Review of Delayed Reactions to 15 Hyaluronic Acid Fillers

Abstract

BACKGROUND Delayed-onset reactions are increasingly relevant given the growing use of hyaluronic acid dermal fillers. There is poor understanding of the phenomenon's etiology and incidence. OBJECTIVE To highlight differences between the dermal filler products with an emphasis on delayed-onset reaction incidence, pathogenesis, prevention, and treatment. METHODS A literature review was performed for delayed-onset reactions following hyaluronic acid dermal filler injection using PubMeb and Embase. Articles were included based on relevance, quality, and the predetermined definition of “delayed-onset reaction” (>30 days post injection). A total of 28 studies were included in the data analysis. RESULTS A total of 13,136 subjects from 28 studies treated with 15 filler types were included in the analysis. VYC-15L dermal filler injections carried the highest risk of delayed reaction with a mean incidence of 3.83% (n = 46/1,202), followed by VYC-20L (0.92%) and VYC-17.5L (0.88%). The mean incidence of delayed reactions among all filler types was 1.13%. CONCLUSION Incidence of delayed reaction to hyaluronic fillers ranges from 0% to 3.83% (mean = 1.13%) and varies by filler type. The exact etiology of these delayed reactions remains disputed. Future studies should report reaction description, precise timeline, and posttreatment immunologic history to better delineate the incidence of delayed-onset hypersensitivity reactions.

Recurrent delayed hypersensitivity reaction to a hyaluronic acid soft-tissue filler following COVID-19 vaccination: a case report

“…Delayed hypersensitivity reactions typically occur 48 to 72 hours after injection, but can occur as late as several weeks or months later, and are mediated by T lymphocytes rather than antibodies. Unlike acute hypersensitivity reactions, they can occur in both previously injected patients and patients who have received their first injections [3,8]. The incidence of delayed hypersensitivity reactions following HA soft-tissue filler injections was previously reported to be about 1.13% [3].…”

“…Unlike acute hypersensitivity reactions, they can occur in both previously injected patients and patients who have received their first injections [3,8]. The incidence of delayed hypersensitivity reactions following HA soft-tissue filler injections was previously reported to be about 1.13% [3].…”

“…Delayed hypersensitivity reactions, also known as type 4 hypersensitivity reactions, are T-cell mediated and generally occur 48 to 72 hours after the injection, though they can follow an asymptomatic period of weeks to months. The reported incidence of delayed hypersensitivity reactions following HA soft-tissue filler injections is about 1.13% [3]. With the emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), concerns have arisen about interactions between HA soft-tissue fillers and COVID-19 infection or vaccination.…”

Case report of possible iatrogenic Cushing's disease with low‐dose prednisone to treat dermal filler hypersensitivity

“…The use of a second dermal filler is recommended in the case of a previous reaction to a first filler and after pretreatment skin tests, 6 but these tests are not mandatory in all cases. The incidence of delayed inflammatory reaction (DIR) to dermal fillers is very low but its exact etiology still remains uncertain 1,2,6 . In addition to hypersensitivity issues, triggers such as viral infection, active sinusitis, product combination, and dental procedures have been associated with DIR 1 .…”

“…Although this is frightening for some patients, it is not considered a risk of a fatal complication. Since the etiology is still uncertain, this situation leads to some treatment options 2 . A common treatment option includes topical or systemic glucocorticoids since one of the assumed causes is associated with a hypersensitivity reaction.…”