Potential complications associated with temporary soft tissue fillers can be categorized by the time of onset (Box 26.2). In general, adverse events can be subdivided into acute and delayed reactions. Acute reactions are procedural or related to injection technique. They are usually transient and are manifested by erythema, edema, ecchymosis, pruritus, and pain in the first week after injection. Delayed reactions are related to the product itself, or the interaction between the filler and the host response. They are usually manifested by persistent erythema, swelling, nodules, and indurations developing months to years after. The nature of these reactions and their treatment will be summarized in this chapter.

Box 26.2

Onset of adverse events

Early (occurring up to 1 week after treatment)

Injection site reactions

Delayed (occurring from weeks to years after treatment)

Infection

Biofilm formation

Granuloma formation

Injection site reactions

The most common adverse events associated with fillers are local injection site reactions, manifested by pain, erythema, and edema. They are typically mild, localized, and transient, resolving within 4–7 days. A recent study by Brandt et al evaluating the efficacy and safety of biphasic hyaluronic acid Restylane^® and Perlane^® in the lower face revealed that the majority of patients treated with both small and large gel-particle hyaluronic acid experienced at least one injection site reaction. The reported events in decreasing order of occurrence consisted of bruising, tenderness, swelling, and redness. In another study comparing hyaluronic acid (Restylane^®) with collagen (Zyplast^®) for the treatment of nasolabial folds in contralateral sides, injection site reactions occurred at 93.5% and 90.6% of the hyaluronic acid and collagen treated sites, respectively. The bruising can be severe, especially in patients who have taken antiplatelet agents such as aspirin or non-steroidal anti-inflammatory agents, as shown in Figure 26.1.

Figure 26.1 Severe periocular ecchymosis 7 days following injection of hyaluronic acid deep into the supraperiosteal fat pads.

Pearl 2

Most patients will develop a local injection site reaction: erythema, edema, or ecchymosis. They are usually transient and resolve in the first week after injection. Make patients aware of this before injecting them.

Pain

Pain is often one of the commonly reported adverse events associated with filler agents. Pain is often attributable to hydrostatic dissection of tissue during injection, as well as the discomfort of numerous needle punctures during the implantation of the product. Certain anatomical sites such as the lips and perioral region are more sensitive as a result of increased sensory innervation of these sites. A number of techniques may be utilized to minimize the pain associated with injections. These include the use of topical anesthetics, application of ice before and after injection, and vibratory distraction. Some clinicians also utilize infraorbital and mental nerve blocks. Placement of small aliquots of lidocaine along a few points of the gingival sulcus has also been found to be beneficial in minimizing pain associated with injections of the lips. In the past 18 months, a number of fillers have begun to package the filler syringe pre-mixed with lidocaine.

Pearl 3

Pre-treatment of the site with a topical mixture of betacaine / lidocaine / tetracaine 30 minutes prior to treatment and the use ice pre-treatment can minimize pain associated with injections.

Edema and ecchymosis

Some of the most common post-procedure adverse events are bruising and swelling secondary to local trauma from the injection (Fig. 26.1). Reviewing all medications and supplements with the patient can minimize the degree of edema and ecchymosis. Avoidance of agents that inhibit coagulation is recommended, including aspirin (unless taking for ‘therapeutic’ indications) and non-steroidal anti-inflammatory medications, as well as supplements such as garlic and Ginkgo biloba that have an inhibitory effect on platelets. Other supplements such as vitamin E, fish oil, glucosamine, ginger, ginseng, green tea, and celery root can inhibit coagulation pathways and further increase bleeding and bruising. It is recommended to withhold these supplements at least 5 days prior to treatment.

Pearl 4

Avoiding anticoagulants that are not medically necessary and a thorough pre-treatment review of all supplements will minimize post-treatment ecchymosis and edema.

Bruising can often be minimized by choosing the injectable filler least likely to cause this problem. Collagen-based fillers were less likely to cause ecchymosis secondary to their inherent platelet-aggregating properties. However, they are not available at the time of this writing. Conversely, it has been suggested that hyaluronic acid fillers have an anticoagulant effect and can cause more swelling and bruising because they are structurally similar to heparin.

When bruising occurs there are a few things that can be employed to minimize the degree and duration of the ecchymosis. Some advocate supplements such as bromelain and homeopathic Arnica in reducing post-treatment ecchymosis. Bromelain been shown to decrease vascular permeability in animal models by lowering the levels of bradykinin, thereby potentially resulting in less edema, pain, and inflammation. Helenalin, an extract of Arnica, has been shown to possess anti-inflammatory effects and inhibits platelet function in vitro. Clinical studies of both these compounds have provided conflicting results, with some revealing a decrease in post-treatment bruising, whereas others show no statistical difference. Further investigations are needed to substantiate their effect. Aside from these ‘natural’ remedies, some physicians choose to minimize post-treatment ecchymosis by utilizing their vascular laser at purpuric treatment settings.