Juvenile Rheumatic Diseases Research Articles

Disease impact and disease-unrelated strain in parents of children with rheumatic disease: Is there an influence on disease-related information needs?*

Objective. To explore the information needs of parents of children with juvenile idiopathic arthritis and other rheumatic diseases with emphasis on possible intervening factors, such as disease-related or disease-unrelated strain.Methods. A cross-sectional, anonymous survey using a purpose-designed questionnaire, incorporating, among others, the Impact on Family Scale. The questionnaire was sent to 146 families continuously attending a pediatric rheumatology outpatient clinic. The response rate was 80%. The mean age of the children was 6.9 (±4.3) years. Mean CHAQ score was 0.259 (±0.45; range 0.0 to 2.13).Results. Parents considered themselves well-informed. They frequently mentioned having received information on core domains of medical aspects. They described deficits related to psychosocial impact, to vocational education and to complementary therapy. However, their interest in further information was high, almost irrespective of the amount of prior information. Unexpectedly, neither disease impact on the family nor the presence and number of disease-unrelated life events seemed to have an influence (positive or negative) on the parents’ information needs.Conclusion. With respect to individually tailored information strategies, it should be taken into account that even for topics largely covered by usual medical advice, residual interest and information needs remain high. We were furthermore able to ascertain topics of particular interest but failed to substantiate our clinical impression that families who feel burdened with disease-related and or disease-unrelated stressors are less likely to be interested in further disease-related information.

The differential effect of child age on the illness intrusiveness–parent distress relationship in juvenile rheumatic disease.

Examine age-related patterns of association between parent-reported illness intrusiveness and parent distress in parents of youth with juvenile rheumatic diseases (JRDs). Cross-sectional multiple regression analysis tested child age as a moderator in the illness intrusiveness-distress relationship. Fifty-two parents of children ages 9-17 diagnosed with JRD. The Illness Intrusiveness Scale--Parent Version and the Brief Symptom Inventory. Parent-reported illness intrusiveness demonstrated a significant main effect on distress for all parents in the sample. This was qualified by an Illness Intrusiveness x Child Age interaction. Illness intrusiveness was found to be significantly related to distress among parents of older youth, but was only marginally related to distress for parents of younger children. Results are consistent with family life cycle development models of adjustment to childhood chronic illness. The clinical implications of the findings are also discussed.

Antibodies to mutated citrullinated vimentin and antibodies to cyclic citrullinated peptides in juvenile idiopathic arthritis

The goal of the study was to assess the presence of antibodies to mutated citrullinated vimentin (anti-MCV) and cyclic citrullinated peptides (anti-CCP) in patients with juvenile idiopathic arthritis (JIA) compared with patients with other juvenile onset rheumatic diseases. The study included 56 patients who fulfilled the International League of Associations for Rheumatology (ILAR) classification criteria for JIA, and 17 control patients with other juvenile onset rheumatic diseases. Data on six core outcome variables and the Sharp score were collected for patients with JIA. Sera and synovial fluid, if available, were tested for anti-CCP and anti-MCV antibodies using a commercial enzyme-linked immunosorbent assay (ELISA). Anti-MCV antibodies were positive in 3/56 (5.4%) and anti-CCP in 1/56 (1.8%) of patients with JIA. Two out of three anti-MCV positive patients (one of them also anti-CCP positive) were found to be rheumatoid factor (RF)-positive with polyarticular disease. Within the control group, anti-MCV was positive in 4/17 (23.5%) patients, while anti-CCP positivity was not observed. No correlation between anti-MCV with anti-CCP antibody levels was found for any of the six core outcome variables or for the adapted Sharp score. Our results show that antibodies targeting citrullinated proteins are not a useful diagnostic marker for JIA, but can indicate severe patterns of disease in JIA.

