors influencing these outcomes. Methods: This cross-sectional study evaluated 112 patients at the Division of Pediatric Rheumatology, Semmelweis University (2015–2016). Participants completed psychological assessments using the Child Behavior Checklist and Woodcock–Johnson III Tests. Examined variables included demographic (age and sex), clinical (age at diagnosis and disease activity), and treatment-related factors (therapy type and duration). Treatment groups comprised (a) combination therapy with TNF inhibitor and methotrexate (MTX) (n = 60), (b) MTX monotherapy (n = 34), and (c) TNF inhibitor monotherapy (n = 18). Results: Neuropsychological variables showed no clinically significant differences between treatment groups. These skills were unaffected by age, sex, therapy duration, or disease activity. Pathological behavioral scores were significantly higher (p < 0.05) in younger patients (<7 years), with females showing greater susceptibility to anxiety and depression (p < 0.05). Conclusions: No clinically significant psychological impairments were observed in our cohort. Further research is warranted to clarify the significance of abnormal behavioral scores. Psychological care provision remains vital for improving the quality of life in JIA patients. Full article
(This article belongs to the Special Issue Advances in Pediatric Rheumatology: Focus on Juvenile Idiopathic Arthritis)
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12 pages, 451 KiB  
Article
Medical Post-Traumatic Stress Disorder Symptoms in Children and Adolescents with Chronic Inflammatory Arthritis: Prevalence and Associated Factors
by Leah Medrano, Brenda Bursch, Jennifer E. Weiss, Nicholas Jackson, Deborah McCurdy and Alice Hoftman
Children 2025, 12(8), 1004; https://doi.org/10.3390/children12081004 - 30 Jul 2025
Viewed by 275
Abstract
Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic [...] Read more.
Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article
(This article belongs to the Special Issue Advances in Pediatric Rheumatology: Focus on Juvenile Idiopathic Arthritis)
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15 pages, 760 KiB  
Article
Forecasting Achievement of Inactive Disease in Juvenile Idiopathic Arthritis with Artificial Intelligence
by Ana I. Rebollo-Giménez, Francesca Ridella, Silvia Maria Orsi, Elena Aldera, Marco Burrone, Valentina Natoli, Silvia Rosina, Alessandro Consolaro, Esperanza Naredo, Angelo Ravelli and Davide Cangelosi
Children 2025, 12(6), 741; https://doi.org/10.3390/children12060741 - 7 Jun 2025
Viewed by 530
Abstract
Objective: to seek for predictors of inactive disease (ID) in juvenile idiopathic arthritis (JIA) with artificial intelligence. Methods: The clinical charts of patients seen within 6 months after disease onset between 2007 and 2019 and with follow-up visits at 6, 12, 18, and [...] Read more.
Objective: to seek for predictors of inactive disease (ID) in juvenile idiopathic arthritis (JIA) with artificial intelligence. Methods: The clinical charts of patients seen within 6 months after disease onset between 2007 and 2019 and with follow-up visits at 6, 12, 18, and 24 months were reviewed retrospectively. Sixty-eight potential predictors were recorded at each visit. The primary endpoint was ID at 24 months by 2004 Wallace criteria. Data obtained from diverse combinations of visits were examined to identify the best forecasting model. After pre-processing, the cohort was divided into training (50%) and testing (50%) cohorts. Multivariate time series forecasting, coupled with the Random Forest method, was used to train the machine learning (ML) forecasting model. Predictive performance was assessed through the Matthews correlation coefficient (MCC). Results: A total of 414 patients were included. The best performance in predicting ID at 24 months in the training cohort was provided by the 0–12 months interval (MCC = 0.68). In the testing cohort, the same ML model confirmed a high forecasting performance (MCC = 0.65). Assessment of feature importance and impact analysis showed that the most relevant predictor of ID was the physician’s global assessment (PhGA), followed by the count of active joints (AJC). Conclusions: PhGA and AJC values over the first 12 months were the strongest predictors of ID at 24 months. This finding highlights the importance of regular quantitative assessment of disease activity by the caring physician in monitoring the course of the patient toward achievement of complete disease quiescence. Full article
(This article belongs to the Special Issue Advances in Pediatric Rheumatology: Focus on Juvenile Idiopathic Arthritis)
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