Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

Fibromyalgia can be defined as a chronic pain condition, affecting the musculoskeletal system, etiology and pathophysiology of which is sufficiently understudied. Despite the fact that many authors consider this entity to be a manifestation of central sensitization, and not an autoimmune disease, the high prevalence of fibromyalgia in patients with post-COVID-19 conditions requires taking a fresh look at the causes of the disease development. During the patient examination, the authors identified a combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19, physical traumatization of one particular tendon and the development of the fibromyalgia pain syndrome during the next several weeks. As well as an increase in the titer of antinuclear antibodies and some other systemic inflammation factors. It can be assumed with great caution that local damage to the connective tissue in patients with joint hypermobility, having COVID-19 as a trigger factor can lead to the development of fibromyalgia syndrome. This article presents three clinical cases that illustrated this hypothesis.

Chronic pain may affect 30–50% of the world’s population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

Recent studies provide some evidence for the contribution of antibody-mediated autoimmune mechanisms to the nature of fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Much attention was paid to the autoantibodies (AAb) targeting G protein-coupled receptors as natural components of the immune system. However, the natural AAb network is much more extensive, and has not been previously investigated in these disorders. The enzyme immunoassays ELI-Viscero-Test and ELI-Neuro-Test were used to determine changes in serum content of 33 natural AAb to neural, organ-specific and non-tissue-specific autoantigens (a) in 11 ME/CFS patients with comorbid FM; (b) in 11 ME/CFS patients without FM; (c) in 11 healthy controls. Individual AAb profiles and their correlation with some clinical symptoms were analyzed. Both patients with ME/CFS(−)FM and ME/CFS(+)FM were characterized by more frequent and pronounced deviations in the immunoreactivity to GABA-receptors than healthy controls. Although the level of other natural AAb did not differ between study groups, AAb correlation signatures were altered in patients compared to healthy controls. Both in patients and healthy controls the level of natural AAb to various neural and tissue-specific antigens correlated with the severity of fatigue, bodily pain, depression, anxiety, physical and mental health-related quality of life. Notably, widely different correlation patterns were observed between study groups. Findings from this pilot study provide some evidence that the homeostasis of autoimmune relationships, which are possibly a physiological part of our immune system, may be altered in FM and ME/CFS. The correlation of disease-induced perturbations in individual AAb profiles with some clinical symptoms may arise from the immune system’s ability to reflect qualitative and quantitative changes in antigenic composition of the body.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown etiology, sharing a similar clinical presentation with the increasingly recognized post-COVID syndrome. We performed the first cross-sectional study of ME/CFS in a community population in Russia. Then we described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves as suffering from ME/CFS, 56 were diagnosed with ME/CFS by clinicians according to ≥1 of the four most commonly used case definitions. Of the cohort of 14 individuals with post-COVID-19 syndrome, 14 met the diagnostic criteria for ME/CFS. The severity of anxiety/depressive symptoms did not correlate with the severity of fatigue either in ME/CFS or in post-COVID ME/CFS. Still, a positive correlation was found between the severity of fatigue and 20 other symptoms of ME/CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, “dysfunction of the autonomic nervous system”, “neurological sensory/motor disorders” and “pain syndromes”. Immunological abnormalities were identified in 12/12 patients with ME/CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed in the active orthostatic test amounted to 37.5% in ME/CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02). There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified laser doppler flowmetry pattern corresponded to the hyperemic form of microcirculation disorders usually observed in acute inflammatory response or in case of systemic vasoconstriction failure.

Sarcoidosis (SC) is a granulomatous disease of an unknown origin. The most common SC-related neurological complication is a small fiber neuropathy (SFN) that is often considered to be the result of chronic inflammation and remains significantly understudied. This study aimed to identify the clinical and histological correlates of small fiber neuropathy in sarcoidosis patients. The study was performed in 2018–2019 yy and included 50 patients with pulmonary sarcoidosis (n = 25) and healthy subjects (n = 25). For the clinical verification of the SFN, the “Small Fiber Neuropathy Screening List” (SFN-SL) was used. A punch biopsy of the skin was performed followed by enzyme immunoassay analysis with PGP 9.5 antibodies. Up to 60% of the sarcoidosis patients reported the presence of at least one complaint, and it was possible that these complaints were associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular and musculoskeletal systems and the gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed. In patients with pulmonary sarcoidosis, small fiber neuropathy might develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction.