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BACKGROUND: Hyaluronidase is used as an adjunct or main treatment to manage complications associated with cosmetic hyaluronic acid (HA) filler injections such as necrosis, blindness, hypersensitivity, delayed nodules, and poor aesthetic outcomes. OBJECTIVE: To systematically map the available evidence and identify the gaps in knowledge on the effectiveness of hyaluronidase use in managing the aesthetic complications associated with HA injections (vascular occlusion, blindness, nodules, delayed hypersensivity, granuloma, poor aesthetic outcome). METHODS: PubMed, Medline, Embase and Cochrane databases were used up to May 2022, to look for randomized clinical trials (RCTs), clinical trials, and retrospective case-control studies reporting on the use of hyaluronidase for managing the HA filler injection complications. RESULTS: The database search yielded 395 studies; of those 5 RCTs (all carried out in the USA) were selected (53 subjects), indicating the effectiveness of hyaluronidase for removal of un-complicated injected HA nodules (forearm, upper arm, or back skin). The follow-ups ranged from 14 days to 4 years. The amount of HA filler injected into each site varied from 0.2 to 0.4 mL. A dose dependent response was observed for most HA fillers. No major adverse reactions were reported. Overall, for removal of every 0.1 mL of HA filler they injected 1.25-37.5 units of hyaluronidase (single injections). When 3 consecutive weekly hyaluronidase injection was used much lower doses of 0.375-2.25 unit was utilised. There was no evidence in a form of RCTs, clinical trials, and retrospective case-control studies on the removal/reversal of HA injections in the facial skin, or management of over-corrections, inflammatory nodules, or tissue ischemia/necrosis associated with HA filler injection. CONCLUSION: Based on studies on the forearm, upper arm and back skin, hyaluronidase can be used for the reversal of uncomplicated HA filler injection nodule. However, further adequately powered studies are warranted to establish the ideal treatment protocol/dose of hyaluronidase for reversal of HA filler injections in the facial region or management of complications associated with aesthetic HA injection. LEVEL OF EVIDENCE III: 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 .
Borzabadi‐Farahani et al. (Mon,) studied this question.