Allergic Complications of Hyaluronidase Injection: Risk Factors, Treatment Strategies, and Recommendations for Management.

BACKGROUND: Hyaluronidase is used as a reversal agent for hyaluronic acid fillers and to increase the diffusion of other medications after infiltration. Cases of hyaluronidase allergy have been described in the literature since 1984. However, it is still frequently misdiagnosed. This review aims to summarize the current literature to describe the clinical picture of hyaluronidase allergy and identify any risk factors associated with its development, as well as provide recommendations for management in plastic surgery. METHODS: A digital search of PubMed, Scopus, and Embase databases was performed by two reviewers following the PRISMA guidelines. This search identified 247 articles. RESULTS: Two hundred forty-seven articles were identified, and 37 of them met the eligibility criteria. One hundred six patients with a mean age of 54.2 years were included in these studies. History of allergy to other substances (timothy grass, egg white, horse serum, penicillin, insect bites, wasp venom, thimerosal, potassium, histamine, phenylmercuric acetate, and nickel) and allergic diseases (asthma, dermatitis, atopy, rhinitis) was reported. A large portion of the patients with a history of repeated exposure (2-4) experienced the symptoms with their second injection. Nonetheless, there was no significant association between time to allergy development and the number of exposures (P = 0.3). Treatment with steroids +/- antihistamines resulted in the rapid and predominantly complete reversal of the symptoms. CONCLUSIONS: Prior injections or sensitization by insect/wasp venom might be the primary factor associated with hyaluronidase allergy development. The time between the repeated injections is not a likely contributor to the presentation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .