title: Adverse reactions to injectable soft tissue permanent fillers.
abstract: BACKGROUND
  Synthetic injectable facial fillers with a permanent effect are widely atoxic and nonimmunogenic, but they differ with respect to composition and in chemical and biologic characteristics. Yet, they all act as foreign bodies in the tissues eliciting a host response that try to remove the gel. Inflammatory nodules may develop at the sites of injection-for some fillers, many years later, for others, not. Why is that?
  
  
  METHODS
  Biopsies were contributed by various plastic surgeons from Europe and Australia after requests were made at international congresses and workshops. The study was based on (a) 5 biopsies from unreactive tissue obtained at different times after injection of polyacrylamide hydrogel (Aquamid); (b) 28 biopsies from intermediate or late inflammatory nodules after injection of polyacrylamide hydrogel (Aquamid) (20 cases), a hyaluronic acid-polyhydroxyethylmethacrylate/ethylmethacrylate gel (Dermalive) (2 cases), and a gel consisting of polylactic acid in mannitol/carbomethoxycellulose (New-Fill) (6 cases); and (c) a review of the literature on adverse reactions after injection with permanent fillers.
  
  
  RESULTS
  Clinically unreactive tissues after injection with Aquamid showed modest or no host reaction. Inflammatory nodules showed an increased foreign body reaction and a bacterial infection after injection with Aquamid, and a combination of moderate foreign body reaction, fibrosis, and in some cases also bacterial infection after injection with Dermalive and New-Fill. According to the literature, inflammatory nodules occur no later than 1 year after injection with polyacrylamide hydrogel, but up to 6 years after injection of combination gels (Artecol), and up to 28 years after injection of silicone gel.
  
  
  CONCLUSIONS
  Inflammatory nodules are likely to be caused by a low-grade infection maintained within a biogfilm surrounding the hydrophobic silicone gel and the combination gels. Aquamid gel may prevent formation of a biofilm through its high water-binding capacity, explaining why late inflammatory nodules are not seen after injection of this polyacrylamide hydrogel product.
authors.affiliation: Department of Pathology, Rigshospitalet Fred., Copenhagen, Denmark. liserh01870christensen@rh.dk
authors.forename: Lise
authors.initials: L
authors.lastname: Christensen
authors.forename: Vibeke
authors.initials: V
authors.lastname: Breiting
authors.forename: Martin
authors.initials: M
authors.lastname: Janssen
authors.forename: Jens
authors.initials: J
authors.lastname: Vuust
authors.forename: Estrid
authors.initials: E
authors.lastname: Hogdall
mesh_terms: D000179:Acrylates / Q000009:adverse effects; D000180:Acrylic Resins / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects*; D002482:Cellulose / Q000009:adverse effects; D003094:Collagen / Q000009:adverse effects; D003357:Cosmetic Techniques / Q000009:adverse effects; D005145:Face / Q000601:surgery; D005260:Female; D005549:Foreign-Body Reaction / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D005782:Gels / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000009:adverse effects; D020100:Hydrogels / Q000009:adverse effects; D007267:Injections / Q000009:adverse effects; D019344:Lactic Acid / Q000009:adverse effects; D008297:Male; D008353:Mannitol / Q000009:adverse effects; D008875:Middle Aged; D011108:Polymers / Q000009:adverse effects; D019904:Polymethyl Methacrylate / Q000009:adverse effects; D019736:Prostheses and Implants / Q000009:adverse effects*; D020034:Silicone Gels / Q000009:adverse effects; D013997:Time Factors
chemical_list: D000179:Acrylates; D000180:Acrylic Resins; C486838:Aquamid; C445359:Artecoll; D001672:Biocompatible Materials; C068018:Bioplastique; C482306:Dermalive; D005782:Gels; D020100:Hydrogels; C482305:New-Fill; D011108:Polymers; D020034:Silicone Gels; D019344:Lactic Acid; D008353:Mannitol; D002482:Cellulose; D006820:Hyaluronic Acid; D003094:Collagen; D019904:Polymethyl Methacrylate