ASIA syndrome (Schonfeld syndrome) is a complex of autoimmune reactions that develop in predisposed individuals in response to the introduction of adjuvant substances into the body. It includes such nosologies as silicosis, macrophage myofasciitis, postvaccinal syndrome, etc. Various forms of the syndrome have common manifestations: arthralgia, myalgia, vasculitis, unmotivated subfebrility, chronic fatigue. The diagnosis is established on the basis of a previous medical history, blood test, the presence of antibodies, HLA-typing data, and biopsy. Treatment is carried out with NSAIDs, glucocorticoids, cytostatics.
General information
ASIA-syndrome (autoimmune syndrome caused by adjuvants) was first described by Israeli immunologist I. Schonfeld in 2011. The second, eponymous name of the pathology is Schonfeld syndrome. The disease is the subject of ongoing discussions in the scientific community. To date, clear criteria have not been developed and indisputable evidence of its existence has not been presented, and the nosology itself is not included in the ICD-10. Schonfeld and his followers are accused of anti-vaccination propaganda. At the same time, over 4 thousand have already been described. clinical cases of ASIA syndrome, dozens of articles and discussions at international congresses have been devoted to it.
Causes
The development of ASIA syndrome is associated with the ingestion of adjuvants and the emergence of a hyperergic immune response. Adjuvants are chemicals that can enhance and prolong the antigen-specific immune response, but should not have their own immunoreactivity. The salts of aluminum, silicon, squalene, silicone, and many other components that are part of vaccines, implants, and fillers are most often used as such compounds in the modern pharmaceutical industry.
According to modern concepts, ASIA syndrome develops as a result of the presence of an individual genetic predisposition due to the carrier of certain mutations of HLA genes (HLA-DRB1, HLA-DRB4, HLA-DQA1, HLA-DQB1, etc.). The immediate causes of ASIA syndrome are called:
Immunization. The question of whether vaccine adjuvants are capable of causing autoimmune disorders is highly controversial. On the one hand, there are studies that reliably refute the connection of vaccination with SLE, multiple sclerosis, DM, and other autoimmune pathologies. Meanwhile, supporters of ASIA syndrome point to the existing relationship between vaccination against HPV, hepatitis B, influenza and other infections and the development of autoimmune reactions.
Implantation of silicone prostheses. Silicone implants used for breast augmentation, buttocks, shins, have a certain immunogenicity, causing an increase in the level of CRP, RF, pro-inflammatory factors, autoantibodies. Local reactions are represented by the rejection of the implant or the formation of a fibrous capsule. In recent years, more and more people have been talking about the disease of breast implants, although not all specialists recognize the fact of its existence.
Injections of hyaluronic acid. Clinical observations are described when subcutaneous administration of hyaluronic acid alone or in combination with acrylic hydrogels caused the development of collagenoses, autoimmune thyropathies.
Tattooing. Some pigments contained in dyes for permanent makeup can cause systemic reactions such as vasculitis, nephrotic syndrome, granulomatous lung damage.
Pathogenesis
The mechanism of occurrence of ASIA-syndrome is insufficiently studied. It is assumed that adjuvants cause immunological reactions in several ways. Being non-immunogenic by nature, these excipients contribute to the deposition of antigens with which they are associated at the injection site and prolonged antibody synthesis. Some adjuvants stimulate the production of pro-inflammatory factors: cytokines, chemokines, interleukins (IL-1ß, IL-4, IL-6, IL-12, IL-18), which support a chronic inflammatory response.
In addition, adjuvants are able to induce humoral immunity by stimulating Th2 lymphocytes. Finally, adjuvants can directly activate the main histocompatibility complex in genetically predisposed individuals.
Classification
The term “ASIA syndrome” combines a group of independent syndromes that have their own causes and clinical manifestations. A common criterion for them is the alleged connection with the introduction of adjuvant substances into the body that provoke an autoimmune reaction. There are 5 forms of ASIA syndrome.
1. Siliconosis. Occurs in less than 1% within 6-15 years after the implant is installed. Implant ruptures and gel migration increase the risk of autoimmune pathologies. Silicon compounds present in silicone prostheses can contribute to the development of sarcoidosis of the skin and lungs, rheumatoid arthritis, Shagren’s disease, systemic vasculitis.
2. Postvaccinal phenomenon. It is associated with the presence of adjuvants such as aluminum hydroxide in vaccine preparations. The manifestations of ASIA include:
- Guillain-Barre syndrome, which develops after the introduction of an anti-influenza and anti-hepatitis vaccine;
- rheumatoid arthritis on the background of immunization against tick-borne encephalitis, influenza;
- SLE associated with immunization against HPV, rubella, measles, tuberculosis, hepatitis B.
3. Macrophage myofascial syndrome. It is believed that the surge in the incidence of macrophage myofasciitis is associated with the transition to mass administration of vaccines in the deltoid muscle and quadriceps femoris. This explains the typical localization of local inflammation, specific histological findings (deposits of aluminum hydroxide nanocrystals). It is noted in patients after vaccination for hepatitis A, B, tetanus.
4. “Sick building” syndrome. This phenomenon is mentioned if at least 20% of people experience similar pathological symptoms when they are in the same room. It occurs more often in office workers, sometimes in residents of the same house. Among the most frequent complaints are lacrimation, nasal congestion, itching and dry skin, drowsiness. It is assumed that this variant of ASIA syndrome is associated with chemicals used in air conditioning systems, possibly mold antigens, phthalates.
5. The Gulf War syndrome. It was first recorded in servicemen who took part in hostilities in this region in 1991. The cause of this syndrome, accompanied by muscle and joint pain, ataxia, cephalgia, fever, skin rashes, gastrointestinal disorders, sleep disorders, is considered to be multiple vaccinations of the military in combination with psychological stress and increased physical exertion.
Symptoms
Signs of ASIA syndrome can develop in a wide time frame – from 2 days to 20 years or more after the intended exposure (immunization, augmentation mammoplasty, administration of hyaluronic acid, tutuage). Early complaints are nonspecific, including unexplained weakness, persistent subfebrility, arthralgia of various localization or polyarthritis, muscle and spine pain. In the future, asthenia increases, insomnia, shortness of breath may bother.
Some patients with various variants of ASIA syndrome complain of the appearance of hemorrhagic rash on the skin, dry mouth, hair loss, brittle nails. Sometimes there is a Raynaud phenomenon. The development of irritable bowel syndrome is possible. In later periods, amnesia, cognitive decline, as a consequence of demyelination, may be observed.
A distinctive feature of ASIA syndrome is the regression of most clinical and laboratory manifestations after removal of the provoking agent (silicone, pigment and others).
Complications
From the moment the first signs of Schonfeld syndrome appear to its diagnosis, years and decades pass. All this time, patients receive inadequate treatment, undergo frequent hospitalizations, suffer from a decrease in the quality of life. ASIA syndrome can lead to the manifestation of various autoimmune pathologies: systemic vasculitis, rheumatoid arthritis, SLE, Sjogren’s disease, multiple sclerosis. The long-term presence of adjuvants in the body (for example, silicone implants) is accompanied by constant stimulation of immune reactions, which is a risk factor for the occurrence of pseudolymphoma, as well as non-Hodgkin’s lymphoma.
Diagnostics
Immunologists and rheumatologists are engaged in the examination and observation of patients with manifestations of ASIA syndrome. Currently, special criteria are proposed for the diagnosis of this pathology. Mandatory criteria include:
- association of symptoms with external influences (infection, immunization, silicone injection);
- muscle syndrome (myalgia, myositis, paresis);
- articular syndrome (arthralgia, arthritis);
- asthenia (fatigue, weakness, sleep disorders);
- psychopathological manifestations (memory disorder, cognitive deficits);
- pyrexia;
- xerostomy.
The small criteria of ASIA syndrome include the detection of At to the presumed adjuvant, specific HLA-halotypes, signs of systemic diseases, other manifestations (IBS).
- Study of blood parameters. ESR is increased in the blood, positive CRP is determined, the level of fibrinogen, LDH, and alkaline phosphatase is increased. Markers of autoimmune diseases (anti-CCP, antinuclear factor, At to dsDNA, RF, At to Sm antigen, etc.) are often detected.
- Tissue biopsy. Biopsies of skin, muscles, blood vessels, lymph nodes, and sometimes internal organs are examined. In the focus of adjuvant administration, a characteristic histological picture of immune inflammation develops: lymphohistiocytic infiltration of tissues, scleropodobnye and granulomatous changes.
- Instrumental studies. To assess the integrity of breast implants, ultrasound of the mammary glands is performed, if necessary, MRI control. In case of damage to internal organs, kidney ultrasound, lung CT is prescribed. In Raynaud’s syndrome, capillaroscopy is performed.
Treatment
To eliminate pathological symptoms, it is necessary to eliminate the provoking factor (remove implants and fillers, refuse to use an air conditioner, change your place of work / residence). NSAIDs (nimesulide, etoricoxib, ibuprofen) are used to relieve symptoms. If necessary, pulse therapy with methylprednisolone, penicillamine, antimetabolites (methotrexate) are added to the scheme of basic anti-inflammatory therapy.
Prognosis and prevention
The correlation dependence of ASIA syndrome on the administration of adjuvants needs further study and recognition by the medical community. To date, the effect of adjuvants on the development of systemic diseases remains unproven. The ASIA syndrome clinic often disappears after the trigger is eliminated. However, the FDA recommends that plastic surgeons avoid implanting breast prostheses with silicone gel due to their high immunogenicity in favor of saline implants. Before medical manipulations related to the introduction of foreign substances, it is necessary to conduct a thorough immunological examination of patients.
Literature
- The ASIA syndrome: basic concepts/ A. Watad, K. Sharif, Y. Shoenfeld// Mediterranean Journal of Rheumatology. – 2017. link
- Modern understanding of Schoenfeld syndrome and the possibility of early screening of patients belonging to the risk group/ Dubov V.S., Kuryndina I.A.// Scientific dialogue: Questions of medicine. – 2017.
- Autoimmune/inflammatory syndrome associated with adjuvants/ Radenska-Lopovok S.G., Volkova P.// Archive of Pathology. – 2018. – №5.