Brief Report: Illness Intrusiveness and Adjustment among Native American and Caucasian Parents of Children with Juvenile Rheumatic Diseases

To investigate cognitive appraisal-adjustment relationships in Native American (NA) and Caucasian parents of children diagnosed with juvenile rheumatic diseases. NA (n = 16) and Caucasian (n = 24) parents completed measures of disease status, illness intrusiveness, and adjustment; the rheumatologist provided estimates of disease severity. Hierarchical regression analysis revealed a moderating effect for racial group membership on the illness intrusiveness-parent adjustment relationship. Specifically, parent-perceived illness intrusiveness was more closely related to poorer adjustment among NA parents relative to Caucasian parents. Post hoc tests indicated that illness intrusiveness was significantly associated with poorer adjustment in NA parents, but was unrelated to parent adjustment in the Caucasian sample. Results highlight the importance of examining racial group differences in cognitive appraisal-adjustment outcome relationships. Results are discussed with respect to the need for incorporating cultural issues into pediatric chronic illness research and treatment.

Role for Leptin and Prolactin in Human Juvenile Rheumatic Diseases

This study was done to evaluate the relation between the level ofleptin, prolactin, IL-4 and IL-5 with the activity of Rheumatoid Arthritis (RA) and Lupus erythematosus (SLE). The study included 33 patients divided into two groups. Group 1 included twenty-one patients with Juvenile rheumatoid arthritis (13 males and 8 females) with age 11.9 +/- 3.6 years and twelve patients with systemic lupus erythematosus were enrolled as group 2 (2 males and 10 females) with age 15.8 +/- 2.9 years. Twenty-one healthy children with matched age, sex and anthropometrics measures were included in the study to serve as control group (group 3). There were significant increases in the levels of Leptin (<0.038), Prolactin (p < 0.021) IL-4 (p < 0.005) in Juvenile Rheumatoid Arthritis group with insignificant decrease in IL-5 (p < 0.724) in comparison to control group. Systemic Lupus group show a significant increase in level of Leptin (p < 0.05), Prolactin (p < 0.02) and IL-4 (p < 0.000) with an insignificant increase in IL-5 (p < 0.685) in comparison to control group. RA patients show a positive significant correlation between Prolactin, IL-5 and activity with negative insignificant correlation between IL-4 and activity. Where in Lupus patients there was a positive significant correlation between Prolactin, IL-4 and activity with negative insignificant correlation between IL-5 and activity. There was no correlation between Leptin and activity in both diseases (RA, SLE). There's a highly significant positive correlation between serum Leptin levels and BMI among all patients of RA and Lupus (p < 0.000, p < 0.003), respectively. There was a difference in the Leptin level between male and female patients with a significant increase in the female than male (p < 0.05). We can conclude from our results that Leptin cannot be used to assess disease activity in RA and SLE where Prolactin can be used to assess disease activity in RA and SLE.

A Cognitive Diathesis-Stress Model of Depressive Symptoms in Children and Adolescents With Juvenile Rheumatic Disease

In this study we tested a cognitive diathesis-stress theory of depressive symptoms (i.e., learned hopelessness theory) in children with juvenile rheumatic disease (JRD). Participants ages 9 to 17 with JRD completed measures of depressive symptoms, perceived control over daily illness symptoms, and attributions for disease-unrelated negative events. Results revealed that general negative attributions were associated with greater depressive symptoms only under conditions of low perceived control, after controlling for disease and demographic variables. Findings support a cognitive diathesis-stress conceptualization of depressive symptoms in children with JRD, suggesting the importance of interventions that target both illness-related (i.e., perceived control) and unrelated cognitive appraisals (i.e., general negative attributions).

Pain, Fatigue, Family Functioning, and Attitude Toward Illness in Children with Juvenile Rheumatic Diseases

Pain and fatigue adversely affect the physical and psychosocial functioning of children with Juvenile Rheumatic Diseases (JRDs). Research investigating relations among disease severity and family functioning has produced mixed results. There is scant research examining the relations among illness attitudes and disease severity. Children (50 girls and 32 boys) with a JRD and their parents participated in this study. Parents completed a scale assessing family functioning and children completed information about their experience of pain and fatigue and attitude toward their illness. Regression analyses indicated that children experiencing more pain and fatigue were apt to hold negative attitudes toward their illness, and that parents reported lower family functioning when children were experiencing higher levels of fatigue. Research examining relations among child and reports of family functioning and children’s attitudes toward their illness will provide information for health care teams serving these children and their families.

School Support and Functioning for Children with Juvenile Rheumatic Diseases

Information about ways to support children with Juvenile Rheumatic Diseases (JRDs) in school will help maximize their involvement in this setting. For this study, children with JRDs provided their views about the support they need from school nurses, teachers, classmates, friends and leaders of after school activities. Parents provided information about their child’s disease and about family functioning. Results indicated that positive family functioning was related to lower needs for support from school nurses, teachers, and classmates. Family functioning was not related to the support children needed from good friends. Receiving help during after school activities and school nurse availability were areas of concern for some children. Future studies should continue to assess needs for school support for adolescents, who may need more support at school due to a decreased reliance on family support.

Echocardiographic patterns of juvenile rheumatic heart disease at the Kenyatta National Hospital, Nairobi

To describe the echocardiographic features of children with rheumatic heart disease seen at the Kenyatta National Hospital. A retrospective study. The Kenyatta National Hospital Heart Unit. Patients aged 20 years and less with echocardiographic diagnosis of rheumatic heart disease. Two hundred and twenty four echocardiograms were analysed. Seventy six point four of cases were aged between 5 and 15 years, while on 3% were less than five years. The combinations mitral and aortic regurgitation was the most common lesion followed by isolated mitral regurgitation. Isolated aortic regurgitation was as rare as isolated mitral stenosis in the paediatric age group 1.8% and 2.7% respectively. When seen in the younger age group, the leaflet morphology in mitral regurgitation was predominantly thickening and clubbing of the leaflets while in the older children the pathology was of marked fibrosis of the sub-valvular apparatus. Leaflet prolapse and commissural fusion was the major pathology in aortic regurgitation. Pulmonary hypertension was the most common complication commonly seen in mitral valve disease. Calcification was a rare encounter in this age bracket. Rheumatic heart disease in the paediatric age commonly presents as isolated mitral regurgitation or in combinations of mitral and aortic regurgitation. The complications of pulmonary hypertension was predominant in mitral valve disease. Valvular calcification is rare in juvenile rheumatic heart disease.

What are the costs of childhood-onset rheumatic disease?

Juvenile rheumatic diseases have important impacts on health, i.e. on patients' body functions and structures, activities, and social participation. The identification and treatment of these disorders is costly. Treatment involves periods of hospitalization, the use of physicians and other professional services, drugs and other treatments. Frequent outpatient visits are needed, as may be surgery. This all imposes a large financial burden on health-care systems and on families of children who suffer from rheumatic illnesses. Costs borne by families are both out-of-pocket as well as related to time spent in providing care, which may involve loss of income. Of course, the burdens are not only monetary, and they sometimes continue for life. The measurement of the different types of cost is essential to get a full picture of the burden of childhood-onset rheumatic illnesses. This chapter presents data on the costs of these illnesses, and introduces methodologies and their limitations for cost evaluation within paediatric rheumatology.

Lack of association between TNFα gene polymorphism at position –308 and risk of acute rheumatic fever in Turkish patients

Objective: Acute rheumatic fever (ARF) is a multisystem inflammatory disease process that follows nasopharyngeal infection caused by group A streptococcus (GAS) (Streptococcus pyogenes). Recent studies have demonstrated that allelic variations at the tumour necrosis factor alpha (TNFα) locus are involved in the nature of rheumatic diseases such as juvenile idiopathic arthritis and rheumatic heart disease. Thus, TNFα polymorphisms at –308 in ARF patients might be useful in contributing to identification of the primary factors associated with pathogenesis of ARF.Methods: We performed a case–control association study between the common G/A promoter polymorphism at position –308 in the TNFα gene and ARF in Turkish patients, investigating whether this locus acts as a risk factor or has a modifying effect.Results and Conclusion: Previous studies have reported that TNFα plays a major role in the pathogenesis of a number of autoimmune and inflammatory diseases. Moreover, significantly elevated TNFα levels were reported in patients with ARF. However, in our sample of patients with ARF (n = 66), no such association was found. No interactive effect was found between the TNFα polymorphism at position –308 and no association was detected with disease progression. These findings suggest that the role of TNFα in ARF may be in linkage disequilibrium with some other severity genes not yet genetically determined.

Learned helplessness in children and adolescents with juvenile rheumatic disease

Objective To examine a learned helplessness conceptualization of psychological sequela in children and adolescents with juvenile rheumatic diseases (JRD) via an experimental procedure utilizing behavior–outcome contingent and noncontingent feedback. Methods Thirty-eight children and adolescents with JRD completed measures of transient affect, self-efficacy for functional ability, and causal attributions prior to and immediately following a computerized learned helplessness induction procedure. Results Children across contingent and noncontingent feedback conditions experienced decreased positive affect with a slightly more pronounced decline in the noncontingent condition. Noncontingent feedback resulted in poorer internalization of success for problem solving, while contingent feedback resulted in greater internalization of success for problem solving. Additionally, posttreatment control self-efficacy was significantly greater for children in the contingent condition that initially endorsed higher levels of internal task attributions. Conclusions Children with JRD who experience behavior–outcome contingency in their environment may develop increased perceptions of control over functional ability. Furthermore, environmental noncontingency may result in poorer internalization of success, whereas contingent reinforcement may enhance cognitive appraisal mechanisms (i.e., causal attributions) associated with favorable disease outcome. Despite a modest decline in positive affect for children in the noncontingent condition, mood dysfunction is not entirely explicable within the context of noncontingent reinforcement.

Recent developments in immunomodulatory peptides in juvenile rheumatic diseases: from trigger to dimmer?

Current therapy for juvenile rheumatic diseases is based on general immune suppression or blocking inflammatory pathways. These treatments do not induce long-term disease remission and have a risk of side effects; this is especially unfavorable in children. It is better to focus on induction of tolerance mechanisms than on suppression of inflammation. This promotes epitope specific immunotherapy as a possible safe treatment option. In the search for specific peptides for immunotherapy in autoimmunity, the focus is shifting from purported triggers of disease to peptides that regulate the ongoing inflammation. These so-called 'immunomodulatory peptides' are important in every healthy immune system. Several juvenile rheumatic diseases have been linked to certain immunomodulatory peptides. In juvenile dermatomyositis, peptides from human skeletal myosin play a role in the perpetuation of the disease. In systemic lupus erythematosus, the focus is mostly on DNA-derived peptides and peptides from anti-DNA antibodies. In juvenile idiopathic arthritis, heat shock proteins have been shown to contain important immunomodulatory epitopes. Immunomodulatory peptides play an important role in juvenile rheumatic diseases. Promising candidates for immunotherapy have been identified. This opens the possibility of clinical testing in rheumatic diseases of childhood.

Children's Perceived Illness Uncertainty as a Moderator in the Parent-Child Distress Relation in Juvenile Rheumatic Diseases.

Children’s perceived illness uncertaintymoderated the parent-distress/child-depressive-symptom relation. Parent distress was associated with childdepressive symptoms only under conditions of high child-perceived uncertainty; under conditions of lowillness uncertainty, parent distress was unrelated to child depressive symptoms.

Peer rejection, social behavior, and psychological adjustment in children with juvenile rheumatic disease.

To examine the associations among disease status, social competence, and depressive symptoms in children with juvenile rheumatic disease (JRD) and to test the hypothesis that individual differences in children's social competence account for a significant proportion of variance in depressive symptoms after controlling for disease status variables. Thirty-six children with JRD completed standardized instruments to assess pain, health status, and depressive symptoms. The rheumatologist completed a disease severity measure, and teachers provided ratings of peer rejection and social behavior. Pain, peer rejection, and problematic social behavior were all positively associated with depressive symptoms. Social variables remained significantly associated with depressive symptoms after controlling for level of pain. In addition, peer rejection moderated the association between pain and depressive symptoms, such that children with high levels of pain and high levels of peer rejection reported the highest frequency of depressive symptoms. Health care providers should assess the social functioning of children with JRD in order to identify socially vulnerable children who may be at increased risk for internalizing problems.

The influence of parental distress on child depressive symptoms in juvenile rheumatic diseases: the moderating effect of illness intrusiveness.

To examine the role of children's illness-related cognitive appraisals in the parent-child adjustment relationship in a sample of children and adolescents with juvenile rheumatic disease (JRD). Specifically, we tested the moderating effect of children's perceived illness-induced barriers (i.e., illness intrusiveness) in the parent distress-child depressive symptom relationship. Participants were 45 children and adolescents (ages 9-17) diagnosed with JRD. Children completed measures of depressive symptoms (Children's Depression Inventory), functional disability (Juvenile Arthritis and Functional Assessment Report), and illness intrusiveness (Illness Intrusiveness Scale-adapted for children); parents completed a brief measure of global distress (Brief Symptom Inventory). The pediatric rheumatologist provided functional disability ratings following a routine physical exam. Both increased parental distress and child illness intrusiveness were associated with greater child depressive symptoms. Direct effects were qualified by a significant Parent Distress x Illness Intrusiveness interaction. The influence of general parental distress on child depressive symptoms was enhanced under conditions of increased child-reported illness intrusiveness. Results support transactional conceptualizations of child adjustment to chronic illness. Findings also emphasize the need to examine the interaction of parent and child variables, particularly cognitive appraisals, in child adjustment. Results and treatment implications for children with JRD are discussed in terms of reinforcement theories of depression.

Antiphospholipid antibodies in pediatric and adult patients with rheumatic disease are associated with parvovirus B19 infection.

To show a possible association between parvovirus B19 infection and the presence of antiphospholipid antibodies (aPL) in patients with rheumatic diseases. Serum samples obtained from 88 children with various forms of juvenile rheumatic disease and from 40 adults with systemic lupus erythematosus, the antiphospholipid syndrome, or other rheumatic disease, who had previously been tested and shown to be positive for IgG aPL, were analyzed for the presence of B19 DNA, for antibodies against the B19 viral proteins VP1, VP2, and NS1, and for IgG aPL (anticardiolipin, anti-beta(2)-glycoprotein I, and antiphosphatidylserine). As controls, serum samples obtained from 135 children with noninflammatory bone diseases or growth retardation were also analyzed. Twenty-four (27%) of the 88 children with rheumatic diseases had detectable amounts of IgG aPL. Fourteen (58%) of these 24 IgG aPL-positive patients showed IgG against VP1/VP2 and viral genomes, indicating the presence of acute (2 patients) or persistent (12 patients) infection. Past parvovirus B19 infection was identified in 7 (29%) of 24 IgG aPL-positive children, as indicated by VP1/VP2-specific IgG in the absence of viral DNA. Three (12%) of 24 IgG aPL-positive children had not been infected with B19. Sixty-nine (51%) of 135 control children displayed VP1/VP2-specific IgG. Three (2%) of these 135 children were IgG aPL positive (2 children had past parvovirus B19 infection, and 1 was negative for parvovirus B19). Analysis of the parvovirus B19 status of 40 adult IgG aPL-positive patients showed that 33 (83%) were anti-IgG VP1/VP2-positive, and viral DNA was detected in 11 patients (28%). Ten of these 11 viremic patients were in the subgroup of 28 IgG aPL-positive SLE patients. Antiphospholipid antibodies are preferentially found in serum of children with juvenile idiopathic arthritis who have been previously infected with parvovirus B19 and have established, persistent infection. Adult patients with IgG aPL positivity have a high incidence of persistent parvovirus B19 infection. We conclude that parvovirus B19 might be directly involved in the elicitation of autoimmune reactions partly mediated by aPL.

