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

• Published in: British journal of dermatology (1951) Vol. 155; no. 2; pp. 429 - 436
• Main Authors: Smits, T., Kleinpenning, M.M., Van Erp, P.E.J., Van De Kerkhof, P.C.M., Gerritsen, M-J.P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2006; Blackwell
• Subjects: 5-aminolaevulinic acid; Adult; Aminolevulinic Acid - administration & dosage; Biological and medical sciences; Cell Differentiation; Cell Proliferation; Dermatology; Diseases of the skin. Cosmetics; Dose Fractionation; Drug Administration Schedule; Epidermis - pathology; Female; fluorescence diagnosis; Humans; Male; Medical sciences; Middle Aged; Photochemotherapy - methods; photodynamic therapy; Photosensitizing Agents - administration & dosage; protoporphyrin IX; Protoporphyrins - metabolism; psoriasis; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis - metabolism; Psoriasis - pathology; Psoriasis. Parapsoriasis. Lichen; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Severity of Illness Index; Skin - immunology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - radiation effects; Treatment Outcome; Human; Immunohistochemistry; Skin disease; Photodynamic therapy; protoporphyrin IX; Psoriasis; Levulinic acid(5-amino); Dermatology; Fluorescence; 5-aminolaevulinic acid; Accumulation; 5-Aminolevulinic acid; Anatomic pathology; Protoporphyrin; Treatment; Efficiency; Placebo; Clinical trial; Diagnosis; fluorescence diagnosis
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2006.07290.x

Summary 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. Methods  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.