We have analysed the expression of keratins in the epidermis of normal human palm and sole skin (ridged skin) using immunohistochemistry and in situ hybridization. The epidermis of human ridged skin expresses a more complex pattern of keratins than thin skin, which is probably due to the greater stress that ridged skin has to withstand. In addition to keratin K9, we document specific expression patterns of keratins K6, K16 and K17 which are suggestive of regional adaptations of this epidermis to a high cell turnover rate. In particular, the sequestered location of nests of K17-positive cells at the bottom of the deep primary epidermal ridges supports the notion of functional heterogeneity of basal cells and suggests that the K17-positive sites may include stem cells. Expression of K6 and K16 in some basal and most suprabasal keratinocytes is compatible with a constitutively high proliferative activity of normal ridged epidermis, but may also reflect different physical properties of the suprabasal cells, in contrast with regions expressing K9. The distinct labelling patterns observed in primary and secondary epidermal ridges as well as epidermal layers above dermal papillae suggest the existence of local microenvironmental niches leading to differences in keratinocyte differentiation.

We describe a 28-year-old woman with characteristic clinical signs of Comèl-Netherton syndrome (CNS) who showed numerous plane warts on her face and forearms and papillomatous skin tumours affecting her groins and genitoanal skin. Using human papillomavirus (HPV) type-specific primers for cutaneous and mucosal HPV types we identified HPV 16-specific sequences in plane warts and HPV 51- and HPV 52-specific DNA in papillomatous skin from the patient's groins, suggesting a pathogenetic role (cofactor) for HPV in the development of verrucous skin lesions in patients with CNS. Whether the susceptibility to HPV infections is due to decreased cellular immunity or epidermal defence mechanisms remains to be seen.

A 66-year-old woman presented with a bullous skin eruption and chronic diarrhoea. Lesional skin showed subepidermal blistering, and direct immunofluorescence of perilesional skin revealed linear deposits of IgA at the dermoepidermal junction, establishing a diagnosis of linear IgA disease (LAD). Chronic watery diarrhoea complicated by substantial loss of body weight preceded the skin eruption for several months. On endoscopy, the colon appeared macroscopically normal. On histology, the colon mucosa showed increased numbers of intraepithelial lymphocytes and infiltrates of mononuclear cells in the lamina propria, indicative of lymphocytic colitis. Treatment with methylprednisolone and dapsone led to complete clearing of the bullous skin eruption and marked improvement of the patient's diarrhoea. Gastrointestinal disorders such as lymphocytic colitis have rarely been reported in patients with LAD. Whether the simultaneous occurrence of these two diseases is coincidental or due to related pathogenetic mechanisms remains to be seen.