Skip to main content
NCBI home page
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1989 May;150(5):590–596.

Chronic fatigue syndrome. A critical appraisal of the role of Epstein-Barr virus.

D Koo
PMCID: PMC1026689  PMID: 2545048

Abstract

The symptom complex currently designated the chronic fatigue syndrome was previously termed the chronic or chronic active Epstein-Barr virus syndrome or the chronic mononucleosis syndrome, prematurely assuming an etiologic role for the Epstein-Barr virus (EBV). This presumption derived from the fact that some patients with the chronic fatigue syndrome have very high or very low titers of certain antibodies to EBV. A review of seroepidemiologic patterns of response to EBV and of studies of patients with the chronic fatigue syndrome shows that these antibody titers overlap considerably both with those of controls or other healthy persons and with those of patients with other illnesses. Given the high prevalence of exposure to EBV, it would be difficult to determine whether the virus caused the syndrome or whether the antibody elevations resulted from the illness, even if distinct differences in titers existed. Other methodologic issues of control selection, laboratory test comparability, and differing case definitions pose problems in studying this syndrome. The recently published working case definition should facilitate the continuing search for causes.

Full text

PDF
590

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ablashi D. V., Salahuddin S. Z., Josephs S. F., Imam F., Lusso P., Gallo R. C., Hung C., Lemp J., Markham P. D. HBLV (or HHV-6) in human cell lines. Nature. 1987 Sep 17;329(6136):207–207. doi: 10.1038/329207a0. [DOI] [PubMed] [Google Scholar]
  2. Behan P. O., Behan W. M., Bell E. J. The postviral fatigue syndrome--an analysis of the findings in 50 cases. J Infect. 1985 May;10(3):211–222. doi: 10.1016/s0163-4453(85)92488-0. [DOI] [PubMed] [Google Scholar]
  3. Buchwald D., Sullivan J. L., Komaroff A. L. Frequency of 'chronic active Epstein-Barr virus infection' in a general medical practice. JAMA. 1987 May 1;257(17):2303–2307. [PubMed] [Google Scholar]
  4. DuBois R. E. Gamma globulin therapy for chronic mononucleosis syndrome. AIDS Res. 1986 Dec;2 (Suppl 1):S191–S195. [PubMed] [Google Scholar]
  5. DuBois R. E., Seeley J. K., Brus I., Sakamoto K., Ballow M., Harada S., Bechtold T. A., Pearson G., Purtilo D. T. Chronic mononucleosis syndrome. South Med J. 1984 Nov;77(11):1376–1382. doi: 10.1097/00007611-198411000-00007. [DOI] [PubMed] [Google Scholar]
  6. Fleisher G., Bolognese R. Persistent Epstein-Barr virus infection and pregnancy. J Infect Dis. 1983 Jun;147(6):982–986. doi: 10.1093/infdis/147.6.982. [DOI] [PubMed] [Google Scholar]
  7. Hanto D. W., Frizzera G., Gajl-Peczalska K. J., Sakamoto K., Purtilo D. T., Balfour H. H., Jr, Simmons R. L., Najarian J. S. Epstein-Barr virus-induced B-cell lymphoma after renal transplantation: acyclovir therapy and transition from polyclonal to monoclonal B-cell proliferation. N Engl J Med. 1982 Apr 15;306(15):913–918. doi: 10.1056/NEJM198204153061506. [DOI] [PubMed] [Google Scholar]
  8. Henle W., Henle G. E., Horwitz C. A. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Hum Pathol. 1974 Sep;5(5):551–565. doi: 10.1016/s0046-8177(74)80006-7. [DOI] [PubMed] [Google Scholar]
  9. Henle W., Henle G., Andersson J., Ernberg I., Klein G., Horwitz C. A., Marklund G., Rymo L., Wellinder C., Straus S. E. Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci U S A. 1987 Jan;84(2):570–574. doi: 10.1073/pnas.84.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988 Mar;108(3):387–389. doi: 10.7326/0003-4819-108-3-387. [DOI] [PubMed] [Google Scholar]
  11. Holmes G. P., Kaplan J. E., Stewart J. A., Hunt B., Pinsky P. F., Schonberger L. B. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987 May 1;257(17):2297–2302. [PubMed] [Google Scholar]
  12. Horwitz C. A., Henle W., Henle G., Rudnick H., Latts E. Long-term serological follow-up of patients for Epstein-Barr virus after recovery from infectious mononucleosis. J Infect Dis. 1985 Jun;151(6):1150–1153. doi: 10.1093/infdis/151.6.1150. [DOI] [PubMed] [Google Scholar]
  13. Horwitz C. A., Henle W., Henle G., Schmitz H. Clinical evaluation of patients with infectious mononucleosis and development of antibodies to the R component of the Epstein-Barr virus-induced early antigen complex. Am J Med. 1975 Mar;58(3):330–338. doi: 10.1016/0002-9343(75)90599-9. [DOI] [PubMed] [Google Scholar]
  14. 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 Jan;102(1):1–7. doi: 10.7326/0003-4819-102-1-. [DOI] [PubMed] [Google Scholar]
  15. Jones J. F., Shurin S., Abramowsky C., Tubbs R. R., Sciotto C. G., Wahl R., Sands J., Gottman D., Katz B. Z., Sklar J. T-cell lymphomas containing Epstein-Barr viral DNA in patients with chronic Epstein-Barr virus infections. N Engl J Med. 1988 Mar 24;318(12):733–741. doi: 10.1056/NEJM198803243181203. [DOI] [PubMed] [Google Scholar]
  16. Kibler R., Lucas D. O., Hicks M. J., Poulos B. T., Jones J. F. Immune function in chronic active Epstein-Barr virus infection. J Clin Immunol. 1985 Jan;5(1):46–54. doi: 10.1007/BF00915168. [DOI] [PubMed] [Google Scholar]
  17. Komaroff A. L. The 'chronic mononucleosis' syndromes. Hosp Pract (Off Ed) 1987 May 30;22(5A):71–75. [PubMed] [Google Scholar]
  18. Lamy M. E., Favart A. M., Cornu C., Mendez M., Segas M., Burtonboy G. Study of Epstein Barr virus (EBV) antibodies: IgG and IgM anti-VCA, IgG anti-EA and Ig anti-EBNA obtained with an original microtiter technique: --serological criterions of primary and recurrent EBV infections and follow-up of infectious mononucleosis--seroepidemiology of EBV in Belgium based on 5178 sera from patients. Acta Clin Belg. 1982;37(5):281–298. doi: 10.1080/22953337.1982.11718879. [DOI] [PubMed] [Google Scholar]
  19. Miller G., Grogan E., Rowe D., Rooney C., Heston L., Eastman R., Andiman W., Niederman J., Lenoir G., Henle W. Selective lack of antibody to a component of EB nuclear antigen in patients with chronic active Epstein-Barr virus infection. J Infect Dis. 1987 Jul;156(1):26–35. doi: 10.1093/infdis/156.1.26. [DOI] [PubMed] [Google Scholar]
  20. Niederman J. C., Evans A. S., Subrahmanyan L., McCollum R. W. Prevalence, incidence and persistence of EB virus antibody in young adults. N Engl J Med. 1970 Feb 12;282(7):361–365. doi: 10.1056/NEJM197002122820704. [DOI] [PubMed] [Google Scholar]
  21. POSKANZER D. C., HENDERSON D. A., KUNKLE C., KALTER S. S., CLEMENT W. B., BOND J. O. Epidemic neuromyasthenia; an outbreak in Punta Gorda, Florida. N Engl J Med. 1957 Aug 22;257(8):356–364. doi: 10.1056/NEJM195708222570802. [DOI] [PubMed] [Google Scholar]
  22. Porter D. D., Wimberly I., Benyesh-Melnick M. Prevalence of antibodies to EB virus and other herpesviruses. JAMA. 1969 Jun 2;208(9):1675–1679. [PubMed] [Google Scholar]
  23. SHELOKOV A., HABEL K., VERDER E., WELSH W. Epidemic neuromyasthenia; an outbreak of poliomyelitislike illness in student nurses. N Engl J Med. 1957 Aug 22;257(8):345–355. doi: 10.1056/NEJM195708222570801. [DOI] [PubMed] [Google Scholar]
