T helper (Th) 17 cells are a novel T-cell subset that has been very recently implicated in the pathogenesis of psoriasis. The survival and proliferation of Th17 cells is stimulated by interleukin 23, that thus regulates Th17 cells. Interleukin 23 also stimulates dermal Th17 cells to produce the so-called “Th17 cytokines” (IL-17A, IL-17F, tumor necrosis factor, IL-21, and IL-22). One of these cytokines, IL-22, has been shown to be induce keratinocyte hyperproliferation in psoriasis. Targeting of these cytokines may be very effective to lead to dramatic clinical improvement in patients with psoriasis in the future. In the May issue of the Journal of Investigative Dermatology, a group of researchers from New York show for the first time that IL-17A-producing cells (Th17 cells) are present in the dermis of psoriatic plaques. Psoriasis plaque dermis contained a mean of 6.2% of cells secreting IL-17A, while normal-appearing skin contained a mean of 0.5% of cells. These results, as well as those from other recent works published in research journals suggest that IL-23 and Th17 cells are key mediators of disease pathogenesis. Some drugs targeting the IL-23/Th17 cell inflammatory pathway are being tested right now and their potential role in the treatment of psoriasis will soon be known.

Psoriasis Vulgaris Lesions Contain Discrete Populations of Th1 and Th17 T Cells

Lowes MA, et al

Journal of Investigative Dermatology 2008; 128:1207–1211.

The importance of T helper 17 (Th17) cells in inflammation and autoimmunity is now being appreciated. We analyzed psoriasis skin lesions and peripheral blood for the presence of IL-17-producing T cells. We localized Th17 cells predominantly to the dermis of psoriasis skin lesions, confirmed that IL-17 mRNA increased with disease activity, and demonstrated that IL-17 mRNA expression normalized with cyclosporine therapy. IL-22 mRNA expression mirrored IL-17 and both were downregulated in parallel with keratin 16. Th17 cells are a discrete population, separate from Th1 cells (which are also in psoriasis lesions), and Th2 cells. Our findings suggest that psoriasis is a mixed Th1 and Th17 inflammatory environment. Th17 cells may be proximal regulators of psoriatic skin inflammation, and warrant further attention as therapeutic targets.

The 88th Annual Meeting of the BAD will be held in Liverpool from the 1st to the 4th of July 2008. (more…)

The 34th Annual Meeting of the Society for Pediatric Dermatology will be held in Snowbird, Utah (United States) from 9th to 12th of July 2008.

The XXIX Symposium of the International Society of Dermatopathology will be held in Graz (Austria) in October 2008. This meeting will provide several sessions and lectures on particular problems in dermatopathology.

Severe psoriasis can be treated with several systemic therapies, like retinoids, methotrexate, cyclosporin, and the new biological treatments (etanercept, efalizumab, infliximab). Cyclosporin is a calcineurin inhibitor that has been shown to be very efficacious. However it has a risk of nephrotoxicity that precludes long lasting treatment. In a recent multicenter study from Canada published in the Lancet the investigators studied the effect of a new calcineurin inhibitor, ISA247. This molecule has a slight chemical modification from cyclosporin that makes it more potent (in terms of calcineurin inhibition) and with a shorter half-life. In this phase III clinical trial 451 patients with stable psoriasis were randomly assigned to receive placebo or ISA247 at one of three doses (0.2, 0.3, or 0.4 mg/kg) orally twice a day for 12 weeks. After that those in the placebo group received ISA247 0.3 mg/kg twice a day for the second 12 weeks. After 12 weeks, 25% of the patients treated with ISA247 achieved PASI 75 (44% in the 0.4 mg/kg group) versus 4% in the placebo group. Adverse events were frequent but mild (headache, nasopharyngitis, and upper respiratory tract infections), and only 3.6% had to discontinue treatment due to adverse events. Mild to moderate reductions of glomerular filtration rate were seen in 2% of the patients but were transient. No significant changes in blood pressure or mean lipid concentrations were observed. Therefore the authors suggest that treatment with this new calcineurin inhibitor is efficacious and seems to bear a better safety profile than cyclosporin for the treatment of patients with plaque psoriasis. However, the risk of chronic nephrotoxicity induced by ISA247 cannot be reliably predicted with short-term study. In addition, a trial comparing ISA247 with cyclosporin would be needed to sustain the claim it is safer than cyclosporin. (more…)