title: Heterogeneity of fluorescence in psoriasis after application of 5-aminolaevulinic acid: an immunohistochemical study.
abstract: BACKGROUND
  Psoriasis has been shown to highly accumulate protoporphyrin IX (PpIX), but a variable distribution within plaques after fluorescence diagnosis is seen. It is unknown what causes this heterogeneity of fluorescence in psoriatic skin, despite adequate keratolytic treatment. Variations in fluorescence might explain the variable and the mostly partial clinical response of psoriasis seen after photodynamic therapy (PDT).
  
  
  OBJECTIVE
  This study examines morphological and immunohistochemical differences in inhomogeneous PpIX-induced fluorescence in stable plaque psoriasis.
  
  
  METHODS
  Fourteen patients with stable plaque psoriasis were included in this study. In each patient one psoriatic plaque was incubated with 20% 5-aminolaevulinic acid (ALA) ointment for 3 h after keratolytic treatment. Fluorescence diagnosis with ALA-induced porphyrins (FDAP) was performed and subsequently high- and low-fluorescent psoriatic skin samples were biopsied. Biopsies were investigated with respect to histological hyperkeratosis (thickness of stratum corneum), proliferation (Ki-67 antigen), keratinization (K10, filaggrin) and inflammation (CD3). Digital images acquired with FDAP were analysed using image analysis software.
  
  
  RESULTS
  Inhomogeneous fluorescence was seen in 12 of the 14 plaques. A significantly thicker stratum corneum was found in low-fluorescent psoriatic skin compared with highly fluorescent skin. Fluorescence intensity and thickness of the stratum corneum proved to be negatively correlated. The variable-fluorescent parts of the lesional psoriatic skin showed no differences in epidermal proliferation, keratinization or inflammation.
  
  
  CONCLUSIONS
  Heterogeneous ALA-induced fluorescence in psoriasis plaques related to inhomogeneous distribution of PpIX in the epidermis may result from differences in penetration of ALA and/or light within a plaque caused by differences in stratum corneum thickness. The variable clinical response seen after PDT in psoriasis could be explained by this. These findings are consistent with the general assumption that optimal desquamation prior to FDAP or PDT is required for the most favourable results.
authors.affiliation: Department of Dermatology, Radboud University Nijmegen Medical Center, Rene Descartesdreef 1, 6525 GL Nijmegen, the Netherlands. m.kleinpenning@derma.umcn.nl
authors.forename: M M
authors.initials: MM
authors.lastname: Kleinpenning
authors.forename: T
authors.initials: T
authors.lastname: Smits
authors.forename: E
authors.initials: E
authors.lastname: Ewalds
authors.forename: P E J
authors.initials: PE
authors.lastname: van Erp
authors.forename: P C M
authors.initials: PC
authors.lastname: van de Kerkhof
authors.forename: M J P
authors.initials: MJ
authors.lastname: Gerritsen
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics*; D001706:Biopsy; D002454:Cell Differentiation; D049109:Cell Proliferation; D004817:Epidermis / Q000473:pathology; D005260:Female; D000091344:Filaggrin Proteins; D005453:Fluorescence; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012869:Skin Absorption; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX