Current thinking in the management of temporomandibular disorders in children: A narrative review.

The aim of this narrative review is to discuss current opinions on paediatric temporomandibular disorders (TMDs) due to their increasing incidence in routine secondary care maxillofacial clinics. A MEDLINE and EMBASE search was performed of the literature published in the past three years concerning paediatric TMD. Of 261 papers identified, 89 were selected for relevance, of which 52 full texts were eligible and 41 included. The narrative of this paper follows three domains: myogenous and arthogenous pain, juvenile idiopathic arthritis (JIA), and reconstruction. The principles of treating mild TMD in children are similar to those in adults, with even more emphasis on the management of psychosocial issues and self-care. The use of medication, however, needs to be more cautious. Symptomatic disc displacement should be treated to reduce inflammation, so early arthrocentesis or arthroscopy is relevant. Controversy exists on disc repositioning to reduce or even reverse condylar degeneration in the growing condyle. If undertaken it should ideally be performed arthroscopically by surgeons with significant experience. Arthritic disease is usually associated with JIA so a multidisciplinary approach is the focus of treatment. The role of arthroscopy in the management of symptoms is increasing but it does not prevent disease progression. Surgical correction may be required for secondary deformity. Reconstruction remains a challenge with no ideal autogenous method. Alloplastic joints are gaining popularity, but the long-term outcomes are unknown. Surgery can be undertaken with minimal morbidity, and the use of joint replacements, even as space maintainers, may therefore be more beneficial than repeated failed autogenous treatments.

Investigation of Physical Fitness in Children and Adolescents with Juvenile Idiopathic Arthritis: A Case-Control Study.

Swelling, effusion, tenderness, and pain seen in the joints of juvenile idiopathic arthritis (JIA). This disease may cause limitation in joint movements, muscle weakness, atrophy, balance, and gait disorders. Physical fitness is accepted as an important determinant of health in both childhood and adolescence. The aim was to evaluate the physical fitness of children/adolescents with JIA and compare it with healthy peers. Seventy children/adolescents were included (35 JIA and 35 healthy). The Childhood Health Assessment Questionnaire (CHAQ) and the Brockport physical fitness test battery were used for evaluation. The Brockport physical fitness test battery consists of dominant handgrip strength, curl-up, push-up, trunk lift, shoulder stretch, sit and reach tests, skinfold thickness (calf/triceps/subscapular) measurements, and PACER 20 m test. A significant difference was found in all sub-parameters of CHAQ (P < .05) and dominant hand grip strength (P = .037), curl-up test (P < .001), trunk lift test (P = .018), shoulder stretch (P < .001) and PACER 20 m test (P < .001) tests in favor of the healthy group. Children/adolescents with JIA demonstrated lower performance compared to their healthy peers in muscular and cardiovascular capacity tests (curl-up test, PACER 20 m test, trunk lift test, dominant hand grip strength test, and shoulder stretch test). Their functional abilities are more impaired, and they experience higher levels of pain and lower levels of general well-being compared to healthy peers.

Physical (in)activity and screen-based media use of adolescents with juvenile idiopathic arthritis over time - data from a German inception cohort.

BACKGROUND: Regular physical activity (PA) has been proven to help prevent non-communicable diseases and is beneficial for disease management in chronically ill populations. Physical inactivity and recreational screen-based media (SBM) use are related to poor health outcomes and common among youth. This study aimed to (1) investigate PA levels and recreational SBM use of adolescents with JIA over time and (2) compare these behaviours with those of their peers. METHODS: Data from JIA patients and their peers enrolled in the inception cohort study ICON at 11 German centers were analyzed. Individuals aged 13 and over were followed prospectively with questionnaires concerning PA level, recreational SBM use, and health-related quality of life (HRQoL) at a two-year interval. Group by time interactions were analyzed using linear mixed models. RESULTS: Data of 214 patients (mean age at first documentation 14.4 ± 0.9 years, female 63%) and 141 peers could be considered. At first documentation, patients were less physically active compared to their peers (p < 0.001). In contrast to their peers, patients' PA levels increased over time (OR 3.69; 95% CI: 1.01-13.50, p = 0.048). Mean screen time did not differ significantly between patients and peers (first documentation: 3.5 h vs. 3.0 h, p = 0.556; follow-up: 3.6 h vs. 3.3 h, p = 0. 969). During the observation period, male patients reported higher PA levels than female patients, but also higher screen time levels. While low socioeconomic status (SES) (OR 14.40; 95%-CI: 2.84-73.15) and higher cJADAS-10 score (OR 1.31; 95%-CI: 1.03-1.66) increased the likelihood for high SBM use (≥ 4.5 h/d), higher PedsQL psychosocial health score (OR 0.93; 95%-CI: 0.88-0.99) was associated with a decreased likelihood. CONCLUSIONS: Adolescents with JIA become more physically active over the disease course and achieve comparable levels of PA and recreational screen time to their peers. However, the vast majority appear to be insufficiently physically active. Future interventions to promote healthy lifestyles should include gender and SES as important determinants to reach most vulnerable groups.

