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BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.

BackgroundMagnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear.ObjectiveWe examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD).DesignThis prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants.ResultsBaseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with

Obese (OB) youth demonstrate altered knee mechanics and worse lower-extremity performance compared with healthy weight (HW) youth. Our objectives were to compare sagittal plane knee landing mechanics between OB and HW youth and to examine the associations of knee and hip extension peak torque with landing mechanics in OB youth. Twenty-four OB and 24 age- and sex-matched HW youth participated. Peak torque was measured and normalized to leg lean mass. Peak knee flexion angle and peak internal knee extension moment were measured during a single-leg hop landing. Paired t tests, Pearson correlation coefficients, and Bonferroni corrections were used. OB youth demonstrated worse performance and lower knee extension (OB: 12.76 [1.38], HW: 14.03 [2.08], P =.03) and hip extension (OB: 8.59 [3.13], HW: 11.10 [2.89], P =.005) peak torque. Furthermore, OB youth demonstrated lower peak knee flexion angles (OB: 48.89 [45.41 to 52.37], HW: 56.07 [52.59 to 59.55], P =.02) and knee extension moments (OB: −1.73 [−1.89 to −1.57], HW: −2.21 [−2.37 to −2.05], P =.0001) during landing compared with HW youth. Peak torque measures were not correlated with peak knee flexion angle nor internal knee extension moment during landing in either group (P >.01). OB youth demonstrated altered landing mechanics compared with HW youth. However, no associations among peak torque measurements and knee landing mechanics were present. [ABSTRACT FROM AUTHOR]

Objective: Polyautoimmunity (PA) with systemic lupus erythematosus (SLE) is reported as a poor prognostic factor, but little is known about its effect in childhood-onset SLE (cSLE). We describe PA in cSLE within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry and evaluate its association to lupus disease outcomes. Methods: CARRA Legacy Registry is the largest pediatric rheumatology registry that collected data at enrollment and every 6 months thereafter. We describe the co-occurrence of selected autoimmune disorders (autoimmune thyroid diseases, autoimmune hepatitis, celiac disease and type 1 diabetes mellitus) in cSLE. To assess outcomes, we studied measures of lupus disease activity, complications, and patient's quality of life (QoL). Comparisons by PA status were made using chi-square, Fisher's exact test, two-sample t-tests, Wilcoxon rank sum tests, and mixed effects models as appropriate. Results: 1285 patients met the American College of Rheumatology criteria for SLE. Of those, 388 (30%) had data on comorbidity. The prevalence of PA was 8.8%. Patients with PA reported more hospitalizations and aggressive immunotherapy use. SLEDAI and PGA scores improved over time, but did not differ by PA status. No significant differences were found in QoL measures or their trajectory over time by PA status. Conclusion: In cSLE, PA is associated with more hospitalizations and aggressive immunotherapy use. Although lupus disease activity improved over time, patients' QoL neither improved over time nor differed by having other autoimmune disease. Prospective, case-control, long-term follow-up studies on cSLE are needed to validate our results. MeSH Key Indexing Terms: Pediatric systemic lupus erythematosus; Autoimmune diseases; Outcome assessment [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the longitudinal effects of metabolic and bariatric surgery (MBS) on the prevalence of musculoskeletal and lower extremity (LE) pain, physical function, and healthrelated quality of life. METHODS: The Teen Longitudinal Assessment of Bariatric Surgery study (NCT00474318) prospectively collected data on 242 adolescents undergoing MBS at 5 centers over a 3-year follow-up. Joint pain and physical function outcomes were assessed by using the Health Assessment Questionnaire Disability Index, Impact of Weight on Quality of Life -- Kids, and the Short Form 36 Health Survey. Adolescents with Blount disease (n = 9) were excluded. RESULTS: Prevalent musculoskeletal and LE pain were reduced by 40% within 12 months and persisted over 3 years. Adjusted models revealed a 6% lower odds of having musculoskeletal pain (odds ratio = 0.94, 95% confidence interval: 0.92-0.99) and a 10% lower odds of having LE pain (odds ratio = 0.90, 95% confidence interval: 0.86-0.95) per 10% reduction of BMI. The prevalence of poor physical function (Health Assessment Questionnaire Disability Index score >0) declined from 49% to <20% at 6 months (P < .05), Physical comfort and the physical component scores, measured by the Impact of Weight on Quality of Life -- Kids and the Short Form 36 Health Survey, improved at 6 months postsurgery and beyond (P < .01). Poor physical function predicted persistent joint pain after MBS. CONCLUSIONS: Joint pain, impaired physical function, and impaired health-related quality of life significantly improve after MBS. These benefits in patient-reported outcomes support the use of MBS in adolescents with severe obesity and musculoskeletal pain and suggest that MBS in adolescence may reverse and reduce multiple risk factors for future joint disease. [ABSTRACT FROM AUTHOR]

