title: Electron microscopic documentation of late changes in permanent fillers and clinical management of granulomas in affected patients.
abstract: BACKGROUND
  The manufacturers of permanent injectable fillers claim that their products are widely inert, biocompatible, atoxic, and nonimmunogenic. There are polymer gels without microparticles on the market and combination products that use collagen suspension or a hyaluronic acid gel as a vector to which polymer microspheres or polygonal particles are added. The filling effect of the polymer gels is based on the volume injected and, for the combination gels, partly on the volume injected and partly on the intended host foreign-body reaction to the microparticles. Foreign body reactions that are seen as inflammatory, sometimes disfiguring, nodules may develop years later at the injection sites.
  
  
  OBJECTIVE
  Permanent fillers differ with respect to composition and chemical and biological characteristics. There have been reports that intend to explain how host tissue reacts with different permanent fillers and how adverse reactions differ depending on the filler used. The changes that some of the permanent fillers undergo during years of residence in human tissue have not been included in this discussion. These structural changes may be one of the reasons why adverse reactions to permanent fillers occur clinically with a delay of several years.
  
  
  METHODS
  In a series of 10 patients who had been injected with a permanent filler of hydroxymethylmethacrylate and ethylmethacrylate (40%) in hyaluronic acid gel (60%) and had developed adverse reactions with inflammatory nodules after variable time elapsed, biopsies could be obtained for histologic and electron microscopic examinations.
  
  
  RESULTS
  After 2 years in all specimens, changes of degradation of the filler material could be detected. Bacteria were not found in any of the specimen. In 40% of the particles, the size of the particles did not correspond to the size declared by the manufacturer (45-65 microm) and was smaller, thus being more susceptible to phagocytosis.
  
  
  CONCLUSIONS
  Inflammatory nodules due to adverse reactions to permanent fillers containing microparticles with a hydrophobic surface were treated with good results with a regimen of allopurinol and intralesional injections with a mixture of fluorouracil and low-dose triamcinolon.
authors.affiliation: Ueber der Klause, München, Germany. lwiest@ivprojekt.com
authors.forename: Luitgard G
authors.initials: LG
authors.lastname: Wiest
authors.forename: Wilhem
authors.initials: W
authors.lastname: Stolz
authors.forename: Josef A
authors.initials: JA
authors.lastname: Schroeder
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D001706:Biopsy; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005145:Face; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D015745:Granuloma, Foreign-Body / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000009:adverse effects* / Q000737:chemistry; D015552:Injections, Intralesional; D008768:Methylmethacrylates / Q000009:adverse effects; D008854:Microscopy, Electron; D008875:Middle Aged; D012060:Rejuvenation; D012189:Retrospective Studies; D015595:Skin Aging; D016896:Treatment Outcome; D014221:Triamcinolone / Q000627:therapeutic use
chemical_list: D001672:Biocompatible Materials; D003879:Dermatologic Agents; D004338:Drug Combinations; D008768:Methylmethacrylates; D014221:Triamcinolone; C021302:hydroxymethylmethacrylate; D000493:Allopurinol; C009931:poly(ethylmethacrylate); D006820:Hyaluronic Acid; D005472:Fluorouracil