Sebaceous Gland Atrophy in Psoriasis: An Explanation for Psoriatic Alopecia?

Abstract

In a transcriptome study of lesional psoriatic skin (PP) versus normal skin, we found a coexpressed gene module (N5) enriched 11.5-fold for lipid biosynthetic genes. We also observed fewer visible hairs in PP skin, compared with uninvolved nonlesional psoriatic skin or normal skin (P < 0.0001). To ask whether these findings might be due to abnormalities of the pilosebaceous unit, we carried out three-dimensional morphometric analysis of paired PP and nonlesional psoriatic skin biopsies. Sebaceous glands were markedly atrophic in PP versus nonlesional psoriatic skin (91% average reduction in volume, P = 0.031). Module N5 genes were strongly downregulated in PP versus normal skin (fold change < 0.25, 44.4-fold) and strongly upregulated in sebaceous hyperplasia (fold change > 4, 54.1-fold). The intersection of PP-downregulated and sebaceous hyperplasia-upregulated gene lists generated a gene expression signature consisting solely of module N5 genes, whose expression in PP versus normal skin was inversely correlated with the signature of IL17-stimulated keratinocytes. Despite loss of visible hairs, morphometry identified elongated follicles in PP versus nonlesional psoriatic skin (average 1.7 vs. 1.2 μm, P = 0.020). These results document sebaceous gland atrophy in nonscalp psoriasis, identify a cytokine-regulated set of sebaceous gland signature genes, and suggest that loss of visible hair in PP skin may result from abnormal sebaceous gland function.