The Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria among youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria.

This was a retrospective cross-sectional sample of youth diagnosed with juvenile SpA who met the axJSpA classification criteria. Demographics, clinical manifestations, and physician and patient-reported outcomes were abstracted from medical records. Magnetic resonance imaging (MRI) scans underwent central imaging review by at least two central raters. Differences between groups were compared using Wilcoxon signed-rank test or chi-square test, as appropriate.

Of 158 patients who met axJSpA criteria, 107 patients (68%) met the PRINTO provisional criteria for enthesitis/spondylitis-related arthritis. A total of 41 patients (26%) did not fulfill any of the three major PRINTO criteria due to lack of peripheral disease manifestations. Demographics, prevalence of inflammatory or structural lesions on MRI, family history of SpA, and duration of pain were not statistically different between those who did and did not meet PRINTO criteria. Those who fulfilled the PRINTO criteria had significantly more peripheral arthritis, enthesitis, and HLA-B27 positivity but reported less sacral/buttock pain.

Phenotypic differences of children with axJSpA between those who were and were not classified by the PRINTO criteria were primarily due to peripheral disease manifestations and HLA-B27 positivity. Modification of the PRINTO provisional criteria may facilitate capture of youth with primarily axial disease.

Neutrophilic urticarial dermatosis (NUD) is a distinctive dermatological manifestation that is commonly associated with systemic autoinflammatory and autoimmune diseases. This review comprehensively explores NUD in the context of five major conditions: Schnitzler syndrome, Still's disease, cryopyrin-associated periodic syndrome, systemic lupus erythematosus, and VEXAS syndrome. For each condition, a detailed discussion of the underlying mechanisms, clinical presentations, diagnostic criteria, and treatment strategies is provided. In addition, cases exhibiting features similar to NUD are emphasized, with a comprehensive examination of the pathological characteristics, particularly focusing on neutrophilic epitheliotropism. This review underscores the significance of identifying NUD as a potential indicator of systemic autoimmune disorders and discusses the role of skin biopsy and laboratory tests in diagnosing the underlying etiology. Finally, a diagnostic framework for NUD is proposed, highlighting the importance of a multidisciplinary assessment to ascertain the underlying systemic condition responsible for the dermatological manifestations. The objective of this review is to enhance the comprehension of NUD, thereby facilitating early diagnosis and the implementation of targeted strategies for affected patients.

Spondyloarthropathies (SpAs) represent a diverse group of seronegative immune-mediated inflammatory diseases characterized by a genetic predisposition and an association with human leukocyte antigen-B27. This narrative review aims to explore juvenile spondyloarthropathies (JSpAs), their classification, clinical manifestations, diagnostic challenges, and contemporary treatment strategies. According to the International League of Associations for Rheumatology criteria, JSpAs include several specific forms: enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Despite established classifications, the terms and definitions surrounding these conditions can often lead to confusion among healthcare professionals. This ambiguity underscores the need for a standardized approach to nosological classification. The clinical presentation of JSpAs can be multifaceted, encompassing both articular and extra-articular manifestations. Articular symptoms may include enthesitis and varying forms of arthritis, while extra-articular involvement can range from uveitis to gastrointestinal, cardiovascular, pulmonary, neurological, and renal complications. These diverse manifestations highlight the systemic nature of the disease and the importance of a holistic approach to diagnosis and treatment. While laboratory tests for SpAs are often non-specific, imaging modalities such as musculoskeletal ultrasound and magnetic resonance imaging play a crucial role in the early detection of inflammatory lesions. These imaging techniques can provide valuable insights into disease progression and aid in the formulation of appropriate treatment plans. Current treatment guidelines advocate for a "stepwise" approach to therapy, beginning with nonsteroidal anti-inflammatory drugs and progressing to glucocorticoids, disease-modifying antirheumatic drugs, and biological agents, particularly anti-tumor necrosis factor alpha agents. The primary objective of treatment is to achieve clinical remission or, at a minimum, to attain low disease activity. Regular monitoring of disease activity is imperative; however, the lack of validated assessment tools for the pediatric population remains a significant challenge. JSpAs pose unique challenges in terms of diagnosis and management due to their diverse manifestations and the complexities of their classification. Ongoing research and clinical efforts are essential to refine our understanding of these conditions, improve treatment outcomes, and enhance quality of life for affected children and their families. Effective management hinges on early detection, individualized treatment plans, and continuous monitoring, ensuring that patients receive the most appropriate care tailored to their specific needs.

Still's disease (SD), including systemic juvenile idiopathic arthritis (sJIA) and adult-onset SD (AOSD), is an inflammatory condition typically characterized by daily fever, arthritis, and skin rash together with neutrophilic leukocytosis, thrombocytosis, and increased acute phase reactants. The reported differences between sJIA and AOSD appear to reflect variations along an inflammatory spectrum influenced by age, rather than differences in the underlying pathology.

In February 2023, an expert meeting, including pediatric and adult rheumatologists, was held in Rome, Italy, with the aim of defining more precise and timely strategies for disease management. The following four topics were discussed: (1) early recognition and diagnosis of SD; (2) pathogenetic pathways and possible biomarkers for diagnosis and response; (3) refractory disease and risk factors, and (4) treatment of SD and its complications.

The development of improved diagnostic criteria and validation of biomarkers are important steps towards achieving early diagnosis, although several biomarkers remain to be universally validated and available for clinical practice. Additionally, awareness of important complications of SD, including macrophage activation syndrome and lung disease, is crucial for improving patient outcomes, alongside an improved understanding of risk factors for the development of refractory disease. While interleukin (IL)-1 and IL-6 inhibitors have improved the treatment landscape of SD, harmonizing the therapeutic approach across centers and countries, together with developing treatment strategies for refractory patients, still represents a challenge.

Here, we summarize the results of discussions among experts, supplemented by relevant literature, and highlight unmet needs in the diagnosis and management of SD.

Juvenile idiopathic arthritis is a heterogeneous group of chronic childhood arthritis. We planned to classify patients with oligoarticular, rheumatoid factor (RF)-negative polyarticular and undifferentiated groups according to the International League of Associations for Rheumatology criteria, most of them in other or undifferentiated groups according to the new proposed PRINTO (Pediatric Rheumatology International Trials Organization) criteria, into more homogeneous groups according to their clinical and laboratory findings.

Two hundred three patients with oligoarticular, RF-negative polyarticular and undifferentiated juvenile idiopathic arthritis were included in the study. Sixteen clinical and laboratory variables were evaluated using TwoStep Cluster analysis. Clinical and laboratory characteristics of the resulting clusters were then compared with each other.

Two clusters were generated as the result of cluster analysis. Cluster 1 had 138 (68%) and cluster 2 had 65 (32%) patients. The main indicators differentiating 2 clusters were wrist and elbow involvement and the number of affected joints. The number of affected joints was 2 (1-8) and 6 (1-26) in cluster 1 and cluster 2 (p < 0.001). Wrist and shoulder involvements were seen only in cluster 2 (p < 0.001). Ankle, elbow, small joint, and temporomandibular joint involvements were higher in cluster 2. Corticosteroids, disease-modifying antirheumatic drugs, and biologics were used at higher rates, and remissions at the 12th month and last visit were lower in cluster 2.

Our results classified patients with oligoarticular, RF-negative polyarticular, and undifferentiated arthritis into 2 clusters. Wrist and elbow involvements and the number of involved arthritis were the most important factors in differentiating the 2 groups.

The aim of this study was to investigate the effects of multimodal rheumatologic complex treatment (MRCT) in childhood and adolescence. MRCT means a high-frequency treatment program of at least 11 h per week.

MRCTs in children, carried out between May 2009 and May 2022 at the Department of Pediatrics of the University Hospital in Halle (Saale), were included in this study. The effects of the MRCT were evaluated based on inflammatory activity, functionality (using the Childhood Health Assessment Questionnaire (CHAQ)), subjective statements regarding pain intensity, state of health, and coping with the illness, as well as the objective determination of joint mobility. Data were analyzed retrospectively using t-tests to compare different groups and values before and after treatment.

During the study period, N = 133 MRCTs were conducted in n = 95 children. The most common diagnosis was juvenile idiopathic arthritis (83.2%). The c-reactive protein (CRP) fell from an average of 25.3 mg/L to 7.3 mg/L, and the erythrocyte sedimentation rate (ESR) fell from 29.5 mm in the first hour to 17.9 mm. Pain intensity was reduced from 5.4 to 4.0. The state of health and coping with the illness also improved. The disability index showed a moderate reduction from 0.92 to 0.81. Furthermore, an improvement in joint mobility was observed. Positive effects were also shown in patients with somatoform disorders.

Due to the positive effects of MRCT on subjective well-being and physical health, the treatment program can be recommended for affected children, including patients with an additional diagnosed somatoform disorder.

To analyze disease activity and treatment in patients with juvenile idiopathic arthritis (JIA) before transfer to adult care.

We retrospectively collected the clinical data of 230 JIA patients (range 14-18 years) in our center from January 2013 to December 2022. We evaluated the clinical features, disease activity, and medication use across various JIA subtypes.

230 patients with JIA were included, and 144 (63%) were male. The distribution of JIA subtypes was dominated by enthesitis-related arthritis (32%), polyarthritis (31%), systemic JIA (27%), and oligoarthritis (10%). Disease activity assessment showed that 87 JIA (38%) were in active disease; while 143 JIA (62%) were in inactive disease, of which 59 patients achieved clinical remission on medicine and 13 patients achieved clinical remission off medicine. Conventional synthetic disease-modifying anti-rheumatic drugs were used in 83% of JIA patients, and biologics in 56%. Clinical characteristics and medication use differed between different subtypes of JIA. The oligoarthritis group had earlier disease onset (P = 0.020) and longer disease duration (P = 0.009) compared to other subtypes. Patients in the RF-positive polyarthritis group had a significantly lower rate of disease inactivity (39%, P = 0.004) than the other subtypes, and a relatively lower proportion of patients achieved clinical remission on medication or discontinuation of medication (18%, P = 0.024).

Some JIA patients were still in active disease before transfer to adult clinics, failing to achieve clinical remission and discontinuation of medication, and required continued treatment. Patients in the RF-positive polyarthritis group were less likely to achieve clinical remission.

