Classical Examples of the Concept of the ASIA Syndrome

Abstract

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.

Polymyalgia rheumatica as uncommon adverse event following immunization with COVID‐19 vaccine: A case report and review of literature

“…Three major criteria were present, that is a previous exposure to an external stimulus, and the development of some “typical” clinical manifestations, such as myalgia/myositis, arthralgia/arthritis, and pyrexia. 16 The onset of PMR and PMR‐like syndromes after exposure to adjuvant is very uncommon. For instance, only four cases of PMR/PMR‐like syndromes were reported in the ASIA syndrome international registry, which lists > 500 cases.…”

“…Did our patient have an ASIA syndrome? Three major criteria were present, that is a previous exposure to an external stimulus, and the development of some “typical” clinical manifestations, such as myalgia/myositis, arthralgia/arthritis, and pyrexia 16 . The onset of PMR and PMR‐like syndromes after exposure to adjuvant is very uncommon.…”

Will the COVID‐19 pandemic trigger future occurrence of autoimmunity like Sjögren’s syndrome?

“…In the proposed entities for the diagnosis of “ASIA,” “exposure to external stimuli” is one of the major criteria. According to the concept, SS is a typical example of “ASIA” 23 …”

“…Conversely, because of the mimicry between viral spike protein and human cells, whether the messenger RNA (mRNA)‐based anti‐SARS‐CoV‐2 vaccines might stimulate an unwanted immune reaction in individuals with immune dysfunctions is controversial 32 . The speculation may not be limited to mRNA vaccines, as an association between specific vaccination (eg, influenza vaccine) and SS or the production of anti‐Ro/anti‐La antibodies has been reported 23 . Thus, the infection and/or vaccination might trigger or accelerate autoimmune responses against the spike protein of the SARS‐CoV‐2 in genetically susceptible individuals or patients with immune dysfunction.…”

“… 32 The speculation may not be limited to mRNA vaccines, as an association between specific vaccination (eg, influenza vaccine) and SS or the production of anti‐Ro/anti‐La antibodies has been reported. 23 Thus, the infection and/or vaccination might trigger or accelerate autoimmune responses against the spike protein of the SARS‐CoV‐2 in genetically susceptible individuals or patients with immune dysfunction. In this concern, not only autoimmune rheumatic diseases but also other autoimmunity entities such as hepatitis 33 and thyroiditis 34 have been reported to emerge after vaccination against SARS‐CoV‐2.…”