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Foreign body granulomas after injection of Bio-alcamid for lip augmentation
Available online at www.sciencedirect.com
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356 – 359 www.elsevier.com/locate/amjoto
Foreign body granulomas after injection of Bio-alcamid for lip augmentation Sharon Akrish, DDSa , Dan Dayan, DMDa , Shlomo Taicher, DMDb,c , Iris Adam, DMDb , Rafael M. Nagler, MD, DMD, PhDd,⁎ a
Department Oral Pathology and Medicine, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel b Department of Oral and Maxillofacial Surgery, Sheba Medical Center, Tel Hashomer c Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel d Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Received 20 March 2008
Abstract
Bio-alcamid is one of the newest agents on the market for soft tissue augmentation. Seven studies were documented in the medical literature that examined the safety of Bio-alcamid (Polymekon, Brindisy, Italy); all reported no cases of tissue migration, foreign body granulomas, allergenicity, or interference with the control of cell proliferation. On 2 separate occasions, a woman who had recently undergone lip augmentation presented at our hospital with submucosal nodules of the lip. Histologic examination revealed multiple foreign body–type granulomas composed of giant cells, epithelioid cells, and chronic inflammation of the lip. Efforts to produce a cosmetic material that fulfills all the criteria as an “ideal” agent has not yet been found because all injectable foreign agents have the potential to induce adverse reactions. Caution must be exercised in all cases and the risks explained to the patient before its use. © 2009 Elsevier Inc. All rights reserved.
1. Introduction During the past 15 years, remarkable progress in cosmetic surgery has been made due to the increasing demand for aesthetic enhancement. Various materials have been introduced, some based on natural materials such as collagen or polysaccharide and some on synthetic materials such as silicone or polymethacrylate (Table 1). The rate of complications in these materials varies; for instance, whereas Aquamed (Ocala, FL), a polyacrylamide-hydrogel-based filler is now banned in some parts of the world due to its
⁎ Corresponding author. Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Tel.: +972 77 344 2003; fax: +972 4 654 1295. E-mail address: [email protected] (R.M. Nagler). 0196-0709/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2008.07.001
negative side effects, other materials such as Bio-alcamid (Polymekon, Brindisy, Italy) have been considered safe [1]. Bio-alcamid, one of the newest agents on the market for soft tissue augmentation, was introduced in 1999 as a synthetic, nonresorbable cosmetic filler composed of 96% unpyrogenic water and 4% alkylimide-amide group [2,3]. Bio-alcamid, known as an endoprosthesis, is an intermediate between an injectable filler and a common prosthesis. It is used for treatment of posttraumatic injuries; postsurgical scars; lipodystrophy; common cosmetic defects such as lip, cheek, bone, and chin hypovolumetry; and serious congenital facial and body microgenia [4]. All 7 animal or human studies conducted to measure the safety of the product and documented in the medical literature concluded that Bio-alcamid had a high degree of biocompatibility. There were no cases of tissue migration, foreign body granulomas, allergenicity, or interference with the control of cell proliferation [2-8]. We present the first 2 case reports of patients who experienced a foreign body granuloma and
S. Akrish et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356–359
357
Table 1 Most commonly used fillers for soft tissue augmentation Agent
Main ingredients
Hyaluronic acid
Mammalian polysaccharide Injectable bovine Bovine collagen collagen Injectable liquid Dimethylsiloxanes silicone Artecoll Polymethacrylate in bovine collagen Bioplastique Vulcanized methylsiloxane in bovine collagen Gore-tex Synthetic polymer
Foreign body reaction
Natural/synthetic combination
Permanent/ nondegradable
Silicone content
Collagen content
FDA approved
Yes
Natural
No
No
No
No
Yes
Natural
No
No
Yes
1981
Yes
Synthetic
No
Yes
No
Yes
Combination
Yes
No
Yes
Outlawed its use in 1999 No
Yes
Combination
Yes
Yes
Yes
No
Yes
Synthetic
Yes
No
No
Yes
FDA indicates Food and Drug Administration.
