Idiopathic chronic fatigue

Last updated
Idiopathic Chronic Fatigue
Other namesChronic Idiopathic Fatigue (CIF), insufficient/idiopathic fatigue (ISF), unexplained chronic fatigue
Specialty Family medicine, Internal medicine, Musculoskeletal
Symptoms Chronic fatigue
Usual onsetAcquired (not lifelong) [1]
DurationAt least six consecutive months
CausesUnknown
Diagnostic method Based on symptoms. Diagnosis of exclusion requiring laboratory evaluation, physical and biopsychosocial assessment. [1]
Differential diagnosis Occupational burnout; chronic fatigue due to a known medical condition such as chronic fatigue syndrome, overtraining
Treatment Symptomatic
Frequency6.2 to 64.2 per 1000 [2]

Idiopathic chronic fatigue (ICF) or chronic idiopathic fatigue or insufficient/idiopathic fatigue [3] is a term used for cases of unexplained fatigue that have lasted at least six consecutive months [1] and which do not meet the criteria for Myalgic Encephalomyelitis/chronic fatigue syndrome. [4] Such fatigue is widely understood to have a profound effect on the lives of patients who experience it. [1] [5]

Contents

Definition

A 1994 definition of ICF was a physical medical condition of unknown origin, persisting or relapsing for a minimum of six consecutive months, where CFS symptoms are not met. [6]

Classification

ICF does not have a dedicated diagnostic code in the World Health Organization's ICD-11 classification. [7]

ICF is sometimes diagnosed under physical symptom classifications such as MG22 (Fatigue) in the ICD-11, and R53.8 (Other malaise and fatigue) in the ICD-10. This allows ICF to be coded as fatigue or unspecified chronic fatigue, and help distinguish it from other forms of fatigue including cancer-related fatigue, chronic fatigue syndrome, fatigue due to depression, fatigue due to old age, weakness/asthenia, and in the ICD-10, also from fatigue lasting under 6 months. [8] [9] The ICD-11 MG22 Fatigue code is also shared with lethargy, and exhaustion, which may not be as long lasting. [7]

The WHO does not recognize any kind of fatigue-based psychiatric illness (unless it is accompanied by related psychiatric symptoms). [10] [11]

Diagnosis

There are no agreed upon international criteria for idiopathic chronic fatigue, however the CDC's 1994 Idiopathic Chronic Fatigue criteria, known as the Fukuda ICF criteria, are commonly used. [1] [5]

Signs and symptoms

Exclusions

Other medical causes of fatigue must also be ruled out before a diagnosis of ICF can be made. These include

2023 guidance [12] for fatigue stated that when unexplained, clinically evaluated chronic fatigue could be separated into ME/CFS and ICF. [13]

Differential diagnosis

Differences from chronic fatigue

ICF differs from chronic fatigue since it is unexplained rather than linked to a medical or psychological illness (for example, diabetes or depression). [6] This means that ICF patients have reduced treatment options: there is no underlying disease or known cause that could be treated in order to reduce the degree of fatigue, which results in a poorer prognosis for ICF. [14]

In ICF, the fatigue lasts for a minimum of six months, but chronic fatigue is usually (but not always) considered to last for a minimum of six months to be considered chronic, and if lasting between one and six months it is considered prolonged fatigue.

Chronic fatigue is the term used when medical tests and a mental and physical assessment has not yet been carried out. ICF can only be diagnosed after these are done and the results show no underlying untreated cause. [6]

Differential diagnosis from chronic fatigue syndrome

Chronic fatigue syndrome (CFS) requires the additional symptoms of:

  1. post-exertional malaise (significantly worsening symptoms with activity which results in a significant reduction in daily activities, which may be delayed by up to 3 days
  2. sleep dysfunction
  3. either:

A range of other symptoms commonly result from CFS including headaches, muscle and joint pain and low-grade fever. [15]

ICF requires:

  1. only one symptom: chronic fatigue
  2. does not need a significant reduction in activities: some people are able to push through the fatigue to continue activities
  3. is only diagnosed if CFS symptoms are not met [6]

Prevalence of ICF is between 3-15%, which is two to ten times higher than CFS [14] Older age at onset is more common in ICF, particularly from age 50, [14] while in CFS age at onset is typically 16-35 years old [15]

The recovery rate within a year is significantly higher for ICF patients, 30-50% compared to under 10% in CFS [14] [15]

ICF is categorized within general signs and symptoms by the World Health Organization, [7] while CFS is categorized as a neurological disease [16]

Ability to tolerate exertion including exercise has been shown to be greater in ICF patients compared to CFS patients, particularly on consecutive days, and this applies to both men and women. [17] [18] [19]

Severity of illness in ICF is typically less than in CFS, with some relatively small studies finding no severe ICF patients, the same studies found fibromyalgia was significantly less common in ICF. [18] [19]

Differences from neurasthenia

Neurasthenia was a diagnosis in the World Health Organization's ICD-10, but deprecated, and thus no more diagnosable, in ICD-11. [20] [21] It also is no longer included as a diagnosis in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders . [22]

  • ICF has no known cause, and psychological factors such as stress have been ruled out, but neurasthenia was believed to be caused by the stresses of the modern age and psychological or psychosocial factors were seen as important. [24] [20]
  • Neurasthenia has been very rarely reported since the 21st century, and was deprecated in the World Health Organization's most recent International Classification of Diseases, known as the ICD-11. [7] Neurasthenia had previously been categorized as a psychological illness, [24] and originally as neurological. ICF is not psychological- the WHO does not have a classification for any fatigue-only psychiatric illness. [9] [7]

Management

Idiopathic chronic fatigue is typically managed in general medicine rather than by referral to a specialist. There is no cure, no approved drug, and treatment options are limited. [25] Management may involve a form of counseling, or antidepressant medication, although some patients may prefer herbal or alternative remedies. [1]

Counseling

A form of counseling known as cognitive behavioral therapy may help some people manage or cope with idiopathic chronic fatigue. [1]

Medication

There are no approved drugs for ICF. [25]

Antidepressants

Antidepressants drugs such as tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) may be appropriate if symptoms are exacerbated by suspected or diagnosed serotonin related health issues, such as depression. [1]

Alternative and complementary treatments

Only limited trials had been conducted for alternative and complementary treatments; there is no clear evidence of these treatments being effective for ICF due to a lack of randomized controlled trials. [25]

Prognosis

Between 30% and just under 50% of patients recover within one year. [1] [26]

Epidemiology

Fatigue is common in the general population and often caused by overwork, too much activity or a specific illness or disease. Around 20% of patients who visit their clinician report fatigue. [1] Prolonged fatigue is fatigue that persists for more than a month, and chronic fatigue is fatigue that lasts at least six consecutive months, which may be caused by a physical or psychological illness, or may be idiopathic (no known cause). [1] Chronic fatigue with a known cause is twice as common as idiopathic chronic fatigue. [6]

Idiopathic chronic fatigue affects between 2.4% and 6.42% of patients, [27] with females more likely to be affected than men. [1] Age at onset is typically over 50 years of age. [14] A significant number of patients present with idiopathic chronic fatigue as part of a mix of medically unexplained symptoms, while others present with a primary problem of fatigue alone. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Fatigue</span> Range of afflictions, usually associated with physical or mental weakness

Fatigue describes a state of tiredness, exhaustion or loss of energy.

Neurasthenia is a term that was first used as early as 1829 for a mechanical weakness of the nerves. It became a major diagnosis in North America during the late nineteenth and early twentieth centuries after neurologist George Miller Beard reintroduced the concept in 1869.

<span class="mw-page-title-main">ME Association</span> UK charitable organization

The ME Association is a UK health charitable organization that provides information, advocacy, and services to persons and families affected by ME/CFS, and raises funds for research into ME/CFS. It has been reported to be one of the two largest UK charities for ME/CFS.

<span class="mw-page-title-main">Exercise intolerance</span> Medical condition

Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe post-exercise pain, fatigue, nausea, vomiting or other negative effects. Exercise intolerance is not a disease or syndrome in and of itself, but can result from various disorders.

Rintatolimod, sold under the tradename Ampligen, is a medication intended for treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). There is some evidence it may improve some ME/CFS symptoms.

<span class="mw-page-title-main">History of ME/CFS</span> Review of the topic

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a long history with an evolution in medical understanding, diagnoses and social perceptions.

Management of ME/CFS focusses on symptoms management, as no treatments that address the root cause of the illness are available. Pacing, or regulating one's activities to avoid triggering worse symptoms, is the most common management strategy for post-exertional malaise. Clinical management varies widely, with many patients receiving combinations of therapies.

<span class="mw-page-title-main">Controversies related to ME/CFS</span>

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness with a long history of controversy. Some professionals within the medical community do not recognize ME/CFS as a genuine condition, nor is there agreement on its prevalence. There has been much disagreement over the pathophysiology of ME/CFS, how it should be diagnosed, and how to treat it.

<span class="mw-page-title-main">Clinical descriptions of ME/CFS</span> Review of the topic

Clinical descriptions of ME/CFS vary. Different groups have produced sets of diagnostic criteria that share many similarities. The biggest differences between criteria are whether post-exertional malaise (PEM) is required, and the number of symptoms needed.

The Lightning Process (LP) is a three-day personal training programme developed and trademarked by British osteopath Phil Parker. It makes unsubstantiated claims to be beneficial for various conditions, including chronic fatigue syndrome, depression and chronic pain.

Graded exercise therapy (GET) is a programme of physical activity that starts very slowly and gradually increases over time, intended as a treatment for chronic fatigue syndrome. Most public health bodies, including the CDC and NICE, consider it ineffective, and its safety is disputed. However, GET still enjoys support among a minority of clinicians and organizations.

<span class="mw-page-title-main">Myalgic encephalomyelitis/chronic fatigue syndrome</span> Chronic medical condition

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term medical condition. People with ME/CFS experience delayed worsening of the illness after minor physical or mental activity, which is the hallmark symptom of the illness. Other core symptoms are a greatly reduced ability to do tasks that were previously routine, severe fatigue that does not improve much with rest, and sleep disturbances. Further common symptoms include dizziness or nausea when sitting or standing, along with memory and concentration issues and pain.

Jennifer Brea is an American documentary filmmaker and activist. Her debut feature, Unrest, premiered at the 2017 Sundance Film Festival and received the US Documentary Special Jury Award For Editing. Brea also co-created a virtual reality film which premiered at Tribeca Film Festival.

Rosamund Vallings is a medical doctor, known as one of the leading authorities on Chronic Fatigue Syndrome (ME/CFS) in New Zealand.

<span class="mw-page-title-main">Post-exertional malaise</span> Worsening of symptoms with activity

Post-exertional malaise (PEM), sometimes referred to as post-exertional symptom exacerbation (PESE) or post-exertional neuroimmune exhaustion (PENE), is a worsening of symptoms that occurs after minimal exertion. It is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and common in long COVID and fibromyalgia. PEM is often severe enough to be disabling, and is triggered by ordinary activities that healthy people tolerate. Typically, it begins 12–48 hours after the activity that triggers it, and lasts for days, but this is highly variable and may persist much longer. Management of PEM is symptom-based, and patients are recommended to pace their activities to avoid triggering PEM.

Pacing is an activity management technique for managing a long-term health condition or disability, aiming to maximize what a person can do while reducing, or at least controlling, any symptoms that restrict activity. Pacing is commonly used to help manage conditions that cause chronic pain or chronic fatigue.

Peter C. Rowe is a physician and academic. A leading researcher in chronic fatigue syndrome, he is Professor of Pediatrics, Sunshine Natural Wellbeing Foundation Professor of Chronic Fatigue and Related Disorders, and Director of the Children's Center Chronic Fatigue Clinic at Johns Hopkins University School of Medicine.

