Chronic Fatigue Syndrome in Adolescents: treatment, clinical features and epidemiology

This thesis describes the treatment, epidemiology and clinical features of the adolescent chronic fatigue syndrome (CFS). Fatigue is a common complaint among adolescents, with a reported incidence of up to 20% in girls. This fatigue however is not chronic, does not debilitate and has an identifiable cause. CFS is characterized by profound and debilitating fatigue lasting for more than 6 months, with subsequent detrimental effects on social and academic development. The epidemiology of CFS was assessed by calculating incidence and prevalence rates, based on clinical diagnoses. Incidence rates were derived from the Dutch Pediatric Surveillance Unit. Prevalence was assessed using a representable sample among general practitioners. Yearly incidence rate was estimated at 12:100.000, with a prevalence of 0.01%. The cornerstone of this thesis was the Fatigue In Teenagers on the interNET (FITNET) randomized controlled trial, where web-based cognitive behavioral therapy (CBT) was compared to usual care. All children were diagnosed by a specialized pediatrician at the University Medical Center Utrecht. FITNET treatment was delivered by the trained psychotherapists of the Expert Centre Chronic Fatigue, St. Radboud University Nijmegen. Assessments where made at study enrollment, 6 and 12 months after treatment, and at long term follow-up (on average 2.7 years after study enrollment). At these measurements several clinical features of CFS were scored as well, providing longitudinal and interventional data. One-hundred-and-thirty-five adolescents participated in the FITNET trial, of whom 97% completed 6-months follow-up and 88% long term follow-up. Recovery was defined as a combined endpoint of four parameters: fatigue, physical functioning, school participation and self-rated improvement. All had to be scored within two SDs of a healthy peer group. Recovery rate after FITNET treatment was 63%, compared to 8% in the usual care group, at 6 months follow-up (NNT 1.8). The FITNET treatment effects proved sustainable at long term follow-up. The usual care group recovered as well, some after cross-over to FITNET, but at a slower pace. Prognostic factors for nonrecovery were a longer disease duration prior to diagnosis and a maternal focus on bodily symptoms. Pain thresholds and pain experience were longitudinally assessed. Although treatment was aimed at fatigue, the pain symptoms diminished after successful treatment. This implies pain is an intrinsic feature of CFS and doesn’t warrant separate treatment. Intelligence was tested at diagnosis and compared with pre-high school performance tests (CITO). IQ at diagnosis was lower than expected based on CITO scores and compered to their healthy peers. Based on CITO-scores, CFS adolescents did commence on the appropriate school level before disease effects could manifest. Whether IQ increases after successful treatment will be part of future research. Hypothalamus-Pituitary-Adrenal-axis activity was assessed using the salivary cortisol awakening response. A mild hypocortisolism was found compered to their healthy peers. Normalization of cortisol levels were predictive of therapy response. We suggest that this finding may have clinical implications with regard to treatment possibilities. In conclusion, CFS remains a relatively rare but debilitating condition. It can successfully be treated with web-based CBT. A quick diagnosis and prompt referral to specialized treatment does not only reduce the burden to the patient, but also has a positive effect on chances of recovery