We conducted a randomized, double-blind, placebo-controlled trial to assess the atrophogenicity of tacrolimus ointment. In a combined group of atopic dermatitis patients (n = 14) and healthy volunteers (n = 12), 0.3% tacrolimus, 0.1% tacrolimus, betamethasone-valerate, and a vehicle control were applied in a randomized order to nonsymptomatic, 4 cm x 4 cm regions of abdominal skin. After 7 d of treatment under occlusion, the carboxy- and amino-terminal propeptides of procollagen I (PICP, PINP) and the amino-terminal propeptide of procollagen III (PIIINP) were measured from suction blister fluid with specific radioimmunoassays. In addition, ultrasound measurements of skin thickness were taken. Betamethasone-treated areas showed median PICP, PINP, and PIIINP concentrations of 17.0%, 17.6%, and 39.5% of the vehicle control at the end of the treatment period, respectively, whereas the 0.1% and 0.3% tacrolimus-treated areas showed median concentrations of approximately 100% of the vehicle control (p < 0.001). Betamethasone was also the only treatment to reduce skin thickness; the median decrease in skin thickness was 7.4% relative to 0.1% tacrolimus, 7.1% relative to 0.3% tacrolimus, and 8.8% relative to the vehicle control (p < 0.01). Results for atopic dermatitis patients and healthy volunteers were similar. These findings suggest that tacrolimus does not cause skin atrophy.

Use of LW mesh for Lichtenstein hernia repair did not affect recurrence rates, but improved some aspects of pain and discomfort 3 years after surgery.

Although cyclosporin is effective for the treatment of severe atopic dermatitis, phototherapy is the standard second-line treatment for this disease. An open, randomized, controlled, parallel-group study was conducted to compare the efficacy, influence on quality of life and safety of cyclosporin and UVAB phototherapy during 1 year of intermittent treatment of atopic dermatitis in adult patients. The main endpoints of the study were the number of days in remission and the influence on quality of life. Seventy-two patients were treated, 36 in each group. Cyclosporin produced significantly more days in remission than UVAB phototherapy during the 1-year study period. At the end of the study no difference between the 2 groups was noted in terms of quality of life. A significant increase in serum creatinine occurred in 2 patients and 7 patients developed mild or moderate hypertension during cyclosporin treatment. It can be concluded that intermittent cyclosporin seems to be more effective than UVAB and is reasonably safe for the treatment of atopic dermatitis over a 1-year treatment period.

The efficacy of cyclosporin (CyA) in the induction of remission in atopic dermatitis has been documented in controlled studies. However, little information is available on the duration of remission after CyA treatment. We studied the length of remission in 43 patients with severe atopic dermatitis after a 6-week treatment period with CyA at 5 mg/kg per day. After a follow-up of 6-26 weeks, depending on the time-point of relapse, a second treatment period with CyA, identical to the first, was performed. Disease activity was evaluated bi-weekly, using six different parameters: 1, a total body disease activity score; 2, the extent of the disease; 3, the occurrence of itch; 4, the occurrence of sleep disturbance; 5, the use of topical emollients; and 6, the use of topical hydrocortisone. A significant decrease in disease activity was observed. The total body disease activity score decreased from the baseline score of 31 to 11.6 at the end of the first part and to 13.4 at the end of the second part of the study. An almost maximal response to treatment was already apparent after 2 weeks of treatment. All the other efficacy parameters studied also showed a significant response to CyA treatment. A similar response to CyA was seen when the patients were re-treated. After both treatment periods, approximately half of the patients relapsed after 2 weeks (42% first part; 54% second part). After 6 weeks follow-up, the relapse rates were 71 and 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Tacrolimus (FK506) is an effective and well tolerated immunosuppressant used to prevent allograft rejection. We describe the evaluation of two tacrolimus ointment formulations for treatment of chronic plaque-type psoriasis. This was a microplaque assay with randomized, double-blind design. Sixteen patients (15 men, one woman, all white and 28-69 years old) with chronic plaque-type psoriasis participated. Six different ointments were applied to discrete microplaques, 17 mm in diameter, on a descaled psoriasis lesion: these were tacrolimus ointment with diisopropyl adipate as penetration enhancer, tacrolimus ointment without diisopropyl adipate, 0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol ointment and, as controls, the ointment bases for tacrolimus and betamethasone. Ointments were reapplied and the area was sealed every 2-3 days during the 14-day treatment period. After 7 and 14 days, erythema and infiltration were graded on a scale of 0-4, and superficial blood flow was measured with a laser Doppler flowmeter. Epidermal thickness was measured histologically at the end of treatment. Compared with the vehicle controls, sites treated with tacrolimus ointment (with or without penetration enhancer) showed a significant reduction in erythema and infiltration (P < 0. 001), a significant reduction in superficial blood flow (P < 0.01) and a significant decrease in epidermal thickness (P < or = 0.001). Results for betamethasone and calcipotriol, when compared with the vehicle controls, were similar. These results suggest that, under conditions of descaling and occlusion, tacrolimus ointment is effective in the treatment of psoriasis.