CMAJ • August 15, 2006; 175 (4). doi:10.1503/cmaj.1060137.
© 2006 CMA Media Inc. or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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Letters

Chronic fatigue

Jacques Cornuz*, Bernard Favrat* and Idris Guessous{dagger}

Department of Community Medicine and Public Health, University Outpatient Clinic;* Department of Medicine, University of Lausanne, Lausanne, Switzerland{dagger}

[The authors respond:]

We agree with Riccardo Baschetti that hypocortisolism is one of the reported laboratory abnormalities of patients with chronic fatigue syndrome and that hypoactivity of the hypothalamic–pituitary–adrenal axis is a potential pathophysiologic mechanism. However, as recently stressed by Cho and colleagues,1 the question of whether such hypoactivity is a cause or a consequence of chronic fatigue syndrome remains unanswered. Our review2 was intended to cover the diagnostic approach to chronic fatigue, rather than treatment, but we can mention here that the results of trials evaluating hydrocortisone therapy have been inconsistent. The first trial assessing this pharmaceutical approach3 showed only a modest benefit at the expense of adrenal suppression. To our knowledge, the promising results of a second randomized trial assessing lower dose4 have never been replicated.

As noted by Prasanta Padhan, the workup for chronic fatigue should be adapted to the local context according to the prevalence of diseases causing fatigue, including bacterial infections. Fatigue has been described in both early and chronic Lyme borreliosis. In one prospective study, fatigue was present in more than half of patients with early Lyme disease, and fatigue was more frequent than arthralgia, myalgia or headache.5 In addition, Lyme disease may lead to a post-Lyme borreliosis syndrome including fatigue.6 However, the appropriateness of serological testing depends on the probability of disease. Although such testing would be appropriate for a patient with fatigue and a history of erythema migrans (i.e., high pretest probability), it could be inappropriate for a patient suffering fatigue with no objective signs (i.e., low pretest probability) because of the high risk of false-positive results.7 The pretest probability should also be considered for brucellosis and tuberculosis testing. Chlamydia and Mycoplasma have been found in patients with chronic fatigue and might be associated with the severity of symptoms.8

David Barton is correct that most test results for patients with fatigue will be normal, and we agree that physicians must avoid performing diagnostic procedures simply to address their anxiety about a lack of diagnosis. Because our teaching case report represented an amalgamation of cases, there is no follow-up information. However, in a trial involving women with fatigue9 (on which one of us [B.F.] was a coauthor) celiac disease was diagnosed by serologic testing and then small-intestine biopsy in 2 patients. One of these patients was lost during follow-up but the other undertook a gluten-free diet and was followed clinically after diagnosis for 12 months. After a few months, she felt better and her fatigue subsided. She underwent a second biopsy 12 months after the diagnosis, which showed no histologic abnormalities.

REFERENCES

  1. Cho HJ, Skowera A, Cleare A, et al. Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology. Curr Opin Psychiatry 2006;19 (1):67-73.[Medline]
  2. Cornuz J, Guessous I, Favrat B. Fatigue: a practical approach to diagnosis in primary care. CMAJ 2006;174(6):765-7.[Free Full Text]
  3. McKenzie R, O'Fallon A, Dale J, et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. JAMA 1998;280(12):1061-6.[Abstract/Free Full Text]
  4. Cleary AJ, Hean E, Malhi GS, et al. Low-dose hydrocortisone in chronic fatigue syndrome: a randomized crossover trial. Lancet 1999;353:455-8.[CrossRef][Medline]
  5. Nadelman RB, Nowakowski J, Forseter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996;100(5):502-8.[CrossRef][Medline]
  6. Cairns V, Godwin J. Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms. Int J Epidemiol2005;34(6):1340-5.[Abstract/Free Full Text]
  7. DePietropaolo DL, Powers JH, Gill JM, et al. Diagnosis of lyme disease. Am Fam Physician 2005;72(2):297-304.[Medline]
  8. Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS 2003;111(5):557-66.[CrossRef][Medline]
  9. Verdon F, Burnand B, Stubi CL, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ 2003;326:1124.[Abstract/Free Full Text]




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