Background
Hyaluronic acid-based dermal fillers are the most commonly used in the aesthetics market. Hyaluronic acid, a glycosaminoglycan and a chief component of the extracellular matrix, is mainly responsible for maintaining hydration in the dermis. It is a linear polysaccharide chain composed of alternating monosaccharides, d-glucuronic acid, and N-acetyl-d-glucosamine.
Hyaluronidases are enzymes (endoglycosidases) capable of depolymerizing hyaluronic acid, leading to its degradation. In the UK, hyaluronidase is licensed for enhancing the permeation of subcutaneous or intramuscular injections, local anesthetics, and subcutaneous infusions, and to promote the resorption of excess fluids and blood. However, there is substantial evidence for their off-label use in aesthetic medicine for addressing issues such as vascular compromise, over-correction, asymmetry, and lumps and nodules caused by hyaluronic acid filler injections.
There are several sources of hyaluronidase, divided into three subgroups: mammalian (obtained from the testis), hookworm/leech, and microbial. Recombinant human hyaluronidase (Hylenex, from Halozyme Therapeutics, San Diego, California) is now available, boasting a purity 100 times higher than some currently used bovine preparations, and is likely to have a lower proportion of allergic reactions. This guidance refers to the use of Hyalase® (Wockhardt), which is readily available in the UK as a 1500 unit ampoule of powder for reconstitution and is of ovine (sheep) origin.
Off-Label Use of Hyaluronidase
Although hyaluronidase is not licensed for correcting issues with dermal filler injections and off-label promotion is not allowed by Article 87 of Directive 2001/83/EC, its use is permissible provided the patient’s best interest and autonomy are respected, forming part of the informed consent (MHRA, 2009).
What Should Be Treated?
Vascular Compromise: Vascular compromise resulting from hyaluronic acid filler injection should be treated immediately. Signs of impending necrosis include pain, prolonged blanching, and coolness of the skin. Hyaluronidase should be administered promptly to prevent or reduce the severity of tissue necrosis if it cannot be resolved with hot compress and massage.
The Tyndall Effect: This refers to the scattering of light seen in some patients after hyaluronic acid injection, resulting in a bluish hue of the skin. It is often caused by superficial injection, large boluses of product in one area, or using an inappropriate product. Hyaluronidase can correct this problem by degrading the hyaluronic acid.
Overcorrection or Misplacement: These issues, often caused by poor injection technique or product choice, can be successfully treated with hyaluronidase.
Lumps or Nodules: Lumps or nodules appearing several months after the initial treatment may be treatable with hyaluronidase. If the nodule is thought to be infective, antibiotics should be administered to prevent the spread of infection.
Storage and Reconstitution
Hyaluronidase should be stored at cool temperatures (2-8°C) to guarantee product quality over a long period. At room temperature (25°C), stability is only guaranteed for 12 months. Hyalase® may be reconstituted with saline or water for injection, with saline being recommended due to less stinging.
Dosages of Hyaluronidase
Hyaluronidase may degrade the body’s natural hyaluronic acid in preference to foreign hyaluronic acid filler. However, our bodies are constantly making hyaluronic acid so this will be replaced overtime. The required dosage depends on several factors, including the type of hyaluronic acid filler, the amount of cross-linking, and the concentration of hyaluronic acid. It is recommended to treat to effect rather than using an absolute dosage.
Intradermal Patch Testing
A test patch is recommended, except when treating vascular compromise where delay could result in further harm. An intradermal injection of 4-8 Units of hyaluronidase in the forearm is advised, with observation of results after 20-30 minutes. A positive reaction is identified by a weal and itching at the injection site.
Drug Interactions
Common interactions occur with furosemide, benzodiazepines, phenytoin, dopamine, and α-adrenergic agonists. Several drugs act as antagonists to hyaluronidase, including anti-inflammatory drugs, antihistamines, mast cell stabilizers, Vitamin C, flavonoids, and antioxidants.
Administration
The area should be inspected, palpated, and marked out if needed. The procedure should be carried out using aseptic techniques. A 27G or 30G needle should be used, and administration should be accurate and limited to the affected area. For vascular compromise, serial puncture should be used to inject hyaluronidase along the vessel’s course. Results are often seen almost immediately, though it may take 48 hours for denser products.
Complications
The most common complication is an allergic reaction. Local reactions are the most frequent, with signs including edema, erythema, pain, and itching. Urticaria and angioedema are less common. Anaphylaxis has occurred with high doses and intravenous administration. Patients should be observed for 30 minutes post-administration to ensure no adverse reactions occur.
In Conclusion
Overall, Hyaluronidase is a valuable tool in aesthetic practice for managing complications related to hyaluronic acid fillers. Its proper use, guided by evidence and clinical guidelines, can enhance patient safety and treatment outcomes.
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