  24. Sakamoto K., Greally J., Gilfillan R. F., Sexton J., Barnabei V., Yetz J., Bechtold T., Seeley J. K., O'Dwyer E., Purtilo D. T. Epstein-Barr virus in normal pregnant women. Am J Reprod Immunol. 1982 Aug;2(4):217–221. doi: 10.1111/j.1600-0897.1982.tb00169.x. [DOI] [PubMed] [Google Scholar]
  25. Salahuddin S. Z., Ablashi D. V., Markham P. D., Josephs S. F., Sturzenegger S., Kaplan M., Halligan G., Biberfeld P., Wong-Staal F., Kramarsky B. Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science. 1986 Oct 31;234(4776):596–601. doi: 10.1126/science.2876520. [DOI] [PubMed] [Google Scholar]
  26. Schooley R. T., Carey R. W., Miller G., Henle W., Eastman R., Mark E. J., Kenyon K., Wheeler E. O., Rubin R. H. Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitis. Clinical and serologic features and response to antiviral chemotherapy. Ann Intern Med. 1986 May;104(5):636–643. doi: 10.7326/0003-4819-104-5-636. [DOI] [PubMed] [Google Scholar]
  27. Schrier R. W. Treatment of hyponatremia. N Engl J Med. 1985 Apr 25;312(17):1121–1123. doi: 10.1056/NEJM198504253121709. [DOI] [PubMed] [Google Scholar]
  28. 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 Dec 29;319(26):1692–1698. doi: 10.1056/NEJM198812293192602. [DOI] [PubMed] [Google Scholar]
  29. Straus S. E. EB or not EB--that is the question. JAMA. 1987 May 1;257(17):2335–2336. [PubMed] [Google Scholar]
  30. Straus S. E. The chronic mononucleosis syndrome. J Infect Dis. 1988 Mar;157(3):405–412. doi: 10.1093/infdis/157.3.405. [DOI] [PubMed] [Google Scholar]
  31. Straus S. E., Tosato G., Armstrong G., Lawley T., Preble O. T., Henle W., Davey R., Pearson G., Epstein J., Brus I. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985 Jan;102(1):7–16. doi: 10.7326/0003-4819-102-1-7. [DOI] [PubMed] [Google Scholar]
  32. Sumaya C. V. Endogenous reactivation of Epstein-Barr virus infections. J Infect Dis. 1977 Mar;135(3):374–379. doi: 10.1093/infdis/135.3.374. [DOI] [PubMed] [Google Scholar]
  33. Sumaya C. V., Henle W., Henle G., Smith M. H., LeBlanc D. Seroepidemiologic study of Epstein-Barr virus infections in a rural community. J Infect Dis. 1975 Apr;131(4):403–408. doi: 10.1093/infdis/131.4.403. [DOI] [PubMed] [Google Scholar]
  34. Sumaya C. V. Serological testing for Epstein-Barr virus--developments in interpretation. J Infect Dis. 1985 Jun;151(6):984–987. doi: 10.1093/infdis/151.6.984. [DOI] [PubMed] [Google Scholar]
  35. Tischendorf P., Shramek G. J., Balagtas R. C., Deinhardt F., Knospe W. H., Noble G. R., Maynard J. E. Development and persistence of immunity to Epstein-Barr virus in man. J Infect Dis. 1970 Nov;122(5):401–409. doi: 10.1093/infdis/122.5.401. [DOI] [PubMed] [Google Scholar]
  36. 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 Jan 9;1(8263):61–64. doi: 10.1016/s0140-6736(82)90210-0. [DOI] [PubMed] [Google Scholar]
  37. Tosato G., Magrath I., Koski I., Dooley N., Blaese M. Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis. N Engl J Med. 1979 Nov 22;301(21):1133–1137. doi: 10.1056/NEJM197911223012101. [DOI] [PubMed] [Google Scholar]
  38. Virelizier J. L., Lenoir G., Griscelli C. Persistent Epstein-Barr virus infection in a child with hypergammaglobulinaemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet. 1978 Jul 29;2(8083):231–234. doi: 10.1016/s0140-6736(78)91744-0. [DOI] [PubMed] [Google Scholar]
  39. WHITE D. N., BURTCH R. B. Iceland disease: a new infection simulating acute anterior poliomyelitis. Neurology. 1954 Jul;4(7):506–516. doi: 10.1212/wnl.4.7.506. [DOI] [PubMed] [Google Scholar]
  40. Weinstein L. Thyroiditis and "chronic infectious mononucleosis". N Engl J Med. 1987 Nov 5;317(19):1225–1226. doi: 10.1056/nejm198711053171914. [DOI] [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES