Aktuelle Rheumatologie 2002; 27(2): 90-96
DOI: 10.1055/s-2002-25725
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Das chronische Erschöpfbarkeitssyndrom (CFS)

The Chronic Fatigue Syndrome (CFS)M.  Späth1
  • 1Friedrich-Baur-Institut (Leitender Arzt: Prof. Dr. med. D. Pongratz), Ludwig-Maximilians-Universität München
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Publikationsverlauf

Publikationsdatum:
25. April 2002 (online)

Zusammenfassung

Das chronische Erschöpfbarkeitssyndrom (CFS) ist ein Symptomenkomplex, der, einem Katalog von Klassifikationskriterien folgend, nach Ausschluss anderer, die chronische abnorme Erschöpfbarkeit evtl. erklärender Erkrankungen die Zuordnung des Beschwerdebildes zu einem CFS zulässt. Dieser „Rahmen” wurde zur Vereinheitlichung der Durchführung wissenschaftlicher Studien konzipiert. Solche Studien erbrachten bisher zahlreiche Hinweise auf mögliche Störungen der komplexen Interaktionen von HPA-Achse, Neurotransmittersystemen und Mediatoren des Immunsystems, jedoch keinen spezifischen diagnostischen Marker. Die bisherigen Forschungsergebnisse zu Ätiologie und Pathogenese werden ebenso referiert wie die Studien zu möglichen Therapieansätzen.

Abstract

Chronic fatigue syndrome (CFS) is an illness defined exclusively by a group of symptoms, according to a case definition developed under the leadership of the US Centers for Disease Control and Prevention (CDC). All of the symptoms are nonspecific and occurring in many illnesses. There are no biological markers or any results from other methods which provide a specific diagnostic test for clinical use. However, there is evidence from many studies that alterations within the complex network of HPA axis, neurotransmitter systems and mediators of the immune system play a crucial role for the pathogenesis of CFS. Both these findings and the therapeutic approaches are reviewed.

