Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response.

OBJECTIVE: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM. METHODS: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up. The expression levels of five type I IFN-stimulated genes, MX1, IFI44, IFI44L, LY6E and IFIT3, were measured by RT-qPCR to determine the IFN signature and calculate an IFN score. IFN-inducible plasma proteins CXCL10 and galectin-9 were measured by multiplex immunoassay. RESULTS: Siglec-1 and IFN score were increased in JDM patients compared with controls and correlated with clinical disease activity. Stratification of patients by Siglec-1 expression at diagnosis identified those with high Siglec-1 expression as having a higher risk of requiring treatment intensification within the first 3 months after diagnosis (55% vs 0% of patients, P = 0.01). Siglec-1 expression strongly correlated with plasma levels of previously validated biomarkers CXCL10 (rs = 0.81, P < 0.0001) and galectin-9 (rs = 0.83, P < 0.0001), and was superior to the IFN score in predicting treatment response (area under the curve 0.87 vs 0.53, P = 0.01). CONCLUSION: Siglec-1 on monocytes is a novel IFN-inducible biomarker in JDM that correlates with clinical disease activity and identifies patients at risk for a suboptimal treatment response. Further studies are required to validate these findings and their clinical potential.

Differences in presentation between paediatric- and adult-onset primary Sjögren's syndrome patients.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a rare disease in paediatric patients. Presenting symptoms differ from those in adult patients. The aim of this study was to evaluate presenting symptoms, classification criteria and clinical assessments, including salivary gland ultrasonography (SGUS), at disease onset in paediatric and adult patients with pSS. METHODS: Data of 23 paediatric- and 33 adult-onset patients with pSS were obtained from our standardised multidisciplinary REpSULT and RESULT cohorts, respectively. Clinical, patient-reported, serological, functional, biopsy and SGUS parameters were compared. RESULTS: In paediatric-onset pSS (pedSS) patients, recurrent parotid gland swelling (91% vs. 49%, p<0.001) and fever (30% vs. 3%, p=0.006) were more often present than in adult-onset patients. In contrast, sicca symptoms of mouth (52% vs. 79%, p=0.046) and eyes (26% vs. 73%, p<0.001) were less common in pedSS patients. In paediatric patients, the entry criteria of the ACR/EULAR classification were most often met due to activity in the glandular domain of the ESSDAI. When applying the ACR/EULAR classification criteria, only 78% of pedSS fulfilled these criteria compared to 100% of adult patients. Abnormal glandular function tests had a greater contribution to fulfilling the criteria in adults, while the biopsy had a greater contribution in paediatric patients. Anti-SSA/Ro serology had similar contribution for both cohorts. SGUS Hocevar score was significantly higher in paediatric compared to adult patients (median 25 vs. 18, p=0.004). CONCLUSION: PedSS has a different presentation than adult-onset pSS. Recurrent parotid gland swelling in paediatric patients should alert clinicians to the potential presence of pSS.

Alagille Syndrome and Chronic Arthritis: An International Case Series.

We describe 10 children with Alagille syndrome and inflammatory arthritis. In our centers, the prevalence of chronic arthritis in patients with Alagille syndrome is approximately 50 times higher compared with the general population. Arthritis was refractory to most treatment. Patients with Alagille syndrome should routinely be screened for musculoskeletal symptoms.

Role of FDG-PET/CT in children with fever of unknown origin.

PURPOSE: To determine the role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) in children with fever of unknown origin (FUO). METHODS: This retrospective single-center study included 110 children (0-18 years) with FUO who underwent FDG-PET/CT between 2010 and 2019. The diagnostic value of FDG-PET/CT for identifying cause of fever was calculated, treatment modifications after FDG-PET/CT were assessed, and logistic regression analyses were performed to identify clinical and biochemical factors associated with FDG-PET/CT outcome. RESULTS: In 53 out of 110 patients (48%), FDG-PET/CT identified a (true positive) cause of fever. Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) were the most common causes of FUO. In 42 patients (38%), no cause of fever was found on FDG-PET/CT. In 58 out of 110 patients (53%), treatment modifications were made after FDG-PET/CT. FDG-PET/CT achieved a sensitivity of 85.5%, specificity of 79.2%, positive predictive value of 84.1%, and negative predictive value of 80.9%. On multivariate logistic regression, C-reactive protein was positively associated with finding a true positive focus of fever on FDG-PET/CT (OR = 1.01 (95% CI 1.00-1.02) per mg/L increase in CRP), while leukocyte count was negatively associated with finding a true positive focus of fever (OR = 0.91 (95% CI 0.85-0.97) per 109 leukocytes/L increase). CONCLUSION: FDG-PET/CT is a valuable diagnostic tool in the evaluation of children with FUO, since it may detect a true underlying cause in almost half (48%) of all cases where none was found otherwise. It allows full-body evaluation in patients without disease-specific symptoms on one examination. CRP and leukocyte count were significantly associated with FDG-PET/CT results, which may contribute to a priori assessment on the outcome of FDG-PET/CT. Future research could be aimed at evaluating more patient-specific factors to prospectively estimate the added value of FDG-PET/CT in children with FUO.

