Barrier function parameters in various keratinization disorders: transepidermal water loss and vascular response to hexyl nicotinate

Abstract

In this study, we characterized the stratum corneum barrier function in 39 patients with various keratinization disorders (autosomal dominant ichthyosis vulgaris [ADI] [n = 7], X-linked recessive ichthyosis [XRI] [n = 6], autosomal recessive congenital ichthyosis [CI] [n = 10], dyskeratosis follicularis [Darier's disease; DD] [n = 8], erythrokeratoderma variabilis [EKV] [n = 8]), and 21 healthy volunteers, using two non-invasive methods: transepidermal water loss (TEWL) measuring outward transport of water through the skin by evaporimetry, and the vascular response to hexyl nicotinate (HN) penetration into the skin as determined by laser-Doppler flowmetry. Significantly increased TEWL values were found on the volar forearm in all three forms of ichthyosis, compared with the healthy control group, with the highest TEWL values in the CI group. The penetration of HN on the volar forearm was accelerated in patients with ADI, XRI and CI, as indicated by a shorter lag time (t0) between HN application and initial vascular response. However, differentiation between CI and the other ichthyoses was not possible by this method. When using both methods in DD and EKV, no differences compared with the healthy controls could be detected on the volar forearm, where the skin was principally unaffected; only the measurements from the affected skin on alternative sites demonstrated significantly increased TEWL values. In ADI and CI, however, normal-appearing skin also showed impaired values. We conclude that both TEWL and the vascular response to penetration of HN are suitable methods to monitor the skin barrier function in keratinization disorders, and are helpful in discriminating between these disorders.

Filaggrin Genotype in Ichthyosis Vulgaris Predicts Abnormalities in Epidermal Structure and Function

“…However, the functional differences between patients and controls were small (Figure 2). This is in concordance with earlier reports in human subjects 41,45 and with data from animal models. 26 -29 In the latter, permeability was increased for exogenous chemicals such as allergens despite functional differences being small.…”

“…36 Since FLG peptides normally associate with both the CE [37][38][39] and keratin filaments, 40 FLG deficiency could compromise permeability barrier function by either mechanism, by both mechanisms, or by a mechanism that is unique to IV. Although in the pre-genotype era, barrier function was shown to be moderately abnormal in IV and AD patients, [41][42][43][44][45] this has not been assessed in genotyped, FLG-deficient IV patients, and there is little evidence for the mechanisms of a potential barrier defect. Therefore, we asked here whether FLG deficiency provokes allele-, and dose-dependent changes in epidermal function, and set out to clarify the subcellular basis for such abnormalities.…”

Cathepsin D is involved in the regulation of transglutaminase 1 and epidermal differentiation

“…In accordance, mice heterozygous for a truncated keratin K10, as a model for the ichthyosis called epidermolytic hyperkeratosis, which is caused by point mutations in the suprabasal K1 or K10 (Cheng et al, 1992;Chipev et al, 1992;Rothnagel et al, 1992;Yang et al, 1997;Suga et al, 1998;Ishida-Yamamoto et al, 2000), did not show K6/K16 protein expression in flank skin (Porter et al, 1998). Ichthyosis is a group of skin disorders with different causes, showing disturbed epidermal differentiation with variable effects on the permeability barrier (Lavrijsen et al, 1993).…”

Migratory Ichthyosiform Dermatosis With Type 2 Diabetes Mellitus and Insulin Resistance

“…Frost et al 14 reported a 1.2-to 1.4-fold increase in TEWL level in a cohort of patients with ichthyosis. Lavrijsen et al 15 analyzed the water barrier function in different types of keratinization disorders and showed that an elevated TEWL level discriminates differences in skin function between most patients with ichthyosis and normal volunteers.…”

“…[15][16][17] In most of these studies, including our own, TEWL was measured solely at baseline. Even in situations where TEWL levels are normal or near normal at baseline, an underlying defect often becomes apparent after the presence of stress, as in aging, 18 psychological stress, 19 enviromental stress, 20 and in X-linked recessiveichthyosis.…”