Circumscribed palmar or plantar hypokeratosis: a distinctive epidermal malformation of the palms or soles

BACKGROUND: Epidermal malformations of the skin include a group of heterogeneous developmental defects that result from errors in morphogenesis of the epidermis during intrauterine life. OBJECTIVE: The purpose of this study was to report the clinical and histopathologic features of a distinctive epidermal malformation involving the skin of the palms or soles. METHODS: Ten patients were included in this study. All of them showed the same clinical features that consisted of a solitary circumscribed and circular area of erythematous depressed skin on the palm or on the sole. Diagnosis was confirmed by histopathologic study. RESULTS: All patients were middle aged or elderly. Nine patients were women and one was a man. The lesions showed predilection for the skin of the thenar and hypothenar regions of the palm or the medial side of the sole. Histopathologic study demonstrated a depression of the epidermis, with a sharp stair between normal and involved skin. The epidermis covering the depression showed markedly thinner horny layer and a slightly diminished granular cell layer when compared with adjacent noninvolved skin. Keratinocytes of the squamous cell layer, granular cells, and corneocytes showed, otherwise, a normal appearance. Serial sections failed to demonstrate cornoid lamellation. CONCLUSION: On the basis of the clinical and histopathologic findings in these 10 patients, we have named this malformation circumscribed palmar or plantar hypokeratosis. This lesion seems to be a distinctive entity that has not been previously described.     

Surface area measurements of psoriatic corneocytes: effects of intralesional steriod therapy

Quantitative measurements of surface areas of corneocytes from the desquamating portion of psoriatic lesions in 11 patients showed that psoriatic corneocytes were much smaller (27%) than corneocytes from noninvolved normal skin in the same patients. Corneocyte surface areas gradually increased in size following one intralesional injection of triamcinolone acetonide suspension and were almost normal approximately 6 weeks after treatment. These findings support other observations suggesting that rapidly proliferating epidermal cells have smaller surface areas than normal cells.     

Pitted keratolysis

Pitted keratolysis is a skin disorder that affects the stratum corneum of the plantar surface and is caused by Gram-positive bacteria. A 30-year-old male presented with small punched-out lesions on the plantar surface. A superficial shaving was carried out for scanning electron microscopy. Hypokeratosis was noted on the plantar skin and in the acrosyringium, where the normal elimination of corneocytes was not seen. At higher magnification (x 3,500) bacteria were easily found on the surface and the described transversal bacterial septation was observed.     

Adherence of arthroconidia and germlings of anthropophilic and zoophilic varieties of Trichophyton mentagrophytes to human corneocytes as an early event in the pathogenesis of dermatophytosis

The association (adherence) between human corneocytes and arthroconidia of Trichophyton mentagrophytes strains 121 and 126, and T. interdigitale strain 4 was studied in vitro. Adherence of arthroconidia to corneocytes from either the palm and sole occurred and increased with time up to 6 h, by which time germination of arthroconidia had started. Significant differences were seen between the T. mentagrophytes strains and T. interdigitale in their adherence to corneocytes from the palm. When adherence values for plantar corneocytes were compared, significant differences were found between T. mentagrophytes had T. interdigitale. Not all corneocytes from either site had adherent arthroconidia, although there was a time-dependent increase in the numbers of corneocytes with adherent fungal cells. By scanning and transmission electron microscopy it was seen that there was a loose association between arthroconidia and corneocytes with no apparent damage to the corneocytes membrane. Adherence of germlings of T. interdigitale to corneocytes from the palm appeared to be mediated by germling outer cell wall fibrils. Hyphal branches and secondary germlings were observed to enhance the attachment of the parent hypha to adjacent corneocytes.     

Adherence of Candida species to human epidermal corneocytes and buccal mucosal cells: correlation with cutaneous pathogenicity

Adherence of microorganisms to epidermal corneocytes may be a prerequisite for cutaneous colonization and infection. Six species of Candida were assayed in vitro for adherence to human epidermal corneocytes and buccal mucosal cells, and compared to previous studies of pathogenicity in a rodent model of cutaneous candidiasis. C. albicans and C. stellatoidea exhibited marked adherence to both epithelial cell types over time, and were cutaneous pathogens in the rodent model. The remaining species showed little or no adherence, and were nonpathogenic to skin. Adherence to corneocytes was not inhibited by ethylenediamine tetraacetic acid, mannan polysaccharide, or concanavalin A lectin. Fresh human serum, but not heat-inactivated serum, inhibited C. albicans adherence by 50%, and was associated with the deposition of complement components, C3 and factor B on blastospores. Adherence to epithelial corneocytes and mucosal cells is a property of pathogenic species of Candida, and may participate in cutaneous colonization and infection mechanisms. Adherence was time-dependent, and did not require divalent cations. Cell wall mannan may participate in the "adhesin" complex. Mannan activation of serum complement and deposition of C3 and factor B on blastospores may provide a protective action by inhibiting Candida adherence to corneocytes.     

Effects of retinoic acid on adult human epidermis in whole skin organ culture

Summary Adult human skin was cultured in wholeskin organ culture under chemically defined conditions. Retinoic acid was added to the culture at final concentrations of 5×10^-7 and 5×10^-6 M. Both concentrations elicited cell death in the upper epidermal layers and prevented the terminal differentiation of the cells to mature corneocytes. The inhibition of terminal differentiation was not permanent, as the corneocytes produced later during the culture showed no signs of inhibition. The upper vital cells in epidermis cultured with retinoic acid were very flattened and contained reduced amounts of cytoskeleton components. Fine, granular material not present in normal epidermis was oberved in both the intercellular spaces and the intracytoplasmic vesicles of retinoid-treated epidermis. The present results indicate that the response of normal human skin to retinoic-acid treatment involves the same kind of modulation of the epidermal structure previously described in embryonic avian and diseased human skin.     

The organization of human epidermis: functional epidermal units and phi proportionality

The concept that mammalian epidermis is structurally organized into functional epidermal units has been proposed on the basis of stratum corneum (SC) architecture, proliferation kinetics, melanocyte:keratinocyte ratios (1:36), and, more recently, Langerhans cell: epidermal cell ratios (1:53). This article examines the concept of functional epidermal units in human skin in which the maintenance of phi (1.618034) proportionality provides a central organizing principle. The following empirical measurements were used: 75,346 nucleated epidermal cells per mm2, 1394 Langerhans cells per mm2, 1999 melanocytes per mm2, 16 (SC) layers, 900-microm2 corneocyte surface area, 17,778 corneocytes per mm2, 14-d (SC) turnover time, and 93,124 per mm2 total epidermal cells. Given these empirical data: (1) the number of corneocytes is a mean proportional between the sum of the Langerhans cell + melanocyte populations and the number of epidermal cells, 3393/17,778-17,778/93,124; (2) the ratio of nucleated epidermal cells over corneocytes is phi proportional, 75,346/17,778 approximately phi3; (3) assuming similar 14-d turnover times for the (SC) and Malpighian epidermis, the number of corneocytes results from subtraction of a cellular fraction equal to approximately 2/phi2 x the number of living cells, 75,436 - (2/phi2 x 75,346) approximately 17,778; and (4) if total epidermal turnover time equals (SC) turnover time x the ratio of living/dead cells, then compartmental turnover times are unequal (14 d for (SC) to 45.3 d for nucleated epidermis approximately 1/2phi) and cellular replacement rates are 52.9 corneocytes/69.3 keratinocytes per mm2 per h approximately 2/phi2. These empirically derived equivalences provide logicomathematical support for the presence of functional epidermal units in human skin. Validation of a phi proportional unit architecture in human epidermis will be important for tissue engineering of skin and the design of instruments for skin measurement.     

Corneocyte morphology and formation rate in lichen planus and experimental parakeratosis in subjects with and without psoriasis

In a recent paper changes in corneocyte morphology and formation rate in psoriasis have been established. In the present study the specificity of these alternations were analysed in two situations. Early lichen planus papules were chosen as a model of hyperproliferation with hypergranulosis and orthohyperkeratosis. Hyperproliferation with parakeratosis was induced by nonanoic acid (CH3(CH2)7COOH) as an experimental model in psoriatics and non-psoriatics. In lichen planus papules, the rate of corneocyte layer formation was 2.4 times that of the non-involved skin. In psoriasis, a similar rate was found in parts with hypergranulosis. A 13% decrease in corneocyte diameter took place in lichen planus lesions--similar to that found in psoriasis. The corneocytes in lichen planus were also thicker than normal cells, though their volumes were similar. Thickness decreased in more superficial locations of these corneocytes. Swelling was a finding during the histological procedure, Corneocytes in the lesion increased markedly in volume, due to swelling. The parakeratosis elicited by nonanoic acid showed cells with irregular membranes and nuclei with non-flattened and irregular borders. The rate of corneocyte layer formation was 2.6 times that of the normal skin. The epidermal reaction to the superficial damage by nonanoic acid did not differ between psoriatics and non-psoriatics. This type of parakeratosis was distinctly different from that present in psoriasis.     

