title: Does iatrogenic scleroderma due to injection-site reaction to enfuvirtide impair absorption of the drug?
abstract: BACKGROUND
  Chronic iatrogenic scleroderma is a possible obstacle to the absorption of subcutaneously administered drugs. This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV.
  
  
  METHODS
  Fourteen patients treated with an enfuvirtide-based antiretroviral regimen for a median of 45 weeks were enrolled and their ISRs were evaluated. Twelve patients with evidence of ISRs underwent cutaneous biopsies using a 4-mm punch. The maximum plasma enfuvirtide concentration (Cmax) and the area under the enfuvirtide concentration-time curve (AUC) were assessed using blood sampling.
  
  
  RESULTS
  Four different macroscopic patterns of ISR were identified: A--no evidence of cutaneous lesions; B--transient infiltrative lesions that auto-resolved within 24 hours; C--transient nodular lesions that auto-resolved within 7-15 days; and D--stable lesions after more than 30 days. Histological examination showed three morphological patterns: (1) acute urticaria/vasculitis-like pattern, (2) subacute pattern and (3) chronic scleroderma-like pattern. No differences among patients with the various patterns of ISRs were observed, except for a higher Cmax and AUC in patients with pattern 1.
  
  
  CONCLUSIONS
  These results confirm that although iatrogenic scleroderma is not related to impaired enfuvirtide absorption, higher Cmax and AUC values are observed in patients with urticaria/vasculitis-like patterns.
authors.affiliation: Clinica delle Malattie Infettive, University of Bari, Bari, Italy. p_maggi@yahoo.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Maggi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Filotico
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Anna
authors.initials: A
authors.lastname: Volpe
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellacosa
authors.forename: Eliana
authors.initials: E
authors.lastname: Cinori
authors.forename: Daniel Gonzalez
authors.initials: DG
authors.lastname: de Requena
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000009:adverse effects* / Q000493:pharmacokinetics*; D006801:Humans; D007049:Iatrogenic Disease; D007275:Injections, Intravenous / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012594:Scleroderma, Localized / Q000139:chemically induced* / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D014581:Urticaria / Q000473:pathology; D014657:Vasculitis / Q000473:pathology
chemical_list: D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D000077560:Enfuvirtide