Abstract
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Background: Hyaluronidase, a glycosidase enzyme known for its ability to degrade hyaluronic acid (HA), has become increasingly central in aesthetic medicine, not only for managing filler-related complications but also for a growing range of off-label indications.
Objective: This review aims to examine the main off-label uses of hyaluronidase in aesthetic medicine, summarize current evidence from the literature, and evaluate its clinical applications, effectiveness, and safety profile.
Methods: A comprehensive analysis of in vitro and in vivo studies, clinical reports, and expert guidelines was conducted. Particular attention was given to dose-response data, enzymatic specificity across HA fillers, and case-based applications in managing vascular occlusion, nodules, asymmetries, and aesthetic corrections.
Results: Findings reveal significant variability in the sensitivity of HA fillers to hyaluronidase depending on cross-linking, molecular structure, and filler type. Off-label use is most common in dissolving HA-related complications, especially in cases of vascular compromise, where early administration (<4 h) markedly reduces tissue necrosis risk. Animal and human studies confirm a dose- and time-dependent enzymatic effect. Emerging applications include hematoma resorption, fibrosis prevention, and adjuvant roles in drug diffusion. Despite its benefits, allergic reactions—especially in patients sensitized to hymenoptera venom—require pre-use testing in elective settings.
Conclusion: Hyaluronidase is a powerful and versatile tool in aesthetic practice. While its use remains off-label in many contexts, growing evidence supports its safety and efficacy. Knowledge of filler composition, enzymatic dynamics, and patient risk factors is essential for safe and effective application.
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