Disease experience and psychosocial adjustment in children with juvenile rheumatoid arthritis: children's versus mothers' reports.

Adjustment in children with juvenile rheumatoid arthritis (JRA) has been evaluated most frequently by parental or teacher reports and with reference to disease severity. In this study, 38 children, ages 7 to 13 with JRA, and their mothers were interviewed. Modest correlations were found between children and mothers in their assessments of children's perceived competence in several domains (i.e., athletic competence, social acceptance, physical attractiveness, and global self-worth) and in their perceptions of how JRA is experienced by children and families. Children's perceptions of the disease experience were significantly correlated with the four measures of perceived competence, even after controlling for disease severity. The results highlight the importance of cross-validating parental reports with children's self-reports, and demonstrate the need to consider variables other than disease severity--in particular how JRA is interpreted by children--in predicting their adjustment.     

Comparing parental distress,family functioning,and the role of social support for caregivers with and without a child with juvenile rheumatoid arthritis

OBJECTIVE: To assess parental distress, family functioning, and social support among parents of children with a lifetime diagnosis of juvenile rheumatoid arthritis (JRA) and comparison families. METHODS: Parents of 64 children with JRA (64 mothers, 46 fathers) completed questionnaires and in-home interviews along with 64 matched comparison families. Average time since diagnosis for children with JRA was 70 months. RESULTS: Families of children with JRA generally reported levels of parental distress, family functioning, and social support similar to those for comparison families. More mothers of children with JRA exceeded the clinical cutoff on the SCL-90-R than comparison mothers. Although disease characteristics and social support did not distinguish subgroups of parents at greater risk for problems, family supportiveness and conflict were associated with caseness for mothers of children with JRA. CONCLUSIONS: Families of children with JRA exhibited substantial resilience over the long term. Further multisite study of children recently diagnosed and with more severe forms of JRA is warranted to determine intervention needs, especially for mothers.     

Interactions between children with juvenile rheumatoid arthritis and their mothers

OBJECTIVE: To determine the degree to which mothers of children with juvenile rheumatoid arthritis (JRA) show an overprotective or highly controlling interaction style. METHOD: We videotaped 84 mother-child pairs (42 JRA and 42 healthy, ages 6 to 13) while working on a collaborative problem-solving task. Based on physical therapy evaluations, children in the JRA group were assigned to "more severe" (n = 19) and "milder" (n = 22) arthritis subgroups. RESULTS: Results showed numerous differences between mothers of children with more severe arthritis and the other mothers (no differences between the milder arthritis and healthy comparison groups were found). Compared to mothers in the other two groups, mothers of children with more severe arthritis were more directive of their children's behavior during the task, showing higher rates of structure and rule setting, general clues, and prompting the child for an answer. DISCUSSION: Sequential analyses showed that mothers in the more severe group appeared to treat the task in a more evaluative manner, being more likely than other mothers to respond to correct answers with positive feedback and to incorrect answers with structure and rule setting. Mothers in the other groups were more likely to respond to both correct and incorrect answers with specific clues. CONCLUSIONS: We discuss how these differences in interactional style might impact the social development of children with JRA.     

Functioning among mothers and fathers of children with juvenile rheumatic disease: a longitudinal study.

Examined the adaptation of mothers and fathers of children with juvenile rheumatic disease on two occasions, 1 year apart, using 159 married couples at Time 1, and 111 of these couples at Time 2. A stress and coping model was tested in which parental functioning is determined by ongoing life stressors (patient and spouse dysfunction), family resources, and parents' illness-related coping. Mothers reported more depression than fathers did. However, poorer concurrent functioning among both mothers and fathers was explained partly by patients having more functional disability, pain, and psychosocial problems. In addition, spouse's dysfunction and the parent's use of avoidance coping were related to poorer parental adaptation, both concurrently and 1 year later. The implications of the findings for developing stress and coping models of parental adaptation to having a chronically ill child, and for intervention strategies with parents, patients, and families, are discussed.     

Living with a chronic illness: a measure of social functioning for children and adolescents

OBJECTIVE: To describe the development and initial psychometric evaluation of a measure of social functioning in children and adolescents with chronic medical conditions, Living with a Chronic Illness (LCI), designed to distinguish social difficulties related to the illness from those social difficulties associated with other factors (e.g., limited income). METHODS: Parents (n = 108) and youths (n = 115) completed the LCI, along with other psychological measures (e.g., Youth Self-Report). Teachers completed the Teacher Report Form and provided grade and absence data. Health care utilization data were obtained from medical charts. RESULTS: Statistical analyses supported the internal consistency and initial validity of LCI scores. Correlational results strongly point to the distinction made between illness-related and non-illness-related social difficulties and suggest that the LCI has some relation to existing measures (e.g., Child Behavior Checklist), while still providing a unique perspective on children's social functioning. Univariate and regression analyses revealed significant relations between LCI scores and health care utilization. CONCLUSIONS: These findings support the initial psychometric properties and clinical utility of the LCI scores. We discuss strengths and limitations of this study, as well as potential clinical applications for the LCI questionnaire.     

Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile idiopathic arthritis and rheumatoid arthritis

We tested the possible association of the 14-bp polymorphism of the HLA-G gene in the course of two inflammatory diseases, rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Patients and controls were genotyped for the 14-bp polymorphism by polymerase chain reaction with specific primers for the exon 8 of the human leukocyte antigen (HLA)-G gene and the amplified fragment was visualized in a 6% polyacrylamide gel. A total of 106 JIA patients, 265 RA patients, 356 healthy adults and 85 healthy children were genotyped for the 14-bp polymorphism. Female JIA patients presented a higher frequency of the -14 bp allele when compared with female healthy children (0.743 and 0.500, corrected P=0.003), which reflected in the JIA group as a whole. This increased frequency of the -14-bp allele was observed in all JIA subtypes. In RA patients, no differences in allelic and genotypic frequencies were observed between patients and controls. No correlations were observed among genotype and disease severity or clinical manifestations. Our data suggest that the HLA-G -14 bp allele is probably a risk factor for JIA, mainly in females. Considering the differences observed in relation to gender, we suggest that hormonal differences can interfere with the development of JIA. Considering the RA patients, our data agree with results from the literature and highlight the differences in the etiology of RA and JIA.     

Leflunomide in the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic and highly morbid disease affecting approximately 1% of the world’s population. With the advent of disease-modifying antirheumatic drugs, patients are increasingly able to maintain control of their arthritis and prevent joint destruction. However, not all patients respond adequately to any single disease-modifying antirheumatic drug, and many newer parenteral therapies are cost prohibitive. Leflunomide, an inhibitor of pyrimidine biosynthesis, is the first oral disease-modifying antirheumatic drug to have been approved for rheumatoid arthritis in the USA in the last 15 years, and is now widely used in over 70 countries around the world. Leflunomide is efficacious when used as monotherapy or in combination with methotrexate to treat patients with rheumatoid arthritis, and is generally well tolerated. As clinical use increases, new ways to use leflunomide in order to minimize toxicity and maximize efficacy are being explored.     

Local synthesis of both macrophage and T cell cytokines by synovial fluid cells from children with juvenile rheumatoid arthritis.

The production of tumour necrosis factor-alpha (TNF-alpha), TNF-beta and IL-6 in synovial fluid was studied in 50 samples of synovial fluid from 44 children with juvenile rheumatoid arthritis (JRA) by identifying cytokine production at a single-cell level. Post Ficoll-separated synovial fluid mononuclear cells were permeabilized and then intracellular TNF-alpha, TNF-beta and IL-6 protein production was examined using indirect immunofluorescence and murine anti-cytokine MoAbs. All three cytokines were measured in 37 of the 50 samples. In 25 of the 37 samples there was complete concordance; all three cytokines were present in six and absent in 19 samples. At least one cytokine was present in 27/50 (54%) of synovial fluid samples. Overall, TNF-alpha was detected in 22/49 (45%) samples, TNF-beta in 15/41 (37%) and IL-6 in 16/45 (36%) samples. Five patients had serial arthrocentesis, and in these samples there were two patients who had initially positive cytokine production, which on subsequent measurement was negative; in the other three patients there was no change from the previous cytokine production. We provide evidence that synovial fluid mononuclear cells produce monocyte and T cell cytokines in JRA. These findings suggest a role for both T cell and macrophage products in the pathogenesis of JRA, and the potential for modulation of cytokine production as a target for therapeutic intervention.     

The impact of disability and disease duration on social support of women with rheumatoid arthritis

The objective was to investigate the impact of physical disability and disease duration on the amount of social support received by female patients with rheumatoid arthritis. Two hundred sixty-four patients were assessed in a cross-sectional study. Disease duration had a negative relationship to daily emotional support; the length of disease duration was related to less emotional support. A combination of long disease duration and high disability was related to a low degree of problem-oriented emotional support. High physical disability was associated with less social companionship. Patients with high disability and few friends and patients with high disability and few neighbours reported less social companionship than patients with high disability and four or more friends or three or more neighbours. The combination high disability and few friends were associated with less problem-oriented instrumental support. Number of friends, age, and personality type all contributed to the variance in social support.     

