Curtis, Julia A. MD; Tristani-Firouzi, Payam MD; Bowen, Anneli R. MD

To the Editor:

As the use of cosmetic fillers has increased, so have adverse reactions to these substances. The diagnosis of adverse reaction patterns can be difficult for several reasons. Reactions may be delayed for months to years and substances may have migrated from the original injection site. Patients may not be aware of substances used in fillers, or they may be reluctant to share this information. Additionally, unfamiliar histopathological patterns emerge as new substances appear in the market. Although granulomatous response is by far the most commonly reported reaction pattern, hypertrophic scarring, ulceration, infection, sterile abscess, and filler embolism have been recognized.¹ Recently, the development of xanthelasma palpebrarum of the bilateral lower eyelids after hyaluronic acid injections was reported in 2 patients.² Here, we report a case of xanthelasma palpebrarum after polymethylmethacrylate collagen injections.

A 58-year-old woman without a history of hyperlipidemia presented for evaluation of yellow plaques overlying the bilateral tear trough area (Fig. 1). The patient had Artecoll (Suneva Medical Inc, San Diego, CA), a polymethylmethacrylate collagen filler, placed 6 months previously. She noted bruising and swelling immediately after placement followed by the appearance of yellow plaques 1 month later. A punch biopsy of the right infraorbital plaque was performed that revealed collections of foam cells with small rounded nuclei in the papillary and upper reticular dermis. Deeper in the dermis and subcutaneous fat were small, uniform clear spaces surrounded by foreign body multinucleated giant cells. On higher magnification and lowering of the condenser, small, regular, nonbirefringent beads were easily visualized in the vacuoles (Fig. 2). Her fasting lipid panel was normal.

Figure 1

Figure 2

Artecoll is a biphasic filler composed of 30- to 50-μm polymethylmethacrylate smooth permanent microspheres suspended 1:3 in 3.5% degradable bovine collagen suspension with 0.3% lidocaine.³ It has been used in Europe under the name Artecoll since 1994 and as Artefill since 2006 in the United States for the correction of deep facial wrinkles.⁴ It is now available as Bellafill and is Food and Drug Administration-approved for use in the nasolabial folds and atrophic acne scars on the cheeks for patients aged over 21 years.⁵ The filler must be placed in the deep reticular dermis just above the subcutaneous fat for the proper effect.⁴ The microspheres stimulate fibroblasts to replace atelocollagen by the body's own connective tissue after 3 months.⁴

Previous reported adverse effects to Artecoll include allergic reactions, telangiectasias, hypertrophic scarring, as well as foreign body granuloma formation.^4,6,7 Histologically, foreign body granulomas are nodular or diffuse and may involve the dermis, subcutaneous fat, or even skeletal muscle. Within these, foreign body granulomas are uniform, clear vacuoles that contain the polymethylmethacrylate beads. Rudolph et al⁷ note that polymethylmethacrylate microspheres are transparent and nonpolarizable but can be seen under phase-contrast microscopic conditions within vacuoles those appear empty with traditional light microscopy. These authors visualized the polymethylmethacrylate beads by lowering the condenser of the microscope, a simple, yet underutilized, way to use phase-contrast microscopy in daily practice. Silicone granulomas show similar microscopic features to polymethylmethacrylate microsphere granulomas but can be distinguished because the vacuoles in silicone granulomas are devoid of foreign material by polariscopic or phase-contrast methods.

The occurrence of xanthelasma palpebrarum after Artecoll (polymethylmethacrylate collagen) implantation has not been previously reported; however, D'Acunto et al² described 2 patients who developed xanthelasma palpebrarum after hyaluronic acid injections. As a possible mechanism, the authors note that in animal models, hyaluronic acid is known to bind extravasated low-density lipoproteins, and this complex is internalized by macrophages that can subsequently transform into foam cells.^2,8 Other reports have implicated the role of trauma in the development of xanthelasma, specifically related to contact with boiling oil.⁹ Our patient reported bruising and swelling shortly after the Artecoll injections that transitioned directly to the clinical appearance of xanthelasma, which suggests a causal relationship, although the mechanism is unclear. We suspect the development of xanthelasma may be a response to the trauma, edema, and inflammation of injection into an anatomically predisposed site (periorbital) or possibly the binding of Artecoll filler material to extravasated lipids, as previously proposed for hyaluronic acid-induced xanthelasma. Our patient was pleased with the removal of most of the xanthelasma by this technique and elected to undergo a therapeutic punch excision on her left infraorbital xanthelasma.

Xanthelasma palpebrarum should be recognized as a potential adverse event following tear trough injection of the dermal fillers: Artecoll (polymethylmethacrylate collagen) and hyaluronic acid.

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