Tacrolimus Ointment does not Affect Collagen Synthesis: Results of a Single-Center Randomized Trial

Abstract

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.

Tacrolimus Ointment 0.03% Is Safe and Effective for the Treatment of Mild to Moderate Atopic Dermatitis in Pediatric Patients: Results From a Randomized, Double-Blind, Vehicle-Controlled Study

“…Topical applications of tacrolimus ointment result in minimal systemic absorption, do not cause a decrease in collagen synthesis or skin thickness, and have not been associated with limiting adverse events thus far. [16][17][18][19][20][21] Tacrolimus ointment (0.03% and 0.1%) has been clinically shown to reduce the extent, severity, and symptoms of moderate to severe AD in children as young as 2 years of age and to be safe and effective for long-term use for up to 4 years. [22][23][24][25][26][27] However, it has not been evaluated for treatment of mild to moderate cases.…”

Tacrolimus tópico nas lesões cutâneas refratárias da dermatomiosite juvenil

“…Na literatura médica, prurido, ardor e eritema têm sido descritos (9) . Entretanto, telangiectasias e atrofia cutânea, efeitos comuns dos corticosteróides tópicos, não ocorrem com o tacrolimus tópico 0,03% (22) . Este estudo reforça a segurança e a eficácia do tacrolimus tópico como alternativa nas lesões cutâneas da DMJ, refratárias à terapia-padrão, particularmente quando introduzido precocemente no curso da doença.…”

Current Views on the Pathogenesis and Principles of External Treatment of Atopic Dermatitis in Children

“…При этом сигнальная транс-дукция и транскрипция нескольких провоспалительных цитокинов в лимфоцитах подавляется [41], а другие вос-палительные клетки (тучные или базофилы) блокируются. В отличие от тГКС, тИК не ингибируют пролиферацию кератиноцитов или фибробластов, поэтому не вызывают атрофии кожи [42]. В дополнение к противовоспалитель-ному действию тИК оказывают непосредственное воз-действие на нервные окончания кожи, обладают выра-женным противозудным действием [43,44].…”