Pediatric Rheumatology - Latest Articles

Pain experience in children with juvenile idiopathic arthritis treated with anti-TNF agents compared to non-biologic standard treatment

Johanne Lomholt — 2013-05-06T00:00:00Z

Background: Anti-TNF agents have proven efficacy in children with severe juvenile idiopathic arthritis (JIA) who are unresponsive to standard therapy. Therefore pain reduction or elimination could be expected. The aim of this study was to compare the pain experience in children with JIA treated with anti-TNF agents (n = 41) or non-biologic standard treatment (n = 50). Methods: All children completed a 2-week pain diary and, for children treated with anti-TNF agents, measures of pain-coping and pain-specific beliefs. Parents rated the child’s level of functional disability. Clinical data were collected from the pediatric rheumatologists. Results: No significant differences were found between the anti-TNF group and non-biologic standard treatment group for average pain score, number of children with daily pain reported in the pain diary, or level of functional disability. Significantly more children in the anti-TNF group reported no pain at all. Children undergoing standard treatment had significantly higher disease activity. Significant differences were found between the high pain patients treated with anti-TNF agents and the rest of the anti-TNF group in regards to their pain-specific beliefs of disability and harm, and the pain-coping strategy of catastrophizing. Conclusion: These results indicate that a great proportion of children treated with anti-TNF agents respond well to the treatment in regards to disease activity and pain, but pain was still a problem for a subgroup of children though they were in remission with biological agents. More focus on pain management is needed.

Rheumatic symptoms in childhood leukaemia and lymphoma-a ten-year retrospective study

Luca Zombori — 2013-05-04T00:00:00Z

Background: The initial symptoms of childhood leukaemia and lymphoma are often similar to those of juvenile idiopathic arthritis (JIA). In our study, we analyzed the frequency and characteristics of musculoskeletal complaints as the initial presenting symptoms of newly diagnosed leukaemia and lymphoma patients in the past 10 years in our clinic. Methods: Using the Hungarian Tumour Register, we performed a retrospective analysis of the medical records of 166 new leukaemia and 95 new lymphoma pediatric patients treated from 1999 to 2009 at the 2nd. Dept. of Paediatrics of the Semmelweis University in Budapest. Results: Twenty percent of the leukaemic (33 children) and 2% of the lymphoma patients (2 children) had musculoskeletal symptoms at first presentation. Two-thirds of both groups of patients had other general symptoms like fever and/or fatigue. The hip was the most frequently affected joint (7/33) in the leukaemic patients. Twenty-four percent of all the children had been previously evaluated by an orthopaedist; 12% had visited another rheumatologist prior to diagnosis. Imaging had been done in an unexpectedly low number of patients prior to referral to our unit (radiographs: 16 or 48%, ultrasound: 5 patients or 15%). Radiographs of the affected joints were abnormal in only one case (1/16, 6%). The joint ultrasound was abnormal in only three children of 5 studied (3/5, 60%). Anaemia (26/32, 6%), thrombocytopenia (78%) and LDH elevation (3–4 times the normal count) were frequent in the leukaemic patients. Half of the cases had a normal leukocyte count. The lymphoma group had similar results. Two patients of the leukaemia group received steroid treatment before the final diagnosis. Severe pain out of proportion to physical findings is another clue. Conclusions: Haematologic malignancies must be excluded before initiation of therapy for childhood arthritis among children presenting with musculoskeletal signs and symptoms, particularly in atypical cases. Malignancies are to be suspected when pain is disproportionately severe compared to the physical examination findings, and when anaemia, thrombocytopenia, and an elevated LDH level are present. Diagnosing leukaemia early is important because the use of steroids and immunosuppressive medications may mask and delay its diagnosis. Additionally, pre-treatment of presumed JIA patients with these drugs who eventually are diagnosed to have a malignancy may lead to the malignancy being steroid-resistant and more difficult to treat.

Limb girdle muscular dystrophy type 2B masquerading as inflammatory myopathy: case report

Hannah Jethwa — 2013-05-03T00:00:00Z

Limb girdle muscular dystrophy type 2B is a rare subtype of muscular dystrophy, the predominant feature of which is muscle weakness. The disease is caused by an autosomal recessively inherited reduction/absence of muscle dysferlin due to a mutation in dysferlin gene at 2p12-14. We report a 10 year old boy who presented with severe non-transient right knee pain and swelling, which later became bilateral. His pain was worst in the morning and during rest. Blood tests revealed markedly raised creatine kinase values (highest 22, 297 U/l), raising the possibility of an inflammatory myositis. MRI showed bilateral asymmetrical muscle involvement of thighs and calves with oedematous changes mimicking the imaging appearances of inflammatory myositis. CRP and ESR levels were consistently within normal limits. Over several months his knee pain worsened and limited walking. Muscle biopsy revealed a severe reduction of dysferlin immunostaining, indicating the diagnosis, which was confirmed by 2 compound heterozygous pathogenic mutations in the dysferlin gene. It is not unusual for this subtype of the disease to mimic myositis: however, significant pain is a rare presenting symptom. Given the significant overlap between this form of muscular dystrophy and inflammatory myopathies, a high index of suspicion is needed to ensure an accurate and timely diagnosis. Furthermore, characteristic inflammatory-related morning pain should not rule out consideration of non-inflammatory causes.

