OBJECTIVES:This study examined a wide array of clinical factors to evaluate their influence on fracture risk and T scores in women with rheumatoid arthritis (RA) and determine if women with RA who ...are at risk for osteoporosis (OP) are adequately treated with OP medications.
METHODS:Data from 8419 female RA patients participating in the Consortium of Rheumatology Researchers of North America registry from March 02, 2006 to August 15, 2006 was evaluated. Covariates included medication subgroups, demographic, and clinical parameters. Lumbar spine and hip T scores and fracture rates were studied in relation to the variables. Use of OP medications in patients with OP risk factors was also evaluated.
RESULTS:Postmenopausal status and higher modified health assessment questionnaire score (mHAQ) had a negative effect on lumbar spine score, while marriage, education, and body mass index had a positive effect. A similar trend was found with hip T scores. Increase in overall fracture risk correlated with postmenopausal status, mHAQ, and prednisone use, while tumor necrosis factor monotherapy was associated with decreased overall fracture risk. mHAQ was also associated with nonhip/nonspine fractures. Eighty percent of patients had at least 1 risk factor for OP, but only 32% were on OP medications. Only 54% of patients with 3 risk factors were on OP medication.
CONCLUSIONS:In RA, postmenopausal status, mHAQ, and prednisone use were associated with a higher overall fracture risk. Women with RA who were at risk for OP may have been inadequately treated with OP medications.
Objective To evaluate an autoantibody profile in pediatric-onset systemic lupus erythematosus (SLE) patients to determine clinical and statistical associations with disease-associated manifestations. ...Methods Sera from 53 SLE patients and 22 healthy individuals were collected. Antibodies to C1q, histone, chromatin, ribosomal P, dsDNA, and high-avidity dsDNA were measured by enzyme-linked immunosorbent assays. Patient records were evaluated for clinical and laboratory associations. Results The most prevalent autoantibodies found in the SLE cohort were anti-C1q antibodies ( n = 32, 60%), which correlated significantly with proteinuria and decreased complement levels ( P < 0.05). Anti-C1q and antihistone antibodies were significantly elevated in patients with class III/IV nephritis compared with class I/II/V nephritis ( P = 0.041). SLE patients with active nephritis at the time of sample collection demonstrated significantly elevated levels of anti-C1q antibodies compared with those without active nephritis, also exhibiting 100% sensitivity for active nephritis, proteinuria, and urinary casts. Antibodies to C1q, dsDNA, histone, and chromatin were significantly elevated in patients with active disease ( P < 0.01). Chart-documented anti-dsDNA antibodies were positive in 28 SLE patients, INOVA anti-dsDNA antibodies in 25 patients, and high-avidity anti-dsDNA antibodies in 8 patients. Antihistone correlated significantly with leukopenia and hemolytic anemia ( P < 0.05). Conclusions This study indicates the importance of measuring anti-C1q antibodies in pediatric-onset SLE patients because elevated anti-C1q antibodies may be more indicative of renal disease activity, showing significant correlation with proteinuria, urinary casts, and active nephritis. Antibodies to C1q, histone, chromatin, and dsDNA exhibited the strongest association with clinical features, indicating the importance of measuring all of these antibodies in pediatric-onset SLE patients.
A small percentage of children with Henoch-Schönlein purpura (HSP) develop a chronic form of the disease that often requires prolonged corticosteroid therapy. Disease modifying anti-rheumatic agents ...(DMARDs) or biologics have been successfully used to treat those refractory cases. Azathioprine is a DMARD that has been reported to be effective in HSP nephritis and in adult cutaneous leukocytoclastic vasculitis, a condition with cutaneous histology similar to HSP.
A description of 6 cases with relapsing HSP without significant renal involvement, treated with azathioprine are reported. All 6 cases met the classification criteria for the diagnosis of HSP, had relapsing symptoms despite corticosteroid use, were successfully treated with azathioprine and were tapered off of corticosteroids. The duration of azathioprine therapy ranged from 7-21 months and no adverse events were reported.
Azathioprine is effective in controlling prolonged relapsing symptoms of HSP, allowing earlier discontinuation of corticosteroids. This report shows that azathioprine can be included in the therapeutic options for relapsing HSP and is the first case series in the literature of azathioprine use in HSP without significant renal involvement.
Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been found in sera of 76% of patients with rheumatoid arthritis (RA), mainly in rheumatoid factor (RF) positive patients, with a ...specificity of 96%. We evaluated the presence of anti-CCP antibodies in patients with juvenile idiopathic arthritis (JIA) and assessed the possibility of synthetic citrullinated peptides as antigenic determinants in JIA.
The presence of anti-CCP antibodies was determined using 3 synthetic citrullinated peptide variants and 2 commercial kits (Inova Diagnostics and Axis-Shield Diagnostics) optimized for detecting JIA-specific antibodies in serum by an ELISA based assay. We evaluated 66 patients with JIA (16 RF positive polyarthritis, 18 RF negative polyarthritis, 19 oligoarthritis, and 13 systemic arthritis). We also tested 9 adult RA patients, 34 patients with systemic lupus erythematosus (SLE), and 25 healthy persons as controls.
