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With a prevalence of 1 in 6,000 births, tuberous sclerosis is a relatively frequent hamartoma and tumor syndrome inherited as an autosomal dominant trait, which manifests primarily on the skin and in the central nervous system. Decisive factors for morbidity and mortality and thus for the prognosis are the changes in the central nervous system in the form of cortical hamartomas. Treatment for many years consisted solely in using nonspecific symptomatic approaches; dermatological therapy comprised mainly laser or electroacoustic ablation of facial angiofibromas. New models of therapy hinder the pathogenesis of tuberous sclerosis. Various studies provided evidence that the macrolide rapamycin decreases growth of brain and kidney tumors by specific inhibition of mTOR kinase. Synergistic effects were observed in combination therapy with the cytokine IFN-gamma.

The recent identification of the nitric oxide synthase (NOS) pathway in various cell types in the skin has provided important insight into the molecular mechanisms underlying regulatory and homeostatic functions of the skin. Many studies also point to perturbations or defects in the signaling cascade of nitric oxide (NO) and reactive nitrogen intermediates as key players in skin disease pathogenesis. A critical role for NO is now established for a subset of human skin diseases, and new mechanism-based therapies may be available in the near future. This remarkable progress and the implications it may have for common forms of skin disease are reviewed here.