A placebo-controlled randomized study on the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in fractionated 5-aminolaevulinic acid-photodynamic therapy in patients with psoriasis

Br J Dermatol. 2006 Aug;155(2):429-36. doi: 10.1111/j.1365-2133.2006.07290.x.

Abstract

Background: Topical 5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT) for the treatment of psoriasis has been evaluated in a few studies. In these studies different treatment parameters were used, there was a variable clinical response, and a nonhomogeneous fluorescence was seen after irradiation with Wood's light.

Objectives: To study the clinical effectiveness, immunohistochemical changes and protoporphyrin IX accumulation in ALA-PDT in patients with psoriasis. Eight patients with stable plaque psoriasis with symmetrical involvement were included in the study. Two symmetrical plaques were randomly allocated to PDT either with 10% ALA or with placebo. Irradiation consisted of 2 and 8 J cm(-2) with a dark interval of 2 h (Waldmann PDT 1200 L, 600-750 nm, 40 mW cm(-2)) once weekly for 4 weeks. Before, during and after irradiation, fluorescence diagnosis was performed. Biopsies were taken at baseline, week 1 and week 6 for immunohistochemical assessment. Psoriatic plaques were clinically assessed using the plaque severity (sum) score. Fluorescence diagnosis was performed and expression of immunohistochemical markers for proliferation, differentiation and T-cell infiltration [Ki67, keratin 10 (K10), CD4, CD8 and CD45RO] was assessed.

Results: From week 1 up to week 6, ALA-PDT gave a significant reduction in the number of Ki67+ nuclei, while the K10 expression increased. After 6 weeks significant improvement was observed for CD8 and CD45RO. These changes were absent in the placebo-treated lesions. The sum scores were also significantly lower in the ALA-treated plaques. Heterogeneity of macroscopic fluorescence was observed during treatment despite keratolytic treatment.

Conclusions: The present study shows that clinical improvement during fractionated ALA-PDT in psoriasis parallels histological improvement as seen in normalization of epidermal proliferation, differentiation and infiltration of relevant T-cell subsets. Optimizing the current treatment protocol may increase clinical efficacy further.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminolevulinic Acid / administration & dosage*
  • Cell Differentiation
  • Cell Proliferation
  • Dose Fractionation, Radiation
  • Drug Administration Schedule
  • Epidermis / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Photochemotherapy / methods*
  • Photosensitizing Agents / administration & dosage*
  • Protoporphyrins / metabolism*
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Severity of Illness Index
  • Skin / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / radiation effects
  • Treatment Outcome

Substances

  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX