The role of interleukin 10 in children with juvenile idiopathic arthritis

This thesis investigates the function of the IL-10 5' flanking region haplotypes and the association of these haplotypes in children with Juvenile Idiopathic Arthritis (JIA). We have shown that children with extended oligoarticular JIA are less likely to have a genotype containing the ATA haplotype than children with oligoarticular JIA (p<0.05, OR = 1.9,95% Cl: 1 to 3.5). The ATA haplotype is associated with lower reporter gene expression in transfection studies (Crawley, 1999c). The ATA/ATA genotype was shown to be associated with lower IL-10 production using whole blood culture in controls (p<0.02). This is consistent with the observation that mean IL-10 production was lower in the parents of those with extended oligoarticular disease when compared to the parents of children with oligoarticular disease (p=0.03, 95% Cl 88 to 2016). A similar effect was seen in asthma where those with severe asthma were less likely to have ATA containing genotypes than controls (p=0.04, OR1.57, Cl: 1.01 to 2). We did not show a difference in genotype distribution between patients with SLE and controls. The transmission disequilibrium test (TDT) demonstrated an increase in transmission of the ATA haplotype to patients with oligoarticular onset JIA (p=0.05). There was also increased transmission of both the ACC and the ATA haplotype to patients with uveitis (p=0.014 for each transmission). Strong linkage disequilibrium was demonstrated (p<0.0005) between these haplotypes and a microsatellite at -1000 in the IL-10 5' flanking region which has previously been shown to be associated with rheumatoid arthritis and systemic lupus erythematosus. Treatment of patients with methylprednisolone was associated with large changes in ex vivo stimulated IL-10 production which was strongly correlated with the change in ESR (correlation coefficient 0.922, p<0.01). To investigate whether the IL-10 5' flanking region haplotypes affected transcription, THP-1 cells were transfected with IL-10 luciferase DNA reporter constructs. Overall, reporter gene expression was higher with the GCC than the ATA construct when the THP-1 cells were transfected using Effectene Liposomes (median fold difference 1.71, range 1.12 to 5.49)

Treatment for paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) and comorbid depression:a systematic review

OBJECTIVES: At least 30% of young people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) also have symptoms of depression. This systematic review aimed to establish which treatment approaches for depression are effective and whether comorbid depression mediates outcome. SETTING: A systematic review was undertaken. The search terms were entered into MEDLINE, EMBASE, PsycInfo and the Cochrane library. PARTICIPANTS: Inclusion and exclusion criteria were applied to identify relevant papers. Inclusion criteria were children age <18, with CFS/ME, defined using CDC, NICE or Oxford criteria, and having completed a valid assessment for depression. RESULTS: 9 studies were identified which met the inclusion criteria, but none specifically tested treatments for paediatric CFS/ME with depression and none stratified outcome for those who were depressed compared with those who were not depressed. There is no consistent treatment approach for children with CFS/ME and comorbid depression, although cognitive–behavioural therapy for CFS/ME and a multicomponent inpatient programme for CFS/ME have shown some promise in reducing depressive symptoms. An antiviral medication in a small scale, retrospective, uncontrolled study suggested possible benefit. CONCLUSIONS: It is not possible to determine what treatment approaches are effective for depression in paediatric CFS/ME, nor to determine the impact of depression on the outcome of CFS/ME treatment. Young people with significant depression tend to have been excluded from previous treatment studies

Pediatric chronic fatigue syndrome:current perspectives

Esther CrawleyCentre for Child and Adolescent Health, Bristol Medical School, University of Bristol, Bristol, UKAbstract: Pediatric chronic fatigue syndrome is an important illness as it is relatively common and also very disabling with a wide range of impacts on the child, the family, and health care systems. It is a complicated illness but the majority of children get better with specialist treatment. This literature review provides an update on the epidemiology of chronic fatigue syndrome / myalgic encephalomyelitis, including factors associated with it, and discusses the current evidence for treatment.Keywords: CFS, ME, myalgic encephalomyelitis, epidemiology, pediatri

Psychological wellbeing and quality-of-life among siblings of paediatric CFS/ME patients:a mixed-methods study

Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a disabling condition known to have a negative impact on all aspects of a child’s life. However, little is understood about the impact of CFS/ME on siblings. A total of 34 siblings completed questionnaires measuring depression (Hospital Anxiety and Depression Scale (HADS)), anxiety (HADS and Spence Children’s Anxiety Scale (SCAS)) and European Quality-of-life-Youth (EQ-5D-Y). These scores were compared with scores from normative samples. Siblings had higher levels of anxiety on the SCAS than adolescents of the same age recruited from a normative sample; however, depression and quality-of-life were similar. Interviews were undertaken with nine siblings of children with CFS/ME who returned questionnaires. Interview data were analysed using a framework approach to thematic analysis. Siblings identified restrictions on family life, ‘not knowing’ and lack of communication as negative impacts on their family, and change of role/focus, emotional reactions and social stigma as negative impacts on themselves. They also described positive communication, social support and extra activities as protective factors. Paediatric services should be aware of the impact of CFS/ME on the siblings of children with CFS/ME, understand the importance of assessing paediatric CFS/ME patients within the context of their family and consider providing information for siblings about CFS/ME

Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence:Population birth cohort study

Although many studies have investigated the overlap between pain phenotypes and chronic fatigue syndrome (CFS) in adults, little is known about the relationship between these conditions in adolescents. The study's aim was therefore to identify whether a relationship exists between chronic widespread pain (CWP) and CFS in adolescents and investigate whether the two share common associations with a set of covariates. A questionnaire was administered to offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 17, asking about site, duration, and pain intensity, from which participants with CWP were identified. At the same research clinic, a computer-based Revised Clinical Interview Schedule was filled out, from which a classification of CFS was obtained. The relationship between selected covariates and CFS and CWP was investigated using a variety of logistic, ordinal logistic, and multinomial regressions. We identified 3,214 adolescents with complete data for all outcomes and covariates. There were 82 (2.6%) individuals classified as CFS and 145 (4.5%) as CWP. A classification of CFS resulted in an increased likelihood of having CWP (odds ratio = 3.87; 95% confidence interval, 2.05–7.31). Female adolescents were approximately twice as likely to have CFS or CWP, with multinomial regression revealing a greater sex effect for CWP compared with CFS. Those with exclusive CFS were more likely to report higher levels of pain and greater effect of pain compared with those without CFS, although associations attenuated to the null after adjustment for covariates, which did not occur in those with exclusive CWP. Multinomial regression revealed that relative to having neither CFS nor CWP, a 1-unit increase in the depression and anxiety scales increased the risk of having exclusive CFS and, to a greater extent, the risk of having comorbid CFS and CWP, but not exclusive CWP, which was only related to anxiety. PERSPECTIVE: In this cohort, 14.6% of adolescents with CFS have comorbid CWP. The likely greater proportion of more mild cases observed in this epidemiological study means that prevalence of overlap may be underestimated compared with those attending specialist services. Clinicians should be aware of the overlap between the 2 conditions and carefully consider treatment options offered

Who should we ask about mental health symptoms in adolescents with CFS/ME? Parent-child agreement on the Revised Children’s Anxiety and Depression Scale

Background:One in three adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have mental health problems. Multi-informant perspectives are key to psychological assessment. Understanding parent-child agreement is crucial to accurate diagnosis, particularly where severe fatigue limits self-report.Methods:Agreement on the revised children’s anxiety and depression scale (RCADs) was assessed between parents and children with CFS/ME (n = 93) using Bland-Altman plots, cross tabulations and regression analyses.Results:Diagnostic thresholds were met more frequently based on child-report. Parent- and child-report had similar sensitivity and specificity on RCADS compared to gold-standard diagnostic interviews. Regression analysis found similar accuracy between both reports. For anxiety diagnoses, odds ratio (OR) for child-report was 1.10 (CI = 1.06–1.14), and 1.10 (CI = 1.05–1.14) for parent-report. For depression, OR for child report was 1.26 (CI = 1.11–1.43), while for parent-report is was 1.25 (CI = 1.10–1.41). For total score, OR for child-report was 1.10 (CI = 1.05–1.13) while OR for parent-report was 1.09 (CI = 1.05–1.13).Conclusions:Reasonable agreement was observed between parent- and child-report of mental health symptoms in paediatric CFS/ME. While parent-report can facilitate psychological evaluation in CFS/ME, this is not a substitute for a child’s own report