Differential type I and type III interferon expression profiles in rheumatoid and juvenile idiopathic arthritis.

Background: The role of type I and type III interferons (IFNs) in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) is still poorly understood. The objective of this study was to examine the hypothesis that IFN expression profiles in the peripheral blood differ between subsets of arthritic subjects. Multiple type I and type III IFNs were examined in patients with RA and JIA, as well as among subtypes of JIA. Methods: Treatment-naïve RA and JIA patients were enrolled. Droplet digital PCR was used to measure the expression of type I, II, and III interferons in blood and synovial fluid leukocytes. Dendritic cell subsets were isolated from synovial fluid to examine IFN expression in each subset. Additionally, synovial mononuclear cells and JIA-derived fibroblast-like synoviocytes were stimulated with TNF, IFNγ, and poly(I:C) to examine inducible IFN expression. Results: The predominant type I IFN gene expressed by blood leukocytes was IFNκ and was significantly lower in RA than JIA and controls. Oligoarticular and psoriatic JIA subgroups showed higher IFNκ expression compared to polyarticular JIA and RA. JIA synovial fluid leukocytes expressed abundant IFNγ and type III IFNs (IFNλ1, IFNλ3), with distinct dendritic cell subset contributions. JIA fibroblast-like synoviocytes produced IFNß, IFNλ1, and IFNλ2 mRNA upon poly(I:C) stimulation. Conclusion: This study revealed differences in IFN expression patterns in RA and JIA, with notable differences between JIA subtypes. The expression levels of IFNκ, IFNγ, IFNλ1 and IFNλ3 in JIA suggest specific roles in disease pathology, influenced by disease subtype and joint microenvironment. This study contributes to understanding IFN-mediated mechanisms in arthritis, potentially guiding targeted therapeutic strategies.

Evaluation of postoperative outcomes after cataract surgery in patients with Juvenile Idiopathic Arthritis-Associated Uveitis.

PURPOSE: To evaluate the postoperative outcomes of cataract surgery and intraocular lens (IOL) implantation on visual outcomes and complications in pediatric patients with Juvenile Idiopathic Arthritis-Associated Uveitis. METHODS: This study included 25 patients (30 eyes) with uveitis and cataracts who underwent cataract surgery. The study was conducted as a retrospective study. Patients were divided into two groups based on their preoperative treatment: those who received immunomodulatory therapy (IMT) along with systemic corticosteroids and those who received IMT in combination with a biologic therapy. Best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), macular volume (MV), and postoperative complications were assessed at various time points up to 12 months. All surgeries were performed by a single surgeon. RESULTS: Significant improvement in BCVA were observed postoperatively in both study groups, with approximately 80% of eyes showing improvement. Mean BCVA improved from 0.89 ± 0.63 to 0.37 ± 0.33 in group 1and from 0.82 ± 0.68 to 0.35 ± 0.31 in group 2 after 12 months. Postoperatively, there was a decrease in mean IOP, with no significant variance observed between the two groups. Complications were observed in 73% of cases, including posterior capsular opacification (PCO), secondary glaucoma, and macular edema (ME), but did not significantly differ between groups. CONCLUSION: Cataract surgery in children with uveitis associated with JIA presents significant challenges due to the risk of postoperative complications, even with adequate preoperative and postoperative care. The similar improvement in BCVA observed in both groups suggests that different systemic therapies were sufficient for satisfactory control of inflammation before and after surgery.

Incidence and outcomes for children with idiopathic inflammatory myopathy in Western Australia-a long-term population-based study.

AIM: To determine the incidence and health outcomes for juvenile idiopathic inflammatory myopathy (JIIM) in a long-term whole-population study. METHODS: We included patients under 18 years hospitalized in Western Australia (WA) from 1985 and 2015 with incident JIIM as defined by pertinent diagnostic codes for dermatomyositis (JDM) polymyositis (JPM), other JIIM and overlap myositis (JOM). We compared clinical outcomes and modified Charlson comorbidity scores with age and gender matched (2:1 ratio) patients with new onset juvenile idiopathic arthritis (JIA). Trends over time for annual incidence rate per million child-population (AIR) were analyzed by least square regression and survival by Kaplan-Meier curves. RESULTS: We included 40 patients with JIIM (63% female, median age 8.5 years) for an average AIR of 2.52 per million (CI 1.09-5.57). AIR was stable over time leading to a point prevalence of 52.61 (CI 40.57-67.06) in 2015. Most patients (80%) were classified as JDM with an AIR for JDM of 2.02 (CI 1.09-5.58) and AIR for the combined other JIIM at 0.51 (CI 0.24-1.15). There was female preponderance (62.5%) in both JIIM groups, but no evidence of seasonality. Over a median follow-up of 13 years, one- and ten-year survival was 94.1%. Compared to JIA patients, readmission (80.4 vs. 63.7, p = .02) and infection rates (15.2 vs. 9.6, p < .01) per 100 person-years were higher for JIIM, with similar frequency of interstitial lung disease, fractures, and thrombotic events. At last observation, nearly all patients in both JIIM cohorts (97.5 vs. 92.5%) had accrued some form of comorbidity. CONCLUSIONS: The overall incidence of JIIM leading to hospitalization in WA was stable over 30 years. JIIM prognosis remains suboptimal due to early mortality and accrual of long-term comorbidity.

Imaging in Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) poses clinical challenges because of its heterogeneous categories of chronic arthritis. Although conventional radiography aids with assessment of joint damage, MRI and ultrasound offer more sensitive evaluation of joint changes related to inflammation and damage in JIA. MRI and ultrasound have the potential to complement clinical assessment, monitor inflammation and damage, guide treatment decisions, and improve outcomes in JIA. Future research aims to enhance standardization and reliability and bolster the predictive value of imaging in clinical practice.

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis - results from the south-Swedish juvenile idiopathic arthritis cohort.

BACKGROUND: There is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden. METHODS: Autoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000-2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models. RESULTS: During the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13-7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76-15.65) and hypothyroidism (HR 3.74, 95% CI 1.14-12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64-23.55) for ANA positive individuals. CONCLUSIONS: Individuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

Juvenile idiopathic arthritis management: insights into the utilization of intra-articular corticosteroid injections.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a common chronic rheumatic disease in children, requiring careful management to reduce both short- and long-term morbidity. In this study, our objective was to assess the clinical features of patients diagnosed with JIA who received intra-articular corticosteroid injections (IACI). METHODS: In this retrospective study, we evaluated the clinical and laboratory characteristics of 225 JIA patients monitored from January 2012 to October 2023 at a tertiary care center. We focused on patients who underwent intra-articular corticosteroid injections (IACI) as part of their treatment. Triamcinolone hexacetonide (TH) was used due to its demonstrated safety and efficacy. RESULTS: Our analysis revealed that IACI, particularly utilizing TH, was a widely employed and effective adjunct therapy, contributing to rapid symptom relief and local disease control. Patients receiving IACI exhibited earlier symptom onset, younger age at diagnosis, longer follow-up durations, and higher cumulative treatment burden (p < 0.001, p < 0.001, p < 0.01, p < 0.001 respectively). Despite inconclusive acute-phase reactants, a higher frequency of ANA positivity and elevated initial lymphocyte counts were associated with increased IACI use (p < 0.001, p < 0.001 respectively). Importantly, on a joint basis, a high percentage of arthritis remission following IACI underscores its efficacy and favorable safety profile. CONCLUSIONS: Notably, the high percentage of arthritis remission achieved with intra-articular corticosteroid injections (IACI) on a joint-specific basis highlights its efficacy and favorable safety profile. A lymphocyte count exceeding 5000/mm3 at the time of diagnosis may serve as an early indicator for considering intra-articular steroid administration. These findings emphasize the need for nuanced and individualized treatment strategies in JIA management to optimize outcomes for affected children.

Algorithm for Growth Evaluation in Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) includes a range of inflammatory conditions that exhibit chronic arthritis with various clinical presentations. The disease's heterogeneity leads to different impacts on children's health, both short and long-term. Compromised growth, seen as growth retardation and delayed puberty, is a common complication in children with JIA, severely impacting their quality of life. This impairment is linked to disease duration and activity, with severe cases in systemic and polyarticular subtypes. Literature reports growth retardation incidence from 8% to 41%, but data on pubertal impairment is lacking. Growth in children is influenced by systemic and local mechanisms. Chronic inflammation, prolonged glucocorticosteroid (GCS) use, and nutritional issues contribute to growth stunting and pubertal delays. Chronic inflammation in JIA flattens growth curves, while steroid treatment impairs growth and causes weight gain. Disruption of the GH/IGF1 axis is known, but data on systemic hormonal resistance in JIA are insufficient. Optimizing JIA treatment, including biological therapies, is expected to improve growth velocity and reduce long-term impacts by better disease control and reduced GCS doses. Thyroid function also influences growth and puberty, but comprehensive studies on thyroid involvement in JIA are lacking. Given the early onset of chronic inflammatory consequences, preventive auxological screening measures are necessary for children with JIA. Early detection of developmental disorders can enhance therapeutic management. This article summarizes information from a cohort study on growth in children with JIA and proposes a diagnostic algorithm for clinical use.

Implementation study of the CARRA Uveitis Consensus Treatment Plans: feasibility for clinical practice and applicability for research.

BACKGROUND: Chronic anterior uveitis (CAU) carries a significant risk for eye complications and vision loss. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) introduced consensus treatment plans (CTPs) to standardize treatment for CAU and facilitate future comparative effectiveness studies. Two CTPs were developed to address: 1) initiation of methotrexate (MTX) in patients with CAU naïve to steroid-sparing therapy, and 2) initiation of a TNF inhibitor (TNFi) in patients with severe uveitis or uveitis refractory to MTX. We evaluated implementation of the uveitis CTPs using existing CARRA Registry infrastructure and assessed feasibility of the CTPs for comparative effectiveness research. METHODS: This prospective observational cohort study was conducted at nine pilot sites between February 2020 and August 2022. Patients with JIA-associated CAU (JIA-U) were treated according to either the MTX or TNFi CTP. Uveitis activity and medication use were recorded at 0, 3, and 6 months. We assessed patient enrollment rates, CTP arm selection, uveitis control, and quality of data collection. We also evaluated CTP arm selection in a retrospective cohort of similar JIA-U patients enrolled in the CARRA Registry during the same study period. RESULTS: Seventeen patients were included in the pilot cohort. Eight were treated with the MTX CTP (4 oral MTX, 4 subcutaneous MTX), and 9 with the TNFi CTP (9 received standard-dose adalimumab, none selected high-dose adalimumab or infliximab). Uveitis was controlled in 13 of 17 patients by 6 months. Query of the CARRA-wide Registry identified 42 patients with JIA-U who were treated according to the MTX or TNFi CTPs. Among these, 26 were treated with MTX (8 oral, 18 subcutaneous) and 16 with TNFi (12 standard dose adalimumab, 2 high dose adalimumab, and 2 infliximab). CONCLUSION: Both the MTX and TNFi uveitis CTPs can practically be implemented in clinical settings and are currently being utilized across Registry sites. However, in patients starting TNFi therapy, all pilot study participants and most patients across the CARRA Registry were treated with a standard dose of adalimumab. This consensus on the treatment approach underscores its broad acceptance but also limits the applicability of the uveitis TNFi CTP for comparative effectiveness research.

Exploring the role of gut microbiome in autoimmune diseases: A comprehensive review.

As the industrialized society advances, there has been a gradual increase in the prevalence of autoimmune disorders. A probe into the fundamental causes has disclosed several factors in modern society that have an influence on the gut microbiome. These dramatic shifts in the gut microbiome are likely to be one of the reasons for the disarray in the immune system, and the relationship between the immune system and the gut microbiome emerging as a perennial hot topic of research. This review enumerates the findings from sequencing studies of gut microbiota on seven autoimmune diseases (ADs): Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Ankylosing Spondylitis (AS), Systemic Sclerosis (SSc), Sjögren's Syndrome (SjS), Juvenile Idiopathic Arthritis (JIA), and Behçet's Disease (BD). It aims to identify commonalities in changes in the gut microbiome within the autoimmune disease cohort and characteristics specific to each disease. The dysregulation of the gut microbiome involves a disruption of the internal balance and the balance between the external environment and the host. This dysregulation impacts the host's immune system, potentially playing a role in the development of ADs. Damage to the gut epithelial barrier allows potential pathogens to translocate to the mucosal layer, contacting epithelial cells, disrupting tight junctions, and being recognized by antigen-presenting cells, which triggers an immune response. Primed T-cells assist B-cells in producing antibodies against pathogens; if antigen mimicry occurs, an immune response is generated in extraintestinal organs during immune cell circulation, clinically manifesting as ADs. However, current research is limited; advancements in sequencing technology, large-scale cohort studies, and fecal microbiota transplantation (FMT) research are expected to propel this field to new peaks.

Vitamin D as a Modifiable Risk Factor for Juvenile Idiopathic Arthritis: A Systematic Review and Meta-analysis of Observational Studies Comparing Baseline Vitamin D in Children with JIA to Individuals Without.

CONTEXT: The varying interactions contributing to the development of juvenile idiopathic arthritis (JIA) drive the struggle to understand its etiology. Among the environmental risk factors, vitamin D has been posited to have a component in disease progression, acting as an inflammatory mediator. OBJECTIVE: To investigate the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels, indicative of vitamin D, among patients diagnosed with JIA compared with control participants. The aim was to elucidate potential therapeutic implications of vitamin D in the management of JIA. DATA SOURCES: A systematic search of 6 electronic databases (MEDLINE, Embase, Scopus, CINAHL, Web of Science, and Cochrane Library) was performed until February 2023. Inclusion criteria required participants to be <16 years old (either clinically diagnosed with JIA or a matched control participant), with vitamin D levels measured through serum laboratory methods. Exclusion criteria omitted studies in which participants used vitamin D supplementation or medications affecting vitamin D levels without corresponding statistical analyses on their association with vitamin D levels. DATA EXTRACTION: Each article was reviewed by at least 2 independent reviewers to assess eligibility for analysis. DATA ANALYSIS: Data were qualitatively analyzed to compare means of serum 25(OH)D levels (ng/mL) between patients with JIA and control participants, followed by a meta-analysis to obtain effect size. RESULTS: Ten eligible studies were included qualitatively, and eight were included in the meta-analysis. Seven studies found a statistically significant difference in vitamin D levels between control participants and patients with JIA, with five of these reporting a lower mean vitamin D level in patients with JIA. A random-effects model using standardized mean difference found a statistically significant difference in vitamin D levels between control participants and patients with JIA (-0.49; 95% CI, -0.92 to -0.06). CONCLUSIONS: The findings from the analysis indicate vitamin D levels were lower in patients with JIA as compared with healthy control participants at baseline. It is recommended that research into vitamin D supplementation and JIA should be conducted.

Multicentric Osteolysis Nodulosis and Arthropathy (MONA): A Case Series and Review of the Literature.

Multicentric Osteolysis Nodulosis and Arthropathy (MONA) is a rare skeletal disorder driven by mutations in the MMP2 gene, leading to bone and joint degradation. This case series presents three unique MONA cases, highlighting clinical, radiological, and genetic aspects. These insights shed light on the complexities of MONA, aiding early diagnosis and multidisciplinary management. Case 1 is a 13-year-old male, born to consanguineous parents, presented with a 5-year history of progressive joint deformities, pain, and difficulty walking. Initially diagnosed as juvenile idiopathic arthritis (JIA), despite treatment, his symptoms persisted. Examination revealed multiple clinical findings, including joint contractures and nodules. Genetic analysis identified a pathogenic variant in the MMP2 gene, confirming MONA. Case 2 and Case 3 were two siblings, aged 12 and 17 years respectively, who presented progressive joint contractures in their hands and feet since early childhood. Clinical examinations revealed contractures and subcutaneous nodules. Genetic analysis confirmed MONA with a shared homozygous pathogenic MMP2 variant, emphasising the genetic basis of this rare disorder.

Symptomatic Pachydermodactyly: A Case Report.

