title: Granulomatous foreign-body reactions to permanent fillers: detection of CD123+ plasmacytoid dendritic cells.
abstract: BACKGROUND
  Soft-tissue augmentation with permanent fillers can lead to severe granulomatous foreign-body reactions (GFBRs), but the immune pathomechanism of this complication is still unknown. We performed conventional histologic examination and immunostaining for plasmacytoid dendritic cells (pDCs) in skin sections from patients with GFBR to 4 permanent filler agents, which have been widely used in recent decades.
  
  
  METHODS
  Twenty-one skin biopsies were studied from 19 patients with GFBR to polyalkylimide 4% gel (PAIG, n = 10), polyacrylamide 2.5% gel (PAAG, n = 2), hydroxyethyl methacrylate/ethyl methacrylate in hyaluronic acid (HEMA/EMA, n = 4), or liquid injectable silicone (n = 5). GFBRs were analyzed in hematoxylin and eosin stained sections and pDCs detected using CD123 antibodies. Anti-CD11c immunostaining was performed for comparison.
  
  
  RESULTS
  Grading of the inflammatory infiltrates observed histologically did not correlate with the clinical features of inflammation. Immunostaining for CD123 did not detect pDCs in 8 of 10 polyalkylimide gel, 1 of 2 polyacrylamide gel, and the 5 liquid injectable silicone biopsies. In contrast, all 4 HEMA/EMA biopsies contained collections of pDCs in lymphocytic infiltrates close to filler particles and adjacent sarcoidal granulomas.
  
  
  CONCLUSIONS
  Our data suggest that pDCs contribute to the sarcoidal granulomas associated with injected HEMA/EMA. Recruited pDCs may exert their pro-inflammatory effects by the release of interferon-α at the site of these filler deposits.
authors.affiliation: Departments of *Dermatology, and †Pathology, Free University Medical Center (VUmc), Amsterdam, the Netherlands; and ‡Department of Pathology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kadouch
authors.forename: Wim
authors.initials: W
authors.lastname: Vos
authors.forename: Erik W P
authors.initials: EW
authors.lastname: Nijhuis
authors.forename: Rick
authors.initials: R
authors.lastname: Hoekzema
mesh_terms: D000180:Acrylic Resins / Q000009:adverse effects; D000328:Adult; D000368:Aged; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects*; D001706:Biopsy; D039521:CD11c Antigen / Q000032:analysis; D003357:Cosmetic Techniques / Q000009:adverse effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005782:Gels; D015745:Granuloma, Foreign-Body / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D053650:Interleukin-3 Receptor alpha Subunit / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011102:Polyhydroxyethyl Methacrylate / Q000009:adverse effects / Q000031:analogs & derivatives; D011237:Predictive Value of Tests; D012828:Silicones / Q000009:adverse effects
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D039521:CD11c Antigen; D005782:Gels; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D012828:Silicones; C016680:polyacrylamide gels; D011102:Polyhydroxyethyl Methacrylate; C047731:hydroxyethyl methacrylate-ethyl methacrylate