Effectiveness of low doses of hyaluronidase to remove hyaluronic acid filler nodules a randomized clinical trial

Murad Alam*, Rosemara Hughart, Amelia Geisler, Kapila Paghdal, Amanda Maisel, Alexandra Weil, Dennis P. West, Emir Veledar, Emily Poon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)765-772
Number of pages8
JournalJAMA dermatology
Issue number7
StatePublished - Jul 2018

ASJC Scopus subject areas

  • Dermatology


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