title: Sebaceous gland, hair shaft, and epidermal barrier abnormalities in keratosis pilaris with and without filaggrin deficiency.
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.
authors: Department of Dermatology and Venereology, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria. Electronic address: r.gruber@i-med.ac.at.
authors: Robert
authors: R
authors: Gruber
authors: Department of Dermatology, University of California, San Francisco, California.
authors: Jeffrey L
authors: JL
authors: Sugarman
authors: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, California.
authors: Debra
authors: D
authors: Crumrine
authors: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, California.
authors: Melanie
authors: M
authors: Hupe
authors: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, California.
authors: Theodora M
authors: TM
authors: Mauro
authors: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Elizabeth A
authors: EA
authors: Mauldin
authors: Department of Dermato-Allergology, Gentofte University Hospital, University of Copenhagen, Hellerup, Denmark.
authors: Jacob P
authors: JP
authors: Thyssen
authors: Department of Dermatology and Venereology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors: Johanna M
authors: JM
authors: Brandner
authors: Center for Dermatogenetics, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria.
authors: Hans-Christian
authors: HC
authors: Hennies
authors: Department of Dermatology and Venereology, Division of Human Genetics, Innsbruck Medical University, Innsbruck, Austria.
authors: Matthias
authors: M
authors: Schmuth
authors: Dermatology Service, Department of Veterans Affairs Medical Center, University of California, San Francisco, California.
authors: Peter M
authors: PM
authors: Elias
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D062445:Claudin-1 / Q000378:metabolism; D007644:Darier Disease / Q000235:genetics / Q000473:pathology*; D046169:Dermoscopy; D003896:Desmosomes / Q000378:metabolism; D004817:Epidermis / Q000002:abnormalities* / Q000648:ultrastructure; D005138:Eyebrows / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D000091344:Filaggrin Proteins; D005838:Genotype; D006197:Hair / Q000002:abnormalities* / Q000648:ultrastructure; D006801:Humans; D007381:Intermediate Filament Proteins / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010539:Permeability; D010641:Phenotype; D012627:Sebaceous Glands / Q000002:abnormalities* / Q000473:pathology / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D062445:Claudin-1; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins