Bart W. Boom

Determination of the photoprotective efficacy of a topical sunscreen against UVB-induced DNA damage in human epidermis

The ability of a chemical sunscreen with a sun protection factor of ten to protect human skin in situ against UVB-induced DNA damage (cyclobutyl thymine dimers) was evaluated. Biopsies were taken from the left buttock of ten human volunteers prior to UVB (280-315 nm) exposure. Subsequently, a sunscreen (n = 6) or vehicle (n = 4) was applied to a delineated area on the right buttock. After a period of 30 min, the entire buttock area was irradiated in a UVB cabin with one minimal erythema dose. Immediately after irradiation, biopsy specimens were obtained from the UVB-exposed sunscreen- or vehicle-treated right buttock and from the non-treated UVB-exposed left buttock. Dimers were assayed in skin sections by immunofluorescence microscopy with a monoclonal antibody against the cyclobutyl thymine dimer. The dimer-specific fluorescence from the epidermal cell nuclei, identified by counterstaining with propidium iodide, was quantified through computer-mediated image processing and analysis in skin sections of one sunscreen-treated and one vehicle-treated volunteer. After a single dose of UVB, significant dimer-specific nuclear fluorescence was observed and measured in the non-treated biopsy specimens. No nuclear fluorescence was observed and very little could be measured in the non-UVB-exposed skin and in the sunscreen-treated UVB-exposed skin respectively, indicating that the sunscreen offered good protection against the induction of cyclobutyl thymine dimers by UVB. This visual scoring is in general semiquantitative, but quantification through computer-mediated image processing was performed in one case for sunscreen-treated skin and in one case for vehicle-treated skin. Both assessments resulted in similar conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Minimising the Risks of PUVA Treatment

SummaryPsoralen photochemotherapy (PUVA) is a combination of orally administered psoralen and long wave ultraviolet-A radiation (UVA), and is one of the most effective forms of therapy for psoriasis. The unwanted effects of PUVA therapy can be divided into short and long term adverse effects. The short term adverse effects include erythema, pruritus, nausea and headache. While short term adverse effects are limited and reversible after discontinuation of treatment, potential long term adverse effects such as chronic actinic skin damage, dyskeratotic and precancerous skin conditions, nonmelanoma skin cancer, immunological alterations and cataract formation are of greater concern.Long term risks associated with PUVA therapy can be minimised by several measures. Careful patient selection is mandatory; for example, patients with chronic actinic damage and a history of skin cancer may bear a higher risk for the development of new cancers, and previous arsenic intake and ionising radiation also increase the risk of nonmelanoma skin cancers. Certain drug combinations make it possible to lower the UVA dose, which is important because of the dose-dependent increase in the incidence of squamous cell carcinomas in patients treated with PUVA. It has been demonstrated that 200 treatments or a total UVA dose of 1200 J/cm2 seems to be the threshold for development of nonmelanoma skin cancer. Shielding male genitalia during PUVA treatment is essential because of the increased risk of genital squamous cell carcinomas. Yearly dermatological examination to detect skin cancer at an early stage is highly advisable. Sunscreen use, protective clothing and avoidance of sun exposure reduce the uncontrolled dose of solar UV radiation. Other psoralens with a less carcinogenic potential can be used. UVA-opaque sunglasses during the entire period of increased photosensitivity after psoralen ingestion help avoid cataract formation.Assignment to PUVA ought to be based on the risk-benefit ratio for the individual patient and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians.

Decreased expression of decay-accelerating factor on endothelial cells of immune complex-mediated vasculitic skin lesions.

Endothelial cells may be damaged directly by the membrane attack complex of complement in immune complex vasculitis of the skin. However, for endothelial cell membrane injury to occur, normal regulatory mechanisms must fail. One of the main complement regulatory proteins of endothelial cells is decay-accelerating factor, a surface protein which interferes with either the classical or alternative pathway C3 and C5 convertases. We have investigated the expression of decay-accelerating factor in 4 patients with histologically proven cutaneous immune complex vasculitis, using an immuno-electronmicroscopic technique. We demonstrated that endothelial cells of upper dermal vessels in vasculitic lesions were almost completely devoid of decay-accelerating factor. By contrast, the expression of this protein on endothelial cells in uninvolved skin of the patients was the same as in skin of healthy volunteers. As yet, the mechanism responsible for depletion of decay-accelerating factor is not clear. Absence of decay-accelerating factor may follow enzymatic release from the phosphatidylinositol anchor, proteolytic stripping from the cell membrane or a down-regulation of decay-accelerating factor synthesis. Regardless of mechanism, endothelial cell injury or death could serve a phlogistic function to facilitate complement-mediated destruction of endothelial cells for removal and repair.

Presence and interpretation of vascular immune deposits in human skin: The value of direct immunofluorescence

Direct immunofluorescence investigation of the skin is an easy and valuable technique to establish the diagnosis immune complex vasculitis. Vascular immune deposits can be found in 60-80% of all cases. Absence of vascular immune deposits, however, does not exclude vasculitis per se, since the dynamics of the vasculitic process limit their presence in time. Knowledge of these dynamics is indispensable for both the clinician and the interpreter. Several practical options are discussed that may increase sensitivity. The specificity of vascular immune deposits has become a complex matter. Different immunoglobulin classes have different specificity, indicating that specificity also depends on the relative incidence of individual immunoglobulin classes. Some of these relative incidences seem to have changed over the years. Furthermore, several non-vasculitic diseases and conditions have now been described, that may show fluorescent pictures similar to vasculitis and thus decrease specificity.