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

TY - JOUR

T1 - Sebaceous gland, hair shaft, and epidermal barrier abnormalities in keratosis pilaris with and without filaggrin deficiency

AU - Gruber, Robert

AU - Sugarman, Jeffrey L

AU - Crumrine, Debra

AU - Hupe, Melanie

AU - Mauro, Theodora M

AU - Mauldin, Elizabeth A

AU - Thyssen, Jacob P

AU - Brandner, Johanna M

AU - Hennies, Hans-Christian

AU - Schmuth, Matthias

AU - Elias, Peter M

N1 - Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

KW - Abnormalities, Multiple

KW - Adult

KW - Aged

KW - Claudin-1

KW - Darier Disease

KW - Dermoscopy

KW - Desmosomes

KW - Epidermis

KW - Eyebrows

KW - Female

KW - Genotype

KW - Hair

KW - Humans

KW - Intermediate Filament Proteins

KW - Male

KW - Middle Aged

KW - Mutation

KW - Permeability

KW - Phenotype

KW - Sebaceous Glands

KW - Young Adult

U2 - 10.1016/j.ajpath.2014.12.012

DO - 10.1016/j.ajpath.2014.12.012

M3 - Journal article

C2 - 25660180

SN - 0002-9440

VL - 185

SP - 1012

EP - 1021

JO - American Journal of Pathology

JF - American Journal of Pathology

IS - 4

ER -