What are the guidelines for elective use of hyaluronidase (enzyme) in a patient with a history of allergies and previous reactions?

Elective Hyaluronidase Use in Patients with Allergy History

Hyaluronidase can be used electively in patients with a history of allergies, but is absolutely contraindicated in those with bee sting/venom allergy due to cross-reactivity, and skin testing should be performed before elective use in patients with other allergy histories to minimize the risk of hypersensitivity reactions. 1

Absolute Contraindication: Bee Venom Allergy

• Do not administer hyaluronidase to any patient with a known bee sting or bee venom allergy due to documented cross-reactivity between bee venom antigens and hyaluronidase enzyme. 1, 2
• This contraindication applies to all elective uses including dermatologic surgery, filler correction, and anesthetic adjuncts. 1

Pre-Treatment Allergy Assessment Algorithm

For patients without bee venom allergy:

• Perform intradermal skin testing (prick testing) when allergy to hyaluronidase is in question or when the patient has a history of other drug allergies or atopic conditions. 1, 3
• Skin testing is recommended before use because most allergic responses to hyaluronidase are immediate hypersensitivity reactions (Type I), which can be predicted by skin testing. 3, 4
• Important caveat: Some patients experience delayed allergic reactions (Type IV hypersensitivity), which skin tests may not predict, so monitoring for 7+ days post-injection is necessary even with negative skin testing. 3, 5

Safety Profile in Elective Settings

Frequency of allergic reactions:

• Allergic reactions (urticaria or angioedema) occur in less than 0.1% of patients receiving hyaluronidase according to FDA labeling. 6
• A 2024 survey of 264 practitioners found that 92% had never observed an acute reaction to hyaluronidase, and only 1% had ever observed anaphylaxis. 7
• Most allergic reactions are local (erythema, swelling, pain at injection site) rather than systemic. 6, 3, 5

Common non-allergic adverse effects:

• Mild local injection site reactions (erythema, pain, swelling, itching) are the most frequently reported adverse effects. 6
• Hyaluronidase may enhance adverse reactions associated with co-administered drugs. 6

Elective Clinical Applications Where Hyaluronidase May Be Used

Dermatologic surgery:

• Hyaluronidase may be added to local infiltration anesthesia to enhance diffusion and reduce tissue contour distortion, though insufficient data exist to support routine use in dermatologic surgery. 1
• The typical dose is 7.2 IU mixed with local anesthetic for skin surgeries. 1

Hyaluronic acid filler correction:

• Hyaluronidase is the standard treatment for dissolving unwanted hyaluronic acid filler depots or correcting complications from HA filler injections. 3, 8
• A sufficient amount must be injected close to the filler location for effective dissolution. 3

Chemotherapy extravasation:

• For vinca alkaloid extravasation, 1-6 mL of 150 U/mL hyaluronidase solution is injected through the existing IV line (usual dose: 1 mL hyaluronidase per 1 mL extravasated drug). 1

Important Drug Interactions and Incompatibilities

Absolute incompatibilities (do not co-administer):

• Furosemide, benzodiazepines, phenytoin, dopamine, and alpha-agonists are incompatible with hyaluronidase. 6
• Lidocaine 2% with epinephrine 1:100,000 or 1:200,000 is incompatible due to sodium metabisulfite content. 6

Drugs requiring dose adjustment:

• Patients taking salicylates (aspirin), corticosteroids, estrogens, or antihistamines may require larger amounts of hyaluronidase for equivalent dispersing effect, as these drugs render tissues partially resistant to hyaluronidase action. 6

Patient Counseling Requirements

• Inform patients that hyaluronidase increases dispersion and absorption of fluids or injected drugs. 6
• Advise that mild local injection site reactions (redness, swelling, itching, pain) may occur. 6
• Warn that rare anaphylactic-like reactions and allergic reactions (hives) have been reported. 6
• Obtain consent before injecting HA filler that discusses the possible future requirement for hyaluronidase (74% of practitioners always obtain this consent). 7

Common Pitfalls to Avoid

• Never assume negative allergy history means no risk: Even patients with previous uneventful hyaluronidase exposure can develop allergic reactions on subsequent administrations. 4
• Do not confuse local allergic reactions with infection: Focal erythematous plaques at injection sites continuing for 7 days can represent delayed hypersensitivity rather than infection (patients are typically afebrile with normal blood tests). 5, 4
• Avoid using hyaluronidase to enhance local anesthetic spread without understanding the trade-off: While it hastens onset and reduces swelling, it also shortens duration of action and increases systemic absorption/reaction risk. 6