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The Effect of Hyaluronidase on Depth of Necrosis in Hyaluronic Acid Filling-Related Skin Complications

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  • Non-Surgical Aesthetic
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In this clinical study, 16 female patients with vascular compression and occlusion-related ischemia and skin necrosis after hyaluronic acid filling injection were analyzed retrospectively. Dose, timing, and efficacy of hyaluronidase use in skin necrosis are discussed.

Patients and Methods

In a total of 841 cases, aged between 18 and 60 years, hyaluronic acid filling injections were performed. All patients were followed up for 3–24 months. Filling injected areas include nasolabial (391 cases), lip (225 cases), glabella–forehead (90 cases), infraorbital (46 cases), malar region (25 cases), chin (24 cases), and nose (40 cases). Skin complications occurred in four cases during the application and in 12 cases 6–24 h after the procedure. Only palliative treatment was performed in six cases, while hyaluronidase was used in 10 cases in addition to palliative treatment. Hyaluronidase injection was performed 30 s after filling injection in four cases and 6–24 h after the injection in the remaining six cases. A total of 1500 units of hyaluronidase was applied to each case in average.


Recovery period of the patients who received palliative treatment only lasted 40–60 days. The area of necrosis was limited in these patients who did heal well only with some change of pigmentation and no obvious scar. In the patient group who received hyaluronidase in addition to palliative treatment, a large necrosis area was observed at the same time in four patients. Despite the hyaluronidase treatment in this group, recovery period was 20–90 days. The affected and necrosis areas were large. The cause of ischemia depended both on occlusion and on compression. While four patients healed with a scar, the remaining 12 patients healed without any significant scar.


Hyaluronidase injection provides earlier recovery of limited skin necrosis. Immediate hyaluronidase injection allows small damage to heal in a short time; however, it does not completely eliminate large necrosis, although it limits the necrotic area.

Level of Evidence IV

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  2. Narins RS, Jewell M, Rubin M, Cohen J, Strobos J (2006) Clinical conference: management of rare events following dermal fillers-focal necrosis and angry red bumps. Dermatol Surg 32(3):426–434

    CAS  PubMed  Google Scholar 

  3. Hirsh RJ, Cohen JL, Carruthers JD (2007) Successful management of an unusual presentation of impending necrosis following a hyaluronic acid injection embolus and a proposed algorithm for management with hyaluronidase. Dermatol Surg 33(3):357–360

    Google Scholar 

  4. King M, Convery C, Davies E (2018) This month’s guideline: the use of hyaluronidase in aesthetic practice (v2.4). J Clin Aesthet Dermatol 11(6):E61–E68

    PubMed  PubMed Central  Google Scholar 

  5. Sito G, Manzoni V, Sommariva R (2019) Vascular complications after facial filler injection: a literature review and meta-analysis. J Clin Aesthet Dermatol 12(6):E65–E72

    PubMed  PubMed Central  Google Scholar 

  6. Beleznay K, Carruthers JDA, Humphrey S, Carruthers A, Jones D (2019) Update on avoiding and treating blindness from fillers: a recent review of the world literature. Aesthet Surg J 39(6):662–674

    Article  Google Scholar 

  7. Thanasarnaksorn W, Cotofana S, Rudolph C, Kraisak P, Chanasumon N, Suwanchinda A (2018) Severe vision loss caused by cosmetic filler augmentation: case series with review of cause and therapy. J Cosmet Dermatol 17(5):712–718

    Article  Google Scholar 

  8. Loh KTD, Phoon YS, Phua V, Kapoor KM (2018) Successfully managing impending skin necrosis following hyaluronic acid filler injection, using high-dose pulsed hyaluronidase. Plast Reconstr Surg Glob Open 6(2):e1639

    Article  Google Scholar 

  9. Zhang L, Feng X, Shi H, Wu WTL, Wu S (2019) Blindness after facial filler injections: the role of extravascular hyaluronidase on intravascular hyaluronic acid embolism in the rabbit experimental model. Aesthet Surg J.

    Article  PubMed  Google Scholar 

  10. Han SW, Park MJ, Lee SH (2019) Hyaluronic acid-induced diffuse alveolar hemorrhage: unknown complication induced by a well-known injectable agent. Ann Transl Med 7(1):13

    Article  CAS  Google Scholar 

  11. Ansari ZA, Choi CJ, Rong AJ, Erickson BP, Tse DT (2019) Ocular and cerebral infarction from periocular filler injection. Orbit 38(4):322–324

    Article  Google Scholar 

  12. Chen H, Wang H, Yang Z (2018) A case of hyaluronic acid induced blindness with ophthalmoplegia and ptosis. Ophthalmic Plast Reconstr Surg 34(6):e184–e186

    Article  Google Scholar 

  13. Rivers JK, Mistry BD (2018) Soft-tissue infection caused by streptococcus anginosus after intramucosal hyaluronidase injection: a rare complication related to dermal filler injection. Dermatol Surg 44(Suppl 1):S51–S53

    Article  CAS  Google Scholar 

  14. Lee W, Oh W, Oh SM, Yang EJ (2020) Comparative effectiveness of different interventions of perivascular hyaluronidase. Plast Reconstr Surg.

    Article  PubMed  Google Scholar 

  15. Lee W, Oh W, Ko HS, Lee SY, Kim KW, Yang EJ (2019) Effectiveness of retrobulbar hyaluronidase injection in an iatrogenic blindness rabbit model using hyaluronic acid filler injection. Plast Reconstr Surg 144(1):137–143

    Article  CAS  Google Scholar 

  16. Grunebaum LD, Bogdan Allemann I, Dayan S, Bauman L (2009) The risk of alar necrosis associated with dermal filler injection. Dermatol Surg 35(Supp 2):1635–1640

    Article  CAS  Google Scholar 

  17. Ohen JL (2008) Understanding, avoiding, and managing dermal filler complications. Dermatol Surg 34:S92–S99

    Google Scholar 

  18. Vasquez RAS, Park K, Braunlich K, Aguilera SB (2019) Prolonged periorbicular edema after injection of hyaluronic acid for nasojugal groove correction. J Clin Aesthet Dermatol 12(9):32–35

    PubMed  PubMed Central  Google Scholar 

  19. Kleydman K, Cohen JL, Marmur E (2012) Nitroglycerin: a review of its use in the treatment of vascular occlusion after soft tissue augmentation. Dermatol Surg 38(12):1889–1897

    Article  CAS  Google Scholar 

  20. Yang Q, Qiu L, Yi C, Xue P, Yu Z, Ma X, Su Y, Guo S (2017) Reversible alopecia with localized scalp necrosis after accidental embolization of the parietal artery with hyaluronic acid. Aesthet Plast Surg 41(3):695–699

    Article  Google Scholar 

  21. Coleman SR (2002) Avoidance of arterial occlusion from injection of soft tissue fillers. Aesthet Surg J 22(6):555–557

    Article  Google Scholar 

  22. Woodward J (2016) Review of periorbital and upper face: pertinent anatomy, aging, injection techniques, prevention, and management of complications of facial fillers. J Drugs Dermatol 15(12):1524–1531

    PubMed  Google Scholar 

  23. Lin CH, Chiang CP, Wu BY, Gao HW (2017) Filler migration to the forehead due to multiple filler injections in a patient addicted to cosmetic fillers. J Cosmet Laser Ther 19(2):124–126

    Article  Google Scholar 

  24. Snozzi P, van Loghem JAJ (2018) Complication management following rejuvenation procedures with hyaluronic acid fillers-an algorithm-based approach. Plast Reconstr Surg Glob Open 6(12):e2061

    Article  Google Scholar 

  25. Han J, He Y, Liu K, Yang Q (2018) Necrosis of the glabella after injection with hyaluronic acid into the forehead. J Craniofac Surg 29(7):e726–e727

    Article  Google Scholar 

  26. Wang Q, Zhao Y, Li H, Li P, Wang J (2018) Vascular complications after chin augmentation using hyaluronic acid. Aesthet Plast Surg 42(2):553–559

    Article  Google Scholar 

  27. Schanz S, Schippert W, Ulmaer A, Rassner G, Fierlbeck G (2002) Arterial embolization caused by injection of hyaluronic acid (Restylane). Br J Dermatol 146(5):928–929

    Article  CAS  Google Scholar 

  28. Wattanakrai P, Jurairattanaporn N, Rojhirunsakool S, Visessiri Y, Suwanchinda A, Thanasarnaksorn W (2018) The study of histological changes of the arterial vascular structure after hyaluronidase exposure. J Cosmet Dermatol 17(4):632–636

    Article  Google Scholar 

  29. Oh B-L, Jung C, Park KH, Hong YJ et al (2014) Therapeutic intra-arterial hyaluronidase infusion for ophthalmic artery occlusion following cosmetic facial filler (hyaluronic acid) injection. Neuro-Ophthalmology 38:39–43

    Article  Google Scholar 

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Correspondence to Safvet Ors.

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Ethical approval of the retrospective clinical study was granted by the research ethics committee.

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Ors, S. The Effect of Hyaluronidase on Depth of Necrosis in Hyaluronic Acid Filling-Related Skin Complications. Aesth Plast Surg 44, 1778–1785 (2020).

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