Thalidomide in cutaneous lupus erythematosus

Abstract

Thalidomide (α-N-phthalimidoglutarimide) was initially introduced into clinical practice in the mid-1950s; since that time, it has had a remarkable checkered history. It was used early on as an over-the-counter sedative (Mellin and Katzenstein 1962), and then in the treatment of morning sickness in pregnancy. However, in 1961, thalidomide was withdrawn from the market because of the discovery of its potential teratogenicity it was associated with up to 12,000 cases of birth defects, particularly phocomelias (Mellin 1962, Randall 1990). Four years later, Sheskin serendipitously discovered that thalidomide had marked clinical efficacy in erythema nodosum leprosum (Sheskin 1965). Subsequently, a variety of conditions, including infectious, autoimmune, inflammatory, and malignant, have been shown to respond to thalidomide. Examples of these conditions include human immunodeficiency virus (HIV) infection (Reyes-Teran et al. 1996), rheumatoid arthritis (Guti?rez-Rodriguez et al. 1989),Behcet s syndrome (Hamuryudan et al. 1998), graft-versus-host disease (Vogelsang et al. 1993), multiple myeloma (Singhal et al. 1999), and cutaneous features of lupus erythematosus (LE) (Knop et al. 1983). The latter include systemic LE (SLE) with cutaneous features, discoid LE (DLE), and subacute cutaneous LE (SCLE). The common denominator of the previously mentioned differing conditions seems to be that they are all characterized by inflammation,immune dysregulation, or both. Thalidomide has been shown to have immunomodulatory, immunosuppressive, and anti-inflammatory actions, which may explain its therapeutic efficacy. Furthermore, thalidomide is often effective in conditions in which standard therapies have failed to make an impression, for example, severe ulceration in Behcet s syndrome or severe cutaneous lupus. Clinical use of thalidomide must, of course, be tightly regulated and supervised, not only because of the potential for teratogenicity, especially as many patients with lupus are young women,but also for the development of peripheral neuropathy. In this article,we discuss possible mechanisms of action and the clinical experience of thalidomide in the treatment of cutaneous features of LE.