Juvenile dermatomyositis at diagnosis: clinical characteristics of 79 children.

OBJECTIVE: To evaluate demographic and clinical characteristics, duration of time between disease onset (date of first rash and/or weakness), and diagnosis/therapy, as well as socioeconomic status, of children with newly diagnosed juvenile dermatomyositis (JDM). METHODS: Structured telephone interview of families of a cohort of 79 children with JDM: interval between onset of symptoms to diagnosis, median of 3 months (range 0.5-20.0). RESULTS: At diagnosis, all the children had rash (100%) and proximal muscle weakness (100%); 58 (73%) had muscle pain; 51 (65%) fever; 35 (44%) dysphagia; 34 (43%) hoarseness; 29 (37%) abdominal pain; 28 (35%) arthritis; 18 (23%) calcinosis, and 10 (13%) melena. Muscle derived enzymes were normal in 10% of the children. Of the 43 children who had an electromyogram (EMG), 8 (19%) had normal results. Fifty-one children had a muscle biopsy; the results were normal/nondiagnostic in 10 (20%). Median time from disease onset to diagnosis was different between racial groups: Caucasians (n=59) 2.0 months: for minorities (n=20), 6.5 months, (p=0.0008). The median time from disease onset to therapy was: Caucasians. 3.0 months; minorities, 7.2 months (p=0.002). Report of calcinosis was associated with increased time to diagnosis and therapy (p=0.04). In the 33 children whose first symptom occurred in June-September, rash preceded or accompanied onset of muscle weakness in 83% (n=27). Ninety-one percent of the children were given steroid therapy and 9% received methotrexate as well. CONCLUSION: The results of an undirected site for muscle biopsy or EMG may not be diagnostic. Minority children had a longer interval between first JDM symptom and diagnosis/therapy than Caucasian children. Delay in diagnosis/therapy was associated with calcinosis.

Immunogenetic studies in families of children with juvenile dermatomyositis.

OBJECTIVE: We reported an association between juvenile dermatomyositis (JDMS) and the HLA-DQA1*0501 allele. The purpose of this study was to determine whether there is evidence for linkage between JDMS and the DQA1*0501 allele in JDMS families. METHODS: The study population included 18 unrelated patients with JDMS, their parents, and 49 unaffected siblings. Using molecular genetic techniques, we studied the HLA genes, DRB1, DQA1, and tumor necrosis factor-alpha. RESULTS: Using the transmission disequilibrium test, we confirmed our earlier observations that the HLA-DQA1*0501 allele confers primary susceptibility to JDMS. CONCLUSION: DQA1*0501 confers genetic risk for JDMS; we cannot exclude the effects of alleles at other linked loci that were not studied or interactive effects between DQA1 alleles and alleles at other loci.

Psychopathology and health care use among preschool children: a retrospective analysis.

OBJECTIVE: To examine the relationship between psychopathology and health care utilization beginning in the preschool (ages 2 to 5) years. METHOD: Five hundred ten preschool children were enrolled through 68 primary care physicians. The test battery used for diagnoses included the Child Behavior Checklist, a developmental evaluation, the Rochester Adaptive Behavior Inventory, and a videotaped play session. Consensus DSM-III-R diagnoses were assigned using best-estimate procedures. Frequency of primary care visits was established through 1-year retrospective record review; mothers estimated total visits and emergency department (ED) use. RESULTS: Logistic regression models showed that a DSM-III-R diagnosis was related to increased ED use but not primary care or total visits. Greater functional impairment was associated with fewer primary care visits and more ED visits. Total, internalizing, and externalizing behavior problem scores were associated with increased primary care and total visits; ED visits were associated with increased total and internalizing problems. Child's health status consistently correlated with utilization. CONCLUSION: There is a consistent relationship between health care use and child psychopathology beginning in the preschool years.

New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis.

OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.

Lack of detection of enteroviral RNA or bacterial DNA in magnetic resonance imaging-directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis.

