ABSTRACT
In the 1970s and 1980s dermatology was exploring and developing systemic retinoid therapy as a treatment for a wide variety of disorders of cornification (DOC). This direction was not based on a detailed understanding either of the molecular mechanisms of retinoid action nor an understanding of the pathophysiologic mechanisms causing the clinical disorders. At the time this was developing, there was no knowledge of the nuclear retinoid receptors and X-linked ichthyosis due to steroid sulfatase deficiency was the only main DOC whose pathophysiology was even barely understood. Today our understanding of the genes involved in a wide spectrum of DOC’s has exploded, revealing that these disorders are caused by a wide spectrum of diverse mechanistic abnormalities that include abnormal keratin intermediate filament structural proteins, connexins , transglutaminase, filaggrin, lipozygenases, transport proteins, etc. It is amazing that disorders with such a broad spectrum of diverse etiologies could respond to the same few systemic retinoid drugs. At the same time, progress has been made in understanding of molecular mechanisms underlying retinoid action. Despite this enormous progress in understanding both pharmacology and pathophysiology, this knowledge has not translated into the development of more compounds for treatment of the DOC’s.
