Correlation between diffuse pigmentation and keratinocyte‐derived endothelin‐1 in systemic sclerosis

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Abstract
Background  The precise mechanism of diffuse pigmentation in systemic sclerosis (SSc) is still unknown. We suspected the participation of endothelin‐1 (ET‐1), which is produced by keratinocytes, in the hyperpigmentation in SSc. The aims of this study are to demonstrate the hyperproductivity of ET‐1 from epidermal cells in SSc by in situ hybridization histochemistry, and to show a correlation between the hyperproductivity of ET‐1 in keratinocytes and skin hyperpigmentation.Methods  In situ hybridization histochemistry was performed on nine SSc specimens (five cases of diffuse scleroderma (dSSc), four cases of acrosclerosis (lSSc)), and compared with four normal control specimens. We counted the grains on 10 × 10 μm2 of epidermis and microvessels in each histology and examined the degree of skin pigmentation using the skin reflectance factor (Y).Results  In the specimens of the SSc patients, the number of grains on the epidermis was remarkably higher than those of the control specimens (P < 0.01). We found a close correlation between the number of grains and the skin reflectance factor in dSSc patients (P = 0.02). Correlations were not identified between serum ET‐1 and skin pigmentation and between serum ET‐1 and the frequency of grains on the epidermis. As for grains on microvessels, lSSc patients showed a greater frequency than dSSc patients.Conclusions  The findings of this study suggest that an increase in the ET‐1 productivity of keratinocytes is experienced in SSc patients, especially in dSSc patients. The results suggest a strong correlation between the ET‐1 productivity of keratinocytes and skin pigmentation in severe cases of SSc. We conclude from these results that keratinocyte‐derived ET‐1 plays an important role in the pathogenesis of the hyperpigmentation of the skin in SSc patients.