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      A Scoping Review of Hyaluronidase Use in Managing the Complications of Aesthetic Interventions

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          Abstract

          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.

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          Most cited references82

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          PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation

          Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation. The checklist was developed by a 24-member expert panel and 2 research leads following published guidance from the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network. The final checklist contains 20 essential reporting items and 2 optional items. The authors provide a rationale and an example of good reporting for each item. The intent of the PRISMA-ScR is to help readers (including researchers, publishers, commissioners, policymakers, health care providers, guideline developers, and patients or consumers) develop a greater understanding of relevant terminology, core concepts, and key items to report for scoping reviews.
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            Hyaluronidase: from clinical applications to molecular and cellular mechanisms

            Over the past 60 years, hyaluronidase has been successfully utilized in ophthalmic surgery and is now being implemented in dermatosurgery as well as in other surgical disciplines. The enzyme is considered a “spreading factor” as it decomplexes hyaluronic acid (also called hyaluronan, HA), an essential component of the extracellular matrix (ECM). When applied as an adjuvant, hyaluronidase enhances the diffusion capacity and bioavailability of injected drugs. Therefore, the enzyme has been used as a local adjuvant to increase the diffusion capacity of local anesthetics, increasing the analgesic efficacy, and the anesthetized area particularly in the first minutes following injection, resulting in diminished intra- and postoperative pain. In aesthetic medicine, the off-label use of hyaluronidase is considered the gold standard for the management of HA-filler-associated complications. Here, we review the clinical use, underlying biological mechanisms, and future directions for the application of hyaluronidase in surgical and aesthetic medicine.
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              Complications of injectable fillers, part I.

              Dermal filling has rapidly become one of the most common procedures performed by clinicians worldwide. The vast majority of treatments are successful and patient satisfaction is high. However, complications, both mild and severe, have been reported and result from injection of many different types of dermal fillers. In this Continuing Medical Education review article, the author describes common technical errors, the signs and symptoms of both common and rare complications, and management of sequelae in clear, easily adaptable treatment algorithms.
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                Author and article information

                Contributors
                faraortho@yahoo.com
                Journal
                Aesthetic Plast Surg
                Aesthetic Plast Surg
                Aesthetic Plastic Surgery
                Springer US (New York )
                0364-216X
                1432-5241
                19 December 2022
                19 December 2022
                2024
                : 48
                : 6
                : 1193-1209
                Affiliations
                [1 ]Division of Surgery & Interventional Science (Minimally Invasive Aesthetics), University College London (UCL), ( https://ror.org/02jx3x895) London, WC1E 6BT UK
                [2 ]Crouch End Orthodontics, 72 Crouch End Hill, London, N8 8AG England UK
                [3 ]GRID grid.83440.3b, ISNI 0000000121901201, Department of Plastic Surgery, , Royal Free Hospital, University College London, ; London, UK
                Author information
                http://orcid.org/0000-0002-3729-2348
                Article
                3207
                10.1007/s00266-022-03207-9
                10999391
                36536092
                16282d4c-318a-4803-88a8-35f4fbd314eb
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 July 2022
                : 19 November 2022
                Categories
                Review
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2024

                Surgery
                hyaluronidase,hyaluronic acid,ha filler,aesthetic medicine
                Surgery
                hyaluronidase, hyaluronic acid, ha filler, aesthetic medicine

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