Real-World Experience With Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis.

INTRODUCTION: 5-fluorouracil (5-FU) is one of the most effective topical treatments for actinic keratosis (AK). A new 4% formulation of 5-FU was recently approved in Europe. OBJECTIVES: This study aimed at evaluating 4% 5-FU cream safety and effectiveness in a real-world setting. METHODS: Adult AK patients were retrospectively selected from the University of Campania Dermatology Unit database. Selection criteria included a diagnosis of non-hyperkeratotic, non-hypertrophic AK (Olsen grade I and II) of the face, ears, and/or scalp, treatment with 4% 5-FU once daily for 4 weeks, and at least 3 follow-up visits (4 and 8 weeks after treatment initiation, and 6 months after treatment end). The primary objectives were to evaluate AK lesions improvement at 8 weeks and relapse rate at 6 months. Patient-reported erythema and burning sensation intensity were also assessed at 4 weeks. RESULTS: Ninety-eight patients were included in this analysis (male/female 80/18, mean age 74.7 years). AK lesions improvement at 8 weeks resulted complete or significant in 74.5% and 20.4% of the patients, respectively. At 6 months, 65.3% of the patients did not show AK relapses. Burning sensation at 4 weeks was reported as light, moderate, or absent by 44.9%, 22.4%, and 31.6% of the patients, respectively. Erythema was reported as light, moderate, or absent by 37.8%, 51%, and 10% of the patients, respectively. Burning sensation and erythema disappeared gradually during follow-up. No other side effects were reported. CONCLUSIONS: In this real-world study 4% 5-FU proved to be highly effective for AK lesions clearance with a favorable safety profile.

In vitro effect of 5-aminolaevulinic acid plus visible light on Candida albicans.

Photodynamic therapy, currently used as an alternative technique for the treatment of superficial non-melanoma skin cancers, has been employed in vitro to kill different species of microorganisms. Here the development of Candida albicans colonies has been measured after application of 5-aminolaevulinic acid (ALA) plus visible light (VIS) irradiation. C. albicans suspensions (10 colony forming units microl(-1)) have been prepared. For the experiment 30 microl of suspension have been incubated in the dark for 3 h, with increasing concentrations of ALA (125, 250, 300, 350, 400, 450, 500, 550, 600, 750, 1000 mg ml(-1)) and then irradiated with a fixed dose (40 J cm(-2)) of VIS. Immediately after the irradiative session, the C. albicans suspensions were disseminated on dishes containing a Sabouraud agar + CAF medium and cultured in the dark at 27 degree C; after 48 h colony development has been measured. In the same way four controls have been prepared: (i)C. albicans suspensions not treated with ALA-PDT; (ii)C. albicans suspensions incubated with increasing ALA concentrations without VIS; (iii)C. albicans suspensions irradiated with 40 J cm(-2) of VIS without ALA; (iv)C. albicans suspensions irradiated immediately after the addition of increasing concentrations of ALA without the 3 h incubation. Colonies treated with ALA-PDT have been studied with electron microscopy (E.M.). It was found that: (i) none of the controls prepared modified the development of C. albicans colonies; (ii) ALA plus VIS inhibited C. albicans growth in a concentration-dependent way: up to 250 mg ml of ALA concentrations did not affect C. albicans cells, 300 mg ml(-1) induced a 50% reduction in the number of colonies, a complete inhibition started from concentrations of 600 mg ml(-1); (iii) after ALA-PDT E.M. showed modifications of the cell membranes. From the results it is concluded ALA plus VIS light is able to kill C. albicans colonies, at least in vitro. Although other pharmacological approaches are available, further studies could show that PDT is a potential treatment for candidosis.

Hyperpigmentation induced by topical 5-aminolaevulinic acid plus visible light.

UNLABELLED: 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.