Sebaceous gland, hair shaft, and epidermal barrier abnormalities in keratosis pilaris with and without filaggrin deficiency

Robert Gruber, Jeffrey L. Sugarman, Debra Crumrine, Melanie Hupe, Theodora M. Mauro, Elizabeth A. Mauldin, Jacob P. Thyssen, Johanna M. Brandner, Hans Christian Hennies, Matthias Schmuth, Peter M. Elias

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Abstract

Although keratosis pilaris (KP) is common, its etiopathogenesis remains unknown. KP is associated clinically with ichthyosis vulgaris and atopic dermatitis and molecular genetically with filaggrin-null mutations. In 20 KP patients and 20 matched controls, we assessed the filaggrin and claudin 1 genotypes, the phenotypes by dermatoscopy, and the morphology by light and transmission electron microscopy. Thirty-five percent of KP patients displayed filaggrin mutations, demonstrating that filaggrin mutations only partially account for the KP phenotype. Major histologic and dermatoscopic findings of KP were hyperkeratosis, hypergranulosis, mild T helper cell type 1-dominant lymphocytic inflammation, plugging of follicular orifices, striking absence of sebaceous glands, and hair shaft abnormalities in KP lesions but not in unaffected skin sites. Changes in barrier function and abnormal paracellular permeability were found in both interfollicular and follicular stratum corneum of lesional KP, which correlated ultrastructurally with impaired extracellular lamellar bilayer maturation and organization. All these features were independent of filaggrin genotype. Moreover, ultrastructure of corneodesmosomes and tight junctions appeared normal, immunohistochemistry for claudin 1 showed no reduction in protein amounts, and molecular analysis of claudin 1 was unremarkable. Our findings suggest that absence of sebaceous glands is an early step in KP pathogenesis, resulting in downstream hair shaft and epithelial barrier abnormalities.

Original languageEnglish
Pages (from-to)1012-1021
Number of pages10
JournalAmerican Journal of Pathology
Volume185
Issue number4
Early online date7 Feb 2015
DOIs
Publication statusPublished - Apr 2015
Externally publishedYes

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Gruber, R., Sugarman, J. L., Crumrine, D., Hupe, M., Mauro, T. M., Mauldin, E. A., ... Elias, P. M. (2015). Sebaceous gland, hair shaft, and epidermal barrier abnormalities in keratosis pilaris with and without filaggrin deficiency. American Journal of Pathology, 185(4), 1012-1021. https://doi.org/10.1016/j.ajpath.2014.12.012