What is the best treatment to dissolve a hyaluronic acid (HA) filler nodule?

Treatment of Hyaluronic Acid Filler Nodules

Hyaluronidase injection is the definitive treatment for dissolving hyaluronic acid filler nodules, with doses ranging from 1.5 to 37.5 units per 0.1 mL of filler depending on the clinical scenario, injected directly into the palpable nodule for optimal dissolution. 1, 2, 3

Mechanism and Pharmacology

Hyaluronidase works by hydrolyzing hyaluronic acid through cleavage of the glucosaminidic bond between C1 of an N-acetylglucosamine moiety and C4 of a glucuronic acid moiety, temporarily decreasing the viscosity of the cellular cement and promoting dispersion of the filler material. 1

• The enzyme must interact directly with binding sites within the hyaluronic acid to achieve dissolution, requiring injection close to or into the filler itself. 4
• Hyaluronidase is rapidly degraded and deactivated in the body, necessitating sufficient dosing at the correct anatomical location. 4
• The dermal barrier begins restoration at 24 hours post-injection (incomplete and inversely related to dose) and is completely restored by 48 hours. 1

Dosing Protocols Based on Clinical Indication

For Uncomplicated Nodules or Aesthetic Overcorrection

Low-dose hyaluronidase (1.5-9.0 units per 0.1 mL) injected directly into palpable HA masses provides effective dissolution with dose-dependent response. 3, 5

• Single injection protocol: 1.25-37.5 units of hyaluronidase per 0.1 mL of HA filler removed. 2
• The 9.0-unit dose demonstrates significantly greater resolution compared to 1.5-unit doses at both 4 weeks and 4 months, particularly for more cross-linked fillers. 5
• For subcutaneously placed filler, inject hyaluronidase directly into the filler itself for optimal effect. 4

For Multiple Weekly Treatments

• When using 3 consecutive weekly injections, much lower doses of 0.375-2.25 units are sufficient due to cumulative effect. 2
• This approach may be preferred for gradual correction or when conservative dissolution is desired. 2

For Vascular Complications (Tissue Ischemia/Necrosis)

High-dose hyaluronidase requires immediate flushing of the ischemic area, not just focal injection into the filler. 3

• If filler is within a blood vessel, inject hyaluronidase in the vicinity of the vessel rather than attempting direct intravascular injection. 4
• This represents a medical emergency requiring aggressive dosing compared to aesthetic overcorrection scenarios. 3

Technical Considerations

Factors Affecting Dissolution Efficacy

The reaction of HA filler to hyaluronidase depends on three critical variables: 4

• Hyaluronic acid concentration in the filler product
• Number of cross-links in the gel matrix (more cross-linking = more resistant to degradation)
• Form of the filler (cohesive vs. non-cohesive gels)

Different HA filler brands demonstrate variable sensitivity to hyaluronidase degradation, requiring awareness of the specific product being dissolved. 3

Injection Technique

• Inject a constant volume (0.1 mL) of variable-dose hyaluronidase directly into each palpable nodule. 5
• Use sufficient volume to ensure adequate enzyme-filler interaction at the treatment site. 4
• For subcutaneous placement, direct injection into the filler mass is essential; for suspected intravascular placement, perilesional injection suffices. 4

Safety Profile and Adverse Effects

Hypersensitivity Reactions

Allergic reactions represent the most common side effect, with most being immediate hypersensitivity reactions, though delayed reactions can occur. 4

• Skin testing is recommended before use to identify immediate hypersensitivity, though it cannot predict delayed allergic reactions. 4
• Despite theoretical concerns, hypersensitivity reactions to hyaluronidase have not been reported in the dermatologic literature as of 2015. 3
• Most allergic reactions are local rather than systemic. 4

FDA-Approved Products

• FDA-approved hyaluronidases provide predictable results and can be used interchangeably. 3
• Physicians must be familiar with specific characteristics of non-FDA-approved hyaluronidases if using alternative products. 3

Expected Timeline for Resolution

• Significant difference in nodule detectability (both visual and palpable) is evident at 4 weeks post-treatment compared to saline control. 5
• Resolution continues through 4 months, with higher doses (9.0 units) showing sustained superiority over lower doses (1.5 units). 5
• Both physician assessment and patient self-assessment demonstrate parallel improvement trajectories. 5

Critical Pitfalls to Avoid

• Do not use insufficient doses for the amount of filler present—calculate based on estimated filler volume (1.25-37.5 units per 0.1 mL). 2
• Do not inject hyaluronidase distant from the filler location—the enzyme must be in direct contact with the HA to achieve dissolution. 4, 3
• Do not delay treatment in vascular emergencies—high-dose flushing must be immediate for tissue ischemia scenarios. 3
• Do not assume all HA fillers respond identically—more heavily cross-linked products require higher doses for equivalent dissolution. 4, 5
• Do not skip skin testing in patients with unknown allergy history—though rare in dermatologic use, hypersensitivity can occur. 4