Skin irritation due to repetitive application of adhesive tape: the influence of adhesive strength and seasonal variability

BACKGROUND/PURPOSE: Influence of the repetitive application of pressure-sensitive adhesive tapes on skin was evaluated. METHODS: Two kinds of tapes with different adhesive strengths were repetitively applied to the inside of the forearm of six volunteers in winter and summer, in order to examine the dermal peeling force, the amount of stripped corneocytes, transepidermal water loss (TEWL), hydration and deepened skin furrows (changes in skin surface topography) in the epidermal stratum corneum. RESULTS AND CONCLUSION: As adhesive tapes were applied repetitively, dermal peeling force gradually increased while the amount of stripped corneocytes decreased. As the cumulative amount of stripped corneocytes increased with repetitive applications, the skin irritation worsened as measured by increased destruction of the skin surface topography and TEWL. These phenomena were more marked with the stronger adhesive tape, and there was seasonal variability.     

Glucocorticoid receptor localization in human epidermal cells

Glucocorticoids, which are widely used in therapy, exert their immunosuppressive actions through specific receptors. These receptors have been characterized in cultured human skin fibroblasts and keratinocytes, but their localization in vitro and in vivo has not been established. To determine the tissue and cellular distribution of glucocorticoid receptors (GR), two specific polyclonal rabbit anti-human GR antibodies were used to detect these receptors in skin biopsy specimens, in freshly isolated and cultured human epidermal cells and in keratinocyte cell lines. Immunoreactive GR were only faintly detected in normal and abnormal differentiated cells and as well as those in the stratum granulosum and corneocytes. These immunolocalization studies were confirmed by fluorescence cell sorter analysis of isolated basal and suprabasal keratinocytes. Immunoreactive GR were highly expressed in normal cultured human keratinocytes, Langerhans cells and several cell lines whereas they were less expressed in melanocytes. Based upon these results the main targets of glucocorticoids in the epidermis appear to be basal and Langerhans cells. Received: 6 February 1995     

Scanning electron microscopy of skin surface and the internal structure of corneocyte in normal human skin. An application of the osmium-dimethyl sulfoxide-osmium method

Summary A horny layer of normal human skin prepared according to the newly developed osmium-dimethyl sulfoxide-osmium method was examined using scanning electron microscopy. On the skin surface, cytomembranes of the uppermost corneocytes frequently had unilateral, very slightly flat-elevated, zonal areas along the junctions between the corneocytes. The uppermost corneocytes peeled off along the junctions, leaving the remnants of their cell bodies in the junctional areas. In the cracked surface, cytomembranes of the corneocytes protruded from the plane of their cytoplasmic surface. In the lateral junction between the corneocytes, the cytomembranes of the corneocytes were in tight contact with each other, while occasionally the marginal bands had become detached from the cytomembranes. In the vertical connection, cleavages formed between the cytomembranes of the corneocytes. There were thick woollen thread-like structures about 10–30 nm thick in the cytoplasm of the corneocytes. They formed fine irregular meshworks, with their tips projecting digitally: Transmission electron microscopy revealed these structures as most likely being keratin bundles transformed during processing.     

Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses

Corneodesmosin (CDSN) was identified 20 years ago by raising monoclonal antibodies against human plantar stratum corneum. The protein is specific to corneodesmosomes, cell-junction structures that, in humans, are found in the epidermis, the hard palate epithelium, and the inner root sheath of the hair follicles. Synthesized by the granular keratinocytes and secreted via the lamellar bodies, CDSN is incorporated into the desmoglea of the desmosomes, shortly before their transformation into corneodesmosomes during cornification. CDSN displays adhesive properties, mostly attributable to its N-terminal glycine-rich domain, and is sequentially proteolyzed as corneocytes migrate towards the skin surface prior to desquamation. The recent inactivation of Cdsn in mice induced a lethal epidermal barrier disruption and hair follicle degeneration, related to corneodesmosome dysfunction. That confirmed the essential role of the protein in maintaining integrity of the epidermis and the hair follicle. The CDSN gene is located in PSORS1, the major psoriasis susceptibility locus on the chromosome 6, but to date its involvement in the disease pathophysiology is not clear. By contrast, two different monogenic diseases associated with nonsense mutations in CDSN, were recently identified. First, hypotrichosis simplex of the scalp in which mutated CDSN accumulates in the dermis and forms amyloid deposits; then, peeling skin disease in which the genetic defect induces dyscohesion of the stratum corneum, responsible for abnormal desquamation and increased skin penetration of allergens.     

Three-dimensional analyses of individual corneocytes with atomic force microscope: morphological changes related to age, location and to the pathologic skin conditions

Background/aims: The past morphological studies on individual corneocytes have so far mainly focused on their two-dimensional characteristics, particularly on their projected area, which have been widely employed for the estimation of the turnover rate of the stratum corneum because of the practical use. However, sometimes a poor correlation has been reported between the projected area of corneocytes and actually measured turnover time of the stratum corneum. The objective of the present study is to perform detailed three-dimensional measurements of individual corneocytes with atomic force microscope. Through analyses of the obtained data, we tried to find morphological parameters that reflect more closely the differentiation process of the corneocytes in the stratum corneum than the frequently used two-dimensional projected area. Methods: We measured such morphological parameters as the volume, average thickness and real surface area of individual corneocytes isolated from the covered skin (the flexor surface of the upper arm) and the exposed skin (the cheek) of 12 healthy individuals belonging to different age brackets, in addition to their projected area. We further introduced a new parameter, a flatness index calculated by dividing the projected area of corneocytes by their thickness. Similarly, we measured corneocytes obtained from eight patients with atopic dermatitis (AD) and psoriatic patients. Results: Obtained results showed that most of these morphological parameters varied greatly depending upon the anatomical location and age of the subjects. Needless to say great differences were found between healthy skin and lesional skin of atopic dermatitis or psoriasis. However, the volume and thickness of corneocytes collected from the same location of normal skin of the covered area (upper arm) with tape-strippings were noted to decrease as they differentiated in the stratum corneum, showing an increase in their surface area and projected area with a resultant increase in the flatness index. Moreover, the corneocyte collected from the lesional skin of AD or psoriasis showed a great decrease in flatness index, reflecting their poor differentiation in the stratum corneum due to its enhanced turnover rate. Most of all, we found a poor correlation between the projected area and the various three-dimensional morphologic parameters of the corneocytes, indicating that the projected area does not reflect the volume or thickness of corneocytes that are also greatly influenced by the differentiation process of corneocytes in the stratum corneum. Conclusions: To estimate the differentiation speed of the corneocytes, we suggest using their flatness index rather than the two-dimensional cell surface area, because the former is a concept that takes into account the three-dimensional characteristics of corneocytes.     

Cryoscopy: a novel enhancing method of in vivo skin imaging

BACKGROUND: It is a common observation that superficial freezing of normal skin and skin tumors may create a transient superficial whitening effect. In this respect, cryoscopy refers to the direct observation by dermoscopy, with or without digital recording, of the visual alterations of the frozen tissues. AIMS: To define the optimal method of cryoscopy and to describe the cryoscopy patterns of normal skin and selected skin lesions. MATERIALS AND METHODS: The influence of (a) different cryogenic sources [solid carbon dioxide (-78.5 degrees C), liquid nitrogen (N(2), -196 degrees C), and a mixture of dimethyl ether and propane (-57 degrees C)], (b) various application methods (spraying, cotton chill tips, copper plate), and (c) freezing time was assessed with regard to clinical feasability, visualization quality, and persistance time of the whitening effect. Cryoscopy patterns of normal skin, callosities and of histologically proven seborrheic keratoses, verrucous hamartomas, molluscum contagiosum, keratoacanthomas, viral warts, condylomas, actinic keratoses, dermatofibromas, skin tags, basal cell carcinomas, angiomas, and melanocytic naevi were assessed. RESULTS: The cryoscopy images of skin highlighted the skin lines. They appeared similar regardless of the freezing source and the application method. The aspects differed according to the nature of the lesions. The cotton chill tip method provided a longer whitening period compared with the other cold sources, both in normal and lesional skin. Hence, it represented the most convenient way for performing digital recording cryoscopy. On normal skin, cryoapplication was limited to about 1.5 s due to pain, resulting in whitening times ranging from 6 to 9 s, which was too short for easy digital recording. On all studied skin tumors, a 10-s N(2) freezing time was not experienced as painful, and blanching time persisted for 20-34 s, allowing easy digital recording. The whitening time was longer with increasing freezing time on both normal and lesional skin. Every single examined normal skin site and all the skin lesions showed a strong whitening effect, except heavily cornified structures, including some keratoses, callosities, and viral warts. Increased contrast of the skin surface texture was observed in almost every studied lesion. CONCLUSION: The N(2) cotton chill tip technique appeared to be the most convenient technique for cryoscopy and provided longer whitening periods compared with the other freezing sources. Pain prevented its use on normal skin, but a series of exophytic skin lesions was conveniently accessible to cryoscopy. The differences in whitening periods of various epidermal components resulted in increased visual contrast, creating typical cryoscopy images for the different exophytic skin tumors. Cryoscopy represents a novel in vivo skin imaging technique that is rapid, non-invasive, cost-effective, and easily performed. It shows both investigative and diagnostic potentials. It is remarkable that cryoscopy pictures closely resemble those yielded by skin capacitance imaging.     

An experimental study on corneocytes of acutely and chronically irritated skin

Summary An experimental study concerning the effect of acute and chronic irritation on corneocytes was made in relation to cell number, size, and shape. Corneocytes from skin acutely irritated with a rough towel differed from those of normal skin: There was about a 60% decrease in the count and the corneocytes were 14% smaller in size on day 1 of the experiment. These parameters became normal in count and size after 10 days and 5 days, respectively. Concerning the morphological classification of cell outlines, there was no significant difference between the experimental and control groups except for slightly increased numbers of irregular cells in the experimental group.For the chronic irritation study, subjects were scrub nurses who had worked in the operating room for more than 3 years; ward nurses were used as a control group. Corneocytes from scrub nurses differed from those of the nonirritated skin of ward nurses; the number was twice as high on day 1 of the experiment. Two and four days later, the cell number markedly decreased and was similar to that in the control group. Throughout the experimental period, the surface of the corneocytes was 15% smaller in the experimental group than in the control group. There was no significant difference between the two groups with regard to corneocyte morphology.     

Therapeutic effect of vitamin A acid (retinoic acid) in various forms of palmar/plantar hyperkeratoses: experimental studies on 68 patients]

Up to date, the treatment of palmar/plantar hyperkeratoses presents a therapeutic problem. The known therapeutic procedures result in short-term improvement only, if any at all. In these investigations involving 68 patients suffering from palmar/plantar hyperkeratoses of different etiology, small doses of vitamin A acid (retinoic acid) topically applied, produced a striking improvement in hypertrophic lichen planus of palms or soles: the regression was complete and in most cases permanent. The skin texture of patients with genetic keratoses and callosities became normal within a few weeks: but this condition remained free of symptoms only as long as vitamin A acid was used as a maintenance dose once or twice weekly. In hyperkeratotic exzema, pityriasis rubra pilaris, and in verrucae plantaris vitamin A acid topically applied was found to be unsuitable for treatment. The possible side effects of this treatment are mentioned. Several possibilities regarding the way of action of vitamin A acid are discussed.     

Infant Skin Microstructure Assessed In Vivo Differs from Adult Skin in Organization and at the Cellular Level

Abstract: Functional differences between infant and adult skin may be attributed to putative differences in skin microstructure. The purpose of this study was to examine infant skin microstructure in vivo and to compare it with that of adult skin. The lower thigh area of 20 healthy mothers (ages 25–43) and their biological children (ages 3–24 months) was examined using in vivo noninvasive methods including fluorescence spectroscopy, video microscopy, and confocal laser scanning microscopy. Stratum corneum and supra‐papillary epidermal thickness as well as cell size in the granular layer were assessed from the confocal images. Adhesive tapes were used to remove corneocytes from the outer‐most layer of stratum corneum and their size was computed using image analysis. Surface features showed differences in glyph density and surface area. Infant stratum corneum was found to be 30% and infant epidermis 20% thinner than in adults. Infant corneocytes were found to be 20% and granular cells 10% smaller than adult corneocytes indicating a more rapid cell turnover in infants. This observation was confirmed by fluorescence spectroscopy. Dermal papillae density and size distribution also differed. Surprisingly, a distinct direct structural relationship between the stratum corneum morphology and the dermal papillae was observed exclusively in infant skin. A change in reflected signal intensity at ～100 μm indicating the transition between papillary and reticular dermis was evident only in adult skin. We demonstrate in vivo qualitative and quantitative differences in morphology between infant and adult skin. These differences in skin microstructure may help explain some of the reported functional differences.     

