Acute GVHD classification based on the dynamics of GVHD skin involvement from its appearance to the start of systemic treatment.

We conducted a prospective study aimed at investigating the prognostic value of the dynamic of a-GVHD progression from cutaneous to visceral involvement. In 108 consecutive patients who underwent allogeneic HSCT, we classified a-GVHD according to a "GHVD skin dynamic": 18/82 patients started Corticosteroid (CS) within 48 h (Group 1); 13/82 started CS within days 3-7 (Group 2); Group 3A (n 31) was defined when Skin GVHD Overall Grade 1, left untreated for 1 week, showed an increase in involved body surface area <5 %; Group 3B (n 20), was defined when Skin GVHD Overall Grade 1, left untreated at 1 week, had an increase in involved body surface area >5%. These four groups had distinctive 2-y OS. Patients could be then grouped into "poor risk" (Group 1 and Group 3B) and "good risk" (Group 2 and Group 3A). "Poor risk" had inferior OS in univariate and multivariate analysis, (HR 2.222; 95% CL: 1.017-4.855; p 0.04). Among the patients with skin-only Grade 1 GVHD, subgroup 3A had an OS of 75.1% versus 39.8% found in subgroup 3B (p = 0.03). The dynamic of skin GVHD may be used to classify a-GVHD and guide treatment in Overall Grade 1 skin-only GVHD.

Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y.

The purpose of this article is to characterize skin lesions in cynomolgus monkeys following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral vildagliptin administration caused dose-dependent and reversible blister formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores involving the extremities at ≥5 mg/kg/day and necrosis of the tail and the pinnae at ≥80 mg/kg/day after 3 weeks of treatment. At the affected sites, the media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia. Skin lesion formation was prevented by elevating ambient temperature. Vildagliptin treatment also produced an increase in blood pressure and heart rate likely via increased sympathetic tone. Following treatment with vildagliptin at 80 mg/kg/day, the recovery time after lowering the temperature in the feet of monkeys and inducing cold stress was prolonged. Ex vivo investigations showed that small digital arteries from skin biopsies of vildagliptin-treated monkeys exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding correlated with a specific increase in NPY and in NPY1 receptors observed in the skin of vildagliptin-treated monkeys. Present data provide evidence that skin effects in monkeys are of vascular origin and that the effects on the NPY system in combination with increased peripheral sympathetic tone play an important pathomechanistic role in the pathogenesis of cutaneous toxicity.