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Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler NodulesA Randomized Clinical Trial

Educational Objective:
To learn from this pilot study that titrating hyaluronidase dosing enables potential sculpting of asymmetrical filler sites.
1 Credit CME
Key Points

Question  Can low doses of hyaluronidase safely and effectively dissolve hyaluronic acid filler nodules?

Findings  In this randomized clinical trial of 9 women and 72 injection sites, small unit doses of hyaluronidase allowed removal of minute quantities of filler without removing the entire implant.

Meaning  Minor asymmetries after filler can be corrected by the injector in a manner convenient for patients.

Abstract

Importance  Although hyaluronidase is known to remove hyaluronic acid fillers, use of low doses has not been well studied.

Objective  To assess the effectiveness and dose-related effect of small quantities of hyaluronidase to treat hyaluronic acid filler nodules.

Design, Setting, and Participants  Split-arm, parallel-group, randomized clinical trial at an urban academic center. Participants were 9 healthy women. Recruitment and follow-up occurred from February 2013 to March 2014; data analysis occurred from February to July 2016.

Interventions  Each participant received aliquots (buttons) of either of 2 types of hyaluronic acid fillers into bilateral upper inner arms, respectively. At 1, 2, and 3 weeks each button was treated with a constant volume (0.1 mL) of variable-dose hyaluronidase (1.5, 3.0, or 9.0 U per 0.1 mL) or saline control.

Main Outcomes and Measures  Both a blinded dermatologist and the participant independently assessed detectability.

Results  Seventy-two treatment sites on 9 women (mean [SD] age, 45.8 [15.7] years) received all interventions and were analyzed. There was a significant difference in physician rater assessment between saline and hyaluronidase at 4 weeks (visual detection: mean difference = 1.15; 95% CI, 0.46-1.80; P < .001; palpability: mean difference = 1.22; 95% CI, 0.61-1.83; P < .001) and 4 months (visual detection: mean difference = 0.77; 95% CI, 0.33-1.26; P = .001; palpability: mean difference = 0.82; 95% CI, 0.38-1.25; P < .001) that was mirrored by participant self-assessment at 4 weeks (visual detection: mean difference = 0.87; 95% CI, 0.26-1.48; P = .006; palpability: mean difference = 1.59; 95% CI, 1.41-1.77; P < .001) and 4 months (visual detection: mean difference = 1.31; 95% CI, 1.09-1.53; P < .001; palpability: mean difference = 1.52; 95% CI, 1.03-2.01; P < .001), and hyaluronidase was associated with greater resolution of buttons compared with normal saline. The 9.0-unit hyaluronidase injection sites were significantly less palpable than the 1.5-unit sites at both 4 weeks (mean difference = 0.50; 95% CI, 0.01-.99; P = .045) and 4 months (mean difference = 0.47; 95% CI, 0.14-0.81; P = .007). Dose dependence was more notable for Restylane-L.

Conclusions and Relevance  Although very small doses of hyaluronidase can remove hyaluronic acid fillers from patient skin, slightly higher doses often result in more rapid resolution.

Trial Registration  clinicaltrials.gov Identifier: NCT01722916

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Article Information

Accepted for Publication: December 12, 2017.

Corresponding Author: Murad Alam, MD, Department of Dermatology, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (m-alam@northwestern.edu).

Published Online: April 25, 2018. doi:10.1001/jamadermatol.2018.0515

Author Contributions: Dr Alam had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Alam, Hughart, Geisler, West, Poon.

Acquisition, analysis, or interpretation of data: Alam, Geisler, Paghdal, Maisel, Weil, Veledar, Poon.

Drafting of the manuscript: Alam, Hughart, Geisler, Poon.

Critical revision of the manuscript for important intellectual content: Alam, Paghdal, Maisel, Weil, West, Veledar, Poon.

Statistical analysis: Maisel, Weil, Veledar.

Obtained funding: Alam.

Administrative, technical, or material support: Hughart, Paghdal, Maisel, West.

Study supervision: Alam, Hughart.

Conflict of Interest Disclosures: Dr Alam is employed at Northwestern University. Dr Alam has been a consultant for Amway and Leo Pharma, both unrelated to this research. Grants: Northwestern University has a clinical trials unit that receives grants from very many corporate and governmental entities to perform clinical research. Dr Alam has been principal investigator on studies funded in part by Allergan, Medicis, Bioform, and Ulthera. In all cases, grants and gifts in kind have been provided to Northwestern University and not Dr Alam directly, and Dr Alam has not received any salary support from these grants. Dr Alam receives royalties from Elsevier for technical books he has edited. No other disclosures are reported.

Funding/Support: This study was supported by departmental research funds, Department of Dermatology, Northwestern University.

Role of the Funder/Sponsor: Northwestern University had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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