Intravenous Hyaluronidase with Urokinase as Treatment for Arterial Hyaluronic Acid Embolism

Sir: We read with great interest the article by Chiang et al.1 on hyaluronic acid injection published recently, concerning the topic of complications of arterial embolism. The authors present an interesting rat model analyzing tissue necrosis and flap survival after hyaluronic acid intraarterial injection with very promising results, using combination of hyaluronidase and urokinase to treat arterial hyaluronic acid embolism. The use of injectable fillers is not new and has been expanding in recent years. However, injection indications and guidelines need to be followed to minimize the risk of complication. A 35-year-old, nonsmoking female patient presented to our service after hyaluronic acid injection on the glabella following botulinum toxin injection on the same spot 1 month previously. The hyaluronic acid injection had been injected 1 hour before the patient came to our accident and emergency department. She was scheduled for immediate hyaluronidase subcutaneously and urokinase intravenously. The patient’s history revealed that she had previously been injected with 0.25 ml of hyaluronic acid in the right supratrochlear area, which resulted in typical supratrochlear artery distribution skin ischemia, which presented as a white, demarcated area on her forehead (Fig. 1, above).Fig. 1.: (Above) Ischemia on the forehead caused by supratrochlear hyaluronic acid embolism. (Below) Twenty-four hours after treatment with hyaluronidase, urokinase, and methylprednisolone.For treatment, the patient was injected with 1 ml divided into five 0.2-ml doses of a 15-IU/ml solution of hyaluronidase (Injectable Hyaluronidase; Shanghai First Biochemical/Pharmaceutical Group, Shanghai, People’s Republic of China) administered subcutaneously in the ischemic area, and at the same time she received 2 ml of urokinase 50,000 IU/kg normal saline solution intravenously (injectable urokinase; Livzon Pharmaceutical Group, GuangZhou, People’s Republic of China). Furthermore, she started methylprednisolone, 16 mg/day, for 3 days, orally. The patient was discharged and instructed to keep her forehead warm with warm compresses regularly. At 24 hours, the color of the ischemic area changed back to normal levels (Fig. 1, below). In our opinion, a possible reason for effective treatment is that therapy started soon enough before irreversible pathophysiologic alterations appeared. Another possible reason is that hyaluronidase and urokinase were not administered intravenously as Chiang et al.1 have proposed, but instead urokinase intravenously and hyaluronidase subcutaneously. Which is the most effective way that medications should be administered in similar cases is a question that remains to be answered. Similar cases presented in the literature resulted in necrotic skin areas that needed to be débrided surgically, leaving permanent scars.2,3 Use of a few medications has been proposed in the management of arterial hyaluronic acid embolism.4,5 Because of the small number of cases in the literature, the experience on dealing with these cases is limited. Further research needs to be performed to understand the nature of this complication and pathways for treatment. The article presented by Chiang et al.1 is a positive step in this direction. DISCLOSURE The authors have no financial interest in any of the products, devices, or drugs mentioned in this communication. Leonidas Pavlidis, M.D., Ph.D.Georgia Alexandra Spyropoulou, M.D., Ph.D.Plastic Surgery Department Aspasia Deliligka, M.D., Ph.D.Department of Forensic Medicine and Toxicology Efterpi Demiri , M.D., Ph.D.Plastic Surgery DepartmentAristotle University of ThessalonikiThessaloniki, Greece