ARTICLE | AESTHETIC SOLUTIONS |
Hyaluronidase specificity Hyaluronidase
D-glucuronic acid COOH O OH OH CH2 COOH O OH OH OH OH D-glucuronic acid HN O N-Acetyl-D-glucosamine Hyaluronic acid Granuloma
Hyaluronic acid is a polymer formed by thousands of alternative units of N-acetylglucosamine and glucuronic acid. It is therefore a heteropolysaccharide. Hyaluronic acid is usually used in the cross-linked form, mainly with the aim to correct volume; the face, lips, hands and body can be treated. Any excess of product gives an unaesthetic result, but fortunately, slowly disappears within a few months owing to the activity of natural hyaluronidase enzymes. As hyaluronic acid is a natural polymer, widely present in human tissues and especially the skin, it is usually not recognised as a foreign body. In certain cases, nevertheless, the body considers injected hyaluronic acid (or some impurities of it) as a foreign molecule, and can induce an immune reaction that can appear after even after a number of years, as well as the formation of granuloma. In this case, the symptoms of inflammation are visible (rubor, tumour, dolor, calor) and sustained. The granuloma may persist for a long time before natural resolution or surgical extraction. Native hyaluronidase, present in the dermis, will sometimes have no access to the hyaluronic acid when it is considered a foreign body, and the product could be slowly eliminated through an inflammatory reaction and phage cells.
Hyaluronidase Hyaluronidase is a natural enzyme produced by the body, which decreases fibrosis and, in some cases, symptoms of inflammation. It helps spermatozoids to penetrate the ovule, for example. On the other hand, some cancer cells also use hyaluronidase to aid diffusion into tissues. Some animals inject hyaluronidase together with venom in order to increase the diffusion of toxins. Hyaluronidase is able to cut the long hyaluronic acid polymer into oligomers, which will no longer be
32 ❚ April/May 2012 |
prime-journal.com CH3 O OH O O OH O N-Acetyl-D-glucosamine
Allergy to hyaluronidase Hyaluronidase has been used for many years. The lead author first used the product in 1977 in order to undo cellulitis fibrosis. It is also widely used in anaesthesia as it helps local anaesthetic to spread to the tissues. Reports of sensitivity or allergy to hyaluronidase are rare, and are usually related to ophthalmic surgery using retrobulbar or peribulbar anaesthetia. An immediate allergic reaction (anaphylactic shock) has been described in one case of epidurally administred hyaluronidase1
. However,
most patients will usually develop an allergy only after having received at least one injection in the past, allowing a sensitivity to develop and express during further injections. Nevertheless, it is theoretically possible that any type of allergy could occur during the first injection, making a test before every injection of hyaluronidase necessary. Allergic reactions are considered as either type I or
Hyaluronidase is able to cut
the long hyaluronic acid polymer into oligomers, which will no longer be considered a foreign body by the immune system.
type IV hypersensitive reactions, having an immediate onset (anaphylactic shock), an intermediate (after a few hours), or a delayed onset (a few days or weeks after the injection). Type I immediate reactions are particularly marked by oedema, rash, itching, pain, respiratory distress, nausea, vomiting, and hypotension. These reactions require immediate medical treatment. Immediate reactions such as anaphylactic shock, general urticaria and respiratory distress, usually appear after intravascular injection, and have been described during hyaluronidaseÐ chemotherapeutic agent injections for cancer. Clinical symptoms of the allergic reaction are efficiently treated with corticoid injection, eventually associated with adrenaline and
antihistamine. Symptoms of low blood pressure should be immediately treated using a pressor agent. After repeated subcutaneous injection, the occurrence
of a transitory delayed or intermediate (24 hours) reaction is not uncommon and takes the appearance of large, reddish, swollen and itchy macules that disappear after a few days without any treatment. Topical corticoid cream can also be used during the active period of allergic reaction. Furthermore, hyaluronidase injections have to be entirely avoided in such cases. Intradermal tests are more sensitive than prick tests
and are important to gauge a potential allergy to hyaluronidase. Prick tests and blood immunoglobulin E (IgE) levels are not always sufficient to predict an
HN CH3 O CH2 OH O OH
considered a foreign body by the immune system. The activity of the enzyme is very specific, hydrolysing the links between N-acetyl-D-glucosamine and D-glucuronic acid. There is, therefore, no way
to hope that
hyaluronidase could aid in cases of excess injections of another kind of molecule (e.g. polylactic acid, collagen, silicone), or in cases of immune reactions to these products. Hyaluronidase is usually presented in a lyophilised form, 1500 IU to be mixed with a sterile saline solution. It does not contain conservative products and must be used immediately after reconstitution.
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