Therapeutic interventions in mice with chronic proliferative dermatitis (cpdm/cpdm)

Chronic proliferative dermatitis (cpd) is a spontaneous mutation in C57BL/K a mice (cpdm/cpdm). The dermatitis is characterized by redness, hairless, s caling, pruritus and histologically by epithelial hyperproliferation, infil tration of eosinophils, macrophages and mast cells. Lesions similar to thos e in the skin occur in the esophagus and forestomach. In this paper, we des cribe the effect of drug treatments directed against epidermal hyperprolife ration (calcipotriene and etretinate), against inflammation (corticosteroid s and dapsone) and against pruritus (loratidine and capsaicin). The criteri a used to objectively estimate the effect of the treatment were 1) macrosco pic evaluation of the lesions (cpd score), 2) degree of epithelial hyperpro liferation assessed by BrdU incorporation and epithelial thickness, and 3) microscopic evaluation of the inflammatory cells in the skin samples. Treat ment of the cpdm/cpdm mice with calcipotriene (5 mu g/day for 3 weeks) inhi bited epidermal proliferation and the number of eosinophils. Systemic etret inate treatment (30 mu g/g/day for 3 weeks) was not very effective, Topical corticosteroids (0.05 mu g/day, for 3 weeks) exerted a therapeutic effect on the hyperproliferation and the number of eosinophils. Oral dapsone treat ment (34 mu g/g/day, for 5 weeks) reduced the BrdU incorporation in the ski n and the epithelial thickness in the esophagus, The anti-histamine loratid ine (orally, 1.7 mu g/g/day, for 3 weeks) reduced the severity of the lesio ns macroscopically, probably by suppressing the pruritus. Capsaicin (topica lly, 30 mM, for 5 weeks) also reduced the severity of the macroscopic obser vable lesions. Moreover, capsaicin reduced the dorsal and ventral epidermal thickness. The results from this and previous studies indicate that steroi ds (topically and systemically) and less strongly calcipotriene are the mos t effective treatments for the lesions observed in the cpdm/cpdm mice, sinc e both hyperproliferation and the influx of eosinophils are reduced. Althou gh the pathogenesis of the cpd lesions remains to be determined, our result s indicate that the cpdm/cpdm mouse can be used to investigate new drugs fo r their possible application in chronic dermatitis.