Cyclosporin for psoriasis : clinical and immunopathological studies
Ten patients with severe intractable psoriasis were treated with cyclosporin (CyA) at an average dose of 3 mg/kg/day for a period of 12 weeks. At the end of the study, 5 patients had a greater than 90% reduction in their PASI (psoriasis area severity index) score, 3 an 80%, one a 69% and one a 52% reduction. In a long term study, 13 patients with severe psoriasis were treated with CyA for an average duration of 2.5 years. The average dose of CyA was 3 mg/kg/day, with a range of 1 - 5 mg/kg/day. The average reduction in mean PASI score throughout the study was 70 - 80%. Seven of the 13 patients developed a rise in blood pressure, 3 of whom required antihypertensive therapy. Studies on possible nephrotoxicity showed that 4 of the 13 had a greater than 30% rise in their serum creatinine compared to their baseline value. 6 of the 13 patients had a low glomerular filtration rate (GFR) at the end of the study, but this rose in all 6 when CyA was discontinued, and to normal levels in 5 patients. In the sixth, a renal biopsy was performed which showed no structural damage due to CyA. In a further 11 patients, the mean GFR was shown to fall significantly after 9 weeks of CyA. Thus, CyA causes impairment of renal function with a dose of 3 mg/kg/day, but this impairment appears to be reversible when CyA is stopped. Six patients with plaque psoriasis were treated with topical CyA, and a further 10 with intralesional CyA. Topical CyA was ineffective, but intralesional CyA was effective in clearing psoriasis, implying that failure of topical preparations is probably due to lack of penetration. T cell and dendritic cell subsets in psoriasis were studied during oral CyA, and at the end of intralesional CyA treatment. After oral CyA, total CD4 and CD8, and DR+CD8 cells were decreased in the epidermis and dermis. However, DR+CD4 cells were decreased in the dermis but not the epidermis. After intralesional CyA, total and DR+CD4 and CD8 cells were decreased in both dermis and epidermis. The most significant effect of both intralesional and oral CyA on the dendritic cells was the decrease of the DR+CD1-subset.