Pachydermodactyly, an uncommon variant of digital fibromatosis, predominantly affects young men and results in fibrous swelling on the sides of the proximal interphalangeal joints. It is generally considered benign and asymptomatic, requiring only regular follow-up. Nevertheless, the absence of established diagnostic criteria has led to misdiagnoses, prompting the administration of unnecessary medications. In this report, we present a 14-year-old Japanese male with symptomatic pachydermodactyly, necessitating careful differentiation from juvenile idiopathic arthritis (JIA) due to the presence of morning stiffness. Despite exhibiting typical pachydermodactyly features, the patient's age and symptoms suggested rheumatoid factor-negative polyarticular JIA. However, the lack of inflammatory findings precluded a JIA diagnosis. Following confirmation of the absence of uveitis and progression of bone destruction, the morning stiffness spontaneously resolved without active treatment. However, the patient underwent surgery for aesthetic reasons to alleviate the persistent swelling. Our case highlights the nuances of symptomatic pachydermodactyly, with a literature review revealing similarities between symptomatic and asymptomatic cases. This challenges the suitability of asymptomatic status as a definitive diagnostic criterion. Our findings contribute to the ongoing efforts in establishing diagnostic criteria for pachydermodactyly, aiming to reduce misdiagnoses and unnecessary medications in patients.

Acute myeloid leukemia developed through myeloproliferative features during immunosuppressive therapy for juvenile idiopathic arthritis.

A 17-year-old male with thrombocytosis and exacerbation of arthralgia during intensified immunosuppressive therapy with tocilizumab, prednisolone, and methotrexate for juvenile idiopathic arthritis (JIA) was referred to our department. Bone marrow examination revealed myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U). Peripheral myeloblasts disappeared temporarily after discontinuation of tocilizumab but progressed to acute myeloid leukemia six months after the development of MDS/MPN-U. The patient sustained complete remission after unrelated bone marrow stem cell transplantation, followed by chemotherapy. The arthralgia also improved after chemotherapy. The possibility of developing malignancies during immunosuppressive therapy in patients with JIA should be considered. J. Med. Invest. 71 : 335-339, August, 2024.

Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis.

Selenoprotein P (SELENOP) controls selenium (Se) transport, and glutathione peroxidase 3 (GPx3) elicits antioxidant activity in blood. Inflammation associates with Se deficiency, but knowledge concerning selenoproteins in inflammatory rheumatic musculoskeletal diseases (iRMD) is limited. We compared three Se biomarkers in patients with rheumatoid (RA), psoriatic (PsA), and juvenile idiopathic arthritis (JIA) in comparison to osteoarthritis (OA) and healthy subjects, to improve the data base on selenoprotein expression in iRMD. The cross-sectional study enrolled n=272 patients with RA (n=131), PsA (n=67), JIA (n=22) and OA (n=52). Serum Se was quantified by total reflection X-ray fluorescence, SELENOP by ELISA and GPx3 by an enzymatic test. Data from the EPIC trial served as reference. Impairment of daily life was assessed by the Functional Ability Questionnaire (FfbH). Serum SELENOP and Se concentrations correlated linearly in all groups and were below the average measured in EPIC. Se concentration was not different between the patient groups. Compared to controls, SELENOP levels were low in iRMD patients. GPx3 activity was particularly low in JIA and PsA. Seropositive but not seronegative RA patients displayed a disrupted interaction between GPx3 and Se or SELENOP. SELENOP associated with the functional status measured by the FfbH, most pronounced in OA (R=0.76, P < .01). The data indicate selenoprotein deficiency in the majority of patients with iRMD, and a positive relation of SELENOP with functional status in OA. Since increased Se supply improves selenoprotein biosynthesis, a personalized correction of diagnosed deficiency merits consideration to improve Se transport and ameliorate disease burden.

Duration of effect in treatment of methotrexate intolerance in juvenile idiopathic arthritis using Eye Movement Desensitization and Reprocessing (EMDR) can be improved by Bi-lateral Alternating Stimulation Tactile (BLAST) wristbands.

