Postviral fatigue syndrome

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Postviral Fatigue Syndrome. The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome. —Behan et al. (2007)
Quote from: Behan, et al. (2007). Enteroviruses and Postviral Fatigue Syndrome.

Postviral Fatigue Syndrome (PVFS) refers to a chronic fatiguing illness which begins after a virus. PVFS has many similarities to myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS).[1][2] Since not all cases of ME or CFS are preceded by a viral infection, the term PVFS has become outdated and is nowadays seldom used in scientific literature. As ME expert Peter Behan explained these developments: “It became abundantly, crystal clear that several patients had developed the syndrome, the identical syndrome but they had developed the syndrome not following a viral or other infection but due to their reaction to a particular form of physical or psychological stress.”[3][4]

Symptoms[edit | edit source]

By 1990, a group of core and minor symptoms of Postviral Fatigue Syndrome were described:

Lask and Dillon (1990) also reported:

Behan and Behan (1988) also reported:

Behan et al. (2007) also reported:

In children, symptoms may include:

  • lethargy
  • headache
  • abdominal pain
  • subjective muscular weakness[1]

These symptoms were altered and adapted over time, with over 20 different sets of diagnostic criteria being published, and psychological symptoms including depression and emotional lability regarded as potential consequences of the illness, rather than diagnostic symptoms.[7][8]

Diagnostic criteria[edit | edit source]

The most commonly used diagnostic criteria is the 1994 Fukuda criteria, uses the name chronic fatigue syndrome, and allows for non-viral triggers.[7] This requires at least 6 months of "persistent or relapsing" fatigue which persists despite rest, has a significant impact on daily life, and includes at least four of the following symptoms:

  • post-exertional malaise (PEM) lasting more than 24 hours
  • substantial impairment in short-term memory or concentration
  • sore throat
  • tender lymph nodes
  • muscle pain
  • multi-joint pain without swelling or redness
  • headaches of a new type, pattern, or severity
  • unrefreshing sleep[7]

More recent definitions have emphasized post-exertional malaise rather than fatigue, and used alternative for the illness, including the Systemic Exertion Intolerance Disease (2015) and the International Consensus Criteria for ME (2011).[9][10][11]

Viruses[edit | edit source]

Many different viruses have been reported immediately before the onset of postviral fatigue syndrome, including:

Classification [edit | edit source]

ICD-10 title[edit | edit source]

Postviral fatigue syndrome is the official concept title of code G93.3 in the ICD-10,[16] the medical classification list of the World Health Organization (WHO). "Benign myalgic encephalomyelitis" is inscribed as an inclusion, while "chronic fatigue syndrome" is listed only in the index. Since postviral fatigue syndrome is seldom used in scientific research and clinical practice, some argue it should be removed as a concept title. Mary Dimmock and Suzy Chapman for example propose to list PVFS in the upcoming ICD-11 as a synonym term under a new concept title "Myalgic encephalomyelitis".[17] The proposal of the IACFS/ME, written by Lily Chu[18], however suggests to retain the term PVFS as a concept title and to simply elevate the terms "chronic fatigue syndrome" (CFS) and "myalgic encephalomyelitis" (ME) to concept titles at the same level, with each of the three terms given a unique code. Both proposals to the ICD-11 advocate to maintain the classification of these three terms in the neurological chapter.

Post-infectious Fatigue Syndrome[edit | edit source]

The Oxford criteria has a post-infectious fatigue syndrome (PIFS) as one of its definitions.[19] The Argus Report article US NIH Report Calls for UK Definition of ME/CFS to be Scrapped states: "The NIH has issued a draft report that highlights the dire need for scientific research that will help find a cure for the millions of people suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) worldwide. The report also highlights the fact that the decades-old UK Royal Society of Medicine’s Oxford criteria for ME/CFS are severely “flawed,” and that continuing to use these criteria may “cause harm.” Further, the NIH report says that the Royal Society definition should “be retired” and replaced with a single case definition agreed to by the ME/CFS community."[20][10]

Post-EBV ME/CFS[edit | edit source]

Several studies have performed an extensive follow-up on adolescents with infectious mononucleosis resulting from the Epstein-Barr virus (EBV). In general these studies have found that approximately 10% of the sample meets the diagnosis of ME/CFS after 6 months, though the percentage decreases as time moves on. Research has not been able to identify significant predictors of ME/CFS diagnosis except for the severity of the acute Epstein-Barr virus (EBV) infection.

