Corticosteroid use in childhood-onset systemic lupus erythematosus-practice patterns at four pediatric rheumatology centers.

OBJECTIVE: To evaluate corticosteroid prescribing patterns in childhood-onset systemic lupus erythematosus (SLE), comparing four academic pediatric rheumatology practices. METHODS: Patients with childhood-onset SLE (n=72) treated at four large pediatric rheumatology centers were studied at 3-month intervals for 18 months. Information on medication use, disease activity as measured by the SLEDAI and the SLAM; and disease damage by the SLICC/ACR Damage Index was collected. RESULTS: At the time of enrollment, patients at each center were similar for disease duration, age, frequency of renal involvement and disease damage. Prednisone (mean 9 mg/day) was continued during 72% of periods of inactive disease for at least 3 months (SLEDAI=0). Centers differed in the use of intravenous pulse methylprednisolone (p<0.0001). Even when adjusted for between-center differences in patient weight, race and disease activity, centers also significantly differed in the dose of prednisone (p<0.05). The center with the largest between-patient variability in the dose of prednisone prescribed to its patients showed the smallest between-patient variance in patient disease activity. CONCLUSIONS: Corticosteroids are commonly used for the treatment of childhood-onset SLE, even when the disease is inactive. There appears to be important between-center differences in the use of intravenous and oral corticosteroids for childhood-onset SLE therapy that cannot be explained by patient disease activity corticosteroid prescribing patterns influence disease control. Further studies are needed to determine whether differences in practice patterns lead to significant differences in longer-term disease outcomes with childhood-onset SLE.

Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII).

The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and >or=1 year follow-up were studied in two groups: jSLE (diagnosed at

Making the diagnosis of systemic lupus erythematosus in children and adolescents.

Approximately 15% of patients with systemic lupus erythematosus (SLE) will have the onset of their disease in childhood or adolescence. Due to the broad range of possible clinical features of SLE, the diagnosis may be difficult to make in a general pediatric or community setting. The common symptoms of SLE in children and adolescents include fever, fatigue, weight loss, arthritis, rash and renal disease. SLE is more common in non-Caucasian ethnic groups and should be considered in the differential diagnosis of a multisystem disease in these patients. In this article, the classification criteria for SLE are discussed, and an approach to making an accurate and timely diagnosis of this disease is considered.

Outcome measures in childhood rheumatic diseases.

The childhood rheumatic diseases are a group of chronic disorders with variable courses, morbidity, and outcomes ranging from complete remission to long-term disability. The major childhood rheumatic disorders are juvenile idiopathic arthritis (systemic onset, polyarticular, oligoarticular, enthesitis-related, psoriatic), juvenile dermatomyositis, systemic lupus erythematosus, and the vasculitides. In this review, the current status of outcomes measurement application to pediatric rheumatology will be discussed.

kappa-opioid receptor-mediated analgesia: hotplate temperature and sex differences.

The present experiment was designed to investigate the dose-effect and time-effect functions of the kappa-opioid receptor agonist [5alpha,7alpha, 8beta)-(-)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4, 5)dec-8-yl]benzeneacetamide] (U69,593) in intact and gonadectomized male and female rats as a function of hotplate temperature (45 degrees C or 51 degrees C). At 45 degrees C baseline lick latencies were longer in female rats than in male rats. Lick latencies increased dose-dependently in all subjects except intact female rats. U69,593 increased lick latencies as a function of time since its administration in all subjects. At 51 degrees C baseline lick latencies did not differ between groups and they increased dose-dependently in all subjects. The effectiveness of U69,593 decreased as a function of time since its administration, but not in castrated male rats. These observations suggest that gonadal hormones could play a role in modulating the behavioral effects of U69,593 when subjects are tested at different hotplate temperatures.

L-DOPA-induced air-stepping in the preweanling rat: electromyographic and kinematic analyses.

