Conventional High-Dose vs Low-Dose Hyaluronidase for Skin Necrosis after Hyaluronic Acid Fillers: A Systematic Review and Pilot Meta-Analysis

Abstract

Background: Hyaluronidase remains the mainstay treatment for skin necrosis due to vascular occlusion after hyaluronic acid (HA) dermal fillers. There is wide variability in protocols for the administration of hyaluronidase. Most protocols, however, lack strong evidence regarding hyaluronidase dosages.

Methods: We conducted a systematic review and pilot meta-analysis, searching four international databases from inception until December 2023 for clinical studies reporting on two or more patients receiving hyaluronidase for skin necrosis after hyaluronic acid fillers. Random-effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the pooled proportion of complete scar resolution. We rated intra-study risk of bias using the Joanna Briggs Institute checklists and assessed the certainty of evidence using the GRADE approach.

Results: We included 15 studies totaling 223 patients. The pooled proportion of complete scar resolution after hyaluronidase administration was 77.8% (95%-CI: 65.5% to 86.6%, p_egger = 0.093, low certainty). Patients treated with high doses of hyaluronidase (>500 international units [IUs]) had lower rates of resolution of 69.6% (95%-CI: 41.2% to 88.3%) compared to those treated with low doses (500IU or less) that had 88.1% rate of resolution (95%-CI: 86.0% to 96.2%), though not statistically significant (p= 0.18). The use of adjunct therapies did not have a statistically significant effect on outcomes.

Conclusion: A higher proportion of patients receiving low doses (500IU or less) (88.1%) had complete scar resolution compared to patients receiving high doses (69.7%), though not statistically significant (p=0.18). Future studies should provide more granular details on their protocols to benefit the formulation of evidence-based guidelines in future.

Level of evidence i: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Protocol registration: CRD42024538661.

Keywords: Fillers; Hyaluronic acid; Hyaluronidase; Meta-analysis; Skin necrosis.