Long-term low-dose cyclosporine therapy for severe psoriasis: effects on renal function and structure.

BACKGROUND: The effectiveness of cyclosporine in the treatment of severe psoriasis is well known. OBJECTIVE: We evaluated the efficacy and toxicity of systemic cyclosporine in patients with severe psoriasis, observing short-term (12 weeks) and long-term (3 to 5 years) effects. METHODS: To further elucidate efficacy and safety, 42 patients with severe psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treatment for 3.5 years to study the long-term effects of cyclosporine on renal function and structure. Renal biopsies were performed after 2.5 years and 3.5 years of treatment. Renal histologic findings were correlated with renal function. RESULTS: By weeks 8 and 12, 64% (n = 27) and 86% (n = 36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not respond to 5 mg/kg daily but improved when the dose was increased to 6 mg/kg daily. Clearance or near clearance was achieved in 67% of this subpopulation after 4 weeks. For the 29 patients whose glomerular filtration rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p < 0.05). This change was reversible when dosage was reduced by 1 mg/kg per day in each of these patients. Patients older than 45 years of age experienced significant elevation of mean diastolic blood pressure and had reduced GFR and increased serum creatinine. After 2.5 years, of the 14 patients who continued maintenance treatment, two had biopsy specimens that showed moderate interstitial fibrosis and tubular atrophy. The remainder showed only minimal to mild structural damage. After 3.5 years of cyclosporine treatment, repeat renal biopsy specimens revealed slight increases in structural changes in nine subjects. These changes correlated with increasing age and drug-induced hypertension. CONCLUSION: We conclude that 5 mg/kg of cyclosporine daily is usually an effective initial dose for psoriasis. Patients who do not respond will often benefit from elevation of the dose to 6 mg/kg daily. Older patients experience cyclosporine-induced hypertension and changes in renal function and structure more frequently than do younger patients.

Photoreactions with a fluoroquinolone antimicrobial: evening versus morning dosing.

Quinolone antimicrobials absorb ultraviolet radiation and, with appropriate drug concentrations, may cause photoreactions. Photoreactions have been reported for several quinolones, including lomefloxacin, a difluorinated quinolone antimicrobial. This study was designed to determine whether the interval between administration of lomefloxacin and exposure to ultraviolet A (UVA) light would affect skin responses. The minimal erythema dose (MED) and severity of local reactions were the main parameters of evaluation. Exposure to UVA radiation 2 hours after morning dosing caused an increase in skin sensitivity as assessed by changes in MED (p < 0.05). No changes were observed with exposure 16 hours after evening dosing (p = 1.00). Edema and blisters at the radiation sites were observed in only the morning dosing group. A significant negative correlation was observed between lomefloxacin plasma concentrations and change MEDs (r = -0.72; p < 0.05). An evening dosing strategy may minimize the risk of phototoxic effects.

Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone.

UVB radiation is beneficial for the treatment of psoriasis vulgaris. Patients with recalcitrant disease, however, are slow to respond to UVB phototherapy with and without the use of coal tars or emollients. Etretinate and, more recently, acitretin have proved useful, but clinical improvement is slow when they are used as monotherapy in plaque psoriasis. Each drug also produces side effects, some of which are dose related. This study was designed to compare results of treatment with UVB combined with either acitretin (50 mg/day) or placebo to determine if psoriasis would respond faster and to less cumulative exposure to UVB and acitretin. The psoriatic disease cleared to a greater degree in patients treated with acitretin-UVB with fewer treatments and smaller amounts of UVB radiation than in patients treated with either placebo-UVB or acitretin alone.

Indoor and outdoor efficacy testing of a broad-spectrum sunscreen against ultraviolet A radiation in psoralen-sensitized subjects.

The efficacy of a sunscreen containing an investigational drug, butyl methoxydibenzoylmethane in combination with padimate O against the erythemogenic effect of ultraviolet A (UVA) radiation was evaluated in two double-blind studies involving subjects sensitized with topical 8-methoxypsoralen. UVA radiation was supplied from either a filtered solar simulator (indoors) or filtered sunlight (outdoors). Five formulations were tested: 3% butyl methoxydibenzoylmethane and 7% padimate O, 7% padimate O, 5% octyl salicylate, and 3% oxybenzone, 3% butyl methoxydibenzoylmethane alone, 7% padimate O alone, and vehicle. Sunscreen protection against the erythemogenic effect of UVA radiation was expressed as phototoxic protection factors. The phototoxic protection factor for each sunscreen was derived from a ratio of the minimal phototoxic dose of UVA radiation that produced delayed erythema on sunscreen-protected and unprotected skin. The combination of 3% butyl methoxydibenzoylmethane and 7% padimate O provided significantly greater protection than the other sunscreen formulations, and for each sunscreen the phototoxic protection factors determined indoors and outdoors were comparable.

PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methoxypsoralen.

A direct clinical comparison has been made of the efficacy of oral 8-methoxypsoralen with bath-water delivery of 8-methoxypsoralen during psoralen ultraviolet A (PUVA) phototherapy for a group of forty patients with stable plaque-type psoriasis vulgaris. The 8-methoxypsoralen concentration was 3.7 mg/liter in the bath water. The efficacy of these treatments was assessed by their ability to improve or clear the psoriasis. The skin of eight of the twenty patients with oral psoralen cleared, and another eight showed good improvement. Of the twenty patients who received 8-methoxypsoralen in bath water, eight patients had clearing of the skin, whereas nine patients had good improvement during the initial 8-week treatment period. Administration of 8-methoxypsoralen in bath water required much lower ultraviolet A irradiance to achieve maximum improvement. There were no systemic side effects in the patients treated by bath-water delivery; however, some patients did develop phototoxic erythema. Minimal phototoxic doses were also studied in patients and in volunteers using both routes of psoralen delivery. The minimal phototoxic dose threshold after psoralen bath delivery gradually declined over five treatments from 5.3 +/- 0.6 joules/cm2 to 2.8 +/- 0.3 joules/cm2, suggesting an accumulation of psoralen in the skin with this method of drug delivery. Bath-water delivery of 8-methoxypsoralen was therefore found to be as effective as oral administration of 8-methoxypsoralen and yet required smaller amounts of ultraviolet A radiation and yielded fewer side effects. It would thus seem to be confirmed as a useful alternative means of 8-methoxypsoralen administration in PUVA therapy.