title: Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands.
abstract: OBJECTIVE
  Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples.
  
  
  METHODS
  29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures).
  
  
  RESULTS
  Data were available for 7041 UK and 1392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: 'full' polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; 'pain-only' (muscle/joint) 20.3%; 'sore throat/painful lymph node' 4.5%; and 'oligosymptomatic' (median 1, IQR 0-2 symptoms) 4.7%. Two 'partial' polysymptomatic phenotypes were similar to the 'full' phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data.
  
  
  CONCLUSIONS
  Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. Electronic address: simon.collin@bristol.ac.uk.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Collin
authors.affiliation: Expert Centre for Chronic Fatigue, Radboud University Medical Centre Nijmegen, The Netherlands.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nikolaus
authors.affiliation: School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Heron
authors.affiliation: Expert Centre for Chronic Fatigue, Radboud University Medical Centre Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Knoop
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Peter D
authors.initials: PD
authors.lastname: White
authors.affiliation: School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.
authors.forename: Esther
authors.initials: E
authors.lastname: Crawley
mesh_terms: D000328:Adult; D003071:Cognition; D060825:Cognitive Dysfunction / Q000209:etiology; D015331:Cohort Studies; D015897:Comorbidity; D003863:Depression / Q000209:etiology; D004244:Dizziness / Q000209:etiology; D015673:Fatigue Syndrome, Chronic / Q000150:complications* / Q000175:diagnosis / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000209:etiology; D009325:Nausea / Q000209:etiology; D009426:Netherlands; D010612:Pharyngitis / Q000209:etiology; D010641:Phenotype; D020377:Self Efficacy; D012893:Sleep Wake Disorders / Q000209:etiology; D006113:United Kingdom
keywords: Chronic fatigue syndrome; Latent class analysis; Phenotypes; Symptom profiles