To our knowledge, limited information is available about the differences in the characteristics of rheumatoid factor (RF)-negative polyarticular juvenile idiopathic arthritis (JIA) throughout the world. This study was aimed to compare the demographic and clinical features of patients with RF-negative polyarthritis across the world.

Patients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment regimens, and disease status in patients from different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and collection of ongoing medications.

Among the 9081 patients enrolled in the EPOCA study, 2141 patients (23.6%) with RF-negative polyarthritis were included in the present analysis. The prevalence of RF-negative polyarthritis was highest in North America and lowest in Southeast Asia (12.7%). The age at disease onset was lower in Northern and Southern Europe, where the highest prevalence of uveitis was found. Uveitis was rare in Southeast Asia, Africa & Middle East and Latin America. Patients from Eastern Europe, Latin America and Africa and Middle East presented with the highest prevalence of active joints at the visit. The combination of early onset, ANA positivity, and uveitis was observed mainly in Southern Europe (39%).

Our results confirm the wide heterogeneity of the clinical presentation and outcome of children with RF-negative polyarticular JIA throughout the world. In particular, relevant differences in the onset age were observed across geographic areas. The group of children with early onset polyarthritis, ANA positivity, and risk of uveitis is remarkably frequent in Southern Europe.

The International League of Associations for Rheumatology (ILAR) juvenile idiopathic arthritis (JIA) classification was revisited by the Pediatric Rheumatology International Trials Organization (PRINTO) in 2018. Classifications should establish uniform groups to assist physicians in providing optimal care. Therefore, we evaluated changes proposed by PRINTO to highlight their impact on forming consistent groups regarding uveitis and treatment responses, particularly focusing on early-onset anti-nuclear antibody (ANA)-positive JIA.

Pediatric patients diagnosed with JIA according to ILAR and PRINTO classification, with a minimum of 1-year of follow-up, were enrolled, excluding those meeting the exclusion criteria for both the oligoarticular JIA and the early-onset ANA-positive JIA groups.

Among the 139 enrolled patients, 110 (79.1%) had oligoarticular JIA, while 15 (10.8%) had early-onset ANA-positive JIA. The below-age-5 criterion demonstrated the strongest association with uveitis, while the below-age-7 provided similar associations without substantial exclusions (odds ratio (OR) 8.62 [2.50-29.81] vs 7.45 [2.37-26.66]). Patients with a single ANA positivity at a titer ≥ 1/160 and age of onset below 7 had a notably higher risk of new-onset uveitis and biologic DMARD requirement (OR 7.95 [2.37-26.66] and 3.6 [1.42-9.09], respectively).

The inclusion of age of disease onset and ANA positivity with a titer ≥ 1/160 has enhanced uniformity in uveitis risk and treatment response, including failure of conventional synthetic DMARDs. Additionally, a single ANA positivity at a ≥ 1/160 titer rather than requiring two instances yields similar consistency. However, the joint count criteria failed to form consistent groups. PRINTO's classification places a significant proportion of patients into the "other JIA" group, necessitating further classification for improved clinical utility. Key Points •Inclusion of age and ANA positivity criteria increased uniformity among the subgroups. •Single ANA positivity at a ≥ 1/160 titer can be sufficient instead of twice. •Early utilization of bDMARDs may be beneficial for early-onset ANA-positive JIA group. •PRINTO classification must further classify the "other JIA" before being implemented in clinical practice.

Elderly-onset rheumatoid arthritis (EORA) may have peculiar findings compared to juvenile-onset RA (JORA). The aim of the work was to present and compare the clinical characteristics of RA patients with JORA and elderly-onset EORA to a group of cases with adult-onset (AORA) and to contrast the findings worldwide.

The study included 1100 adult RA patients: 209 JORA and 329 EORA, compared with 562 AORA extracted from a big data national study on 10,364 RA patients. Clinical characteristics, laboratory investigations, medications received, and co-morbidities were recorded. The disease activity index (DAS28) and health assessment questionnaire (HAQ) were estimated.

The JORA cases represented 19% and EORA 29.9% of the included cohort. The mean age at onset for JORA, EORA, and AORA were 15.1 ± 2.1, 64 ± 4.2, and 36.4 ± 10 years (p < 0.0001), and the female-male ratio was 6.2:1, 2.7:1, and 7.3:1 (p < 0.0001), respectively. In EORA, body mass index (28.8 ± 5.8) and frequencies of smokers (11.6%), diabetes (12.2%), hypertension (19.8%), and osteoporosis (5.2%) were significantly higher than in JORA (26.02 ± 5; 5.3%, 2.9%, 3.8%, and 1%) and AORA (27.6 ± 5.6; 3%, 8.4%, 14.9%, and 2.3%, p = 0.016) (p < 0.0001, p = 0.001, p < 0.0001, and p = 0.009, respectively). In JORA, oral ulcers were significantly more frequent (p = 0.04); in EORA, cardiovascular manifestations (p < 0.0001) and hypothyroidism (p = 0.039) were more frequent; and DAS28 (p = 0.01) and HAQ (p = 0.038) were higher. Fibromyalgia and methotrexate administration were significantly more frequent in AORA (p < 0.0001 and p = 0.04, respectively). Rheumatoid factor, anti-cyclic citrullinated peptide, and double seropositivity were significantly more frequent in EORA (p < 0.0001, p = 0.008, and p = 0.002, respectively).

Comorbidities, cardiovascular manifestations, hypothyroidism, higher disease activity, and functional disability are more common in EORA patients. Key Points • Juvenile-onset and elderly-onset RA patients have notable differences compared to the adult-onset cases. • Co-morbidities and certain manifestations, including cardiovascular disease and hypothyroidism, as well as higher disease activity and functional disability, are more common in elderly-onset patients. • Fibromyalgia remains more frequent in adult-onset cases.

We have previously shown that HLA-B27 was negatively associated with remission status eight years after the onset of juvenile idiopathic arthritis (JIA). We now aimed to study the associations of HLA-B27 with clinical features and disease outcomes 18 years after the onset of JIA.

We studied 434 patients from the population-based Nordic JIA cohort. Demographic and clinical data, including remission status, were collected consecutively at baseline, eight years after disease onset, and 18 years after disease onset and presented in relation to HLA-B27 status.

The HLA-B27 status was available for 416 of the 434 participants (96%) and was positive for 93 participants (22.4%), more often in men (P = 0.01). The sacroiliac, hips, and subtalar joints were more frequently involved in individuals who were HLA-B27 positive than in individuals who were HLA-B27 negative. In almost half of the individuals with HLA-B27 positivity and uveitis, the uveitis was asymptomatic. Uveitis, inflammatory back pain, sacroiliitis, arthritis in hip, tarsal, and subtalar joints, and enthesitis during the disease course were all associated with a lower rate of remission off medication. HLA-B27 positivity was significantly associated with a higher risk of not being in remission off medication after 18 years (odds ratio [OR] 2.6), especially in men (OR 5.6).

Clinical features related to spondylarthropathies were more common in patients who were HLA-B27 positive and associated with worse outcomes and nonremission 18 years after disease onset, particularly in men. Our results underline the adverse impact of having HLA-B27 positivity on long-term outcomes in individuals with JIA.

The objective of this study is to develop evidence-based recommendations for the diagnosis and management of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in the African context. The recommendations for ERA and JPsA were combined into a single document. The steering committee and task force identified 15 key questions and formulated 35 research questions. A comprehensive literature review, utilizing Medline and a manual search for African local data, was conducted to gather evidence. Following this synthesis, the task force developed draft recommendations and engaged in a Delphi process with an expert panel, including 17 African and three international experts, to reach a consensus and ensure alignment with global standards. The final recommendations were assigned a level of evidence and subsequently approved by the task force members, the expert panel, and the PAFLAR Board. Fifteen recommendations on the diagnosis and management of ERA and JPsA were developed, covering the role of the pediatric rheumatologist in multiple aspects of disease management, including diagnosis, monitoring of disease and extra-articular manifestations, determining treatment strategies, and guiding interventions. The level of evidence supporting these recommendations was variable, leading to the identification of a research agenda to address African particularities and answer pending questions. The final recommendations achieved a high level of agreement, with consensus ranging from 90 to 100%. These recommendations represent an important achievement for pediatric rheumatology in Africa, being the first of their kind, tailored specifically to the region. Developed through a rigorous methodology and collaboration between international and African experts, they aim to standardize care and address the unique challenges faced in African setting.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and adolescents. Currently, JIA is classified into seven categories according to the International League of Associations for Rheumatology (ILAR) criteria. Diagnosis is primarily clinical and involves excluding age-specific differential diagnoses, which can be particularly challenging in very young children. Early and effective treatment is crucial to minimize disease burden, chronic morbidity and reduced quality of life. Treatment strategies depend on the JIA category and comorbidities. The treatment should follow consensus treatment plans/strategies published by the German initiative Protocols for Classification, Monitoring and Therapy in Pediatric Rheumatology (ProKind) considering the treat-to-target strategy. Since a significant number of patients continue to have symptoms into adulthood, a well-structured transition from pediatric to adult rheumatology care is essential.

This retrospective observational study aimed to evaluate the effectiveness and hepatoprotective effects of combination therapy with tocilizumab (TCZ) and total glycosides of peony (TGP) in treating systemic juvenile idiopathic arthritis (sJIA). Among the 119 sJIA patients enrolled, 49 received TCZ combined with TGP (study group) and 70 received TCZ not combined with TGP (control group). We compared clinical characteristics, 5 liver function indices (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]/alkaline phosphatase/γ-glutamyltransferase/total bilirubin), transaminase (ALT/AST) Kaplan-Meier curves, and inflammatory indices between the groups. The study group showed significantly lower rates of abnormal ALT, AST, alkaline phosphatase, and γ-glutamyltransferase levels (P < .05). Among patients with abnormal liver function indices, transaminase abnormalities were the most common (87.50%), particularly after the first TCZ administration (44.64%). Analysis of Kaplan-Meier curves for transaminases for different treatment durations indicated significantly lower abnormal rates (ALT/AST > 1 and 3 × upper limit of normal) in the study group (P < .05). The Cox regression model and forest plot identified the group with the highest risk ratio (study group vs control group, hazard ratio = 3.985, 95% confidence interval: 1.997-7.952) as an independent risk factor for transaminase abnormalities. A comparison of therapeutic outcomes revealed a more obvious decrease in the number of patients with abnormal inflammation indices in the study group before and after treatment. Moreover, the erythrocyte sedimentation rate value in the study group at the last follow-up significantly lower than that in the control group (P < .05). The combination of TCZ and TGP effectively reduced inflammation and lowered the incidence of liver injury, suggesting it may be the preferred combination therapy for sJIA.

Research and management of juvenile idiopathic arthritis (JIA) are challenging due to its heterogeneous nature, chronicity, and unpredictable, multidimensional long-term outcomes.

Long-term studies have consistently shown that a majority of children with JIA reach adulthood with ongoing disease activity, on medication, or with recurrent flares. The heterogeneity is evident both between and within the present JIA categories based on The International League of Associations for Rheumatology (ILAR) JIA classification system. Several baseline predicting factors are known, but prediction modelling is only in the initial phase, and more models need to be tested in independent cohorts and possibly also supplemented with new biomarkers. Many have criticized the ILAR classification system, but new or updated classification systems have not yet been validated and proved their superiority. The lack of prediction possibilities for long-term outcomes and the limited alignment between JIA classification categories and adult rheumatic conditions are challenges for research, may limit the accessibility to treatment, and hamper a smooth transition to adult care.

We need more prospective, long-term studies based on unselected JIA cohorts with disease onset in the biologic era that can aid decision-making for individualized early treatment, suggest intervention studies, and ensure our patients the best possible transition to adulthood and the best likelihood of optimal health and quality of life.

A limp is an abnormal, uneven or laboured gait typically resulting from pain, weakness, or structural deformity involving the hip, lower limb, spine or abdominopelvic abnormalities. Limps in children are common and have diverse causes that can be benign to life-threatening including trauma, congenital malformations, and neoplastic diseases. Diagnosis involves identifying gait abnormality thoroughly examining history and physical exam, assessing tenderness and range of motion, and completing targeted lab and radiographic studies. We present an imaging review of various usual and unusual causes of limp in different age groups such as in toddlers (1-3 years), children (4-10 years), and adolescents (11-16 years) with a comprehensive literature review.

Interleukin-1 receptor-associated kinase1 (IRAK1) plays a considerable role in the inflammatory signaling pathway. The current study aimed to identify any association between (rs1059703) single nucleotide polymorphism (SNP) and vulnerability to rheumatological diseases in the pediatric and adult Egyptian population.

The current study included four patient groups: adult Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), juvenile systemic lupus erythematosus (JSLE), and juvenile idiopathic arthritis (JIA). Two healthy matched age and sex groups were included as controls. Genotypes of IRAK1 (rs1059703) SNP in patients and controls were determined using the TaqMan allelic discrimination method.

The frequency of AA homozygous genotype and allele A of IRAK1 (rs1059703) SNP is higher in adult SLE patients compared to adult healthy controls (p-value < 0.005). No similar association was detected regarding RA, JSLE, or JIA. However, JSLE patients carrying the A allele have a higher SLE International Collaborating Clinics (SLICC) damage index (SDI) SDI score and a higher stage of renal biopsy than those carrying the G allele (p-value < 0.005).

Carriers of the A allele and its homozygous genotype of rs1059703 SNP are more prone to develop SLE in adult life and to have a more severe form of the disease in children in Egypt. No significant association was detected between this SNP and RA or JIA.

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder in children, posing significant physical and emotional challenges due to its chronic nature and the need for prolonged immunosuppressive therapies. Uveitis is the most common extra-articular manifestation of JIA, and it can be a sight-threatening condition. Despite advances in biologic treatments, JIA continues to present substantial therapeutic challenges, necessitating multiple treatment attempts and close monitoring for secondary failures. JIA-associated uveitis remains one of the most challenging and aggressive types of uveitis, particularly in children, due to its early onset, chronicity, and limited therapeutic responses despite new treatments. Early recognition and prompt treatment of both arthritis and uveitis are essential for achieving sustained remission and preventing complications. Effective management of JIA-uveitis requires a collaborative approach between pediatric rheumatologists and ophthalmologists to ensure timely assessments, regular screenings, and necessary therapy adjustments. This integrated care approach is crucial for achieving optimal outcomes. Therefore, this review aims to extensively analyze the pathogenesis, diagnosis, and therapy of JIA and its associated uveitis.

The purposes of this study were to assess the clinical characteristics of patients with juvenile idiopathic arthritis (JIA) who fulfill the ClASsification criteria for Psoriatic ARthritis (CASPAR) 18 years after disease onset in a population-based setting and to identify features likely to predict psoriatic arthritis (PsA).

Patients with JIA from defined geographic regions of Denmark, Finland, Norway, and Sweden with disease onset from 1997 to 2000 were enrolled prospectively and followed up for 18 years. Clinical, laboratory, and heredity data for psoriasis were collected. Patients were classified according to the International League of Associations for Rheumatology (ILAR) criteria at baseline, and we applied ILAR and CASPAR criteria at 18 years. Logistic regression was performed to study the effects of JIA-related characteristics and heredity for psoriasis on being classified for PsA.

Among the 510 patients enrolled, 434 participated in the 18-year follow-up, 28 (6.5%) met the ILAR criteria, and 41 (9.4%) fulfilled the CASPAR criteria. Patients with wrist or subtalar joint involvement at onset had higher odds of being classified with PsA at 18 years (odds ratio [OR] 3.3, P = 0.02 and OR 12.9, P = 0.01, respectively). Presence of psoriasis, nail abnormalities, or dactylitis showed significant association with development of PsA (OR 20.2, P < 0.001; OR 11.6, P = 0.002; and OR 43.4, P < 0.001, respectively).

CASPAR criteria identify more patients with PsA compared with ILAR criteria and may better capture the heterogeneous nature of the disease. Presence of psoriasis and dactylitis at disease onset were the strongest predictors for the development of PsA. Further studies on the utility of CASPAR criteria in patients with JIA are needed.

To find a distinct non-coding RNA characteristic for idiopathic uveitis in the pediatric population. To explore the autoimmune-related miRNA expression profile in pediatric patients with idiopathic uveitis (IU) and juvenile idiopathic arthritis-associated uveitis (JIA-AU) and find a common molecular background for idiopathic uveitis and other autoimmune diseases. The expression levels of miRNAs were analyzed by quantitative real-time PCR using serum samples from patients with idiopathic uveitis (n = 8), juvenile idiopathic arthritis-associated uveitis (n = 7), and healthy controls. We selected the most promising miRNAs from the original research papers: miR-16-5p, miR-26a-5p, miR-145-5p, and miR-451a as markers for juvenile idiopathic arthritis; miR-23a-3p, miR-29a-3p, miR-140-5p, miR-193a-5p, and miR-491-5p for uveitis in the adult population; and miR-125a-5p, miR-146a-5p, miR-155-5p, miR-223-5p, and miR-223-3p characteristic for both diseases and confirm their expression changes in serum from children with idiopathic uveitis. We comprehensively reviewed the literature enrolling the papers that met the inclusion criteria (miRNA and non-infectious uveitis/juvenile idiopathic arthritis) and performed target prediction analysis of appoint miRNAs. It additionally confirmed that altered miRNAs target the immunologically involved genes. Immunological-involved miRNAs such as miR-146a-5p and miR-155-5p show diverse expression levels in different patients as they interact with multiple targets. miR-204-5p is downregulated in both patient groups compared to healthy controls. miR-204-5p and miR-155-5p are candidates for molecular markers of autoimmune uveitis. We did not identify the miRNAs specific only to idiopathic uveitis, but for the first time in the pediatric population, we confirmed that this disease entity shares a molecular basis with other autoimmune diseases. Further studies are required to elucidate the molecular interactions among miRNAs, cytokines, and transcription factors within the intricate immune response, particularly in the eye.

Growing research has demonstrated that alterations in Th2 and Th17 cell composition were linked to systemic juvenile rheumatoid arthritis (sJRA). Nevertheless, whether these associations indicate a causal link remains unclear, and the potential effects of Th2/Th17-related molecules have not been clarified.

Mendelian randomization (MR) alongside transcriptome examination was implemented to ascertain the links between the Th2/Th17 cells and sJRA. Subsequently, we established an innovative machine learning (ML) framework encompassing 12 ML approaches and their 111 permutations to generate a unified Th2/Th17 classifier, which underwent verification across three separate cohorts. The hub Th2/Th17-related genes' level in the sJRA patients was substantiated via qRT-PCR. Lastly, the SHapley Additive exPlanations (SHAP) in conjunction with the XGBoost algorithm to pinpoint ideal Th2/Th17-linked genes.

Based on MR analyses of two sJRA GWAS, 2 immunophenotypes (lymphocyte and IgD+ B cell) were causally linked to sJRA. Based on IOBR algorithms, we revealed that lymphocyte Th2/Th17 proportion was markedly changed in sJRA from seven cohorts. WGCNA and differential analysis in two merged GEO cohorts identified 64 Th2/Th17-related genes. Based on the average AUC (0.844) and model stability in four cohorts, we converted 12 ML techniques into 111 combinations, from which we chose the optimal algorithm to generate an ML-derived diagnostic signature (Th2/Th17 classifier). qRT-PCR verified results. Moreover, immune cell infiltration and functional enrichment analysis suggested hub Th2/Th17-related gene potentially mediated sJRA onset. XGBoost algorithm and SHAP detected HRH2 as crucial genetic markers, which may be an important target for sJRA.

A diagnostic model (Th2/Th17 classifier) via 111 ML algorithm combinations in six independent cohorts was generated and validated, which stands as an effective instrument for sJRA detection. The identification of essential immune components and molecular cascades, along with HRH2, could emerge as vital therapeutic targets for sJRA intervention, providing an enhanced understanding of its fundamental processes.

(1) characterizing a group of spondyloarthritis (SpA) patients with systemic auto-inflammatory symptoms (S-SpA); (2) comparing SpA features with and without auto-inflammatory symptoms; (3) comparing the auto-inflammatory features of S-SpA and Still's disease (SD).

Retrospective observational study. Clinical data of adult and pediatric patients with S-SpA, SD or SpA were collected retrospectively and analyzed.

Forty-one subjects with S-SpA, 39 with SD and 42 with SpA were enrolled. The median latency between systemic and articular manifestations in S-SpA was 4.4 (IQR: 7.2) years. S-SpA and SpA had similar frequency of peripheral arthritis and enthesitis (N.S.), while tenosynovitis was more frequent (P=0.01) and uveitis less frequent (P<0.01) in S-SpA. MRI showed signs of sacroiliac inflammation and damage in both S-SpA and SpA equally (N.S.). S-SpA patients had less corner inflammatory lesions (P<0.05) and inflammation at the facet joints (P<0.01), more interspinous enthesitis (P=0.01) and inter-apophyseal capsulitis (P<0.01). Compared to SD, S-SpA patients had lower-grade fever (P<0.01), less rash (P<0.01) and weight loss (P<0.05), but more pharyngitis (P<0.01), gastrointestinal symptoms (P<0.01) and chest pain (P<0.05). ESR, CRP, WBC, ANC, LDH tested higher in SD (P<0.01). Resolution of systemic symptoms was less frequent in S-SpA than SD on corticosteroid (P<0.01) and methotrexate (P<0.05) treatment. When considering all SD patients, a complete response to corticosteroids in the systemic phase significantly reduced the likelihood of developing SpA (OR=0.06, coefficient -2.87 [CI: -5.0 to -0.8]).

SpA should be actively investigated in patients with auto-inflammatory manifestations, including undifferentiated auto-inflammatory disease and SD.

The goal was to develop and validate classification criteria for axial juvenile spondyloarthritis (SpA; AxJSpA).

This international initiative consisted of four phases: (1) item generation, (2) item reduction, (3) criteria development, and (4) validation of the AxJSpA criteria by an independent team of experts in an internationally representative validation cohort.

These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians, which collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included the following: imaging of active inflammation, imaging of structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% confidence interval [CI] 91.4%-99.7%), sensitivity of 64.3% (95% CI 54.9%-73.1%), and area under the receiver operating characteristic curve of 0.81 (95% CI 0.76%-0.86%).

The new AxJSpA classification criteria require an entry criterion and a physician diagnosis of juvenile SpA and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies.

To analyse the similarity in clinical manifestations and laboratory findings between systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD).

Three systematic reviews (SR) were performed. One included cohort studies comparing sJIA versus AOSD that described clinical and biological manifestations with at least 20 patients in each group (SR1). The second identified studies of biomarkers in both diseases and their diagnostic performance (SR2). The last focused on diagnostic biomarkers for macrophage activation syndrome (MAS, SR3). Medline (PubMed), Embase and Cochrane Library were systematically searched. The risk of bias was assessed with an adapted form of the Hoy scale for prevalence studies in SR1 and the Quality Assessment of Diagnostic Accuracy Studies-2 in SR2 and SR3. We performed meta-analyses of proportions for the qualitative descriptors.

Eight studies were included in SR1 (n=1010 participants), 33 in SR2 and 10 in SR3. The pooled prevalence of clinical manifestations did not differ between sJIA and AOSD, except for myalgia, sore throat and weight loss, which were more frequent in AOSD than sJIA because they are likely ascertained incompletely in sJIA, especially in young children. Except for AA amyloidosis, more frequent in sJIA than AOSD, the prevalence of complications did not differ, nor did the prevalence of biological findings. Ferritin, S100 proteins and interleukin-18 (IL-18) were the most frequently used diagnostic biomarkers, with similar diagnostic performance. For MAS diagnosis, novel biomarkers such as IL-18, C-X-C motif ligand 9, adenosine deaminase 2 activity and activated T cells seemed promising.

Our results argue for a continuum between sJIA and AOSD.

CRD42022374240 and CRD42024534021.

Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are considered the same disease, but a common approach for diagnosis and management is still missing.

In May 2022, EULAR and PReS endorsed a proposal for a joint task force (TF) to develop recommendations for the diagnosis and management of sJIA and AOSD. The TF agreed during a first meeting to address four topics: similarity between sJIA and AOSD, diagnostic biomarkers, therapeutic targets and strategies and complications including macrophage activation syndrome (MAS). Systematic literature reviews were conducted accordingly.

The TF based their recommendations on four overarching principles, highlighting notably that sJIA and AOSD are one disease, to be designated by one name, Still's disease.Fourteen specific recommendations were issued. Two therapeutic targets were defined: clinically inactive disease (CID) and remission, that is, CID maintained for at least 6 months. The optimal therapeutic strategy relies on early use of interleukin (IL-1 or IL-6 inhibitors associated to short duration glucocorticoid (GC). MAS treatment should rely on high-dose GCs, IL-1 inhibitors, ciclosporin and interferon-γ inhibitors. A specific concern rose recently with cases of severe lung disease in children with Still's disease, for which T cell directed immunosuppressant are suggested. The recommendations emphasised the key role of expert centres for difficult-to-treat patients. All overarching principles and recommendations were agreed by over 80% of the TF experts with a high level of agreement.

These recommendations are the first consensus for the diagnosis and management of children and adults with Still's disease.

Apply the PRINTO classification proposal for diagnosing Juvenile Idiopathic Arthritis (JIA) to Mexican patients, analyzing demographic, clinical, and laboratory characteristics.