Ontogenetic changes in intralimb coordination may result from maturation of the central pattern for locomotion, maturation of peripheral efferents, changes in afferent modulation of the centrally generated pattern, interactions with the substrate, biomechanical changes within the limb itself, or a combination of these. Electromyograms obtained from three hindlimb extensors of rats on Postnatal Days (PND) 5, 10, 15, or 20, during episodes of coordinated L-DOPA-induced air-stepping, showed that muscle activation preceded extension of the corresponding joints at all ages. The delay between the onset of extensor activity and the onset of joint extension increased during ontogeny and was greatest at PND 20. Ontogenetic changes in the relative timing of muscle activity and corresponding joint movements probably resulted from changes in biomechanical factors, changes in afferent modulation of central motor output, or both.

Soluble adhesion molecules in juvenile rheumatoid arthritis.

OBJECTIVE: To determine serum levels of soluble (s) adhesion molecules in patients with juvenile rheumatoid arthritis (JRA), and to determine whether differences exist in these levels among the 3 subtypes of JRA, and whether levels of these molecules correlate with other measures of disease activity. METHODS: Serum levels of soluble forms of intercellular adhesion molecule-1 (ICAM-1), ICAM-3, vascular (V) CAM-1, L-selectin, and E-selectin were determined by sandwich ELISA in 16 patients with JRA (6 systemic, 6 polyarticular, 4 pauciarticular). Differences in levels among JRA subtypes were determined by ANOVA, and correlations between levels and the following clinical variables were assessed by linear regression analysis: erythrocyte sedimentation rate (ESR), total white blood cell count (WBC), hematocrit (HCT), platelet count (PLT), and total swollen joint count (JC). RESULTS: sE-selectin levels were significantly higher in patients with systemic disease compared to other subtypes (p<0.04). Furthermore, there was a trend toward higher levels of sICAM-1 in systemic disease, which did not reach statistical significance. Significant correlations were found between sE-selectin and ESR (r = 0.68, p<0.006), WBC (r = 0.70, p<0.003), and PLT (r = 0.54, p<0.05) and between sL-selectin and WBC (r = 0.55, p<0.03). CONCLUSION: Because of the small number of patients studied, and the lack of age matched control data, our results must be interpreted with caution. Nonetheless, levels of sE-selectin, and possibly ICAM-1 appear to be relatively elevated in systemic JRA, and may indicate cytokine induction and endothelial cell activation in that subtype. Several molecules, especially sE-selectin, correlate with hematologic variables in JRA. These results suggest that serum levels of these molecules may provide a useful additional marker for disease activity in certain patients.

Malignancies in children who initially present with rheumatic complaints.

OBJECTIVE: Children ultimately diagnosed with malignancy are referred to pediatric rheumatology clinics with provisional rheumatic diagnoses. We aimed to distinguish the features in these patients that lead to the correct diagnosis of malignancy. STUDY DESIGN: A retrospective review of the case records of 29 children (19 boys and 10 girls, aged 1 to 15.5 years) with malignancy who were referred to 2 pediatric rheumatology centers between 1983 and 1997. RESULTS: The suspected diagnoses on referral were: juvenile rheumatoid arthritis (12), nonspecific connective tissue disease (4), discitis (3), spondyloarthropathy (3), systemic lupus erythematosus (2), Kawasaki disease (2), Lyme disease (1), mixed connective tissue disease (1), and dermatomyositis (1). The final diagnoses were leukemia (13), neuroblastoma (6), lymphoma (3), Ewing's sarcoma (3), ependymoma (1), thalamic glioma (1), epithelioma (1), and sarcoma (1). Patients had features typical of many rheumatic disorders including musculoskeletal pains (82%), fever (54%), fatigue (50%), weight loss (42%), hepatomegaly (29%), and arthritis (25%). Features that were suggestive of malignancy included nonarticular "bone" pain (68%), back pain as a major presenting feature (32%), bone tenderness (29%), severe constitutional symptoms (32%), clinical features "atypical" of most rheumatic disease (48%), and abnormal initial investigations (68%). The atypical features included night sweats (14%), ecchymoses and bruising (14%), abnormal neurologic signs (10%), abnormal masses (7%), and ptosis (3%). Initial investigations with abnormal findings included complete blood count/smear (31%), discordant erythrocyte sedimentation rate and platelet count (28%), elevated lactate dehydrognease level (24%), plain skeletal x-ray films (28%), bone scan (21%), and abdominal ultrasonography (17%). Findings of investigations done before referral to the rheumatology clinic were not recognized as abnormal in 11 (40%) patients. CONCLUSIONS: Patients with a diverse group of malignancies, other than leukemia, may present to the pediatric rheumatologist. Pediatric care providers should be familiar with typical features of childhood rheumatic disorders, and rheumatic diagnoses should be reevaluated in the presence of any atypical or discordant clinical features.

