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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., (© 2014 by The Author(s).)

A brief review of the limited sources in the literature on secondary amenorrhea indicates that this symptom may, in many cases, be psychogenic in origin. The disorder in such instances is often short term, spontaneously reversible, and occurs as a reaction to stress or a traumatic event. Most of these women are basically healthy, psychologically speaking. In some cases, however, this menstrual disturbance may continue for months or longer. In such instances, one may expect to find a neurotic conflict related to feminine identity as the cause. The therapeutic approach in these two alternative forms of secondary psychogenic amenorrhea (SPA) will differ; hence, it is essential that the gynecologist and psychiatrist distinguish between them. A case illustration is presented, describing in detail the treatment of a women with longstanding SPA which resolved with dynamically-oriented psychotherapy.