Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis

Abstract

Background-Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with longwave UV radiation in the A range (PUVA), oral retinoids, and methotrexate.We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506).Observations-All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy.Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes.Tacrolimus was well tolerated during the 5.5 to 14 months of observation.Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage.Conclusions-Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis.The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function.Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.Psoriasis, a common heritable disease that affects the skin, the joints, or both, has many characteristics of an immunologically mediated disease.Included, among these characteristics are a variable HLA association, lymphocytic infiltration of skin lesions, and evidence of cytokine activity or increased expression of new antigens during exacerbations. 1,2Circumstantial evidence for an immune etiology is the striking remission of psoriatic lesions that can be achieved with cyclosporine, 3-6 an immunosuppressive drug whose use for this purpose has been limited its by nephrotoxicity, hypertension, and other dose-related side effects.We report our experience with tacrolimus (FK 506), another immunosuppressive drug that is unrelated chemically to cyclosporine but also inhibits helper T-lymphocyte activation and the synthesis and expression of cytokines. 6,7Encouraging results with tacrolimus have been reported in trials of whole organ transplantation. 8-10 PATIENTS AND METHODSClinical features are summarized in Table 1.Amelioration of psoriasis in four patients was incidental to the primary objective, preventing organ rejection of heart (one patient) or liver transplantation (three patients).The liver disease in one of the latter patients was caused by