Management of Hyaluronidase Allergies: The Importance of Specialist Evaluation

It was with great enthusiasm that we read the recent report by Currie et al entitled “The Use of Hyaluronidase in Aesthetic Practice: A Comparative Study of Practitioner Usage in Elective and Emergency Situations,” published in the June 2024 issue of Aesthetic Surgery Journal.¹ We applaud the authors for their contribution to the literature regarding the ways in which hyaluronidase is used by practitioners, particularly their insight into allergic reactions to hyaluronidase and how practitioners anticipate this concern.

As a board-certified allergist/immunologist and a plastic surgeon, we read this article with particular interest related to the potential for allergic reactions to hyaluronidase and how to respond to such an event. We wanted to highlight one important point that the authors astutely mention but is worth bringing to the forefront. Although allergic reactions to hyaluronidase are rare, the authors are correct that this is likely underreported in the aesthetic literature. It seems to be more commonly reported in the ophthalmologic literature.² The potential for cross-reactivity to Hymenoptera insects (the order of arthropods which includes stinging insects, honeybees, and vespids such as wasps, hornets, and yellow jackets) is notable, and worth taking into consideration when discussing hyaluronidase with patients. Clarifying the nature of the Hymenoptra venom allergy with the patient is important: many patients may report an “allergic reaction” in reference to large local swelling or similar cutaneous reactions that do not significantly increase the risk of future systemic reaction; true anaphylaxis is much less common.³ In cases of local or cutaneous reactions to Hymenoptera venom, the risk of future anaphylaxis to Hymenoptera sting is low and, by extension, cross-reactivity between venom allergy and hyaluronidase is unlikely to be clinically significant. Especially in emergent situations, such a low-risk history should not change management when assessing the need for hyaluronidase. Local swelling after hyaluronidase injection likewise is not necessarily indicative of a Type 1 allergy or due to cross-reactivity from the phospholipase; patients should be counseled on the possibility of localized swelling and irritation after injection.

Additionally, we would like to emphasize the value of specialty evaluation by a board-certified allergist/immunologist. We concur with the authors that it is concerning how many practitioners perform skin testing (also known as intradermal testing) prior to injection due to concern about a potential allergic reaction. Skin testing can be difficult to perform correctly and interpret without significant experience, and in almost all cases the allergen is diluted significantly prior to skin testing to a nonirritating concentration to avoid false-positives. Allergy and immunology societies specifically recommend against the routine use of skin testing if the patient has no previous history suggestive of Type I immediate hypersensitivity reaction because the skin testing for most drugs besides penicillin is not validated, and pre-emptive testing for hyaluronidase would be no exception.⁴ For patients without a consistent history, the likelihood of a false-positive result outweighs the benefit of testing otherwise and is not recommended. We have previously published recommendations for practitioners concerned about potential hyaluronidase allergy, and in general recommend evaluation by an allergist if the practitioner has significant concern about reaction to either the hyaluronidase or a concerning history of venom allergy.² In an emergency situation, such as blindness from ophthalmic artery occlusion or other highly time-sensitive clinical scenarios, treatment with hyaluronidase should not be delayed but clinicians should be prepared to recognize and treat allergic reaction should it occur.

Once again, we appreciate the authors' efforts to emphasize how hyaluronidase is used by practitioners and to highlight some concerning findings in the survey. Their research underscores the importance of interdisciplinary communication between specialties to optimize patient outcomes and minimize inappropriate or delayed treatment, particularly in emergency situations. We hope that our comments here will help with understanding the importance of allergy evaluation if a practitioner is concerned about future or potential allergic reactions, while emphasizing the need for further studies and education to promote appropriate avenues for treatment.

Disclosures

The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Funding

The authors received no financial support for the research, authorship, and publication of this article.

REFERENCES

Author notes