Bovine-derived Hase (Hase-5 and Hase-3 [Hylase Dessau, Riemer Pharma, GmbH, Germany]) produced severe erythema and burning immediately after injection (Table 6). Mild erythema persisted after 24 hours, and mild edema was also observed. Hase-3 also caused moderate erythema immediately after injection of which little remained after 24 hours. As hypothesized, the human recombinant Hase did not produce any inflammatory response (Table 5).
Differences among HA-containing dermal filler gel products include HA particle size, total HA concentration, the extent of HA cross-linking, and the degree of hydration, resulting in gels with different elasticity and viscosity.5 These properties will affect the way they behave in the skin including the amount of structural support or lift they provide. In addition to affecting the performance and durability of each product, these factors will also affect their susceptibility to degradation by Hase.30,34
Few studies have assessed the stability of HA products when exposed to Hase. One in vitro study assessed the stability of HA products exposed to Hase by measuring the formation or concentration of N-acetyl-D-glucosamine, one of the components of the HA disaccharide units.35 The results showed that the sensitivity of HA gels to the effect of enzyme degradation decreased as a function of the extent of HA cross-linking. Another in vitro study demonstrated degradation times for several HA filler products increased with increasing HA molecular weights.36
The study demonstrates that HA-3 (Juvéderm Voluma, Allergan, Inc., Irvine, CA) (Vycross) is not an easily dissolvable product, probably requiring the greatest concentration of Hase and longer time for dissolution. Clinical implication suggesting that injections should be conservative in the amount injected at 1 setting. This suggests that small bolus not larger than 0.2 mL should be applied. HA-3 (Hylacross) and HA-5 (Cohesive Polydensified Matrix) have comparable sensitivity to Hase, but HA-4 is more durable because it is a volumizer and has greater cross-linking.
The results of this study demonstrate the wide range in sensitivity of HA products to the action of Hase. Similarly, there is a wide range in enzyme activity among Hase products. Overall, the ovine Hase product Hase-1 displayed the greatest activity against the range of HA products. Dermatologists who routinely use these products should familiarize themselves with their different characteristics. These differences may avoid errors in treating HA-related adverse events across various HA products because there may be a 3-fold difference in the amount of Hase required to degrade the same volume of HA. Different Hase products demonstrate different activity because the extent of cross-linking and the molecular weight of HA of each product have a significant effect on resistance to degradation.
A safety issue is the tolerability of Hase. Hase-1 proved to be the most potent and effective Hase, but eosinophilic reactions may be expected at doses greater than 150 IU. Dose higher than 300 U may induce inflammation and eosinophil recruitment, thereby increasing the risk of Type-1 hypersensitivity reactions such as urticaria and angioedema.33 It would be prudent to observe at-risk patients at risk of at least 2 hours after treatment with Hase. Endogenous HA becomes diminished at Hase-1 doses greater than 300 IU.
Differences in HA particle size, total HA concentration, the extent of HA cross-linking, and the degree of hydration result in HA dermal filler gel products with different degrees of elasticity and viscosity. These properties also determine the sensitivity of these products to degradation by Hase. There are also substantial differences in the activity of available Hase products. Dermatologists should familiarize themselves with these product differences.
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