Kathleen A. Haines

Neutrophil gelatinase–associated lipocalin is a predictor of the course of global and renal childhood‐onset systemic lupus erythematosus disease activity

OBJECTIVEnTo determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE).nnnMETHODSnOne hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physicians assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models.nnnRESULTSnSignificant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.nnnCONCLUSIONnSerial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity.

Initial validation of a novel protein biomarker panel for active pediatric lupus nephritis.

Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS proteins for detecting activity of LN over time. Using surface-enhanced or matrix-assisted laser desorption/ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalin-type prostaglandin-D synthetase (L-PGDS), albumin, and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African American) and 30 controls with juvenile idiopathic arthritis. All urinary PS proteins were significantly higher with active vs. inactive LN or in patients without LN (all p < 0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 mo before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001), and L-PGDS (p < 0.01) occurred, indicating that these PS proteins are biomarkers of LN activity and may help anticipate the future course of LN.

Consensus treatments for moderate juvenile dermatomyositis: Beyond the first two months. Results of the Second Childhood Arthritis and Rheumatology Research Alliance Consensus Conference

To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment.

Treatment of pediatric localized scleroderma: results of a survey of North American pediatric rheumatologists.

Objective. We surveyed pediatric rheumatologists (PR) in North America to learn how they treat pediatric localized scleroderma (LS), a disease associated with significant morbidity for the growing child. Methods. A Web-based survey was sent to the 195 PR members of the pediatric rheumatology research alliance CARRA (Childhood Arthritis and Rheumatology Research Alliance). Members were asked which medications they use to treat LS and which factors modify their treatment strategies. Clinical vignettes were provided to learn the specific treatment regimens used. Results. A total of 158 PR from over 70 clinical centers in the United States and Canada participated in the survey, representing 81% of the CARRA membership. These PR saw over 650 patients with LS in the prior year. Nearly all respondents treated LS with methotrexate (MTX) and corticosteroids; most of them intensify treatment for lesions located on the face or near a joint, and about half intensify treatment for recent disease onset (< 6 months). Most PR reserve topical medications for limited treatment situations. Clinical vignettes showed that PR use a broad range of treatment doses and durations for MTX and corticosteroids. Conclusion. Most PR in North America treat localized scleroderma with a combination of MTX and corticosteroids. However, there is no consensus on specific treatment regimens. There is a need for controlled treatment trials to better determine optimal therapy for this potentially disabling disease.

Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma.

To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U‐DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions.

Cancer risk in childhood-onset systemic lupus

IntroductionThe aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE).MethodsWe ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population.ResultsThere were 1020 patients aged <18 at cohort entry. Most (82%) were female and Caucasian; mean age at cohort entry was 12.6xa0years (standard deviation (SD)u2009=u20093.6). Subjects were observed for a total of 7,986 (average 7.8) patient-years. Within this interval, only three invasive cancers were expected. However, 14 invasive cancers occurred with an SIR of 4.7, 95% confidence interval (CI) 2.6 to 7.8. Three hematologic cancers were found (two non-Hodgkin’s lymphoma, one leukemia), for an SIR of 5.2 (95% CI 1.1 to 15.2). The SIRs stratified by age group and sex, were similar across these strata. There was a trend for highest cancer occurrence 10 to 19xa0years after SLE diagnosis.ConclusionsThese results suggest an increased cancer risk in pediatric onset SLE versus the general population. In absolute terms, this represents relatively few events. Of note, risk may be highest only after patients have transferred to adult care.

Effects of obesity on health-related quality of life in juvenile-onset systemic lupus erythematosus

Objective This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE). Methods Obesity was defined as a body mass index (BMI) ≥95th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures. Results Among the 202 jSLE patients, 25% (nu2009=u200951) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains. Conclusion Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE.

