Gail Cawkwell

Etanercept in children with polyarticular juvenile rheumatoid arthritis

BACKGROUND We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. METHODS Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. RESULTS At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events. CONCLUSIONS Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

Diversity in presenting manifestations of systemic lupus erythematosus in children

OBJECTIVE To describe the diversity in presenting manifestations of systemic lupus erythematosus (SLE) in children. STUDY DESIGN Initial clinical and laboratory manifestations of 39 children, who fulfilled >/=4 American College of Rheumatology criteria for SLE, were retrospectively analyzed. RESULTS Median age at onset was 12 years. The male to female ratio was 1:18.5, and racial/ethnic backgrounds were white 41%, black 33%, and Hispanic 26%. Initial manifestations included musculoskeletal 74%, cutaneous 72%, constitutional 67%, neurologic 28%, renal 28%, lymphadenopathy 15%, and Raynauds phenomenon 10%. Laboratory abnormalities at presentation to our clinic included elevated erythrocyte sedimentation rate 87%, anemia 72%, lymphopenia 59%, leukopenia 31%, proteinuria or cellular casts 44%, low C(3) or C(4) level 77%, antinuclear antibodies 97%, and anti-double-stranded DNA 95%. One third (33%) presented with features not initially suggestive of SLE. Six patients presented with unusual manifestations including parotitis, quadriplegia, chorea, severe abdominal pain, persistent cough, and dizziness. However, 85% of patients with atypical manifestations had abnormal complete blood count or urinalysis results at presentation. CONCLUSION Presenting manifestations of SLE in children are diverse. A detailed history, thorough review of systems, complete physical examination, complete blood count, urinalysis, and a high index of suspicion help to make the correct diagnosis of SLE in patients with atypical presentations.

Drug Treatment in Children with Juvenile Rheumatoid Arthritis: Past, Present, and Future

Rheumatology made its debut as a legitimate subspecialty of pediatrics sometime in the 1940s in Europe, and in the 1970s in North America. Therapy of juvenile rheumatoid arthritis has evolved from salicylates and gold injections to newer, less toxic nonsteroidal anti-inflammatory drugs and methotrexate. Corticosteroids remain as important drugs when life-threatening complications or blinding iridocyclitis develop. Immune response modifiers and gene therapies offer considerable potential for eventually halting or curing the disease but have yet to make a substantial impact on therapy. Methods for the correct conduct and interpretation of data from clinical trials are discussed.

The Role of Aggressive Corticosteroid Therapy in Patients With Juvenile Dermatomyositis : A Propensity Score Analysis

OBJECTIVE To compare outcomes at 36 months in patients newly diagnosed with juvenile dermatomyositis (DM) treated with aggressive versus standard therapy. METHODS At diagnosis, 139 untreated juvenile DM patients were given aggressive therapy (intravenous methylprednisolone or oral prednisone 5-30 mg/kg/day; n = 76) or standard therapy (1-2 mg/kg/day; n = 63) by the treating physician. Aggressive therapy patients were more ill at diagnosis. Matching was based on the propensity for aggressive therapy because propensity scoring can reduce confounding by indication. Logistic regression of the matched data determined predictors of outcomes, controlling for clinical confounders and propensity score. Outcomes comprised Disease Activity Score (DAS) for skin and muscle, range of motion (ROM), and calcification. RESULTS Sex, race, and age were similar between groups, and initial DAS weakness and ROM significantly predicted the therapy chosen. Based on propensity scores, 42 patients from each group were well matched. In the matched pairs, there were no significant differences in outcomes. Methotrexate use (odds ratio [OR] 3.6, 95% confidence interval [95% CI] 1.15-11.5) and duration of untreated disease (OR 1.2, 95% CI 1-1.38) were associated with ROM loss, hydroxychloroquine use (OR 11.2, 95% CI 3.7-33) and calcification (OR 6.8, 95% CI 1.8-25.4) with persistent rash, abnormal baseline lactate dehydrogenase (OR 11.2, 95% CI 1.4-92) and age at onset (OR 1.3, 95% CI 1-1.4) with weakness, and duration of untreated disease (OR 1.2, 95% CI 1-1.39) with calcification. CONCLUSION Using a retrospective, nonrandomized design with propensity score matching, there was little difference in efficacy outcomes between aggressive and standard therapy; however, the sickest patients were treated with aggressive therapy and were not included in the matched analysis. Comprehensive clinical studies are needed to determine therapeutic pathways to the best outcome.

Movement Artifact and Dual X-ray Absorptiometry

Abstract Dual-energy X-ray absorptiometry (DXA) scanning is used with increasing frequency to measure bone mass and body composition in adults as well as children. Without sedation, children may move during the study. The effect of movement decreases the precision of DXA scanning ( 1 ). However, the amount and types of movements that alter scan results are not known. Eleven adults were scanned five times using a Hologic QDR-2000. Prescribed movements were designed to simulate movements that may occur in the clinical setting. These movements included: slow horizontal movements, fast horizontal movements, isolated movements of the extremities and head, and slow vertical movements. In addition, 90 sequential DXA scans were reviewed for movement. Movement was noted in 23% of 90 sequential DXA scans ordered for clinical purposes at a childrens hospital. Equal percents of subjects over 15 and 15 or younger moved during DXA scans. Movement during DXA scanning results in unpredictable alterations in the assessment of bone mineral content (BMC), lean mass, and fat mass. Movement artifact, especially vertical movements, may be difficult to detect on DXA printouts.

Pulmonary vasculitis presenting as atypical asthma

CASE REPORT A 9-year-old female was referred to our clinics in January 1998 because of multisystem complaints. The patient had a 2-year history of cough, episodes of chest pain, and tightness upon increasing activity. The patient had minimal response to 2-agonists and was noted to improve upon treatment with oral glucocorticosteroids. She was diagnosed with atypical asthma and was treated with inhaled glucocorticosteroids and 2-agonists. Concomitant with chest symptoms, the patient experienced frequent arthralgias, fatigue, generalized lymphadenopathy, hypertension, transient ischemic attacks, Raynaud’s phenomenon, growth failure, abdominal pain, headaches, and frequent infections characterized as recurrent otitis media and sinusitis. Her medications included beclomethasone inhaler double strength 2 puffs bid, albuterol inhaler every 4 to 6 hours as needed, fluticasone nasal spray 1 spray qd, loratidine 5 mg qd, sucralfate 1 g tid, nifidipine 30 mg qd, baby aspirin 81 mg qd, ibuprofen every 6 to 8 hours as needed and growth hormone injection qd. The patient was admitted to the hospital for further evaluation and treatment. On physical examination, the patient weighed 25.6 kg (5th percentile) and was 126 cm in height ( 5th percentile). Pertinent findings included mobile and tender cervical, axillary, and inguinal lymphadenopathy; clear breath sounds; mild epigastric tenderness; and hepatosplenomegaly. Capillary nail beds were abnormal in that they exhibited telangiectasia and vascular dropout. The skin was dry with a fixed salmoncolored macular rash on the upper chest and neck. The rest of the physical examination was unremarkable.