Factors associated with poor prognosis of hip arthritis in juvenile idiopathic arthritis: Data from the JIR cohort.

OBJECTIVES: Hip involvement remains a predictor of severe juvenile idiopathic arthritis (JIA) course and carries a high risk of disability. This study aims to determine the factors of poor prognosis of hip involvement in patients with JIA and to assess the treatment response. METHODS: This is a multicenter observational cohort study. Patients were selected from the JIR Cohort database. Hip involvement was defined as clinically suspected and confirmed by an imaging tool. Follow-up data were collected during 5 years. RESULTS: Among the 2223 patients with JIA, 341(15%) patients had hip arthritis. Male gender, enthesitis-related arthritis, and North African origin were factors associated with hip arthritis. Hip inflammation was associated with disease activity parameters during the first year, particularly Physician Global Assessment, joint count, and inflammatory marks. Structural hip progression was associated with early onset of the disease, a longer time to diagnosis, geographic origin, and JIA subtypes. Anti-TNF therapy was found to be the only treatment able to effectively reduce structural damage progression. CONCLUSION: The early onset diagnostic delay, origin, and systemic subtype of JIA predict a poor prognosis of hip arthritis in children with JIA. The use of anti-TNF was associated with a better structural prognosis.

Is an association of acro-osteolysis, bone fragility, and enchondromatosis a newfound disease caused by an amplification of PTHLH? A case report.

BACKGROUND: Acro-osteolysis (AO) refers to resorption of the distal finger and toe phalanges. It displays two patterns: (i) diffuse AO and (ii) transverse or bandlike AO. AO can be a sign of local distress (e.g. of toxic origin), but is very often a sign of a constitutional or systemic acquired disorder. CASE PRESENTATION: A 15-year-old girl was referred to a paediatric rheumatologist for recurrent pain in her fingertips. She presented a particular cross-sectional AO associated with the presence of intraosseous cysts and bone fragility with atypical fractures. Initial laboratory tests and radiological examination did not allow an etiological diagnosis. Genetic studies revealed a 12p11.22-p11.23 microduplication of 900 kb including the PTHLH (parathyroid hormone-like hormone) gene, which encodes for a hormone involved in the regulation of endochondral ossification and differentiation of chondrocytes, via its PTHLH receptor. CONCLUSIONS: To date, 12p11.22-p11.23 duplications have been reported in five families with skeletal abnormalities, and in particular AO and enchondromatosis associated with bone fragility. This new observation, added to the other reported cases, suggests a close relationship between the presence of this microduplication and the skeletal abnormalities found in the patient. We suggest the descriptive name ABES (acro-osteolysis, bone fragility and enchondromatosis syndrome) to designate this disorder.

Maximal Fat Oxidation During Exercise Is Already Impaired in Pre-pubescent Children With Type 1 Diabetes Mellitus.

Objective: We evaluated substrate utilization during submaximal exercise, together with glycemic responses and hormonal counter-regulation to exercise, in children with type 1 diabetes mellitus (T1DM). Methods: Twelve pre-pubescent children with T1DM and 12 healthy children were matched by sex and age. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates by indirect calorimetry. Levels of glycemia, glucagon, cortisol, growth hormone, noradrenaline, adrenaline, and insulin were monitored until 120 min post-exercise. Results: Absolute peak oxygen uptake (VO2 peak) was significantly lower in the children with T1DM than in the healthy controls (1131.4 ± 102.5 vs. 1383.0 ± 316.6 ml.min-1, p = 0.03). Overall carbohydrate and lipid oxidation rates were the same in the two groups, but for exercise intensities, higher than 50% of VO2 peak, fat oxidation rate was significantly lower in the children with T1DM. The absolute maximal lipid oxidation rate was significantly lower in the T1DM children (158.1 ± 31.6 vs. 205.4 ± 42.1 mg.min-1, p = 0.005), and they reached a significantly lower exercise power than the healthy controls (26.4 ± 1.2 vs. 35.4 ± 3.3 W, p = 0.03). Blood glucose responses to exercise were negatively correlated with pre-exercise blood glucose concentrations (r = -0.67; p = 0.03). Conclusion: Metabolic and hormonal responses during sub-maximal exercise are impaired in young children with T1DM.

Access to paediatric rheumatology care in juvenile idiopathic arthritis: what do we know? A systematic review.

OBJECTIVE: This review examines time to access appropriate care for JIA patients and analyses the referral pathway before the first paediatric rheumatology (PR) visit. We also describe factors associated with a longer referral. METHODS: We performed a systematic literature review, screening electronic databases (PubMed, Web of Science, EMBASE, Cochrane library and Open Grey database) up to February 2020. Articles written before 1994 (i.e. before the introduction of the unifying term JIA) were excluded. RESULTS: From 595 nonduplicate citations found, 15 articles were finally included in the review. Most of the studies took place in Europe. The median time to first PR visit ranged from 3 to 10 months, with some disparities between referral pathway and patient characteristics. Patients with systemic-onset JIA had the shortest time to referral. Some clinical and biological factors such as swelling, fever, and elevated CRP and/or ESR were associated with a shorter time to first PR visit. Conversely, enthesitis, older age at symptom onset or pain were associated with a longer time. Whatever the country or world region, and despite disparities in healthcare system organization and healthcare practitioner availabilities, times to access PR were not wide-ranging. CONCLUSION: This is the first systematic review to summarize research on access to PR for JIA patients. The pathway of care for JIA patients remains complex, and reasons for delayed referral depend on several factors. Standardized clinical guidelines and fast-track pathways to facilitate prompt referral to specialized teams have to allow for worldwide disparities in healthcare provision.

TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis.

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) have impaired physical abilities. TNF-α plays a crucial role in this pathogenesis, but it is also involved in the use of lipids and muscle health. Objective of this study was to explore substrate oxidation and impact of TNF blockade on energy metabolism in children with JIA as compared to healthy children. METHODS: Fifteen non-TNF-blockaded and 15 TNF-blockaded children with JIA and 15 healthy controls were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test on ergocycle to determine fat and carbohydrate oxidation rates by indirect calorimetry. RESULTS: The maximal fat oxidation rate during exercise was lower in JIA children untreated by TNF blockade (134.3 ± 45.2 mg.min- 1) when compared to the controls (225.3 ± 92.9 mg.min- 1, p = 0.007); but was higher in JIA children under TNF blockade (163.2 ± 59.0 mg.min- 1, p = 0.31) when compared to JIA children untreated by TNF blockade. At the same relative exercise intensities, there was no difference in carbohydrate oxidation rate between three groups. CONCLUSIONS: Lipid metabolism during exercise was found to be impaired in children with JIA. However, TNF treatment seems to improve the fat oxidation rate in this population. TRIAL REGISTRATION: In ClinicalTrials.gov, reference number NCT02977416 , registered on 30 November 2016.

Impaired Muscular Fat Metabolism in Juvenile Idiopathic Arthritis in Inactive Disease.

Objectives: The objective of this study was to evaluate muscular metabolic function in children with inactive juvenile idiopathic arthritis (JIA). Methods: Fifteen children with inactive JIA and fifteen healthy controls were matched by sex, biological age, and Tanner stage. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates. Results: Between the two groups, heart rate values and carbohydrate oxidation rates were the same, regardless of the relative intensity of exercise. Lipid oxidation rates were lower in JIA patients, regardless of the percentage of VO2 peak (p < 0.05). Respiratory exchange ratios beyond 50% of VO2 peak were higher in patients with JIA (p < 0.05). Respective maximal fat oxidation rates (MFO) for controls and children with JIA were 218.7 ± 92.2 vs. 157.5 ± 65.9 mg ⋅ min-1 (p = 0.03) and 4.9 ± 1.9 vs. 3.4 ± 1.2 mg ⋅ min-1 ⋅ kg-1 (p = 0.04). There was no difference between the two groups in heart rate, percentage of VO2 peak, or power of exercise to achieve MFO. Controls reached their MFO at an exercise power significantly higher than did JIA subjects (42.8 ± 16.8 and 31.9 ± 9.8 W, p = 0.004). Conclusion: Children with JIA show metabolic disturbance during exercise, even when the disease is considered inactive. This disturbance is seen in a lower lipid oxidation rate during submaximal exercise.

Medical pathways of children with juvenile idiopathic arthritis before referral to pediatric rheumatology centers.

OBJECTIVE: A better understanding about the referral pathway of patients suffering from juvenile idiopathic arthritis (JIA) is required The aim of this study was to describe and analyze time from onset of symptoms to first pediatric rheumatology (PR) visit and the referral pathway of children with incident JIA in two French competence centers. METHODS: From October 2009 to October 2017, new JIA patients were registered in the "Auvergne-Loire cohort on JIA". We collected referral pathway, symptom onset, biological and clinical data at first assessment in PR department. RESULTS: In all, 111 children were included. Median time to first PR visit was 3.3 months [interquartile range (IQR) 1.3, 10.7] with a significant difference between JIA subtypes. After exclusion of systemic JIA, older age at onset of symptoms, and presence of enthesitis or joint pain were significantly associated with a longer time to first PR visit, while joint swelling or limping, abnormal ESR or CRP were associated with a shorter time. The median number of health care practitioners met was 3 [IQR 3, 4]. Orthopedists referred children to a PR center in 64% of cases, pediatricians in 50%, emergency care practitioners in 27% and general practitioners in 25%. Although non-systemic JIAs are not an emergency, 45% were referred to the emergency room. CONCLUSION: Time to first PR visit is rather short compared to other countries but remains too long. Pediatric rheumatologists should offer primary care providers basic training on JIA and fast direct access to PR departments if JIA is suspected.

Corrigendum to "Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers".

[This corrects the article DOI: 10.1155/2018/9365745.].

Inflammatory Response 24 h Post-Exercise in Youth with Juvenile Idiopathic Arthritis.

The aim of this study was to measure the impact, at 24 h post-exercise, of a single exercise bout on plasma inflammatory markers such as calprotectin, IL-6, sIL-6 R, sgp130 and the hypothalamic-pituitary-adrenal (HPA) axis in children with juvenile idiopathic arthritis (JIA).Twelve children with JIA attended the laboratory on three consecutive days (control day, exercise day and 24 h post-exercise), including a 20-min exercise bout on a cycle-ergometer at 70% of max. HR at 8:30 a.m. on day 2. Plasma concentrations of calprotectin, IL-6, sIL-6 R, sgp130, cortisol, ACTH and DHEA were measured on venous blood samples taken every day.at rest and at 8:30, 8:50, 9:30, 10:30 a.m. and 12:00, 3:00, 5:30 p.m.A single exercise bout increased plasma calprotectin 1.7-fold (p<0.001) but did not increase IL-6 and soluble IL-6 receptors in short-term post-exercise recovery. However, at 24 h post-exercise, calprotectin, IL-6 and its receptors had decreased compared to control-day levels. There was a transient 2-fold increase in post-exercise self-evaluated pain (p=0.03) that disappeared in the evening without repercussions the following day.Physical activity in children with JIA results in a slight transient systemic inflammation but seems to be followed by counter-regulation at 24 h post-exercise with a decrease in proinflammatory markers.

Single Bout Exercise in Children with Juvenile Idiopathic Arthritis: Impact on Inflammatory Markers.

Objective: In a context of inflammatory disease such as juvenile idiopathic arthritis (JIA), we do not know what impact physical activity may have on a deregulated immune system. The objective is to measure the impact of a single bout of exercise on plasma inflammatory markers such as calprotectin, IL-6, sIL-6R, sgp130, and the hypothalamic-pituitary-adrenal axis in children with juvenile idiopathic arthritis. Methods: Twelve children with JIA performed a nonexercise control day and a consecutive day that included a 20 min exercise bout at 70% of max-HR at 08:30 am. Venous blood samples were taken at 08:30, 08:50, 09:30, 10:30 am, and 12:00 pm to measure plasma concentrations of calprotectin, IL-6, sIL-6R, sgp130, cortisol, and ACTH. Pain was evaluated at 08:30, 08:50 am, and 06:00 pm. Results: There was a transient twofold increase in postexercise self-evaluated pain (p = 0.03) that disappeared in the evening. A single bout of exercise resulted in a 1.7-fold increase in plasma calprotectin (p < 0.001) but not IL-6 and its soluble receptors. Calprotectin levels returned to baseline within 3 hours after cessation of exercise. Conclusion: Acute exercise in children with JIA induced slightly musculoskeletal leg pain and transient increased plasma calprotectin levels but not IL-6 levels. Trial registration in ClinicalTrials.gov, reference number NCT 02502539, registered on 29 May 2015.

MISS questionnaire in French version: a good tool for children and parents to assess methotrexate intolerance.

