Aesthetic Plastic Surgery

, Volume 44, Issue 1, pp 148–159 | Cite as

PMMA Safety for Facial Filling: Review of Rates of Granuloma Occurrence and Treatment Methods

  • Bruno Peres PaulucciEmail author
Original Article Non-Surgical Aesthetic


PMMA is composed of microspheres suspended in bovine collagen. Once injected in a dermal area, the carrier is absorbed, giving place to collagen that gives volume and maintains the spheres in the place. This process may give origin to exacerbate foreign body reaction and granuloma. The frequency of such complication is not clear. The primary objective was to review and compare the frequencies of granuloma between the published studies. The secondary aim was to compare the therapies and efficacies. The series of cases in which PMMA was used as facial filler were reviewed, and the rate of granulomas was compared; the case report studies describing those complications were also reviewed, and the therapies and outcomes were quantified. The data showed general frequency of PMMA-related complications of 4.9% and granulomas 1.9%; the incidence of granuloma was 1/2075 patients-year, and the time to development ranged from 6 to 180 months. The most used therapies were steroid, surgery or both, with satisfactory results. In conclusion, considering the actual risks and benefits of PMMA, we may affirm that it is a safe filler; doctors and patients must be conscious of potential risks when deciding for its use.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors


PMMA Granuloma Polymethylmethacrylate Complication Face Filler 


Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

For this type of study, informed consent is not required.


