Fatigue as the Chief Complaint-Epidemiology, Causes, Diagnosis, and Treatment.

BACKGROUND Fatigue is a main or secondary reason for 10-20% of all consultations with a primary care physician. METHODS This review is based on pertinent publications retrieved by a comprehensive, selective literature search on the epidemiology, etiology, and diagnostic evaluation of fatigue as a leading symptom of disease, as well as on the treatment of its common causes. Information was also included from the literature search we conducted for the German clinical practice guideline on fatigue that was issued by the German College of General Practitioners and Family Physicians (Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, DEGAM). RESULTS Fatigue can be due to any of a broad spectrum of diseases, including decompensation of already known conditions. Sleep disorders and sleep-related disorders of breathing, depression (18.5%), and excessive psychosocial stress are the most common causes of persistent fatigue. Previously undiagnosed cancer is a rare cause, accounting for only 0.6% of cases (95% confidence interval [0.3; 1.3]). Anemia and other organic causes are rare as well (4.3% [2.7; 6.7]). Investigations beyond the history, physical examination, and simple laboratory tests are needed only in the presence of additional symptoms or findings. If the diagnosis remains unclear, watchful waiting and regularly scheduled follow-up help prevent an excessive focus on somatic causes, leading to overdiagnosis. Irrespective of specific causes, psychoeducative and psychotherapeutic approaches should be discussed with the patient, as well as an individually adapted exercise program. CONCLUSION The work-up of fatigue as a chief complaint should be guided by investigating common and/or potentially dangerous disorders. Since the latter are rare, an exclusively somatic focus should be avoided in order to prevent overdiagnosis.

[1]  Raveendhara R. Bannuru,et al.  Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease , 2020, Arthritis & rheumatology.

[2]  Eric E. Smith,et al.  Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue following Stroke, 6th edition update 2019 , 2019, International journal of stroke : official journal of the International Stroke Society.

[3]  C. Son,et al.  Review of case definitions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) , 2020, Journal of Translational Medicine.

[4]  J. Bartzis,et al.  Association of subjective health symptoms with Indoor Air Quality in European office buildings: The OFFICAIR project. , 2020, Indoor air.

[5]  C. Scheibenbogen,et al.  Systematic Review of the Epidemiological Burden of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Across Europe: Current Evidence and EUROMENE Research Recommendations for Epidemiology , 2020, Journal of clinical medicine.

[6]  F. Roila,et al.  Cancer-related fatigue: ESMO Clinical Practice Guidelines for diagnosis and treatment. , 2020, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  Eun-su Jang,et al.  Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) , 2020, Journal of Translational Medicine.

[8]  Jiaomei Liu,et al.  The association between allergic rhinitis and sleep: A systematic review and meta-analysis of observational studies , 2020, PloS one.

[9]  Eva M. Klein,et al.  Somatic Symptoms in the German General Population from 1975 to 2013 , 2020, Scientific Reports.

[10]  C. Son,et al.  Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) , 2020, Journal of Translational Medicine.

[11]  D. Gozal,et al.  Obstructive Sleep Apnea Screening with a 4-Item Instrument, Named GOAL Questionnaire: Development, Validation and Comparative Study with No-Apnea, STOP-Bang, and NoSAS , 2020, Nature and science of sleep.

[12]  B. Riegel,et al.  A Qualitative Metasynthesis of the Experience of Fatigue Across Five Chronic Conditions , 2019, Journal of pain and symptom management.

[13]  B. Jiang,et al.  Efficacy and Placebo Response of Multimodal Treatments for Primary Insomnia: A Network Meta-Analysis. , 2019, Clinical neuropharmacology.

[14]  Kristina Schmiedchen,et al.  Methodological limitations in experimental studies on symptom development in individuals with idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) – a systematic review , 2019, Environmental Health.

[15]  P. Vollenweider,et al.  Prevalence and factors associated with fatigue in the Lausanne middle-aged population: a population-based, cross-sectional survey , 2019, BMJ Open.

[16]  V. Werth,et al.  Fatigue in systemic lupus erythematosus and other autoimmune skin diseases , 2019, The British journal of dermatology.

[17]  M. Beutel,et al.  Somatic symptom load in men and women from middle to high age in the Gutenberg Health Study - association with psychosocial and somatic factors , 2019, Scientific Reports.

[18]  N. Freemantle,et al.  Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis , 2019, The Lancet.

[19]  G. Rørtveit,et al.  Quality of life and its association with irritable bowel syndrome and fatigue ten years after giardiasis , 2019, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[20]  Sally J. Singh,et al.  Exercise-based cardiac rehabilitation for adults with heart failure. , 2019, The Cochrane database of systematic reviews.

[21]  Rachel Churchill,et al.  Behavioural therapies versus other psychological therapies for depression. , 2018, The Cochrane database of systematic reviews.

[22]  D. Freeman,et al.  Sleep Disorders in Early Psychosis: Incidence, Severity, and Association With Clinical Symptoms , 2018, Schizophrenia bulletin.

[23]  S. Fisher,et al.  Hypercalcemia and cancer: Differential diagnosis and treatment , 2018, CA: a cancer journal for clinicians.

[24]  E. Litton,et al.  Intravenous iron therapy for non-anaemic, iron-deficient adults. , 2018, The Cochrane database of systematic reviews.

[25]  Geir Bjorklund,et al.  Mercury exposure and health impacts in dental personnel. , 2018, Environmental research.

[26]  P. Benkert,et al.  Prodromal symptoms of multiple sclerosis in primary care , 2018, Annals of neurology.

[27]  S. Hofmann,et al.  Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: a meta-analytic review , 2018, Expert opinion on pharmacotherapy.

[28]  A. Malizia,et al.  Antidepressants for insomnia in adults. , 2018, The Cochrane database of systematic reviews.

[29]  J. Ioannidis,et al.  Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis , 2018, The Lancet.

[30]  I. Yang,et al.  COPD‐X Australian and New Zealand guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 2017 update , 2017, The Medical journal of Australia.

[31]  F. Paul,et al.  Fatigue as a symptom or comorbidity of neurological diseases , 2017, Nature Reviews Neurology.

[32]  P. Wennberg,et al.  Fatigue in the general population- associations to age, sex, socioeconomic status, physical activity, sitting time and self-rated health: the northern Sweden MONICA study 2014 , 2017, BMC Public Health.

[33]  Suzanne M. Miller,et al.  Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis , 2017, JAMA oncology.

[34]  P. Enck,et al.  Incidence of irritable bowel syndrome and chronic fatigue following GI infection: a population-level study using routinely collected claims data , 2017, Gut.

[35]  K. Petrowski,et al.  Frequency of somatic symptoms in the general population: Normative values for the Patient Health Questionnaire-15 (PHQ-15). , 2017, Journal of psychosomatic research.

[36]  E. Prescott,et al.  Vital Exhaustion and Coronary Heart Disease Risk: A Systematic Review and Meta-Analysis , 2017, Psychosomatic medicine.

[37]  E. Beller,et al.  Educational interventions for the management of cancer-related fatigue in adults. , 2016, The Cochrane database of systematic reviews.

[38]  A. Becker,et al.  The differential diagnosis of tiredness: a systematic review , 2016, BMC Family Practice.

[39]  P. Cuijpers,et al.  How effective are cognitive behavior therapies for major depression and anxiety disorders? A meta‐analytic update of the evidence , 2016, World psychiatry : official journal of the World Psychiatric Association.

[40]  L. Bratzke,et al.  A Systematic Review of Relaxation, Meditation, and Guided Imagery Strategies for Symptom Management in Heart Failure , 2016, The Journal of cardiovascular nursing.

[41]  K. Booker,et al.  Prodromal myocardial infarction symptoms experienced by women. , 2016, Heart & lung : the journal of critical care.

[42]  D. Lawlor,et al.  Exercise for Depression. , 1978, The Physician and sportsmedicine.

[43]  L. Katz,et al.  Interventions for the management of fatigue in adults with a primary brain tumour. , 2016, The Cochrane database of systematic reviews.

[44]  T. Furukawa,et al.  Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis. , 2016, The Cochrane database of systematic reviews.

[45]  H. Abdullah,et al.  STOP-Bang Questionnaire: A Practical Approach to Screen for Obstructive Sleep Apnea. , 2016, Chest.

[46]  Stefan R Bornstein,et al.  Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. , 2016, The Journal of clinical endocrinology and metabolism.

[47]  H. E. van der Horst,et al.  Explaining fatigue: An examination of patient causal attributions and their (in)congruence with family doctors’ initial causal attributions , 2015, The European journal of general practice.

[48]  D. Wedekind,et al.  Efficacy of treatments for anxiety disorders: a meta-analysis , 2015, International clinical psychopharmacology.

[49]  J. L. Harmon,et al.  Fatigue in HIV-Infected People: A Three-Year Observational Study. , 2015, Journal of pain and symptom management.

[50]  N. Spike,et al.  Investigation of fatigue by Australian general practice registrars: a cross-sectional study. , 2015, Journal of primary health care.

[51]  H. van Marwijk,et al.  Pharmacological interventions for somatoform disorders in adults. , 2014, The Cochrane database of systematic reviews.

[52]  W. Rief,et al.  Drug Treatment of Primary Insomnia: A Meta-Analysis of Polysomnographic Randomized Controlled Trials , 2014, CNS Drugs.

[53]  Pierre Philip,et al.  Insomnia and accidents: cross‐sectional study (EQUINOX) on sleep‐related home, work and car accidents in 5293 subjects with insomnia from 10 countries , 2014, Journal of sleep research.

[54]  R. Feelders,et al.  The burden of Cushing's disease: clinical and health-related quality of life aspects. , 2012, European journal of endocrinology.

[55]  M. Ohayon,et al.  Sleep disorders, medical conditions, and road accident risk. , 2011, Accident; analysis and prevention.

[56]  T. Tammela,et al.  A Systematic Evaluation of Factors Associated With Nocturia—The Population-based FINNO Study , 2009, American journal of epidemiology.

[57]  A. Zautra,et al.  Daily fatigue in women with osteoarthritis, rheumatoid arthritis, and fibromyalgia , 2007, Pain.

[58]  J. Ricci,et al.  Fatigue in the U.S. Workforce: Prevalence and Implications for Lost Productive Work Time , 2007, Journal of occupational and environmental medicine.

[59]  Dalete Mota,et al.  Self-Report Instruments for Fatigue Assessment: A Systematic Review , 2006, Research and Theory for Nursing Practice.

[60]  A. Lerdal,et al.  Fatigue in the general population: A translation and test of the psychometric properties of the Norwegian version of the fatigue severity scale , 2005, Scandinavian journal of public health.

[61]  M. Hotopf,et al.  A systematic review and meta-analysis of the incidence and severity of postoperative fatigue. , 2004, Journal of psychosomatic research.

[62]  I. Kant,et al.  Fatigue as a risk factor for being injured in an occupational accident: results from the Maastricht Cohort Study , 2003, Occupational and environmental medicine.

[63]  A. Hinz,et al.  Fatigue in the General Population , 2003, Oncology Research and Treatment.

[64]  P Bech,et al.  Fatigue in the Danish general population. Influence of sociodemographic factors and disease , 2000, Journal of epidemiology and community health.

[65]  S. Horning,et al.  Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition. , 2000, The oncologist.

[66]  J. Lépine,et al.  Identification of depressed patient types in the community and their treatment needs: findings from the DEPRES II (Depression Research in European Society II) survey. DEPRES Steering Committee. , 1999, International clinical psychopharmacology.

[67]  D. Cella,et al.  Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition. , 1997, Seminars in hematology.

[68]  P. Slocum,et al.  Chronic fatigue complaints in primary care: Incidence and diagnostic patterns , 1996, The Journal of the American Osteopathic Association.

[69]  K Kroenke,et al.  Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study. , 1994, JAMA.

[70]  P Wallace,et al.  Population based study of fatigue and psychological distress , 1994, BMJ.

[71]  K. Vosteen,et al.  Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) , 1992, Unfallchirurgie.

[72]  D. Wood,et al.  Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. , 1988, JAMA.

[73]  G. M. Dyrdal,et al.  Mindfulness-based stress reduction (MBSR) for improving health, quality of life and social functioning in adults: a systematic review and meta-analysis , 2017 .

[74]  M. Weickert,et al.  Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. , 2017, The New England journal of medicine.

[75]  John W Ely,et al.  Diagnostic Errors in Primary Care: Lessons Learned , 2012, The Journal of the American Board of Family Medicine.

[76]  J. Steurer,et al.  Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease. , 2009, The Cochrane database of systematic reviews.

[77]  F. Cramp,et al.  Exercise for the management of cancer-related fatigue in adults. , 2008, The Cochrane database of systematic reviews.

[78]  T. Chalder,et al.  Treatments for chronic fatigue syndrome. , 2005, Occupational medicine.

[79]  I. Okkes,et al.  The probability of specific diagnoses for patients presenting with common symptoms to Dutch family physicians. , 2002, The Journal of family practice.

[80]  B. Spiegel,et al.  NISAS-2000: Die "Nationwide Insomnia Screening and Awareness Study". Prävalenz und Verschreibungsverhalten in der allgemeinärztlichen Versorgung. , 2001 .

[81]  W. Browner,et al.  Case-finding instruments for depression. Two questions are as good as many. , 1997, Journal of general internal medicine.

[82]  J Ormel,et al.  Common mental disorders and disability across cultures. Results from the WHO Collaborative Study on Psychological Problems in General Health Care. , 1994, JAMA.

[83]  R. Monson,et al.  Patients with multiple unexplained symptoms. Their characteristics, functional health, and health care utilization. , 1986, Archives of internal medicine.

[84]  K.-J. Dreibholz Gefahren der somatischen Fixierung , 1986 .