Diagnosis and Treatment
15 December 1994

The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study

Publication: Annals of Internal Medicine
Volume 121, Number 12

Abstract

The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.
*For a listing of members of the Study Group, see Appendix.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988; 108:387-9.
2.
Lloyd AR, Wakefield D, Boughton C, Dwyer J. What is myalgic encephalomyelitis? (Letter). Lancet. 1988; 1:1286-7.
3.
Lloyd AR, Hickie I, Boughton CR, Spencer O, Wakefield D. Prevalence of chronic fatigue syndrome in an Australian population. Med J Aust. 1990; 153:522-8.
4.
Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, et al. A report-chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991; 84:118-21.
5.
Holmes GP. The chronic fatigue syndrome. In: Schlossberg D, ed. Infectious Mononucleosis. 2nd ed. New York: Springer-Verlag; 1989:172-93.
6.
Klonoff DC. Chronic fatigue syndrome. Clin Infect Dis. 1992; 15:812-23.
7.
Shafran SD. The chronic fatigue syndrome. Am J Med. 1991; 90:730-9.
8.
Wilson A, Hickie I, Lloyd A, Wakefield D. The treatment of chronic fatigue syndrome: science and speculation. Am J Med. 1994; 96:544-50.
9.
Wilson A, Hickie I, Lloyd A, Hadzi-Pavlovic D, Boughton C, Dwyer J, et al. Longitudinal study of outcome of chronic fatigue syndrome. BMJ. 1994; 308:756-9.
10.
Peterson PK, Schenck CH, Sherman R. Chronic fatigue syndrome in Minnesota. Minn Med. 1991; 74:21-6.
11.
Manu P, Matthews DA, Lane TJ. The mental health of patients with a chief complaint of chronic fatigue. A prospective evaluation and follow-up. Arch Intern Med. 1988; 148:2213-7.
12.
Manu P, Matthews DA, Lane TJ. Panic disorder among patients with chronic fatigue. South Med J 1991; 84:451-6.
13.
Manu P, Lane TJ, Matthews DA. Somatization disorder in patients with chronic fatigue. Psychosomatics. 1989; 30:388-95.
14.
Kruesi MJ, Dale J, Straus SE. Psychiatric diagnoses in patients who have chronic fatigue syndrome. J Clin Psychiatry. 1989; 50:53-6.
15.
Wessely S, Powell R. Fatigue syndromes: a comparison of chronic postviral fatigue with neuromuscular and affective disorders. J Neurol Neurosurg Psychiatry. 1989; 52:940-8.
16.
Swartz MN. The chronic fatigue syndrome—one entity or many? N Engl J Med. 1988; 319:1726-8.
17.
Pawlikowska T, Chalder T, Hirsch SR, Wallace P, Wright DJ, Wessely SC. Population based study of fatigue and psychological distress. BMJ. 1994; 308:763-6.
18.
Price RK, North CS, Wessely S, Fraser VJ. Estimating the prevalence of chronic fatigue syndrome and associated symptoms in the community. Public Health Rep. 1992; 107:514-22.
19.
Walker EA, Katon WJ, Jemelka RP. Psychiatric disorders and medical care utilization among people in the general population who report fatigue. J Gen Intern Med. 1993; 8:436-40.
20.
Kroenke K, Wood DR, Mangelsdorff AD, Meier NJ, Powell JB. Chronic fatigue in primary care. Prevalence, patient characteristics, and outcome. JAMA. 1988; 206:929-34.
21.
Sharpe M, Hawton K, Seagroatt V, Pasvol G. Follow up of patients presenting with fatigue to an infectious diseases clinic. BMJ. 1992; 305:147-52.
22.
Bates DW, Schmitt W, Buchwald D, Ware NC, Lee J, Thoyer E, et al. Prevalence of fatigue and chronic fatigue syndrome in a primary care practice. Arch Intern Med. 1993; 153:2759-65.
23.
Mawle AC, Reyes M, Schmid DS. Is chronic fatigue syndrome an infectious disease? Infect Agents Dis. 1994; 2:333-41.
24.
Schluederberg A, Straus SE, Peterson P, Blumenthal S, Komaroff AL, Spring SB, et al. NIH conference. Chronic fatigue syndrome research. Definition and medical outcome assessment. Ann Intern Med. 1992; 117:325-31.
25.
Straus SE. Defining the chronic fatigue syndrome (Editorial). Arch Intern Med. 1992; 152:1569-70.
26.
Matthews DA, Lane TJ, Manu P. Definition of the chronic fatigue syndrome (Letter). Ann Intern Med. 1988; 109:511-2.
27.
Holmes GP, Kaplan JE, Schonberger LB, Straus SE, Zegans LS, Gantz NM, et al. Definition of the chronic fatigue syndrome (Letter). Ann Intern Med. 1988; 109:512.
28.
Hickie I, Lloyd A, Hadzi-Pavlovic D, Parker G, Bird K, Wakefield D. Can the chronic fatigue syndrome be defined by distinct clinical features? Psychol Med. (In press.)
29.
Gunn WJ, Connell DB, Randall B. Epidemiology of chronic fatigue syndrome: the Centers for Disease Control study. In: Bock G, Whelan J, eds. Chronic Fatigue Syndrome. New York: Wiley; 1993:83-101. (Ciba Foundation symposium 173).
30.
Lane TJ, Matthews DA, Manu P. The low yield of physical examinations and laboratory investigations of patients with chronic fatigue. Am J Med Sci. 1990; 299:313-8.
31.
Kroenke K. Chronic fatigue: frequency, causes, evaluation, and management. Compr Ther. 1989; 15:3-7.
32.
Kuczmarski RJ. Prevalence of overweight and weight gain in the United States. Am J Clin Nutr. 1992; 55(2 Suppl):495S-502S.
33.
Bray GA. Pathophysiology of obesity. Am J Clin Nutr. 1992; 55(2 Suppl):488S-94S.
34.
Robins LN, Wing J, Wittchen HU, Helzer JE, Babor TF, Burke J, et al. The Composite International Diagnostic Interview. An epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Arch Gen Psychiatry. 1988; 45:1069-77.
35.
Robins LN, Helzer JE, Croughan J, Ratcliff KS. National Institute of Mental Health Diagnostic Interview Schedule. Its history, characteristics, and validity. Arch Gen Psychiatry. 1981; 38:381-9.
36.
Spitzer RL, Williams JB, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry. 1992; 49:624-9.
37.
Schwartz JE, Jandorf L, Krupp LB. The measurement of fatigue: a new instrument. J Psychosom Res. 1993; 37:753-62.
38.
Piper BF, Lindsey AM, Dodd MJ, Perketich S, Paul SM, Weller S. The development of an instrument to measure the subjective dimension of fatigue. In: Funk SG, Tournquist PM, Campagne MT, Archer Gopp L, Wiese RA, eds. Key Aspects of Comfort. Management of Pain, Fatigue and Nausea. New York: Springer; 1989:199-208.
39.
Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989; 46:1121-3.
40.
Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, et al. Development of a fatigue scale. J Psychosom Res. 1993; 37:147-53.
41.
Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994; 38:383-92.
42.
Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992; 30:473-83.
43.
Bergner M, Bobbitt RA, Carter WB, Gilson BS. The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981; XIX:787-805.
44.
Katon W, Russo J. Chronic fatigue syndrome criteria. A critique of the requirement for multiple physical complaints. Arch Intern Med. 1992; 152:1604-9.
45.
Lewis G, Wessely S. The epidemiology of fatigue: more questions than answers. J Epidemiol Community Health. 1992; 46:92-7.
46.
Barofsky I, Legro MW. Definition and measurement of fatigue. Rev Infect Dis. 1991; 13(Suppl 1):S94-7.