Composition and biological behaviour of immune complexes isolated from synovial fluid of patients with juvenile rheumatoid arthritis (JRA)

Data published from In vitro studies have shown that IgM-rheumatoid factor (RF)-bearing immune complexes possess several biological features that may contribute to their pathogenicity. However, no studies have demonstrated that such complexes exist at sites of inflammation in children with rheumatoid disease. We used two methods of sequential column chromatography to purify immune complexes from synovial fluids of children with JRA. We demonstrate that high molecular weight complexes contain IgM-RF, have not bound C4 in vivo, but activate the classical pathway in vitro. In contrast, complexes which have bound C3 in vivo do not contain IgM- RF and are weak complement activators in vitro.     

Brief report: adjustment to juvenile rheumatoid arthritis: a family systems perspective

OBJECTIVE: To examine the relations of the family environment to adjustment to juvenile rheumatoid arthritis (JRA), and to examine how those relations are influenced by child sex and age. METHOD: Ninety-four children with JRA completed a questionnaire on family environment and adjustment. RESULTS: Family cohesion was related to good adjustment, whereas family conflict was related to poor adjustment. Some relations of family cohesion to adjustment were stronger for younger than for older children. The relations of child autonomy to adjustment depended on child sex and age. CONCLUSION: The relations of the family environment to adjustment to JRA are dependent on child sex and age.     

Brief report: use of complementary and alternative medicine and psychological functioning in Latino children with juvenile idiopathic arthritis or arthralgia

OBJECTIVE: To describe the use of complementary and alternative medicine (CAM) and its relationship to symptoms of anxiety, depression, and dysthymia in Latino children with juvenile idiopathic arthritis (JIA) or arthralgia. METHODS: Parents of 36 children between the ages of 6 and 16 years with either JIA (n = 17) or arthralgia (n = 19) completed questionnaires during routine pediatric rheumatology clinic visits assessing use of CAM and psychological functioning. RESULTS: CAM was used by the majority of children primarily to treat pain episodes. The most common modalities were prayer and massage therapy. CAM use was associated with decreased symptoms of anxiety and dysthymia in children with arthralgia, but not in children with JIA. CONCLUSION: Preliminary findings suggest that CAM use is associated with improved psychological functioning in children with arthralgia. Healthcare providers are encouraged to routinely screen for CAM usage and to educate families about the potential benefits and limitations of CAM.     

Polysomnography and self-reported sleep, pain, fatigue, and anxiety in children with active and inactive juvenile rheumatoid arthritis

OBJECTIVE: To compare polysomnography (PSG) and self-reported sleep, symptoms (pain and fatigue), and anxiety between children with active and inactive juvenile rheumatoid arthritis (JRA) and examine relations among sleep, symptoms, and anxiety. METHODS: Two consecutive nights of PSG, self-reported sleep, and symptoms were obtained in 70 children 6-11 years of age with active (n = 35) or inactive (n = 35) JRA. RESULTS: On the second (study) night, PSG and self-reported sleep variables were not different, but pain and fatigue were significantly higher (both p <.02) in children with active compared to inactive disease. In a stepwise regression, age, medications, disease status, anxiety, evening pain, total sleep time, and arousals explained 36% of the variance in fatigue and age, disease status, and evening pain were significant (all p <.04) predictors of fatigue. All children showed longer sleep latency and reduced sleep efficiency on the first night in the laboratory. CONCLUSIONS: Sleep was not altered in children with active JRA, however, the "first night effect" suggests that valid laboratory sleep assessments require an adaptation night.     

Risk and resistance factors in the adaptation in mothers of children with juvenile rheumatoid arthritis

OBJECTIVE: To examine the importance of illness severity, child functional status, psychosocial stress, intrapersonal factors, stress processing, and social-ecological factors in predicting psychological symptoms among mothers of children with juvenile rheumatoid arthritis (JRA). METHODS: Mothers of 92 children with JRA completed surveys while waiting with their children for physician appointments or during JRA meeting breaks. RESULTS: Mothers reported higher mean levels of psychological symptoms than a normative group. Higher levels of psychosocial stress predicted increased psychological symptoms after accounting for disease severity and functional status. Maternal appraisal of the illness tended to moderate the relationship between illness stress and psychological symptoms, and maternal education moderated the relationship between daily hassles stress and psychological symptoms. CONCLUSIONS: These data indicate that mothers of children with JRA are at risk for psychological distress. Inteventions that take into account the buffering effects of maternal education and appraisal may serve to decrease the effects of maternal stress.     

The putative oncoprotein DEK, part of a chimera protein associated with acute myeloid leukaemia, is an autoantigen in juvenile rheumatoid arthritis.

The 45-kD autoantigen associated with juvenile rheumatoid arthritis (JRA) has been isolated from HeLa cell nuclei and purified about 2500-fold to near homogeneity in a five-step chromatographic procedure. Purification of the antigen was monitored by immunoblot assays using a nearly monospecific anti-45-kD serum from a child with JRA. Tryptic peptide mapping and partial amino acid sequencing of the purified 45-kD antigen demonstrated its identity with the DEK protein. DEK is a 43-kD protein of unknown function expressed by the putative oncogene dek located on chromosome 6. As a result of a (6;9) translocation offociated with a rare subtype of acute myeloid leukaemia a chimeric protein containing most of DEK amino acids at the N-terminus is found in leukaemic cells (von Linden et al., Mol Cell Biol. 1992; 12: 1687-97). The 43-kD DEK was detected by immunoblotting with serum from a patient with JRA in a variety of rat tissues, and was most abundant in the spleen and in bone marrow.     

Parental distress, family functioning, and social support in families with and without a child with neurofibromatosis 1

Objective To compare parental adjustment, social support, andfamily functioning between families of children with neurofibromatosis1 (NF1) and a group of demographically similar comparison families,and to examine the impact of disease severity. Methods Questionnaireswere completed at home by parents of 54 children with NF1 (54mothers and 42 fathers) and 51 comparison children (49 mothersand 32 fathers). Results Few differences between groups wereidentified for parental distress, social support, or familyenvironment. Greater neurological impairment in children withNF1 was associated with greater distress, more family conflict,less positive mealtime interactions, and less social supportfrom the perspectives of mothers. Conclusions Overall, parentsof children with NF1 appear similar to parents of comparisonchildren. Mothers who have children with NF1 characterized bygreater neurological impairment may be at risk for more difficulties.Future work exploring long-term adjustment for these mothersas well as interventions to ameliorate any potential difficultiesmay be appropriate.     

Psychological adjustment of children and adolescents with chronic arthritis: a meta-analytic review

OBJECTIVE: To review studies of psychological adjustment among children and adolescents with chronic arthritis to determine whether they are at more risk for development of adjustment problems than controls. METHODS: We used meta-analytic techniques to review 21 studies reporting overall adjustment problems, internalizing symptoms, externalizing symptoms, or self-concept among youths with arthritis. RESULTS: Youths with arthritis displayed increased risk for overall adjustment problems and internalizing symptoms, but not for externalizing symptoms or poor self-concept. Risk was greater in studies making comparisons to study controls rather than to norms and in studies including mixed disease samples (arthritis plus other rheumatic diseases) rather than samples of youths with arthritis only. CONCLUSIONS: Results suggest the importance of assessing for internalizing problems among youths with chronic arthritis. Future research may benefit from inclusion of child self-report of adjustment problems, diagnostic specificity in reporting results, and use of adjustment measures without somatic items.     

Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis

Systemic-onset juvenile idiopathic arthritis (sJIA) is a severe and steroid-dependent disease of unknown etiology that sometimes progresses to a fatal disease known as the macrophage activation syndrome. The investigation of inflammatory cytokines and receptor levels revealed an increase in interleukin (IL)-6 and soluble IL-6 receptor (sIL-6R) in serum of patients with active sJIA. The clinical symptoms and signs of the disease are presumably attributable to the continuous elevation of IL-6 and sIL-6R levels in serum. The characteristic fever spikes parallel IL-6 levels. In children, a long-term exposure to high levels of IL-6 causes severe growth impairment, as suggested by recently established studies of IL-6 transgenic mice. The biological functions of IL-6 are expressed through the binding of IL-6/IL-6R complex to gp130. The administration of tocilizumab (a recombinant humanized anti-IL-6R monoclonal antibody) exerts its action by preventing the binding of IL-6 to its receptor and, therefore, preventing the activation of gp130. After a few cases of compassionate use of tocilizumab, phase I and II studies of tocilizumab were conducted in children with sJIA, revealing that tocilizumab abruptly reduced the typical symptoms of inflammation and improved laboratory abnormalities. This article describes the experience in Japan regarding the treatment of sJIA with tocilizumab and supports the hypothesis that high levels of IL-6 may play an important role in the pathogenesis and maintenance of this disease. A confirmation of the role of tocilizumab in the treatment of sJIA will be provided by the results of the ongoing phase III study in Japan.