title: Acitretin treatment in (pre)malignant skin disorders of renal transplant recipients: Histologic and immunohistochemical effects.
abstract: BACKGROUND
  The incidence of (pre)malignant skin lesions after renal transplantation is high. Acitretin treatment appears to decrease the number of new squamous cell carcinomas and ameliorates the aspect and reduces the number of actinic keratoses. However, no histologic and immunohistochemical studies have been performed to further substantiate these observations.
  
  
  METHODS
  In 33 renal transplant recipients, biopsies were taken before and after 3 months of treatment with acitretin in doses up to 0.4 mg/kg/day. Histologic and immunohistochemical parameters for dysplasia, epidermal thickness, proliferation, differentiation, apoptosis, and dermal inflammation were analyzed.
  
  
  RESULTS
  Following acitretin treatment, a significant reduction in epidermal thickness (P =.002) and a significant increase in normal differentiation parameter K10 (P =.02) was observed. Epidermal proliferation did not change, nor did apoptosis, inflammation, keratinocytic epidermal neoplasia score, or transglutaminase staining. At baseline, in 8 actinic keratoses, a single cell expression pattern of K13 and/or K19 was found. This was associated with high levels of parameters indicative of high-risk lesions (P <.05). After acitretin treatment, an increase in K13 (P =.006) and K19 (P =.05) was found, together with a change in expression towards a focal or band-like staining pattern.
  
  
  CONCLUSIONS
  Acitretin improves the aspect of actinic keratoses via alteration of keratinization, resulting in peeling of the stratum corneum. No significant change in proliferation was found, which may explain the rapid recurrence of actinic keratoses seen after cessation of acitretin treatment.
authors.affiliation: Departments of Dermatology, University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jürgen V
authors.initials: JV
authors.lastname: Smit
authors.forename: Ruud G L
authors.initials: RG
authors.lastname: de Sévaux
authors.forename: Willeke A M
authors.initials: WA
authors.lastname: Blokx
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Hoitsma
authors.forename: Elke M G J
authors.initials: EM
authors.lastname: de Jong
mesh_terms: D017255:Acitretin / Q000627:therapeutic use*; D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000517:prevention & control*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007641:Keratolytic Agents / Q000627:therapeutic use*; D007642:Keratosis / Q000209:etiology / Q000517:prevention & control*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000209:etiology / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*
chemical_list: D007641:Keratolytic Agents; D017255:Acitretin