OBJECTIVE: To investigate for the presence of increased titers of circulating antibody to putative infectious agents and for detectable viral RNA or bacterial DNA in children with active recent-onset juvenile dermatomyositis (DM). METHODS: Magnetic resonance imaging-directed muscle biopsies were performed in 20 children with active, untreated, recent-onset juvenile DM and in age-matched children with neurologic disease. Sera were tested for complement-fixing antibody to Coxsackievirus B (CVB), influenza A and B, parainfluenza 1 and 3, Mycoplasma pneumoniae, mumps, respiratory syncytial virus, and Reovirus; and by immunofluorescence for IgG antibody to Toxoplasma gondii cytomegalovirus and IgM antibody to Epstein-Barr virus. Muscle from juvenile DM patients and control children, CD-1 Swiss mice with and without CVB1 infection, and viral stock positive for CVB1-6 were tested using reverse-transcriptase polymerase chain reaction with 5 primer sets, 4 probes (1 Coxsackievirus, 3 Enterovirus), and universal primers for DNA. RESULTS: No increased antibody, viral RNA, or bacterial DNA was present in the juvenile DM patients or the control children. CONCLUSION: Juvenile DM may be triggered by unidentified agent(s) in the genetically susceptible host.

Interrater reliability of the DSM-III-R with preschool children.

Little attention has been paid to evaluating the use of DSM-III-R with preschool children. Children (N = 510) ages 2 to 5 years who were screened at the time of a pediatric visit were selected to participate in an evaluation which included questionnaires, a semistructured interview, developmental testing, and a play observation. Following the evaluation, two clinical child psychologists independently assigned DSM-III-R diagnoses. For each diagnostic category, kappa and Y coefficients were calculated; Y coefficients are less sensitive to base rates of disorders. For overall agreement, the weighted mean kappa (.61), and mean Y (.66) were moderately high. Overall agreement that the child had at least one of the disruptive disorders was substantial (kappa = .64; Y = .65); agreement that there was at least one of the emotional disorders was moderate for kappa (.54), but substantial for Y (.70). Kappa coefficients were higher for major categories of disorder than for specific disorders; however, Y coefficients did not show a decline for specific disorders. Interrater reliability of DSM-III-R appears to be similar for preschoolers and older children.

Psychological factors affecting reported pain in juvenile rheumatoid arthritis.

Examined the extent to which psychological variables are correlated with pain reported by children with juvenile rheumatoid arthritis (JRA). In a hierarchical multiple regression analysis with pain as the dependent variable, four psychological measures of child and family functioning resulted in a significant increase in R2 = .31, p < .0001, after the effects of disease characteristics were considered. Greater emotional distress in the child, greater emotional distress of the mother, and greater family harmony were related to higher reported pain. Findings suggest that more attention should be given to nonpharmacological aspects of pain and pain management in children with JRA.

Behavioral and emotional problems among preschool children in pediatric primary care: prevalence and pediatricians' recognition. Pediatric Practice Research Group.

This study examined how well private-practice pediatricians can identify emotional/behavioral problems among preschool children. Children aged 2 through 5 (N = 3876) were screened during a visit to 1 of 68 pediatricians who rendered an opinion about the presence of emotional/behavioral problems. Subsequently, children who scored above the 90th percentile for behavioral problems on the Child Behavior Checklist, along with children matched on age, sex, and race who had screened low, were invited for an intensive second-stage evaluation. There were 495 mothers and children who participated in that evaluation, which included a behavioral questionnaire, maternal interview, play observation, and developmental testing. Two PhD-level clinical child psychologists rendered independent opinions about the presence of an emotional/behavioral disorder. The psychologists identified significantly higher rates of problems overall--13.0% when the criterion was independent agreement that the child had an emotional/behavioral problem and a regular psychiatric diagnosis was assigned, vs 8.7% based on pediatricians' ratings. Prevalence rates based on psychologists' independent ratings were significantly higher than pediatricians' for both sexes, 4- through 5-year-olds, and whites, but not for 2- through 3-year-olds, African-Americans, and all minorities. Prevalence rates based on psychologists' ratings were significantly higher than the pediatricians' for all subgroups when V-code diagnoses were included in the psychologists' ratings. Overall, pediatricians' sensitivity was 20.5%, and specificity was 92.7%. At least 51.7% of the children who had an emotional/behavioral problem based on the psychologist's independent agreement had not received counseling, medication, or a mental health referral from the pediatrician.(ABSTRACT TRUNCATED AT 250 WORDS)

Conceptions of illness by children with juvenile rheumatoid arthritis: a cognitive developmental approach.

Investigated the conceptions of illness and accuracy of understanding about their disease for children with juvenile rheumatoid arthritis (JRA). 54 children between the ages of 6 and 17 were interviewed individually about various aspects of JRA, with results suggesting that accuracy and illness conceptions could be reliably measured. As predicted, children's understanding about their disease followed a developmental progression, with older children demonstrating a more sophisticated understanding of JRA than younger children (significant differences between age groups on 3 of the 5 questions). Multiple regression analysis indicated that conceptual level (p < .001) was a better predictor of the child's accuracy of knowledge than was age (ns). Despite the developmental progression, there were a significant number of children functioning below the level expected for their age. In fact, the majority (75%) of children exhibited an understanding of JRA at the concrete operational level of cognitive development. The within-subject variability and striking misconceptions argue for ongoing evaluation of each child's understanding as a way to improve educational efforts.

Evaluation of a psychological treatment package for treating pain in juvenile rheumatoid arthritis.

We examined the utility of psychological treatment procedures for children with high levels of pain associated with juvenile rheumatoid arthritis (JRA). By the use of a multiple baseline across subjects design, four children were assigned to an immediate treatment group, and four children to a delayed treatment group. The six-session treatment included relaxation training, electromyogram, and thermal biofeedback for the child; mothers were trained in the use of behavioral techniques for managing physical therapy and school attendance. Visual inspection of the data indicates small changes on children's self-reported pain diary scores for mean pain and ratings of high (greater than 5 on a 10-point visual analogue scale) pain periods, with 50% to 62% showing at least a 25% reduction in pain immediately after treatment, and 62% to 88% showing a 25% reduction by 6-month follow-up. Maternal reports of changes paralleled those of the children. Comparisons of Mann-Whitney U-tests conducted pre- and posttreatment indicated no differences for children's ratings of mean pain or +5 pain ratings between the immediate and delayed treatment groups; greater improvement for the immediate treatment group was noted on maternal reports of both mean pain (p < 0.05) and +5 pain (p < 0.5) ratings. The reduction of pain reports from pretreatment to follow-up was significant for children's mean pain (p = 0.02), +5 pain ratings (p = 0.02), and mother's reports of mean pain (p = 0.03) and +5 pain periods (p = 0.01). Maternal reports of the number of pain-related behaviors that the child exhibited also declined (p < 0.05). No reduction in physical therapist's ratings of pain during evaluation were noted. No increases in maternal reports of child's psychological adjustment problems were reported following treatment. Results provide modest support for the use of psychological interventions with patients with JRA.

Validity of reported pain as a measure of clinical state in juvenile rheumatoid arthritis.

Reported pain is one valid indicator of clinical state which should be used in the assessment and management of children with juvenile rheumatoid arthritis. Parents' reports of children's pain for 101 children with juvenile rheumatoid arthritis differed significantly by type of juvenile rheumatoid arthritis. When multiple regression was used separately for pauciarticular and polyarticular classifications of juvenile rheumatoid arthritis a measure of clinical state, which reflected joint activity, morning stiffness, and overall disease activity as rated by the doctor, had a significant and independent effect upon pain reported by parents. The child's age was not significantly related to the pain reported by parents. Children's pain reports did not differ significantly between older and younger children.

Age related changes in the concentration of serum keratan sulphate in children.

Serum was obtained from 155 children at the time of admission to hospital for elective surgery. The concentration of serum keratan sulphate was determined by an ELISA which uses an antibody specific for keratan sulphate, a molecule found predominantly in cartilage. Concentrations of keratan sulphate rise progressively during the first four years of life (0-2: mean = 357 micrograms/l; 2-4: mean = 422 micrograms/l) and then remain high until 12 years of age (mean = approx. 500 micrograms/l). At this time, concentrations drop markedly (13-year olds: mean = 377 micrograms/l; 14-year olds: mean = 318 micrograms/l). After age 15, concentrations continue to fall toward the concentrations found in normal adults. Serum concentrations did not show significant differences with respect to disease category, sex or race but were found to vary, sometimes markedly, from child to child at any one age. The results suggest human cartilage undergoes significant changes in metabolic activities during maturation. Measurements of keratan sulphate concentration in serum may prove useful in studying the biochemical and physiological bases of these changes and in monitoring growth or endochondral ossification during maturation.

Factors related to grade retention in children with short stature.

A recent study by Holmes et al. (1982) revealed a high degree (23%) of grade retention in a group of children with significant short stature secondary to growth hormone deficiency (GHD), constitutional delay (CD); or Turner's Syndrome (TS). Parents indicated in a free response format that 'immaturity' and 'small size' were the reasons for retention. The present follow-up study obtained academic achievement data on 47 of the 56 short children from the Holmes et al. (1982) study to assess what role academic factors, not spontaneously mentioned by parents, may have had in the retention decision. Results indicated that despite repeating a year in the primary grades, the group of retained children were still functioning 6 months below grade expectation, compared to grade appropriate achievement in the never-retained group. Parents and teachers were both accurate in their perceptions of children's academic achievement. Behavioural ratings by teachers indicated more adjustment difficulties for retained children, while parent ratings of behaviour showed a similar high level of problems for short children regardless of retention status. Although both groups of children possessed average intellectual abilities, the retained children obtained lower IQ scores than the never retained children. In summary, a majority of short children were achieving appropriate grade levels, but a substantial minority were experiencing under-achievement, behaviour problems, and grade retention, despite average intelligence.

A survey of cognitive functioning at difference glucose levels in diabetic persons.

Cognitive functioning was assessed in diabetic patients during hypoglycemia (60 mg/dl), euglycemia/control (110 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels were set and maintained to within 4% of targeted levels by an artificial insulin/glucose infusion system (Biostator). Attention and fine motor skills, assessed by visual reaction time, was slowed at altered glucose levels. Performance was less impaired during hyperglycemia than hypoglycemia when a longer interstimulus interval was used, although it was still slower than normal. The time required to solve simple addition problems was increased during hypoglycemia, although reading comprehension was not affected. The possibility that some automatic brain skills are disrupted at altered glucose concentrations is discussed, while associative or inferential skills may be less affected.

Validity of urine glucose measurements for estimating plasma glucose concentration.

Both physicians and diabetic patients have traditionally relied on measurement of glycosuria as an indirect method of estimating plasma glucose concentration to guide adjustment of insulin and diet therapy. Our observations on the correlation between mean plasma glucose concentration with simultaneous urine glucose concentration or excretion rate re-emphasize the limitations of this approach. Although our observations show a significant correlation (P less than 0.0001) between plasma glucose concentration and urine glucose concentration or urine glucose excretion rate, the wide confidence limits [95% confidence limits (minimum) +/- 150 mg/dl] on plasma glucose concentration estimated from urine glucose measurements limit the clinical applicability of such estimates. Differences among subjects in the renal resorption of glucose contribute to the wide variance of estimates. However, significant variability in renal glucose resorption within individuals is documented, further reinforcing the limitations of urine glucose determinations for reliable estimates of plasma glucose concentrations. Diabetologists need to reconsider the applicability of urine glucose measurements in evaluation of adequacy of therapy and in adjustment of insulin dosage.

Methylphenidate treatment of hyperactive children: effects on the hypothalamic-pituitary-somatomedin axis.

To further define the influence of methylphenidate on the growth hormone-somatomedin axis and prolactin secretion, serum growth hormone and prolactin concentrations were assessed over 24 hours and in response to provocative stimuli. The nine hyperactive subjects were all studied during methylphenidate therapy and after drug discontinuation, Diurnal patterns of growth hormone and prolactin concentrations were assessed using an ambulatory, continuous blood withdrawal procedure to ensure that activity, caloric intake, and sleep patterns mimicked normal schedules. No significant difference in integrated concentration of growth hormone, fasting somatomedin concentration, or prolactin integrated concentration was detected between subjects receiving or not receiving methylphenidate. There was a significant increase in peak growth hormone response to arginine stimulation among subjects receiving methylphenidate therapy; however, this appeared to correlate with acute methylphenidate administration. These data do not support the hypothesis that growth defects in hyperactive children treated with methylphenidate are caused by alteration in the hypothalamic-pituitary-somatomedin axis.

Hyperthyroidism caused by inappropriate thyrotropin hypersecretion: studies in patients with selective pituitary resistance to thyroid hormone.

We have identified the condition of thyrotropin (thyroid-stimulating hormone [TSH])-induced hyperthyroidism secondary to selective pituitary insensitivity to thyroid hormone in three patients. Each patient was clinically hyperthyroid, with elevated serum levels of thyroxine (T4) and triiodothyronine (T3) and detectable levels of serum TSH before therapy. After therapy each patient had notably elevated TSH levels at a time that peripheral levels of thyroid hormones were in the hyperthyroid range. Before and after therapy, serum levels of TSH were suppressed by therapy with liothyronine sodium and were stimulated by protirelin (thyrotropin-releasing hormone) both before and after liothyronine and dexamethasone treatment. Dexamethasone therapy decreased the levels of TSH, protirelin-stimulated TSH, and circulating T4 and T3. Serum levels of glycoprotein alpha-subunit were 0.6 to 2.4 ng/ml, values considerably lower than found in patients with TSH-secreting pituitary tumors. We suggest that the frequency of TSH-induced hyperthyroidism secondary to pituitary insensitivity to thyroid hormone may be higher than presently indicated in the medical literature.