HA, produced by fibroblasts, is a key component of the extracellular matrix (ECM).2 Hyaluronidase hydrolyzes HA, reducing ECM viscosity, facilitating dispersal of injected substances and increasing bioavailability leading to its use in aiding the diffusion of local anesthetic injections.2,4
Hyaluronidase is used in dermatological conditions in which excessive or abnormal ECM is implicated, such as mucin deposition disorders (resulting in increased glycosaminoglycans) and scars, and where dissolution of physiological HA may be advantageous. We present the wide usage of hyaluronidase in dermatology beyond its cosmetic uses.
Hyaluronidase as an Enzyme
Hyaluronidase is a soluble enzyme, available endogenously in six variants (HYAL1,2,3,4, PH-20, and HYALP1)5 and exogenously as bovine (Hylase® Dessau, Riemser Pharma GmbH, Greifswald, Germany), ovine (Vitrase®, Bausch & Lomb, Rochester, NY, USA), or human recombinant (Hylenex® Halozyme Therapeutics, San Diego, California, USA) preparations. Its dosing is expressed in international units (IU) and the dose per preparation depends on the manufacture brand. Its main mechanism of action is degradation of HA through hydrolysis with resultant ECM alteration. Hyaluronidase is licensed by the FDA for increasing absorption and dispersion of other injected drugs, for hypodermoclysis, and as an adjunct in subcutaneous urography.6 In the European Union, hyaluronidase is licensed for adjunctive subcutaneous drug administration, for increasing LA coverage area, for promoting contrast medium reabsorption in urology, and for promoting reabsorption of subcutaneous hematomas.2,7-8 Across the world, its most recognized use off-label is for dissolving injected HA or filler-related vascular complications.8
Most side-effects are minor and transient and consist of post-injection pruritus, bruising, and swelling.9 The risk of anaphylaxis is reportedly increased in those with wasp allergies.8 Two case reports of shock1 with co-administration of chemotherapy10 and one report of anaphylaxis11 have been observed.8
Allergy to bee or wasp stings might be associated with an increased risk of allergic reaction to hyaluronidase due to cross-reactivity.1 A pre-treatment patch test or skin-prick testing might be considered for ovine and bovine preparations as these formulations contain an antigen that can be allergenic.12 The risk of allergic reactions increases with higher doses.8