Meta‐analysis: rapid infliximab infusions are safe

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99086/1/apt12389.pd

Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis

Abstract Background Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome. Case presentation A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation. Conclusions This is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.https://deepblue.lib.umich.edu/bitstream/2027.42/142870/1/40842_2018_Article_58.pd

Pulmonary Hypertension and Other Potentially Fatal Pulmonary Complications in Systemic Juvenile Idiopathic Arthritis

Objective Systemic juvenile idiopathic arthritis (JIA) is characterized by fevers, rash, and arthritis, for which interleukin‐1 (IL‐1) and IL‐6 inhibitors appear to be effective treatments. Pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and alveolar proteinosis (AP) have recently been reported with increased frequency in systemic JIA patients. Our aim was to characterize and compare systemic JIA patients with these complications to a larger cohort of systemic JIA patients. Methods Systemic JIA patients who developed PAH, ILD, and/or AP were identified through an electronic Listserv and their demographic, systemic JIA, and pulmonary disease characteristics as well as their medication exposure information were collected. Patients with these features were compared to a cohort of systemic JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. Results The patients (n = 25) were significantly ( P < 0.05) more likely than the CARRA registry cohort (n = 389) to be female; have more systemic features; and have been exposed to an IL‐1 inhibitor, tocilizumab, corticosteroids, intravenous immunoglobulin, cyclosporine, and cyclophosphamide. Twenty patients (80%) were diagnosed with pulmonary disease after 2004. Twenty patients (80%) had macrophage activation syndrome (MAS) during their disease course and 15 patients (60%) had MAS at pulmonary diagnosis. Sixteen patients had PAH, 5 had AP, and 7 had ILD. Seventeen patients (68%) were taking or recently discontinued (<1 month) a biologic agent at pulmonary symptom onset; 12 patients (48%) were taking anti–IL‐1 therapy (primarily anakinra). Seventeen patients (68%) died at a mean of 10.2 months from the diagnosis of pulmonary complications. Conclusion PAH, AP, and ILD are underrecognized complications of systemic JIA that are frequently fatal. These complications may be the result of severe uncontrolled systemic disease activity and may be influenced by medication exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97453/1/21889_ftp.pd

Evidence for Updating the Core Domain Set of Outcome Measures for Juvenile Idiopathic Arthritis: Report from a Special Interest Group at OMERACT 2016

Objective. The current Juvenile Idiopathic Arthritis (JIA) Core Set was developed in 1997 to identify the outcome measures to be used in JIA clinical trials using statistical and consensus-based techniques, but without patient involvement. The importance of patient/parent input into the research process has increasingly been recognized over the years. An Outcome Measures in Rheumatology (OMERACT) JIA Core Set Working Group was formed to determine whether the outcome domains of the current core set are relevant to those involved or whether the core set domains should be revised.Methods. Twenty-four people from the United States, Canada, Australia, and Europe, including patient partners, formed the working group. Guided by the OMERACT Filter 2.0 process, we performed (1) a systematic literature review of outcome domains, (2) a Web-based survey (142 patients, 343 parents), (3) an idea-generation study (120 parents), (4) 4 online discussion boards (24 patients, 20 parents), and (5) a Special Interest Group (SIG) activity at the OMERACT 13 (2016) meeting.Results. A MEDLINE search of outcome domains used in studies of JIA yielded 5956 citations, of which 729 citations underwent full-text review, and identified additional domains to those included in the current JIA Core Set. Qualitative studies on the effect of JIA identified multiple additional domains, including pain and participation. Twenty-one participants in the SIG achieved consensus on the need to revise the entire JIA Core Set.Conclusion. The results of qualitative studies and literature review support the need to expand the JIA Core Set, considering, among other things, additional patient/parent-centered outcomes, clinical data, and imaging data

Efficacy of an Interinstitutional Mentoring Program Within Pediatric Rheumatology.

OBJECTIVE: The small size of many pediatric rheumatology programs translates into limited mentoring options for early career physicians. To address this problem, the American College of Rheumatology (ACR) and the Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed a subspecialty-wide inter-institutional mentoring program, the ACR/CARRA Mentoring Interest Group (AMIGO). We sought to assess the impact of this program on mentoring within pediatric rheumatology. METHODS: In a longitudinal 3-year study, participant ratings from the AMIGO pilot program were compared with those after the program was opened to general enrollment. Access to mentoring as a function of career stage was assessed by surveys of the US and Canadian pediatric rheumatologists in 2011 and 2014, before and after implementation of AMIGO. RESULTS: Participants in the pilot phase (19 dyads) and the general implementation phase (112 dyads) reported comparable success in establishing mentor contact, suitability of mentor-mentee pairing, and benefit with respect to career development, scholarship, and work-life balance. Community surveys showed that AMIGO participation as mentee was high among fellows (86%) and modest among junior faculty (31%). Implementation correlated with significant gains in breadth of mentorship and in overall satisfaction with mentoring for fellows but not junior faculty. CONCLUSION: AMIGO is a career mentoring program that serves most fellows and many junior faculty in pediatric rheumatology across the US and Canada. Program evaluation data confirm that a subspecialty-wide inter-institutional mentoring program is feasible and can translate into concrete improvement in mentoring measurable at the level of the whole professional community. This article is protected by copyright. All rights reserved