  • 1 Acheson E D. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland diseases and epidemic neuromyasthenia.  Am J Med. 1959;  26 569-595
  • 2 Allain T J, Bearn J A, Coskeran P, Jones J, Checkley A, Butler J, Wessely S, Miell J P. Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome.  Biol Psychiatry. 1997;  41 567-573
  • 3 Bakheit A M, Behan P O, Dinan T G, Gray C E, O’Keane V. Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.  BMJ (Clinical Research Ed.). 1992;  304 1010-1012
  • 4 Bakheit A M, Behan P O, Watson W S, Morton J J. Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome.  Acta Neurol Scand. 1993;  87 234-238
  • 5 Barnes P R, Taylor D J, Kemp G J, Radda G K. Skeletal muscle bioenergetics in the chronic fatigue syndrome.  J Neurol Neurosurg Psychiatry. 1993;  56 679-683
  • 6 Beard G M. Neurasthenia or nervous exhaustion.  Boston Med Surg. 1869;  J III 217-221
  • 7 Bearn J, Allain T, Coskeran P, Munro N, Butler J, McGregor A, Wessely S. Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in chronic fatigue syndrome.  Biol Psychiatry. 1995;  37 245-252
  • 8 Behan P O, Behan W M. Postviral fatigue syndrome.  Crit Rev Neurobiol. 1988;  4 157-178
  • 9 Behan P O, Behan W M, Gow J W, Cavanagh H, Gillespie S. Enteroviruses and postviral fatigue syndrome (discussion 154 - 149).  Ciba Found Symp. 1993;  173 146-154
  • 10 Behan P O, Behan W M, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome.  Acta Neurol Scand. 1990;  82 209-216
  • 11 Behan W M, More I A, Behan P O. Mitochondrial abnormalities in the postviral fatigue syndrome.  Acta Neuropathol (Berl). 1991;  83 61-65
  • 12 Bennett A L, Fagioli L R, Schur P H, Schacterle R S, Komaroff A L. Immunoglobulin subclass levels in chronic fatigue syndrome.  J Clin Immunol. 1996;  16 315-320
  • 13 Bennett A L, Mayes D M, Fagioli L R, Guerriero R, Komaroff A L. Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome.  J Psychiatr Res. 1997;  31 91-96
  • 14 Brooks J C, Roberts N, Whitehouse G, Majeed T. Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome.  Br J Radiol. 2000;  73 1206-1208
  • 15 Buchwald D, Ashley R L, Pearlman T, Kith P, Komaroff A L. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.  J Med Virol. 1996;  50 25-30
  • 16 Buchwald D, Garrity D. Comparison of patients with chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities.  Arch Intern Med. 1994;  154 2049-2053
  • 17 Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff A L. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system.  Ann Intern Med. 1995;  123 81-88
  • 18 Buchwald D, Wener M H, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and chronic fatigue syndrome.  J Rheumatol. 1997;  24 372-376
  • 19 Butler S, Chalder T, Ron M, Wessely S. Cognitive behaviour therapy in chronic fatigue syndrome.  Journal Of Neurology, Neurosurgery And Psychiatry. 1991;  54 153-158
  • 20 Byrne E, Trounce I. Chronic fatigue and myalgia syndrome: mitochondrial and glycolytic studies in skeletal muscle.  J Neurol Neurosurg Psychiatry. 1987;  50 743-746
  • 21 Cleare A J, Bearn J, Allain T, McGregor A, Wessely S, Murray R M, O’Keane V. Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.  J Affect Disord. 1995;  34 283-289
  • 22 Cleare A J, Heap E, Malhi G S, Wessely S, O’Keane V, Miell J. Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.  Lancet. 1999;  353 455-458
  • 23 Coyle P K, Krupp L B, Doscher C, Amin K. Borrelia burgdorferi reactivity in patients with severe persistent fatigue who are from a region in which Lyme disease is endemic.  Clin Infect Dis. 1994;  18 Suppl 1 S24-27
  • 24 Crofford L J. The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome.  Z Rheumatol. 1998;  57 67-71
  • 25 Crofford L J, Demitrack M A. Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome.  Rheum Dis Clin North Am. 1996;  22 267-284
  • 26 de Meirleir K, Bisbal C, Campine I, de Becker P, Salehzada T, Demettre E, Lebleu B. A 37 kDa 2 - 5A binding protein as a potential biochemical marker for chronic fatigue syndrome.  Am J Med. 2000;  108 99-105
  • 27 Deale A, Chalder T, Marks I, Wessely S. Cognitive behavior therapy for chronic fatigue syndrome: a randomized controlled trial.  Am J Psychiatry. 1997;  154 408-414
  • 28 Demitrack M A. Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management.  Psychiatr Clin North Am. 1998;  21 671-692
  • 29 Demitrack M A, Crofford L J. Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.  Ann N Y Acad Sci. 1998;  840 684-697
  • 30 Dismukes W E, Wade J S, Lee J Y, Dockery B K, Hain J D. A randomized, double-blind trial of nystatin therapy for the candidiasis hypersensitivity syndrome.  N Engl J Med. 1990;  323 1717-1723
  • 31 Dykman K D, Tone C, Ford C, Dykman R A. The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome.  Integr Physiol Behav Sci. 1998;  33 61-71
