Objective. Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the ...epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. Methods. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Results. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. Conclusion. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.
As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) ...(mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R2 for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.
To describe the health and functional status of children with juvenile rheumatoid arthritis (JRA) diagnosed in the early 1990s.
Patients were obtained from the Pediatric Rheumatology Disease ...Registry, a database of patients seen in pediatric rheumatology centers across the United States. Questionnaires designed to be filled out after retrospective chart review were sent to pediatric rheumatologists caring for children diagnosed with JRA between 1992 and 1997.
We studied 703 patients -- 376 with pauciarticular onset (pauci), 232 with polyarticular onset (poly), and 95 with systemic onset JRA (systemic). At 1 year after diagnosis, half of the pauci and systemic patients no longer required medication, compared to 78% of the poly patients; 98% of the patients functioned in Steinbrocker classes I and II. Six percent of pauci, 27% of poly, and 11% of systemic patients had limitations in school function. Nearly 1/3 of poly patients already had joint space narrowing on radiograph. By 5 years after diagnosis, all pauci, 88% of poly, and 70% of systemic patients were in Steinbrocker classes I and II; but 6% of pauci, 28% of poly, and 44% of systemic patients had limitations in school function. Nearly 2/3 of poly and systemic patients had joint space narrowing.
In these children treated prior to the era of biologic therapy, at 5 years after onset, > 25% of poly and nearly half of systemic patients had functional limitations that required modifications in their school schedule. Radiographically evident joint space damage was seen within a year of onset in poly patients, and by 5 years 2/3 of poly and systemic patients had damage.
Human populations are endowed with a sophisticated genetic diversity of complement
C4
and its flanking genes
RP,
CYP21,
and
TN
X
in the RCCX modules of the major histocompatibility complex class III ...region. We applied definitive techniques to elucidate (
a) the complement
C4 polymorphisms in gene sizes, gene numbers, and protein isotypes and (
b) their gene orders. Several intriguing features are unraveled, including (1) a trimodular RCCX haplotype with three long
C4 genes expressing C4A protein only, (2) two trimodular haplotypes with two long (L) and one short (S)
C4 genes organized in LSL configurations, (3) a quadrimodular haplotype with four
C4 genes organized in a SLSL configuration, and (4) another quadrimodular structure, with four long
C4 genes (LLLL), that has the human leukocyte antigen haplotype that is identical to ancestral haplotype 7.2 in the Japanese population. Long-range PCR and
PshAI-RFLP analyses conclusively revealed that the short genes from the LSL and SLSL haplotypes are
C4A. In four informative families, an astonishingly complex pattern of genetic diversity for RCCX haplotypes with one, two, three and four
C4 genes is demonstrated; each
C4 gene may be long or short, encoding a C4A or C4B protein. Such diversity may be related to different intrinsic strengths among humans to defend against infections and susceptibilities to autoimmune diseases.
Objective
To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)–positive or RF‐negative polyarticular juvenile idiopathic arthritis (JIA) can induce ...clinical inactive disease within 6 months.
Methods
Between May 2007 and October 2010, a multicenter, prospective, randomized, double‐blind, placebo‐controlled trial of 2 aggressive treatments was conducted in 85 children ages 2–16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months.
Results
By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ2 = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events.
Conclusion
Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent‐onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.
Pediatric-onset mixed connective tissue disease Mier, Richard J; Shishov, Michael; Higgins, Gloria C ...
Rheumatic diseases clinics of North America,
08/2005, Letnik:
31, Številka:
3
Journal Article
Recenzirano
This article discusses the literature on pediatric-onset mixed connective tissue disease (MCTD) and adds 34 new cases. Although not benign, pediatric-onset MCTD carries less mortality than ...adult-onset disease.
Cultured dermal fibroblasts from systemic sclerosis patients express higher levels of intracellular IL-1 alpha than fibroblasts from healthy controls. In this study, we found that systemic sclerosis ...dermal fibroblasts also express higher levels of the intracellular isoform of IL-1 receptor antagonist (icIL-1Ra) than normal fibroblasts after stimulation with IL-1 beta or TNF-alpha. A possible relationship between elevated precursor IL-1 alpha (preIL-1 alpha) and elevated icIL-1Ra was investigated by transducing normal dermal fibroblasts to overexpress preIL-1 alpha, preIL-1 beta, or icIL-1Ra. Fibroblasts that overexpressed icIL-1Ra did not have elevated levels of IL-1 alpha. On the other hand, fibroblasts that overexpressed preIL-1 alpha had at least 4-fold higher basal levels of icIL-1Ra than control fibroblasts and 4-fold higher levels of icIL-1Ra after induction with IL-1 beta or TNF-alpha. Fibroblasts overexpressing preIL-1 beta did not exhibit elevated icIL-1Ra. The differences in icIL-1Ra protein levels were reflected in differences in mRNA. In contrast, IL-1-stimulated levels of MCP-1 and IL-6 were not different in control and preIL-1 alpha-transduced fibroblasts. Addition of neutralizing anti-IL-1 alpha Abs to fibroblast cultures did not diminish basal or stimulated levels of icIL-1Ra in the preIL-1 alpha-transduced cells, supporting an intracellular site of action of preIL-1 alpha. This is the first report of an association between intracellular levels of these IL-1 family members. We hypothesize that intracellular preIL-1 alpha participates in the regulation of icIL-1Ra.
We report a child with persistent fevers, arthritis, and parvoviral infection who subsequently developed unilateral orbital pseudotumor, lytic bone lesions, bilateral anterior uveitis, band ...keratopathy, and migratory polyarthritis. Our working diagnosis was systemic-onset juvenile rheumatoid arthritis, although pseudotumor of the orbit and lytic bone lesions are not found in this disease.
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