Hailey-Hailey disease successfully treated with vitamin D oral supplementation.

Hailey-Hailey disease (HHD) also known as familial benign chronic pemphigus is a rare autosomal dominant genodermatosis. HHD treatment is often not satisfactory and hence, various modalities of treatment have been tried. We describe the case of a 37-year-old woman with a 2 years history of macerated erythematous plaques along with erosions, fissures, and crusts located on axillae and submammary areas, successfully treated with only oral supplementation of vitamin D (800 I.U./die) for 3 months. We reported this case to suggest that oral vitamin D may be enumerated in the various treatments proposed for HHD so far due to its rapid efficacy on skin lesions and symptoms.

Topical delivery of active principles: the field of dermatological research.

To be effective an active drug or principle must cross the stratum corneum barrier; this process can be influenced to obtain better functional and therapeutical effects. In spite of the wide variety of the methods studied in order to improve the transdermal transfer to obtain systemic effects, the applicability is limited in this field. Attention to the epidermal barrier and penetration of active principles has been reported mostly in studies concerning dermocosmetics. Studies regarding methods of penetration are gaining experimental and clinical interest. Cutaneous bioavailability of most commercially available dermatological formulations is low. Increase of intradermal delivery can relate to chemical, biochemical, or physical manipulations. Chemical enhancers have been adopted to: (a) increase the diffusibility of the substance across the barrier; (b) increase product solubility in the vehicle; (c) improve the partition coefficient. Moreover methods of interference with the biosynthesis of some lipids allow the modification of the structure of the barrier to increase the penetration. The main physical techniques that increase cutaneous penetration of substances are: iontophoresis (that increases the penetration of ionized substances), electroporation (that electrically induces penetration through the barrier), and sonophoresis, based on 20 to 25 KHz ultrasound that induces alterations of the horny barrier, allowing penetration of active principles. Recent development of these methods are here reported and underline the importance and role of vehicles and other factors that determine effects of partition and diffusion, crucial to absorption.

Intradermal drug delivery by low-frequency sonophoresis (25 kHz).

UNLABELLED: Ultrasound waves (US) have been proposed to facilitate the absorption of active compounds (transdermal delivery) stimulating some disaggregation of the horny layer and promoting convective movements within the epidermis. Drugs used for alopecia areata, melasma, and lentigo, although proved effective, have limited effects resulting from only partial penetration into the skin. This study has evaluated the efficacy of low-frequency sonophoresis (LFS) at 25 kHz produced by a sonicator apparatus for treatment of alopecia areata, melasma, and solar lentigo. Thirty patients affected by alopecia areata were treated by application of methylprednisolone or cyclosporine solution followed by LFS. In a case-control study 48 women with melasma and 48 with solar lentigo were also treated by depigmenting emulsion and LFS application. For alopecia areata after 36 applications with LFS and 3-month treatment, the results were 57 percent partial regrowth and 29 percent total with methylprednisolone, and 33 percent partial regrowth and 34 percent total when cyclosporine was used. For melasma and solar lentigines the results when the drug application was followed by LFS, were (after twice-a-week application for 3 months) 75 percent complete depigmentation and 25 percent partial for melasma, 43 percent total regression and 57 percent partial for solar lentigo. CONCLUSION: This is the first report of sonophoresis at a frequency of 25 kHz in dermatocosmetology. The study shows that LFS, a not aggressive technique, enhance penetration of topic agents obtaining effects at the level of the epidermis, dermis and appendages (intradermal delivery), giving better results in the treatment of some cosmetic skin disorders.

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.