  • 32 Evengard B, Briese T, Lindh G, Lee S, Lipkin W I. Absence of evidence of Borna disease virus infection in Swedish patients with Chronic Fatigue Syndrome.  J Neurovirol. 1999;  5 495-499
  • 33 Fischler B, Le B on, Hoffmann G, Cluydts R, Kaufman L, de Meirleir K. Sleep anomalies in the chronic fatigue syndrome. A comorbidity study.  Neuropsychobiology. 1997;  35 115-122
  • 34 Fukuda K, Straus S E, Hickie I, Sharpe M C, Dobbins J G, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group.  Annals Intern Med. 1994;  121 953-959
  • 35 Goodnick P J, Sandoval R. Psychotropic treatment of chronic fatigue syndrome and related disorders.  J Clin Psychiatry. 1993;  54 13-20
  • 36 Gow J W, Behan W M, Simpson K, McGarry F, Keir S, Behan P O. Studies on enterovirus in patients with chronic fatigue syndrome.  Clin Infect Dis. 1994;  18 Suppl 1 126-129
  • 37 Gray J B, Martinovic A M. Eicosanoids and essential fatty acid modulation in chronic disease and the chronic fatigue syndrome published erratum appears in Med Hypotheses 1995 Aug;45(2): 219.  Medical Hypotheses. 1994;  43 31-42
  • 38 Holmes G P, Kaplan J E, Gantz N M, Komaroff A L, Schonberger L B, Straus S E, Jones J F, Dubois R E, Cunningham-Rundles C, Pahwa S. et al . Chronic fatigue syndrome: a working case definition.  Ann Intern Med. 1988;  108 387-389
  • 39 Ichise M, Salit I E, Abbey S E, Chung D G, Gray B, Kirsh J C, Freedman M. Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome.  Nucl Med Commun. 1992;  13 767-772
  • 40 Jones J F, Ray C G, Minnich L L, Hicks M J, Kibler R, Lucas D O. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies.  Ann Intern Med. 1985;  102 1-7
  • 41 Kent-Braun J A. Central and peripheral contributions to muscle fatigue in humans during sustained maximal effort.  Eur J Appl Physiol Occup Physiol. 1999;  80 57-63
  • 42 Kent-Braun J A, Sharma K R, Weiner M W, Massie B, Miller R G. Central basis of muscle fatigue in chronic fatigue syndrome.  Neurology. 1993;  43 125-131
  • 43 Komaroff A L. The biology of chronic fatigue syndrome.  Am J Med. 2000;  108 169-171
  • 44 Landay A L, Jessop C, Lennette E T, Levy J A. Chronic fatigue syndrome: clinical condition associated with immune activation.  Lancet. 1991;  338 707-712
  • 45 Lawrie S M, Manders D N, Geddes J R, Pelosi A J. A population-based incidence study of chronic fatigue.  Psychol Med. 1997;  27 343-353
  • 46 Lawrie S M, Pelosi A J. Chronic fatigue syndrome in the community. Prevalence and associations.  Br J Psychiatry. 1995;  166 793-797
  • 47 Le B on, Hoffmann G, Murphy J, de Meirleir K, Cluydts R, Pelc I. How significant are primary sleep disorders and sleepiness in the chronic fatigue syndrome?.  Sleep Res Online. 2000;  3 43-48
  • 48 Lindh G, Samuelson A, Hedlund K O, Evengard B, Lindquist L, Ehrnst A. No findings of enteroviruses in Swedish patients with chronic fatigue syndrome.  Scand J Infect Dis. 1996;  28 305-307
  • 49 Lloyd A, Hickie I, Wakefield D, Boughton C, Dwyer J. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.  Am J Med. 1990;  89 561-568
  • 50 Lloyd A R, Hickie I, Boughton C R, Spencer O, Wakefield D. Prevalence of chronic fatigue syndrome in an Australian population.  Med J Aust. 1990;  153 522-528
  • 51 Manian F A. Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?.  Clin Infect Dis. 1994;  19 448-453
  • 52 Manu P, Lane T J, Matthews D A, Castriotta R J, Watson R K, Abeles M. Alpha-delta sleep in patients with a chief complaint of chronic fatigue.  South Med J. 1994;  87 465-470
  • 53 Mawle A C, Nisenbaum R, Dobbins J G, Gary H E, Jr. , Stewart J A, Reyes M, Steele L, Schmid D S, Reeves W C. Immune responses associated with chronic fatigue syndrome: a case-control study.  J Infect Dis. 1997;  175 136-141
  • 54 Moldofsky H. Fibromyalgia, sleep disorder and chronic fatigue syndrome.  Ciba Found Symp. 1993;  173 262-271
  • 55 Nakaya T, Takahashi H, Nakamur Y, Kuratsune H, Kitani T, Machii T, Yamanishi K, Ikuta K. Borna disease virus infection in two family clusters of patients with chronic fatigue syndrome.  Microbiol Immunol. 1999;  43 679-689
  • 56 Neeck G, Crofford L J. Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome.  Rheum Dis Clin North Am. 2000;  26 989-1002
  • 57 Nix W A, Egle U T. Das chronische Erschöpfbarkeitssyndrom.  Akt Neurologie. 1998;  25 6-12
  • 58 Norregaard J, Bulow P M, Prescott E, Jacobsen S, Danneskiold-Samsoe B. A four-year follow-up study in fibromyalgia. Relationship to chronic fatigue syndrome.  Scand J Rheumatol. 1993;  22 35-38
  • 59 Parker A J, Wessely S, Cleare A J. The neuroendocrinology of chronic fatigue syndrome and fibromyalgia.  Psychol Med. 2001;  31 1331-1345
  • 60 Peakman M, Deale A, Field R, Mahalingam M, Wessely S. Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation.  Clin Immunol Immunopathol. 1997;  82 83-91
  • 61 Peterson P K, Pheley A, Schroeppel J, Schenck C, Marshall P, Kind A, Haugland J M, Lambrecht L J, Swan S, Goldsmith S. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome.  Arch Intern Med. 1998;  158 908-914