Muscles in motion: a randomized controlled trial on the feasibility, safety and efficacy of an exercise training programme in children and adolescents with juvenile dermatomyositis.

OBJECTIVE: To study for the first time in a randomized controlled trial the feasibility, safety and efficacy of an exercise training programme in children and adolescents with JDM. METHODS: Patients were randomly assigned to the Intervention Group (IG; n = 14) or Waiting Control Group (WCG; n = 12). The intervention comprised an individually tailored 12-week home-based exercise programme of treadmill interval training and strength exercises. The efficacy of the IG over usual care (WCG) was examined with mixed linear regression (intention-to-treat). Effect sustainability during 12 weeks follow-up was also examined. RESULTS: Seventy-five percent of the participants completed the intervention. Reasons for discontinuation were motivation/fatigue, recurrent infections and increasing physical complaints. No hospitalizations occurred and immune suppressive therapy remained stable or decreased in the patients who participated in the intervention. The estimated marginal means after the intervention period were significantly in favour of the IG compared with the WCG for standing long jump distance [difference between groups (95% CI): 13 cm (2-23)], the 30-s number of push-ups [8 (3-13)] and sit-ups [4 (0.4-8)], and the parent Childhood Health Assessment Questionnaire 30 + 8 score [-0.13 (-0.24 to - 0.01)] and effects sustained at follow-up. A trend was seen for the maximal oxygen uptake divided by body mass during maximal exercise treadmill testing; the IG scored 3.0 ml/kg/min (-1.3 to 7.3) higher compared with the WCG. Other outcomes (e.g. isometric muscle strength and perception of fatigue) did not differ between IG and WCG. CONCLUSION: Exercise training is of value in the clinical management of JDM.

Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register.

BACKGROUND: Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999. OBJECTIVE: To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA. METHODS: The Arthritis and Biologics in Children register (multicentre prospective observational study) aimed to include all consecutive patients with JIA in the Netherlands who had started biological agents since 1999. Patients were divided according to year of introduction of first biological agent. Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years. RESULTS: 335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010. Etanercept remained the most often prescribed biological agent for non-systemic JIA; anakinra became first choice for systemic JIA. The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased. During these 12 years of observation, biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS (Juvenile Arthritis Disease Activity Score) disease activity. All baseline disease activity parameters were lowered in patients with non-systemic JIA. In systemic JIA, prescription patterns changed towards very early introduction of biological agents (median 0.4 years of disease duration) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates. These changes for both systemic and non-systemic JIA resulted in more patients with inactive disease after 3 and 15 months of treatment. CONCLUSIONS: Biological agents are increasingly prescribed, earlier in the disease and in patients with JIA with lower disease activity. These changes are accompanied by better short-term disease outcomes.

Effectiveness and safety of a second and third biological agent after failing etanercept in juvenile idiopathic arthritis: results from the Dutch National ABC Register.

OBJECTIVE: To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure. METHODS: The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates. RESULTS: Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent. CONCLUSIONS: Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.

Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: results from the Dutch Arthritis and Biologicals in Children Register.

OBJECTIVE: Because TNF inhibitors are not approved for persistent oligoarticular JIA (oJIA), although they are used off-label, we evaluated their effectiveness in patients in this category. METHODS: Persistent oJIA patients were selected from the Dutch Arthritis and Biologicals in Children (ABC) register, an ongoing multicentre prospective study that aims to include all Dutch children with JIA using biologic agents. Response was assessed by the JIA core-set disease activity variables and modified Wallace criteria for inactive disease. RESULTS: Until February 2011, 16 persistent oJIA patients (68.8% females) had been included in the register. Median age of onset was 8.4 years [interquartile range (IQR) 2.1-13.5 years]; history of uveitis in 18.8%; ANA-positive 56.3%. All had previously used MTX, and 81.3% had used IA CSs. Median follow-up after the introduction of biologic treatment was 13.7 months (IQR 8.3-16.7 months). Fourteen patients started etanercept and two patients who had active arthritis as well as uveitis started adalimumab. Although patients with persistent oJIA had few affected joints [median of two active joints at the start of biologic (IQR 1-3)], the patient/parent assessments of pain [median visual analogue score (VAS) 51 (IQR 1-64)] and well-being [median VAS 44 (IQR 6-66)] were high. Additionally, their physician evaluated the disease activity as moderately high [median VAS 36 (IQR 4-65)]. After 3 months this decreased to 0 (IQR 0-30) and 63% achieved inactive disease. After 15 months the disease was inactive in 9/10 observed patients. TNF inhibitors were tolerated well. CONCLUSION: TNF blocking agents seem an effective and justifiable option in persistent oJIA when treatment with IA CS injections and MTX has failed.

Treatment choices of paediatric rheumatologists for juvenile idiopathic arthritis: etanercept or adalimumab?

OBJECTIVES: To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment. METHODS: Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared. Focus group interviews with paediatric rheumatologists were performed to evaluate factors determining treatment choices. RESULTS: A total of 193 patients started treatment with etanercept and 21 with adalimumab. Adalimumab-treated patients had longer disease duration prior to the start of biologics (median 5.7 vs 2.0 years) and more often a history of uveitis (71% vs 4%). Etanercept-treated patients had more disability at baseline (median Childhood Health Assessment Questionnaire score 1.1 vs 0.4) and more active arthritis (median number of active joints 6 vs 4). The presence of uveitis was the most important factor directing the choice towards adalimumab. Factors specific for the paediatric population-such as painful adalimumab injections-as well as the physician's familiarity with the drug accounted for the preference for etanercept. CONCLUSION: Although the two TNF inhibitors are considered equally effective, in daily practice etanercept is most often prescribed; adalimumab is mainly preferred when uveitis is present. In choosing the most suitable biologic treatment, paediatric rheumatologists take into account drug and patient factors, considering newly published data and cautiously implementing this into daily care.

Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial.

IMPORTANCE: The immunogenicity and the effects of live attenuated measles-mumps-rubella (MMR) vaccination on disease activity in patients with juvenile idiopathic arthritis (JIA) are matters of concern, especially in patients treated with immunocompromising therapies. OBJECTIVES: To assess whether MMR booster vaccination affects disease activity and to describe MMR booster immunogenicity in patients with JIA. DESIGN, SETTING, AND PARTICIPANTS: Randomized, multicenter, open-label clinical equivalence trial including 137 patients with JIA aged 4 to 9 years who were recruited from 5 academic hospitals in The Netherlands between May 2008 and July 2011. INTERVENTION: Patients were randomly assigned to receive MMR booster vaccination (n=68) or no vaccination (control group; n=69). Among patients taking biologics, these treatments were discontinued at 5 times their half-lives prior to vaccination. MAIN OUTCOMES AND MEASURES: Disease activity as measured by the Juvenile Arthritis Disease Activity Score (JADAS-27), ranging from 0 (no activity) to 57 (high activity). Disease activity in the year following randomization was compared between revaccinated patients and controls using a linear mixed model. A difference in JADAS-27 of 2.0 was the equivalence margin. Primary immunogenicity outcomes were seroprotection rates and MMR-specific antibody concentrations at 3 and 12 months. RESULTS: Of 137 randomized patients, 131 were analyzed in the modified intention-to-treat analysis, including 60 using methotrexate and 15 using biologics. Disease activity during complete follow-up did not differ between 63 revaccinated patients (JADAS-27, 2.8; 95% CI, 2.1-3.5) and 68 controls (JADAS-27, 2.4; 95% CI, 1.7-3.1), with a difference of 0.4 (95% CI, -0.5 to 1.2), within the equivalence margin of 2.0. At 12 months, seroprotection rates were higher in revaccinated patients vs controls (measles, 100% vs 92% [95% CI, 84%-99%]; mumps, 97% [95% CI, 95%-100%] vs 81% [95% CI, 72%-93%]; and rubella, 100% vs 94% [95% CI, 86%-100%], respectively), as were antibody concentrations against measles (1.63 vs 0.78 IU/mL; P = .03), mumps (168 vs 104 RU/mL; P = .03), and rubella (69 vs 45 IU/mL; P = .01). Methotrexate and biologics did not affect humoral responses, but low patient numbers precluded definite conclusions. CONCLUSION AND RELEVANCE: Among children with JIA who had undergone primary immunization, MMR booster vaccination compared with no booster did not result in worse JIA disease activity and was immunogenic. Larger studies are needed to assess MMR effects in patients using biologic agents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00731965.

[Chronic non-infectious osteomyelitis in children]. / Chronische niet-infectieuze osteomyelitis bij kinderen.

Musculoskeletal pain in common and the differential diagnosis is broad. It is important to recognize the harmful and/or treatable pathology, without performing unnecessary diagnostics. Pattern recognition is crucial. One of the differential diagnostic considerations is chronic non-infectious osteomyelitis (CNO). A relatively unknown auto-inflammatory disease. By presenting three cases, we want to draw attention to this condition and contribute to a better recognition of this disease. We emphasize the importance of doing a total body MRI, when CNO is considered.

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children From Wild-type to Population Immunity: A Prospective Multicenter Cohort Study With Real-time Reporting.

BACKGROUND: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. METHODS: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. RESULTS: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. CONCLUSIONS: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections.

High prevalence of methotrexate intolerance in juvenile idiopathic arthritis: development and validation of a methotrexate intolerance severity score.

OBJECTIVE: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire. METHODS: The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients. RESULTS: The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P = 0.001). CONCLUSION: Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.

Capillary microscopy is a potential screening method for connective tissue disease in children with Raynaud's phenomenon.

BACKGROUND: Nailfold capillary microscopy (NCM) is a cornerstone in the diagnosis of Systemic Sclerosis (SSc) in adulthood. Although Raynaud's phenomenon (RP) is very common in childhood, studies on diagnostic methods to differentiate between primary RP (PRP) and secondary RP (SRP) at a young age are scarce. The aim of this study was to determine the value of NCM in differentiating between PRP and SRP in children and adolescents with RP. METHODS: In this nested case-control study, 83 patients diagnosed with RP and having underwent NCM in childhood were retrospectively included. Based on whether they were diagnosed with a connective tissue disease (CTD) during follow-up, patients were classified as PRP or SRP. NCM was performed by a vascular technician. PRP and SRP patients were compared on demographics, NCM and serology. Variables associated with SRP were included in a multivariate logistic regression model. Predictive values were calculated for NCM, ANA positivity and the combination of NCM and ANA positivity. RESULTS: At the time of the NCM, the mean age of the RP patients was 15.4 ± 2.3 years. Of these patients, 78.3% were classified as PRP and 21.7% as SRP at mean follow-up of 6.4 ± 3.20 years. CTDs were miscellaneous, with only one patient having developed SSc. Of the NCM parameters, only capillary loss was associated with SRP (p = 0.01). In a multivariate logistic regression model including ANA, capillary loss was not a predictor of SRP. In a model without ANAs, capillary loss was an independent predictor (OR = 3.98, CI 95% 1.22-12.99). Capillary loss had a sensitivity of 44.4% and a specificity of 84.4% for SRP. ANA combined with capillary loss had a sensitivity of 66.7% and a specificity of 85.7%. CONCLUSION: Whereas RP in adulthood is most strongly associated with SSc, children with RP seem to be at risk for developing other CTDs with less apparent NCM abnormalities. Of all NCM findings, only capillary loss was predictive for SRP. NCM did not add to the predictive value of ANA screening. However, with a specificity of 84.4% and being non-invasive, NCM shows potential as a screening method for SRP. More research with a larger study population is required before drawing conclusions.

Physical and Psychosocial Health in Pediatric Uveitis Patients.

BACKGROUND: To investigate the possible associations between childhood noninfectious uveitis and cardio-respiratory fitness, physical activity, health related quality of life and fatigue. METHODS: Cross-sectional analysis of 23 patients with noninfectious uveitis, aged 8-18 years. BMI, exercise capacity, muscle strength and physical activity were measured. Health-related quality of life and fatigue were assessed. The results were compared to standardized values for age matched healthy children. RESULTS: Twenty-three patients were included. Children with uveitis had a higher bodyweight and body mass index. Children with uveitis had lower cardio-respiratory fitness and they were less physically active, but they experienced a normal quality of life and normal fatigue. Parents of children with uveitis reported a lower quality of life and more fatigue for their children than parents of healthy children. CONCLUSION: Our study indicates that children with noninfectious uveitis are at risk of developing lower physical and psychosocial health.

Factors associated with care- and health-related quality of life of caregivers of children with juvenile idiopathic arthritis.

OBJECTIVE: This study investigates the relationship of child, caregiver, and caring context measurements with the care-related quality of life (CRQoL) and health-related quality of life (HRQoL) of caregivers of children with juvenile idiopathic arthritis (JIA). METHODS: We performed a cross-sectional analysis of baseline data on caregivers of children with JIA from Canada and the Netherlands collected for the "Canada-Netherlands Personalized Medicine Network in Childhood Arthritis and Rheumatic Diseases" study from June 2019 to September 2021. We used the CRQoL questionnaire (CarerQoL), adult EQ-5D-5L, and proxy-reported Youth 5-Level version of EuroQoL (EQ-5D-5L-Y) to assess caregiver CRQoL, caregiver HRQoL, and child HRQoL, respectively. We used a multivariate analysis to assess the relationship between both caregiver CRQoL and HRQoL and patient, caregiver, and caring context measurements. RESULTS: A total of 250 caregivers were included in this study. Most of the caregivers were from the Netherlands (n = 178, 71%) and 77% were females (n = 193). The mean CarerQoL scores was 82.7 (standard deviation (SD) 11.4) and the mean EQ-5D-5L utility score was 0.87 (SD 0.16). Child HRQoL and employment had a positive relationship with both caregiver CarerQoL and EQ-5D-5L utility scores (p < 0.05), while receiving paid or unpaid help had a negative relationship with both scores (p < 0.05). CONCLUSION: Our findings indicated that to understand the impact of JIA on families, we need to consider socio-economic factors, such as employment and support to carry caregiving tasks, in addition to child HRQoL.

Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus: important lessons from longitudinal follow-up.

OBJECTIVES: To observe if capillary patterns in childhood-onset SLE (cSLE) change over time and find associations between a capillary scleroderma pattern with disease activity, damage or scleroderma-like features. METHODS: Clinical and (yearly) capillaroscopy data from a longitudinal cohort of patients with cSLE (minimum of four Systemic Lupus International Collaborating Clinics (SLICC) criteria, onset <18 years) were analysed. Disease activity was measured by Systemic Lupus Erythematosus Activity Index (SLEDAI) and disease damage by SLICC Damage Index. A scleroderma pattern was defined according to the 'fast track algorithm' from the European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases. An abnormal capillary pattern, not matching a scleroderma pattern, was defined as 'microangiopathy'. RESULTS: Our cohort consisted of 53 patients with cSLE with a median disease onset of 14 years (IQR 12.5-15.5 years), median SLEDAI score at diagnosis was 11 (IQR 8-16), median SLEDAI at follow-up was 2 (IQR 1-6). A scleroderma pattern (ever) was seen in 18.9%, while only 13.2% of patients had a normal capillary pattern. Thirty-three patients had follow-up capillaroscopy of which 21.2% showed changes in type of capillary pattern over time. Type of capillary pattern was not associated with disease activity. Raynaud's phenomenon (ever) was equally distributed among patients with different capillaroscopy patterns (p=0.26). Anti-ribonucleoprotein antibodies (ever) were significantly more detected (Χ2, p=0.016) in the scleroderma pattern subgroup (n=7 of 10, 70%). Already 5 years after disease onset, more than 50% of patients with a scleroderma pattern had SLE-related disease damage (HR 4.5, 95% CI 1.1 to 18.8, p=0.034), but they did not develop clinical features of systemic sclerosis at follow-up. Number of detected fingers with a scleroderma pattern was similar between cSLE, juvenile systemic sclerosis and juvenile undifferentiated connective tissue disease. CONCLUSION: This longitudinal study shows that the majority of capillary patterns in cSLE are abnormal and they can change over time. Irrespective of disease activity, a capillary scleroderma pattern in cSLE may be associated with higher risk of SLE-related disease damage.

Tumour necrosis factor (TNF)-blocking agents in juvenile psoriatic arthritis: are they effective?

OBJECTIVES: To evaluate the effectiveness of tumour necrosis factor (TNF) blockers in juvenile psoriatic arthritis (JPsA). METHODS: The study was a prospective ongoing multicentre, observational study of all Dutch juvenile idiopathic arthritis (JIA) patients using biologicals. The response of arthritis was assessed by American College of Rheumatology (ACR) paediatric response and Wallace inactive disease criteria. The response of psoriatic skin lesions was scored by a 5-point scale. RESULTS: Eighteen JPsA patients (72% female, median age onset 11.1 (range 3.3-14.6) years, 50% psoriatic skin lesions, 39% nail pitting, 22% dactylitis) were studied. The median follow-up time since starting anti-TNFα was 26 (range 3-62) months. Seventeen patients started on etanercept and one started on adalimumab. After 3 months of treatment 83% of the patients achieved ACR30 response, increasing to 100% after 15 months. Inactive disease reached in 67% after 39 months. There was no discontinuation because of inefficacy. Six patients discontinued treatment after a good clinical response. However, five patients flared and restarted treatment, all with a good response. During treatment four patients (two JPsA and two JIA patients with other subtypes) developed de novo psoriasis. In four of the nine patients the pre-existing psoriatic skin lesions improved. CONCLUSION: Anti-TNFα therapy in JPsA seems effective in treating arthritis. However, in most patients the arthritis flared up after treatment discontinuation, emphasising the need to investigate optimal therapy duration. The psoriatic skin lesions did not respond well and four patients developed de novo psoriasis.

Factors associated with treatment response to etanercept in juvenile idiopathic arthritis.

CONTEXT: Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal. OBJECTIVE: To determine the response to therapy after initiation of etanercept therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment. DESIGN, SETTING, AND PATIENTS: The Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, includes all Dutch JIA patients who used biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years. MAIN OUTCOME MEASURES: Excellent response (inactive disease or discontinuation earlier due to disease remission), intermediate response (more than 50% improvement from baseline, but no inactive disease), and poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance) evaluated 15 months after initiation of etanercept. RESULTS: At 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; adjusted odds ratio [OR] per point increase, 0.49; 95% CI, 0.33-0.74); fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43-0.95), and younger age at onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99). Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92; 95% CI, 1.26-6.80), and female sex (adjusted OR female vs male, 2.16; 95% CI, 1.12-4.18). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months (95% CI, 46.4-52.0) for patients with an excellent response after 15 months, 47.5 months (95% CI, 44.9-50.1) for patients with an intermediate response, and 17.4 months (95% CI, 13.6-21.2) for patients with a poor response. CONCLUSIONS: Among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female sex.

Case Report: Systemic Small-Vessel Vasculitis in an Adolescent With Active Ulcerative Colitis.

Introduction: Small-vessel vasculitis (SVV) is a rare immunological disease that affects arterioles, capillaries and venules. It causes purpura, but can also manifest in other organs, including the gastrointestinal tract. SVV and inflammatory bowel disease (IBD) co-occur more frequently than would be expected by chance. Case description: A 16-year-old girl, who had been diagnosed with ulcerative colitis (UC) 2 years earlier at a general hospital, developed purpura, progressive abdominal pain with frequent bloody diarrhea and frontotemporal headache and swelling while on azathioprine and mesalamine maintenance therapy. Serology was positive for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) without antiprotease- or myeloperoixidase antibodies. Endoscopy revealed active left-sided UC and atypical ulcerations in the ascending colon. Biopsies of these ulcerations and of affected skin revealed leukocytoclastic vasculitis. Initially this was interpreted as an extraintestinal manifestation of UC that would subside when remission was induced, consequently infliximab was started. Over the next 3 weeks she developed severe burning pain in her right lower leg that progressed to a foot drop with numbness and the purpura progressed to bullous lesions. The diagnosis was adjusted to ANCA-associated vasculitis with involvement of skin, bowel and peripheral nerves. Infliximab was discontinued and induction treatment with high-dose prednisolone and cyclophosphamide was given until remission of SVV and UC was achieved. Subsequently, infliximab induction and maintenance was re-introduced in combination with methotrexate. Remission has been maintained successfully for over 2 years now. The foot drop only partly resolved and necessitated the use of an orthosis. Conclusion: Pediatric patients with IBD who present with purpuric skin lesions and abdominal pain should be evaluated for systemic involvement of SVV, which includes endoscopic evaluation of the gastrointestinal tract. We discuss a practical approach to the diagnosis, evaluation and management of systemic SVV with a focus on prompt recognition and early aggressive therapy to improve outcome.