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Hyaluronidase in cosmetology: evidence-based medicine review

Vladimirova Elena; Stanislav Vyacheslavovich Murakov; Albertovna Sanchez Elena; Yulia Alexandrovna Markova; Gayane Ernstovna Bagramova;

The purpose of the present review was to analyze current data on hyaluronidase application in cosmetology from the standpoint of evidence-based medicine. Clinical evidence suggests a high efficacy of hyaluronidase for the treatment of asymmetry, hypercorrection, migration, filler visualization, Tyndall effect, vascular complications, impaired visual function and delayed reactions. The dilution and volume of the hyaluronidase to be injected varies depending on the specific indication, the volume of the intradermal implant and the manufacturer’s recommendations. The most significant contraindication for hyaluronidase preparations in cosmetology is the hypersensitivity, therefore, a drug sensitivity test should be performed before the first use.


1. Wang W., Wang J., Li F. Hyaluronidase and chondroitinase. Adv. Exp. Med. Biol. 2017;925:75-87. https://doi.org/10.1007/5584_2016_54
2. Swathi N., Srikanth K., Venipriya S. Does the addition of hyaluronidase improve the quality of peribulbar anesthesia in cataract surgery? A randomized double blinded study. Saudi J. Ophthalmol. 2018;32(3):204-210. https://doi.org/10.1016/j.sjopt.2018.02.013
3. Nehra P., Oza V., Parmar V., Fumakiya P. Effect of addition of fentanyl and clonidine to local anesthetic solution in peribulbar block. J. Pharmacol. Pharmacother. 2017;8(1):3-7. https://doi.org/10.4103/jpp.JPP_109_16
4. Malaisse J., Pendaries V., Hontoir F. [et al.]. Hyaluronan does not regulate human epidermal keratinocyte proliferation and differentiation. J. Biol. Chem. 2016;291(12):6347-6358. https://doi.org/10.1074/jbc.M115.661348
5. Raab S., Yatskayer M., Lynch S. [et al.]. Clinical evaluation of a multi-modal facial serum that addresses hyaluronic acid levels in skin. J. Drugs Dermatol. 2017;16(9):884-890. Available at: https://www.dermastore.co.za/wp-content/uploads/2014/10/H.A.-Intensifier-publication.pdf. Accessed
March 17, 2019.
6. Maytin E. V. Hyaluronan: more than just a wrinkle filler. Glycobiology. 2016;26(6):553-559. https://doi.org/10.1093/glycob/cww033
7. França Wanick F. B., Almeida Issa M. C., Luiz R. R. [et al.]. Skin remodeling using hyaluronic acid filler injections in photo-aged faces. Dermatol. Surg. 2016;42(3):352-359. https://doi.org/10.1097/DSS.0000000000000659
8. Mundada P., Kohler R., Boudabbous S. [et al.]. Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and PET CT. Insights Imaging. 2017;8(6):557-572. https://doi.org/10.1007/s13244-017-0575-0
9. Myung Y., Yim S., Jeong J. H. [et al.]. The classification and prognosis of periocular complications related to blindness following cosmetic filler injection. Plast. Reconstr. Surg. 2017;140(1):61-64. https://doi.org/10.1097/PRS.0000000000003471
10. Lee J. I., Kang S. J., Sun H. Skin necrosis with oculomotor nerve palsy due to a hyaluronic acid filler injection. Arch. Plast. Surg. 2017;44(4):340-343. https://doi.org/10.5999/aps.2017.44.4.340
11. Hirsch R. J., Brody H. J., Carruthers J. D. Hyaluronidase in the office: a necessity for every dermasurgeon that injects hyaluronic acid. J. Cosmet. Laser. Ther. 2007;9(3):182-185. https://doi.org/10.1080/14764170701291674
12. Lacoste C., Hersant B., Bosc R., Noel W., Meningaud J. P. Use of hyaluronidase to correct hyaluronic acid injections in aesthetic medicine. Rev. Stomatol. Chir. Maxillofac. Chir. Orale. 2016;117(2):96-100. https://doi.org/10.1016/j.revsto.2016.01.016
13. Jahn K., Homey B., Gerber P. A. Management of complications after aesthetic hyaluronic acid injections. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2014;65(10):851-853. https://doi.org/10.1007/s00105-014-3511-y
14. Hilton S., Schrumpf H., Buhren B. A., Bolke E., Gerber P. A. Hyaluronidase injection for the treatment of eyelid edema: a retrospective analysis of 20 patients. Eur. J. Med. Res. 2014;19:30. https://doi.org/10.1186/2047-783X-19-30
15. Iverson S. M., Patel R. M. Dermal filler-associated malar edema: treatment of a persistent adverse effect. Orbit. 2017;36(6):473-475. https://doi.org/10.1080/01676830.2017.1337203
