New compounds for the treatment of eczematous skin diseases

Abstract

Eczematous skin diseases, like atopic dermatitis and contact dermatitis have been treated with topical glucocorticosteroids for decades. With the introduction of the immunophyllins FK506 and ascomycin, a new treatment era has begun. The increasing knowledge of pathophysiological interactions and immunological disturbances during the chronic inflammatory process in the skin offers many new therapeutical approaches. These are presented in this review, based on the status of recent patents. Novel therapeutical compounds include cytokine antagonists, cytokine-receptor antagonists, but also molecules interfering with signal transduction pathways. Such molecules inhibit certain intracellular signal transducing phosphatases or act at the molecular level of transcription factors. Recent developments target lymphocyte homing through interference of adhesion molecules and chemokine /chemokine receptors. The diversity of these interactions is extensive and clinical trials will unravel their clinical efficacy. Finally, the developments of glucocorticoid family members, such as retinoids, vitamin D and peroxisome proliferator activated receptor agonists, are discussed. Molecules from members of this family have profound differentiating, antiproliferative, but also immunomodulatory effects, which make them attractive as antieczematous compounds. The design of molecules with high selectivity or in combination formulae highlight them as molecules of interest.

• atopic eczema
• chemokines
• contact dermatitis
• cytokines
• IgE
• retinoids