Comments

0 Comments
Sign In to Submit A Comment
Joseph W Arabasz 23 January 2009
Thiamine anti-metabolites Cause chronic fatigue

To Drs. Fukuda, Straus, Hickie, Sharpe, Dobbins, Komaroff, ICFSSGroup, and Editors at AIM:

In reviewing the Center for Disease Control (CDC) Web Site regarding the Chronic Fatigue Syndrome (CFS) and your December 15, 1994 Article, I found some unusual disparities with a modern day workup for that disease. Perhaps it is time to revisit the Diagnostic Criteria for the CFS and its Idiopathic counterpart.

Specifically, I happen to disagree with the opinion that Primary Care Physicians (most likely referring to General Practitioners, Family Practice Physicians, and those Specialists who partake of either of those Clinical Practices) shouldn't obtain a Laboratory Data Base when working up the patients complaint of chronic fatigue. As you are aware, circumstances and serum levels, etc could possibly be altered with time. I would think that obtaining lab values of Thiamine and Niacin would be most important when gotten early, if the Patient is deficient of either of those essential nutrients. Most Patients don't have more than a week's vacation available to them. Delaying a workup for their fatigue would be ill advised. We are all aware that significant deficiencies of Thiamine and/or Niacin cause severe fatigue and dementia.

A second comment on the AIM CFS Article of December 15, 1994 would be that, while there are recommendations for the measurement of about a dozen lab tests, the Thiamine anti-metabolites, oxythiamine, pyrithiamine (aka neopyrithiamine), amprolium, etc, aren't mentioned at all. Laboratory values should be made for their presence or absence with all Thiamine serum measurements. As has been noted, referring to bacteria, most likely after the Publishing of this AIM Article on the CFS, "pyrithiamine pyrophosphate has been shown to bind and activate the thiamin pyrophosphate (TPP) riboswitch, causing the cell to cease the synthesis and import of TPP. Because pyrithiamine pyrophosphate does not substitute for TPP as a coenzyme, the cell dies (1)."

Oxythiamine, which blocks that essential Vitamine B1 Pathway without reducing the serum Thiamine level, must also be sought for or measured. While oxythiamine supposedly doesn't enter through the Blood Brain Barrier (BBB), it therefore causes a milder disease of fatigue without other Neurologic symptoms, as compared to pyrithiamine. However, if the BBB had been previously disrupted with etoh, or a previous exposure to pyrithiamine, then oxythiamine would enter the Cerebral Spinal Fluid (CSF).

And thirdly, I would tend to disagree with the some of the content of the paragraphs titled, "Conditions That Explain Chronic Fatigue" and "Conditions That Do Not Adequately Explain Chronic Fatigue". I don't think that any previously diagnosed medical condition of a psychological nature should pre-empt a proper metabolic workup for the CFS, especially regarding Thiamine and Niacin deficiencies. As noted in the very next paragraph, "Conditions That Do Not Adequately Explain Chronic Fatigue." The comment is made that "the following conditions do not exclude a patient from the diagnosis of unexplained chronic fatigue (1) and is defined primarily by symptoms that cannot be confirmed by diagnostic laboratory tests, including fibromyalgia, anxiety disorders, somatoforms disorders, nonpsychotic or nonmelancholic depression, neurasthenia, and multiple chemical sensitivity disorder."

Note that almost all psychological diagnoses cannot be confirmed by diagnositic laboratory tests. Their possibly erroneous presence shouldn't prevent a proper workup for the CFS. I think it is time to reconsider the Diagnostic Criteria for the CFS, the Workup of which must include measurements of the synthetic Thiamine anti-metabolites that cause fatigue. The same can be said of Niacin, at the very least. Since the blockage of the Thiamine Pathway by its anti-metabolites are competitive inhibitions, then an appropriately administered pharmacological dose of that essential B Vitamin would overcome the block. This adds credence to the comment made by Dr Adelle Davis RD PhD in her 1968 Text, "Let's Get Well," that "once an increased Minimum Daily Requirement (MDR) occurs for a particular Nutrient, it seldom ever returns to normal."