16. Yu J. T. S., Peng L., Ataullah S. Chronic eyelid edema following periocular hyaluronic acid filler treatment. Ophthalmic Plast. Reconstr. Surg. 2017;33(6):e139-e140. https://doi.org/10.1097/IOP.0000000000000871
17. Khan T. T., Woodward J. A. Retained dermal filler in the upper eyelid masquerading as periorbital edema. Dermatol. Surg. 2015;41(10):1182-1184. https://doi.org/10.1097/DSS.0000000000000442
18. Berguiga M., Galatoire O. Tear trough rejuvenation: a safety evaluation of the treatment by a semi-cross-linked hyaluronic acid filler. Orbit. 2017;36(1):22-26. https://doi.org/10.1080/01676830.2017.1279641
19. Chen W., Wu L., Jian X. L. [et al.]. Retinal branch artery embolization following hyaluronic acid injection: a case report. Aesthet. Surg. J. 2016;36(7):NP219-224. https://doi.org/10.1093/asj/sjw054
20. DeLorenzi C. Complications of injectable fillers, part 2: vascular complications. Aesthet. Surg. J. 2014;34(4):584-600. https://doi.org/10.1177/1090820X14525035
21. Maruyama S. A. Histopathologic diagnosis of vascular occlusion after injection of hyaluronic acid filler: findings of intravascular foreign body and skin necrosis. Aesthet. Surg. J. 2017;37(9):102-108. https://doi.org/10.1093/asj/sjx085
22. Kang B. K., Kang I. J., Jeong K. H., Shin M. K. Treatment of glabella skin necrosis following injection of hyaluronic acid filler using platelet-rich plasma. J. Cosmet. Laser Ther. 2016;18(2):111-112. https://doi.org/10.3109/14764172.2015.1052512
23. Kim D. W., Yoon E. S., Ji Y. H. [et al.]. Vascular complications of hyaluronic acid fillers and the role of hyaluronidase in management. J. Plast. Reconstr. Aesthet. Surg. 2011;64(12):1590-1595. https://doi.org/10.1016/j.bjps.2011.07.013
24. Woodward J. Review of periorbital and upper face: pertinent anatomy, aging, injection techniques, prevention, and management of complications of facial fillers. J. Drugs. Dermatol. 2016;15(12):1524-1531. Available at: http://jddonline.com/articles/dermatology/S1545961616P1524X. Accessed March 17, 2019.
25. Skippen B., Baldelli I., Hartstein M., Casabona G., Montes J. R., Bernardini F. Rehabilitation of the dysmorphic lower eyelid from hyaluronic acid filler: what to do after a good periocular treatment goes bad. Aesthet. Surg. J.2019. pii:sjz078. https://doi.org/10.1093/asj/sjz078
26. Cox S. E. Clinical experience with filler complications. Dermatol. Surg. 2009;35:1661-1666. https://doi.org/10.1111/j.1524-4725.2009.01345.x
27. Jordan D. R., Stoica B. Filler Migration: A number of mechanisms to consider. Ophthalmic Plast. Reconstr. Surg. 2015;31(4):257-262. https://doi.org/10.1097/IOP.0000000000000368
28. Quezada-Gaón N., Wortsman X. Ultrasound-guided hyaluronidase injection in cosmetic complications. J. Eur. Acad. Dermatol. Venereol. 2016;30(10):e39-e40. https://doi.org/10.1111/jdv.13286
29. Stenko A. G., Talybova A. M., Kruglova L. S., Korchazhkina N. B. The use of conjugated hyaluronidase for the prevention and treatment of cicatricial deformities. Kremlevskaia meditcina. Clinicheskii` vestneyk. – Kremlin medicine. Clinical Bulletin. 2018;1:114-119. Available at: http://kremlin-medicine.ru/index.php/km/article/view/1057. Accessed March 17, 2019. (In Russ.).
30. Sidgwick G. P., Iqbal S. A., Bayat A. Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin. Exp. Dermatol. 2013;22(5):377-379. https://doi.org/10.1111/exd.12147
31. Stenko A. G., Talybova A. M., Tchaikovskaya E. A., Kruglova L. S. Post-acne scar correction – use of conjugated hyaluronidase as monotherapy and in combination with laser therapy. Kremlevskaia meditcina. Clinicheskii` vestneyk. – Kremlin medicine. Clinical Bulletin. 2018;2:154-159. Available at: http://kremlin-medicine.ru/index.php/km/article/view/1170. Accessed March 17, 2019. (In Russ.).
32. Wu L., Liu X., Jian X. [et al.]. Delayed allergic hypersensitivity to hyaluronidase during the treatment of granulomatous hyaluronic acid reactions. J. Cosmet. Dermatol. 2017. https://doi.org/10.1111/jocd.12461
33. Kim M. S., Youn S., Na C. H., Shin B. S. Allergic reaction to hyaluronidase use after hyaluronic acid filler injection. J. Cosmet. Laser Ther. 2015;17(5):283-285. https://doi.org/10.3109/14764172.2015.1007069
34. Kim T. W., Lee J. H., Yoon K. B., Yoon D. M. Allergic reactions to hyaluronidase in pain management – a report of three cases. Korean J. Anesthesiol. 2011;60(1):57-59. https://doi.org/10.4097/kjae.2011.60.1.57
35. Raichura N. D., Alam M. S., Jaichandran V. V., Mistry S., Mukherjee B. Hyaluronidase allergy mimicking orbital cellulitis. Orbit. 2018;37(2):149-153. https://doi.org/10.1080/01676830.2017.1383465
36. Leibovitch I., Tamblyn D., Casson R., Selva D. Allergic reaction to hyaluronidase: a rare cause of orbital inflammation after cataract surgery. Graefes Arch. Clin. Exp. Ophthalmol. 2006;244(8):944-949. https://doi.org/10.1007/s00417-005-0190-5
37. Eberhart A. H., Weiler C. R., Erie J. C. Angioedema related to the use of hyaluronidase in cataract surgery. Am. J.Ophthalmol. 2004;138(1):142-143. https://doi.org/10.1016/j.ajo.2004.02.035
38. Weller K., Maurer M., Fridman M., Supina D., Schranz J., Magerl M. Health-related quality of life with hereditary angioedema following prophylaxis with subcutaneous C1-inhibitor with recombinant hyaluronidase. Allergy Asthma Proc. 2017;38(2):143-151. https://doi.org/10.2500/aap.2017.38.4025
39. Ghosh S., Samarasinghe A. E., Hoselton S. A., Dorsam G. P., Schuh J. M. Hyaluronan deposition and co-localization with inflammatory cells and collagen in a murine model of fungal allergic asthma. Inflamm. Res. 2014;63(6):475-484. https://doi.org/10.1007/s00011-014-0719-3
40. Escolano F., Pares N., Gonzalez I. [et al.]. Allergic reaction to hyaluronidase in cataract surgery. Eur. J. Anaesthesiol. 2005;22(9):729-730. https://doi.org/10.4168/aair.2009.1.1.48
41. Koç O., Er. N. Can hyaluronidase be an alternative postoperative anti-edema agent to dexamethasone? Preliminary results of an animal study. J. Oral Maxillofac. Surg. 2018;76(8):1653-1659. https://doi.org/10.1016/j.joms.2018.03.010
42. Sclafani A. P., Fagien S. Treatment of injectable soft tissue filler complications. Dermatol. Surg. 2009;35(2):1672-1680. https://doi.org/10.1111/j.1524-4725.2009.01346.x
43. Park J. H., Park E. J., Yi H. S. Wound healing and anti-inflammatory effects of topical hyaluronic acid injection in surgical-site infection caused by staphylococcus aureus. Int. J. Low. Extrem. Wounds. 2017;16(3):202-207. https://doi.org/10.1177/1534734617714142
44. Tümen İ., Akkol E. K., Taştan H., Süntar I., Kurtca M. Research on the antioxidant, wound healing, and anti-inflammatory activities and the phytochemical composition of maritime pine (Pinus pinaster Ait). J. Ethnopharmacol.
2018;211:235-246. https://doi.org/10.1016/j.jep.2017.09.009
45. Malaisse J., Pendaries V., Hontoir F. [et al.]. Hyaluronan does not regulate human epidermal keratinocyte proliferation and differentiation. J. Biol. Chem. 2016;291(12):6347-6358. https://doi.org/10.1074/jbc.M115.661348
46. Narurkar V. A., Fabi S. G., Bucay V. W. [et al.]. Rejuvenating hydrator: restoring epidermal hyaluronic acid homeostasis with instant benefits. J. Drugs Dermatol. 2016;15(2):s24-37. Available at: http://jddonline.com/articles/dermatology/S1545961616S0024X Accessed March 17, 2019.
47. Kurdykowski S., Mine S., Bardey V. [et al.]. Ultraviolet-B irradiation induces differential regulations of hyaluronidase expression and activity in normal human keratinocytes. Photochem. Photobiol. 2011;87(5):1105-1112. https://doi.org/10.1111/j.1751-1097.2011.00959.x
48. Wohlrab J., Wohlrab D., Wohlrab L. [et al.]. Use of hyaluronidase for pharmacokinetic increase in bioavailability of intracutaneously applied substances. Skin Pharmacol. Physiol. 2014;27(5):276-282. https://doi.org/10.1159/000360545
49. Liu L. Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins. Protein Cell. 2018;9(1):15-32. https://doi.org/10.1007/s13238-017-0408-4
50. Xu K., Lee F., Gao S. [et al.]. Hyaluronidase-incorporated hyaluronic acid-tyramine hydrogels for the sustained release of trastuzumab. J. Control. Release. 2015;216:47-55. https://doi.org/10.1016/j.jconrel.2015.08.015
51. Hill S. L., Davies A. Subcutaneous rituximab with recombinant human hyaluronidase in the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Future Oncol. 2018;14(17):1691-1699. https://doi.org/10.2217/fon-2017-0574
52. King M., Convery C., Davies E. This month’s guideline: The Use of Hyaluronidase in Aesthetic Practice (v2.4). J. Clin. Aesthet. Dermatol. 2018;11(6):E61-E68. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011868/pdf/jcad_11_6_E61.pdf. Accessed March 17, 2019.

Keywords: hyaluronidase, cosmetology, hyaluronic acid, fillers, complications, treatment

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy