Complications of permanent fillers

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27 Complications of permanent fillers

Chad L. Prather, Luitgard G. Wiest

Summary and Key Features

• Permanent fillers comprise mostly synthetic materials that cause collagen deposition via fibroplasia as their mechanism of action

• Permanent fillers are better at facial volumizing and deep structural augmentation than at ‘line filling’

• Silicones, polyalkylimides, polyacrylamides, polymethylmethacrylate, and acrylic hydrogels are the most common permanent fillers worldwide

• All cosmetic fillers, whether temporary or permanent, may induce adverse reactions

• Permanent filler complications may be due to the injection itself, injector-dependent variables, or host tissue and filler interactions

• Permanent filler complications are difficult to treat since the product will not dissipate, but rather remains in vivo

• Foreign-body granulomas and late-onset granulomas are the most challenging permanent filler complications to treat

• Late-onset granulomas are sometimes due to biofilms from bacteria introduced at the time of injection

• Effective treatments of granulomas must target bacterial etiologies and host immune response mechanisms

• Invasive and scarring treatments such as surgery should be reserved and used after more conservative treatments have failed

Introduction

Injectable facial fillers have become a cornerstone of aesthetic medicine over the past two decades. Although soft tissue augmentation using industrial-grade silicones can be traced to early last century, widespread adoption of injectable fillers began in the 1980s with the advent of bovine collagen. Since the 1990s, soft tissue augmentation in order to fill lines and volumize or recontour the face has surged to become the second most popular non-surgical aesthetic procedure in North America and a widespread one beyond. Based on the axiom that an aged facial appearance is due in some part to dermal, subcutaneous, and osseous atrophy that naturally occurs over time, injectable facial fillers offer the ability to replace lost volume and restore youthful proportions, providing a foundation for facial rejuvenation. While resurfacing, relaxing, and redraping procedures help round out the facial cosmetic toolbox, aesthetic physicians now recognize the syringe as a mainstay of their armamentarium.

As with certain other non-surgical aesthetic modalities, facial filling is a product-driven procedure. Beyond an adroit injection technique, judicious use of the appropriate product in the proper location is a prerequisite to success. To know the art of injection, one must know the products, and the products vary significantly. In 2010 more than 200 fillers from over 60 manufacturers worldwide were available for tissue augmentation. Although some share characteristics that may predict a similar clinical response or comparable side effect profile, inappropriate substitution with a dissimilar product, particularly by a novice injector or non-core aesthetic provider, invites complications and ultimately patient dissatisfaction and compromises patient safety.

Products (Box 27.1, Table 27.1)

Fillers may be divided broadly into temporary and permanent categories. Temporary fillers are typically biologically derived products that are eventually broken down in vivo after a period of a few months to a few years. This category includes collagens and hyaluronic acids (HAs), the most predominant fillers worldwide. In contrast, permanent fillers comprise mostly synthetic materials that have an in vivo, biodynamic mechanism of action, causing collagen deposition via fibroplasia. For this reason permanent fillers are better at facial volumizing and deep structural augmentation than at ‘line filling’, which is best accomplished with temporary fillers. It is important to note that ‘permanence’ refers to a lack of degradation of the in vivo material over time rather than to a ‘permanent’ cosmetic result. Once placed, permanent fillers do remain in the skin and subcutaneous tissues enduringly without significant product loss. In contrast, permanent aesthetic results are seldom possible owing to continued tissue volume loss and other factors associated with the aging face. Nevertheless, duration of correction is more extensive than with temporary fillers. As such, permanent fillers are less ‘forgiving’. Experience and precise technique are required in order to achieve favorable outcomes.

Table 27.1 Selected permanent fillers by category and composition

Category	Branded product	Composition
Liquid injectable silicone	Silikon-1000^®	Purified polydimethylsiloxane polymer
Liquid injectable silicone	Adatosil-5000^®	Purified polydimethylsiloxane polymer
Other ‘silicones’	Adulterated and unknown products	Variable and often unknown
Polyalkylimide gels (hydrophilic)	Bio-Alcamid^®	3% or 4% polyalkylimide gel in 97% or 96% sterile water
Polyacrylamide gels (hydrophilic)	Amazingel^®	Polyacrylamide gel in sterile water
Polyacrylamide gels (hydrophilic)	Aquamid^®	2.5% polyacrylamide gel in 97.5% sterile water
Polymethylmethacrylate (hydrophobic)	Arteplast^® (first generation)	30–42 µm PMMA microspheres in a gelatin carrier
	Artecoll^® (second generation)	30–50 µm PMMA microspheres in a bovine collagen carrier
	Artefill^® (third generation)	30–50 µm PMMA microspheres in a bovine collagen carrier
	Metacril^®	PMMA in carboxyglutamate
Acrylic hydrogel (hydroxyethyl-methacrylate / ethylmethacrylate) (hydrophobic)	Dermalive^®	45–65 µm polygonal fragments acrylic hydrogel (40%) in HA (60%)
	Dermadeep^®	80–110 µm polygonal fragments acrylic hydrogel (40%) in HA (60%)

HA, hyaluronic acid; PMMA, polymethylmetacrylate.

Silicone

Silicone is the original permanent filler, and is still widely used today. Silikon-1000^® (Alcon, Fort Worth, TX) and Adatosil-5000^® (Bausch & Lomb, Rochester, NY) are the only US Food and Drug Administration (FDA)-approved silicone products available in the USA. Although injectable silicone has been effectively employed for over 50 years, its use remains controversial owing to the historical widespread reports of complications, most of which are confounded with unknown or impure products labeled as ‘silicone’ and purified silicones injected by improper techniques. When critically evaluating silicone, the distinction must be made between modern products intended for injection (liquid injectable silicone; LIS) in contrast to adulterated or unknown products lumped under the ‘silicone’ label. LIS demonstrates a unique aptness for the correction of specific cutaneous and subcutaneous atrophies owing to its versatility, permanence, excellent cost–benefit profile, and natural texture in vivo. Furthermore, evidence continues to mount demonstrating that modern silicone oils approved by the FDA for injection into the human body may be successfully used off-label when rigorously injected according to strict protocol, which includes using the microdroplet serial puncture technique with limited per-session quantities and adequately spaced treatment sessions. In contrast, adulterated and impure silicone products, even when labeled ‘medical-grade’, are rife with complications.

Bio-Alcamid^® (Polymekon, Italy) was first launched in 2000 as an ‘endoprosthesis’ for the treatment of pectus excavatum, postoperative defects, and aesthetic use in the lips, cheeks, and nasolabial folds (Fig. 27.1). It contains a non-degradable, atoxic, non-immunogenic synthetic polyalkylimide cross-linked polymer suspended in water. Although it is approved in Europe, it is not currently approved by the FDA. Bio-Alcamid^® contains a ratio of either 3% or 4% alkylimide polymer to 97% or 96% sterile water. The product is not a particulate one, but rather a gel that is injected as a large bolus. It is meant to be injected subcutaneously rather than into the dermis. It does not require allergy testing and has been histologically shown to induce fibroplasia once implanted.

Figure 27.1 Granuloma of the nasolabial fold 4 years after injection of Bio-Alcamid^®.

Polyacrylamide gels

Polyacrylamide hydrogels contain a non-degradable, atoxic, non-immunogenic synthetic polyacrylamide cross-linked polymer suspended in water. Although polyacrylamide products listed have obtained CE marks (European conformity) for use in Europe, and are also available in Asia, none is currently approved by the FDA for use in the USA.

Aquamid^® (Contura International, Denmark) contains a 2.5% cross-linked polyacrylamide gel in 97.5% sterile water. It has been in use in Europe and worldwide since 2001, primarily for augmentation of nasolabial folds and lips, facial contouring, and for correction of HIV facial lipoatrophy (Fig. 27. 2). It is also a viscoelastic gel without particles. On histology, Aquamid^® appears as a multivacuolated non-birefringent material with a surrounding layer of thin fibrous connective tissue, macrophages, multinucleated giant cells, and lymphocytes.

Figure 27.2 Aquamid^® granuloma.

Amazingel^® (NanFeng Medical Science and Technology Development Co. Ltd, Shijiazhuang, People’s Republic of China) is an ostensibly similar product manufactured in China and available throughout Asia. Although it is readily available for underground purchase through internet distributors, it has not been extensively studied in the Western medical literature apart from other polyacrylamide products, and manufacturer’s product information is not readily available.

Polymethylmethacrylate

Polymethylmethacrylate (PMMA) is a non-resorbable, biocompatible material first synthesized in the early 1900s and used for such varied medical purposes as intraocular implants and bone cements. It was first engineered for soft tissue augmentation in the early 1980s in an attempt to provide a safe implant, with the theory that such a synthetic material might induce long-lasting tissue fibroplasia, in contrast to the temporary volume displacement seen with collagens. Currently available PMMA products are biphasic and suspended in either bovine collagen (Artefill, Suneva Medical, San Diego, CA) or carboxyglutamate (Metacril, private lab, Rio de Janeiro, Brazil).

Arteplast^® was the first-generation commercial PMMA product with 30–42 µm microspheres suspended in a gelatin carrier. It was used in Germany through the early 1990s, but was found to have a high incidence of granuloma formation within the first 18 months of implantation. Such complications were likely due to an inconsistent particle size and the presence of surface impurities found with processing methods.

Artecoll^® (Rofil Medical International, Breda, The Netherlands) (Fig. 27.3) was then introduced in 1992 as a second-generation product with an improved processing and washing method that reduced impurities. Significantly, the carrier was also reformulated, and the PMMA was suspended as a 20% product in 80% bovine collagen with 0.3% lidocaine for improved comfort. Because of the bovine collagen component, Artecoll^® requires allergy testing prior to injection. As such Artecoll^® is considered a biphasic implant, inducing augmentation through displacement with an early collagen component and later through a fibroplastic component caused by PMMA. In 1998, Artecoll^® was approved in Canada, and processing methods were further improved to reduce particle size variability, resulting in fewer incidences of late granuloma formation compared with Arteplast^®. Histology of skin biopsy specimens from areas treated with Artecoll^® show round, sharply circumscribed, translucent, non-birefringent particles, epithelioid histiocytes, multinucleated giant cells, lymphocytes, and occasional eosinophils surrounding the microspheres.

Figure 27.3 Artecoll^®.

Artefill^®, the third-generation iteration of PMMA, was further improved by enhancing the uniformity of the PMMA particle size and by eliminating nanoparticles that had plagued earlier formulations. The collagen matrix was also improved, and Artefill^® was approved by the FDA in 2006 based on safety studies performed earlier in the USA with Artecoll^®. Importantly, Artefill^® is the only permanent filler currently approved in the USA for aesthetic use. Whereas LIS is approved for intraocular implants, and thus may be used off-label for augmentation, Artefill^® may be used on-label for permanent aesthetic augmentation.

Acrylic hydrogel plus hyaluronic acid

Dermalive^® and Dermadeep^® (Dermatech, Paris, France) are biphasic permanent fillers composed of a mixture of 40% hydroxyethylmethacrylate and ethylmethacrylate particles and 60% biodegradable, fluid cross-linked, bacterially derived HA (Fig. 27.4). The acrylic particles are hydrophobic and irregularly shaped in a polygonal fashion. Dermalive^® contains acrylic particles 45–65 µm in diameter, whereas Dermadeep^® contains particles 80–110 µm in diameter. Both products are intended for injection in the deep dermis and subcutaneous regions, with the Dermadeep product indicated for deep subcutaneous injection only. As with most permanent fillers, injections into the superficial and mid-reticular dermis are not recommended. Both products were CE approved and available in Europe in 1998, but were withdrawn several years ago owing to the high incidence of complications. Neither product has ever been FDA approved for use in the USA. Histology of acrylic hydrogels in tissue reveals pseudocystic structures of different sizes and shapes containing polygonal, pink, translucent, non-birefringent foreign bodies with a surrounding granulomatous reaction of epithelioid histiocytes, multinucleated giant cells, some lymphocytes, and occasional eosinophils surround the microstructures.