The aim of this study was to assess the relevance for children and parents to use the French-validated version of the methotrexate intolerance severity score (MISS), a measure of methotrexate intolerance for children suffering from juvenile idiopathic arthritis. The French-version MISS was developed following the "Guidelines for the process of cross-cultural adaptation of self-report measures." The new version was tested in families of children with juvenile idiopathic arthritis who completed the questionnaire twice at a 2-week interval. Item correlations, Cronbach's alpha, and kappa coefficients were computed to evaluate acceptability, internal consistency, and reproducibility. A culturally acceptable version to French was obtained. A total of 71 individuals were included from May 2015 to November 2015. The results show very good acceptability: good response rate (80%), few missing data (<1%) and good understanding of parents and children. The inter-item, dimension-item, and inter-dimension correlations were satisfactory (except for "vomiting" items-other items correlation). Cronbach's alpha coefficient was well higher than the usually recommended value of 0.6. The results of validity of internal and external consistencies were satisfactory. We also found good agreement between the test-retest for every family. The empirical discriminative cut-off point of 3 showed a sensitivity of 86% and a specificity of 83%. The MISS questionnaire is quick to complete, easy to use. It can be completed by children or their parents with no significant difference. This validated French-version MISS can help study prevalence and risk factors of methotrexate intolerance, better detect this intolerance, and provide better support for patients on long-term treatment.

Why we need a process on breaking news of Juvenile Idiopathic Arthritis: a mixed methods study.

BACKGROUND: Juvenile Idiopathic Arthritis is the most common chronic pediatric rheumatic disease. The announcement of Juvenile Idiopathic Arthritis poses for parents a number of challenges that make it hard to accept a diagnosis of the disease for their child; yet to our knowledge, no study to date has focused on the time period immediately surrounding the diagnosis. This study sets out to describe parents' experiences in engaging with their child's diagnosis of Juvenile Idiopathic Arthritis. METHODS: This is a mixed methods study. Semi-structured interviews of families with a Juvenile Idiopathic Arthritis child were conducted. A grounded-theory thematic analysis was performed. Items that emerged in the interviews were compiled into a self-administered questionnaire. RESULTS: Eleven families participated in the qualitative study. Sixty families responded to the questionnaire. The path of parents was characterized by doubt (before, during and after diagnosis) while the disease tended to take center stage. Doubt was generated through mismatches in perspectives between the parents' circle of acquaintances, physicians, and the parents' own subjective experiences of symptoms. This study also found that social support and parent associations occupied an ambiguous position between help and stigmatization. CONCLUSIONS: Doubt fuels self-energizing spirals that take root as parents learn the news that their child has Juvenile Idiopathic Arthritis. These spirals of doubt may influence parents' experiences at every stage throughout the course of disease. Our data support the implementation of a specific process dedicated to breaking the news of Juvenile Idiopathic Arthritis to parents.

Association of mastocytosis with inflammatory joint diseases: a series of 31 patients.

OBJECTIVES: We studied the clinical phenotypes and tolerance to treatments in a series of patients affected by both inflammatory joint diseases and mastocytosis. METHODS: This retrospective multicenter study was conducted on behalf of 3 networks focused on mastocytosis, pediatric, and adults' inflammatory joint diseases. Patients who displayed both mastocytosis and inflammatory joint diseases were included. RESULTS: A total of 31 patients were included. They had spondyloarthritis (SpA) (16 patients), rheumatoid arthritis (6 patients), juvenile idiopathic arthritis (2 patients), and undifferentiated arthritis (7 patients). The median ages at diagnosis of arthritis and mastocytosis were 44 and 40.5 years, respectively. Disease-modifying anti-rheumatic drugs (DMARDs) were required in 22 patients, comprising mostly methotrexate (13 patients), salazopyrin (8 patients), anti-tumor-necrosis-factor agents (7 patients), and corticosteroids (9 patients). They were well tolerated. Adverse events occurred in 2/24 patients receiving non-steroidal anti-inflammatory drugs. The prevalence of SpA among the 600 patients included in the mastocytosis cohort was 2.33%, which is significantly higher than the prevalence of SpA in the French population (p < 0.001). CONCLUSIONS: This study suggests that mastocytosis is associated with a higher prevalence of SpA than expected, and that DMARDs, notably anti-TNFα agents, are well tolerated in patients with mastocytosis. Mast cells might be involved in the development of SpA.