The Immunogenicity of Hyaluronic Fillers and Its Consequences

Abstract

Hyaluronic acid (HA) is a glycosaminoglycan, a natural component of the extracellular matrix. The identical structure of the molecule in all living organisms is its main advantage, as it translates into the minimal probability of immunogenicity. Therefore, it is the closest to the ideal preparation used as a filler, due to its biocompatibility and stability at the site of implantation. This paper includes the discussion of the potential mechanisms of adverse immune reactions to HA along with the mechanisms of reaction following vaccinations against SARS-CoV-2. Based on the literature, we tried to systematize adverse immune reactions with systemic manifestations to HA. The occurrence of unpredictable reactions to hyaluronic acid indicates that they may not be treated as neutral or non-allergenic. The modifications of the chemical structure of HA, additives and individual tendencies in a patient may be the cause of unpredictable reactions, leading to serious health consequences. Preparations of unknown origin, poorly purified, or including bacterial DNA are particularly dangerous. Therefore, long-lasting follow-up of the patient and the selection of a preparation approved by the FDA or EMA are of high importance. Patients are often unaware of the consequences of cheaper procedures performed by persons without suitable knowledge with the use of unregistered products, so the public should be educated and legal regulations should be introduced.

Midface Infection after COVID-19 Vaccination in a Patient with Calcium Hydroxylapatite Dermal Filler: A Case Report and Literature Review

“…But the use of HA fillers that include high and low HA chains for better longevity has increased the occurrence of such adverse events again, as the modification alters the morphology of HA molecules, potentially affecting their immunogenicity. 3 8 The fact that some manufacturers add other substances such as mannitol or dextran to make the product more hydrophilic increases the risk of antigens triggering an immune response. 8…”

“…3 8 The fact that some manufacturers add other substances such as mannitol or dextran to make the product more hydrophilic increases the risk of antigens triggering an immune response. 8…”

“…3 In addition to that, individual tendencies, such as HLA-B*08 and DR1*03 haplotypes, were found to raise the risk of delayed, immune-mediated, adverse reactions to dermal fillers; as such combinations of human leukocyte antigen subtypes were linked to almost four times higher probability of adverse reactions. 8…”

Treatment of Delayed-onset Inflammatory Reactions to Hyaluronic Acid Filler: An Algorithmic Approach

“…In its native form, HA is not immunostimulatory because it is found in the extracellular matrix of human and animal dermis and has no species specificity. 10 As a result, immune responses to HA fillers were initially thought to be caused by impurities such as DNA fragments, endotoxins, and proteins. Before 1999, the reported rate of delayed inflammatory reactions to HA fillers was 0.7%.…”

Current Practices in Hyaluronic Acid Dermal Filler Treatment in Asia Pacific and Practical Approaches to Achieving Safe and Natural-Looking Results

“…The panel pointed out that although HA fillers are generally well tolerated and have a favorable safety profile, there is differential immunogenicity between different HA fillers, which is influenced by several factors including the molecular weight of HA, crosslinking and manufacturing technologies, etc. 24 The incidence of DIRs to HA filler treatments has been reported to range from around 0%–4.3% across different HA filler products. 16 , 17 Hence, the panel recommended that practitioners be aware of the immunogenicity of different HA fillers and the influencing factors when selecting an appropriate filler for their patients.…”