Hyaluronidase in Dermatology: Uses Beyond Hyaluronic Acid Fillers

October 2020 | Volume 19 | Issue 10 | Original Article | 993 | Copyright © October 2020


Published online September 11, 2020

Tamara Searle BSc,a, Faisal R, Ali PHD MRCPb,c, Firas Al-Niaimi MRCPd

aUniversity of Birmingham Medical School, Birmingham, UK bVernova Healthcare CIC, Macclesfield, UK cSt John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust, Great Maze Pond, London SE1 9RS, UK dDepartment of Dermatology, Aalborg University Hospital, Aalborg, Denmark

Abstract
Hyaluronidase is mostly widely recognized for its off-label use in correction of complications of hyaluronic acid fillers. However, its utility in other aspects of dermatology is less widely acknowledged. We describe the varied uses of hyaluronidase in dermatology and the underlying evidence base for its dermatological indications. This includes its uses in enhancing drug delivery (for local anesthesia, keloid and hypertrophic scars, and for Kaposi’s sarcoma), in the treatment of disorders associated with mucin deposition (myxedema, scleroderma, scleredema, and cutis verticis gyrata) and its potential uses in surgery (as a pre-operative adjuvant in dermatofibrosarcoma protuberans, for periorbital edema, and for hematomas). In select circumstances, hyaluronidase might be more efficacious than more established treatments with fewer adverse effects. We propose hyaluronidase as the latest addition to our global dermatological armamentarium and implore dermatologists to consider its use to enhance their practice.

J Drugs Dermatol. 2020;19(10):993-998. doi:10.36849/JDD.2020.5416

BACKGROUND

Hyaluronidase is an enzyme used in ophthalmic surgery and dermatology. Its use is well-established and is the standard approach in dissolving Hyaluronic acid (HA) fillers (off-label) both in overcorrection and vascular emergencies.1 More recently, its uses in dermatology have expanded to include medical and surgical applications.2,3

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