More fatigue after EBV compared to other infections[edit | edit source]

White et al. showed the percentage of patients developing chronic fatigue syndrome to be significantly higher after an infection with EBV (9-47%) than after an upper respiratory tract infection (0-6%).[21] Other research has shown that persistent fatigue is much more common after infectious mononucleosis than after other infectious diseases such as influenza or tonsillitis.[22]

Independent of psychological factors[edit | edit source]

The study by White et al. demonstrated that EBV does not cause an increase in psychiatric disorder[21] and that psychosocial factors were not predictors of persistent complaints.[23] This indicated that the postviral fatigue syndrome is a distinct disease category.[24] According to the authors, patients with the postviral fatigue syndrome reported more severe physical fatigue, especially after exertion, than patients with psychiatric disorders. A similiar conclusion was drawn by Buchwald et al., who followed up on 150 patients with infectious mononucleosis in the Seattle area. After six months, 12% of the patient sample said they still were not recovered. In agreement with White, the authors stated that they “do not believe that the postinfectious fatigue syndrome after infectious mononucleosis can be explained primarily by psychologic factors.”[25]

Only severity of  the acute illness predicts ME/CFS[edit | edit source]

The most comprehensive study of postviral fatigue syndrome was organized and funded by the CDC in the 2000s. The study focused on Dubbo a remote township in Australia where it is easier to follow up on medical records; 253 patients with either an acute infection with Epstein-Barr virus (EBV), coxiella burnetti (the bacteria that causes Q-fever) or Ross River virus were studied.[14] After six months, 11% of the patient sample met diagnostic criteria for chronic fatigue syndrome, with no significant differences in prevalence between the different infections. ME/CFS was predicted mostly by the severity of the acute infection, rather than by demographic, psychological or microbiological factors. There was no significant difference in cytokine expression[26] or reactivation of herpesviruses (EBV, HHV-6, CMV)[27] between the group that did or did not recover.  

ME/CFS cases decrease over time[edit | edit source]

A study in the Chicago area showed that the percentage of patients meeting ME/CFS criteria after infectious mononucleosis decreases as time moves on. While 13% met ME/CFS criteria at the six-month time interval, this decreased to 7% at 12 months and only 4% at 24 months.[28] The most important predictors of ME/CFS caseness were autonomic symptoms and days spent in bed since mono.[29] This confirmed the main conclusion of the Dubbo studies, namely that the severity of the acute infection is the main predictor of ME/CFS. In the Chicago study however, cytokine expression indicated differences in Th17 function in patients with post-infectious ME/CFS.[30]

Psychosocial factors determine persistent fatigue but not ME/CFS[edit | edit source]

Studies that looked at a broader definition of fatigue after an EBV infection have reached different conclusions. Candy et al. (2003) for example found that persistent fatigue six months after infectious mononucleosis was predicted by certain illness perceptions such as the belief that the illness would take more than one month to recover from and would have serious consequences.[31] Moss-Morris et al. followed-up on 246 patients with glandular fever from New Zealand. After six months, 7.8% still reported severe fatigue. Depression, anxiety and perfectionism were associated with persistent complaints though perceived stress and limiting activity were not.[32] A Norwegian study found that fatigue after acute EBV was predicted by variables related to symptoms and negative emotions instead of immune processes.[33] These findings would later be disrupted, and patient attitudes beliefs are no longer considered influence outcomes.[8][9]

See also
Biopsychosocial model.

Books[edit | edit source]

Articles and blogs[edit | edit source]

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 Lask, B; Dillon, M J (November 1990). "Postviral fatigue syndrome" (PDF). Archives of Disease in Childhood. p. 1198.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Archer, M.I. (1987). "The post-viral syndrome: a review". The Journal of the Royal College of General Practitioners. 37 (298): 212–214. ISSN 0035-8797. PMID 3320358.
  3. ↑ Shepherd, C. (1999). Living with Me: the Chronic, Post-viral Fatigue Syndrome. London: Vermilion. ISBN 0091816793.
  4. ↑ "ME: The Toxic Tiredness (Part 2)". YouTube. forcedout99. February 1, 2012. 35:19.
  5. ↑ 5.0 5.1 Behan, P.O.; Behan, W.M.H.; Gow, J.W.; Cavanagh, H.; Gillespie, S. (2007). "Enteroviruses and Postviral Fatigue Syndrome". In Bock, G.R.; Whelan, J. (eds.). Ciba Foundation Symposium 173 ‐ Chronic Fatigue Syndrome. doi:10.1002/9780470514382.ch9.
  6. ↑ Behan, P.O.; Behan, W.M. (1988). "Postviral Fatigue Syndrome". Critical reviews in neurobiology. PMID 3063394. Retrieved April 28, 2020.
  7. ↑ 7.0 7.1 7.2 Fukuda, K.; Straus, S.E.; Hickie, I.; Sharpe, M.C.; Dobbins, J.G.; Komaroff, A. (December 15, 1994). "The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group" (PDF). Annals of Internal Medicine. American College of Physicians. 121 (12): 953–959. ISSN 0003-4819. PMID 7978722.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 Carruthers, Bruce M.; Jain, Anil Kumar; De Meirleir, Kenny L.; Peterson, Daniel L.; Klimas, Nancy G.; Lerner, A. Martin; Bested, Alison C.; Flor-Henry, Pierre; Joshi, Pradip; Powles, AC Peter; Sherkey, Jeffrey A.; van de Sande, Marjorie I. (2003), "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols" (PDF), Journal of Chronic Fatigue Syndrome, 11 (2): 7–115, doi:10.1300/J092v11n01_02
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Carruthers, BM; van de Sande, MI; De Meirleir, KL; Klimas, NG; Broderick, G; Mitchell, T; Staines, D; Powles, ACP; Speight, N; Vallings, R; Bateman, L; Bell, DS; Carlo-Stella, N; Chia, J; Darragh, A; Gerken, A; Jo, D; Lewis, DP; Light, AR; Light, KC; Marshall-Gradisnik, S; McLaren-Howard, J; Mena, I; Miwa, K; Murovska, M; Stevens, SR (2012), Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners (PDF), ISBN 978-0-9739335-3-6
  10. ↑ 10.0 10.1 Clayton, Ellen Wright; Alegria, Margarita; Bateman, Lucinda; Chu, Lily; Cleeland, Charles; Davis, Ronald; Diamond, Betty; Ganiats, Theodore; Keller, Betsy; Klimas, Nancy; Lerner, A Martin; Mulrow, Cynthia; Natelson, Benjamin; Rowe, Peter; Shelanski, Michael (2015). "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Redefining an Illness" (PDF). National Academies.
  11. ↑ Jason, Leonard A.; Sunnquist, Madison; Brown, Abigail; Newton, Julia L.; Strand, Elin Bolle; Vernon, Suzanne D. (July 3, 2015). "Chronic fatigue syndrome versus systemic exertion intolerance disease". Fatigue: Biomedicine, Health & Behavior. 3 (3): 127–141. doi:10.1080/21641846.2015.1051291. ISSN 2164-1846. PMC 4556426. PMID 26345409.
  12. ↑ Umakanth, M (August 2017). "Post dengue fatigue syndrome" (PDF). Saudi Journal of Medical and Pharmaceutical Sciences. 3 (8): 858–861. doi:10.21276/sjmps.
  13. ↑ Scott, Janet T; Semple, Malcolm G (May 2017). "Ebola virus disease sequelae: a challenge that is not going away". The Lancet. Infectious diseases. 17 (5): 470–471. doi:10.1016/S1473-3099(17)30027-0. ISSN 1473-3099. PMC 5818139. PMID 28094207.
  14. ↑ 14.0 14.1 14.2 Hickie, Ian; Davenport, Tracey; Wakefield, Denis; Vollmer-Conna, Ute; Cameron, Barbara; Vernon, Suzanne D; Reeves, William C; Lloyd, Andrew (September 16, 2006). "Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study". BMJ : British Medical Journal. 333 (7568): 575. doi:10.1136/bmj.38933.585764.AE. ISSN 0959-8138. PMC 1569956. PMID 16950834.
  15. ↑ Lam, Marco Ho-Bun; Wing, Yun-Kwok; Yu, Mandy Wai-Man; Leung, Chi-Ming; Ma, Ronald C.W.; Kong, Alice P.S.; So, W.Y.; Fong, Samson Yat-Yuk; Lam, Siu-Ping (December 14, 2009). "Mental Morbidities and Chronic Fatigue in Severe Acute Respiratory Syndrome Survivors: Long-term Follow-up". Archives of Internal Medicine. 169 (22): 2142–2147. doi:10.1001/archinternmed.2009.384. ISSN 0003-9926.
  16. ↑ World Health Organization. "ICD-10 Version:2016". World Health Organization. Retrieved August 24, 2018.
  17. ↑ Chapman, Suzy; Dimmock, Mary (2017). "Proposal for the ICD-10 G93.3 legacy terms for ICD-11" (PDF). dxrevisionwatch.files.wordpress.com.
  18. ↑ Bested, Alison M. (April 18, 2017). "IACFS/ME Newsletter Volume 10, Issue 2 – April 2017". IACFS/ME.
  19. ↑ Sharpe, Michael; Archard, Len; Banatvala, Jangu; Borysiewicz, Leszek; Clare, Anthony; David, Anthony; Edwards, Richard; Hawton, Keith; Lambert, Harold; Lane, Russell (February 1991). "A report - chronic fatigue syndrome: guidelines for research". Journal of the Royal Society of Medicine. 84: 118–121. PMC 1293107.
  20. ↑ Swift, Penny. "US NIH Report Calls for UK Definition of ME/CFS to be Scrapped". theargusreport.com. Retrieved August 24, 2018.
  21. ↑ 21.0 21.1 White, P. D.; Thomas, J.M.; Amess, J.; Crawford, D.H.; Grover, S.A.; Kangro, H.O.; Clare, A.W. (December 1998). "Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever". The British Journal of Psychiatry: The Journal of Mental Science. 173: 475–481. ISSN 0007-1250. PMID 9926075.
  22. ↑ Petersen, I.; Thomas, J.M.; Hamilton, W.T.; White, P. D. (January 2006). "Risk and predictors of fatigue after infectious mononucleosis in a large primary-care cohort". QJM: monthly journal of the Association of Physicians. 99 (1): 49–55. doi:10.1093/qjmed/hci149. ISSN 1460-2725. PMID 16330509.
  23. ↑ White, P. D.; Thomas, J.M.; Kangro, H.O.; Bruce-Jones, W. D.; Amess, J.; Crawford, D.H.; Grover, S.A.; Clare, A.W. (December 8, 2001). "Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis". Lancet (London, England). 358 (9297): 1946–1954. doi:10.1016/S0140-6736(01)06961-6. ISSN 0140-6736. PMID 11747919.
  24. ↑ White, P. D.; Grover, S.A.; Kangro, H.O.; Thomas, J.M.; Amess, J.; Clare, A.W. (September 1995). "The validity and reliability of the fatigue syndrome that follows glandular fever". Psychological Medicine. 25 (5): 917–924. ISSN 0033-2917. PMID 8588010.
  25. ↑ Buchwald, D. S.; Rea, T. D.; Katon, W.J.; Russo, J.E.; Ashley, R.L. (November 2000). "Acute infectious mononucleosis: characteristics of patients who report failure to recover". The American Journal of Medicine. 109 (7): 531–537. ISSN 0002-9343. PMID 11063953.
  26. ↑ Vollmer-Conna, Uté; Cameron, Barbara; Hadzi-Pavlovic, Dusan; Singletary, Kristi; Davenport, Tracey; Vernon, Suzanne; Reeves, William C.; Hickie, Ian; Wakefield, Denis (September 15, 2007). "Postinfective fatigue syndrome is not associated with altered cytokine production". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 45 (6): 732–735. doi:10.1086/520990. ISSN 1537-6591. PMID 17712757.
  27. ↑ Cameron, Barbara; Flamand, Louis; Juwana, Hedy; Middeldorp, Jaap; Naing, Zin; Rawlinson, William; Ablashi, Dharam; Lloyd, Andrew (October 2010). "Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post-infective fatigue syndrome". Journal of Medical Virology. 82 (10): 1684–1688. doi:10.1002/jmv.21873. ISSN 1096-9071. PMID 20827765.
  28. ↑ Katz, Ben Z.; Jason, Leonard A. (February 2013). "Chronic fatigue syndrome following infections in adolescents". Current Opinion in Pediatrics. 25 (1): 95–102. doi:10.1097/MOP.0b013e32835c1108. ISSN 1531-698X. PMID 23263024.
  29. ↑ Jason, Leonard A.; Katz, Ben Z.; Shiraishi, Yukiko; Mears, Cynthia J.; Im, Young; Taylor, Renee R. (January 1, 2014). "Predictors of post-infectious chronic fatigue syndrome in adolescents". Health Psychology and Behavioral Medicine. 2 (1): 41–51. doi:10.1080/21642850.2013.869176. ISSN 2164-2850. PMC 3956649. PMID 24660116.
  30. ↑ Broderick, Gordon; Katz, Ben Z.; Fernandes, Henrique; Fletcher, Mary Ann; Klimas, Nancy; Smith, Frederick A.; O'Gorman, Maurice R.G.; Vernon, Suzanne D.; Taylor, Renee (September 13, 2012). "Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue". Journal of Translational Medicine. 10: 191. doi:10.1186/1479-5876-10-191. ISSN 1479-5876. PMC 3480896. PMID 22973830.
  31. ↑ Candy, B.; Chalder, T.; Cleare, A.J.; Peakman, A.; Skowera, A.; Wessely, S.; Weinman, J.; Zuckerman, M.; Hotopf, M. (July 2003). "Predictors of fatigue following the onset of infectious mononucleosis". Psychological Medicine. 33 (5): 847–855. ISSN 0033-2917. PMID 12877399.
  32. ↑ Moss-Morris, R.; Spence, M.J.; Hou, R. (May 2011). "The pathway from glandular fever to chronic fatigue syndrome: can the cognitive behavioural model provide the map?". Psychological Medicine. 41 (5): 1099–1107. doi:10.1017/S003329171000139X. ISSN 1469-8978. PMID 20663256.
  33. ↑ Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv Toril; Skovlund, Eva; Tjade, Trygve; Øie, Merete Glenne; Wyller, Vegard Bruun Bratholm (September 25, 2018). "Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study". Brain, Behavior, and Immunity. doi:10.1016/j.bbi.2018.09.023. ISSN 1090-2139. PMID 30261303.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

See post-exertional malaise.

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

World Health Organization (WHO) - "A specialized agency of the United Nations that is concerned with public health. It was established on 7 April 1948, and is headquartered in Geneva, Switzerland. The WHO is a member of the United Nations Development Group. Its predecessor, the Health Organization, was an agency of the League of Nations." The International Statistical Classification of Diseases and Related Health Problems (ICD) is maintained by WHO.

See World Health Organization.

International Classification of Diseases (ICD) - A system of medical diagnostic codes, created by the World Health Organization (WHO), to classify diseases and other health related conditions for the purpose of international diagnostic consistency. By having common diagnostic codes around the world, health researchers are better able to quantify and track disease burdens. The most current version is called ICD-11. (Learn more: www.who.int)

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

See National Institutes of Health.

National Institutes of Health (NIH) - A set of biomedical research institutes operated by the U.S. government, under the auspices of the Department of Health and Human Services.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

graded exercise therapy (GET) - A gradual increase in exercise or activity, according to a pre-defined plan. Focuses on overcoming the patient's alleged unhelpful illness beliefs that exertion can exacerbate symptoms, rather than on reversing physical deconditioning. Considered controversial, and possibly harmful, in the treatment or management of ME. One of the treatment arms of the controversial PACE trial.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.

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