<span class="mw-page-title-main">2-day CPET</span> Medical test for post-exertional malaise

A 2-day CPET is a cardiopulmonary exercise test given on two successive days to measure the effect of post-exertional malaise (PEM) on a patient's ability to exercise. PEM is a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome and is common in long COVID as well.

Andrew Melvin Ramsay (1901–1990) was a British physician, who is known for his research and advocacy on myalgic encephalomyelitis (ME), a chronic disease causing muscle weakness and cognitive dysfunction. Ramsay worked as a consultant at the Royal Free Hospital in London during a mysterious 1955 disease outbreak of what later became known as ME. He studied the disease and similar outbreaks elsewhere. Work by Ramsay showed that although ME seldom caused death, the disease could be highly disabling.

Carmen Scheibenbogen is a German immunologist who is the acting director of the Institute for Medical Immunology of the Charité university hospital in Berlin. She specialises in hematology, oncology and immunology. She leads the Outpatient Clinic for Immunodeficiency and the Fatigue Centre at the Charité hospital. She is one of the few doctors specialised in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Germany, and also researches long COVID.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Saultz, J (2002-09-23). "Care of the Patient with Fatigue". In Taylor, Robert (ed.). Family Medicine: Principles and Practice. Springer Science & Business Media. pp. 465–469. ISBN   978-0-387-95400-4.
  2. ↑ Kim, Tae-Hun; Kim, Do-Hoon; Kang, Jung Won (2020-04-01). "Medicinal herbs for managing fatigue symptoms in patients with idiopathic chronic fatigue: A PRISMA compliant updated systematic review and meta-analysis of randomized controlled trials based on the GRADE approach". European Journal of Integrative Medicine. 35: 101069. doi:10.1016/j.eujim.2020.101069. ISSN   1876-3820. S2CID   214256657.
  3. ↑ Vincent, Ann; Brimmer, Dana J.; Whipple, Mary O.; Jones, James F.; Boneva, Roumiana; Lahr, Brian D.; Maloney, Elizabeth; St. Sauver, Jennifer L.; Reeves, William C. (December 2012). "Prevalence, Incidence, and Classification of Chronic Fatigue Syndrome in Olmsted County, Minnesota, as Estimated Using the Rochester Epidemiology Project". Mayo Clinic Proceedings. 87 (12): 1145–1152. doi:10.1016/j.mayocp.2012.08.015. ISSN   0025-6196. PMC   3518652 . PMID   23140977.
  4. ↑ van Campen, C. (Linda) M. C.; Visser, Frans C. (June 19, 2021). "Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol". Healthcare. 9 (6): 683. doi: 10.3390/healthcare9060683 . PMC   8230194 . PMID   34198946.
  5. 1 2 3 4 Son, Chang-Gue (2019-06-01). "Differential diagnosis between "chronic fatigue" and "chronic fatigue syndrome"". Integrative Medicine Research. 8 (2): 89–91. doi:10.1016/j.imr.2019.04.005. ISSN   2213-4220. PMC   6522773 . PMID   31193269.
  6. 1 2 3 4 5 6 7 8 9 Fukuda, K.; Straus, S. E.; Hickie, I.; Sharpe, M. C.; Dobbins, J. G.; Komaroff, A. (1994-12-15). "The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group". Annals of Internal Medicine. 121 (12). American College of Physicians: 954–957. doi:10.7326/0003-4819-121-12-199412150-00009. ISSN   0003-4819. PMID   7978722. S2CID   510735.
  7. 1 2 3 4 5 "ICD-11 - Mortality and Morbidity Statistics | MG22 Fatigue". World Health Organization. 2019. Retrieved 2023-04-25. MG22 Fatigue
    A feeling of exhaustion, lethargy, or decreased energy, usually experienced as a weakening or depletion of one's physical or mental resource and characterised by a decreased capacity for work and reduced efficiency in responding to stimuli. Fatigue is normal following a period of exertion, mental or physical, but sometimes may occur in the absence of such exertion as a symptom of health conditions.
    Inclusions General physical deterioration Lethargy
    Exclusions Combat fatigue (QE84) Exhaustion due to exposure (NF07.2) heat exhaustion (NF01) Bodily distress disorder (6C20) Depressive disorders (6A70-6A7Z) Sleep-wake disorders (7A00-7B2Z) Bipolar or related disorders (6A60-6A6Z) senile fatigue (MG2A) Chronic fatigue syndrome (8E49) Myalgic encephalomyelitis (8E49) Postviral fatigue syndrome (8E49) pregnancy-related exhaustion and fatigue (JA65).
  8. ↑ National Center for Health Statistics (April 1, 2023). "ICD-10-CM Official Guidelines for Coding and Reporting | FY 2023. Updated April 1, 2023" (PDF). p. 73. Retrieved 2023-04-25. Chapter 18: Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified (R00-R99)
    Chapter 18 includes symptoms, signs, abnormal results of clinical or other investigative procedures, and ill-defined conditions regarding which no diagnosis classifiable elsewhere is recorded. Signs and symptoms that point to a specific diagnosis have been assigned to a category in other chapters of the classification.
  9. 1 2 "ICD-10 Version:2019 | R53". World Health Organization. Retrieved 2023-04-25. R53 Malaise and fatigue.
    R53.0 Neoplastic (malignant) related fatigue. R53.1 Weakness. Asthenia NOS.
    Excludes: age-related weakness (R54) muscle weakness (generalized) (M62.81) sarcopenia (M6 2.84) senile asthenia (R54)
    R53.2 Functional quadriplegia. Excludes: frailty NOS (R54), hysterical paralysis (F44.4), immobility syndrome (M62.3) neurologic quadriplegia (G82.5-) quadriplegia (G82.50).
    R53.8 Other malaise and fatigue
    Excludes: combat exhaustion and fatigue (F43.0) congenital debility (P96.9) exhaustion and fatigue due to excessive exertion (T73.3) exhaustion and fatigue due to exposure (T73.2) exhaustion and fatigue due to heat P'67.-) exhaustion and fatigue due to pregnancy (026.8-), exhaustion and fatigue due to recurrent depressive episode (F33) exhaustion and fatigue due to senile debility (R54)
    R53.81 Other malaise. Chronic debility Debility NOS. General physical deterioration. Malaise NOS. Nervous debility. Excludes: age-related physical debility (R54).
    R53.82 Chronic fatigue, unspecified. Excludes: chronic fatigue syndrome (G93.32) myalgic encephalomyelitis (G93.32) post infection and related fatigue syndromes (G93.39) postviral fatigue syndrome (G93.31)
    R53.83 Other fatigue
    Fatigue NOS. Lack of energy. Lethargy. Tiredness Excludes: exhaustion and fatigue due to depressive episode (F32.-)
    R54 Age-related physical debility.Frailty. Old age. Senescence. Senile asthenia. Senile debility. Excludes: age-related cognitive decline (R41.81) sarcopenia (M62.84) senile psychosis (F03) senilityNOS(R41.81).
    R55 Syncope and collapse...
  10. ↑ Desai, Geetha; Sagar, Rajesh; Chaturvedi, Santosh K. (November 2018). "Nosological Journey of Somatoform Disorders: From Briquet's Syndrome to Bodily Distress Disorder". Indian Journal of Social Psychiatry. 34 (Suppl 1): S29. doi: 10.4103/ijsp.ijsp_37_18 . ISSN   0971-9962. S2CID   149462235.
  11. ↑ Basavarajappa, Chethan; Dahale, Ajit Bhalchandra; Desai, Geetha (September 2020). "Evolution of bodily distress disorders". Current Opinion in Psychiatry. 33 (5): 447–450. doi:10.1097/YCO.0000000000000630. ISSN   0951-7367. PMID   32701520. S2CID   220731306.
  12. ↑
  13. ↑ "Evaluation of fatigue - Differential diagnosis of symptoms". BMJ Best Practice. Archived from the original on 2023-12-03. Retrieved 2024-03-25.
  14. 1 2 3 4 5 Valiani, Vincenzo; Corbett, Duane B.; Knaggs, Jeffrey D.; Manini, Todd M. (November 2016). "Metabolic Rate and Perceived Exertion of Walking in Older Adults With Idiopathic Chronic Fatigue". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 71 (11): 1444–1450. doi:10.1093/gerona/glw108. ISSN   1758-535X. PMC   5975719 . PMID   27271253.
  15. 1 2 3 "What is ME/CFS? | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)". Centers for Disease Control and Prevention. 12 July 2018. Archived from the original on 17 August 2020. Retrieved 21 May 2020.
  16. ↑ 8EF9 - Postviral syndrome,Chronic fatigue syndrome, Myalgic Encephalomyelitis ICD-11. WHO. 2023-01.
  17. ↑ Vermeulen, Ruud CW; van Vermeulen Eck, Ineke WG (2014-01-23). "Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome". Journal of Translational Medicine. 12 (1): 20. doi: 10.1186/1479-5876-12-20 . ISSN   1479-5876. PMC   3903040 . PMID   24456560.
  18. 1 2 van Campen, C. (Linda) M. C.; Visser, Frans C. (June 2021). "Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol". Healthcare. 9 (6): 682. doi: 10.3390/healthcare9060682 . ISSN   2227-9032. PMC   8229058 . PMID   34198913.
  19. 1 2 van Campen, C. (Linda) M. C.; Visser, Frans C. (June 2021). "Comparing Idiopathic Chronic Fatigue and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in Males: Response to Two-Day Cardiopulmonary Exercise Testing Protocol". Healthcare. 9 (6): 683. doi: 10.3390/healthcare9060683 . ISSN   2227-9032. PMC   8230194 . PMID   34198946.
  20. 1 2 3 Connor, Henry (2022-10-20). "Doctors and 'Educational Overpressure' in Nineteenth-Century Britain: A Fatigue State that Divided Medical Opinion". European Journal for the History of Medicine and Health. 80 (1): 3–38. doi: 10.1163/26667711-bja10026 . ISSN   2666-7703.
  21. ↑ World Health Organization. "ICD-11 for Mortality and Morbidity Statistics" . Retrieved 2023-04-24.
  22. ↑ Dimsdale, Joel E.; Xin, Yu; Kleinman, Arthur; Patel, Vikram; Narrow, William E.; Sirovatka, Paul J.; Regier, Darrel A. (2 March 2009). Somatic Presentations of Mental Disorders: Refining the Research Agenda for DSM-V. American Psychiatric Pub. p. 58. ISBN   978-0-89042-656-2.
  23. ↑ Beard, G (1869). "Neurasthenia, or nervous exhaustion". The Boston Medical and Surgical Journal. 80 (13): 217–221. doi:10.1056/NEJM186904290801301.
  24. 1 2 3 WHO (2007). "Chapter V Mental and behavioural disorders (F00-F99)" . Retrieved 2009-10-09.
  25. 1 2 3 Adams, Denise; Wu, Taixiang; Yang, Xunzhe; Tai, Shusheng; Vohra, Sunita (2009). "Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome". Cochrane Database of Systematic Reviews (4): CD006348. doi:10.1002/14651858.CD006348.pub2. ISSN   1465-1858. PMID   19821361.
  26. ↑ Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. Quarterly Journal of Medicine 1997;90:223‐233.
  27. ↑ Wessely, S.; Chalder, T.; Hirsch, S.; Wallace, P.; Wright, D. (1997). "The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: A prospective primary care study". American Journal of Public Health. 87 (9): 1449–1455. doi:10.2105/ajph.87.9.1449. PMC   1380968 . PMID   9314795.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.