Understanding, Avoiding, and Managing Dermal Filler Complications à JOEL L. COHEN,MD BACKGROUND Dermal fillers are increasingly being utilized for multiple cosmetic dermatology indications. The appeal of these products can be partly attributed to their strong safety profiles. Nevertheless, complications can sometimes occur. OBJECTIVE To summarize the complications associated with each available dermal filling agent, strategies to avoid them, and management options if they do arise. METHODS AND MATERIALS Complications with dermal fillers reported in peer-reviewed publications, prescribing information, and recent presentations at professional meetings were reviewed. Recommen- dations for avoiding and managing complications are provided, based on the literature review and the author’s experience. RESULTS Inappropriate placement or superficial placement is one of the most frequent reasons for patient dissatisfaction. Due to the reversibility of hyaluronic acid, complications from these fillers can be easily corrected. Sensitivity to any of the currently approved FDA products is quite rare and can usually be managed with anti-inflammatory agents. Infection is quite uncommon as well and can usually be managed with either antibiotics or antivirals depending on the clinical features. The most concerning complication is cutaneous necrosis, and a protocol to treat the full spectrum of this process is reviewed. CONCLUSIONS Complications with dermal fillers are infrequent, and strategies to minimize their incidence and impact are easily deployed. Familiarity with each family of soft-tissue augmentation products, potential complications, and their management will optimize the use of these agents. Dr. Cohen is a Consultant and Clinical Trial Participant for Allergan, Inc., BioForm Medical, Inc., ColBar Life- Science Ltd., Medicis Pharmaceutical Corporation. ver the past several years, a major shift in treat them. Dermal fillers are commonly categorized Othe use of dermal fillers has occurred in the by duration of effect: temporary, semipermanent cosmetic dermatology arena. The use of these (duration is often longer than 18 months but the products is growing rapidly, due in large part to exact time frame is unknown), and permanent their effectiveness and versatility, increased public options (Table 1). interest, the availability of multiple new options, and a diminishment of the social stigma surrounding Injection Site Reactions their use. Their favorable safety profiles also con- tribute to the popularity of these products.1,2 The most common adverse events associated with However, despite the impressive safety demonstrated fillers are local injection site reactions. In a ran- with these agents, complications and adverse domized, double-blind, multicenter comparison of events can occur. To ensure the best possible hyaluronic acid (Restylane, Medicis Aesthetics Inc., outcomes and greatest patient satisfaction, the der- Scottsdale, AZ) versus collagen (Zyplast, Allergan matologist who injects dermal fillers must have Inc., Santa Barbara, CA) for the treatment of naso- proper training in their use and be aware of the labial folds in contralateral sides in each patient types of unwanted effects that can occur and how to (n = 138), injection site reactions occurred at 93.5% ÃAboutSkin Dermatology and DermSurgery, PC, and Department of Dermatology, University of Colorado, Englewood, Colorado & 2008 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2008;34:S92–S99 DOI: 10.1111/j.1524-4725.2008.34249.x S92 COHEN TABLE 1. Common Dermal Fillers Temporary Bovine collagen (Zyderm, Allergan Inc., Santa Barbara, CA; Zyplast, Allergan Inc., Santa Barbara, CA) Human collagen (CosmoDerm, Allergan Inc, Santa Barbara, CA; CosmoPlast, Allergan Inc., Santa Barbara, CA) Autologous cultured fibroblasts (Isolagen, Isolagen Technologies, Paramus, NJ) Cadaveric collagen (Collagenesis, Beverly, MA; Fascian, Fascia Biosystems LLC, Los Angeles, CA; Cymetra, LifeCell Corp., Branchburg, NJ) Hyaluronic acid (Restylane, Medicis Aesthetics Inc., Scottsdale, AZ.; Hylaform, Allergan Inc., Santa Barbara, CA; Captique, Allergan Inc., Santa Barbara, CA; Juve´ derm, Allergan Inc., Santa Barbara, CA) Calcium hydroxylapatite (Radiesse, BioForm Medical Inc., San Mateo, CA) Semipermanent Poly-L-lactic acid (New-Fill/Sculptra (Dermik Laboratories, Berwyn, PA) Permanent Collagen 1 polymethylmethacrylate (Artecoll/ArteFill, Artes Medical Inc., San Diego, CA) Silicone (Adato SIL-OL 5000 [Bausch & Lomb, Rochester, NY], Silikon 1000 [Alcon Laboratories, Fort Worth, TX]) Soft-form/Gore-Tex (WL Gore & Associates, Flagstaff, AZ) (129/138) and 90.6% (125/138) of the hyaluronic injection site–related swelling or bruising for 4 to 7 acid– and collagen-treated sites, respectively.3 These days. Swelling can often be minimized by avoidance reactions were predominantly mild or moderate in of aspirin compounds (provided the patient’s cardi- intensity, lasted less than 7 days, and generally were ologist or primary physician does not deem them similar between treatments (Table 2). However, be- medically necessary [i.e., patients with a history of cause these adverse events were solicited during the heart attack, stroke, or blood clot]), nonsteroidal study solely through the use of patient diaries anti-inflammatory drugs, and many vitamin (without corroboration by physician evaluation), supplements (vitamin E, ginger, ginseng, ginkgo the rate of adverse events may be lower in routine biloba, garlic, kava kava, celery root, fish oils) for clinical practice. 7 to 10 days prior to the procedure. Patients should be informed of the likelihood of in- jection site reactions, especially in terms of swelling, Inappropriate Placement because most fillers often result in some degree of Inappropriate placement of fillers, including inject- ing too superficially, can lead to lumps of visible product or bluish bumps under the skin (Tyndall TABLE 2. Incidence of Injection Site Reactions effect) with hyaluronic acid fillers (Figure 1).4 Such Occurring with some Dermal Fillers: Results from a Randomized, Double-Blind Trial (N = 138)à reactions can, for the most part, be prevented by use of correct technique. Their occurrence, however, Reaction Restylane (%) Zyplast (%) can result in anxiety and dissatisfaction for patients, Swelling 87.0 73.9 especially in those who rely on their appearance Redness 84.8 84.8 for their livelihood or who cannot adequately Tenderness 77.5 64.5 5 Pain 57.2 42.0 camouflage the reaction. Bruising 52.2 48.6 Itching 30.4 23.9 Lumps and bumps related to superficial placement Other 24.6 23.9 can often be treated simply by local massage or by 4,5 ÃAdapted from Narins RS, Brandt F, Leyden J, et al.3 A random- aspiration or incision and drainage. If the com- ized, double-blind, multicenter comparison of the efficacy and plication is related to a hyaluronic acid product, tolerability of Restylane versus Zyplast for the correction of 5 nasolabial folds. hyaluronidase is an additional treatment option. 34:S1:JUNE2008 S93 UNDERSTANDING, AVOIDING, AND MANAGING DERMAL FILLER COMPLICATIONS Figure 2. Angioedema-type swelling and early vertical and horizontal fissures 1 hour postprocedure in a patient treated Figure 1. Inappropriate placement of fillers can lead to prod- with hyaluronic acid (Restylane) in the lips. Photograph uct visibility under the skin. Photograph courtesy of author. courtesy of Naomi Lawrence, MD. However, because of the rare risk of sensitivity to the some cases with repeated intralesional triamcinolone animal-derived hyaluronidase enzyme, a preliminary injections (starting with intralesional triamcinolone skin test should be performed prior to its use. For 10 mg/ml with subsequent increasing concentrations this test, about 3 units can be injected intradermally, of 20, 30, and 40 mg/ml progressively if needed at and the patient observed for at least 20 minutes or 3- to 4-week intervals) or the use of a pulsed dye even overnight.6 A local wheal-and-flare reaction laser. indicates a positive reaction. Hyaluronidase is available from the following sources: Amphastar If calcium hydroxylapatite (Radiesse, BioForm Pharmaceuticals (Amphadase; Rancho Cucamonga, Medical Inc., San Mateo, CA) is placed too super- CA), Ista Pharmaceuticals Inc. (Vitrase; Irvine, CA), ficially (i.e., in the mid or superficial dermis), white and several compounding pharmacies that nodules may become visible. These can usually be provide formulations that may not be as uniform treated by puncturing the nodules with a No. 11 or consistent as the two commercially available blade or needle and then expressing the contents.8 brands. Similarly, due to the thin skin in the tear trough, injection of calcium hydroxylapatite too superficially Collagen plus polymethylmethacrylate, which is in this area can result in visibility of the filler. Thus, categorized as a permanent filler due to the Lucite- tear trough injections are considered advanced like polymethylmethacrylate beads in the product, is techniques and should be performed only by those less forgiving and also can be associated with com- experienced with using fillers in this area. Migration plications if placed too superficially (Figure 2). In- of product nodules superficially in the lips can occur deed, the most common issues seen with the original despite proper placement of calcium hydroxylapatite formulation of Artecoll (Artes Medical Inc., San to deeper lip levels; this may be