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.
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