material migration after being injected with Bio-alcamid for lip augmentation. 2. Case reports 2.1. Case 1 In 2005, a 41-year-old female presented to our hospital with a chief complaint of 2 nodules in her upper lip at the vermillion border. Clinically, the nodules were pink, measuring approximately 0.3 × 0.4 × 0.4 cm, smooth, and firm (Fig. 1). The patient was asymptomatic. The patient admitted that she had been treated with the cosmetic agent Bio-alcamid for lip augmentation 1 year before developing the nodules. There were no other cosmetic agents injected at that site. The mass was excised and sent for histopathologic examination. Histologically, the soft tissue sample consisted of multiple foreign body–type granulomas composed of giant cells, epithelioid cells, and chronic inflammation within a loose connective tissue
Fig. 1. Clinical presentation of the nodules in the patient's upper lip at the vermillion border. Nodules were pink, measuring approximately 0.3 × 0.4 × 0.4 cm, smooth, and firm.
matrix. The granulomas surrounded collections of a blue/ gray fibrillar foreign material that contained numerous vacuoles. Immunohistochemistry included CD68 and vimentin in which CD68 highlighted the numerous giant cells surrounding the foreign material within a matrix of mesenchymal tissue (Fig. 2). 2.2. Case 2 In 2005, a 43-year-old female presented to our hospital complaining of an annoying sensation on her upper lip. Although not clinically visible, a submucosal nodule was felt when the lip was palpitated. The patient admitted that she had been treated with Bio-alcamid for upper lip augmentation. No other cosmetic agents have been injected in that area. The nodule was excised and submitted for histopathologic examination. The mass measured 0.4 × 0.5 × 0.5 cm on gross examination. Histologically, the soft tissue sample consisted of multiple foreign body–type granulomas
Fig. 2. Histologic examination of the soft tissue sample demonstrating multiple foreign body–type granulomas composed of giant cells, epithelioid cells, and chronic inflammation within a loose connective tissue matrix. The granulomas surrounded collections of a blue/gray fibrillar foreign material that contained numerous vacuoles.
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S. Akrish et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356–359
Fig. 3. Electron microscopy analysis that identified a mass devoid of biological characteristics, limited by a pseudomembrane. In other areas, the material appeared to have a fibrillar structure and was surrounded by a reactive process including connective tissue and collagen fibers.
composed of giant cells, epithelioid cells, and chronic inflammation within a loose connective tissue matrix. The granulomas surrounded collections of a blue/gray fibrillar foreign material that contained numerous vacuoles. Immunohistochemistry included CD68 and vimentin. CD68 highlighted the numerous giant cells surrounding the foreign material within a matrix of mesenchymal tissue. We also performed an electron microscopy analysis and identified the material described above as a mass devoid of biological characteristics, limited by a pseudomembrane. In other areas, the material appeared to have a fibrillar structure (Fig. 3) and was surrounded by a reactive process including connective tissue and collagen fibers. 3. Discussion The primary indication for soft tissue augmentation is upper lip enhancement [9]. To be useful in soft tissue augmentation, a product must be biocompatible, nontoxic, noncarcinogenic, nonallergenic, and nonmigrating [5,6]. The risk of allergenicity and immunogenicity from naturally derived fillers encouraged manufacturers to search for synthetic compounds such as Bio-alcamid, a cosmetic filler composed of 96% unpyrogenic water and 4% alkylimideamide group [3,4]. These chemicals are responsible for its unique characteristics including stability of the polymer, elasticity, and high resistance to water. After subcutaneous injection, the material is surrounded by a fibrous capsule, separating it from the host tissue, and allowing the agent to be removed in the future, should it be necessary [3,8]. In addition to cosmetic enhancement, it is useful in serious congenital defects such as Poland syndrome, postoperative traumas, and lipodystrophy [4]. There have been 7 reports published in which research testing assesses the safety of the product. In the largest series
of tests, 2000 patients injected with Bio-alcamid were observed for 3 years in a multicenter trial led by hospitals and universities in Italy and other countries. Of these 2000 patients, only 3 experienced an adverse effect, all staphylococcus infections. There were no cases of material migration or foreign body granulomas. It was concluded that “it is an almost ideal prosthesis even for the treatment of broad aesthetic defects” [4]. A second study, conducted on animals, conducted a variety of tests to assess the safety of Bio-alcamid, including tests for cytotoxicity, mutagenicity, skin irritation, sensitization, and subcutaneous implant testing. The in vitro cytotoxicity test showed no reduction in cell viability or inhibition of cell growth due to toxic effects. Sensitization and skin irritation tests failed to show any cutaneous reactions, including erythema, edema, and necrosis. The subcutaneous implant test showed an inflammatory response for 14 days followed by formation of a fibrous capsule that surrounded the implanted material. No foreign body granulomas or necrosis was observed. It was concluded that “Bio-alcamid is a nonresorbable material that did not induce foreign body granulomas” [5]. A third study examined 50 patients who were injected with Bio-alcamid in the facial area to create tissue volume. Ultrasound and ultrasound-tomography studies were conducted, and each failed to demonstrate foreign body granuloma reactions either at the site or distant from the site of the injected material. It was concluded that “Bioalcamid be used whenever fat injections do not appear to have a long-lasting effect or are insufficient in creating the desired volume” [8]. The effects of Bio-alcamid on cell proliferation were examined in the fourth study to test its biocompatibility. There was no interference with the control of cell proliferation or significant changes in cell morphology. It was concluded that “Bio-alcamid should be considered totally biocompatible as far as the effects on cell proliferation and cell functions are concerned” [2]. Tissues after skin implantation with Bio-alcamid were examined under the electron microscope in another study to identify the fine morpholo-functional interactions that occur at the interface between Bio-alcamid and the adjacent tissues. Fibrosis was limited to the formation of the capsule around the implant, a normal response of host tissue to a foreign body. No inflammation was seen at the site. It was concluded that “Bio-alcamid is highly compatible with human skin” [6]. Another study examined 73 patients having lipodystrophy who were injected with Bio-alcamid and observed for 3 years. Lipodystrophy is a serious side effect for patients with HIV who receive combined retroviral drug therapy. It was concluded that “no implant dislocation, implant migration, granuloma, allergic reaction, or intolerance was recorded” [3]. The seventh study examined 53 patients with HIV-related facial fat atrophy where Bio-alcamid replaced the sub-
S. Akrish et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356–359
cutaneous fat. The results showed no degradation of the material or chronic inflammation. It was concluded that “Bio-alcamid is an efficient, safe product for the correction of HIV-related facial atrophy” [7]. There are a variety of options on the market for lip augmentation other than Bio-alcamid. The most popular include hyaluronic acid [10], injectable bovine collagen, and injectable liquid silicone as well as permanent nondegradable materials such as polymethyl methacrylate (Artecoll, San Diego, CA), polydimethylsiloxane (Bioplastique, Bioplasty, S. Paul, MN), and polytetrafluoroethylene (Gore-tex, W.L. Gore and Associates, FlagStaff, AZ) [11]. These agents are composed of synthetic materials, naturally derived products, or a combination of both. Materials that contain naturally derived products go through a process whereby the material is autodigested through a naturally occurring event and eventually replaced by a matrix of native collagen and a fibrous capsule. Examples include Bioplastique, Artecoll, and injectable bovine collagen [9,12,13]. This fibrous capsule prevents either migration or absorption of the material [13]. In addition, skin testing is required before their use due to the risk of an allergic reaction [9,13]. Materials that contain silicone such as injectable liquid silicone or Bioplastique may induce a unique type of foreign body granuloma termed siliconoma [9,12]. These granulomas have been misdiagnosed as “well-differentiated liposarcoma” due to their histopathologic similarities [14,15]. Overabuse of the silicone agent and consequent use of impure forms encouraged the Food and Drug Administration to outlaw its use in 1999 [3]. The public interest in cosmetic agents for beauty enhancement is on the rise. As such, there are frenzied efforts to produce a cosmetic material that fulfills all the criteria as an “ideal” agent. To date, this agent has not been found because all injectable foreign agents have the potential to induce adverse reactions. Caution must be exercised in all cases and the risks explained to the patient before its use.
