Demographic, clinical, and treatment characteristics of the juvenile primary fibromyalgia syndrome cohort enrolled in the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

BackgroundTo describe the demographic, clinical, and treatment characteristics of youth diagnosed with juvenile primary fibromyalgia syndrome (JPFS) who are seen in pediatric rheumatology clinics.MethodsInformation on demographics, symptoms, functioning, and treatments recommended and tried were obtained on patients with JPFS as part of a multi-site patient registry (the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry). Data were summarized using descriptive statistics. In a subset of patients completing registry follow-up visits, changes in symptoms, pain, and functioning were evaluated using growth modeling.ResultsOf the 201 patients with JPFS enrolled in the registry, most were Caucasian/White (85%), non-Hispanic (83%), and female (84%). Ages ranged from 9 to 20 years (M = 15.4 + 2.2). The most common symptoms reported were widespread musculoskeletal pain (91%), fatigue (84%), disordered sleep (82%), and headaches (68%). Pain intensity was rated as moderate to severe (M = 6.3 + 2.4/10). Scores on measures of functioning indicated mild to moderate impairment, with males observed to report significantly greater impairments. For the 37% of the initial cohort having follow-up data available, indicators of function and well-being were found to either worsen over time or remain relatively unchanged.ConclusionsThe symptoms of JPFS remained persistent and disabling for many patients treated by pediatric rheumatologists. Further study appears warranted to elucidate gender differences in the impact of JPFS symptoms. Work also is needed to identify accessible and effective outpatient treatment options for JPFS that can be routinely recommended or implemented by pediatric rheumatology providers

Comorbidities and Treatments in United States Youth with Chronic Musculoskeletal Pain

Introduction: Chronic musculoskeletal (MSK) pain has been associated with chronic illnesses and high rates of pain medication use, often in referral centers, European populations, or studies focused on single drug classes. We aimed to characterize patterns of comorbidities and treatments associated with chronic MSK pain in a nationally-representative sample of US youth. Methods: We used the National Ambulatory Medical Care Survey (2002-2015) and National Hospital Ambulatory Medical Care Survey (2002-2011), which contain cross-sectional data for US outpatient visits. The study included all visits for youth age 8-24, excluding those with malignancy or sickle cell disease. We compared comorbidities and drugs ordered in visits for chronic MSK pain with (1) visits for any reason besides MSK pain and (2) visits for acute MSK pain, using chi-square tests and logistic regression, adjusting for several covariates. Results: Chronic non-psychiatric diseases were more common among visits for chronic MSK pain (32.0%) in comparison to both visits for acute MSK pain (17.9%) and visits for other reasons (18.8%). Nonsteroidal anti-inflammatories were less commonly ordered at visits for chronic MSK pain in comparison to acute MSK pain (adjusted odds ratio [aOR]: 0.63, 95% CI 0.50-0.80). Opioids, gabapentinoids, and alternative medicine were each ordered more commonly at visits for chronic MSK pain in comparison to visits for acute MSK pain and other visits. Conclusion: US youth with chronic MSK were more likely to have chronic non-psychiatric medical conditions compared to youth without pain. Additionally, opioids, gabapentinoids, and alternative medicine were ordered more often in chronic MSK visits, which warrants further study

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

The Effect of BAFF Inhibition on Autoreactive B-Cell Selection in Murine Systemic Lupus Erythematosus

Abstract The goal of this study was to determine how B-cell-activating factor of the TNF family (BAFF) availability influences selection of the autoreactive B-cell repertoire in NZB/W and NZW/BXSB lupus-prone mice bearing the site-directed heavy-chain transgene 3H9 that encodes for anti-dsDNA and anti-cardiolipin (CL) autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild-type cells and could be identified by green fluorescent protein. The light-chain repertoire associated with the 3H9 heavy chain in naive and antigen-activated B-cell subsets was assessed using single-cell polymerase chain reaction. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability, and there were only modest and physiologically non-relevant effects on the naive B-cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9-encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain, BAFF inhibition did not alter the selection of 3H9-encoded B cells in the germinal center, but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B-cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans

Spleen cell phenotype in NZW/BXSB^TLR7-/Yaa mice (n = 10) and WT littermates (n = 5): A: T cell, B cell and dendritic cell percentages. CD4, CD8, CD19 and CD11B subsets are shown as a percentage of the parental cell type. B: Total spleen cell numbers of T cells, B cells and dendritic cell total numbers. Note the decrease in activated (CD69⁺) and effector/memory (CD44⁺/CD62L^-) CD4 T cells, activated (CD69⁺) B cells and dendritic cells in the TLR7^-/Yaa mice. C: B cell subsets as a percentage of spleen lymphocytes. D: Total B cell numbers per spleen. Note the decrease in follicular and class switched B cells and the preservation of T2 cells in the NZW/BXSB^TLR7-/Yaa mice. * p < 0.05, † p < 0.01.

<p>Spleen cell phenotype in NZW/BXSB^TLR7-/Yaa mice (n = 10) and WT littermates (n = 5): A: T cell, B cell and dendritic cell percentages. CD4, CD8, CD19 and CD11B subsets are shown as a percentage of the parental cell type. B: Total spleen cell numbers of T cells, B cells and dendritic cell total numbers. Note the decrease in activated (CD69⁺) and effector/memory (CD44⁺/CD62L^-) CD4 T cells, activated (CD69⁺) B cells and dendritic cells in the TLR7^-/Yaa mice. C: B cell subsets as a percentage of spleen lymphocytes. D: Total B cell numbers per spleen. Note the decrease in follicular and class switched B cells and the preservation of T2 cells in the NZW/BXSB^TLR7-/Yaa mice. * p < 0.05, † p < 0.01.</p

Attenuated disease in NZW/BXSB ^TLR7-/Yaa males.

<p>A: Titers of IgG anti-CL antibodies were lower in NZW/BXSB^TLR7-/Yaa males (grey) compared with their WT littermates (black). B: Autoantibody secreting cells (ASC) were decreased in NZW/BXSB^TLR7-/Yaa males (grey) compared with their WT littermates (black). B, C: NZW/BXSB^TLR7-/Yaa males had a delay in onset of proteinuria (C) and an improved survival (D) compared with their WT littermates or historical male controls. * p < 0.05, † p < 0.01, ‡ p<.001.</p