- A panoply of unexplained subjective and autonomic-related symptoms is present in patients with ASIA syndrome.
- Small fiber neuropathy is an important clinical manifestation of ASIA.
- ASIA can be induced by breast implants, polypropylene meshes, and Essure sterilization devices.
- COVID-19 and HPV vaccines and (infrequently) tattoos, metal implants, mineral oils, and fillers may also induce ASIA
- In ASIA, autoantibodies directed against G-protein coupled receptors (GPCRs) are associated with dysautonomia.
In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld’s syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis.
During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in susceptible individuals. Adjuvants are compounds that, when introduced into the body, enhance a specific immune reaction resulting in higher titters of antibodies, for instance against specific pathogens. Well-known examples of adjuvants are aluminum hydroxide, squalene, and silica as well as various infectious agents. During the last decade, it became clear that human medical implants, including injectables such as silicones and polypropylene meshes may act as adjuvants as well.
A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as:
1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and
2) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of ‘dysautonomia’ reported in many ASIA patients.
Typical clinical symptoms of ASIA are: chronic fatigue, arthralgias, myalgias, pyrexia, sicca symptoms, cognitive impairment, and or (atypical) neurological symptoms. Typically, patients present with severe fatigue, nonrestorative sleep, and a majority reporting post-exertional malaise as is observed in ME/CFS. Sleep disturbances such as problems falling asleep and/or staying asleep are common with poor sleep quality being linked to greater fatigue. Another early symptom is the occurrence of arthralgias and most patients fulfill the 2016 criteria for fibromyalgia. Patients often suffer from severe morning stiffness, myalgias and/or muscle weakness. Weakness can be severe and may render the patient bedridden. Furthermore, most patients report pyrexia and night sweats, while others report dry eyes and/or a dry mouth. Dry eyes are often severe and may result in blurred vision and/or a keratitis sicca if left untreated. Symptoms of cognitive impairment are not infrequent manifesting as mental fogginess, memory deficits, absent-mindedness, anomic dysphasia, and inattention.
In some patients, the neurological manifestations are very disturbing and patients may present with a stroke or multiple sclerosis-like attacks. Patients may suffer from allergies and gastrointestinal symptoms such as abdominal pain with changes in bowel movement patterns typical of irritable bowel syndrome. New-onset Raynaud’s phenomenon can be present as well, while in other instances pain and burning sensations (“pins and needles”) of the skin points towards a diagnosis of small fiber neuropathy. Patients may have recurrent hives or ill-defined skin rashes, unexplained (sometimes severe) pruritus and/or alopecia. Cardiovascular complaints include signs of orthostatic intolerance such as dizziness, and disturbed balance as observed in postural tachycardia syndrome (POTS). Finally, a substantial number of patients have interstitial cystitis.
After the launch of the ASIA Syndrome in 2011, the expansion and recognition of this syndrome by different researchers from different countries began. In 2012, a special issue of the LUPUS journal was dedicated to ASIA. In this special issue, a series of articles from different countries were published and provide the clinical and experimental bases for support the existence of ASIA. More than a decade has passed since the initial description of the ASIA syndrome. New cases from ASIA have been described and new adjuvants have been added. Substances other than silicone and mineral oil, previously described, may be associated with the development of ASIA syndrome after injection of bioimplants for aesthetic purposes, such as, hyaluronic acid, methacrylate, polyacrylamide, polyalkylimide, and metals in implants as used in orthopedic surgery and/or in birth control devices.
Polyacrylamide as an example
Polyacrylamide is a type of plastic. It is a synthetic polymer made from the monomer acrylamide. Polyacrylamide is a water-soluble polymer that is used in a variety of applications. Even though it is directly linked to cancer, it is available online at the moment of this review.
Acrylamide is produced by the hydration of acrylonitrile in the presence of a catalyst, such as sulfuric acid or hydrochloric acid at a temperature of 100-150°C and a pressure of 10-20 atmospheres. It is then polymerized to form polyacrylamide, and the most common method is to use a free radical initiator, such as potassium persulfate.
Acrylonitrile is produced commercially by the process of propylene ammoxidation, in which propylene, ammonia, and air are reacted in a fluidized bed in the presence of molybdenum and bismuth oxides at a temperature of 400-500°C and a pressure of 10-20 atmospheres. The resulting acrylonitrile is then purified by distillation.
Propylene is produced primarily as a by-product of petroleum refining and of ethylene production by steam cracking of hydrocarbon feedstocks. Steam cracking is a process in which hydrocarbons are heated to a high temperature in the presence of steam. This causes the hydrocarbons to break down into smaller molecules, including ethylene and propylene.
Studies have found that acrylamide exposure increases the risk for several types of cancer. In the body, acrylamide is converted to a compound called glycidamide, which causes mutations in and damage to DNA.
The National Toxicology Program’s Report on Carcinogens considers acrylamide to be reasonably anticipated to be a human carcinogen, based on studies in laboratory animals given acrylamide in drinking water.
Studies of workplace exposure have shown that high levels of occupational acrylamide exposure (which occurs through inhalation) cause neurological damage, for example, among workers using acrylamide polymers to clarify water in coal preparation plants. However, studies of occupational exposure have not suggested increased risks of cancer.
Conclusions
From its launch in 2011 until today, the ASIA syndrome (Shoenfeld’s syndrome) have been dramatically expanded and recognized by many researchers. New cases of ASIA associated with new adjuvants (e.g. polypropylene meshes) were described. New subtypes of the ASIA syndrome have been introduced, related to exposure to different types of vaccines (e.g., HPV and COVID vaccines) in genetically predisposed individuals, i.e., HLA DRB1 haplotypes. Recent evidence describing a clear association between the removal of a specific adjuvant (e.g. silicone implants, mesh, Essure sterilization devices, metal implants or even porcelain-fused-to-metal dental crowns) followed by symptoms relieve/disappearance in ASIA patients, strengthen some of the criteria of ASIA syndrome. Finally, new findings, such as a potential dysfunction of autoantibodies directed against GPCRs of the autonomic nervous system and the presence of SFN, are being suggested as new criteria for ASIA and as an explanation for the dysautonomia that is often reported in ASIA patients.
https://www.sciencedirect.com/science/article/pii/S1568997223000216
https://www.cancer.gov/about-cancer/causes-prevention/risk/diet/acrylamide-fact-sheet
https://academic.oup.com/jscr/article/2021/6/rjab276/6307494
https://dermalclinik.com/product/buy-aquamid-1x1ml/