bluuebunny/crossref_metadata_2025_split huggingface dataset:
A6: Tapering and Withdrawal of Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis in Inactive Disease: Results From an Alternative Dosing Regimen in the TENDER Study
Authors: De Benedetti Fabrizio , Ruperto Nicolino , Brunner Hermine , Grom Alexei A. , Wulffraat Nico , Henrickson Michael , Jerath Rita , Kimura Yuki , Kadva Alysha K. , Wang Jianmei , Martini Alberto , Lovell Daniel J. 
Published: March 2014

Background/Purpose:The TENDER clinical trial is a 3‐part, 5‐year, phase 3 study with tocilizumab (TCZ) in patients with active systemic juvenile idiopathic arthritis (sJIA). After 2 years of treatment, sJIA patients who have maintained clinically inactive disease for 3 months are given the option to participate in an alternative TCZ dosing regimen aimed at spacing the infusions and eventually withdrawing TCZ. Herein we describe the patients registered to participate in the optional alternative dosing schedule in the TENDER study.Methods:To qualify for the optional alternative dosing schedule, patients had to be in the study for 2 years and had to achieve American College of Rheumatology JIA inactive disease status. Among the 112 patients enrolled, 39 (35%) entered the optional alternative dosing regimen. This entailed a staged prolongation of the time interval between TCZ infusions from 2 weeks (standard interval) to 3 weeks, then 4 weeks, with the option of terminating TCZ after the discontinuation of any treatment.Results:Twenty‐three male and 16 female patients entered the optional alternative dosing schedule. Their mean baseline characteristics were 14.2 active joints, 15.4 joints with limitation of motion, physician global VAS score of 58.5, CHAQ‐DI score of 1.62, and erythrocyte sedimentation rate (ESR) of 56.8. Fifteen had fever. Of these 39 patients, 13 patients lost clinically inactive disease status while on the optional alternative dosing schedule. In these 13 patients, the time to loss of inactive disease status ranged from 1.4 to 16.8 months from initiation of the optional alternative dosing schedule (n = 4 on 3‐week dosing; n = 6 on 4‐week dosing; n = 3 off TCZ). Risk for losing inactive disease status on the optional alternative dosing schedule was similar in patients treated with methotrexate (6/16, 37.5% flared) and in those not treated with methotrexate (7/23, 30.4% flared). Inactive disease status was maintained in 26 of the 39 patients entering the optional alternative dosing schedule. Dosing intervals were every 3 weeks in 3 patients and every 4 weeks in 14 patients; 9 patients have been able to discontinue TCZ (range of time since discontinuation: 3.6–13.4 months). At baseline, these 9 patients were clinically similar to other patients entering the optional alternative dosing schedule (mean characteristics: age 9.1 years, 10.9 active joints, 10.9 joints with limitation of motion, physician global VAS score of 45.4, CHAQ‐DI score of 1.4, ESR of 47.2; 4 patients with fever at baseline).Conclusion:Patients with sJIA who maintain clinically inactive disease status can progressively space TCZ infusions, with one‐fourth of them able to discontinue all treatments, including TCZ.
A26: Longitudinal Disease Trajectory of Juvenile Dermatomyositis
Authors: Hoon Lim Lily Siok , Pullenayegum Eleanor , Gladman D. D. , Silverman Earl D. , Feldman Brian M. 
Published: March 2014

Background/Purpose:1) To determine the longitudinal disease activity trajectory of an inception cohort of Juvenile Dermatomyositis (JDM) patients, 2) To identify predictor(s) for longitudinal disease activity trajectory of JDM.Methods:A single‐center, inception cohort of juvenile dermatomyositis (JDM) patients (age of diagnosis <18 years old), recruited within 1 year of their initial presentation was studied. The patients were accrued from January 1991 to December 2010, in a JDM subspecialty clinic. Patients were evaluated at every clinic visit for disease activity with the modified Disease Activity Score (mDAS). Baseline disease features–DASm, swallowing difficulty, skin ulcer, calcinosis, duration of symptoms before evaluation, age and gender–were evaluated as predictors of the longitudinal trajectory of JDM. Time‐varying treatment effects were also tested. Longitudinal trajectory modeling was performed with mixed random effects modeling (random slopes).Results:Ninety‐five JDM patients (33 males, 35%) were studied. The median age of onset was 7.8 (25th–75th percentile (P): 4.9–12.1) years. The median mDAS score at presentation was 7 (25th–75th P: 6–9), the median skin subscale score was 3 (25th–75th P: 2–4), the median musculoskeletal subscale was 4 (25th–75th P: 3–6). The median duration of follow‐up was 4.6 (25th–75th P: 2.4–6.9) years. All patients in the cohort were treated with a standardized protocol comprising prednisone alone (before 2000) or methotrexate (MTX) and prednisone (after 2000). The disease trajectory of mDAS in this inception cohort followed a rapid reduction of activity within the first 2 years with a minor flare in disease activity beyond 2 years. Baseline nailfold abnormality predicted a slower improvement in mDAS trajectory. Higher baseline mDAS predicted faster improvement in mDAS trajectory. Treatment with MTX and prednisone predicted reductions in disease activity 3 and 6 months later respectively.Conclusion:Disease activity trajectory of JDM showed a general rapid reduction of mDAS followed by a small flare of disease activity beyond 2 years. Baseline nailfold abnormality and mDAS predicted future evolution of disease trajectory. The effects of treatment were observed only 3–6 months after.
A37: Children with Small Joint Oligoarticular Onset Juvenile Idiopathic Arthritis Are More Likely to Develop Extended Arthritis
Authors: Barbar‐Smiley Fatima , Thompson Susan D. , Higgins Gloria C. 
Published: March 2014

Background/Purpose:Oligoarticular (oligo) onset juvenile idiopathic arthritis (JIA) is defined as 4 or fewer affected joints within 6 mo of disease onset. This JIA subtype typically involves large joints. Patients who develop arthritis in >4 joints after the first 6 mo are considered to have extended oligo JIA, and have a worse prognosis. Patients with polyarticular (poly) onset JIA, defined 5 or more affected joints within 6 mo of disease onset, overall have a poorer prognosis than either oligo or extended oligo JIA patients. Poly onset JIA typically involves small joints such as joints of the fingers and toes. It has not been previously determined whether oligo onset JIA patients with small joint involvement are more likely to develop extended oligo JIA. The objective of this study was to compare the incidence of extended oligo JIA between oligo JIA patients with only small versus only large joint involvement at disease onset.Methods:We conducted a retrospective cohort study comparing patients with oligo onset JIA with only small joint (n=24) versus only large joint involvement (n= 47). All patients from our clinic from 2006–2013 with only small joint oligo JIA in the first 6 months of disease were included in the cohort. Because of the rarity of such patients, we also included small joint oligo onset JIA patients from a multicenter JIA genomics study based at Cincinnati Children's Hospital Medical Center. The large joint group was randomly selected from our clinic population of oligo JIA patients with only large joint involvement in the first 6 mo. The two groups were compared using the Wilcoxon rank sum test for continuous variables and Pearson's Chi‐square test or Fisher's exact test for categorical variables.Results:9 out of 24 (37.5%) patients with oligo onset JIA involving only small joints developed extended arthritis (>4 joints), compared to 3 out of 47 (6.38%) of patients with only large joint oligo onset JIA [p = 0.002]. Although not statistically significant, there was a trend towards female gender in the small joint group [79% females in the small joint only group, and 57% females in the large joint only group; P = 0.07], and in length of follow up with a mean of 71 months in the small joint group (median: 65, range 12–183 months) and 53 months in the large joint group (median: 45, range 9–165 months) [P = 0.07]. There was no statistically significant difference in percent of patients with positive ANA or mean age of onset between the two groupsConclusion:Patients with oligo onset JIA involving only small joints are more likely to develop extended arthritis. These patients may warrant more aggressive early treatment compared to their peers with large joint oligo onset JIA. Further studies with a larger cohort are needed before changes to treatment approaches can be recommended. The heterogeneity demonstrated within oligo onset JIA highlights the limitations of the current JIA subtype classification criteria.
