Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination?

Abstract:

Fibromyalgia is a disorder characterized by chronic widespread pain and non-pain symptoms, such as fatigue, dysautonomia, and cognitive and sleep disturbances. Its pathogenesis and treatment continue to be the subject of debate. We highlight the role of three mechanisms-autoimmunity, neuroinflammation, and small fiber neuropathy in the pathogenesis of the disease. These mechanisms are shown to be closely interlinked (also on a molecular level), and the review considers the implementation of this relationship in the search for therapeutic options.

We also pay attention to chronic fatigue syndrome, which overlaps with fibromyalgia, and propose a concept of “autoimmune hypothalamopathy” for its pathogenesis. Finally, we analyze the molecular mechanisms underlying the neuroinflammatory background in the development of adverse events following HPV vaccination and suggesting neuroinflammation, which could exacerbate the development of symptoms following HPV vaccination (though this is hotly debated), as a model for fibromyalgia pathogenesis.

Source: Ryabkova VA, Churilov LP, Shoenfeld Y. Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination? Int J Mol Sci. 2019 Oct 18;20(20). pii: E5164. doi: 10.3390/ijms20205164. https://www.mdpi.com/1422-0067/20/20/5164 (Full article)

Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial and poorly undersood disabling disease. We present epidemiological, clinical and experimental evidence that ME/CFS constitutes a major type of adverse effect of vaccines, especially those containing poorly degradable particulate aluminum adjuvants.

Evidence has emerged very slowly due to the multiplicity, lack of specificity, delayed onset, and frequent medical underestimation of ME/CFS symptoms. It was supported by an epidemiological study comparing vaccinated vs unvaccinated militaries that remained undeployed during Gulf War II.

Affected patients suffer from cognitive dysfunction affecting attention, memory and inter-hemispheric connexions, well correlated to brain perfusion defects and associated with a stereotyped and distinctive pattern of cerebral glucose hypometabolism. Deltoid muscle biopsy performed to investigate myalgia typically yields macrophagic myofasciitis (MMF), a histological biomarker assessing longstanding persistency of aluminum agglomerates within innate immune cells at site of previous immunization. MMF is seemingly linked to altered mineral particle detoxification by the xeno/autophagy machinery.

Comparing toxicology of different forms of aluminum and different types of exposure is misleading and inadequate and small animal experiments have turned old dogma upside down. Instead of being rapidly solubilized in the extracellular space, injected aluminum particles are quickly captured by immune cells and transported to distant organs and the brain where they elicit an inflammatory response and exert selective low dose long-term neurotoxicity. Clinical observations and experiments in sheep, a large animal like humans, confirmed both systemic diffusion and neurotoxic effects of aluminum adjuvants. Post-immunization ME/CFS represents the core manifestation of “autoimmune/inflammatory syndrome induced by adjuvants” (ASIA).

Copyright © 2019. Published by Elsevier B.V.

Source: Gherardi RK, Crépeaux G, Authier FJ. Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system. Autoimmun Rev. 2019 May 3. pii: S1568-9972(19)30109-0. doi: 10.1016/j.autrev.2019.05.006. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31059838

Vaccine-Related Chronic Fatigue Syndrome In An Individual Demonstrating Aluminium Overload

A team of scientists have investigated a case of vaccine-associated chronic fatigue syndrome (CFS) and macrophagic myofasciitis in an individual demonstrating aluminium overload.

This is the first report linking aluminium overload with either of the two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in a patient.

The team, led by Dr Chris Exley, of the Birchall Centre at Keele University in Staffordshire, UK, has found a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events that are associated with autoimmune conditions, including chronic fatigue syndrome and macrophagic myofasciitis.

The CFS in a 43-year-old man, with no history of previous illness, followed a course of five vaccinations, each of which included an aluminium-based adjuvant. The latter are extremely effective immunogens in their own right and so improve the immune response to whichever antigen is administered in their presence. While the course of vaccinations was cited by an industrial injuries tribunal as the cause of the CFS in the individual, it was not likely to be a cause of the elevated body burden of aluminium. The latter was probably ongoing at the time when the vaccinations were administered and it is proposed that the cause of the CFS in this individual was a heightened immune response, initially to the aluminium in each of the adjuvants and thereafter spreading to other significant body stores of aluminium.

The result was a severe and ongoing immune response to elevated body stores of aluminium, which was initiated by a course of five aluminium adjuvant-based vaccinations within a short period of time. There are strong precedents for delayed hypersensitivity to aluminium in children receiving vaccinations which include aluminium-based adjuvants, with as many as 1% of recipients showing such a response.

While the use of aluminium-based adjuvants may be safe, it is also possible that for a significant number of individuals they may represent a significant health risk, such as was found in this case. With this in mind the ongoing programme of mass vaccination of young women in the UK against the human papilloma virus (HPV) with a vaccine which uses an aluminium based adjuvant may not be without similar risks.

Recent press coverage of myalgic encephalomyelitis (ME) or chronic fatigue syndrome has highlighted the potentially debilitating nature of this disease and related conditions. The cause of CFS is unknown.

 

Source: Keele University. (2008, November 18). Vaccine-Related Chronic Fatigue Syndrome In An Individual Demonstrating Aluminium Overload. ScienceDaily. Retrieved March 4, 2017 from  https://www.sciencedaily.com/releases/2008/11/081118141856.htm

 

A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.

Abstract:

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

 

Source: Exley C, Swarbrick L, Gherardi RK, Authier FJ. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome. Med Hypotheses. 2009 Feb;72(2):135-9. doi: 10.1016/j.mehy.2008.09.040. Epub 2008 Nov 11. https://www.ncbi.nlm.nih.gov/pubmed/19004564

 

Chronic fatigue syndrome in patients with macrophagic myofasciitis

Macrophagic myofasciitis (MMF), a condition first reported in France in 1998, is defined by the presence of a stereotyped and immunologically active lesion at deltoid muscle biopsy . It was recently demonstrated that this lesion is an indicator of long-term persistence of the immunologic adjuvant aluminum hydroxide within the cytoplasm of macrophages at the site of previous intramuscular (IM) injection. MMF is typically detected in patients with diffuse arthromyalgias that have appeared subsequent to aluminum hydroxide administration in the absence of a clearly defined anatomic substratum. Patients also report unexplained chronic fatigue. These manifestations are reminiscent of the so-called chronic fatigue syndrome (CFS), a poorly understood condition manifesting as disabling fatigue, musculoskeletal pain, sleep disturbance, impaired concentration, and headaches. The present study was conducted to determine the proportion of MMF patients fulfilling international criteria for CFS.

You can read the rest of this article here: http://onlinelibrary.wiley.com/doi/10.1002/art.10740/full

 

Source: Authier FJ, Sauvat S, Champey J, Drogou I, Coquet M, Gherardi RK. Chronic fatigue syndrome in patients with macrophagic myofasciitis. Arthritis Rheum. 2003 Feb;48(2):569-70. http://onlinelibrary.wiley.com/doi/10.1002/art.10740/full (Full article)