Archives of Plastic Surgery

Korean Society of Plastic and Reconstructive Surgeons (대한성형외과학회)
권호 표지
DOI QR코드

DOI QR Code

Foreign Body Granulomas after the Use of Dermal Fillers: Pathophysiology, Clinical Appearance, Histologic Features, and Treatment

  • Lee, Jeong Min (Department of Plastic and Reconstructive Surgery, Gachon University Gil Medical Center) ;
  • Kim, Yu Jin (Department of Plastic and Reconstructive Surgery, Gachon University Gil Medical Center)
  • Received : 2014.08.07
  • Accepted : 2014.09.18
  • Published : 2015.03.15
Download PDF
⟨ Previous Next ⟩

Abstract

A foreign body granuloma is a non-allergic chronic inflammatory reaction that is mainly composed of multinucleated giant cells. Foreign body granulomas may occur after the administration of any dermal filler. Factors such as the volume of the injection, impurities present in the fillers, and the physical properties of fillers affect granuloma formation. The formation of granulomas involves five phases: protein adsorption, macrophage adhesion, macrophage fusion, and crosstalk. The clinical and pathologic features of granulomas vary depending on the type of filler that causes them. Foreign body granulomas can be treated effectively with intralesional corticosteroid injections. Surgical excisions of granulomas tend to be incomplete because granulomas have ill-defined borders and moreover, surgical excisions may leave scars and deformities.

Keywords

References

  1. Anderson JM, Rodriguez A, Chang DT. Foreign body reaction to biomaterials. Semin Immunol 2008;20:86-100. https://doi.org/10.1016/j.smim.2007.11.004
  2. Micheels P. Human anti-hyaluronic acid antibodies: is it possible? Dermatol Surg 2001;27:185-91.
  3. Ko CJ, Glusac EJ, Shapiro PE. Noninfectious granulomas. In: Lever WF, Elder DE, editors. Lever's histopathology of the skin. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2009. p.373-87.
  4. Lemperle G, Gauthier-Hazan N, Wolters M, et al. Foreign body granulomas after all injectable dermal fillers: part 1. Possible causes. Plast Reconstr Surg 2009;123:1842-63. https://doi.org/10.1097/PRS.0b013e31818236d7
  5. Williams GT, Williams WJ. Granulomatous inflammation: a review. J Clin Pathol 1983;36:723-33. https://doi.org/10.1136/jcp.36.7.723
  6. Murphy KM, Travers P, Walport M. Janeway's immunobiology. New York: Garland Science; 2008.
  7. Rubin E, Farber JL. Pathology. Philadelphia: Lippincott-Raven; 1999.
  8. Lemperle G, Gauthier-Hazan N. Foreign body granulomas after all injectable dermal fillers: part 2. Treatment options. Plast Reconstr Surg 2009;123:1864-73. https://doi.org/10.1097/PRS.0b013e3181858f4f
  9. Duranti F, Salti G, Bovani B, et al. Injectable hyaluronic acid gel for soft tissue augmentation. A clinical and histological study. Dermatol Surg 1998;24:1317-25.
  10. Bentkover SH. The biology of facial fillers. Facial Plast Surg 2009;25:73-85. https://doi.org/10.1055/s-0029-1220646
  11. Grainger DW. All charged up about implanted biomaterials. Nat Biotechnol 2013;31:507-9. https://doi.org/10.1038/nbt.2600
  12. Freitas RA. Nanomedicine. Austin, TX: Landes Bioscience; 2003.
  13. Lemperle G, Romano JJ, Busso M. Soft tissue augmentation with artecoll: 10-year history, indications, techniques, and complications. Dermatol Surg 2003;29:573-87.
  14. Zimmermann US, Clerici TJ. The histological aspects of fillers complications. Semin Cutan Med Surg 2004;23:241-50. https://doi.org/10.1016/j.sder.2004.09.004
  15. Lemperle G, Rullan PP, Gauthier-Hazan N. Avoiding and treating dermal filler complications. Plast Reconstr Surg 2006;118:92S-107S. https://doi.org/10.1097/01.prs.0000234672.69287.77
  16. Orentreich DS. Liquid injectable silicone: techniques for soft tissue augmentation. Clin Plast Surg 2000;27:595-612.
  17. Achauer BM. A serious complication following medical-grade silicone injection of the face. Plast Reconstr Surg 1983;71:251-4. https://doi.org/10.1097/00006534-198302000-00020
  18. Jones DH, Carruthers A, Orentreich D, et al. Highly purified 1000-cSt silicone oil for treatment of human immunodeficiency virus-associated facial lipoatrophy: an open pilot trial. Dermatol Surg 2004;30:1279-86.
  19. Duffy DM. Tissue injectable liquid silicone: new perspectives. In: Klein AW, editor. Tissue augmentation in clinical practice: procedures and techniques. 2nd ed. New York: Taylor & Francis; 2005. p. 159-162.
  20. Champion J, Mitragotri S. Recognition of the size of polymer drug carriers by macrophages [Internet]. San Francisco, CA: American Institute of Chemicla Enginerrs Anuunal Meeting; 2006 [cited 2009 Mar 30]. Available from: https://aiche.confex.com/aiche/2006/techprogram/P66762.HTM.
  21. Lemperle G, Hazan-Gauthier N, Lemperle M. PMMA microspheres (Artecoll) for skin and soft-tissue augmentation. Part II: Clinical investigations. Plast Reconstr Surg 1995;96:627-34. https://doi.org/10.1097/00006534-199509000-00015
  22. Cooperman LS, Mackinnon V, Bechler G, et al. Injectable collagen: a six-year clinical investigation. Aesthetic Plast Surg 1985;9:145-51. https://doi.org/10.1007/BF01570347
  23. Requena C, Izquierdo MJ, Navarro M, et al. Adverse reactions to injectable aesthetic microimplants. Am J Dermatopathol 2001;23:197-202. https://doi.org/10.1097/00000372-200106000-00006
  24. Wong KT, Lee PS, Chan YL, et al. Paraffinoma in anterior abdominal wall mimicking liposarcoma. Br J Radiol 2003;76:264-7. https://doi.org/10.1259/bjr/31110098
  25. Legaspi-Vicerra ME, Field LM. Paraffin granulomata, "Witch's Chin," and nasal deformities: excision and reconstruction with reduction chinplasty and open rhinotomy resection. J Clin Aesthet Dermatol 2010;3:54-8.
  26. Uchida Y, Yoshii N, Kubo H, et al. Facial paraffinoma after cosmetic paraffin injection. J Dermatol 2007;34:798-800. https://doi.org/10.1111/j.1346-8138.2007.00388.x
  27. Evstatiev D. Late complications after injections of hydrogel in the breast. Plast Reconstr Surg 2004;113:1878. https://doi.org/10.1097/01.PRS.0000119877.63517.8B
  28. Tvede M, Christense L. Treatment guidelines [Internet]. Soeborg: AQUAMID; 2013 [cited 2014 Oct 13]. Available from: http://www.aquamid.com/wp-content/uploads/2014/03/Treatment_Guidelines_EN.pdf.
  29. Andre P, Lowe NJ, Parc A, et al. Adverse reactions to dermal fillers: a review of European experiences. J Cosmet Laser Ther 2005;7:171-6. https://doi.org/10.1080/14764170500344393
  30. Lemperle G, Morhenn V, Charrier U. Human histology and persistence of various injectable filler substances for soft tissue augmentation. Aesthetic Plast Surg 2003;27:354-66. https://doi.org/10.1007/s00266-003-3022-1
  31. Heise H, Zimmermann R, Heise P. Temporary granulomatous inflammation following collagen implantation. J Craniomaxillofac Surg 2001;29:238-41. https://doi.org/10.1054/jcms.2001.0222
  32. Ozturk CN, Li Y, Tung R, et al. Complications following injection of soft-tissue fillers. Aesthet Surg J 2013;33:862-77. https://doi.org/10.1177/1090820X13493638
  33. Delustro F, Mackinnon V, Swanson NA. Immunology of injectable collagen in human subjects. J Dermatol Surg Oncol 1988;14:49-55. https://doi.org/10.1111/j.1524-4725.1988.tb04040.x
  34. Geisler D, Shumer S, Elson ML. Delayed hypersensitivity reaction to Restylane. Cosmet Dermatol 2007;20:784-6.
  35. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg 2005;31:1616-25.
  36. Swanson NA, Stoner JG, Siegle RJ, et al. Treatment site reactions to Zyderm Collagen Implantation. J Dermatol Surg Oncol 1983;9:377-80. https://doi.org/10.1111/j.1524-4725.1983.tb00819.x
  37. Tujebajeva RM, Graifer DM, Matasova NB, et al. Selective inhibition of the polypeptide chain elongation in eukaryotic cells. Biochim Biophys Acta 1992;1129:177-82. https://doi.org/10.1016/0167-4781(92)90484-H
  38. Conejo-Mir JS, Sanz Guirado S, Angel Munoz M. Adverse granulomatous reaction to Artecoll treated by intralesional 5-fluorouracil and triamcinolone injections. Dermatol Surg 2006;32:1079-81.
  39. Al-Qattan MM. Late artecoll granulomas aggravated by pregnancy. Ann Plast Surg 2007;58:592. https://doi.org/10.1097/01.sap.0000258127.15139.68
  40. Park TH, Seo SW, Kim JK, et al. Clinical experience with polymethylmethacrylate microsphere filler complications. Aesthetic Plast Surg 2012;36:421-6. https://doi.org/10.1007/s00266-011-9803-z
  41. Lupton JR, Alster TS. Cutaneous hypersensitivity reaction to injectable hyaluronic acid gel. Dermatol Surg 2000;26:135-7. https://doi.org/10.1046/j.1524-4725.2000.99202.x
  42. Senet P, Bachelez H, Ollivaud L, et al. Minocycline for the treatment of cutaneous silicone granulomas. Br J Dermatol 1999;140:985-7. https://doi.org/10.1046/j.1365-2133.1999.02853.x
  43. Yang JH, Lee SM, Won CH, et al. Foreign body granuloma caused by hyaluronic acid/dextranomer microsphere filler injection. Int J Dermatol 2012;51:1517-8. https://doi.org/10.1111/j.1365-4632.2010.04795.x
  44. Espana A, Solano T, Quintanilla E. Bleomycin in the treatment of keloids and hypertrophic scars by multiple needle punctures. Dermatol Surg 2001;27:23-7.
  45. Saray Y, Gulec AT. Treatment of keloids and hypertrophic scars with dermojet injections of bleomycin: a preliminary study. Int J Dermatol 2005;44:777-84. https://doi.org/10.1111/j.1365-4632.2005.02633.x
  46. Lemperle G, Duffy DM. Treatment options for dermal filler complications. Aesthet Surg J 2006;26:356-64. https://doi.org/10.1016/j.asj.2006.04.002
  47. Arin MJ, Bate J, Krieg T, et al. Silicone granuloma of the face treated with minocycline. J Am Acad Dermatol 2005;52:53-6.
  48. Garcia VS, Trelles AS. Superficial granulomatous pyoderma: successful treatment with minocycline. J Eur Acad Dermatol Venereol 2006;20:1134-5. https://doi.org/10.1111/j.1468-3083.2006.01625.x
  49. Reisberger EM, Landthaler M, Wiest L, et al. Foreign body granulomas caused by polymethylmethacrylate microspheres: successful treatment with allopurinol. Arch Dermatol 2003;139:17-20. https://doi.org/10.1001/archderm.139.1.17
  50. de Barros Silveira LK, de Oliveira FL, Alves Tde B, et al. The therapeutic benefit of allopurinol in the treatment of foreign body granulomas caused by polymethylmethacrylate microspheres. Case Rep Dermatol Med 2012;2012:945205.
  51. Aivaliotis M, Kontochristopoulos G, Hatziolou E, et al. Successful colchicine administration in facial granulomas caused by cosmetic implants: report of a case. J Dermatolog Treat 2007;18:112-4. https://doi.org/10.1080/08910600601149619
  52. Baumann LS, Kerdel F. The treatment of bovine collagen allergy with cyclosporin. Dermatol Surg 1999;25:247-9. https://doi.org/10.1046/j.1524-4725.1999.8228a.x
  53. Alijotas-Reig J, Garcia-Gimenez V. Delayed immune-mediated adverse effects related to hyaluronic acid and acrylic hydrogel dermal fillers: clinical findings, long-term follow-up and review of the literature. J Eur Acad Dermatol Venereol 2008;22:150-61.
  54. Lee SC, Kim JB, Chin BR, et al. Inflammatory granuloma caused by injectable soft tissue filler (Artecoll). J Korean Assoc Oral Maxillofac Surg 2013;39:193-6. https://doi.org/10.5125/jkaoms.2013.39.4.193

Cited by

  1. Complications of hyaluronic acid fillers and their managements vol.20, pp.2, 2015, https://doi.org/10.1016/j.jdds.2016.01.001
  2. Atypical Facial Filler Granuloma: Comparative Histologic Analysis with Paraffinoma vol.17, pp.3, 2015, https://doi.org/10.7181/acfs.2016.17.3.169
  3. Foreign body reaction triggered by cytotoxic T lymphocyte‐associated protein 4 blockade 25 years after dermal filler injection vol.175, pp.6, 2016, https://doi.org/10.1111/bjd.14674
  4. Understanding How to Prevent and Treat Adverse Events of Fillers and Neuromodulators vol.4, pp.12, 2015, https://doi.org/10.1097/gox.0000000000001154
  5. Volume correction in the aging hand: role of dermal fillers vol.9, pp.None, 2016, https://doi.org/10.2147/ccid.s92853
  6. Injectable facial fillers: imaging features, complications, and diagnostic pitfalls at MRI and PET CT vol.8, pp.6, 2015, https://doi.org/10.1007/s13244-017-0575-0
  7. Reflective account of when adverse events occur following dermal filler treatments vol.6, pp.7, 2015, https://doi.org/10.12968/joan.2017.6.7.356
  8. Ultrasound-guided Removal of Retained Soft Tissue Foreign Body with Late Presentation vol.130, pp.14, 2015, https://doi.org/10.4103/0366-6999.209910
  9. Ultrasound and Histologic Examination after Subcutaneous Injection of Two Volumizing Hyaluronic Acid Fillers: A Preliminary Study vol.5, pp.2, 2015, https://doi.org/10.1097/gox.0000000000001222
  10. Granulomatous reaction to Belotero Balance: A case study vol.19, pp.5, 2015, https://doi.org/10.1080/14764172.2017.1299188
  11. Usefulness of the Versajet Hydrosurgery System for the Removal of Foreign Body Granuloma vol.44, pp.4, 2015, https://doi.org/10.5999/aps.2017.44.4.352
  12. Nail bed granuloma as a complication of nail bed injuries vol.42, pp.8, 2017, https://doi.org/10.1177/1753193417703932
  13. Late-Onset Inflammatory Response to Hyaluronic Acid Dermal Fillers vol.5, pp.12, 2015, https://doi.org/10.1097/gox.0000000000001532
  14. Magnetic resonance imaging appearance of foreign-body granulomatous reactions to dermal cosmetic fillers vol.47, pp.4, 2017, https://doi.org/10.5624/isd.2017.47.4.281
  15. Autoimmune/inflammatory syndrome induced by mineral oil: a health problem vol.37, pp.6, 2015, https://doi.org/10.1007/s10067-018-4078-2
  16. Skin bacterial flora as a potential risk factor predisposing to late bacterial infection after cross-linked hyaluronic acid gel augmentation vol.11, pp.None, 2015, https://doi.org/10.2147/idr.s154328
  17. Oral foreign body granuloma to soft tissue fillers. Report of two cases and review of the literature vol.10, pp.2, 2015, https://doi.org/10.4317/jced.54191
  18. Delayed Granulomas after Filler Injection in an Immunosuppressed Patient: A Case Report vol.24, pp.2, 2018, https://doi.org/10.14730/aaps.2018.24.2.91
  19. Granulomatous reaction to hyaluronic acid filler material in oral and perioral region: A case report and review of literature vol.17, pp.4, 2015, https://doi.org/10.1111/jocd.12374
  20. The Abuse of Dermal Fillers: A Clinico-Epidemiological Study of 35 Cases vol.9, pp.2, 2015, https://doi.org/10.4236/jcdsa.2019.92008
  21. Subcutaneous Injection of Myrrh Essential Oil in Mice: Acute and Subacute Toxicity Study vol.2019, pp.None, 2015, https://doi.org/10.1155/2019/8497980
  22. A case report on dermal filler-related periorbital granuloma formation vol.38, pp.2, 2015, https://doi.org/10.1080/01676830.2018.1477806
  23. Role of mechanical and thermal damage in pericapsular inflammatory response to injectable silicone in a rabbit model vol.14, pp.5, 2015, https://doi.org/10.1371/journal.pone.0216926
  24. Foreign body granuloma treatment with 22‐MHz ultrasound‐guided corticoid infiltration vol.18, pp.3, 2019, https://doi.org/10.1111/jocd.12750
  25. HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study vol.17, pp.3, 2019, https://doi.org/10.1177/2280800019867075
  26. High frequency ultrasound imaging as a “potential” way of evaluation modality in side effects of lip augmentation - case report vol.21, pp.4, 2015, https://doi.org/10.1080/14764172.2018.1511910
  27. The case of the eyelid silicone granulomas vol.40, pp.5, 2015, https://doi.org/10.1016/j.amjoto.2019.05.010
  28. Efficacy of HYADD®4-G single intra-discal injections in a rabbit model of intervertebral disc degeneration vol.30, pp.4, 2019, https://doi.org/10.3233/bme-191062
  29. Measurement of the Force Required by Blunt-Tipped Microcannulas to Perforate the Facial Artery vol.35, pp.5, 2015, https://doi.org/10.1097/iop.0000000000001302
  30. Delayed sclerosing granulomatous reaction to dermal filler injection of poly‐hydroxyethyl‐methacrylate suspended in hyaluronic acid: Histochemical and confocal laser scanning microscopic vol.7, pp.11, 2015, https://doi.org/10.1002/ccr3.2478
  31. Retroperitoneal Fibrosis after Chronic Abscesses of Silicone Fluid Fillers in a Case of Gluteal Augmentation vol.2020, pp.None, 2015, https://doi.org/10.1155/2020/7236295
  32. Polycaprolactone: How a Well-Known and Futuristic Polymer Has Become an Innovative Collagen-Stimulator in Esthetics vol.13, pp.None, 2020, https://doi.org/10.2147/ccid.s229054
  33. Safety Assessment of High- and Low-Molecular-Weight Hyaluronans (Profhilo®) as Derived from Worldwide Postmarketing Data vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/8159047
  34. Management of granulomatous foreign body reaction to fillers with methotrexate vol.34, pp.4, 2015, https://doi.org/10.1111/jdv.16027
  35. The surface stress of biomedical silicones is a stimulant of cellular response vol.6, pp.15, 2015, https://doi.org/10.1126/sciadv.aay0076
  36. Early lipogranuloma formation after foreign material injection to the face vol.4, pp.9, 2015, https://doi.org/10.28982/josam.710826
  37. Dermal filler migration complications following lip augmentation procedures vol.9, pp.7, 2015, https://doi.org/10.12968/joan.2020.9.7.276
  38. Dermal fillers may induce late‐onset adverse skin reactions in patients under BRAF inhibitors vol.34, pp.11, 2015, https://doi.org/10.1111/jdv.16550
  39. Dermal fillers do not induce upregulation of NLRP3 inflammasomes or expression of inflammatory cytokines in granulomas vol.19, pp.11, 2020, https://doi.org/10.1111/jocd.13341
  40. “New classification of late and delayed complications after dermal filler: Localized or Generalized?” vol.22, pp.6, 2015, https://doi.org/10.1080/14764172.2021.1922703
  41. Direct Observations of Silver Nanowire-Induced Frustrated Phagocytosis among NR8383 Lung Alveolar Macrophages vol.124, pp.51, 2015, https://doi.org/10.1021/acs.jpcb.0c08132
  42. Treatment of linear scleroderma “En coup de Sabre” with single‐stage autologous fat grafting: A case report and review of the literature vol.20, pp.1, 2021, https://doi.org/10.1111/jocd.13490
  43. The Immunogenicity of Hyaluronic Fillers and Its Consequences vol.14, pp.None, 2021, https://doi.org/10.2147/ccid.s316352
  44. Mandibular osteomyelitis after hyaluronic acid injection vol.20, pp.2, 2015, https://doi.org/10.1111/jocd.13575
  45. Hyaluronic acid dermal fillers and autoimmune disorders: a case report and discussion of a late-onset complication vol.10, pp.suppl1, 2015, https://doi.org/10.12968/joan.2021.10.sup1.28
  46. Evaluation and management of facial granuloma caused by various injection materials vol.22, pp.1, 2015, https://doi.org/10.7181/acfs.2020.00689
  47. A case of oral foreign‐body granuloma due to diatoms vol.48, pp.3, 2015, https://doi.org/10.1111/cup.13922
  48. Disease presentation and surgical treatment of patients with foreign-body granulomas and ASIA syndrome: case series vol.48, pp.4, 2015, https://doi.org/10.5999/aps.2020.02152
  49. Outcomes and Complications of Surgical Removal of Foreign Body Granulomas Due to Illicit Polymer Injection for Cosmetic Purposes vol.41, pp.9, 2021, https://doi.org/10.1093/asj/sjab172
  50. Foreign body reaction to ruptured follicular cysts in dogs vol.7, pp.5, 2021, https://doi.org/10.1002/vms3.542
  51. A foreign body granuloma after dermal filler injection successfully treated with a combination of high‐intensity focused ultrasound and quantum molecular resonance technology device vol.27, pp.6, 2015, https://doi.org/10.1111/srt.13055
  52. Periorbital lipogranuloma after facial injection of autologous fat: A retrospective study of 18 cases vol.31, pp.6, 2021, https://doi.org/10.1177/1120672120938574
  53. Injected Breast Materials: Review of Imaging Features and Characteristics vol.3, pp.6, 2015, https://doi.org/10.1093/jbi/wbab035