Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules: A Randomized Clinical Trial

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