title: Enfuvirtide injection site reactions: a clinical and histopathological appraisal.
abstract: OBJECTIVE
  Enfuvirtide was the first of a new class of antiretroviral agents termed 'fusion inhibitors' used for the treatment of HIV-1 infection. Enfuvirtide is administered subcutaneously and injection site reactions (ISR) are commonplace (98%). The aim of this study was to analyse in detail the histopathological changes associated with striking ISR seen in four patients.
  
  
  METHODS
  Biopsies were obtained at various times post-injection and were reviewed histologically. The changes in epidermal, dermal and subcutaneous connective tissue and the presence and nature of the inflammatory cellular infiltrate were noted. An immunohistochemical assessment was undertaken.
  
  
  RESULTS
  All biopsy specimens demonstrated striking changes in the dermal connective tissue. Alteration in collagen was the most prominent feature and resembled a morphoea/scleroderma-like process. These changes persisted well beyond cessation of enfuvirtide (>1 year). The relative populations of dermal dendritic cells (DDC) (types 1 (Factor XIIIa) and 2 (CD34+)) were analysed and a reciprocal relationship between DDC subpopulations was observed akin to that observed in other sclerosing and fibrosing conditions.
  
  
  CONCLUSIONS
  This study details histopathological changes associated with enfuvirtide ISR. We postulate that changes in DDC populations may contribute to the pathogenesis of the sclerotic process observed with enfuvirtide ISR.
authors.affiliation: Department of Dermatology, St Vincent's Hospital, New South Wales, Australia. bwallace@med.usyd.edu.au
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Wallace
authors.forename: King-Bing
authors.initials: KB
authors.lastname: Tan
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Pett
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Steven
authors.initials: S
authors.lastname: Kossard
authors.forename: Margot J
authors.initials: MJ
authors.lastname: Whitfeld
mesh_terms: D001706:Biopsy; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects*; D023581:HIV Fusion Inhibitors / Q000009:adverse effects*; D006801:Humans; D007279:Injections, Subcutaneous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012867:Skin / Q000187:drug effects* / Q000473:pathology*
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide