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

Abstract

Delayed inflammatory reactions (DIRs) are rare but increasingly relevant complications of hyaluronic acid (HA) fillers. The aim of this review was to examine the incidence and characteristics of DIRs secondary to HA fillers for facial aesthetic indications. The authors systematically reviewed studies published before December 3, 2024, from PubMed and Embase, using a random-effects meta-analysis model to compute pooled incidence rates of DIR with 95% CIs. Subgroup analyses were performed according to filler crosslinking technology. Case data were analyzed descriptively. The meta-analysis included 242 studies, and case data were 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 1 year of follow-up. When analyzed by crosslinking technology, incidence rates per patient-year were 0.0044 (95% CI, 0.0006-0.0314) for SHAPE (Stabilized Hyaluronic Acid And Purification Enhancement), 0.0022 (95% CI, 0.0011-0.0043) for Vycross, 0.0007 (95% CI, 0.0003-0.0017) for NASHA (Non-Animal Stabilized Hyaluronic Acid), and 0.0006 (95% CI, 0.0002-0.0025) for HICE (High Concentration Equalized); several filler technologies, including CPM (Cohesive Polydensified Matrix)-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. The management often involved hyaluronidase, corticosteroids, and antibiotics. 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. Level of Evidence: 3 (Therapeutic).