PSORIASIS - IMMUNOPATHOLOGY AND LONG-TERM TREATMENT WITH CYCLOSPORINE

Psoriasis is a disorder of abnormal keratinocyte proliferation mediated by T lymphocytes. Initiation of psoriasis is associated with an influx and activation of CD4 T lymphocytes into the dermis and epidermis, and resolution with an influx and activation of CD8 T lymphocytes within the epidermis. As a result of these observations it was postulated that cyclosporin (CsA) should prove to be an effective treatment for psoriasis. A total of 82 patients with psoriasis have been treated with CsA. Thirty patients with moderate disease were treated for periods up to 12 weeks, and comprised a short-term study. Two groups have been treated with long-term CsA. A group of 18 patients have been treated for >1 year but <3 years, (mean 2.1) and a group of 10 patients for 4.0-5.5 (mean 5) years. A total of 15% of patients can be maintained on ≤2 mg/kg/day; 55% on 3 mg/kg/day, 80% on 4 mg/kg/day, and 92% on 5 mg/kg/day. Hypertension occurred in 17% of patients in the short-term study, 29% in the 2.1-year group and 44% in 5-year group. Blood pressure returned to normal in all hypertensive patients when CsA was discontinued for 1 month. Nephrotoxicity was assessed by serum creatinine levels and glomerular filtration rate (GFR) and renal biopsy in the 5-year group. In the short-term group there was no significant rise in the serum creatinine. In the 2.1-year group two patients had a rise >50% base line value, and in the 5-year group two patients a rise >30% and two others a rise >50%. In patients with a rise >30%, and in the 2.1-year group patients with a rise of >50%, the serum creatinine returned to pretreatment levels 1 month after discontinuing CsA. However the levels remained above the 30% value in the two patients in the 5-year group who had rises >50%. GFR studies showed that 75% of patients will have some impairment of renal function whilst taking CsA and although this improves when CsA is discontinued for 1 month the values have not returned to pretreatment values in all patients. Two of the nine patients who had renal biopsies after 5 years of treatment showed definite changes of CsA nephrotoxicity. In patients with low GFR and renal biopsies abnormalities, CsA should be discontinued and patients monitored to see if these changes are reversible. © 1992.