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Notes: This study examines the prevalence of sun-related damage to the skin in a caucasian population in north-west England. The importance of constitutional factors (complexion, skin type and age) as well as environmental and occupational exposures for the development of actinic keratosis (AK) and skin cancers was assessed in people over 40 years of age attending outpatient clinics (non-dermatology) at four centres in north-west England (Mersey region). Nine hundred and sixty-eight volunteers (531 men and 437 women) were recruited. The overall prevalence of AK was 15·4% in men and 5·9% in women. The prevalence was strongly related to age in both sexes, being 34·1% and 18·2%, respectively, in men and women aged 70 years and above, and was most strongly related to two objective signs of sun exposure, namely degree of solar elastosis and presence of solar lentigines. The prevalence of AK was higher in subjects with red hair and freckles, particularly women. There was no evidence of an increased prevalence of AK in relation to any occupation. There was a high prevalence of seborrhoeic keratosis and viral warts in both sexes, which was age-related in the case of seborrhoeic keratosis. Ten cases of basal cell carcinoma, eight cases of Bowen’s disease and one case of malignant melanoma were identified. This study shows that the sun exposure received in ‘normal’ life in England is sufficient to cause potentially malignant skin damage in a significant proportion of the population.

Notes: Background Hydrophilic drugs are poorly absorbed when applied topically, due to low partitioning through the lipid matrix of the stratum corneum. Cutaneous blood flow rapidly clears the absorbed drug, which may result in low tissue levels. This is of importance for topically applied drugs whose site of action is within the epidermis or dermis. Dermal drug levels can be measured using cutaneous microdialysis, which is a means of continuously sampling substances from the dermal extracellular fluid. Objectives To measure the contribution of stratum corneum barrier and microvascular perfusion in determining dermal tissue levels of hydrophilic drugs (aciclovir and penciclovir) in vivo. Methods Studies were performed using microdialysis of the volar surface of the forearm of healthy volunteers (n = 55) over a 5-h collection period. Stratum corneum was removed by tape stripping, and barrier disruption quantified by measurement of transepidermal water loss (TEWL); dermal microvascular perfusion was modulated by inclusion of noradrenaline in the microdialysis perfusate. Results With intact skin and normal cutaneous blood flow the concentration of penciclovir recovered was below assay threshold (0·05 ng mL−1). With noradrenaline-induced local vasoconstriction, the area under the curve of drug absorbed through normal skin (± SEM) was 13·3 ± 2·9 ng mL−1 h(0−5) for penciclovir and 27·6 ± 10·6 ng mL−1 h(0−5) for aciclovir. Removal of the stratum corneum (to glistening) by tape stripping increased penciclovir absorption by 1300-fold and aciclovir absorption by 440-fold, confirming the stratum corneum as the major barrier to hydrophilic drug absorption. Sequential barrier disruption by tape stripping gave a close correlation between penciclovir concentration absorbed per hour and barrier disruption measured by TEWL (r2 = 0·9283). There was a 15·6-fold difference in the recovery of penciclovir through barrier-deficient skin with and without cutaneous blood flow. There was no relationship between fibre depth and amount of drug dialysed, which suggests free movement of antiviral drug on reaching the aqueous environment of the dermis. Conclusions This study defines for the first time the relationship between the degree of mechanical barrier impairment and drug absorption at the same anatomical site in humans, and the role of blood flow in drug clearance in vivo.