What Is Hyaluronidase? Chemical and Biological Basis of the Enzyme
Hyaluronidase is a glycoprotein enzyme that cleaves hyaluronic acid polymers at beta-1,4 glycosidic bonds. With a molecular weight of approximately 60 kDa, this enzyme occurs naturally in the body: in sperm cells during fertilization, in tissue repair, in the inflammatory cascade, and in extracellular matrix remodeling. In medical aesthetics practice, it is injected externally to dissolve HA-based fillers.
The biochemical properties and clinical profiles of hyaluronidase preparations derived from different sources differ from one another. These differences are decisive for duration of action, allergy risk, and potency of interaction with filler products. The clinician must know the source type and activity units of the preparation used; otherwise, particularly in emergencies, the dose calculation may be insufficient.
Three main source types are available on the market:
- Bovine-derived hyaluronidase: The longest-used form. Allergy risk is higher compared to the others (0.05–0.1%).
- Ovine (sheep)-derived hyaluronidase: Similar profile to bovine; licensed in some countries.
- Recombinant human hyaluronidase (rHuPH20, Hylenex): Produced by biotechnological methods. More favorable allergy profile. FDA-approved.
Commonly used preparations include Hyalase (bovine) and Hylase Dessau. The recombinant form is not yet widely available. Whichever preparation is used, careful attention to product selection outside of emergencies and consideration of a test dose is appropriate.
Which Fillers Does It Dissolve — and Which Doesn't It Dissolve?
Hyaluronidase is effective only on hyaluronic acid-based fillers. It does not dissolve fillers containing poly-L-lactic acid (Sculptra/PLLA), calcium hydroxyapatite (Radiesse), polymethylmethacrylate (PMMA), or silicone. It is therefore mandatory to verify the composition of the filler used before planning dissolution.
| Filler Type | Response to Hyaluronidase | Notes |
|---|---|---|
| Hyaluronic acid filler (Juvederm, Restylane, Teosyal, etc.) | Effective | Dose may vary depending on cross-link density |
| Poly-L-lactic acid (Sculptra) | Ineffective | Surgical intervention may be required |
| Calcium hydroxyapatite (Radiesse) | Ineffective | No dissolution option available |
| PMMA (permanent fillers) | Ineffective | Surgery required |
Indications for Dissolution: When Is Hyaluronidase Used?
Hyaluronidase use is evaluated in two main categories: emergency indications and elective indications.
Emergency Indications (Act Without Delay)
- Vascular occlusion: When filler blocks or externally compresses a vessel, tissue ischemia develops. If this spreads to the ophthalmic artery it can lead to blindness. When pale white-grey discolouration, pain, or prolonged capillary refill is observed, immediately and at high dose hyaluronidase must be administered.
- Suspected retinal ischemia: In any patient with sudden visual loss or blurring, an aggressive protocol including retroorbital block is initiated alongside ophthalmology consultation.
Elective Indications
- Overfilling / over-correction: Dissatisfaction by patient or physician.
- Tyndall effect: Blue-purple discolouration under the eyes and surrounding areas following superficial injection; low-dose hyaluronidase is sufficient for correction.
- Nodularity and granuloma: Indication is limited but valuable in late-onset formations.
- Asymmetry correction: Unilateral partial dissolution.
- Patient dissatisfaction: Complete dissolution of all filler for the unsatisfied patient.
Dosing Guide: Area-by-Area Table
The hyaluronidase dose is determined by the volume of filler injected, the cross-link density of the filler, the time elapsed, and the dissolution target. High cross-link (firm) fillers may require higher doses.
| Area / Indication | Recommended Dose (IU) | Re-evaluation |
|---|---|---|
| Tyndall effect (under eye) | 15–75 IU | 24–48 hours later |
| Lips — partial dissolution | 75–150 IU | 48–72 hours later |
| Lips — complete dissolution | 150–300 IU | 72 hours later |
| Nasolabial fold | 150–300 IU | 48–72 hours |
| Cheek / mid-face filler | 300–600 IU | 72 hours–1 week |
| Chin / jawline filler | 150–450 IU | 48–72 hours |
| Full-face dissolution | 1000–1500 IU | 1 week later |
| Vascular occlusion (EMERGENCY) | ≥1500 IU — administer immediately | Re-evaluate 30–60 min later |
Important note: The doses above are guidance only. The physician must calculate an individual dose for each patient and filler. In vascular occlusion, do not hesitate over the dose; an adequate dose can be life-saving.
