The worldwide incidence of severe sensorineural deafness is approximately 1:2000 and at least 50% of cases are hereditary. 2 Of these, 70% are non-syndromic and autosomal recessive. 2 Mutations of ...the connexin 26 gene are thought to account for the majority of such deafness. 2 The aetiology of progressive deafness in Cryopyrin associated periodic syndromes (CAPS) is unknown, but recent work showing that CIAS1 is highly expressed in chondrocytes 3 and cochlear enhancement on MRI scan in patients with CAPS suggests an inflammatory cause. 4 We propose that synergistic heterozygosity between disease causing mutations in the MEFV gene and non-disease causing or low penetrance sequence variations of the CIAS1 gene may have resulted in the clinical phenotype of FMF with progressive sensorineural deafness as seen in CAPS, possibly due to the role of both genes in the regulation of interleukin-1.
We have identified six children with a distinctive facial phenotype in association with mental retardation (MR), microcephaly, and short stature, four of whom presented with Hirschsprung (HSCR) ...disease in the neonatal period. HSCR was diagnosed in a further child at the age of 3 years after investigation for severe chronic constipation and another child, identified as sharing the same facial phenotype, had chronic constipation, but did not have HSCR. One of our patients has an interstitial deletion of chromosome 2, del(2)(q21q23). These children strongly resemble the patient reported by Lurie et al with HSCR and dysmorphic features associated with del(2)(q22q23). All patients have been isolated cases, suggesting a contiguous gene syndrome or a dominant single gene disorder involving a locus for HSCR located at 2q22-q23. Review of published reports suggests that there is significant phenotypic and genetic heterogeneity within the group of patients with HSCR, MR, and microcephaly. In particular, our patients appear to have a separate disorder from Goldberg-Shprintzen syndrome, for which autosomal recessive inheritance has been proposed because of sib recurrence and consanguinity in some families.
BackgroundChildren with juvenile idiopathic arthritis (JIA) often exhibit joint symptoms in the lower limb. Prolonged joint disease may cause further physical and functional impairment, which can ...lead to significant disturbances in gait such as abnormal pressure distributions and sub-optimal peak plantar pressures 1-3. Recent studies have shown that children with JIA compared to an age and sex matched cohort displayed significantly higher peak pressures (PP) in most areas of the plantar foot 2. Research also showed that children with JIA are displaying elevated pressure time integrals (PTI), meaning they are spending higher amounts of time in the stance phase of gait and less in the swing phase and thus a less propulsive gait 2. To our knowledge only one previous clinical trial has explored the effect of a mechanical intervention such as foot orthoses (FOs) to improve the distribution of peak plantar pressures in children with JIA 4.ObjectivesThe aim of our randomised clinical trial is to further evaluate the effect of customised prefabricated FOs in improving PTI and PP in children with JIA.MethodsA multicentre, parallel design, single-blinded randomised clinical trial was used to assess the impact of customised preformed FOs on plantar pressures in children with JIA. Children with a diagnosis of JIA, exhibiting lower limb symptoms and aged 5-18 were eligible. The trial group received a low-density full length, Slimflex Simple device which was customised chair side and the control group received a sham device. PP and PTI were used as the main gait outcomes and were measured using portable Tekscan gait analysis technology at baseline, 3 and 6 months. PP were measured using kilo pascals (kPa) and PTI measured kPa per seconds (kPa/s). Differences at each follow-up were assessed using the Wilcoxon rank sum test.ResultsA total of 66 participants were recruited. Customised prefabricated FOs were effective in altering plantar pressures in children with JIA versus a control device. Reductions of PP in the heel (baseline p=<0.001 (-104.33 kPa), 3-month p=0.004 (-126.16 kPa)), forefoot (baseline p=0.027 (-131.5 kPa)), 5th metatarsophalangeal joint (baseline p=0.007 (-37.17 kPa), 3-month p=0.001 (-69.5 kPa), 6-month p=0.016 (-50.91 kPa)) were statistically significant in favour of the trial group. These results were also positively correlated with PTI with the trial group spending less time and pressure on the heel, forefoot and rearfoot than the control. Finally, PP and PTI reductions were also associated with statistically significant increased midfoot contact with the trial device at baseline (29.84 kPa), 3 (24 kPa) and 6-month (43.75 kPa) data collections, showing that the trial intervention was successful in capturing the arch profile of participants and redistributing pressure. The trial intervention was safe and well accepted by participants, which is reflected in the high retention rate (92%).ConclusionClinicians may prescribe customised prefabricated FOs in children with JIA to deflect pressure from painful joints and redistribute from high pressure areas such as the rearfoot and forefoot.References1Woolnough L, Pomputius A, Vincent HK. Juvenile idiopathic arthritis, gait characteristics and relation to function. Gait & Posture. 2021;85:38-54.2Merker J, Hartmann M, Haas J-P, Schwirtz A. Combined three-dimensional gait and plantar pressure analyses detecting significant functional deficits in children with juvenile idiopathic arthritis. Gait & Posture. 2018;66:247-54.3Hartmann M, Kreuzpointner F, Haefner R, Michels H, Schwirtz A, Haas J. Effects of juvenile idiopathic arthritis on kinematics and kinetics of the lower extremities call for consequences in physical activities recommendations. International journal of pediatrics. 2010;2010.4Coda A, Fowlie PW, Davidson JE, Walsh J, Carline T, Santos D. Foot orthoses in children with juvenile idiopathic arthritis: a randomised controlled trial. Archives of Disease in Childhood. 2014;99(7):649-51.Acknowledgements:NIL.Disclosure of InterestsNone declared.
