Conclusion
Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause fibromyalgia or chronic fatigue syndrome (CFS).
Epidemiological Evidence
The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), found no relevant studies of quality in the literature assessing an association between fibromyalgia and MMR, influenza, hepatitis B or DTaP vaccines, or between CFS and MMR vaccine 1. A 2013 self-controlled case series in the UK found no association between CFS and bivalent HPV vaccine (Cervarix®) 2. Two Norwegian register-based studies published in 2015 and 2017 found no increased risk of CFS following pH1N1 vaccination 3 or HPV vaccination 4, respectively. A 2018 Dutch retrospective cohort study and self-controlled case series found no increased incidence of CFS or long-lasting fatigue following bivalent HPV vaccine 5. A 2020 systematic review and meta-analysis found HPV vaccines to have a potential protective effect against CFS 6.
Proposed Biological Mechanism
The etiological causes and underlying pathogenic mechanisms of fibromyalgia and CFS are still unclear and the subject of much debate 7-9. Theories that attempt to explain the mechanisms behind the development of these two disorders generally focus on sympathetic nervous system dysfunction, the inflammatory and oxidative stress pathways and the neuroendocrine system. Symptoms such as pain and fatigue have been associated with chronic inflammation, raised levels of oxidative stress and mitochondrial dysfunction. It has also been suggested that the hypothalamic-pituitary-adrenal axis and cortisol also have a role in the pathogenesis of fibromyalgia and CFS; however, it is still unclear whether these pathways are causes or just byproducts of these syndromes 10,11. Environmental stimuli such as stress or viral infection are thought to be able to trigger the pathogenesis of these disorders in genetically predisposed individuals 8,12.
The IOM concluded that there was no mechanistic evidence for an association between fibromyalgia and MMR, influenza, hepatitis B or DTaP vaccines, or between CFS and MMR vaccine 1.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
References
1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
2. Donegan K, Beau-Lejdstrom R, King B, Seabroke S, Thomson A, Bryan P. Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK. Vaccine 2013; 31(43): 4961-7.
3. Magnus P, Gunnes N, Tveito K, Bakken IJ, Ghaderi S, Stoltenberg C, Hornig M, Lipkin WI, Trogstad L, Haberg SE. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated with pandemic influenza infection, but not with an adjuvanted pandemic influenza vaccine. Vaccine 2015; 33(46): 6173-7.
4. Feiring B, Laake I, Bakken IJ, Greve-Isdahl M, Wyller VB, Haberg SE, Magnus P, Trogstad L. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine 2017; 35(33): 4203-12.
5. Schurink-Van’t Klooster TM, Kemmeren JM, van der Maas NAT, van de Putte EM, Ter Wolbeek M, Nijhof SL, Vanrolleghem AM, van Vliet JA, Sturkenboom M, de Melker HE. No evidence found for an increased risk of long-term fatigue following human papillomavirus vaccination of adolescent girls. Vaccine 2018; 36(45): 6796-802.
6. Willame C, Gadroen K, Bramer W, Weibel D, Sturkenboom M. Systematic Review and Meta-analysis of Postlicensure Observational Studies on Human Papillomavirus Vaccination and Autoimmune and Other Rare Adverse Events. The Pediatric infectious disease journal 2020; 39(4): 287-93.
7. Bazzichi L, Sernissi F, Consensi A, Giacomelli C, Sarzi-Puttini P. Fibromyalgia: a critical digest of the recent literature. Clin Exp Rheumatol 2011; 29(6 Suppl 69): S1-11.
8. Moss-Morris R, Deary V, Castell B. Chronic fatigue syndrome. Handbook of clinical neurology 2013; 110: 303-14.
9. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue S, Board on the Health of Select P, Institute of M. The National Academies Collection: Reports funded by National Institutes of Health. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US)
Copyright 2015 by the National Academy of Sciences. All rights reserved.; 2015.
10. Romano GF, Tomassi S, Russell A, Mondelli V, Pariante CM. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med 2015; 34: 61-77.
11. Martinez-Martinez LA, Mora T, Vargas A, Fuentes-Iniestra M, Martinez-Lavin M. Sympathetic nervous system dysfunction in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis: a review of case-control studies. J Clin Rheumatol 2014; 20(3): 146-50.
12. Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmun Rev 2008; 8(1): 41-3.
