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The clinical descriptions of chronic fatigue syndrome (CFS) vary by agency, researcher, community and country. Different agencies and scientific bodies have produced different guidelines to define the condition, with some overlap of symptoms between descriptions. The diagnosis is quite controversial, with bitter disagreements over etiology, pathophysiology, treatment, management and naming between medical practitioners, researchers, patients and advocacy groups. Some believe CFS is not caused by a single infection, reaction or event, but rather a variety of unrelated conditions that produce the same symptoms, which makes defining, naming and researching CFS more difficult.

Definitions

Holmes, 1988

Holmes et al (1988) scoring system. Also sometimes called "CDC 1988," to distinguish from the newer CDC system.

Oxford

Oxford criteria (1991)

CDC 1994 criteria

The criteria most used in scientific research are those of the Centers for Disease Control and Prevention of 1994 by Fukuda e.a. The following conditions must be met.

Primary symptom

Clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is:

• of new or definite onset (has not been lifelong);
• is not the result of ongoing exertion;
• is not substantially alleviated by rest;
• and results in substantial reduction in previous levels of occupational, educational, social, or personal activities.

Additional requirement

The concurrent occurrence of four or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue:

1. self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities;
2. sore throat;
3. tender cervical or axillary lymph nodes;
4. muscle pain;
5. multi-joint pain without joint swelling or redness;
6. headaches of a new type, pattern, or severity;
7. unrefreshing sleep;
8. post-exertional malaise lasting more than 24 hours.

Final requirement

All other known causes of chronic fatigue must have been ruled out, specifically clinical depression, side effects of medication, eating disorders and substance abuse.

The clinical evaluation should include:

1. A thorough history that covers medical and psychosocial circumstances at the onset of fatigue; depression or other psychiatric disorders; episodes of medically unexplained symptoms; alcohol or other substance abuse; and current use of prescription and over-the-counter medications and food supplements.
2. A mental status examination to identify abnormalities in mood, intellectual function, memory, and personality. Particular attention should be directed toward current symptoms of depression or anxiety, self-destructive thoughts, and observable signs such as psychomotor retardation. Evidence of a psychiatric or neurologic disorder requires that an appropriate psychiatric, psychological, or neurologic evaluation be done.
3. A thorough physical examination.
4. A minimum battery of laboratory screening tests including complete blood count with leukocyte differential; erythrocyte sedimentation rate; serum levels of alanine aminotransferase, total protein, albumin, globulin, alkaline phosphatase, calcium, phosphorus, glucose, blood urea nitrogen, electrolytes, and creatinine; determination of thyroid-stimulating hormone; and urinalysis.

According to Fukuda e.a., other tests have no known value, unless indicated on an individual basis to confirm or exclude a differential diagnosis, such as multiple sclerosis.

Australian

Definitions for CFS have been produced by Australia.

Canadian

Carruthers et al (2003) Canadian Case definition for ME/CFS

UK NICE 2007

The UK National Institute for Health and Clinical Excellence (NICE), published a multidisciplinary clinical practice guideline in 2007 in which the following criteria are employed:

• fatigue that is new, persistent and/or recurrent, not explained by other conditions and has resulted in a substantial reduction in activity level characterised by post-exertional malaise and/or fatigue (typically delayed, for example by at least 24 hours, with slow recovery over several days) and
• one or more of the following list of symptoms: difficulty with sleeping, muscle and/or joint pain at multiple sites without evidence of inflammation, headaches, painful lymph nodes that are not pathologically enlarged, sore throat, cognitive dysfunction, worsening of symptoms by physical or mental exertion, general malaise, dizziness and/or nausea and palpitations with no identifiable heart problem.

The diagnosis should be reconsidered if none of the following symptoms remain: post-exertional fatigue or malaise, cognitive difficulties, sleep disturbance, chronic pain.

The guideline requires fatigue to have been present for 4 months in an adult or 3 months in a child. It expects a diagnosis in a child to be made by a pediatrician. The guideline states that a referral to a ME/CFS specialist should be offered immediately to the severely ill.

The NICE criteria have been criticized by patients' associations for being far too relaxed, recommending controversial CBT/GET and ignoring the WHO classification of CFS/ME as a neurological condition.