Cross-sectional study analyzing patients diagnosed with JIA using International League of Associations for Rheumatology (ILAR 2001) criteria over two years at a national rheumatic disease center. Reclassification was done using the Pediatric Rheumatology International Trials Organization (PRINTO) proposal. Comparisons were made between antinuclear antibodies (ANAs) positive vs. negative and rheumatoid factor (RF) positive vs. negative patients.

Seventy-six patients were analyzed, mostly female. Median age was lower in systemic JIA (sJIA) and early onset JIA with positive ANAs (eoANA JIA). ANAs was present in 78.6% of patients. Reclassification according to PRINTO disorders showed RF positive polyarticular JIA, sJIA, and enthesitis-related JIA (ER JIA) reclassified to RF JIA, sJIA, and enthesitis/spondylitis-related JIA (ESR JIA) by 100%, 94.7%, and 80%, respectively. The ILAR category with the most variation was RF negative polyarticular JIA. Early disease onset was associated with a lower probability of positive RF after adjusting for sex, age, and ANAs. No association was found between ANAs positive vs. negative in adjusted multivariate analysis.

We found compatibility of sJIA, RF positive polyarticular JIA, and RE JIA categories with sJIA, RF JIA, and ESR JIA disorders, respectively. Differences were noted in variables such as sex and the number of affected joints. There was high ANAs positivity; however, few patients were classified into eoANA JIA disorder, with only one presenting uveitis. Most patients were classified as other JIA.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness of conservative, non-pharmacological interventions for chronic pain management in children and adolescents with juvenile idiopathic arthritis (JIA). A comprehensive search strategy was implemented across PubMed, PEDro, and Web of Science databases, utilizing predefined terms and strict inclusion and exclusion criteria. The initial search yielded 1,308 studies, which were subsequently narrowed to 65 relevant articles. Following a rigorous evaluation, 14 studies met the inclusion criteria for final review, with an average PEDro scale score of 6.1/10, indicating fair to good methodological quality. The included RCTs focused on various interventions, including physical exercise (five studies), hydrotherapy (three studies), orthoses (two studies), online cognitive behavior therapy for pain management (two studies), low-level laser therapy (one study), and video games (one study). A random-effects model meta-analysis was performed for interventions and outcome measures that were comparable across at least three RCTs. Physical exercise interventions met this criterion and were thus subjected to meta-analytic evaluation. The pooled analysis demonstrated a statistically significant beneficial effect of exercise interventions on chronic pain (mean difference (MD) = -1.37, 95% CI = -2.19 to -0.55, p < 0.01). Subgroup analyses further supported the efficacy of exercise compared to both other active interventions (MD = -1.37, 95% CI = -2.25 to -0.5, p < 0.01) and control conditions (MD = -1.69, 95% CI = -3.09 to -0.29, p = 0.02). These findings suggest that conservative, non-pharmacological interventions, particularly physical exercise, show promise as a component of a multidisciplinary pain management strategy for patients with JIA. While further high-quality research is needed to bolster the evidence base, our findings highlight the potential efficacy of integrating physical exercise interventions into comprehensive pain management strategies for this pediatric population.

Interstitial lung disease (ILD) is a serious complication in systemic juvenile idiopathic arthritis (SJIA). This study aimed to identify the clinical characteristics and prognosis of SJIA-ILD.

A two-center retrospective cohort study was conducted on patients newly diagnosed with SJIA in China from October 2010 to December 2021. Clinical characteristics, laboratory parameters, outcomes, and relapse rates were compared between ILD and non-ILD groups.

A total of 176 children with SJIA were included, including 35 in ILD group and 141 in non-ILD group. The median age at onset of SJIA was 5.8 years (range 4.4-9.5) in patients with SJIA-ILD. It exhibited higher incidences of cervical spine (28.6%) and hip involvement (40.0%) in ILD group (P = 0.031 and P = 0.029, respectively). The incidence of macrophage activation syndrome (MAS) in ILD group reached up to 40%, significantly elevated than that in non-ILD group (P = 0.047). Children with ILD demonstrated a stronger inflammatory response and were more prone to developing lymphopenia (P = 0.009), requiring more combination therapy (P = 0.006) to control disease activity. 54.3% of patients received biologic therapies, with only three patient receiving biologics (one with IL-6 blockade, two with TNF inhibitor) prior to ILD onset and none receiving IL-1 blockade. The median follow-up duration was 6.0 years (range 3.9-9.5). The proportions of patients with SJIA-ILD achieving clinical inactive disease without glucocorticoids within 6 to 12 months of the treatment were significantly lower than control group (45.7% vs. 70.2%, P = 0.006). In ILD group, only 54.3% of patients achieved complete remission, and 17.1% were in a non-remission state, among whom two deaths from respiratory failure. There was no significant difference in disease relapse rates between the two groups (P > 0.05).

Patients with SJIA-ILD exhibited heightened inflammation, increased hip joint and cervical spine involvement, and were more susceptible to developing lymphopenia and MAS, suggesting a relatively poor prognosis. They required a prolonged time to control inflammation and more aggressive treatment strategies to achieve inactive status. The unsatisfactory rate of complete remission highlighted an urgent need for focused clinical strategies.

We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.

Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0.

Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48.

In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48.

NCT01500551.