A48: Durometer Measures Discriminate Affected versus Normal Skin in Pediatric Localized Scleroderma
Authors: Poff Sarah , Li Suzanne C. , Kelsey Christina , Foeldvari Ivan , Torok Kathryn S. 
Published: March 2014

Background/Purpose:Localized scleroderma (LS) is an autoimmune, inflammatory disease of the skin and subdermal tissues, resulting in fibrosis and atrophy. Outcomes are monitored by scoring signs of inflammation and damage to compose the LS cutaneous assessment tool (LoSCAT). The utility of skin scoring is limited by the need for training and ongoing practice and its inherent subjectiveness. Establishing an objective, simple, measure of skin disease would facilitate standardized outcomes for multicenter studies. One component of the LoSCAT is skin thickness (ST), graded by the clinician using the Rodnan Skin Score (0–3 ST). A surrogate for ST is skin hardness, which can be measured by a tool called a durometer, in durometer units. Among adults with systemic sclerosis, the durometer is a valid measure of skin hardness with high intra– and inter–rater reliability, correlation to skin scores, and sensitivity to change over time. This study was undertaken to examine the validity of the durometer as a measure of disease in pediatric LS.Methods:Patients from two separate clinics who attended regular appointments for LS were eligible to participate. After consent, durometer measures were taken of a single LS lesion, the “study lesion,” as well as an area of normal skin, typically in a contralateral location. Measures were taken in triplicate on either edge of the study lesion and normal skin and at approximately 1cm intervals from edge to edge. Durometer readings were repeated at up to 5 follow–up visits. The highest durometer reading from the study lesion and corresponding normal skin at each patient's initial visit was used for statistical analysis. Affected and unaffected skin was compared using a paired sample t–test. At each visit concurrent standardized clinic outcome measures were obtained, including the LoSCAT.Results:Seventeen patients were included in the analysis; most were female (76%) and Caucasian (88%) with a linear subtype of LS (41%). Mean age was 13.5 yrs old during the study and 9.0 yrs old at the onset of disease. Seven patients had study lesions on the chest or back, 2 on the abdomen, and 8 on the limbs. Analysis revealed a significant difference between durometer measures of affected and unaffected skin with a p–value of <0.001. The median durometer reading was 40 (IQR: 25–48) for study lesions and 19.5 (IQR: 12.75–29) for normal skin. An upward trend was seen for durometer measures of study lesions with increasing ST scores (see figure) imageConclusion:Among pediatric patients with LS the durometer serves as an objective measure of skin hardness, discriminating affected versus unaffected skin on the trunk and limbs. This tool may serve as a surrogate for ST, though further analysis is needed to examine its sensitivity to change over time. A larger study would be helpful to further correlate durometer ranges with ST scores.
A49: Intra‐Articular Corticosteroids Injections in the Lower Extremities: How Do Ankles Respond?
Authors: Proulx‐Gauthier Jean‐Philippe , LeBlanc Claire , ChéAaedeville GaëAdelle 
Published: March 2014

Background/Purpose:Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in childhood. Intra‐articular corticosteroids injections (IAS) are a safe and effective therapeutic option for affected children. The response of the ankle joint to IAS is thought to be less favourable than other joints. To date, little evidence is available to support this observation and there is insufficient research evaluating the response of the ankle compared to other joints of the lower extremities.Methods:JIA patients 0–18 years old followed at the Montreal Children's Hospital undergoing IAS (blindly or with fluoroscopy) in the lower extremities from January 1st 2005 to December 30th 2012 were included in a retrospective cohort study. Data obtained through chart review encompassed demographics, IAS method, and response to IAS. Response was evaluated at 6 weeks, 3 months, 6 months, 12 months and 24 months post‐procedure. Patients without available data for at least 3 months following intervention were excluded. Non‐response to IAS was determined within the first 3 months after IAS. Time to flare was assessed in subsequent visits up to 24 months.Results:Data from 70 patients included in our study are presented. Median age at diagnosis was 4.7 years with 64% affected with oligoarthritis and 69% of female gender. Median age at the time of IAS was 7.8 years. Triamcinolone hexacetonide was administered in 98% of cases. IAS were performed in 97 knees, 50 ankles and 20 subtalar joints. At 3 months post IAS, 34.0% of ankles, 15.0% of subtalar joints and 11.3% of knees failed to demonstrate a clinical response. The median time to flare after IAS was 7.7 months for the ankles, 7.8 months for the subtalar joints and 8.1 months for the knees. Only two patients developed a complication (subcutaneous atrophy).Conclusion:To date, we report a higher rate of non‐response following blind IAS ankle injections compared to other lower extremities joints. Future analysis of the entire cohort will assess the factors associated with a non‐response to IAS as well as the factors associated with a longer duration of remission. Our findings may reflect inaccurate needle placement and/or non‐treatment of associated tenosynovitis and suggest the need to modify the approach to IAS in the ankles by performing ultrasound‐guided injections to improve outcomes.