  1. 1.
    Greco TM, Antunes MB, Yellin SA (2012) Injectable fillers for volume replacement in the aging face. Facial Plast Surg 28(1):8–20PubMedGoogle Scholar
  2. 2.
    Cohen SR, Berner CF, Busso M, Gleason MC, Hamilton D, Holmes RE, Romano JJ, Rullan PP, Thaler MP, Ubogy Z, Vecchione TR (2006) ArteFill: a long-lasting injectable wrinkle filler material-summary of the U.S. Food and Drug Administration trials and a progress report on 4- to 5-year outcomes. Plast Reconstr Surg 118(3 Suppl):64S–76SPubMedGoogle Scholar
  3. 3.
    Alcalay J, Alkalay R, Gat A, Yorav S (2003) Late-onset granulomatous reaction to Artecoll. Dermatol Surg 29(8):859–862PubMedGoogle Scholar
  4. 4.
    Cohen SR, Berner CF, Busso M, Clopton P, Hamilton D, Romano JJ, Rullan PP, Thaler MP, Ubogy Z, Vecchione TR (2007) Five-year safety and efficacy of a novel polymethylmethacrylate aesthetic soft tissue filler for the correction of nasolabial folds. Dermatol Surg 33(Suppl 2):S222–S230PubMedGoogle Scholar
  5. 5.
    Cohen S, Dover J, Monheit G, Narins R, Sadick N, Werschler WP, Karnik J, Smith SR (2015) Five-year safety and satisfaction study of PMMA-collagen in the correction of nasolabial folds. Dermatol Surg 41(Suppl 1):S302–S313PubMedPubMedCentralGoogle Scholar
  6. 6.
    Salles AG, Lotierzo PH, Gemperli R, Besteiro JM, Ishida LC, Gimenez RP, Menezes J, Ferreira MC (2008) Complications after polymethylmethacrylate injections: report of 32 cases. Plast Reconstr Surg 121(5):1811–1820PubMedGoogle Scholar
  7. 7.
    Park TH, Seo SW, Kim JK, Chang CH (2012) Clinical experience with polymethylmethacrylate microsphere filler complications. Aesthet Plast Surg 36(2):421–426Google Scholar
  8. 8.
    Conejo-Mir JS, Sanz Guirado S, Angel Muñoz M (2006) Adverse granulomatous reaction to Artecoll treated by intralesional 5-fluorouracil and triamcinolone injections. Dermatol Surg 32(8):1079–1081PubMedPubMedCentralGoogle Scholar
  9. 9.
    Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A, Moschetti I, Phillips B, Thornton H (2011) Explanation of the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence (Background Document). Oxford Centre for Evidence-Based MedicineGoogle Scholar
  10. 10.
    Cohen SR, Holmes RE (2004) Artecoll: a long-lasting injectable wrinkle filler material: report of a controlled, randomized, multicenter clinical trial of 251 subjects. Plast Reconstr Surg 114(4):964–976PubMedGoogle Scholar
  11. 11.
    Bagal A, Dahiya R, Tsai V, Adamson PA (2007) Clinical experience with polymethylmethacrylate microspheres (Artecoll) for soft-tissue augmentation: a retrospective review. Arch Fac Plast Surg 9(4):275–280Google Scholar
  12. 12.
    Solomon P, Sklar M, Zener R (2012) Facial soft tissue augmentation with Artecoll(®): a review of eight years of clinical experience in 153 patients. Can J Plast Surg 20(1):28–32PubMedPubMedCentralGoogle Scholar
  13. 13.
    Mani N, McLeod J, Sauder MB, Sauder DN, Bothwell MR (2013) Novel use of polymethyl methacrylate (PMMA) microspheres in the treatment of infraorbital rhytids. J Cosmet Dermatol 12(4):275–280PubMedGoogle Scholar
  14. 14.
    Lemperle G, Gauthier-Hazan N, Lemperle M (1998) PMMA-microspheres (Artecoll) for long-lasting correction of wrinkles: refinements and statistical results. Aesthet Plast Surg 22(5):356–365Google Scholar
  15. 15.
    Carvalho Costa IM, Salaro CP, Costa MC (2009) Polymethylmethacrylate facial implant: a successful personal experience in Brazil for more than 9 years. Dermatol Surg 35(8):1221–1227PubMedGoogle Scholar
  16. 16.
    Karnik J, Baumann L, Bruce S, Callender V, Cohen S, Grimes P, Joseph J, Shamban A, Spencer J, Tedaldi R, Werschler WP, Smith SR (2014) A double-blind, randomized, multicenter, controlled trial of suspended polymethylmethacrylate microspheres for the correction of atrophic facial acne scars. J Am Acad Dermatol 71(1):77–83PubMedGoogle Scholar
  17. 17.
    Mills DC, Camp S, Mosser S, Sayeg A, Hurwitz D, Ronel D (2013) Malar augmentation with a polymethylmethacrylate-enhanced filler: assessment of a 12-month open-label pilot study. Aesthet Surg J. 33(3):421–430PubMedGoogle Scholar
  18. 18.
    Nácul AM (2005) Contour of the lower third of the face using an intramusculary injectable implant. Aesthet Plast Surg. 29(4):222–229Google Scholar
