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The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T-cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/ betamethasone, but not by betamethasone. Immunohistochemical analysis revealed that calcipotriol/betamethasone reduced the numbers of CD4+ and CD8+ T cells and Tregs in psoriatic lesions more than betamethasone. Flow cytometric analyses demonstrated that calcipotriol/betamethasone decreased the numbers of circulating CD8+ T cells, Tregs, skin-homing Th17 memory cells and Th22 memory cells, while betamethasone had little or no effect. Glucocorticoid receptors GRα and GRß were expressed in psoriatic skin. In conclusion, calcipotriol increases the immunosuppressive power of betamethasone by suppressing the inflammatory TNF-α - IL-23 - IL-17 axis. [ABSTRACT FROM AUTHOR]

Tacrolimus ointment is a topical calcineurin inhibitor for the treatment of atopic dermatitis. The primary objective of this open-label study was to assess the long-term safety of tacrolimus ointment. The primary end-point was the incidence of adverse events. Secondary end-points included the Eczema Area and Severity Index and a modified version of this index. A total of 466 children with atopic dermatitis, aged 2–15 years, applied 0.03% or 0.1% tacrolimus ointment twice daily for up to 29.5 months. Skin burning and pruritus were the most common application site events; their prevalence decreased over time. There was no increase in viral infections or other adverse events over time. Laboratory profiles were consistent with those reported in atopic populations. Substantial improvement in all efficacy end-points was observed by week 2 and maintained throughout the study. Long-term treatment with tacrolimus ointment is safe and effective in these patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Objectives and methods:Topical therapy is the first-line treatment in mild and moderate psoriasis. We performed a real-life study on topical therapies in psoriasis and observed a variation in the amounts of ointment patients applied during the study. Results:A statistically significant correlation was found between gender and the total amount of ointment used: women used more than men (p = .020). Also, heavier patients tended to use less ointment (p = .038). Conclusions:We look forward to seeing whether the current pressure to improve psoriasis treatment leads to more patients receiving systemic therapies or to better adherence to, and persistence with, topical therapies. [ABSTRACT FROM PUBLISHER]

Antimicrobial peptides (AMP) are evolutionary ancient molecules produced by nearly all living organisms, both prokaryotic and eukaryotic cells. More than 2000 AMPs have now been identified. These peptides are produced by most human cell types, such as those in the skin and mucous membranes and blood. Each tissue has a different spectrum of AMPs. Antimicrobial capacity depends on the structural characteristics such as charge and amphiphilicity that allow the insertion and/or penetration of AMP into the membranes of microorganisms or other cells. AMPs may have importance in the pathogenesis of neurodegenerative diseases and type 2 diabetes. The most investigated AMPs are defensins and cathelicidin LL-37.

The production of cathelicidin, an antimicrobial peptide is strongly increased in rosacea. Cathelicidin activates innate immunity, inflammation and angiogenesis. Cutaneous proteases produce inflammatory fragments of cathelicidin. UV-B irradiation and microbial components increase vitamin D3 and TLR2 expression in keratinocytes leading to an increase of cathelicidin production. Retinoids and doxycycline inhibit inflammation, proteases, angiogenesis and TLR2 expression. A multicenter study 2010 proved that isotretinoin with a dose of 0,3 mg/kg/d for 12 weeks and doxycycline with the dose of 100 mg/d for 14 days followed with 50 mg/d were equally effective. Doxycycline 40 mg/d is also effective in milder cases.

The innate and adaptive immune responses have been better understood after the discovery of Toll-like receptors (TLRs), antimicrobial peptides and different populations of dendritic cells. In the skin there are 1 million T-cells per 1 cm2 and 20 billion in total. Naive T-cells activated by antigen-presenting cells can polarize in four directions and they express homing receptor CLA for operating in the skin when the antigen is first detected in the skin area. In psoriasis Th17 activation increases antimicrobial peptides. The IL-23/Th17 axis is largely absent in atopic dermatitis and may result in infections.