  • 62 Peterson P K, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.  Am J Med. 1990;  89 554-560
  • 63 Plioplys A V, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.  Neuropsychobiology. 1997;  35 16-23
  • 64 Preedy V R, Smith D G, Salisbury J R, Peters T J. Biochemical and muscle studies in patients with acute onset post-viral fatigue syndrome.  J Clin Pathol. 1993;  46 722-726
  • 65 Price J R, Couper J. Cognitive behaviour therapy for adults with chronic fatigue syndrome.  Cochrane Database Syst Rev. 2000;  CD 001 027
  • 66 Prins J B, Bleijenberg G, Bazelmans E, Elving L D, de Boo T M, Severens J L, van der Wilt G J, Spinhoven P, van der Meer J W. Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial.  Lancet. 2001;  357 841-847
  • 67 Reeves W C, Stamey F R, Black J B, Mawle A C, Stewart J A, Pellett P E. Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study.  Clin Infect Dis. 2000;  31 48-52
  • 68 Rowe P C, Calkins H, DeBusk K, McKenzie R, Anand R, Sharma G, Cuccherini B A, Soto N, Hohman P, Snader S, Lucas K E, Wolff M, Straus S E. Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.  Jama. 2001;  285 52-59
  • 69 Schutzer S E, Natelson B H. Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome.  Neurology. 1999;  53 1340-1341
  • 70 Schwartz R B, Komaroff A L, Garada B M, Gleit M, Doolittle T H, Bates D W, Vasile R G, Holman B L. SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression.  AJR. 1994;  162 943-951
  • 71 Sharpe M, Clements A, Hawton K, Young A H, Sargent P, Cowen P J. Increased prolactin response to buspirone in chronic fatigue syndrome.  Journal Of Affective Disorders. 1996;  41 71-76
  • 72 Sharpe M, Hawton K, Clements A, Cowen P J. Increased brain serotonin function in men with chronic fatigue syndrome.  BMJ (Clinical Research Ed.). 1997;  315 164-165
  • 73 Sharpe M C, Archard L C, Banatvala J E, Borysiewicz L K, Clare A W, David A, Edwards R H, Hawton K E, Lambert H P, Lane R J. et al . A report-chronic fatigue syndrome: guidelines for research.  J R Soc Med. 1991;  84 118-121
  • 74 Spaeth M, Stratz T, Schmalisch P, Mueller W, Pongratz D. Carnitine deficiency and fibromyalgia.  Arthritis Rheum. 1999;  42 150
  • 75 Späth M, Welzel D, Farber L. Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists-preliminary results.  Scand J Rheumatol Suppl. 2000;  113 72-77
  • 76 Straus S E, Dale J K, Peter J B, Dinarello C A. Circulating lymphokine levels in the chronic fatigue syndrome.  J Infect Dis. 1989;  160 1085-1086
  • 77 Straus S E, Dale J K, Tobi M, Lawley T, Preble O, Blaese R M, Hallahan C, Henle W. Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial.  N Engl J Med. 1988;  319 1692-1698
  • 78 Suhadolnik R J, Peterson D L, O’Brien K, Cheney P R, Herst C V, Reichenbach N L, Kon N, Horvath S E, Iacono K T, Adelson M E, de Meirleir K, de Becker P, Charubala R, Pfleiderer W. Biochemical evidence for a novel low molecular weight 2 - 5A-dependent RNase L in chronic fatigue syndrome.  J Interferon Cytokine Res. 1997;  17 377-385
  • 79 Swanink C M, van der Meer J W, Vercoulen J H, Bleijenberg G, Fennis J F, Galama J M. Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay.  Clin Infect Dis. 1995;  20 1390-1392
  • 80 Swanink C M, Vercoulen J H, Bleijenberg G, Fennis J F, Galama J M, van der Meer J W. Chronic fatigue syndrome: a clinical and laboratory study with a well matched control group.  J Intern Med. 1995;  237 499-506
  • 81 Tobi M, Morag A, Ravid Z, Chowers I, Feldman-Weiss V, Michaeli Y, Ben-Chetrit E, Shalit M, Knobler H. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection.  Lancet. 1982;  1 61-64
  • 82 Vercoulen J H, Swanink C M, Zitman F G, Vreden S G, Hoofs M P, Fennis J F, Galama J M, van der Meer J W, Bleijenberg G. Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome.  Lancet. 1996;  347 858-861
  • 83 Vollmer-Conna U, Hickie I, Hadzi-Pavlovic D, Tymms K, Wakefield D, Dwyer J, Lloyd A. Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome.  Am J Med. 1997;  103 38-43
  • 84 Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study.  Am J Public Health. 1997;  87 1449-1455
  • 85 Wessely S, Nimnuan C, Sharpe M. Functional somatic syndromes: one or many ?.  Lancet. 1999;  354 936-939
  • 86 Wessely S, Powell R. Fatigue syndromes: a comparison of chronic “postviral” fatigue with neuromuscular and affective disorders.  J Neurol Neurosurg Psychiatry. 1989;  52 940-948
  • 87 Whiting P, Bagnall A M, Sowden A J, Cornell J E, Mulrow C D, Ramirez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review.  Jama. 2001;  286 1360-1368

Dr. med. M. Späth

Friedrich-Baur-Institut · Universität München

Ziemssenstraße 1a · 80336 München ·

Telefon: 089/5160-7420

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eMail: Michael.Spaeth@lrz.uni-muenchen.de

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