Functional analyses of the superficial stratum corneum in atopic xerosis

Dermatologists universally recognize that the unaffected skin of patients with atopic dermatitis tends to be dry and slightly scaly. To characterize the functional properties of the superficial stratum corneum in atopic xerosis, we studied the forearms of 28 patients with atopic dermatitis, aged 14 to 30 years, and 18 age-matched controls, with the use of mainly noninvasive methods. Patients with atopic xerosis showed markedly higher transepidermal water loss and markedly lower skin surface hydration levels than did the controls. The corneocytes in atopic xerosis tended to desquamate in clumps of cell aggregates instead of as individual cells. They contained a substantially lower amount of water-soluble amino acids, which play a role in the water-retaining capacity of stratum corneum, than did those of controls. Although the number of stratum corneum cell layers in atopic xerosis (21 +/- 4) was substantially larger than that in controls (15 +/- 1), its turnover time (7 +/- 2 days) was appreciably shorter than that for controls (14 +/- 2 days). Like those noted in the skin with increased epidermal proliferation, the size of superficial corneocytes in patients with atopic xerosis was substantially smaller than in controls. Histopathologic examination revealed acanthotic epidermis, mild perivascular mononuclear cell infiltrate, and pigment incontinence. Atopic xerosis, the dry skin of patients with atopic dermatitis, shows various stratum corneum functional impairments, probably reflecting increased epidermal proliferation due to a low-level ongoing dermatitis.     

Variations in the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas

We investigated the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas located on the sun-exposed skin of 10 patients. Using adenosine triphosphatase-stained epidermis from the tumors, we compared the Langerhans' cells in squamous cell carcinoma with those in nontumorous skin specimens from the same patient. The nontumorous skin specimen was obtained from either sun-exposed perilesional or non-sun-exposed sites. In three patients a normal number and almost normal morphology of Langerhans' cells were observed within the epidermal component of the tumor. One patient showed a normal number but a profound alteration of the morphology of the cells. In the remaining six patients, a significant decrease in the number of Langerhans' cells was observed. Langerhans' cells within the epidermal component of the tumors of these patients exhibited morphologic alterations in that they were mainly round or oval rather than highly dendritic. In none of our patients was the number of Langerhans' cells in the tumor increased. We conclude that a decreased number and altered morphology of Langerhans' cells occur in some, but not all, squamous cell carcinomas of the skin, and that there is no apparent difference between the number of Langerhans' cells in sun-exposed vs unexposed skin from the same individual.     

Water distribution and related morphology in human stratum corneum at different hydration levels

This study focused on the water distribution in human stratum corneum and on the swelling of the corneocytes. For this purpose stratum corneum was hydrated to various levels and used either for Fourier transform infrared spectroscopy or for cryo-scanning electron microscopy. The images were analyzed with respect to water localization and cell shape. The Fourier transform infrared spectra were measured to study the water-lipid interactions. The results show that water only slightly changes the lipid transitions in the stratum corneum even at a hydration level of 300% wt/wt compared to stratum corneum and that water is inhomogeneously distributed in the stratum corneum. No gradual increase in water level was observed in depth. At 57%-87% wt/wt water content the hydration level in the central part of stratum corneum is higher than in the superficial and deeper cell layers. Water domains are mainly present within the corneocytes and not in the intercellular regions. At a very high hydration level (300% wt/wt), the corneocytes are strongly swollen except for the deepest cell layers adjacent to the viable epidermis. The corneocytes in these layers are not swollen. At 300% wt/wt hydration level water domains are also present in intercellular regions. Between 17% wt/wt and 300% wt/wt the cell thickness increases linearly with the hydration level suggesting that swelling of cells mainly occurs in the direction perpendicular to the skin surface. At an increased hydration level, the corneocyte envelope more efficiently surrounds the cell content compensating for the increased cell volume. The changes in stratum corneum morphology with increasing water level have also been observed in dermatomed skin.