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28 Reversers

Filler complications

Adverse effects following soft tissue augmentation are generally classified as early (up to 1 year) or delayed (appearing over 1 year after treatment) complications (Box 28.1). Delayed-onset reactions are almost always associated with non-biodegradable filling agents.

The most common complications result from inappropriate or too-superficial placement of the filling agent, leading to palpable or visible implants, nodule formation, beading, textural changes, bluish discoloration secondary to the Tyndall effect, and hypertrophic scarring of the treated folds. Intramuscular injection of synthetic fillers, particularly in areas of expression or excessive movement, invariably leads to lumpiness and migration of the filler. Hypersensitivity is rare but can occur with all fillers composed of foreign-body material. These reactions range from persistent itching, burning, and edema to granulomatous foreign-body reactions. A rare but serious complication is vascular compromise by compression, injury, and / or obstruction of the vessel(s), which can lead to necrosis in the glabella or nasolabial folds. Retinal embolism after intravascular injection has been reported.

Late-onset reactions to biodegradable agents usually emerge 5–6 months after treatment but can be quiescent for over a year with more permanent fillers. Indeed, late- and delayed-onset reactions have been reported to occur up to three decades after augmentation with non-biodegradable products. Late adverse effects include excess fullness or persistent nodules, granulomatous or inflammatory reactions, chronic infection, and filler migration. These complications are often the most difficult to treat, and some adverse events, such as excessive fullness or inflammatory reactions in the lips after injection with permanent fillers, cannot be adequately reversed.

It is important to note that many of the treatments aimed at resolving unwanted effects from facial augmentation are associated with their own complications and risks. In a follow-up study within the Injectable Filler Safety (IFS) study, Sperling and colleagues found that 51% of participants experienced adverse reactions to reversal procedures.


The US Food and Drug Administration (FDA) has approved hyaluronidase – a soluble protein enzyme that acts at the site of local injection to break down and hydrolyze HA – for three therapeutic indications: as an adjunct to increase the absorption and dispersion of other injected drugs, particularly retrobulbar anesthetic block in ophthalmologic surgery; for the subcutaneous infusion of fluids (hypodermoclysis), used mostly in the elderly population for mild-to-moderate dehydration and in young infants or children in whom intravenous administration is not possible; and as an adjunct for subcutaneous urography, improving the resorption of radiopaque agents.

Because hylauronidase causes more rapid spreading of subcutaneous injected agents, it has been used extensively with intravenous anesthesia and pain medicine. The addition of hyaluronidase to local anesthesia has been controversial, with some reports citing insufficient evidence or lack of efficacy, while others claim it reduces the anesthetic volume required, increases the area affected, and speeds the onset of aesthetic action. With the enzyme’s ability to reduce traumatic tissue swelling and chronic inflammation, clinicians have begun to investigate its role in the management of chronic pain. Therapeutic off-label applications in dermatology have yielded variable success for the treatment of diabetic scleredema, scleroderma, and pretibial myxedema, along with lymphedema and keloids.

Hyaluronidase in cosmetic dermatology

In 2004, different reports by Soparkar and colleagues and Lambros detailed the use of hyaluronidase to dissolve unwanted side effects after augmentation with HA in the periocular region up to 5 years after initial HA injection. Since then, hyaluronidase has gained enormous popularity among cosmetic practitioners as an off-label ‘eraser’ for HA filling agents, with a reported ability to reverse bluish Tyndall discoloration, lumps and nodules due to overfilling or improper placement, foreign-body reactions, and injection necrosis (Box 28.2).

Several reports have documented the use of hyaluronidase to resolve the slightly bluish effect secondary to the Tyndall effect, caused by too-superficial injections of HA. Brody treated a 64-year-old woman who presented with visible, slightly blue masses beneath each eye 6 weeks after superficial HA injections in the periorbital area. Most of the material disappeared within 24 hours after 75 U of intradermal hyaluronidase; reinjection of the remaining small nodules dissolved the rest of the material within 5 days. In 2006, Hirsch and colleagues reported the case of a woman who developed a large blue ‘egg’ in the subdermal space at the right nasojugal fold 4 days after HA injection. Two injections of 75 U of hyaluronidase a few days apart led to complete resolution. Similar results were reported a year later by Hirsch and colleagues in a 48-year-old woman who received an overabundance of HA for the bilateral treatment of nasojugal folds and subsequently presented with two large, blue-tinted bulbous nodules under each eye. Hyaluronidase dissolved most of the material within 72 hours (Fig. 28.1)

Brody describes a 68-year-old woman who presented with multiple warm, red, indurated nodules after augmentation with HA. Punch biopsy revealed dermal fibrosis and chronic inflammation with focal granulomatous features. Traditional management with intralesional triamcinolone acetonide, antibiotic courses of cephalexin and trimethoprim-sulfisoxazole, and multiple courses of prednisone had little sustaining effect. At 5 months, the one persistent nodule was treated with 15 U of hyaluronidase and disappeared without recurrence within 24 hours.

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