Background
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and adolescents 1. The manifestation of JIA may include joint swelling, tenderness, and painful ...limitation with joint movement. Only few studies have explored the effect of foot orthoses (FOs) alone in children with JIA 2,3. These studies showed FOs can reduce pain in children with JIA, however, further research with larger sample sizes and longer follow-ups are needed 4. Prescribing FOs on the same day of the initial assessment may promote early clinical and targeted intervention, which is the gold standard approach in paediatric rheumatology.
Objectives
This single blinded multicentre randomised clinical trial (RCT) aims to investigate the effect of customised prefabricated FOs in reducing pain amongst children and adolescents with JIA.
Methods
Overall, 66 children and adolescents with JIA presenting with foot symptoms were recruited from the Sydney Children’s Hospitals Network (Westmead and Randwick) and John Hunter Children’s Hospital (Newcastle). The primary outcome measure was pain with a minimal clinical significance of 8mm on the visual analogue scale (VAS). Participants were randomly allocated to receive either customised prefabricated or sham FOs. The trial intervention was a low-density Slimflex Simple device that was customised at chair-side. The control (sham) device was made of 2mm flat leather board with no corrective modifications. Standardised tests such as the Foot Posture Index, navicular drift and drop were used to identify biomechanical abnormalities. The FOs were worn for a total of 12 months, with data collected at baseline, 4 weeks, 3, 6 months and 12 months.
Results
Reduction in self-reported pain was statistically and clinically significant at 4-weeks (p=0.018, -14.92 -27.30, -2.55) and 3 months (p=<0.001, -28.93 -40.90, -16.96) post intervention in favour of the trial group. The 6- and 12-month follow-ups were not statistically or clinically significant. Parent reported pain was statistically and clinically significant at the 3-month (p=<0.001, -21.92 -33.16, -10.67) in the reduction of pain in favour of the trial group. However, parent reported pain was not statistically significant at the 4-week, 6- and 12- month follow-ups. These results are similar to child reported pain with a p-value of less than 0.001 and average coefficients twice that of the clinical significance cut-off for VAS pain in paediatric rheumatology. The trial intervention was safe and tolerated well by participants with high compliance and adherence rates.
Conclusion
Results of this clinical trial indicate customised preformed FOs can be effective in reducing pain and in children with JIA experiencing foot and ankle symptoms. Significant clinical effects appear to be within the first 3-months of intervention prescription and reduce beyond 6 months. Overall, this podiatric intervention was safe, inexpensive, well tolerated and it can be easily implemented as part of the multidisciplinary paediatric rheumatology care.
References
1Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369:767–78.
2Powell M, Seid M, Szer IS. Efficacy of custom foot orthotics in improving pain and functional status in children with juvenile idiopathic arthritis: a randomized trial. J Rheumatol 2005;32:943–50.
3Coda A, Fowlie PW, Davidson JE et al. Foot orthoses in children with juvenile idiopathic arthritis: a randomised controlled trial. Arch Dis Child 2014;99:649–51.
4Fellas A, Coda A, Hawke F. Physical and mechanical therapies for lower-limb problems in juvenile idiopathic arthritis: a systematic review with meta-analysis. Journal of the American Podiatric Medical Association. 2017 Sep;107(5):399-412.
Acknowledgements
We would like to acknowledge all parents and children for their precious time.
Disclosure of Interests
None declared
Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, ...randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.
Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).
...This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434.
Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 29% of 72 patients) than with placebo (37 53% of 70 patients; hazard ratio 0·46, 95% CI 0·27–0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study.
The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections.
Pfizer.
Aim: To determine the magnitude of changes in isokinetic muscle strength in children with juvenile idiopathic arthritis (JIA) after intra-articular (IA) corticosteroid injection of inflamed knee ...joints and to assess the feasibility of a larger study of the same effect. Longitudinal follow-up cohort study assessing isokinetic muscle strength before and after IA corticosteroid injection into an affected knee joint with active arthritis. There was a clinically significant increase in knee extensor strength (measured as ratio...
Thalidomide was withdrawn from world markets in 1961 following recognition of its teratogenic effects. More recently, however, thalidomide treatment has been reintroduced to adult and paediatric ...practice for a variety of dermatologic, immunologic, rheumatologic and neoplastic disorders. Neuropathy is a significant side effect of thalidomide therapy, which may limit its clinical use. We report four cases of sensorimotor axonal neuropathy in children aged 10–15 years, treated with thalidomide for myxopapillary ependymoma, Crohn's disease and recurrent giant aphthous ulceration. Thalidomide neuropathy is often associated with proximal weakness and may progress even after discontinuation of treatment, in the phenomenon of ‘coasting’. Children treated with thalidomide should undergo regular neurophysiologic studies in order to detect presymptomatic or progressive peripheral neuropathy.
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