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Chronic Fatigue Syndrome, Fibromyalgia, and Complex Regional Pain Syndrome Type I

TO THE EDITOR: The diagnosis, etiology, and pathogenesis of "medically unexplained" chronic pain and fatigue are still a matter of controversy.^1,2 In our consultation-liaison practice, we recently saw three patients suffering from chronic fatigue syndrome and fibromyalgia who had a history of complex regional pain syndrome type I (formerly called reflex sympathetic dystrophy).

Case Report

The first patient, Ms. A, was a 22-year-old woman who had developed chronic fatigue syndrome/fibromyalgia some months after complex regional pain syndrome type I in her right leg had been stabilized. She later engaged in an overactive lifestyle (e.g., by combining college and night work as a waitress). She had childhood antecedents of emotional, physical, and sexual abuse. The other patients also had severe psychosocial or psychiatric problems before the appearance of complex regional pain syndrome type I and subsequent chronic fatigue syndrome/fibromyalgia.

Discussion

These patients led us to review the evidence for clinical/epidemiological, etiological, and pathogenetic links between these syndromes, including a possible common role of psychological/psychopathological factors.

The symptom profile of chronic fatigue syndrome and fibromyalgia is considered largely overlapping, although the two conditions are not completely identical.³ Complex regional pain syndrome type I shares many clinical features with chronic fatigue syndrome and fibromyalgia, such as a predominance in women, frequent traumatic onset, allodynia/hyperalgesia, and signs of autonomous nervous dysfunction as well as frequent psychiatric antecedents and comorbidity.⁴ On the other hand, to our knowledge, no epidemiological data are available about the lifetime co-occurrence of chronic fatigue syndrome/fibromyalgia and complex regional pain syndrome type I in the same patient.

A common genetic diathesis (e.g., the human leukocyte antigen genotype) has been hypothesized to exist with the disorders, but there is more convincing evidence for the role of adverse childhood experiences in increasing vulnerability to chronic pain and fatigue and promoting abnormal illness behaviors.⁵ Physical stress, often combined with psychosocial stress, triggers the onset of chronic fatigue syndrome and fibromyalgia;^5,6 this might be the case in complex regional pain syndrome type I as well.⁷ Moreover, subgroups of patients with chronic fatigue syndrome, fibromyalgia, and complex regional pain syndrome type I suffer from the symptoms of posttraumatic stress.^8,9 In the three disorders, symptoms and disability may be perpetuated by similar factors, such as disturbed sleep, comorbid anxiety and depression, and activity avoidance, resulting in physical deconditioning.^1,4

Hypothalamic-pituitary-adrenal axis hyporeactivity and autonomous nervous dysfunction are thought to play a key role in the pathophysiology of chronic fatigue syndrome and fibromyalgia by means of immunological dysregulations (e.g., abnormal cytokine production) and neuronal sensitization processes.¹⁰ Possible disturbances in the interaction between the autonomous nervous system, the neuroendocrine system, and the immune system (e.g., neurogenic inflammation) are also being studied intensively in patients with complex regional pain syndrome type I.⁴ One author has even proposed to rename fibromyalgia "generalized reflex sympathetic dystrophy."¹¹

In conclusion, the evidence for a relationship between chronic fatigue syndrome/fibromyalgia and complex regional pain syndrome type I remains preliminary but deserves further research. The hypothesis of common or similar vulnerability and precipitating and perpetuating factors should preferentially be tested by prospective investigations (although this may be difficult to carry out because of the relatively low incidence of complex regional pain syndrome type I). The role of emotional distress in the syndromes, including stress-related disturbances of nociceptive, healing, and recovery mechanisms, could be clarified by the "bridging" sciences of psychoneuroendocrinology and psychoneuroimmunology.^12–14 This type of research may eventually put to rest the dualistic debates about "organic" versus "psychogenic" causation of chronic fatigue syndrome, fibromyalgia, and complex regional pain syndrome type I and possibly open new treatment perspectives.

REFERENCES

1. Wessely S, Sharpe M, Hotopf M: Chronic Fatigue and Its Syndromes. Oxford, UK, Oxford University Press, 1998
2. Ochoa JL: Truths, errors, and lies around "reflex sympathetic dystrophy" and "complex regional pain syndrome." J Neurol 1999; 246:875-879[Medline]
3. Sullivan PF, Smith W, Buchwald D: Latent class analysis of symptoms associated with chronic fatigue syndrome and fibromyalgia. Psychol Med 2002; 32:881-888[CrossRef][Medline]
4. Harden RN, Baron R, Jänig W (eds): Complex Regional Pain Syndrome: Progress in Pain Research and Management, vol 22. Seattle, IASP Press, 2001
5. Van Houdenhove B, Neerinckx E, Van Onghena P, Lysens R, Vertommen H, Van Houdenhove L, Onghena P, Westhovens R, D'Hooghe MB: Victimization in chronic fatigue syndrome and fibromyalgia in tertiary care: a controlled study on prevalence and characteristics. Psychosomatics 2001; 42:21-28[Abstract/Free Full Text]
6. Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommen H: Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia: an etiological factor or proof of good citizenship? J Psychosom Res 2001; 51:571-576[CrossRef][Medline]
7. Van Houdenhove B, Vasquez G, Onghena P, Stans L, Vandeput C, Vermaut G, Vervaeke G, Igodt P, Vertommen H: Etiopathogenesis of reflex sympathetic dystrophy: a review and biopsychosocial hypothesis. Clin J Pain 1992; 8:300-306[Medline]
8. Cohen H, Neumann L, Haiman Y, Matar MA, Press J, Buskila D: Prevalence of post-traumatic stress disorder in fibromyalgia patients: overlapping syndromes or post-traumatic fibromyalgia? Semin Arthritis Rheum 2002; 32:38-50[CrossRef][Medline]
9. Lebowits AH, Yarmush J, Lefkowitz M: Reflex sympathetic dystrophy and posttraumatic stress disorder: evaluation and treatment. Clin J Pain 1990; 6:153-157[Medline]
10. Buskila D: Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. Curr Opin Rheumatol 2001; 13:117-127[Medline]
11. Martinez-Lavin M: Is fibromyalgia a generalized reflex sympathetic dystrophy? Clin Exp Rheumatol 2001; 19:1-3[Medline]
12. Heim C, Ehlert U, Hellhammer DH: The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 2000; 25:1-35[CrossRef][Medline]
13. Watkins LR, Maier SF: The pain of being sick: implications of immune-to-brain communication for understanding pain. Ann Rev Psychol 2000; 51:29-57[CrossRef][Medline]
14. Kiecolt-Glaser JK, Page GG, Marucha PT, MacCallum RC, Glaser R: Psychological influences on surgical recovery: perspectives from psychoneuroimmunology. Am Psychol 1998; 53:1209-1218[CrossRef][Medline]

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