A65: Procedural Pain with Weekly Injections of Subcutaneous Methotrexate in Children with Rheumatic Disorders
Authors: Bechard Melanie , Lemieux Julie , Roth Johannes , Watanabe Duffy Karen , Duffy Ciaran M. , Aglipay Mary , Barrowman Nick , Jurencak Roman 
Published: March 2014

Background/Purpose:Procedural pain may have long‐term negative effects on children. The aim of this study was to evaluate the amount of pain associated with weekly subcutaneous injections of methotrexate.Methods:A prospective observational cohort study was conducted from June 2013 through August 2013. All patients with appointments in rheumatology clinic during this period were screened for eligibility. Patients between the ages of 4\N17 years who were currently receiving weekly subcutaneous methotrexate injections for at least 4 weeks were invited to participate in the study. Patients and families underwent a focused interview, conducted by one interviewer, exploring their experience with methotrexate injections. Thereafter, they were trained to use the Faces Pain Scale\NRevised (FPS‐R) tool to be able rate pain associated with future methotrexate injections. Associations between pain scores and age, duration of therapy, and presence of side effects were tested using simple and multiple linear regression.Results:41 out of 42 eligible patients consented to the study. Four patients were switched from subcutaneous to oral route of methotrexate at the time of study enrolment. Of the remaining 37 patients, 29 (78%) returned the completed pain scales. The mean age was 11.2 years (SD = 3.9 years) and 68% were female. Most of these patients were diagnosed with JIA (73%). Mean duration of therapy with subcutaneous injections of methotrexate was 2.5 years (SD = 2.1 yrs) and the dosing range was 0.3–1 mg/kg/week (maximum 25 mg/week). The upper arm was the preferred injection site in 71% of patients. Median amount of pain in the subset of 29 patients was 2/10; 18 (62%) patients reported mild pain (FPS‐R score 0–2), 9 (31%) reported moderate pain (FPS‐R score 4–6) and 2 participants reported severe pain (FPS‐R 8–10). In univariate testing, higher intensity of pain was associated with presence of side effects (p = 0.004), but not duration of therapy (p = 0.20) or age (p = 0.24). Results were largely unchanged in multiple linear regression. Injection pain was successfully alleviated by ice in 10/14 patients (71%), comfort positions in 14/21 patients (67%), rewards in 13/20 patients (65%), reassurance in 11/22 patients (50%), distraction in 10/21 patients (48%), and analgesics in 4/9 patients (44%).Conclusion:While the average amount of pain associated with subcutaneous injections of methotrexate is mild, patients who suffer from methotrexate associated side‐effects report significantly higher levels of pain. Patients and families reported using various effective strategies to alleviate injection associated pain.
A73: A Comparison of Serologic Profiles of Children With Sjögren Syndrome Based on the Presence or Absence of Parotitis
Authors: Mehta Jay , Yokogawa Naoto , Lieberman Scott 
Published: March 2014

Background/Purpose:Sjögren syndrome is a complex autoimmune disease that affects lacrimal and salivary glands along with the potential to cause damage to other organs. Diagnosis of childhood Sjögren syndrome is currently based on expert opinion due to the lack of child‐specific diagnostic criteria. Children do not typically present with the sicca symptoms characteristic of adult Sjögren syndrome. While they most commonly present with recurrent parotitis, some children present with other organ involvement in the absence of parotitis. The latter may be severe requiring more extensive immunomodulatory therapy. The goal of this study was to compare serologic profiles of cohorts of children with Sjögren syndrome presenting with or without parotitis to determine if separate serology‐based diagnostic criteria are needed for these two groups.Methods:We retrospectively reviewed childhood Sjögren syndrome cases from a single center as well as those in the published English literature with individual patient data. We collected available data on sicca symptoms, serologies (ANA, anti‐SSA/B, RF), lacrimal and salivary gland function, imaging, and histopathology. For analyses of individual components, cases were excluded if specific data was not explicitly reported, so denominators may vary.Results:We identified 26 cases of childhood Sjögren syndrome diagnosed and followed at The Children's Hospital of Philadelphia and 67 cases in the literature that contained information on individual children. Parotitis status was reported for 82 cases and was a main feature of presentation in 59 (72%) cases. 28 of 51 (55%) children with parotitis and 13 of 22 (59%) children without parotitis presented with sicca symptoms. 53 of 58 (91%) children with parotitis and 21 of 23 (91%) children without parotitis were ANA positive. 49 of 58 (84%) children with parotitis and 20 of 23 (87%) children without parotitis were anti‐SSA/B positive. 42 of 51 (82%) children with parotitis and 7 of 13 (54%) children without parotitis were RF positive. 56 of 58 (97%) children with parotitis and 22 of 23 (96%) children without parotitis were positive for either ANA or anti‐SSA/B.Conclusion:A large majority (96%) of children with Sjögren syndrome have positive ANA and/or anti‐SSA/B, and the serologic profiles do not significantly differ based on the presence or absence of parotitis. Thus, testing for ANA and anti‐SSA/B is warranted in the diagnostic workup of any child suspected of having Sjögren syndrome, especially in patients who do not present with parotitis. Given the selection bias inherent in this approach, development of childhood Sjögren syndrome‐specific diagnostic criteria are needed for future prospective studies to better characterize the prognosis and optimal therapies for this potentially devastating disease.
A85: Effect of Childhood‐Onset Systemic Lupus Erythematosus on Linear Height and Body Mass Index
Authors: Hersh Aimee O. , Son Mary Beth , von Scheven Emily 
Published: March 2014

Background/Purpose:To explore the relationship between childhood‐onset systemic lupus erythematosus (SLE) and anthropomorphic measures including linear height and body mass index (BMI).Methods:Cross‐sectional data were obtained from the CARRAnet registry, a United States pediatric rheumatology database. Subjects included in the database were diagnosed with SLE at ≤18 years of age and were ≤ age 21 at enrollment. Subject height and BMI at registry entry were recorded and compared with the US Centers for Disease Control and Prevention standardized growth charts for age and sex in order to obtain the appropriate percentiles. A history of renal disease was defined by a prior history of a renal biopsy. Chi squared testing was used to examine associations between height and BMI percentiles and history of renal disease and daily, chronic steroid use.Results:Data from 834 subjects were analyzed. Median age of onset was 12.3 years (range 0.88–17.32 years), median age at baseline was 15.5 years (range 3.1–20.4 years); 84% were female. Race/ethnicities included African American (35%), Caucasian (48%), Hispanic/Latino (27%), Asian (12%) and other (5%). The mean height percentile for the entire cohort was 40% (SD ± 30.6) with a median height percentile of 35% (range 1–100). Twenty one percent of the cohort (n = 174) had a height percentile of <10%. Mean height percentiles by age group at registry entry were as follows: <11 years (n = 67), 42%; 11–14 years (n = 159), 43% and >14 years (n = 608), 40%. In univariate analysis, height was not associated with a history of renal disease or long term daily steroid exposure. The mean BMI percentile was 69% (SD ± 38), median percentile was 78% (range 1–100). One‐third of the cohort (n = 276) had a BMI percentile of ≥90%. In univariate analysis, a BMI of ≥90% was associated with renal disease (p = 0.016) but not long term daily steroid exposure.Conclusion:In this large cohort of subjects with childhood‐onset SLE, average height was reduced and BMI was increased as compared to the general population. Longitudinal studies of this population are needed to assess change in height and BMI over time, and to determine the impact of age of disease onset, disease activity and treatment on these important anthropomorphic measures.