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.

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.

Diagnosis and management of rheumatic diseases in adolescence.

The rheumatic diseases constitute a significant group of chronic illnesses affecting children of all ages, including adolescents. This chapter provides an overview of rheumatic diseases and medical treatment options. Issues of sexuality and self-image that may influence treatment course and outcome are explored. The author emphasizes the importance of cooperation and communication between patient and physician, which enable adolescents to participate in the design and maintenance of their regimens.

Sex differences in academic advancement. Results of a national study of pediatricians.

BACKGROUND: Although the numbers of women in training and in entry-level academic positions in medicine have increased substantially in recent years, the proportion of women in senior faculty positions has not changed. We conducted a study to determine the contributions of background and training, academic productivity, distribution of work time, institutional support, career attitudes, and family responsibilities to sex differences in academic rank and salary among faculty members of academic pediatric departments. METHODS: We conducted a cross-sectional survey of all salaried physicians in 126 academic departments of pediatrics in the United States in January 1992. Of the 6441 questionnaires distributed, 4285 (67 percent) were returned. The sample was representative of U.S. pediatric faculty members. Multivariate models were used to relate academic rank and salary to 16 independent variables. RESULTS: Significantly fewer women than men achieved the rank of associate professor or higher. For both men and women, higher salaries and ranks were related to greater academic productivity (more publications and grants), more hours worked, more institutional support of research, greater overall career satisfaction, and fewer career problems. Less time spent in teaching and patient care was related to greater academic productivity for both sexes. Women in the low ranks were less academically productive and spent significantly more time in teaching and patient care than men in those ranks. Adjustment for all independent variables eliminated sex differences in academic rank but not in salary. CONCLUSIONS: Lower rates of academic productivity, more time spent in teaching and patient care and less time spent in research, less institutional support for research, and lower rates of specialization in highly paid subspecialties contributed to the lower ranks and salaries of female faculty members.

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.

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.

Parents of children with rheumatic disease as peer counselors.

OBJECTIVE: A parent consultant program was established to promote active family involvement in the health care process and to provide parent-to-parent support, education, and training. METHODS: Parents of children with rheumatic disease were hired by 7 pediatric rheumatology centers to serve as role models and advocates for other parents whose children attended the clinics. In the clinic, the parent consultants provided support, advocacy, and education regarding specific nonmedical issues. At the local level, they assisted parents in obtaining community-based services, such as individual educational plans at school, local physical therapy, or access to recreational resources. RESULTS: Program impact was evaluated by an anonymous, mail-response questionnaire sent to parents who met with a parent consultant during a clinic visit for their child. Surveys were sent within 6 months of the initial parent consultant meeting; 257 questionnaires were mailed, 33% were returned. The majority of respondents (87%) felt their interaction with the parent consultant was helpful. The general support received and the specific information and/or assistance received were found to be equally useful by respondents. The majority of respondents (98%) stated they would recommend that other parents meet with the parent consultant. CONCLUSION: Parents of children with rheumatic disease are effective peer counselors, providing general support and specific assistance to enhance family involvement in care.

Neuropsychological assessment of children and adolescents with systemic lupus erythematosus.

Neuropsychological assessments of adults with SLE have shown cognitive impairment, sequential processing deficits, memory loss, increased incidence of left handedness, learning disabilities and emotional distress compared with healthy individuals or subjects with other medical conditions. Neuropsychological testing regarding these variables in children and adolescents with SLE has been infrequently reported. For this study, eight children with SLE (age 9-17 years at diagnosis) were assessed with neuropsychological testing at a median of 10.5 months (range 1 week to 30 months) after diagnosis. Tests included Wechsler Intelligence Scale for Children-Revised or Wechsler Adult Intelligence Scale-Revised, Wide Range Achievement Test-Revised, Standard Binet Intelligence Scale Fourth Edition Memory Subtests or Wechsler Memory Scale (all mean = 100 +/- 15) and Gates MacInitie Reading Comprehension Test, Achenbach Child Behavior Checklist and Achenbach Youth Self Report. Mean intellectual scores were in the low average range (Wechsler Full Scale mean = 85.0 +/- 11.9, Verbal Scale mean 85.2 +/- 13.9, Performance Scale mean = 88.0 +/- 13.9). Academic achievement was globally depressed (reading recognition mean = 79.5 +/- 22.0, spelling mean = 78.9 +/- 23.5), especially in arithmetic (mean = 70.5 +/- 14.9). Children with SLE averaged 5 years behind grade placement in reading comprehension. Visual memory was also depressed in patients with SLE. Behavior ratings failed to demonstrate any significant aberrations in the test subjects.

von Willebrand factor in juvenile dermatomyositis.

OBJECTIVE: To evaluate whether plasma von Willebrand factor (vWF) levels are a useful indicator of disease activity in juvenile dermatomyositis (DM). METHODS: Serum vWF levels were prospectively measured in 15 patients with juvenile DM and were compared to serum muscle enzyme levels, muscle strength, and presence of extramuscular manifestations. RESULTS: 6/15 active disease periods were accompanied by an increase in vWF; 9 were not. Elevated vWF levels did not relate to the presence of active skin disease or calcinosis. vWF was not consistently related to muscle strength, CPK, or aldolase in the study group. Two patients had elevations of vWF in association with viral infections while their DM was quiescent. CONCLUSION: An elevated vWF level is often indicative of a disease exacerbation in DM, and thus may be helpful in managing difficult cases. However, it is not consistently elevated in, nor specific for active disease in DM. It therefore cannot be recommended as a routine test in patients with DM. When used, results should be interpreted with caution.