BACKGROUND: Methotrexate (MTX) intolerance in juvenile idiopathic arthritis (JIA) frequently leads to discontinuation due to anticipatory and associative gastrointestinal symptoms. Eye Movement Desensitization and Reprocessing (EMDR) has successfully been used in MTX intolerance, with lasting effects but frequently diminishing efficacy over time. BLAST (bi-lateral alternating stimulation tactile) wristbands utilize a similar process to EMDR. The aim of this study was to determine if utilization of BLAST wristbands could improve and prolong the effect of EMDR on patients with MTX intolerance. METHODS: Consecutive patients admitted to the German Center for Pediatric and Adolescent Rheumatology with JIA and signs of MTX intolerance from October 2016 until March 2024 were included in this study. Treatment was performed using an adapted 8 phase EMDR protocol implementing BAST wristbands. Initial patients were treated with EMDR, subsequent patients additionally with BLAST wristbands. Health-related quality of live was determined using the PedsQL. Measurements of MISS (Methotrexate Intolerance Severity Score) and PedsQL were taken at 4 time points: directly before and after (MISS only) treatment, as well as 4 and 12 months after treatment. Changes in MISS and PedsQL were compared using descriptive statistics and repeated measures ANOVA. RESULTS: 87 patients with MTX intolerance were included, 53 in group 1 without BLAST wristbands and 34 in group 2 which were concurrently treated with BLAST wristbands. All patients reported marked improvement of MTX intolerance symptoms (mean MISS score group 1: 15.0 ± 5.5 before treatment, 1.3 ± 1.5 after treatment, group 2: 16.8 ± 5.6 and 2.5 ± 2.5, respectively). After 4 and 12 months, MISS in group 1 was 8.1 ± 7.1 and 8.7 ± 8.4, and in group 2: 7.1 ± 6.3 and 6.5 ± 5.7. A repeated measures ANOVA showed a significant difference between the MISS results over time (F(3,114) = 64.6, p < 0.001), and also demonstrated a significant difference of the PedsQL results between the two groups over time (F(2,64) = 8.9, p < 0.001). CONCLUSION: Treatment with Eye Movement Desensitization and Reprocessing (EMDR) could present an effective treatment of MTX intolerance, and using BLAST wristbands, further potential improvement is possible.

Clinical characteristics and prognosis of interstitial lung disease in systemic juvenile idiopathic arthritis: a two-center retrospective observational cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Intraarticular corticosteroid injections in pediatric rheumatology: insights from specialists.

Juvenile idiopathic arthritis (JIA) refers to various types of arthritis appearing before age 16, categorized into seven subtypes by ILAR. Treatments target disease control, growth support, and quality of life, utilizing NSAIDs, DMARDs, and intraarticular corticosteroid injections (IACIs). Despite IACIs' efficacy for oligoarticular JIA, their usage and techniques vary due to anecdotal evidence. This study compares IACI strategies among pediatric rheumatologists in Turkey and India as part of a PReS Sister Center activity. A cross-sectional survey via Google Forms gathered IACI practice data from pediatric rheumatologists in Turkey and India. The 33-item questionnaire covered demographics, JIA subtypes treated with IACIs, preferred agents/dosages, injection sites, follow-up, complications, anesthesia, and post-IACI treatments. Seventy clinicians' responses were analyzed, with ethical approval from Gazi University's Ethics Committee. Seventy participants, with a mean age of 39.75 (±8.80) years responded, mostly clinical fellows (38.6%) at university hospitals (58.6%). All utilized IACIs, primarily for oligoarticular JIA (100%), with 20% exclusively using them for this subtype. Triamcinolone hexacetonide (TH) was preferred (74.3%), mainly targeting knee joints (15.7%). Initial side effect follow-up was 1-2 weeks post-IACI (65.7%), with ultrasound guidance used by 17.1%. Common complications included cutaneous hypopigmentation (38.6%) and subcutaneous atrophy (38.6%). Ketamine was the favored anesthesia (44.2%). Post-IACI, 21.4% did not add treatment for new-onset oligoarticular JIA, while NSAIDs and methotrexate were common for polyarticular JIA (51.4%). CONCLUSION: IACIs are widely utilized in pediatric rheumatology for oligoarticular JIA, yet practice variability exists. Standardized protocols through randomized studies can enhance IACI efficacy and patient outcomes. WHAT IS KNOWN: • Intraarticular corticosteroid injections (IACIs) are a widely utilized and effective treatment modality in managing oligoarticular and polyarticular juvenile idiopathic arthritis (JIA), offering rapid symptom relief and the potential to prevent long-term joint deformities. • Despite their widespread use, there is significant variability in the indications, techniques, and anesthetic methods employed for IACI administration among pediatric rheumatologists, and much of the supporting evidence remains anecdotal. WHAT IS NEW: • This study highlights the diverse clinical practices and preferences regarding IACI use in pediatric rheumatology across two different countries, revealing considerable variations in the use of ultrasound guidance, anesthetic approaches, and corticosteroid formulations. • The findings underscore the need for standardized treatment protocols and further research to optimize IACI procedures, aiming to reduce variability and improve outcomes in the management of JIA.