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood.

To find further evidence of the association of parvovirus B19 infection with juvenile rheumatic diseases, and to get new insights into the immunopathogenesis of these diseases. Paired serum and synovial fluid samples from 74 children with rheumatic disease were analyzed with respect to their content of viral DNA and antibodies directed against the B19 viral proteins VP1, VP2, and NS1. Control sera from 124 children with noninflammatory bone diseases or growth retardation were also analyzed. The sequence of the viral DNA, amplified by polymerase chain reaction (PCR), was determined. IgG-complexed virus was isolated from sera and synovial fluid by adsorption to protein A beads. The amount of free virus versus immunocomplexed virus particles was determined by quantification of the viral genomes by quantitative PCR. Twenty-six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1-specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001). In addition, 3 patients (4%) showed VP2-specific IgM. In 15 patients, viral DNA could be repeatedly detected in followup samples of serum and synovial fluid. Sequencing revealed low-degree nucleotide variations that are in the range of genotype 1 of parvovirus B19. Immunocomplexed virus was present in varying amounts, both in the sera and in the synovial fluid samples. Parvovirus B19 is frequently found in serum or synovial fluid of children with rheumatism. The rate of persistent B19 infection in these patients is significantly higher than in age-matched controls.

Minor impact of juvenile arthritis on nutritional status in young adult patients.

Growth abnormalities and poor nutritional status have been reported in children with juvenile idiopathic arthritis (JIA). The aim of this study was to evaluate the impact of juvenile chronic rheumatic disease on current nutritional status in adult patients in remission or with active disease. One hundred thirty-eight women and 82 men, aged >20 years, with JIA were studied after a mean disease duration of 15.5 +/- 2.3 years. Eighty-four (61%) of the women and 49 (60%) of the men were in remission. Forty-one healthy women and 54 healthy men served as a reference group. Body composition was analyzed by dual-energy x-ray absorptiometry. There was no difference in height or body mass index (BMI) between patients and healthy subjects. However, female patients with systemic disease had significantly reduced BMI compared with those with pauciarticular JIA (P < 0.001), and female patients who used or had been using corticosteroids had significantly lower weight, height, and BMI compared with the patients who had never used corticosteroids (P < 0.05). Female patients in remission had significantly more lean body mass compared with healthy controls (P < 0.05) and significantly less body fat was found in both women and men (P < 0.01 for both). Patients with active disease had the same amount of lean body mass as the healthy controls, but significantly less body fat (P < 0.05 for women and P < 0.01 for men). Adult patients with JIA had attained normal height, weight, and BMI, with the exception of women with systemic JIA and those who were using or had used corticosteroids. Patients with JIA in remission seemed to have a better nutritional status than healthy subjects.

Life stressors, social resources, and coping skills in youth: applications to adolescents with chronic disorders.

After setting out a conceptual framework that focuses on how personal and social resources aid adolescents in managing acute and chronic stressors, I describe methods by which to assess adolescents' family environments and specific life stressors and social resources, and the approach and avoidance coping responses adolescents use to manage life stressors. I then review some research that employs these concepts and methods to focus on the families and life contexts, and coping skills, of youth with chronic medical disorders, including juvenile rheumatic disease (JRD). I close by drawing implications for assessment and intervention and describing some fruitful areas for future research, such as examining the reciprocal linkages between parental and youth behavior, how adolescents' personal characteristics shape their life context, and how life crises and transitions enhance adolescents' development and maturation.