Osteochondral lesions in children with juvenile idiopathic arthritis

Liisa Kröger — 2013-05-01T00:00:00Z

Background: Joint pain and swelling are typical symptoms in children with juvenile idiopathic arthritis (JIA) and these are often related to inflammation of the joint. Juvenile osteochondritis dissecans (JOCD), that is separation of a bone-cartilage segment from the articular surface, can manifest with similar symptoms.FindingsWe studied thirteen cases of osteochondritis dissecans lesions (OCD) in children with JIA. There were nine girls and four boys with a mean age of 6.5 (2–12) years at the time of diagnosis of JIA. Mean time between diagnosis of JIA and manifestation of OCD was 5.5 (1–11) years. Indications for MRI were the presence of pain or discomfort in the joint, despite otherwise effective treatment, with no evidence from ultrasound examination of any obvious signs of active inflammation. The most common location of osteochondral lesion was the knee, although the ankle joint was affected in one case. Five patients had lesions in both knees. Operative treatment was needed in eight cases (joints). Conclusions: Pain, and minor dysfunction of the joint are common complaints of children suffering from JIA. Earlier research has discounted the possibility of children who were not athletes presenting with this condition. However, this study demonstrates that these lesions also seem to be relatively common in patients with JIA. When there is no sign of inflammation, the possibility of OCD must therefore be considered in these children.

Maximal mouth opening capacity: percentiles for healthy children 4¿17 years of age

Lukas Müller — 2013-04-22T00:00:00Z

Background: A reduced mouth opening capacity may be one of the first clinical signs of pathological changes in the masticatory system. The aim of this retrospective cross-sectional study was to create age related percentiles for unassisted maximal mouth opening capacity (MOC) of healthy children. Methods: All recordings of MOC as measured at the yearly dental examinations of school children in the city of Zurich, Switzerland, between August 2009 and August 2010 were extracted from the database. The program LMSchartMaker Pro Version 2.43, Huiqi Pan and Tim Cole, Medical Research Council, 1997–2010 was used to calculate age and sex related reference centiles. Results: Records from 22′060 dental examinations were found during the study period. In 1286 (5.8%) the maximal interincisal measurement was missing. Another 55 examinations were excluded because of missing data for sex (7), age at examination (11) or because the value was deemed to be pathologically low (37). Thus, a total of 20′719 measurements (10′060 girls, 10′659 boys) were included in the analysis. The median age (range) was 9.9 years (3.3-18.3) for girls and 10.0 years (2.8-18.7) for boys. The mean MOC (range) was 45 mm (25–69) for girls and 45 mm (25–70) for boys. Age related percentiles were created for girls and boys separately, showing the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentile from 3 through 18 years of age. Conclusions: In these 20′719 unselected school children MOC increased with age but showed a wide range within children of the same age.

Superior efficacy of Adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: Adalimumab as starting anti-TNF-¿ therapy in childhood chronic uveitis

Gabriele Simonini — 2013-04-15T00:00:00Z

Background: Nonetheless biologic modifier therapies are available treatment strategies for sight-threatening uveitis in children, the lack of evidence from head-to-head randomized controlled studies limits our understanding of timing of therapy when to commence therapy, which agent to choose and how long to continue treatment, and, in case of failure, if switching to another anti-TNF-α strategy might be eventually an option. Our aim was to compare the efficacy of Adalimumab when used as first anti-TNFα therapy versus Adalimumab used after the failure of a previous anti-TNFα (Infliximab) in an open-label, comparative, multi-center, cohort study of childhood chronic uveitis. Methods: 26 patients (14 F, 12 M; median age: 8.6 years) with refractory, non-infectious active uveitis were enrolled. Due to the refractory course of uveitis to previous DMARD treatment, Group 1 received Adalimumab (24 mg/sq mt, every 2 weeks), as first anti-TNFα choice; Group 2 received Adalimumab, as second anti-TNFα drug, due to the loss of efficacy of Infliximab, administered after a period of at least 1 year. Both groups received Adalimumab for at least 1 year of treatment. Primary outcome was, once remission was achieved, the time to a first relapse. Results: 14 children (10 with JIA, 3 with idiopathic uveitis, 1 with Behçet’s disease) were recruited in Group 1; 12 children (7 with JIA, 3 with idiopathic uveitis, 1 with early-onset sarcoidosis, 1 with Behçet’s disease) in Group 2. Group 2 showed a lower probability to steroid discontinuation during the first 12 months of treatment (Mantel-Cox χ24.12, p<0.04). In long-term follow-up, Group 1 had higher probability of uveitis remission during the time of treatment on Adalimumab (median ±SE: 18 ±1.1 vs 4 ±0.6 months, CI 95%: 15.6-27.5 vs 2.7-5.2, Mantel-Cox χ210.12, p<0.002). Conclusions: Even if limited to a relatively small group, our study suggests a better efficacy of Adalimumab when used as first anti-TNFα treatment in childhood chronic uveitis.

