Dermatology and venereology

We study gene mutations and pathogenetic mechanisms underlying skin barrier defects. Ichthyosis exhibits generalized hyperkeratosis and epidermolysis bullosa (EB) shows skin fragility. Some are due to dominant keratin mutations disrupting the cytoskeleton. Others are caused by enzyme deficiencies which negatively affect the horny layer. Many patients benefit from treatment with retinoids (vitamin A analogs). Those with associated hyperhidrosis benefit from injections of botulinum toxin. We study the regulation of keratin and other genes by retinoids and RNAi, aiming at improving treatment. We work in a EU network (GeneSkin) and represents a national referral centre for genodermatoses.

Psoriasis is a common disease with three variants - psoriasis vulgaris, psoriatic arthritis and palmoplantar pustulosis (PPP). Psoriasis may have an autoimmune etiologybut no specific autoantigens have yet been identified. Exogenous factors, e g smoking can precipitate the disease.

PPP is associated with several autoimmune disorders. It affects mainly smoking women. The inflammation is directed against the palmo-plantar sweat duct. The inflammation and the influence of smoking is under study; attempts to identify autoantigens are ongoing.

In all types of psoriasis we have found increased numbers of inflammatory cells in the gut mucosa, findings which have generated new ideas concerning the pathogenesis of psoriasis.

In order to study epidermal formation in vitro, a skin explant culture technique has been developed. We utilize fluoroprobe imaging to visualize outgrowth of fresh epithelium on a substrate of cell-free dermis. Growth rates and morphological features of newly formed epidermis are studied. Current research is focused on epidermal growth factor (EGF)-mediated signaling and the effects of antibodies and tyrosine kinase inhibitors targeting EGF receptor family members. Our aim is to identify new means by which growth abnormalities in psoriatic skin and other hyperproliferative disorders can be reversed.