Please note that the unusual practice which seems to be in Vogue with some specialties nowadays to diagnose grammar school children with a psychological illness, would then, according to the Article's criteria, prevent a workup for the CFS later in life. I would suggest that the whole matter of the diagnostic criteria for the CFS be discussed again openly by all of the Medical Community.

Reference

1 Riboswitches as antibacterial drug targets, Nature Biotechnology - 24, 1558 - 1564 (2006)< http://en.wikipedia.org/wiki/Riboswitch >

Conflict of Interest:

None declared

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 121Number 1215 December 1994
Pages: 953 - 959

History

Published in issue: 15 December 1994
Published online: 15 August 2000

Keywords

Authors

Affiliations

Keiji Fukuda, MD, MPH
From the Centers for Disease Control and Prevention, Atlanta, Georgia; the National Institutes of Health, Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney, Australia; University of Oxford and Warneford Hospital, Oxford, United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.
Stephen E. Straus, MD
From the Centers for Disease Control and Prevention, Atlanta, Georgia; the National Institutes of Health, Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney, Australia; University of Oxford and Warneford Hospital, Oxford, United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.
Ian Hickie, MD, FRANZCP
From the Centers for Disease Control and Prevention, Atlanta, Georgia; the National Institutes of Health, Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney, Australia; University of Oxford and Warneford Hospital, Oxford, United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.
Michael C. Sharpe, MRCP, MRC Psych
From the Centers for Disease Control and Prevention, Atlanta, Georgia; the National Institutes of Health, Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney, Australia; University of Oxford and Warneford Hospital, Oxford, United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.
James G. Dobbins, PhD
From the Centers for Disease Control and Prevention, Atlanta, Georgia; the National Institutes of Health, Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney, Australia; University of Oxford and Warneford Hospital, Oxford, United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.
Anthony Komaroff, MD
From the Centers for Disease Control and Prevention, Atlanta, Georgia; the National Institutes of Health, Bethesda, Maryland; Prince Henry Hospital and University of New South Wales, Sydney, Australia; University of Oxford and Warneford Hospital, Oxford, United Kingdom; and Brigham and Women's Hospital and Harvard University, Boston, Massachusetts.
and International Chronic Fatigue Syndrome Study Group.
Corresponding Author: Keiji Fukuda, MD, MPH, Mailstop A15, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.
Acknowledgments: The authors thank Carla Arpino, Judy Basso, Lyria Boast, Janet K. Dale, Karen Ezrine, Marya Grambs, K. Kimberly Kenney, Teruo Kitani, David Klonoff, Dorothy Knight, Gerhard R.F. Krueger, Hirohiko Kuratsune, Gudrun Lindh, Lars Lindquist, Lisa Livens, Alison Mawle, David McCluskey, John O'Connor, Orvalene Prewitt, Bonnie Randall, Karen B. Schmaling, Scott Schmid, John Stewart, Lars Wahlstrom, Denis Wakefield, and Andrew Wilson.

Metrics & Citations

Metrics

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format





Download article citation data for:
Keiji Fukuda, Stephen E. Straus, Ian Hickie, et al; and International Chronic Fatigue Syndrome Study Group.. The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study. Ann Intern Med.1994;121:953-959. doi:10.7326/0003-4819-121-12-199412150-00009

View More

Login Options:
Purchase

You will be redirected to acponline.org to sign-in to Annals to complete your purchase.

Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.

Create your Free Account

You will be redirected to acponline.org to create an account that will provide access to Annals.

View options

PDF/EPUB

View PDF/EPUB

Related in ACP Journals

Full Text

View Full Text

Figures

Tables

Media

Share

Share

Copy the content Link

Share on social media