  19. 19.
    Carle MV, Roe R, Novack R, Boyer DS (2014) Cosmetic facial fillers and severe vision loss. JAMA Ophthalmol 132(5):637–639PubMedGoogle Scholar
  20. 20.
    Castro AC, Collares MV, Portinho CP, Dias PC, Pinto R (2007) Extensive facial necrosis after infiltration of polymethylmethacrylate. Braz J Otorhinolaryngol 73(6):850Google Scholar
  21. 21.
    da Costa Miguel MC, Nonaka CF, dos Santos JN, Germano AR, de Souza LB (2009) Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler. Int J Oral Maxillofac Surg 38(4):385–387PubMedGoogle Scholar
  22. 22.
    Faria KM, Fonseca FP, Silva WG, Silva RN, Vargas PA, de Almeida OP, Lopes MA, Santos-Silva AR (2014) Fine needle aspiration cytology in the diagnosis of perioral adverse reactions to cosmetic dermal fillers. Oral Surg Oral Med Oral Pathol Oral Radiol 117(5):e393–e395PubMedGoogle Scholar
  23. 23.
    Friedmann DP, Kurian A, Fitzpatrick RE (2016) Delayed granulomatous reactions to facial cosmetic injections of polymethylmethacrylate microspheres and liquid injectable silicone: a case series. J Cosmet Laser Ther 18(3):170–173PubMedGoogle Scholar
  24. 24.
    Gelfer A, Carruthers A, Carruthers J, Jang F, Bernstein SC (2007) The natural history of polymethylmethacrylate microspheres granulomas. Dermatol Surg 33(5):614–620PubMedGoogle Scholar
  25. 25.
    Hoffmann C, Schuller-Petrovic S, Soyer HP, Kerl H (1999) Adverse reactions after cosmetic lip augmentation with permanent biologically inert implant materials. J Am Acad Dermatol 40(1):100–102PubMedGoogle Scholar
  26. 26.
    Kadouch JA, Kadouch DJ, Fortuin S, van Rozelaar L, Karim RB, Hoekzema R (2013) Delayed-onset complications of facial soft tissue augmentation with permanent fillers in 85 patients. Dermatol Surg 39(10):1474–1485PubMedGoogle Scholar
  27. 27.
    Limongi RM, Tao J, Borba A, Pereira F, Pimentel AR, Akaishi P, Velasco e Cruz AA (2016) Complications and Management of Polymethylmethacrylate (PMMA) injections to the midface. Aesthet Surg J. 36(2):132–135PubMedGoogle Scholar
  28. 28.
    Lombardi T, Samson J, Plantier F, Husson C, Küffer R (2004) Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. J Oral Pathol Med 33(2):115–120PubMedGoogle Scholar
  29. 29.
    Quirino MR, Neves AC, Campos MS, Brandão AA, Anbinder AL (2012) Oral granuloma formation after injection of cosmetic filler. J Craniomaxillofac Surg 40(7):e194–e197PubMedGoogle Scholar
  30. 30.
    Reisberger EM, Landthaler M, Wiest L, Schröder J, Stolz W (2003) Foreign body granulomas caused by polymethylmethacrylate microspheres: successful treatment with allopurinol. Arch Dermatol 139(1):17–20PubMedGoogle Scholar
  31. 31.
    Rudolph CM, Soyer HP, Schuller-Petrovic S, Kerl H (1999) Foreign body granulomas due to injectable aesthetic microimplants. Am J Surg Pathol 23(1):113–117PubMedGoogle Scholar
  32. 32.
    Ledon JA, Savas JA, Yang S, Franca K, Camacho I, Nouri K (2013) Inflammatory nodules following soft tissue filler use: a review of causative agents, pathology and treatment options. Am J Clin Dermatol 14(5):401–411PubMedGoogle Scholar
  33. 33.
    Silva MT, Curi AL (2004) Blindness and total ophthalmoplegia after aesthetic polymethylmethacrylate injection: case report. Arq Neuropsiquiatr 62(3B):873–874PubMedGoogle Scholar
  34. 34.
    Wolfram D, Tzankov A, Piza-Katzer H (2006) Surgery for foreign body reactions due to injectable fillers. Dermatology 213(4):300–304PubMedGoogle Scholar
  35. 35.
    Wu W, Chayavichitsilp P, Hata T (2012) Extremely delayed granulomatous reaction to soft-tissue injectables (polymethyl methacrylate). J Am Acad Dermatol 67(5):e206–e207PubMedGoogle Scholar
  36. 36.
    Sidwell RU, McL Johnson N, Francis N, Bunker CB (2006) Cutaneous sarcoidal granulomas developing after Artecoll facial cosmetic filler in a patient with newly diagnosed systemic sarcoidosis. Clin Exp Dermatol 31(2):208–211PubMedGoogle Scholar
  37. 37.
    Fischer J, Metzler G, Schaller M (2007) Cosmetic permanent fillers for soft tissue augmentation: a new contraindication for interferon therapies. Arch Dermatol 143(4):507–510PubMedGoogle Scholar
  38. 38.
    Al-Qattan MM (2007) Late artecoll granulomas aggravated by pregnancy. Ann Plast Surg 58(5):592PubMedGoogle Scholar
  39. 39.
    Bisschop C, Bruijn MS, Stenekes MW, Diercks GF, Hospers GA (2016) Foreign body reaction triggered by cytotoxic T lymphocyte-associated protein 4 blockade 25 years after dermal filler injection. Br J Dermatol 175(6):1351–1353PubMedGoogle Scholar
  40. 40.
    Heath CR, David J, Taylor SC (2012) Sarcoidosis: are there differences in your skin of color patients? J Am Acad Dermatol 66(1):121.e1–121.e14Google Scholar
  41. 41.
    Haneke E (2014) Adverse effects of fillers and their histopathology. Fac Plast Surg 30(6):599–614Google Scholar
  42. 42.
    Haneke E (2019) Adverse effects of fillers. Dermatol Ther. 32(2):e12676. CrossRefPubMedGoogle Scholar
  43. 43.
    Lemperle G, Morhenn V, Charrier U (2003) Human histology and persistence of various injectable filler substances for soft tissue augmentation. Aesthet Plast Surg 27(5):354–366Google Scholar
  44. 44.
    Ahn CS, Rao BK (2014) The life cycles and biological end pathways of dermal fillers. J Cosmet Dermatol 13(3):212–223PubMedPubMedCentralGoogle Scholar
  45. 45.
    Fernandez-Cossio S, Castano-Oreja MT (2006) Biocompatibility of two novel dermal fillers: histological evaluation of implants of a hyaluronic acid filler and a polyacrylamide filler. Plast Reconstr Surg 117:1789–1796PubMedPubMedCentralGoogle Scholar
  46. 46.
    Rosa SC, de Magalhães AV, de Macedo JL (2008) An experimental study of tissue reaction to polymethyl methacrylate (PMMA) microspheres (Artecoll) and dimethylsiloxane (DMS) in the mouse. Am J Dermatopathol 30(3):222–227PubMedGoogle Scholar
  47. 47.
    Vargas KF, Borghetti RL, Moure SP, Cherubini K, de Figueiredo MA (2016) Local and systemic tissue response submitted to injection of 2 and 30% polymethylmethacrylate in rats’ tongue. Gerodontology. 33(1):36–43PubMedGoogle Scholar
  48. 48.
    de Melo Carpaneda E, Carpaneda CA (2012) Adverse results with PMMA fillers. Aesthet Plast Surg. 36(4):955–963Google Scholar
  49. 49.
    Saylan Z (2003) Facial fillers and their complications. Aesthet Surg J. 23(3):221–224PubMedGoogle Scholar
  50. 50.
    Signorini M, Liew S, Sundaram H, De Boulle KL, Goodman GJ, Monheit G, Wu Y, Trindade de Almeida AR, Swift A, Vieira Braz A, Global aesthetics consensus: avoidance and management of complications from hyaluronic acid fillers-evidence- and opinion-based review and consensus recommendations (2016) Global aesthetics consensus: avoidance and management of complications from hyaluronic acid fillers-evidence- and opinion-based review and consensus recommendations. Plast Reconstr Surg 137(6):961e–971ePubMedPubMedCentralGoogle Scholar
  51. 51.
    Cotofana S, Schenck TL, Trevidic P, Sykes J, Massry GG, Liew S, Graivier M, Dayan S, de Maio M, Fitzgerald R, Andrews JT, Remington BK (2015) Midface: clinical anatomy and regional approaches with injectable fillers. Plast Reconstr Surg 136(5 Suppl):219S–234SPubMedGoogle Scholar
  52. 52.
    McCracken MS, Khan JA, Wulc AE, Holds JB, Fante RG, Migliori ME, Ebroon DA, Amato MM, Silkiss RZ, Patel BC (2006) Hyaluronic acid gel (Restylane) filler for facial rhytids: lessons learned from American Society of Ophthalmic Plastic and Reconstructive Surgery member treatment of 286 patients. Ophthalmic Plast Reconstr Surg 22(3):188–191PubMedGoogle Scholar
  53. 53.
    Hatcher JL, Goldman ND (2014) Recognition and treatment of non-infectious hyaluronic acid reactions. J Dermatol Treat 25(6):513–515Google Scholar
  54. 54.
    Grunebaum LD, Bogdan Allemann I, Dayan S et al (2009) The risk of alar necrosis associated with dermal filler injection. Dermatol Surg 35:1635–1640Google Scholar
  55. 55.
    Adcock IM, Mumby S (2017) Glucocorticoids. Handb Exp Pharmacol 237:171–196Google Scholar
  56. 56.
    Fischer HJ, Schweingruber N, Lühder F, Reichardt HM (2013) The potential role of T cell migration and chemotaxis as targets of glucocorticoids in multiple sclerosis and experimental autoimmune encephalomyelitis. Mol Cell Endocrinol 380(1–2):99–107PubMedGoogle Scholar
  57. 57.
    Longley DB, Harkin DP, Johnston PG (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3(5):330–338PubMedGoogle Scholar
  58. 58.
    Bijlard E, Steltenpool S, Niessen FB (2015) Intralesional 5-fluorouracil in keloid treatment: a systematic review. Acta Derm Venereol 95(7):778–782PubMedGoogle Scholar
  59. 59.
    de Barros Silveira LK, de Oliveira FL, Alves Tde B, Rambaldi ML, de Andrade FC, Kelmer Sde C, Barbosa FC (2012) The therapeutic benefit of allopurinol in the treatment of foreign body granulomas caused by polymethylmethacrylate microspheres. Case Rep Dermatol Med 2012:945205PubMedPubMedCentralGoogle Scholar
  60. 60.
    Tsai TF, Yeh TY (2010) Allopurinol in dermatology. Am J Clin Dermatol 11(4):225–232PubMedGoogle Scholar
  61. 61.
    Badgwell C, Rosen T (2007) Cutaneous sarcoidosis therapy updated. J Am Acad Dermatol 56(1):69–83PubMedGoogle Scholar
  62. 62.
    Breghoej A, Jemec GB (2005) Low-dose allopurinol in the treatment of cutaneous sarcoidosis: response in four of seven patients. J Dermatol Treat 16:125–127Google Scholar
  63. 63.
    El-Euch D, Mokni M, Trojjet S, Khouaja A, Osman AB (1999) Sarcoidosis in a child treated successfully with allopurinol. Br J Dermatol 140:1184–1185PubMedGoogle Scholar
  64. 64.
    Pfau A, Stolz W, Karrer S, Szeimies RM, Landthaler M (1998) Allopurinol in treatment of cutaneous sarcoidosis. Hautarzt 49:216–218PubMedGoogle Scholar
  65. 65.
    Nakahara T, Morimoto H, Murakami N, Furue M (2018) Mechanistic insights into topical tacrolimus for the treatment of atopic dermatitis. Pediatr Allergy Immunol 29(3):233–238PubMedGoogle Scholar
  66. 66.
    Cury Martins J, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM (2015) Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev 7:CD009864Google Scholar
  67. 67.
    Caproni M, Torchia D, Antiga E et al (2007) The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study. Br J Dermatol 156:312–319PubMedGoogle Scholar
  68. 68.
    Amin AR, Patel RN, Thakker GD, Lowenstein CJ, Attur MG, Abramson SB (1997) Post-transcriptional regulation of inducible nitric oxide synthase mRNA in murine macrophages by doxycycline and chemically modified tetracyclines. FEBS Lett 410:259–264PubMedGoogle Scholar
  69. 69.
    Golub LM, Ramamurthy NS, McNamara TF, Greenwald RA, Rifkin BR (1991) Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med 2:297–321PubMedGoogle Scholar
  70. 70.
    Garrido-Mesa N, Zarzuelo A, Gálvez J (2013) Minocycline: far beyond an antibiotic. Br J Pharmacol 169(2):337–352PubMedPubMedCentralGoogle Scholar
  71. 71.
    Humbert P, Treffel P, Chapuis JF, Buchet S, Derancourt C, Agache P (1991) The tetracyclines in dermatology. J Am Acad Dermatol 25:691–697PubMedGoogle Scholar
  72. 72.
    Sapadin AN, Fleischmajer R (2006) Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol 54:258–265PubMedGoogle Scholar
  73. 73.
    Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L (2001) The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol 137:69–73PubMedGoogle Scholar
  74. 74.
    Korting HC, Schöllmann C (2009) Current topical and systemic approaches to treatment of rosacea. J Eur Acad Dermatol Venereol 23:876–882PubMedGoogle Scholar
  75. 75.
    Marcoval J, Mana J, Moreno A et al (2001) Foreign bodies in granulomatous cutaneous lesions of patients with systemic sarcoidosis. Arch Dermatol 137:427–430PubMedGoogle Scholar
  76. 76.
    Hurst EA, Mauro T (2005) Sarcoidosis associated with pegylated interferon alfa and ribavirin treatment for chronic hepatitis C: a case report and review of the literature. Arch Dermatol 141:865–868PubMedGoogle Scholar
  77. 77.
    Mayberry J, Lee WM (2019) The revolution in treatment of hepatitis C. Med Clin N Am 103(1):43–55PubMedGoogle Scholar
  78. 78.
    Tivol EA, Borriello F, Schweitzer AN et al (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3(5):541–547PubMedGoogle Scholar
  79. 79.
    Bonney EA (2016) Immune regulation in pregnancy: a matter of perspective? Obstet Gynecol Clin North Am 43(4):679–698PubMedPubMedCentralGoogle Scholar
  80. 80.
    Ning F, Liu H, Lash GE (2016) The role of decidual macrophages during normal and pathological pregnancy. Am J Reprod Immunol 75(3):298–309PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2019

Authors and Affiliations

  1. 1.The Princess Alexandra HospitalHarlowUK

Personalised recommendations