Injection Technique: Partial vs. Complete Dissolution
The preferred technique for hyaluronidase injection varies according to the plane in which the filler lies. The general principle is: administering small volumes at multiple points within the same injection plane ensures homogenous dissolution.
- Partial dissolution: Only the excess or problematic area is dissolved. For example, an irregularity confined to the Cupid's bow of the lip. Low dose, targeted injection.
- Complete dissolution: Aims to dissolve all filler. Usually requires 1–2 sessions. After dissolution, the physician reassesses the skin tissue and revises the filler plan.
Cannula use is safer, especially in large areas and high vascular-risk zones (nose, periorbital). When using a needle, the habit of aspirating is critical.
Onset and Duration of Effect: How Soon Does It Work?
The onset of effect after hyaluronidase injection depends on the cross-link density of the product used and the accuracy of the injection:
- Low cross-link fillers (e.g. under-eye fillers): Noticeable softening begins within 6–12 hours.
- High cross-link fillers (e.g. deep cheek or jawline fillers): Effect is seen within 24–48 hours.
- In a vascular occlusion emergency: Do not wait 30–60 minutes; look for immediate perfusion. Monitor capillary refill return and colour improvement. If necessary, administer a second dose within 60 minutes.
For a complete assessment, waiting 48–72 hours is generally recommended. The result may appear insufficient before this time.
Does It Also Dissolve Your Own Tissue HA?
Yes — this is one of the most frequently asked questions from patients. Hyaluronidase breaks down both the injected HA filler and the natural tissue HA in the injected area. However, this effect is temporary. The body regenerates the lost natural HA through fibroblast activity within 4–6 weeks.
After dissolution, patients may therefore experience a few weeks of a "dry period." The skin may feel drier and less plump. This condition is not permanent and lasts until re-filling is performed.
Is a Test Dose Required?
A test dose is not routinely mandatory; however, it may be recommended in patients at risk of allergy when bovine-derived hyaluronidase is used. The following questions should be asked before the procedure:
- Has hyaluronidase been administered before?
- Is there a history of insect-sting allergy or anaphylaxis?
- Is there a history of urticaria or angioedema?
In a vascular occlusion emergency, no test dose is waited for — time is critical. For elective dissolutions in high-risk patients, an intradermal test of 3–5 IU can be administered with 10–15 minutes of observation.
When Can Re-Filling Be Performed?
After dissolution, a minimum of 4 weeks, ideally 6 weeks is recommended to allow natural HA to regenerate and tissue inflammation to resolve. This waiting period is important for obtaining more predictable results, planning the new filler correctly, and allowing tissue inflammation to subside.
If very large areas have been dissolved or multiple sessions of hyaluronidase have been performed, waiting 6–8 weeks is more prudent.
Hyaluronidase Protocol in Vascular Occlusion
Vascular occlusion is the most serious complication of filler injection. The protocol proceeds as follows:
- Stop the procedure immediately.
- Try to disperse the filler in the area with massage.
- Apply heat to the area (warm compress).
- Inject ≥1500 IU hyaluronidase — fan technique across the entire affected area.
- Assess perfusion after 60 minutes; if there is no improvement, administer a second dose.
- Aspirin 300 mg (oral), warm massage, and urgent ophthalmology if ocular signs are present.
- Be prepared with a hospital referral protocol.
Every clinic must keep a hyaluronidase emergency kit ready. At Virtuana Clinic, the vascular occlusion protocol is active and ready for implementation.
Special Uses in Complication Management
Hyaluronidase is not only for vascular occlusion; it is also part of complication management in the following situations:
- Tyndall effect: Low dose, superficial application for blue discolouration resulting from a very superficial injection.
- Late nodule/granuloma: Can be considered alongside steroid injection.
- Asymmetry: For partial dissolution of the fuller side.
- "Pillow face" appearance: Selective volume reduction in over-loaded faces.
Filler Dissolution Approach at Virtuana Clinic
Virtuana Clinic (Izmit/Kocaeli) performs filler dissolution procedures in accordance with clinical aesthetic protocols, under the supervision of a specialist physician. The dissolution decision is made by evaluating the type and volume of filler, the time elapsed, and the patient's expectations. Complication emergency protocols are actively implemented within the clinic. Please contact us for pricing information.
This article is for informational purposes only. Please consult a qualified physician for treatment decisions.