title: Hyperpigmentation induced by topical 5-aminolaevulinic acid plus visible light.
abstract: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an alternative tool for the treatment of superficial non-melanoma skin cancers. Recently ALA-PDT has been employed with encouraging results also for warts, condylomata and psoriasis. In this study the effects of topical ALA plus irradiation with visible light on intact human skin have been evaluated. Five skin areas (A, B, C, D, and E) on the inner upper part of the arms of five healthy volunteers (skin types III and IV) were treated with (A) ALA 20% in base cream without irradiation, (B) only the vehicle (base cream) without ALA, (C, D and E) ALA cream at the concentrations of 5, 10 and 20%, respectively; all treatments were applied with an occlusive dressing. Four hours after ALA or vehicle application areas B, C, D and E were irradiated with a fixed dose of 40 J/cm(2). ALA penetration through the intact skin was evaluated by in vivo fluorescence determination. The effects on healthy skin were evaluated by clinical and chromometric examinations, light microscopy, immunohistochemistry and electron microscopy.
  
  
  RESULTS
  (1) in vivo fluorescence demonstrated that ALA is able to penetrate through the intact skin, when applied with occlusive dressing and induces a classical fluorescence peak due to Protoporphyrin IX (PpIX) formation, which is the active photosensitiser. (2) Skin areas receiving ALA plus irradiation showed erythema and swelling just after the irradiative session and hyperpigmentation 48-72 h later. (3) Colourimetric data confirmed significant skin colour changes: values a* (representing the erythematous changes) increased only on the skin areas where ALA+irradiation were applied and during the 48 h after irradiation, thereafter a* began to decrease; values L* (pigmentation) increased during the 2 weeks following treatment. (4) Histopathological, immunohistochemical (S100, HMB-45) and electron microscopic findings showed an absolute increment of the number of melanocytes, which appeared clearly activated. In conclusion the application of ALA cream followed by irradiation is able to induce a pigmentation response in healthy human skin, at least in skin types III and IV. This melanocytic activation could have a potential for the treatment of skin disorders characterised by hypopigmentation.
authors.affiliation: Department of Dermatology, University Federico II, Via S. Pansini 5, 80131 Napoli, Italy. monfreco@unina.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Monfrecola
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Procaccini
authors.forename: Donatella
authors.initials: D
authors.lastname: D'Onofrio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Roberti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Liuzzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
authors.forename: Alfredo
authors.initials: A
authors.lastname: Manco
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
authors.forename: Pietro
authors.initials: P
authors.lastname: Santoianni
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D003124:Colorimetry; D005260:Female; D006801:Humans; D017495:Hyperpigmentation / Q000139:chemically induced* / Q000209:etiology*; D008027:Light; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010778:Photochemotherapy; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure
chemical_list: D000622:Aminolevulinic Acid