title: The differential diagnosis of tiredness: a systematic review.
abstract: Tiredness is one of the most frequent complaints in primary care. Although often self-limiting and frequently associated with psychosocial stress, patients but also their physicians are often uncertain regarding a serious cause and appropriate diagnostic work-up. We conducted a systematic review and meta-analysis of studies reporting on differential diagnosis of fatigue in primary care.
  
  
  
  MEDLINE, EMBASE and conference abstracts were searched for primary care based studies of patients presenting with tiredness. Twenty-six studies were included. We report on anaemia, malignancy, serious organic disease, depression and the chronic fatigue syndrome (CFS) as causes of tiredness as presenting complaint.
  
  
  
  We found considerable heterogeneity of estimates which was reduced by limiting our analysis to high quality studies. Prevalences were as follows-anaemia: 2.8 % (CI (confidence interval) 1.6-4.8 %); malignancy: 0.6 % (CI 0.3-1.3 %); serious somatic disease: 4.3 % (CI 2.7-6.7 %); depression 18.5 % (CI 16.2-21.0 %). Pooling was not appropriate for CFS. In studies with control groups of patients without the symptom of tiredness, prevalence of somatic disease was identical to those complaining of tiredness. Depression, however, was more frequent among those with tiredness.
  
  
  
  Serious somatic disease is rare in patients complaining of tiredness. Since prevalence is similar in patients without tiredness, the association may not be causal. Extensive investigations are only warranted in case of specific findings from the history or clinical examination. Instead, attention should focus on depression and psychosocial problems.
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany. Rebekka.Stadje@t-online.de.
authors.forename: Rebekka
authors.initials: R
authors.lastname: Stadje
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Dornieden
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Baum
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Becker
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Biroga
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bösner
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Haasenritter
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Keunecke
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Viniol
authors.affiliation: Department of General Practice/Family Medicine, University of Marburg, Karl-von-Frisch-Str. 4, 35043, Marburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Donner-Banzhoff
mesh_terms: D000740:Anemia / Q000150:complications / Q000175:diagnosis*; D003863:Depression / Q000150:complications / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005221:Fatigue / Q000209:etiology*; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis*
keywords: Fatigue; Meta-analysis; Primary care; Tiredness