Incidence and Characteristics of Delayed Inflammatory Reactions Secondary to Hyaluronic Acid Filler Injections: A Systematic Review With Meta-Analysis

Abstract Background Delayed inflammatory reactions (DIRs) are rare but increasingly relevant complications of hyaluronic acid (HA) fillers. Objectives To examine the incidence and characteristics of DIRs secondary to HA fillers for facial aesthetic indications. Methods We systematically reviewed studies published before 3 December 2024 from PUBMED and EMBASE, using a random effects meta-analysis model to compute pooled incidence rates of DIR with 95% confidence intervals (CI). Subgroup analyses were performed according to filler crosslinking technology. Case data were analyzed descriptively. Results The meta-analysis included 242 studies, and case data was supplemented from 71 additional reports. The pooled incidence of DIRs was 0.0005 (95% CI: 0.0002–0.0013) events per patient-years, equivalent to an event occurring for every 2000 patients with one year of follow-up. When analyzed by crosslinking technology, incidence rates per patient-year was 0.0044 (95% CI: 0.0006–0.0314) for SHAPE, 0.0022 (95% CI: 0.0011–0.0043) for Vycross, 0.0007 (95% CI: 0.0003–0.0017) for NASHA and 0.0006 (95% CI: 0.0002–0.0025) for HICE; several filler technologies, including CPM-based fillers, reported no incident DIR cases during follow-up. The median time to onset was 3 months (Range: 2 weeks to 12 years) and time to resolution was 2.9 months (Range: 1 day to 6 years). Common presentations included nodules, redness, swelling and induration. Management often involved hyaluronidase, corticosteroids and antibiotics. Conclusions DIRs are rare adverse events following aesthetic HA filler treatments, exhibiting varied times to onset and resolution. Incidence rates appear to vary by crosslinking technology, and awareness of potential differences can contribute to safe and natural outcomes.