Fibrin D-dimer as a marker of disease activity in systemic onset juvenile rheumatoid arthritis.

OBJECTIVE: To study the prevalence of coagulation abnormalities in children with systemic juvenile rheumatoid arthritis (JRA) using a sensitive marker of fibrin degradation, and to determine whether serial levels of this variable parallel disease activity or predict response to medications in this disease. METHODS: Levels of d-dimer were determined in 24 consecutive patients with systemic JRA in conjunction with complete blood counts, erythrocyte sedimentation rate, maximum fever, duration of morning stiffness, and swollen joint count. Serial levels were then obtained in 11 patients. Linear regression analyses were done to determine any correlations between d-dimer and the other variables; and paired t test was used to compare levels before and after treatment interventions. Levels of d-dimer were also compared against concurrent clinical events such as pericarditis. RESULTS: Elevated levels of d-dimer were found in 23/24 of the patients (96%). When serial levels were analyzed, there were correlations between levels of d-dimer and fever (p = 0.03) and total leukocyte count (p = 0.04), but not with other variables. There was a significant reduction in levels before and after treatment in patients deemed to be clinical responders to immunomodulatory agents (p = 0.02). Elevated levels were also indicative of severe disease over the remainder of followup; lack of d-dimer indicated a benign disease course. CONCLUSION: With the use of a sensitive and specific marker of fibrinolysis known as d-dimer, coagulation abnormalities were more prevalent in children with systemic JRA than previously reported, and are frequently found during periods of active disease. Furthermore, serial levels of d-dimer appear to parallel response to disease modifying agents, and may predict outcome over a short followup period. Fibrin d-dimer may represent a novel marker that, when used in combination with known variables, could enhance that assessment of disease activity and response to medications in children with systemic onset JRA.

Caring for the adolescent with systemic lupus erythematosus.

Nearly 15% of patients with systemic lupus erythematosus (SLE) present during adolescence; it is therefore highly likely that a pediatrician will care for a young adult with SLE in his or her practice. The author stresses the importance of an individualized medical treatment plan that suits the patient and disease stage, as well as the clinician's obligation to provide clear and accurate information to adolescents and their parents. Guidelines to facilitate patient compliance and understanding are also offered.

Prolonged fevers of unknown origin in children: patterns of presentation and outcome.

OBJECTIVE: To review the presentation, clinical characteristics, and outcome of children with prolonged fevers of unknown origin who are referred for pediatric rheumatologic evaluation. METHODS: We used a retrospective review of the charts of the 40 children (23 boys and 17 girls, aged 9 months to 14.6 years) with fevers persisting longer than 1 month who were referred to the Pediatric Rheumatology Clinic between 1984 and 1994, in whom evaluation did not result in diagnosis. Follow-up with children's families, pediatricians, or both was done by telephone. RESULTS: Of the 40 children, 29 had periodic fevers, and 11 had daily fevers without pattern. Patients with periodic fever were younger at onset, had longer duration of symptoms before referral, and higher maximum temperatures. The two groups did not differ in frequency of associated symptoms or signs. At follow-up (mean 60.5 +/- 5 months, n = 37), 10 children with daily fevers (within 24 months) and 23 children with periodic fevers (within 48 months) had completely recovered; three patients continue to have periodic fevers. In patients with daily fevers one had Crohn disease (7 months after initial evaluation) and another had uveitis (4 years after evaluation). One patient with periodic fevers had inflammatory bowel disease 3.5 years after the onset of fevers. Petit mal seizures developed in one patient with periodic fever, and another had mitochondrial encephalopathy. Four children with periodic fevers have attention-deficit hyperactivity disorder, and two have developmental delays. CONCLUSIONS: Fevers without an obvious source usually have a benign outcome, although patients should be monitored for changes in symptoms. Of the children with periodic fevers, 29% were later found to have neurologic problems; the relation to the previous fevers is uncertain.

