Antioxidant Therapies for Ulcerative Dermatitis: A Potential Model for Skin Picking Disorder.

Abstract

Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine's mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated by many patients, intranasal glutathione warrants further study as potential therapy in Skin Picking, trichotillomania and other body-focused repetitive behavior disorders.