Issues with the definitions

Selection bias and inconsistencies

Several studies have found that using different case definitions ( eg broad vs conservative ) has major influence on the types of patients selected and have also supported the distinction between specific subgroups of CFS to be identified and/or for the case definition to be further clarified with emphasis on using empirical studies: A 2003 international CFS study group for the CDC found ambiguities in the CDC 1994 CFS research case definition which contribute to inconsistent case identification. Researchers have found that a difference in the self-reported cause of a patient's CFS is associated with significant differences in clinical measures and outcomes, and concluded it is likely that their response to treatment may vary and the CFS definition should be improved to define more homogeneous groups of patients for the purposes of research and treatment. It also may be inappropriate to synthesize results from CFS studies that use different definitions to select study populations. It has been found that identification of new diagnostic symptoms, the use of severity ratings for symptomatology, and the identification of standardized measures that differentiate cases of CFS from other conditions; all hold promise for improving the sensitivity, specificity, and reliability of the diagnostic criteria for CFS.

Improving accuracy

A study found that the best predictors for people accurately fitting the CDC 1994 definition of CFS were the presence of postexertional malaise, unrefreshing sleep, and impaired memory-concentration, and this accuracy increased when severity of these symptoms were taken into account. Another examination of the CDC's working case definition(s) of CFS found that the differential accuracy is strengthened when eliminating three symptoms (muscle weakness, joint pain, sleep disturbance) and adding two others (anorexia, nausea). It has also been found that the Canadian 2003 definition (a less used but stricter criteria) selects cases with less psychiatric co-morbidity, more physical functional impairment, and more fatigue/weakness, neuropsychiatric, and neurological symptoms.

Subtypes

Studies suggest the existence of CFS subtypes. After examining the 'minor' diagnostic symptoms of CFS in women meeting the CDC 1994 criteria, researchers found that 3 subtypes could be identified; musculoskeletal, infectious and neurological; with associated impairment characteristic of each subtype. "Extreme scores" characterized about 2/3 of the sample, with higher disability in those with the highest scores. Depression and anxiety were not more prevalent in any particular subtype, and did not increase with the severity of specific symptom reports.

Diagnosis inaccuracies

A review published in 2006 found that the accurate diagnosis of CFS is low and another study found that physicians have a tendency to underrecognize psychiatric illness, especially when assessing patients whose chronic fatigue is fully explainable by a psychiatric disorder and who may be misdiagnosed with CFS.

Testing

There is no generally accepted diagnostic test to reliably diagnose or exclude chronic fatigue syndrome. Research has not identified an association between CFS and one particular virus.

According to the CDC, the main purpose of performing diagnostic tests of any sort is to rule out other causes for fatigue and other symptoms of CFS. Routine tests recommended by the CDC:

• Complete blood count
• Blood chemistry (electrolytes, glucose, renal function, liver enzymes, protein levels and calcium)
• Thyroid function tests
• Erythrocyte sedimentation rate (ESR)
• Urinalysis for blood cells, protein and glucose

The 2007 UK NICE guideline includes, in addition to the CDC panel: C-reactive protein (a marker of inflammation), creatine kinase (a muscle-related enzyme), plasma viscosity (optional if ESR done) and serology for celiac disease. Ferritin determination may be performed in children and young people, and in adults only if other tests suggest iron deficiency. The guideline recommends clinical judgement in decisions to perform other tests in addition to the standard set. Testing for infections (e.g. Lyme disease, viral hepatitis, HIV, mononucleosis, toxoplasmosis or cytomegalovirus) is only recommended if the patient gives a specific history for this. Routine performance of the head-up tilt test, auditory brainstem responses and electrodermal conductivity is discouraged.

Suhadolnik, DeMeirleir e.a. developed a test to measure the fragmentation of the enzyme RNAse L. This fragmentation was found to be significant in CFS and has some use as a marker, but the test has limited availability.

References

1. Holmes GP, Kaplan JE, Gantz NM; et al. (1988). "Chronic fatigue syndrome: a working case definition". Ann. Intern. Med. 108 (3): 387–9. PMID 2829679. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Details
2. Sharpe MC, Archard LC, Banatvala JE; et al. (1991). "A report--chronic fatigue syndrome: guidelines for research". J R Soc Med. 84 (2): 118–21. PMC 1293107. PMID 1999813. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Synopsis by . GPnotebook https://www.gpnotebook.co.uk/simplepage.cfm?ID=-476446699. {{cite web}}: Missing or empty |title= (help))
3. ^ Fukuda K, Straus S, Hickie I, Sharpe M, Dobbins J, Komaroff A (1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group". Ann Intern Med. 121 (12): 953–9. PMID 7978722.{{cite journal}}: CS1 maint: multiple names: authors list (link)
4. Australian Guidelines (2004)
5. Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas MD, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, van de Sande MI (2003). "Myalgic encephalomyalitis/chronic fatigue syndrome: Clinical working definition, diagnostic and treatment protocols" (PDF). Journal of Chronic Fatigue Syndrome. 11 (1): 7–36. doi:10.1300/J092v11n01_02.{{cite journal}}: CS1 maint: multiple names: authors list (link)
6. ^ National Institute for Health and Clinical Excellence. Guideline 53: Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy). London, 2007. ISBN 1846294533. NICE CG53 page.
7. "The ME Association - NICE guideline on ME/CFS - MEA statement". Retrieved 2007-10-09.
8. Jason LA, Corradi K, Torres-Harding S, Taylor RR, King C (2005). "Chronic fatigue syndrome: the need for subtypes". Neuropsychol Rev. 15 (1): 29–58. PMID 15929497. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
9. Reeves WC, Lloyd A, Vernon SD; et al. (2003). "Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution". BMC Health Serv Res. 3 (1): 25. doi:10.1186/1472-6963-3-25. PMC 317472. PMID 14702202. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
10. Kennedy G, Abbot NC, Spence V, Underwood C, Belch JJ (2004). "The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfill the criteria". Ann Epidemiol. 14 (2): 95–100. doi:10.1016/j.annepidem.2003.10.004. PMID 15018881. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
11. Jason LA, Helgerson J, Torres-Harding SR, Carrico AW, Taylor RR (2003). "Variability in diagnostic criteria for chronic fatigue syndrome may result in substantial differences in patterns of symptoms and disability". Eval Health Prof. 26 (1): 3–22. PMID 12629919. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
12. King C, Jason LA (2005). "Improving the diagnostic criteria and procedures for chronic fatigue syndrome". Biol Psychol. 68 (2): 87–106. doi:10.1016/j.biopsycho.2004.03.015. PMID 15450690. {{cite journal}}: Unknown parameter |month= ignored (help)
13. Hawk C, Jason LA, Torres-Harding S (2006). "Differential diagnosis of chronic fatigue syndrome and major depressive disorder". Int J Behav Med. 13 (3): 244–51. doi:10.1207/s15327558ijbm1303_8. PMID 17078775.{{cite journal}}: CS1 maint: multiple names: authors list (link)
14. Komaroff AL, Fagioli LR, Geiger AM; et al. (1996). "An examination of the working case definition of chronic fatigue syndrome". Am. J. Med. 100 (1): 56–64. PMID 8579088. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
15. Jason LA, Torres-Harding SR, Jurgens A, Helgerson J (2004). "Comparing the Fukuda et al. Criteria and the Canadian Case Definition for Chronic Fatigue Syndrome". Journal of Chronic Fatigue Syndrome. 12 (1): 37–52. doi:10.1300/J092v12n01_03.{{cite journal}}: CS1 maint: multiple names: authors list (link)
16. Jason LA, Taylor RR, Kennedy CL; et al. (2003). "Chronic fatigue syndrome: symptom subtypes in a community based sample". Women Health. 37 (1): 1–13. PMID 12627607. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
17. Jason LA, Taylor RR, Kennedy CL, Song S, Johnson D, Torres S (2000). "Chronic fatigue syndrome: occupation, medical utilization, and subtypes in a community-based sample". J. Nerv. Ment. Dis. 188 (9): 568–76. PMID 11009329. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
18. Janal MN, Ciccone DS, Natelson BH (2006). "Sub-typing CFS patients on the basis of 'minor' symptoms". Biol Psychol. 73 (2): 124–31. doi:10.1016/j.biopsycho.2006.01.003. PMID 16473456. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
19. Maoz D, Shoenfeld Y (2006). "". Harefuah (in Hebrew). 145 (4): 272–5, 319, 318. PMID 16642629. {{cite journal}}: Unknown parameter |month= ignored (help)
20. Torres-Harding SR, Jason LA, Cane V, Carrico A, Taylor RR (2002). "Physicians' diagnoses of psychiatric disorders for people with chronic fatigue syndrome". Int J Psychiatry Med. 32 (2): 109–24. PMID 12269593.{{cite journal}}: CS1 maint: multiple names: authors list (link)
21. Suhadolnik RJ, Peterson DL, O'Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P, Charubala R, Pfleiderer W (1997). "Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome". J Interferon Cytokine Res. 17 (7): 377–85. PMID 9243369.{{cite journal}}: CS1 maint: multiple names: authors list (link)

• Immune system disorders
• Neurological disorders
• Ailments of unknown etiology
• Syndromes