No abstract

Objective To formulate consensus treatment plans (CTPs) for induction therapy of newly-diagnosed proliferative lupus nephritis (LN) in juvenile systemic lupus erythematosus (jSLE). Methods A structured consensus formation process was employed by the members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) after considering the existing medical evidence and current treatment approaches. Results After an initial Delphi survey (response rate 70%), a 2-day consensus conference, and two follow-up Delphi surveys (response rates 63–79%), consensus was achieved for a limited set of CTPs addressing the induction therapy of proliferative LN. These CTPs were developed for prototypic patients defined by eligibility characteristics, and included immunosuppressive therapy with either mycophenolic acid orally twice per day, or intravenous cyclophosphamide once per month at standardized doses for six months. Additionally, the CTPs describe three options for standardized use of glucocorticoids; including a primarily oral, a mixed oral/intravenous, and a primarily intravenous regimen. There was consensus on measures of effectiveness and safety of the CTPs. The CTPs were well accepted by the pediatric rheumatology providers treating children with LN, and up to 300 children per year in North America are expected to be candidates for the treatment with the CTPs. Conclusion CTPs for induction therapy of proliferative LN in jSLE based on the available scientific evidence and pediatric rheumatology group experience have been developed. Consistent use of the CTPs may improve the prognosis of proliferative LN, and support the conduct of comparative effectiveness studies aimed at optimizing therapeutic strategies for proliferative LN in jSLE.

Objective. To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM). Methods. Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis. Results. Children for which both a parent interview and physician medical records at diagnosis were available (n ‫؍‬ 286) were included. Diagnoses were as follows: definite/probable JDM (n ‫؍‬ 234, 82%), possible JDM (n ‫؍‬ 43, 15%), or rash only (n ‫؍‬ 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were <4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics. Conclusion. This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.

OBJECTIVES To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and Non-Hispanic White (NHW) children. METHODS There were 3,967 NHW and AA children with JIA enrolled in the CARRA Registry. Demographic and disease-related data were collected from time of diagnosis to enrollment. Children with JIA alone were compared to those with JIA-U. Children with JIA-U were then compared by race. RESULTS Mean age of children with JIA-U was 11.4 years (±4.5), 76.9% were female and 2.8% were AA. Children with JIA-U were younger at arthritis onset, female, required more medications, had <5 joints involved, had oligoarticular JIA, and ANA (+), RF (−) and anti-CCP (−). AA children with JIA-U had decreased uveitis frequency, were older at arthritis onset and more frequently diagnosed with enthesitis-related JIA. Predictors of uveitis development include female gender, early age of arthritis onset, and oligoarticular persistent and extended JIA classification, whereas polyarticular RF-positive JIA was protective. CONCLUSIONS The prevalence of JIA-U in AA and NHW children is 11.6% in the CARRA registry. Known risk markers (ANA, age at arthritis onset, and oligoarticular JIA) were more frequent in our JIA-U cohort. AA children had a lower frequency of JIA-U. There were significant differences in age of arthritis onset and JIA subtype between NHW and AA children, although the ANA, RF and HLA-B27 were similar. Exploration of race as a risk factor should be considered.

BackgroundJuvenile idiopathic arthritis-associated uveitis (JIA-U) can lead to poor visual outcomes and impact a child’s quality of life (QOL) and function. Our aim is to identify risk markers of JIA-U and examine differences in the QOL of children with JIA and JIA-U.MethodsRheumatology and ophthalmology record reviews and questionnaires were completed every 4–6 months on 287 children with JIA. We collected arthritis, uveitis, and QOL data. We examined data through last study visit.ResultsThere were 52/287 (18 %) children with JIA-U who were younger at arthritis diagnosis, had oligoarticular persistent JIA, and ANA positive. Confirmed uveitis predictors were age at JIA diagnosis (OR = 0.86) and oligoarticular subtype (OR = 5.92). They had worse vision specific QOL and function, but similar general QOL. Blindness occurred in 17.5 % of children but was more common in African American children compared to non-Hispanic Caucasian children ((5/7 (71 %) vs. 2/29 (7 %), p <0.001) despite a similar uveitis prevalence (22 % vs. 16 %). Both races had similar complications, although band keratopathy was more frequent in African Americans (75 % vs. 15.6 %, p = 0.003).ConclusionsWe confirm young age at JIA diagnosis and the oligoarticular JIA subtype as predictors of uveitis development. Although we were unable to identify predictors of ocular complications or blindness, AA children appeared to have a more severe disease course manifested by increased ocular complications, vision loss and blindness. Potential causes that warrant additional study include underlying disease severity, access to medical care and referral bias. Further investigation of the risk factors for vision-compromising uveitis and its’ long-term effects should be conducted in a large racially diverse population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12969-015-0018-8) contains supplementary material, which is available to authorized users.

No abstract

IgA myeloma proteins of kappa- and lambda-types were isolated from two patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B-cell differentiation. Our results (a) confirm that B lymphocyte precursors in IgA plasma-cell myelomas are involved in the malignant process, (b) show that B lymphocytes of the malignant clone include those expressing each of the major heavy-chain isotypes, mu, delta, gamma, and alpha, and (c) provide strong circumstantial evidence that pre-B-cell members of the malignant clone are also increased in frequency. T cells expressing idiotypic determinants were not detected. These findings argue that the initial oncogenic event may occur in a B-stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre-B-cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. We discuss other implications of these findings and speculate that all of the various phenotypes of B-lineage malignancies may result from oncogenic processes affecting stem cell targets.

Serum S100 levels did not predict maintenance of CID or disease flare, with S100A12 levels only moderately correlating inversely with time to disease flare. This article is protected by copyright. All rights reserved.