359
References [1] Amin SP, Marmur ES, Goldberg DJ. Complications from injectible polyacrylamide gel, a new nonbiodegradable soft tissue filler. Dermatol Surg 2004;30:1507-13. [2] Pacini S, Ruggiero M, Cammarota N, et al. Bio-alcamid, a novel prosthetic polymer, does not interfere with morphological and functional characteristics of human skin fibroblasts. Plast Reconstr Surg 2003;111:489-91. [3] Protopapa C, Sito G, Caporale D, et al. Bio-alcamid in drug induced lipodystrophy. J Cosmet Laser Ther 2003;5:226-30. [4] Pacini S, Ruggiero M, Morucci G, et al. Bio-alcamid: a novelty for reconstructive surgery. It J Anat Embryol 2002;107:209-14. [5] Ramires P, Miccoli M, Panzarini E, et al. In vitro and in vivo biocompatibility evaluation of a polyalkylimide hydrogel for soft tissue augmentation. J Biomed Mater Res B Appl Biomater 2004;72B:230-8. [6] Formigli L, Zecchi S, Protopapa C, et al. Bio-alcamid: an electron microscope study after skin implantation. Plast Reconstr Surg 2004; 113:1104-6. [7] Casavantes LC, Izabal JM. Stability, tolerance and safety of Bioalcamid, an injectible endoprosthesis gel for correction of facial lipoatrophy. Dermatologia, Cosmetica, Medica y Quirurgica 2004; 2:1. [8] Claoue BL, Rabineau P. The polyalkylimide gel: experience with Bioalcamid. Semin Cutan Med Surg 2004;23:236-40. [9] Klein A, Elson M. The history of substances for soft tissue augmentation. Dermatol Surg 2000;26:1096-105. [10] Fernandez-Acenero M, Zamora E, Borbujo J. Granulomatous foreign body reaction against hyaluronic acid: report of a case after lip augmentation. Dermatol Surg 2003;29:1225-6. [11] Hubmer M, Hoffman C, Popper H, et al. Expanded polytetrafluoroethylene threads for lip augmentation induce foreign body granulomatous reaction. Plast Reconstr Surg 1999;103:1277-9. [12] Hoffmann C, Schuller-Petrovic S, Soyer P, et al. Adverse reactions after cosmetic lip augmentation with permanent biologically inert implant materials. J Am Acad Dermatol 1999;40:100-2. [13] Rudolph C, Soyer H, Schuller-Petrovic S, et al. Foreign body granulomas due to injectible aesthetic microimplants. Am J Surg Pathol 1999;23:113-7. [14] Lombardi T, Samson J, Plantier F, et al. Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. J Oral Pathol Med 2004;33:115-20. [15] Maly A, Regev E, Meir K, et al. Tissue reaction to liquid silicone simulating low-grade liposarcoma following lip augmentation. J Oral Pathol Med 2004;33:314-6.
American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356 – 359 www.elsevier.com/locate/amjoto
Foreign body granulomas after injection of Bio-alcamid for lip augmentation Sharon Akrish, DDSa , Dan Dayan, DMDa , Shlomo Taicher, DMDb,c , Iris Adam, DMDb , Rafael M. Nagler, MD, DMD, PhDd,⁎ a
Department Oral Pathology and Medicine, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel b Department of Oral and Maxillofacial Surgery, Sheba Medical Center, Tel Hashomer c Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel d Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Received 20 March 2008
Abstract
Bio-alcamid is one of the newest agents on the market for soft tissue augmentation. Seven studies were documented in the medical literature that examined the safety of Bio-alcamid (Polymekon, Brindisy, Italy); all reported no cases of tissue migration, foreign body granulomas, allergenicity, or interference with the control of cell proliferation. On 2 separate occasions, a woman who had recently undergone lip augmentation presented at our hospital with submucosal nodules of the lip. Histologic examination revealed multiple foreign body–type granulomas composed of giant cells, epithelioid cells, and chronic inflammation of the lip. Efforts to produce a cosmetic material that fulfills all the criteria as an “ideal” agent has not yet been found because all injectable foreign agents have the potential to induce adverse reactions. Caution must be exercised in all cases and the risks explained to the patient before its use. © 2009 Elsevier Inc. All rights reserved.
