Dr Amborish Nath, Plastic surgeon

Hyaluronidase in Aesthetic Practice: A Comprehensive Review of Its Use, Safety, and Emerging Guidelines

Introduction

In recent decades, hyaluronic acid (HA) fillers have emerged as one of the most popular treatments in aesthetic medicine, celebrated for their ability to safely restore facial volume, enhance contours, and rejuvenate skin appearance. However, as with all injectable treatments, HA fillers carry risks. Complications, ranging from minor aesthetic concerns to severe vascular events, necessitate rapid and effective intervention. Central to managing these complications is the enzyme hyaluronidase (HYAL), which enzymatically dissolves HA. Despite its essential role, the clinical practice surrounding hyaluronidase administration remains surprisingly inconsistent, highlighting an urgent need for standardized guidelines.

A recent comprehensive survey-based study published in the Aesthetic Surgery Journal (Currie et al., 2024) sought to examine these inconsistencies and underscore the critical need for establishing clearer guidelines on HYAL’s storage, dosing, and administration in aesthetic practice.

Hyaluronidase: An Essential but Misunderstood Enzyme

Hyaluronidase is an enzyme capable of breaking down hyaluronic acid, an essential component of dermal fillers. It acts rapidly, providing clinicians with a powerful tool to address complications from filler placement, such as vascular occlusion, misplacement, or undesirable aesthetic outcomes. However, despite its importance, significant uncertainties surround its optimal use, leaving practitioners to rely on anecdotal evidence and personal experience rather than universally agreed-upon standards.

Currently, HYAL use is off-label for dissolving HA fillers, which only intensifies the ambiguity surrounding best practices (Goodman et al., 2020).

Clinical Applications and Challenges

The primary uses of HYAL include:

• Treatment of vascular occlusion following HA filler injection.
• Management of delayed inflammatory nodules.
• Correction of aesthetic complications such as overfilling or asymmetry.

Despite these clear indications, variability remains rampant, creating significant safety concerns. The recent survey of practitioners across Australia, New Zealand, and other countries revealed extensive disparities in the way HYAL is employed, highlighting several key areas where consensus is urgently needed.

Current Practitioner Usage Patterns: A Revealing Survey

Currie and colleagues conducted a detailed survey among 264 aesthetic practitioners, including dermatologists, plastic surgeons, aesthetic physicians, nurses, and dentists, alongside a consensus panel of 20 experts. The survey illuminated significant variations across several critical dimensions: dosage, storage, patient management protocols, skin testing practices, and emergency response strategies.

Dosage and Injection Protocols: Inconsistency Rules

One of the most troubling findings was the lack of agreement regarding HYAL dosage and injection frequency during emergencies, particularly in vascular occlusions—a serious complication that can result in tissue necrosis or blindness if inadequately managed.

Dosages varied widely among practitioners:

• Vascular occlusion treatment dosages ranged from 150 IU/ml up to 1500 IU/ml.
• Injection intervals also varied, from every 15 minutes to hourly, with no clear majority consensus on the ideal approach.

Similarly, in the treatment of delayed inflammatory nodules, lower concentrations of HYAL were generally preferred, but considerable inconsistencies persisted. Most practitioners utilized doses ranging between 150 to 750 IU/ml, with intervals of administration varying widely from 24 hours to two weeks.

Such disparities highlight the critical need for clear dosage guidelines to ensure optimal patient outcomes.

Skin Testing Controversies

Another significant finding of the study was the widespread confusion and inconsistency around skin testing prior to HYAL administration.

• 29% of respondents never performed skin testing, whereas 25% always did.
• The expert consensus panel largely advocated against skin testing, considering it unnecessary and potentially dangerous in an emergency context.

The British Society of Allergy and Clinical Immunology (BSACI) supports this cautious approach, noting that skin tests for drug allergy should only be conducted in specialized allergy centers. The rationale is that such testing may cause unnecessary delays during emergencies like vascular occlusions, potentially leading to worse patient outcomes (Krishna et al., 2011).

Hyaluronidase Allergy: Misconceptions and Realities

While practitioner concern over HYAL-related allergies is common, the actual incidence of severe allergic reactions, including anaphylaxis, is exceptionally low. According to the survey results:

• Only 8% had seen any acute reaction requiring medical intervention, and only around 1% had witnessed anaphylaxis.

Furthermore, allergic reactions primarily occurred with animal-derived HYAL products rather than human recombinant HYAL, underscoring the safer profile of the latter (Knowles et al., 2021). These results suggest that practitioner concerns about HYAL allergenicity are often exaggerated, potentially leading to hesitation or inappropriate clinical decisions in emergency situations.

Cross-reactivity Concerns with Bee and Wasp Allergies

Interestingly, the consensus group’s comfort level with administering HYAL in patients with known bee or wasp sting allergies was significantly higher (91%) compared to general respondents (52%). Research indicates an increased allergy risk to HYAL in patients with Hymenoptera venom allergies, suggesting caution—but not absolute contraindication (Bailey et al., 2014). Such nuances should be clearly communicated to practitioners through evidence-based guidelines to avoid confusion or delay in critical emergency scenarios.

Storage and Stability: An Overlooked Safety Factor

Storage of HYAL is another critical yet overlooked factor, as highlighted by Currie et al. The manufacturer’s guidelines often recommend immediate use post-reconstitution. However, nearly half of the survey respondents admitted storing reconstituted HYAL refrigerated for up to four weeks. Practitioners also differed significantly in their storage practices:

• 45% stored HYAL at 4°C (refrigerated),
• 47% at room temperature.

This variability raises legitimate concerns about the enzyme’s stability, potency, and safety when administered weeks after preparation. Such practices underline the need for formal recommendations from professional societies, ensuring consistent, safe, and effective treatment outcomes.

Ethical and Legal Considerations: Informed Consent

A surprisingly overlooked issue is the consent for potential use of HYAL before initial filler administration. Although most practitioners (74%) regularly obtained informed consent, nearly 20% reported rarely or never discussing this with patients. Considering that HA injections inherently carry a risk of severe complications that necessitate HYAL intervention, neglecting informed consent raises significant ethical and medico-legal concerns.

A standardized approach mandating explicit patient consent and thorough education on potential complications and emergency treatments should be implemented to safeguard both patients and practitioners legally and ethically.

Steps Toward Standardized Guidelines

Given the evident gaps revealed by Currie et al.’s survey, the aesthetic medical community must urgently prioritize the development of evidence-based guidelines. These guidelines should clearly outline:

• Optimal dosing protocols tailored to clinical scenarios (vascular complications, nodules, elective dissolutions).
• Recommendations on storage conditions and reconstitution practices.
• Clarification on skin testing protocols and management strategies for patients at risk of allergic reactions.
• Procedures for emergency response, emphasizing the importance of immediate treatment without unnecessary delays due to allergy testing.

Multidisciplinary Collaboration

The survey underscores the benefit of a multidisciplinary approach. Insights from dermatologists, plastic surgeons, nurses, ophthalmologists, and allergy specialists could provide a robust foundation for creating practical and universally applicable guidelines.

Training and Continuing Education

Regular training sessions and updates should be integrated into professional development programs, ensuring practitioners stay informed about the latest protocols, best practices, and emergency management strategies. Increasing practitioner competence through structured, regular training could mitigate the current variability in HYAL administration and improve patient safety significantly.

Future Research Directions

Currie and colleagues highlight key areas where future research is essential:

• Establishing optimal HYAL storage conditions and duration after reconstitution.
• Clarifying precise dosage ranges for specific complications.
• Understanding HYAL’s long-term impacts on skin and soft tissue integrity.
• Exploring the true incidence and risk factors associated with allergic responses to HYAL.

Conclusion

The use of hyaluronidase in aesthetic medicine remains invaluable but significantly undermined by the absence of clear, standardized guidelines. The survey by Currie et al. provides compelling evidence of widespread inconsistency and uncertainty, potentially compromising patient outcomes.

By addressing these gaps through rigorous research, collaborative consensus building, and education, the aesthetic community can ensure that HYAL is used effectively, efficiently, and safely—ultimately raising standards across aesthetic practice.

My personal take:

Before even starting a practice of injectables, i would stock my clinic with Hyaluronidase in case of requirements during emergencies (HA embolisation and vascular occlusion)

I would have an allergy testing done in the 1st visit itself and have it documented

Reference

Currie, E., Granata, B., Goodman, G., et al. (2024). The Use of Hyaluronidase in Aesthetic Practice: A Comparative Study of Practitioner Usage in Elective and Emergency Situations. Aesthetic Surgery Journal, 44(6), 647–657. DOI: 10.1093/asj/sjae009.

---

Did this spark insights or thoughts about your practice? Share your experiences and perspectives in the comments!