Individual and environmental determinants associated with longer times to access pediatric rheumatology centers for patients with juvenile idiopathic arthritis, a JIR cohort study.

BACKGROUND: Despite guidelines, poor access to appropriate care for juvenile idiopathic arthritis (JIA) patients remains a global issue. Prompt referral to a pediatric rheumatology (PR) center and effective care is known to be critical for changing the natural history of the disease and improving long-term prognosis. This project assesses socio-economic factors of delayed referral to a pediatric rheumatologist (PRst) for JIA patients in France and Switzerland within the Juvenile Inflammatory Rheumatism (JIR) Cohort. METHODS: All patients diagnosed with JIA, presenting at one center of the JIRcohort in France or Switzerland with additional data on referral pathway were included. Patient characteristics at first visit to the PR center, dates of visits to healthcare providers during referral, and parent characteristics were extracted from the JIRcohort database. RESULTS: Two hundred fifty children were included. The overall median time to first PR assessment was 2.4 months [1.3; 6.9] and ranged widely across the JIA subtypes, from 1.4 months [0.6; 3.8] for children with systemic juvenile idiopathic arthritis (sJIA) to 5.3 months [2.0; 19.1] for children with enthesitis-related arthritis (ERA). A diagnosis of ERA and an appointment with an orthopedist during the referral pathway were significantly associated with a longer time before the first PR visit (hazard ratio HR 0.50 [95% CI: 0.29; 0.84]) and HR 0.68 [95% CI: 0.49; 0.93], respectively) in multivariable analysis. Having a mother with a post-graduate educational attainment level was tendentially associated with a shorter time before the first PR visit, (HR 1.32 [95% CI: 0.99; 1.78]). CONCLUSIONS: Time to first PRst visit was most often short compared to other studies and close to the British recommendations. However, this time remained too long for many patients. We observed no social inequities in access to a PRst, but we show the need to improve effective pathway and access to a PR center for JIA patients.

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.

Factors impacting referral of JIA patients to a tertiary level pediatric rheumatology center in North India: a retrospective cohort study.

BACKGROUND: JIA studies demonstrate that there is a "window of opportunity" early in the disease course during which appropriate management improves outcomes. No data is available regarding patients' pathway, before first pediatric rheumatology (PR) evaluation in India, a country where health-care costs are self- paid by patients and where a significant shortage of pediatric rheumatologists (PRsts) is known. This study aimed to describe time from onset of symptoms to first PR visit of JIA patients to a tertiary center in India and factors that impact this. METHODS: This retrospective study is from data collected at the PR center, Sir Ganga Ram Hospital (SGRH) in New Delhi. JIA patients fulfilling ILAR 2004 criteria and seen at least twice from 1st October 2013 to 30th September 2018 were included. Data collected were: demographic details, history of disease, referral practitioner, clinical and laboratory features, treatments. Mann-Whitney U-test, Chi square and logistic regression were used as appropriate to study factors that determined time to first PR visit. RESULTS: Five hundred and twenty patients were included: 396 were diagnosed at this PR center (group A), 124 were previously diagnosed as JIA and managed by non PRsts before first PR visit (group B). Median time from symptom onset to first PR visit was 4.1 months and median distance travelled 119.5 km. Despite ongoing treatment, group B patients had more aggressive disease and resided further away as compared to Group A patients. On univariate analysis, factors that predicted PR visit within 3 months were private patients, short distance to travel, family history of inflammatory disease, history of fever, history of acute uveitis or high ESR. On multivariate analysis all these factors were significant except high ESR and acute uveitis. CONCLUSION: Time to first PR assessment at this center was comparable to that seen in western countries. Cost of care and long distance to the center delayed consultation; acuity of complaints and family history of rheumatologic condition hastened referral. Possible solutions to improve referral to PR centers would be to increase the number of PRsts and to improve medical insurance coverage.

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.

Skeletal impairment in Pierson syndrome: Is there a role for lamininß2 in bone physiology?

INTRODUCTION: Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin ß2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. METHODS: We report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty. This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of "normal low" quantity and quality; major radial and cubital deformations were observed. Stainings of laminin ß2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin ß2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone. CONCLUSION: This is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3ß1, receptor for laminin ß2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin ß2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin ß2 in bone physiology.

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.