1. Introduction During the past 15 years, remarkable progress in cosmetic surgery has been made due to the increasing demand for aesthetic enhancement. Various materials have been introduced, some based on natural materials such as collagen or polysaccharide and some on synthetic materials such as silicone or polymethacrylate (Table 1). The rate of complications in these materials varies; for instance, whereas Aquamed (Ocala, FL), a polyacrylamide-hydrogel-based filler is now banned in some parts of the world due to its
⁎ Corresponding author. Department of Oral and Maxillofacial Surgery and Oral Biochemistry Laboratory, Rambam Medical Center, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Tel.: +972 77 344 2003; fax: +972 4 654 1295. E-mail address: [email protected] (R.M. Nagler). 0196-0709/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.amjoto.2008.07.001
negative side effects, other materials such as Bio-alcamid (Polymekon, Brindisy, Italy) have been considered safe [1]. Bio-alcamid, one of the newest agents on the market for soft tissue augmentation, was introduced in 1999 as a synthetic, nonresorbable cosmetic filler composed of 96% unpyrogenic water and 4% alkylimide-amide group [2,3]. Bio-alcamid, known as an endoprosthesis, is an intermediate between an injectable filler and a common prosthesis. It is used for treatment of posttraumatic injuries; postsurgical scars; lipodystrophy; common cosmetic defects such as lip, cheek, bone, and chin hypovolumetry; and serious congenital facial and body microgenia [4]. All 7 animal or human studies conducted to measure the safety of the product and documented in the medical literature concluded that Bio-alcamid had a high degree of biocompatibility. There were no cases of tissue migration, foreign body granulomas, allergenicity, or interference with the control of cell proliferation [2-8]. We present the first 2 case reports of patients who experienced a foreign body granuloma and
S. Akrish et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356–359
357
Table 1 Most commonly used fillers for soft tissue augmentation Agent
Main ingredients
Hyaluronic acid
Mammalian polysaccharide Injectable bovine Bovine collagen collagen Injectable liquid Dimethylsiloxanes silicone Artecoll Polymethacrylate in bovine collagen Bioplastique Vulcanized methylsiloxane in bovine collagen Gore-tex Synthetic polymer
Foreign body reaction
Natural/synthetic combination
Permanent/ nondegradable
Silicone content
Collagen content
FDA approved
Yes
Natural
No
No
No
No
Yes
Natural
No
No
Yes
1981
Yes
Synthetic
No
Yes
No
Yes
Combination
Yes
No
Yes
Outlawed its use in 1999 No
Yes
Combination
Yes
Yes
Yes
No
Yes
Synthetic
Yes
No
No
Yes
FDA indicates Food and Drug Administration.
material migration after being injected with Bio-alcamid for lip augmentation. 2. Case reports 2.1. Case 1 In 2005, a 41-year-old female presented to our hospital with a chief complaint of 2 nodules in her upper lip at the vermillion border. Clinically, the nodules were pink, measuring approximately 0.3 × 0.4 × 0.4 cm, smooth, and firm (Fig. 1). The patient was asymptomatic. The patient admitted that she had been treated with the cosmetic agent Bio-alcamid for lip augmentation 1 year before developing the nodules. There were no other cosmetic agents injected at that site. The mass was excised and sent for histopathologic examination. Histologically, the soft tissue sample consisted of multiple foreign body–type granulomas composed of giant cells, epithelioid cells, and chronic inflammation within a loose connective tissue
Fig. 1. Clinical presentation of the nodules in the patient's upper lip at the vermillion border. Nodules were pink, measuring approximately 0.3 × 0.4 × 0.4 cm, smooth, and firm.
matrix. The granulomas surrounded collections of a blue/ gray fibrillar foreign material that contained numerous vacuoles. Immunohistochemistry included CD68 and vimentin in which CD68 highlighted the numerous giant cells surrounding the foreign material within a matrix of mesenchymal tissue (Fig. 2). 2.2. Case 2 In 2005, a 43-year-old female presented to our hospital complaining of an annoying sensation on her upper lip. Although not clinically visible, a submucosal nodule was felt when the lip was palpitated. The patient admitted that she had been treated with Bio-alcamid for upper lip augmentation. No other cosmetic agents have been injected in that area. The nodule was excised and submitted for histopathologic examination. The mass measured 0.4 × 0.5 × 0.5 cm on gross examination. Histologically, the soft tissue sample consisted of multiple foreign body–type granulomas
Fig. 2. Histologic examination of the soft tissue sample demonstrating multiple foreign body–type granulomas composed of giant cells, epithelioid cells, and chronic inflammation within a loose connective tissue matrix. The granulomas surrounded collections of a blue/gray fibrillar foreign material that contained numerous vacuoles.