Bicipital synovial cysts in juvenile rheumatoid arthritis: clinical description and sonographic correlation.

OBJECTIVE: To describe the presentation and clinical course of bicipital synovial cysts in 6 patients with juvenile rheumatoid arthritis (JRA) and to elucidate their anatomy using ultrasonography. METHODS: A clinical description of the cyst, JRA subtype, activity of concurrent arthritis, systemic disease features, and erythrocyte sedimentation rate was recorded for each patient. Ultrasonographic examination of the cyst was performed for each patient. RESULTS: Bicipital cysts generally presented as a sudden painless swelling on the flexor aspect of the upper arm, but on was in the forearm. Five of 6 patients had systemic disease. All patients had active arthritis when the cysts developed. Five of 6 cysts resolved spontaneously in less than 12 weeks. Ultrasonography confirmed a cystic structure in all patients, and in all cases was associated with thickening of the biceps tendon. Fluid was found within or adjacent to the biceps tendon in all cases. CONCLUSION: Bicipital synovial cysts should be considered a cause of acute arm swelling in patients with JRA, especially those with systemic disease. Ultrasonography is a useful diagnostic adjunct in this condition. This condition is generally self-resolving.

Nonrheumatic conditions in children including infectious diseases and syndromes.

Often, a child is referred for evaluation to a pediatric rheumatologist and found to have a nonrheumatologic disorder. Infections constitute an important group of disorders with potential musculoskeletal system involvement. Reactive arthritis subsequent to infection with Yersinia is discussed, as well as reactive arthritis seen in the course of cystic fibrosis. Musculoskeletal manifestations of tuberculosis and brucellosis are reviewed. The continued presence of acute rheumatic fever in the United States has been documented, but the clinical spectrum of the disease appears to be changing over time. A variety of inherited syndromes may involve the musculoskeletal system, either primarily or as a minor manifestation. The bony dysplasias, another group of disorders, result from abnormal collagen structure and affect musculoskeletal development; clinical findings and new genetic information is reviewed. Descriptions of several rare syndromes (eg, hyaline fibromatosis and hypertrophic osteoarthropathy) also are reviewed here.

Adult- and childhood-onset systemic lupus erythematosus: a comparison of onset, clinical features, serology, and outcome.

This study examines the differences which may distinguish systemic lupus erythematosus (SLE) presenting in adult life or childhood. A common database was established, with analysis of clinical, serological and outcome features of a cohort of patients with SLE, with disease diagnosed before the age of 16 (n = 39) or after the age of 16 (n = 165). Disease onset was generally more severe in the childhood-onset patients. Cardiopulmonary disease was more common in the older-onset group, but major haematological manifestations were more frequent in the childhood-onset group. Serologically, anti-DNA, anti-Sm and anti-RNP antibodies and a low C3 were all found more frequently in the younger patients. Twice as many adult-onset cases had died at the time of the last follow-up (10 vs 5%), but this group had been followed for a longer period (average 7.5 yr, S.D. 3.9 for adults vs average 4.8 yr, S.D. 3.2 for children). However, the younger patients were twice as likely (82 vs 40%) to require high-dose prednisone, although the requirement for immunosuppressive agents was similar in the two groups. Clinicians should anticipate that children with SLE have a more severe disease onset than adults in general.