Reviewer Acknowledgement 2012

Alberto Martini — 2013-04-12T00:00:00Z

Contributing reviewersThe Editors of Pediatric Rheumatology would like to thank all our reviewers who have contributed to the journal in Volume 10 (2012).

MRI guided wire localization muscle biopsy in a child with juvenile dermatomyositis

Victoria Tuen — 2013-04-08T00:00:00Z

A novel technique for preoperative MRI guided wire localization for targeted surgical excisional biopsy of muscle is described in a pediatric patient with juvenile dermatomyositis (JDM). This technique allows for preoperative localization of abnormalities seen only with MRI. Using this technique, the patient underwent successful targeted muscle biopsy for confirmation of the diagnosis and staging of dermatomyositis.

Autoinflammatory gene polymorphisms and susceptibility to UK juvenile idiopathic arthritis

Anne Hinks — 2013-04-02T00:00:00Z

Background: To investigate the autoinflammatory hereditary periodic fever syndrome genes MVK and TNFRSF1A, and the NLRP1 and IL1 genes, for association with juvenile idiopathic arthritis (JIA). Methods: For MVK, TNFRSF1A and NLRP1 pair-wise tagging SNPs across each gene were selected and for IL1A SNPs from a prior meta-analysis were included. 1054 UK Caucasian JIA patients were genotyped by Sequenom iPlex MassARRAY and allele and genotype frequencies compared with 5380 unrelated healthy UK Caucasian controls. Results: Four SNPs were significantly associated with UK JIA: rs2071374 within intron 4 of IL1A (ptrend=0.006), rs2228576 3’ of TNFRSF1A (ptrend=0.009) and 2 SNPs, rs11836136 and rs7957619, within MVK (ptrend=0.006, ptrend=0.005 respectively). In all cases the association appeared to be driven by the systemic-onset JIA (SoJIA) subtype. Genotype data for the two MVK SNPs was available in a validation cohort of 814 JIA (oligoarticular and RF negative polyarticular) cases and 3058 controls from the US. Replication was not confirmed, however, further suggesting that this association is specific to SoJIA. Conclusions: These findings extend the observations of the relevance of studying monogenic loci as candidates for complex diseases. We provide novel evidence of association of MVK and TNFRSF1A with UK JIA, specifically driven by association with SoJIA and further confirm that the IL1A SNP association with SoJIA is subtype specific. Replication is required in independent cohorts.

Out-of-clinic patient communication in paediatric rheumatology: the extent and nature of demand

Debi Feldman — 2013-03-27T00:00:00Z

Background: Traditional funding models for public paediatric rheumatology care are typically based on providing medical services for a defined number of clinics per week. Anecdotally there is significant demand by patients and families for out-of-clinic communication with care providers and services provided under traditional funding models may not meet this need. Our aim was to determine the extent and nature of this ‘hidden’ demand in a tertiary paediatric rheumatology centre. Methods: Communication data and diagnoses were extracted from the Rheumatology service database at our centre for the period 1/1/2009 to 31/12/2011. Clinical activity data over the same time were obtained from hospital clinic databases. Results: There were 5672 instances of communication with 749 patients/families over 3 years, (mean 7.3/weekday). This increased over time in parallel with clinical activity. 41% of clinic patients sought communication with the team out of clinic hours. 58% were telephone calls, 36% emails and 6% letters. The communication topics were for advice, results or general updates (28%), medication queries (24%), appointment/admission coordination (20%), disease flare or other disease events (14%), psychosocial, school or transition issues (6%) and miscellaneous queries (8%). Of the most frequent communicators, those with juvenile idiopathic arthritis were the majority (85%). The remainder had other chronic inflammatory conditions. Conclusions: The communication and support needs of patients with chronic rheumatic diseases and their families extend beyond that which can be provided in the clinic environment. It is essential that funding for paediatric rheumatology services allows for staffing sufficient to meet this need.