The associations among lower extremity functional performance and quality of life in obese youth are unknown. The aims of this study were to compare lower extremity strength, lower extremity functional performance, and health related quality of life between obese and healthy-weight youth and evaluate the relationships between lower extremity performance and health related quality of life in obese youth. Twenty obese and 20 age and sex matched healthy-weight youth were recruited. Peak torque of the major lower extremity muscles were measured. Functional performance was measured with single leg hop and single leg balance tests. The Paediatric Quality of Life questionnaire's physical and psychosocial health subscales were used. Paired t-tests and multiple regression analyses were performed. Obese youth demonstrated decreased peak torque in all muscles measured (P < 0.05), poorer functional performance (P < 0.05), and worse physical health related quality of life (P < 0.05) compared to healthy-weight youth. Lower extremity functional performance was associated with aspects of quality of life in the obese group (P = 0.002), but not in the healthy-weight group (P < 0.05). These results may assist in encouraging best practices in the promotion of exercise, physical activity, and quality of life in obese youth. [ABSTRACT FROM AUTHOR]

Objectives To estimate the incidence of systemic-onset juvenile idiopathic arthritis (SoJIA) within 6 months after treatment for presumed Kawasaki disease (KD) (presumed patients with KD with subsequent diagnosis of SoJIA [pKD/SoJIA]) and describe presentation differences from sole KD. Study design We identified patients treated for KD at Nationwide Children's Hospital and from the Pediatric Health Information System from 2009-2013. We then identified the subset of children, pKD/SoJIA, who received an International Classification of Diseases, Ninth Revision code for SoJIA and had it listed at least once 3 months after and within 6 months after KD diagnosis. Demographic characteristics, readmission rates, treatments, and complications were noted. A literature review was also performed to identify clinical, laboratory, and echocardiographic data of previously documented patients with KD later diagnosed with SoJIA. Results There were 6745 total treated patients with KD in the Pediatric Health Information System database during the study period; 10 patients were identified to have pKD/SoJIA (0.2% of cohort). Those with pKD/SoJIA were predominantly Caucasian compared with patients with KD (90% and 46.8%, respectively; P = .003). Macrophage activation syndrome was more common in patients with pKD/SoJIA than in sole patients with KD (30% and 0.30%, respectively; P < .001). Fifteen cases of pKD/SoJIA were identified by literature and chart review, 12 of whom were initially diagnosed with incomplete KD. Conclusions We reported a 0.2% incidence of pKD/SoJIA, which was associated with Caucasian race, macrophage activation syndrome, and an incomplete KD phenotype. [ABSTRACT FROM AUTHOR]

Objective: 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., Methods: A consensus meeting was held in Chicago on April 23-24, 2010, involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans that represented typical management of moderate juvenile DM. A preconference survey of CARRA, completed by 151 (56%) of 272 members, was used to provide additional guidance to the discussion., Results: Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, or experiencing medication side effects or disease complications. Of particular importance, a single consensus steroid taper was developed., Conclusion: We were able to develop consensus treatment plans that describe therapy for moderate juvenile DM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate juvenile DM., (Copyright © 2012 by the American College of Rheumatology.)