Significant concentrations of anti-CCP antibodies were detected in the majority of RF positive JIA patients with polyarthritis. Using the 2 synthetic linear peptides, 12/16 (75%) were positive; 9/12 (75%) were positive with the Inova kit and 9/10 (90%) were positive with the Axis-Shield kit. However, utilizing the synthetic linear peptides, significant concentrations of anti-CCP antibodies were detected in 51/66 (77%) JIA patients, including 15/18 (83%) RF negative polyarthritis, 16/19 (84%) oligoarthritis, and 8/13 (62%) systemic arthritis patients. No healthy control showed elevated antibody levels. In contrast, 4/9 (44%) patients with adult RA and 2/6 (33%) with SLE had elevated anti-CCP levels. The synthetic cyclic variant cfc-1-cyc yielded significant anti-CCP levels for 13/14 (93%) patients with RF negative polyarthritis, 6/10 (60%) with oligoarthritis, and 3/7 (43%) with systemic arthritis, and 8/9 (88%) RF positive patients. No healthy control had increased anti-CCP levels. However, 4/9 (44%) adult RA and 9/34 (26%) SLE patients were found to have elevated anti-CCP levels. Using the Inova and Axis-Shield kits, much smaller percentages were found in the RF negative patients, with only 4/16 (25%) in the oligoarthritis and RF negative polyarthritis patients with the Inova kits and 0/25 (0%) by the Axis-Shield kits. The Inova kit revealed elevated anti-CCP antibodies in 5/9 (56%) adult RA patients and in 8/34 (24%) SLE patients. No healthy control had elevated anti-CCP antibodies. However, the Axis-Shield kits did not detect anti-CCP antibodies in adult RA (0/9) or SLE (0/34) patients. Moreover, 0/25 (0%) healthy individuals exhibited anti-CCP levels. The presence of anti-CCP antibodies correlated more frequently with the presence of RF.
This study confirms the presence of anti-CCP antibodies in patients with JIA, especially those with RF positive polyarthritis, by all ELISA based methods. Use of synthetic peptides also revealed anti-CCP antibodies in a percentage of RF negative patients with polyarthritis, oligoarthritis, and systemic arthritis; there was a loss in specificity, but an increase in sensitivity. These results suggest that antibodies to these antigenic peptides may be markers for JIA, and indicate a possible role of citrulline-containing epitopes in the pathogenesis of JIA.
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.
Autoimmune diseases often have overlapping symptoms and laboratory somewhat unfamiliar to the non-rheumatologist. Characteristic signs, symptoms, and autoantibodies define specific connective tissue ...diseases. Some patients have some characteristic symptoms, but cannot be definitively classified. Still other patients meet criteria for more than one specific connective tissue disease. These patients can be confusing with regard to diagnosis and prognosis. Clarification of each patient's condition can lead to improved patient care.
Background/Purpose:
IgG anti‐cyclic citrullinated peptide (anti‐CCP) antibodies have been identified in the sera of juvenile idiopathic arthritis (JIA) patients and have been associated with more ...destructive disease. The identity of the target proteins of the citrullinated modification has remained elusive. We attempted to determine the prevalence and significance of different citrullinated epitopes.
Methods:
We evaluated serum from 96 patients with various subtypes of JIA for the presence of antideiminated (citrullinated) fibrinogen, anti‐citrullinated α‐enolase, anti‐citrullinated and native type II collagen, and anti‐vimentin (vim1–16 and vim 59–74) antibodies by enzyme‐linked immunosorbent assays. We correlated the presence of the antibodies with anti‐CCP and rheumatoid factor (RF) isotypes, erythrocyte sedimentation rate (ESR), and C‐reactive protein (CRP) levels.
Results:
31 JIA patients (32%) demonstrated reactivity to anti‐citrullinated fibrinogen, 23 (24%) to anti‐citrullinated type II collagen, 10 (10.5%) to anticitrullinated vimentin I‐16, 9 (9%) to anti‐citrullinated α‐enolase, and 7 (7.4%) to anti‐citrullinated vimentin 59–74 antibodies. One IgM RF positive JIA patient was positive for all 6 of the citrullinated autobodies assayed. The reactivity was higher in those JIA patients positive for IgM RF and IgG/IgM anti‐CCP antibodies.
Conclusion:
The study demonstrates that antibodies to multiple citrullinated epitopes are present in the sera of patients with JIA. A higher percentage of antibodies reacted with citrullinated fibrinogen and citrullinated type II collagen. The more widespread the positivity correlates with more severe disease.
To evaluate safety and clinical response to treatment with etanercept in the polyarticular course of patients with juvenile rheumatoid arthritis (JRA).
Ten patients were studied (8 female, 2 male; 6 ...polyarticular JRA, 4 systemic onset; mean age 13.3 yrs; mean duration of disease 6.6 yrs). Patients received 0.4 mg/kg etanercept subcutaneously twice weekly in addition to their existing therapeutic regimen. Observed duration of treatment ranged between 4 and 12 months.
Patients tolerated treatment with etanercept well. No serious adverse events were noted. Treatment response showed considerable improvement of morning stiffness (mean reduction of 96 min approximately equal to -93%) and joint counts including swollen joints (delta -8.2 approximately equal to -40%), tender joints (delta -9.2 approximately equal to -88%), and total joints (delta -9.8 approximately equal to -37%). Laboratory results included decreases in ESR (delta -46 mm/h approximately equal to -53%) and improvement of anemia.
Our results confirm etanercept is a powerful adjunct in the therapy of polyarticular JRA resistant to conventional treatment regimens.
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