Autoimmune/inflammatory syndrome induced by adjuvants—ASIA—related to biomaterials: analysis of 45 cases and comprehensive review of the literature

Abstract

Systemic autoimmune or granulomatous disorders related to biomaterials of human use have rarely been described. The aim of this study was to report cases of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) related to biomaterial injections and prostheses, mainly silicone, hyaluronic acid, acrylamides and methacrylate compounds in a Spanish patient cohort. This study is a retrospective analysis of clinical, laboratory, histopathological and follow-up data of 45 cases of patients suffering from late-onset, non-infectious inflammatory/autoimmune disorders related to bioimplants. Late onset was defined as 3 months or more post injection. Data were obtained through a further non-systematic but comprehensive review of the literature. Forty-five cases of late-onset adverse reactions related to biomaterial injections or prostheses were reviewed. All cases had systemic complaints that could be categorised as ASIA. In all but four patients, inflammatory features at the implantation site preceded distant or systemic manifestations. Abnormal blood tests were common. Localised inflammatory nodules and panniculitis in 40/45 (88.88%) evolved into a variety of disorders, viz., primary biliary cirrhosis, Sjögren's syndrome, sarcoidosis, human adjuvant disease, vasculitis, inflammatory bowel syndrome and inflammatory polyradiculopathy. Five (11.11%) cases presented primarily with systemic autoimmune disorders. Biomaterials and prostheses can provoke late-onset systemic autoimmune disorders fulfilling ASIA criteria, or present primarily local/regional inflammatory reactions that may eventually evolve into systemic autoimmune and/or granulomatous disorders which fall under ASIA.

Classical Examples of the Concept of the ASIA Syndrome

“…Alijotas-Reig et al observed that 15 out of 185 cases (8%) of patients suffering from inflammatory/autoimmune disorders related to bioimplant injections had systemic or distant and multiple complaints that could be categorized as ASIA. SS was diagnosed in two patients representing a rather infrequent yet possible manifestation following a chronic stimulation from biomaterials used as fillers [ 89 ], an evidence reinforced by a further 3 cases published later on [ 90 ]. Thus, the epidemiology and pathomechanisms possibly linking some agents acting as adjuvants such as vaccines, silica, silicone implants and other biomaterials with SS are yet to be clarified.…”

Mast Cell Biology and Linkages for Non-clonal Mast Cell Activation and Autoimmune/Inflammatory Syndrome Induced by Adjuvants

“…There may be some debate as to whether any silicone-related reaction is always an acquired entity or whether some may have crossreactive or direct immune reactions that are stimulated after non-specific polyclonal activation for other reasons. Whereas silicone has drawn much attention in the ASIA context, various non-silicone adjuvants have also been associated with similar immune activations [61][62][63][64][65][66][67][68]. These include in the least acrylates, hyaluronic acid derivatives, acrylamides, poly-L-lactic acid, dental amalgams, various skin fillers, and vaccine components.…”

“…Even more open is the mechanism in which autoimmunity can be triggered by foreign adjuvants [6,68,70]. Adjuvancy per se conceivably utilizes various pathways, whether innate or adaptive.…”

Acellular Dermal Matrix, the Breast, and the FDA

“…Recent publications have described two patient series suspected of having ASIA associated with implanted medical devices including silicone breast implants, skin fillers, and metal implants. Alijotas-Reig et al (Alijotas-Reig et al, 2018) performed a retrospective analysis of 45 subjects and reported a 6year average latency from implantation to symptoms. Eighty percent (80%) of these subjects tested positive for the production of antinuclear antibody (ANA), a biomarker often associated with connective tissue autoimmune disorders.…”