Making the Case for Low-Dose Hyaluronidase Treatment for Nodules

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Hyaluronidase has been used to reverse adverse effects in dermal fillers (e.g. necrosis, nodules, granuloma). In some way, the dosage of the enzyme could also affect the treatment of adverse effects. High-dose hyaluronidase has been the practice by many clinicians in reversing dermal filler adverse effects. Alam et al. (2018) argues that a low-dose would be as effective and could make corrections when necessary. So what then should be protocol?

Alam et al. argued that one of the advantages of applying low-dose hyaluronidase was the possibility of correcting the volume of the dermal filler. In their study, the fillers used were Juvederm XC and Restylane-L, and applied the low-dose method on nodules.

However, since the dose of hyaluronidase is low, treatment is done in weekly intervals, and there was a 4-month follow-up. The researchers reported no adverse effects. Clinicians may need to use more hyaluronidase when dealing with Juvederm XC due to concentration and cross-linking.

Findings:

  • Nodules were less noticeable over time

  • 9.0 units of hyaluronidase worked best for Restylane-L, while 1.5 units worked for Juvederm XC -- as per physician perception

  • As for participant perception, the effects of 9 Units seemed much better for both dermal fillers

In another research, Menon et al. (2010) used a low dosage of hyaluronidase to treat over corrections. This study is one of the first to examine low-dose of hyaluronidase. Other than this and Alam et al.’s work, there are no more research on the efficacy of the low-dose method.

Literature on reversing hyaluronic acid focus more on the usage of high-dose hyaluronidase. Researchers recommend high-dose hyaluronidase to treat necrosis (Cohen et al., 2015) or ischemia (Hwang, 2016).

Immediate treatment is also needed for ischemia and scarring (Hwang, 2016). In the case of necrosis, immediate high-dose hyaluronidase is imperative (Cavallini et al., 2016).

Such is the case, hyaluronidase could lead to an allergic reaction (Kim et al., 2015) as well. Thus, it is best to conduct allergy testing may be necessary.

While the topic is not prevalent in literature, low-dose hyaluronidase could exhibit efficacy in the long run. Alam and his team could prompt new investigations in applying lower doses of hyaluronidase to prevent allergies and to treat other adverse effects with hyaluronidase with lower doses. The study could open new avenues to examine low-dose hyaluronidase with other dermal fillers and for other adverse effects.

References:

Artzi, O., Loizides, C., Verner, I., & Landau, M. (2016). Resistant and Recurrent Late Reaction to Hyaluronic Acid–Based Gel. Dermatologic Surgery, 42(1), 31-37. doi:10.1097/DSS.0000000000000562

Cavallini, M., Trocchi, G., & Gazzola, R. (2016). The use of Hyaluronidases in Aesthetic Medicine: Indications, technique and complications. Aesthetic Medicine, 2(4), 31-35. Retrieved from http://www.lamedicinaestetica.it/images/files/files-portale/AE_4_2016.pdf#page=31

Chesnut, C. (2017). Restoration of Visual Loss With Retrobulbar Hyaluronidase Injection After Hyaluronic Acid Filler. Dermatologic Surgery, 44(3). doi:10.1097/dss.0000000000001237

Cohen, J. L., Biesman, B. S., Dayan, S. H., Delorenzi, C., Lambros, V. S., Nestor, M. S., . . . Sykes, J. (2015). Treatment of Hyaluronic Acid Filler–Induced Impending Necrosis With Hyaluronidase: Consensus Recommendations. Aesthetic Surgery Journal, 35(7), 844-849. doi:10.1093/asj/sjv018

Hwang, C. (2016). Periorbital injectables: Understanding and avoiding complications. Journal of Cutaneous and Aesthetic Surgery, 9(2), 73. doi:10.4103/0974-2077.184049

Khan, T. T., Colon-Acevedo, B., Mettu, P., Delorenzi, C., & Woodward, J. A. (2016). An Anatomical Analysis of the Supratrochlear Artery: Considerations in Facial Filler Injections and Preventing Vision Loss. Aesthetic Surgery Journal, 37(2), 203-208. doi:10.1093/asj/sjw132

Landau, M. (2015). Hyaluronidase Caveats in Treating Filler Complications. Dermatologic Surgery, 41. doi:10.1097/dss.0000000000000555

Loh, K. T., Phoon, Y. S., Phua, V., & Kapoor, K. M. (2018). Successfully Managing Impending Skin Necrosis following Hyaluronic Acid Filler Injection, using High-Dose Pulsed Hyaluronidase. Plastic and Reconstructive Surgery - Global Open, 6(2), E1639. doi:10.1097/gox.0000000000001639

Reversing Hyaluronic Acid Filler Injections With Hyaluronidase

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It's possible that at some point in your cosmetic clinical career - for whatever reason - you might need to try and minimize or reverse the results of a HA filler injection.

Patient's have been know to 'freak out' when the big lips that they thought they wanted are actually the ones they see in the mirror. It can be something of a challenging conversation.

Fortunately, there's Hyaluronidase, and some researchers have found that even small amounts were effective in dissolving hyaluronic acid fillers.

In a study by Juhász et al. (2017), the researchers found that small amounts of hyaluronidase were effective in treating complications from hyaluronic acid (HA). The study focused on the degradation of HA, and different periods to see its efficacy. Randomized study participants were injected with a HA injectable; Juvederm Ultra XC, Juvederm Ultra Plus, Juvederm Voluma XC, Restylane Silk, Belotero Balance, Restalyne Lyft (Perlane), and Restylane-L. Then patients were injected with saline or 20 or 40 unites of hyaluronidase and monitored over 14 days. 

The results showed that haluronidase was effecive in degrading the filler and that there was no decernable difference between the 20 and 40 unit injections. (So you don't have to use much.)

Here are the findings:

  • Day 1 Post-Injection: JUVEDERM ULTRA PLUS, JUVEDERM VOLUMA XC, RESTYLANE SILK, BELOTERO BALANCE, RESTALYNE LYFT (PERLANE)
  • Day 2 Post-Injection: JUVEDERM ULTRA PLUS, JUVEDERM VOLUMA XC, RESTYLANE SILK, BELOTERO BALANCE, RESTALYNE LYFT (PERLANE), RESTYLANE-L
  • Day 3: JUVEDERM ULTRA PLUS, JUVEDERM VOLUMA XC, RESTYLANE SILK, BELOTERO BALANCE, RESTYLANE-L
  • Day 4: JUVEDERM ULTRA PLUS, JUVEDERM VOLUMA XC, RESTYLANE SILK, BELOTERO BALANCE, RESTALYNE LYFT (PERLANE)
  • Week 1 Post-Injection: JUVEDERM ULTRA PLUS, JUVEDERM VOLUMA XC, RESTYLANE SILK, BELOTERO BALANCE
  • Week 2 Post-Injection: Everything except JUVEDERM ULTRA XC

The researchers also found that dermal fillers like Juvederm Ultra Plus and Restylane-L had a higher concentration, which took longer to dissolve with hyaluronidase, while Belotero Balance was the quickest to degrade.

Previous studies have only given their recommendations on the number units of hyaluronidase, based on experience or training. However the 2017 study presented their recommended dosage in degrading the HA. The authors suggest that a 20 unit injection of hyaluronidase is an effective way to degrade the HA.

One possible complication from using hyaluronidase is an allergic reaction. For patients who incur any allergies from hyaluronidase, there are other treatments for HA complications.

It's highly advisable to conduct allergy testing for patients before administering the dermal filler, which could reduce the incidence of complications. Ablon (2016) reminds medical providers in cosmetic medicine to observe the tissue as the dermal filler is injected.