Reply: Intravenous Hyaluronidase with Urokinase as Treatment for Arterial Hyaluronic Acid Embolism

Sir: We would like to thank Foissac et al. for sharing their experience and their human tissue model. The model they proposed is very interesting and is also meaningful for research of various types of vascular complications. Safe and effective dosage of hyaluronidase for treating hyaluronic acid–induced vascular embolism is a long-debated problem. Sall and Férard pointed out that varying hyaluronic acid products presented different sensitivity to hyaluronidase.1 Flynn et al. demonstrated that different brands of hyaluronic acid products of the same molecular weight class also respond to hyaluronidase differently.2 Therefore, we believe that accurate dosage of hyaluronidase may vary wildly according to the hyaluronic acid product used in actual clinical cases. The diameter of the vessel, location of obstruction, and amount of intravascular hyaluronic acid could also affect the outcome of hyaluronidase treatment. Regardless of the severity of the hyaluronic acid obstruction, it is imperative to begin treatment as soon as signs of vascular embolism are discovered. Local massage could help loosen the clot, which is beneficial when performed with our proposed method. Although allergic reaction of systemic use of hyaluronidase is an issue that should be considered, the benefit of the method can be greater than damage caused by severe hyaluronic acid vascular obstruction. Pillwein et al. added high-dose hyaluronidase to chemotherapy medication for patients with brain tumors.3 According to their results, allergic reactions of systemic hyaluronidase are rare in adults, with a 2 to 3 percent occurrence rate. Should allergic reactions occur, symptoms can improve quickly with immediate discontinuation of hyaluronidase and administration of prednisolone, epinephrine, and dimethindene maleate treatment.3 Urokinase is relatively safe, provided that the patient has no contraindications. Hyaluronidase and urokinase are best used together, as formation of red thrombus can worsen the embolism. We believe our proposed method is safe and feasible when administered under strict supervision, and it might be the sole solution when hyaluronic acid embolism occurs in locations unreachable by local hyaluronidase. DISCLOSURE The authors have no financial interest to declare in relation to the content of this communication. ACKNOWLEDGMENT This research was funded by the National Natural Science Foundation of China (nos. 81272128 and 81471878) and National 863 Key Projects (no. 2014AA020705). ChengAn Chiang, M.D., Ph.D.ShuangBai Zhou, M.D., Ph.D.Kai Liu, M.D., Ph.D.Department of Plastic and Reconstructive SurgeryShanghai Ninth People’s HospitalAffiliated to School of Medicine ShanghaiJiao Tong UniversityShanghai, People’s Republic of China