Validation of the systemic lupus erythematosus responder index for use in juvenile-onset systemic lupus erythematosus

Objectives This study tested the concurrent validity of the systemic lupus erythematosus responder index (SRI) in assessing improvement in juvenile-onset systemic lupus erythematosus (jSLE). Methods The SRI considers changes in the SELENA–SLEDAI, BILAG and a 3-cm visual analogue scale of physician-rated disease activity (PGA) to determine patient improvement. Using prospectively collected data from 760 unique follow-up visit intervals of 274 jSLE patients, we assessed the sensitivity and specificity of the SRI using these external standards: physician-rated improvement (MD-change), patient/parent-rated major improvement of wellbeing (patient-change) and decrease in prescribed systemic corticosteroids (steroid-change). Modifications of the SRI that considered different thresholds for the SELENA–SLEDAI, BILAG and 10-cm PGA were explored and agreement with the American College of Rheumatology/PRINTO provisional criteria for improvement of jSLE (PCI) was examined. Results The sensitivity/specificity in capturing major improvement by the MD-change were 78%/76% for the SRI and 83%/78% for the PCI, respectively. There was fair agreement between the SRI and PCI (kappa=0.35, 95% CI 0.02 to 0.73) in capturing major improvement by the MD-change. Select modified versions of the SRI had improved accuracy overall. All improvement criteria tested had lower sensitivity when considering patient-change and steroid-change as external standards compared to MD-change. Conclusions The SRI and its modified versions based on meaningful changes in jSLE have high specificity but at most modest sensitivity for capturing jSLE improvement. When used as an endpoint of clinical trials in jSLE, the SRI will provide a conservative estimate regarding the efficacy of the therapeutic agent under investigation.

Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions.

To develop standardized treatment regimens for chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), to enable comparative effectiveness treatment studies.

A randomized study of local anesthesia for pain control during intra-articular corticosteroid injection in children with arthritis.

BackgroundIntra-articular corticosteroid injections (IACI) are routinely used by pediatric rheumatologists in the treatment of chronic arthritis. Frequently, topical anesthetics are used to control procedural pain, but their relative efficacy has not been reported. In this study, we evaluated the level of pain associated with different anesthetic methods, Numby® 900 Iontophoretic Drug Delivery System, or EMLA® cream, with or without subcutaneous buffered lidocaine (SQBL), during IACI of the knee in children with arthritis.MethodsWe conducted a prospective study of patients, ages 4 to 21xa0years old, followed at three pediatric rheumatology centers who were undergoing IACI of a knee joint. Patients were randomized into two treatment groups: 1) topical anesthetic only (EMLA® or Numby® (E/N)), or 2) topical anesthetic (E/N) and SQBL. Pain was assessed at baseline, during topical anesthetic placement, and following the IACI (post-procedure). The Faces Pain Scale-Revised (FPS-R), the Face, Leg, Activity, Cry, Consolability (FLACC) behavioral scale and the parental global assessment (PGA) (0u2009=u2009best experience, 10u2009=u2009worst experience) were determined.ResultsSixty-three patients (44 females) with a median [IQR] age of 10.8 [IQRu2009=u2009(8.2–14.4)] years (range 4.7–20 years) with active knee arthritis were consented. FPS-R post-procedure (Pu2009=u20090.03), FLACC (Pu2009=u20090.02) and PGA (Pu2009=u20090.01) scores were significantly lower in females treated with E/N plus SQBL compared to patients treated with E/N only. Females in the E/N only group had a significant worsening of their baseline pain (pu2009<u20090.0004) and a greater magnitude of change in their baseline FPS-R scores (pu2009<u20090.001) from the procedure compared to females in the E/N plus SQBL group who had no worsening of their baseline pain. No significant change in pain level or PGA score was found among males in either treatment group. Pain scores overall were similar to the oligoarthritis patients, a more homogeneous group of patients. Both EMLA® (nu2009=u200933) and Numby® (nu2009=u200929) were equally well tolerated with no significant difference in median FPS-R administration scores overall.ConclusionOur results suggest that a topical anesthetic plus SQBL is more effective for injection pain control than topical anesthesia only. Further studies addressing pain and anxiety will help determine the optimal method of pain control for IACI.