Peri H. Pepmueller

Factors influencing fracture risk, T score, and management of osteoporosis in patients with rheumatoid arthritis in the Consortium of Rheumatology Researchers of North America (CORRONA) registry.

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.

Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

Background Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.

Measurement of autoantibodies in pediatric-onset systemic lupus erythematosus and their relationship with disease-associated manifestations.

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.

The decreasing prevalence of uveitis associated with juvenile rheumatoid arthritis: do NSAIDs play a role?

We studied the prevalence and characteristics of chronic uveitis in a population of children diagnosed with juvenile rheumatoid arthritis (JRA). Uveitis is one of the most important, potentially debilitating extra-articular manifestations of JRA and has been observed in as many as 20% of cases. The medical records of 230 patients diagnosed with JRA and treated at a tertiary care hospital ophthalmology clinic between 1992 and 2000 were retrospectively reviewed.Seventeen patients (7.4%) were found to have clinical features of uveitis. There was a preponderance of female patients (16/17) and pauciarticular disease (13/17). Only 12 of 17 were ANA positive. Six had uveitis at diagnosis. Patients who were receiving naproxen had less incidence of uveitis compared with those receiving other nonsteroidal antiinflammatory drugs. Despite a relatively low prevalence of uveitis, complications occurred in about 24% (4/17) of the patients, even with adequate treatment and close monitoring.The prevalence of uveitis in JRA seems to be decreasing and may be secondary to the increased use of naproxen. However, routine ophthalmologic screening should be continued in patients with JRA to avoid potential complications of chronic uveitis.

Azathioprine therapy for steroid-resistant Henoch-Schönlein purpura: a report of 6 cases.

BackgroundA 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.Case presentationA 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.ConclusionsAzathioprine 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.

Measurement of autoantibodies in pediatric- and adolescent-onset systemic lupus erythematosus and their significant relationship with disease-associated manifestations

Purpose Pediatric-onset systemic lupus erythematosus (SLE) patients are prone to develop major organ involvement and a more severe disease course than adult-onset SLE. Early management of the disease is necessary to prevent further complications, which can partly be accomplished by monitoring autoantibody levels and understanding their significance in the disease process. We evaluated an autoantibody profile in pediatric- and adolescentonset systemic lupus erythematosus (SLE) patients to determine the clinical and statistical associations with disease-related manifestations. Methods Sera from 53 SLE patients and 22 healthy individuals were collected. Antibodies to C1q, histone, chromatin, ribosomal P, double stranded (ds) DNA, and high avidity (HA) dsDNA were measured by enzyme-linked immunosorbent assays. Patient records were evaluated for clinical and laboratory associations. Results SLE patients exhibited significantly elevated levels of all measured autoantibodies when compared to healthy individuals (p<0.05). The most prevalent autoantibody measured in the SLE cohort was anti-C1q antibodies, found in 58% of SLE patients. Anti-C1q antibodies correlated significantly with proteinuria, fever, urinary casts, and decreased complement levels (p<0.05). Anti-C1q antibodies were significantly elevated in SLE patients with active disease (127U) compared to patients who were inactive (63U) (p<0.05). Anti-C1q antibodies and antihistone antibodies were significantly elevated in patients with class III/IV nephritis compared to class I/II/V nephritis (p<0.05). SLE patients with active nephritis at the time of sample collection demonstrated significantly elevated levels of anti-C1q antibodies compared to those without active nephritis (191U v. 80U, p<0.05), also exhibiting 100% specificity for active nephritis, proteinuria, and urinary casts. Chart-documented anti-dsDNA antibodies were positive in 28 SLE patients, INOVA antidsDNA antibodies in 21 patients, and HA anti-dsDNA antibodies in 8 patients. However, measuring HA antidsDNA antibodies rather than conventional anti-dsDNA antibodies may prove more accurate by eliminating low avidity, weakly bound antibodies detected by traditional assays. Anti-histone antibodies correlated significantly with leukopenia, hemolytic anemia, and anti-dsDNA and HA anti-dsDNA antibodies (p<0.05).