Objective: The Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q) is a novel measure of vision-related quality of life (QOL) and function in children. We aim to determine the validity of EYE-Q in childhood uveitis.
Methods: We abstracted medical record data on arthritis and uveitis in a convenience sample of children with juvenile idiopathic arthritis (JIA) and/or uveitis. In addition to the EYE-Q, parents and patients completed questionnaires on overall QOL (Pediatric QOL Inventory - PedsQL), and physical functioning (Childhood Health Assessment Questionnaire - CHAQ).
Results: Among 57 children (8 JIA, 24 JIA and uveitis, 25 uveitis alone), 102 ocular examinations were performed within 1 month of completing questionnaires. Uveitis patients had bilateral disease (69%), anterior involvement (78%), synechiae (51%) and cataracts (49%). Children with vision loss in their better eye (visual acuity (VA) 20/50 or worse) had worse EYE-Q (p = 0.006), and PedsQL (p = 0.028), but not CHAQ scores. The EYE-Q moderately correlated with logMAR VA (rs = −0.43), PedsQL (rs = 0.43) and CHAQ (rs = −0.45), but was not correlated with anterior chamber cells or intraocular pressure. The PedsQL and CHAQ did not correlate with VA or cells. There were strong correlations between the parent and child EYE-Q (rs = 0.62). Cronbach's α for the child report was 0.91. The EYE-Q had strong test-retest reliability (rs=0.75).
Conclusion: The EYE-Q may be an important tool in the assessment of visual outcomes in childhood uveitis and an improvement over general measures in detecting changes in vision-related function.
by
Lisa G. Rider;
Rohit Aggarwal;
Angela Pistorio;
Nastaran Bayat;
Brian Erman;
Brian M. Feldman;
Adam M. Huber;
Rolando Cimaz;
Ruben J. Cuttica;
Sheila Knupp de Oliveira;
Carol B. Lindsley;
Clarissa A. Pilkington;
Marilyn Punaro;
Angelo Ravelli;
Ann M. Reed;
Kelly A. Rouster Stevens;
Annet van Royen-Kerkhof;
Frank Dressler;
Claudia Saad Magalhaes;
Tamas Constantin;
Joyce E. Davidson;
Bo Magnusson;
Ricardo Russo;
Luca Villa;
Mariangela Rinaldi;
Howard Rockette;
Peter A. Lachenbruch;
Frederick W. Miller;
Jiri Vencovsky;
Nicolino Ruperto
To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement ( p=0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p < 0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement.
by
Daniel Lovell;
Anne Johnson;
Yuki Kimura;
Steve Spalding;
Paula Morris;
Beth Gottlieb;
Karen Onel;
Judyann Olson;
Barbara Edelheit;
Michael Shisov;
Lawrence Jung;
Elaine Cassidy;
Sampath Prahalad;
Murray Passo;
Tim Beukelman;
Jay Mehta;
Kara Schmidt;
Dirk Foell;
Claas Hinze;
Bin Huang;
Edward Giannini
Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predisposition to JIA. Describing the genetics is complicated by the heterogeneity of JIA; the International League of Associations for Rheumatology (ILAR) has defined seven categories of JIA based on distinct clinical and laboratory features. Utilizing a variety of techniques including candidate gene studies, the use of genotyping arrays such as Immunochip, and genome wide association studies (GWAS), both human leukocyte antigen (HLA) and non-HLA susceptibility loci associated with JIA have been described. Several of these polymorphisms (e.g. HLA class II, PTPN22, STAT4) are shared with other common autoimmune conditions; other novel polymorphisms that have been identified may be unique to JIA.Associations with oligoarticular and RF-negative polyarticular JIA are the best characterized. A strong association between HLA DRB1:. 11:03/04 and DRB1:08:01, and a protective effect of DRB1:15:01 have been described. HLA DPB1:02:01 has also been associated with oligoarticular and RF-negative polyarticular JIA. Besides PTPN22, STAT4 and PTPN2 variants, IL2, IL2RA, IL2RB, as well as IL6 and IL6R loci also harbor variants associated with oligoarticular and RF-negative polyarticular JIA. RF-positive polyarticular JIA is associated with many of the shared epitope encoding HLA DRB1 alleles, as well as PTPN22, STAT4 and TNFAIP3 variants. ERA is associated with HLA B27. Most other associations between JIA categories and HLA or non-HLA variants need confirmation. The formation of International Consortia to ascertain and analyze large cohorts of JIA categories, validation of reported findings in independent cohorts, and functional studies will enhance our understanding of the genetic underpinnings of JIA.
Purpose of review Systemic lupus erythematosus (SLE) is the prototypic autoimmune condition, often affecting multiple organ systems, including the skin. Cutaneous lupus erythematosus (CLE) is distinct from SLE and may be skin limited or associated with systemic disease. Histopathologically, the hallmark of lupus-specific manifestations of SLE and CLE is an interface dermatitis. The cause of SLE and CLE is likely multifactorial and may include shared genetic factors. In this review, we will discuss the genetic findings related to the cutaneous manifestations of SLE and isolated CLE, with a particular focus on the lupus-specific CLE subtypes.
Recent findings Several major histocompatibility complex and nonmajor histocompatibility complex genetic polymorphisms have been identified which may contribute to the cutaneous manifestations of SLE and to CLE. Most of these genetic variants are associated with mechanisms attributed to the pathogenesis of SLE, including pathways involved in interferon and vitamin D regulation and ultraviolet light exposure. Although there is overlap between the genetic factors associated with SLE and CLE, there appear to be unique genetic factors specific for CLE.
