Would Cyclosporin A Be Beneficial to Mitigate Drug-Induced Toxic Epidermal Necrolysis?

Abstract

Drug-induced toxic epidermal necrolysis (TEN) is a rare life-threatening disease whose mortality remains high. The treatment of the disease is badly settled. Several kinds of drugs have been tested, including systemic corticosteroids, cyclophosphamide, pentoxifylline and thalidomide, but without any clear-cut outcome. Cyclosporin A (CsA) has many inhibitory effects on the main cell populations involved in TEN (T lymphocytes, macrophages and keratinocytes). CsA could also act on tumor necrosis factor α metabolism, a cytokine which is important in TEN epidermal destruction. Moreover, apoptosis is the mechanism leading to keratinocyte death and CsA has antiapoptotic properties. CsA has already been used successfully on a limited series of TEN patients. We have reviewed the potential theoretical useful effects of CsA in TEN. We conclude that CsA could be a good candidate to reverse TEN progression.

Analytical quantification of the inflammatory cell infiltrate and CD95R expression during treatment of drug-induced toxic epidermal necrolysis

“…However, there was no evidence for a benefit in the healing process, while they worsened the prognosis by increasing the risk of septicemia [8]. Only a few case reports have reported other treatment modalities including cyclophosphamide [6], pentoxyfilline [23], thalidomide [31] and cyclosporin A (CsA) [1,9,12,15,18,21,25,26,32]. Although T lymphocytes are the main target of CsA, the drug could also somewhat prevent keratinocyte apoptosis in TEN [15].…”

“…Only a few case reports have reported other treatment modalities including cyclophosphamide [6], pentoxyfilline [23], thalidomide [31] and cyclosporin A (CsA) [1,9,12,15,18,21,25,26,32]. Although T lymphocytes are the main target of CsA, the drug could also somewhat prevent keratinocyte apoptosis in TEN [15]. Some TEN patients have also been treated with intravenous human immunoglobulins (IVIg) [2,10,14,19,20,24,[28][29][30].…”

“…Cyclosporin A was also proposed for reversing TEN progression [1,9,12,15,21,25,26,32]. The suppressive action of CsA primarily targets T-cell functions, and it inhibits the macrophage activation [15].…”

“…The suppressive action of CsA primarily targets T-cell functions, and it inhibits the macrophage activation [15]. CsA also re- duces TNF-a secretion by human epidermal keratinocytes in vitro [15].…”

“…This cytokine is one of the major ones involved in TEN epidermal destruction. Treatment of mice with subcutaneously injected CsA was shown to inhibit TNF-a gene expression by about 70% in the skin [15]. In addition, the CsA immunosuppressive effect may partly be mediated by inhibition of the activation of the FasR-FasL system.…”