TNF Inhibitors in Dermatology: From Thalidomide to Biologics

Abstract

Inflammatory skin diseases represent an important part of dermatological pathology. Recent advances in the understanding of inflammatory processes have identified various cytokines, and in particular Tumor necrosis factor (TNF) as a potent and central proinflammatory cytokine involved in many conditions, including rheumatic, gastrointestinal tract, and skin diseases. Therefore, inhibition of TNF has become a major therapeutic target in the treatment of inflammatory disorders. Thalidomide is one of the first TNF inhibitors that have been used. It was initially prescribed by chance and pragmatically by dermatologists in inflammatory diseases such as erythema nodosum leprosum, lupus and severe aphtosis, but its identification as an inhibitor of TNF is more recent. The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the emergence of 3 new anti-TNF alpha drugs. These so-called biologics are two monoclonal antibodies (infliximab and adalimumab) and one fusion protein composed of a soluble TNF alpha receptor (etanercept) specifically directed against TNF. The first clinical data are very impressive, but new and unexpected side effects have progressively been described. These powerful drugs are increasingly prescribed, and the aim of this work is to summarize the recent knowledge on the old (thalidomide) and new (biologics) TNF inhibitors in dermatological diseases.