<p>Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm</p>

Abstract

Background and Objectives: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose. Materials and Methods: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists. Results: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3-6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement. Conclusion: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.

“COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment”

“…In the 400 subjects studied retrospectively, the authors did not report a DIR related to post viral illness or vaccination [21]. However, several studies have shown that the biphasic highlycrosslinked Juvederm vycross filler product line has a higher than expected rate of DIR [3,5,22]. It is has been reported Fig.…”

“…A recent expert consensus panel defined the duration of DIRs as arising from a normal state 2-4 weeks or longer post-injection [5]. Clinically, they noted that DIRs in HAbased filler injections manifest as erythema, painful nodules, induration, and eyelid edema.…”

“…The authors also acknowledged that certain triggers might be associated with the onset of DIRs, which can include viral infection, active sinusitis, low-quality products, combinations of different products, improper technique, and past and current dental procedures. Lastly, it was mentioned that DIR can occur in the skin at different sites of injection, chiefly dermal and subcutaneous placement, with adipose tissue being the most common placement site [5].…”

“…10 Query of the VAERS database with possible terms specific for cutaneous adverse events yielded 641 cases, with 152 cases linked to edema of the skin that HA-based fillers with a low-molecular weight-degraded products have higher pro-inflammatory activity [5]. Recent reports in the literature have revealed an incidence of DIRs to Juvederm Volbella of 1.0% per patient and 0.8% per syringe, which is higher than the previously reported incidence of 0.02% and more compatible with the 4.25% incidence of DIRs to Juvederm Volbella previously reported by Artzi et al [5,21]. Analysis of the U.S. Food and Drug Administration (FDA) MAUDE database by Ortiz et al identified the Juvederm family of dermal HA fillers with a high risk profile amongst HA fillers for development of DIR [23].…”

“…Conceptually, HA fillers can be seen as long-lasting implants which can persist as long as 2-5 years or longer in certain facial anatomic areas such as the malar cheeks, midface, and tear trough, in varying levels of the dermis, subcutis, and supraperiosteum [4]. Because of this longevity, delayed inflammatory reactions (DIR) to HA filler within the skin have been reported to occur [5]. The exact mechanism of action for the delayed reaction is unclear, likely immune-mediated and multifactorial in nature.…”