Aesthetic Dermatology

Low hyaluronidase doses may be adequate for addressing filler asymmetry



Low doses of hyaluronidase appear to be effective at eliminating unwanted hyaluronic acid filler, and in some cases, slightly larger doses may move things along more rapidly, according to the authors of a small split-arm clinical trial.

“These findings offer clinicians a means to modify and fine-tune filler-associated skin contour without resorting to high-dose injections that completely remove all filler from the treatment site,” wrote the authors, led by Murad Alam, MD, professor of dermatology and chief of cutaneous and aesthetic surgery in the department of dermatology, Northwestern University, Chicago. The study was published online in JAMA Dermatology.

Dr. Murad Alam, vice-chair of the department of dermatology and chief of the division of cutaneous and aesthetic surgery at Northwestern University, Chicago

Dr. Murad Alam

As the authors noted, extensive research has noted the successful use of hyaluronidase for managing filler complications, used at relatively higher doses to treat issues like asymmetry and catastrophic outcomes. The new study was prompted by case reports about the effectiveness of very low doses to address complications.

The study, conducted during 2013-2014, analyzed the impact of various small doses of hyaluronidase on two types of fillers that had been administered into the upper inner arms of nine women (seven white, two black; mean age, 46 years). Another participant withdrew because of a fear of needles.

In one arm in each woman, researchers injected four aliquots of Juvéderm Ultra XC (0.4 mL each). Then, at 1, 2, and 3 weeks, they administered 1.5 U, 3.0 U, or 9.0 U hyaluronidase per 0.1 mL or saline control (at a constant volume of 0.1 mL) into each site. In the other arms, researchers performed the same protocol, but with Restylane-L. A 5-point scale was used to rate detectability of each site ranging from 0 (undetectable) and 1 (faintly perceptible) to 4 (“very” perceptible).

A blinded physician visually rated the effects of saline versus hyaluronidase at 4 weeks and found a significant difference between assessments of the hyaluronidase-treated sites and saline control sites at 4 weeks, favoring the hyaluronidase sites for visual detection (mean difference, 1.15; P less than .001) and palpability (mean difference, 1.22; P less than .001). Participant self-assessments at 4 weeks produced similar results for visual detection (mean difference, 0.87; P = .006) and palpability (mean difference, 1.59; P less than .001).

Similar differences favoring hyaluronidase persisted at 4 months.

The researchers also found that 9.0-U treatments of hyaluronidase led to significantly less palpability than 1.5-U treatments at 4 weeks and 4 months. The researchers noticed a larger dose-related difference for hyaluronidase for Restylane-L sites, and they noted that all the filler nodules diminished over time regardless of the study treatment.

“The clinical relevance of these findings is clear,” they concluded. “Minor filler-associated asymmetries, nodules, and textural abnormalities may be corrected safely and effectively with low-volume, low-dose hyaluronidase. Rather than dissolving all the offending filler, waiting, and then reinjecting fresh filler weeks or months later, dermatologists may precisely sculpt already injected excess filler by titration with low-volume, low-dose hyaluronidase to the desired skin contour.”

Other types of hyaluronidase may work in different ways, the study authors noted, and larger doses may be needed to treat longer-lasting types of fillers.

In an accompanying commentary, Derek H. Jones, MD, of Skin Care and Laser Physicians of Beverly Hills, Calif., praised the study, which he wrote, “proves that smaller, less-concentrated doses of hyaluronidase are capable of removing small amounts of HA [hyaluronic acid] without removing the entire implant.”

Dr. Jones added that he uses 10 U of Vitrase (hyaluronidase) for each 0.1 cc of Juvéderm that he estimates should be removed. He also uses 5 U of Vitrase for each 0.1 cc of Restylane, and 30 U for each 0.1 cc of Juvéderm Voluma.

“When attempting to remove smaller or partial amounts of HA implant,” he added, “I often dilute Vitrase with normal saline to go from 20 U/0.1 cc to 10 U/0.1 cc or less.”

Northwestern University funded the study. Dr. Alam, the lead author, reported various disclosures, and the university disclosed that its clinical trials branch receives various government and corporate grants. The other authors reported no disclosures. Dr. Jones disclosed serving as an investigator, consultant, and/or speaker for Allergan, Merz, and Galderma.

SOURCE: Alam M et al. JAMA Dermatol. 2018 Apr 25. doi: 10.1001/jamadermatol.2018.0515.

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