358
S. Akrish et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356–359
Fig. 3. Electron microscopy analysis that identified a mass devoid of biological characteristics, limited by a pseudomembrane. In other areas, the material appeared to have a fibrillar structure and was surrounded by a reactive process including connective tissue and collagen fibers.
composed of giant cells, epithelioid cells, and chronic inflammation within a loose connective tissue matrix. The granulomas surrounded collections of a blue/gray fibrillar foreign material that contained numerous vacuoles. Immunohistochemistry included CD68 and vimentin. CD68 highlighted the numerous giant cells surrounding the foreign material within a matrix of mesenchymal tissue. We also performed an electron microscopy analysis and identified the material described above as a mass devoid of biological characteristics, limited by a pseudomembrane. In other areas, the material appeared to have a fibrillar structure (Fig. 3) and was surrounded by a reactive process including connective tissue and collagen fibers. 3. Discussion The primary indication for soft tissue augmentation is upper lip enhancement [9]. To be useful in soft tissue augmentation, a product must be biocompatible, nontoxic, noncarcinogenic, nonallergenic, and nonmigrating [5,6]. The risk of allergenicity and immunogenicity from naturally derived fillers encouraged manufacturers to search for synthetic compounds such as Bio-alcamid, a cosmetic filler composed of 96% unpyrogenic water and 4% alkylimideamide group [3,4]. These chemicals are responsible for its unique characteristics including stability of the polymer, elasticity, and high resistance to water. After subcutaneous injection, the material is surrounded by a fibrous capsule, separating it from the host tissue, and allowing the agent to be removed in the future, should it be necessary [3,8]. In addition to cosmetic enhancement, it is useful in serious congenital defects such as Poland syndrome, postoperative traumas, and lipodystrophy [4]. There have been 7 reports published in which research testing assesses the safety of the product. In the largest series
of tests, 2000 patients injected with Bio-alcamid were observed for 3 years in a multicenter trial led by hospitals and universities in Italy and other countries. Of these 2000 patients, only 3 experienced an adverse effect, all staphylococcus infections. There were no cases of material migration or foreign body granulomas. It was concluded that “it is an almost ideal prosthesis even for the treatment of broad aesthetic defects” [4]. A second study, conducted on animals, conducted a variety of tests to assess the safety of Bio-alcamid, including tests for cytotoxicity, mutagenicity, skin irritation, sensitization, and subcutaneous implant testing. The in vitro cytotoxicity test showed no reduction in cell viability or inhibition of cell growth due to toxic effects. Sensitization and skin irritation tests failed to show any cutaneous reactions, including erythema, edema, and necrosis. The subcutaneous implant test showed an inflammatory response for 14 days followed by formation of a fibrous capsule that surrounded the implanted material. No foreign body granulomas or necrosis was observed. It was concluded that “Bio-alcamid is a nonresorbable material that did not induce foreign body granulomas” [5]. A third study examined 50 patients who were injected with Bio-alcamid in the facial area to create tissue volume. Ultrasound and ultrasound-tomography studies were conducted, and each failed to demonstrate foreign body granuloma reactions either at the site or distant from the site of the injected material. It was concluded that “Bioalcamid be used whenever fat injections do not appear to have a long-lasting effect or are insufficient in creating the desired volume” [8]. The effects of Bio-alcamid on cell proliferation were examined in the fourth study to test its biocompatibility. There was no interference with the control of cell proliferation or significant changes in cell morphology. It was concluded that “Bio-alcamid should be considered totally biocompatible as far as the effects on cell proliferation and cell functions are concerned” [2]. Tissues after skin implantation with Bio-alcamid were examined under the electron microscope in another study to identify the fine morpholo-functional interactions that occur at the interface between Bio-alcamid and the adjacent tissues. Fibrosis was limited to the formation of the capsule around the implant, a normal response of host tissue to a foreign body. No inflammation was seen at the site. It was concluded that “Bio-alcamid is highly compatible with human skin” [6]. Another study examined 73 patients having lipodystrophy who were injected with Bio-alcamid and observed for 3 years. Lipodystrophy is a serious side effect for patients with HIV who receive combined retroviral drug therapy. It was concluded that “no implant dislocation, implant migration, granuloma, allergic reaction, or intolerance was recorded” [3]. The seventh study examined 53 patients with HIV-related facial fat atrophy where Bio-alcamid replaced the sub-
S. Akrish et al. / American Journal of Otolaryngology–Head and Neck Medicine and Surgery 30 (2009) 356–359
cutaneous fat. The results showed no degradation of the material or chronic inflammation. It was concluded that “Bio-alcamid is an efficient, safe product for the correction of HIV-related facial atrophy” [7]. There are a variety of options on the market for lip augmentation other than Bio-alcamid. The most popular include hyaluronic acid [10], injectable bovine collagen, and injectable liquid silicone as well as permanent nondegradable materials such as polymethyl methacrylate (Artecoll, San Diego, CA), polydimethylsiloxane (Bioplastique, Bioplasty, S. Paul, MN), and polytetrafluoroethylene (Gore-tex, W.L. Gore and Associates, FlagStaff, AZ) [11]. These agents are composed of synthetic materials, naturally derived products, or a combination of both. Materials that contain naturally derived products go through a process whereby the material is autodigested through a naturally occurring event and eventually replaced by a matrix of native collagen and a fibrous capsule. Examples include Bioplastique, Artecoll, and injectable bovine collagen [9,12,13]. This fibrous capsule prevents either migration or absorption of the material [13]. In addition, skin testing is required before their use due to the risk of an allergic reaction [9,13]. Materials that contain silicone such as injectable liquid silicone or Bioplastique may induce a unique type of foreign body granuloma termed siliconoma [9,12]. These granulomas have been misdiagnosed as “well-differentiated liposarcoma” due to their histopathologic similarities [14,15]. Overabuse of the silicone agent and consequent use of impure forms encouraged the Food and Drug Administration to outlaw its use in 1999 [3]. The public interest in cosmetic agents for beauty enhancement is on the rise. As such, there are frenzied efforts to produce a cosmetic material that fulfills all the criteria as an “ideal” agent. To date, this agent has not been found because all injectable foreign agents have the potential to induce adverse reactions. Caution must be exercised in all cases and the risks explained to the patient before its use.
359
References [1] Amin SP, Marmur ES, Goldberg DJ. Complications from injectible polyacrylamide gel, a new nonbiodegradable soft tissue filler. Dermatol Surg 2004;30:1507-13. [2] Pacini S, Ruggiero M, Cammarota N, et al. Bio-alcamid, a novel prosthetic polymer, does not interfere with morphological and functional characteristics of human skin fibroblasts. Plast Reconstr Surg 2003;111:489-91. [3] Protopapa C, Sito G, Caporale D, et al. Bio-alcamid in drug induced lipodystrophy. J Cosmet Laser Ther 2003;5:226-30. [4] Pacini S, Ruggiero M, Morucci G, et al. Bio-alcamid: a novelty for reconstructive surgery. It J Anat Embryol 2002;107:209-14. [5] Ramires P, Miccoli M, Panzarini E, et al. In vitro and in vivo biocompatibility evaluation of a polyalkylimide hydrogel for soft tissue augmentation. J Biomed Mater Res B Appl Biomater 2004;72B:230-8. [6] Formigli L, Zecchi S, Protopapa C, et al. Bio-alcamid: an electron microscope study after skin implantation. Plast Reconstr Surg 2004; 113:1104-6. [7] Casavantes LC, Izabal JM. Stability, tolerance and safety of Bioalcamid, an injectible endoprosthesis gel for correction of facial lipoatrophy. Dermatologia, Cosmetica, Medica y Quirurgica 2004; 2:1. [8] Claoue BL, Rabineau P. The polyalkylimide gel: experience with Bioalcamid. Semin Cutan Med Surg 2004;23:236-40. [9] Klein A, Elson M. The history of substances for soft tissue augmentation. Dermatol Surg 2000;26:1096-105. [10] Fernandez-Acenero M, Zamora E, Borbujo J. Granulomatous foreign body reaction against hyaluronic acid: report of a case after lip augmentation. Dermatol Surg 2003;29:1225-6. [11] Hubmer M, Hoffman C, Popper H, et al. Expanded polytetrafluoroethylene threads for lip augmentation induce foreign body granulomatous reaction. Plast Reconstr Surg 1999;103:1277-9. [12] Hoffmann C, Schuller-Petrovic S, Soyer P, et al. Adverse reactions after cosmetic lip augmentation with permanent biologically inert implant materials. J Am Acad Dermatol 1999;40:100-2. [13] Rudolph C, Soyer H, Schuller-Petrovic S, et al. Foreign body granulomas due to injectible aesthetic microimplants. Am J Surg Pathol 1999;23:113-7. [14] Lombardi T, Samson J, Plantier F, et al. Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. J Oral Pathol Med 2004;33:115-20. [15] Maly A, Regev E, Meir K, et al. Tissue reaction to liquid silicone simulating low-grade liposarcoma following lip augmentation. J Oral Pathol Med 2004;33:314-6.