Summary Improved understanding of the genetics of CLE may lead to the creation of targeted therapies, improving outcomes for patients with this challenging dermatologic condition.
Objectives
Juvenile idiopathic arthritis (JIA) affects children of all races. Prior studies suggest that phenotypic features of JIA in African American (AA) children differ from those of Non-Hispanic White (NHW) children. We evaluated the phenotypic differences at presentation between AA and NHW children enrolled in the CARRA Registry, and replicated the findings in a JIA cohort from a large center in South Eastern USA.
Methods
Children with JIA enrolled in the multi-center CARRA Registry and from Emory University comprised the study and replication cohorts. Phenotypic data on Non-Hispanic AA children were compared with NHW children with JIA using Chi-square, Fisher's exact and Wilcoxon rank sum tests.
Results
In all, 4177 NHW and 292 AA JIA cases from the CARRA Registry, and 212 NHW and 71 AA cases from Emory were analyzed. AA subjects more often had RF-positive polyarthritis in both CARRA (13.4% vs. 4.7%, p=5.3×10-7) and Emory (26.8% vs. 6.1%, p =1.1×10-5) cohorts. AA children had positive tests for RF and CCP more frequently, but oligoarticular or early onset ANA-positive JIA less frequently in both cohorts. AA children were older at onset in both cohorts and this difference persisted after excluding RF-positive polyarthritis in the CARRA Registry (median age 8.5 vs. 5.0 years; p =1.4×10-8).
Conclusions
Compared to NHW children, AA children with JIA are more likely to have RF/CCP positive polyarthritis, and are older at disease onset, and less likely to have oligoarticular or ANA-positive early onset JIA, suggesting that the JIA phenotype is different in African American children.
Objective
Associations between shared epitope (SE)-encoding HLA-DRB1 alleles and rheumatoid arthritis (RA) are well established but only a limited number of studies have investigated these alleles in childhood onset RA (CORA), defined as rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive juvenile idiopathic arthritis. We sought to investigate the largest cohort of CORA for association with SE alleles, and to determine whether there was a hierarchy of risk based on the amino acid sequence of the SE.
Methods
High resolution HLA-DRB1 genotypes were obtained for 204 children with CORA and 373 healthy controls. Odds ratios (OR) and 95% CI were calculated for different SE-encoding HLA-DRB1 alleles. We also calculated genotypic OR for combinations of SE alleles classified into S2, S3P or L alleles, based on amino acids in positions 70-74 of the DRβ1 chain as proposed by Tezenas Du Montcel et al (2005).
Results
We confirmed associations between HLA-DRB1 SE alleles and CORA (76% of cases versus 46% of controls; OR=3.81 (95%CI 2.4-6.0), p <1×10−7). We also found associations between individual SE alleles (HLA-DRB1*0101, *0401, *0404, *0405, *0408 and *1001) and CORA. Genotype-specific risk estimates suggested a hierarchy of risk, with the highest risk among those heterozygous for S2/S3P (OR=22.3 (9.9-50.5) p <0.0001).
Conclusions
We confirm the association between SE-encoding HLA-DRB1 alleles and susceptibility to CORA. The excess risk conferred by individuals who carry the combination of S2/S3P risk alleles suggests that children with DRβ1 chains containing KRAA and Q/RRRAA are especially prone to RA.
by
David J Cutler;
Michael Zwick;
David T. Okou;
Sampath Prahalad;
Thomas Walters;
Stephen L. Guthery;
Marla Dubinsky;
Robert Baldassano;
Wallace V. Crandall;
Joel Rosh ;
James Markowitz;
Michael Stephens;
Richard Kellermayer;
Marian Pfefferkon;
Melvin B. Heyman;
Neal LeLeiko;
David Mack;
Dedrick Moulton;
Michael D. Kappelman;
Archana Kumar;
Jarod Prince;
Promita Bose;
Kajari Mondal;
Dhanya Ramchandran;
John F. Bohnsack;
Anne M. Griffiths ;
Yael Haberman;
Jonah Essers;
Susan D. Thompson;
Bruce Aronow;
David J. Keljo;
Jeffrey S. Hyams;
Lee A. Denson;
Subra Kugathasan
The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent.
by
Esi Morgan Dewitt;
Yukiko Kimura;
Timothy Beukelman;
Peter A. Nigrovic;
Karen Onel;
Sampath Prahalad;
Rayfel Schneider;
Matthew L. Stoll;
Sheila Angeles-Han;
Diana Milojevic;
Kenneth N. Schikler;
Richard K. Vehe;
Jennifer E. Weiss;
Pamela Weiss;
Norman T. Ilowite;
Carol A. Wallace
Objective. There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies. Methods. Case-based surveys were administered to CARRA members to identify prevailing treatments for new-onset systemic JIA. A 2-day consensus conference in April 2010 employed modified nominal group technique to formulate preliminary treatment plans and determine important data elements for collection. Followup surveys were employed to refine the plans and assess clinical acceptability. Results. The initial case-based survey identified significant variability among current treatment approaches for new-onset systemic JIA, underscoring the utility of standardized plans to evaluate comparative effectiveness. We developed 4 consensus treatment plans for the first 9 months of therapy, as well as case definitions and clinical and laboratory monitoring schedules. The 4 treatment regimens included glucocorticoids only, or therapy with methotrexate, anakinra, or tocilizumab, with or without glucocorticoids. This approach was approved by > 78% of the CARRA membership. Conclusion. Four standardized treatment plans were developed for new-onset systemic JIA. Coupled with data collection at defined intervals, use of these treatment plans will create the opportunity to evaluate comparative effectiveness in an observational setting to optimize initial management of systemic JIA.