Filaggrin expression via immunohistochemistry in basal cell carcinoma and squamous cell carcinoma.

BACKGROUND: Filaggrin is a protein integral to the structure and function of the epidermis. Filaggrin (FLG) loss-of-function (LOF) mutations are common and increase the risk of developing atopic dermatitis (AD) and ichthyosis vulgaris (IV). Epidemiologic data suggest a link between skin cancer and AD. We examined if FLG staining pattern can be used to characterize cutaneous squamous cell carcinomas (SCC), basal cell carcinomas (BCC), and reactive squamous epithelium. METHODS: Tissue microarrays (TMAs) were created from 196 cases of formalin-fixed paraffin-embedded (FFPE) SCC and 144 BCC cases. TMAs and sections of reactive squamous epithelium were stained with optimized anti-FLG antibody and evaluated for FLG expression (normal, abnormal, or negative). RESULTS: FLG was absent in poorly differentiated (PD) compared to well-differentiated (WD) SCC (P < .0001) and moderately-differentiated (MD) (P = .0231) SCC, and in MD compared to WD SCC (P = .0099). Abnormal staining was significantly increased in PD compared to WD cases (P = .0039) and in MD compared to WD cases (P = .0006). Most BCC did not exhibit FLG expression (P < .05). Reactive squamous epithelium demonstrated normal, but exaggerated FLG expression. CONCLUSIONS: Our findings demonstrate the differences in FLG expression patterns in types of keratinocyte carcinomas and their mimickers.

3D-Organotypic Cultures to Unravel Molecular and Cellular Abnormalities in Atopic Dermatitis and Ichthyosis Vulgaris.

Atopic dermatitis (AD) is characterized by dry and itchy skin evolving into disseminated skin lesions. AD is believed to result from a primary acquired or a genetically-induced epidermal barrier defect leading to immune hyper-responsiveness. Filaggrin (FLG) is a protein found in the cornified envelope of fully differentiated keratinocytes, referred to as corneocytes. Although FLG null mutations are strongly associated with AD, they are not sufficient to induce the disease. Moreover, most patients with ichthyosis vulgaris (IV), a monogenetic skin disease characterized by FLG homozygous, heterozygous, or compound heterozygous null mutations, display non-inflamed dry and scaly skin. Thus, all causes of epidermal barrier impairment in AD have not yet been identified, including those leading to the Th2-predominant inflammation observed in AD. Three dimensional organotypic cultures have emerged as valuable tools in skin research, replacing animal experimentation in many cases and precluding the need for repeated patient biopsies. Here, we review the results on IV and AD obtained with epidermal or skin equivalents and consider these findings in the context of human in vivo data. Further research utilizing complex models including immune cells and cutaneous innervation will enable finer dissection of the pathogenesis of AD and deepen our knowledge of epidermal biology.

[ANALYSIS OF ONE-CARBON METABOLISM GENES AND EPIDERMAL DIFFERENTIATION COMPLEX IN PATIENTS WITH ICHTHYOSIS VULGARIS].

The aim of the study was to evaluate the effects of allelic polymorphism of the FLG and MTHFR genes and their associations in gynecological patients with ichthyosis vulgaris. Gynecological disorders are observed in presence of some forms of ichtyosis. From the prospective of improving nation's healthcare, the greatest attention is drawn to reproductive disorders. Based on this, the research was also tasked with studying of the genetic nature of gynecological diseases, as well as the influence of geographical latitude on the frequencies of mutagenic alleles of the FLG gene and heterogeneous carriers of these mutations. The collection of clinical-gynecological history was carried out by the method of single registration of the proband on the basis of the Regional Clinical Dermatological and Venereological Health Center No. 1 and the Dermatovenerological Health Centers of the Kharkiv Region. The diagnosis and form of dermatosis is established on the basis of the analysis of clinical and gynecological data and the results of laboratory tests in accordance with ICD-10: ichthyosis vulgaris (Q 80.1.0, OMIM 146700). The data on 18 women and 20 men from 3 families, aged 26 to 76 years old, suffering from ichthyosis, were analyzed. As a result of the study, a direct correlation was determined between the latitude and frequencies of mutant alleles of the FLG gene, as well as between the geographical latitude and frequency of heterozygous carriers of these mutations. The frequencies of the T allele and the CT genotype according to polymorphic variant C677T of the MTHFR gene demonstrate feedback with the latitude indicators. The frequency distributions of the 2282del4 allele and the CT genotype, the N/2282del4 and CT genotypes, the 2282del4 and T alleles, the N/2282del4 genotype and the T allele have opposite latitudinal zonation. The established connections made it possible to predict the development of gynecological pathologies in women with ichthyosis vulgaris. The prevalence of endometriosis and endometrial cancer in women with ichthyosis vulgaris in the Kharkiv region was 33.3%, while the average for the female population in the region was 0.29-0.35%. The number of children born to women with ichthyosis vulgaris did not differ from the regional index.

Distinguishing ichthyoses by protein profiling.

To explore the usefulness of protein profiling for characterization of ichthyoses, we here determined the profile of human epidermal stratum corneum by shotgun proteomics. Samples were analyzed after collection on tape circles from six anatomic sites (forearm, palm, lower leg, forehead, abdomen, upper back), demonstrating site-specific differences in profiles. Additional samples were collected from the forearms of subjects with ichthyosis vulgaris (filaggrin (FLG) deficiency), recessive X-linked ichthyosis (steroid sulfatase (STS) deficiency) and autosomal recessive congenital ichthyosis type lamellar ichthyosis (transglutaminase 1 (TGM1) deficiency). The ichthyosis protein expression patterns were readily distinguishable from each other and from phenotypically normal epidermis. In general, the degree of departure from normal was lower from ichthyosis vulgaris than from lamellar ichthyosis, parallel to the severity of the phenotype. Analysis of samples from families with ichthyosis vulgaris and concomitant modifying gene mutations (STS deficiency, GJB2 deficiency) permitted correlation of alterations in protein profile with more complex genetic constellations.

Spontaneous atopic dermatitis-like symptoms in a/a ma ft/ma ft/J flaky tail mice appear early after birth.

Loss-of-function mutations in human profilaggrin gene have been identified as the cause of ichthyosis vulgaris (IV), and as a major predisposition factor for atopic dermatitis (AD). Similarly, flaky tail (a/a ma ft/ma ft/J) mice were described as a model for IV, and shown to be predisposed to eczema. The aim of this study was to correlate the flaky tail mouse phenotype with human IV and AD, in order to dissect early molecular events leading to atopic dermatitis in mice and men, suffering from filaggrin deficiency. Thus, 5-days old flaky tail pups were analyzed histologically, expression of cytokines was measured in skin and signaling pathways were investigated by protein analysis. Human biopsies of IV and AD patients were analyzed histologically and by real time PCR assays. Our data show acanthosis and hyperproliferation in flaky tail epidermis, associated with increased IL1ß and thymic stromal lymphopoietin (TSLP) expression, and Th2-polarization. Consequently, NFκB and Stat pathways were activated, and IL6 mRNA levels were increased. Further, quantitative analysis of late epidermal differentiation markers revealed increased Small proline-rich protein 2A (Sprr2a) synthesis. Th2-polarization and Sprr2a increase may result from high TSLP expression, as shown after analysis of 5-days old K14-TSLP tg mouse skin biopsies. Our findings in the flaky tail mouse correlate with data obtained from patient biopsies of AD, but not IV. We propose that proinflammatory cytokines are responsible for acanthosis in flaky tail epidermis, and together with the Th2-derived cytokines lead to morphological changes. Accordingly, the a/a ma ft/ma ft/J mouse model can be used as an appropriate model to study early AD onset associated with profilaggrin deficiency.

Aberrant distribution patterns of corneodesmosomal components of tape-stripped corneocytes in atopic dermatitis and related skin conditions (ichthyosis vulgaris, Netherton syndrome and peeling skin syndrome type B).

BACKGROUND: Atopic dermatitis (AD), Netherton syndrome (NS) and peeling skin syndrome type B (PSS) may show some clinical phenotypic overlap. Corneodesmosomes are crucial for maintaining stratum corneum integrity and the components' localization can be visualized by immunostaining tape-stripped corneocytes. In normal skin, they are detected at the cell periphery. OBJECTIVE: To determine whether AD, NS, PSS and ichthyosis vulgaris (IV) have differences in the corneodesmosomal components' distribution and corneocytes surface areas. METHODS: Corneocytes were tape-stripped from a control group (n=12) and a disease group (37 AD cases, 3 IV cases, 4 NS cases, and 3 PSS cases), and analyzed with immunofluorescent microscopy. The distribution patterns of corneodesmosomal components: desmoglein 1, corneodesmosin, and desmocollin 1 were classified into four types: peripheral, sparse diffuse, dense diffuse and partial diffuse. Corneocyte surface areas were also measured. RESULTS: The corneodesmosome staining patterns were abnormal in the disease group. Other than in the 3 PSS cases, all three components showed similar patterns in each category. In lesional AD skin, the dense diffuse pattern was prominent. A high rate of the partial diffuse pattern, loss of linear cell-cell contacts, and irregular stripping manners were unique to NS. Only in PSS was corneodesmosin staining virtually absent. The corneocyte surface areas correlated significantly with the rate of combined sparse and dense diffuse patterns of desmoglein 1. CONCLUSION: This method may be used to assess abnormally differentiated corneocytes in AD and other diseases tested. In PSS samples, tape stripping analysis may serve as a non-invasive diagnostic test.

Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis.

BACKGROUND: Filaggrin is a key protein involved in maintaining skin barrier function and hydration. Mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and are a major predisposing factor for atopic dermatitis (AD) in individuals of European and Asian descent. It has been proposed that FLG mutations are population specific and a difference in the spectra of mutations between different ancestral groups has been described. However, it is unknown whether FLG mutations in the African population are a causative genetic factor for IV and predispose to AD, or whether other mechanisms are more prominent. OBJECTIVES: The present aim was to investigate the role of FLG mutations as predisposing factors for IV or AD among individuals from Ethiopia. METHODS: A case series of Ethiopian patients with AD (n = 103) and IV (n = 7) together with controls (n = 103; subjects without past or present history of AD, dry skin or atopic manifestations) was collected at the outpatient dermatology clinics at ALERT Dermatology Hospital, Tikur Anbessa Hospital and Gondar University Hospital, Ethiopia. AD was diagnosed by a dermatologist using the U.K. Working Party's diagnostic criteria. The IV diagnosis was based on clinical examination and genetic testing of the steroid sulphatase gene to exclude X-linked recessive ichthyosis. Patients were studied with direct sequencing (n = 40) and/or allelic discrimination (n = 110). Immunohistochemical analysis was performed for filaggrin expression in the skin of patients (n = 7) and controls (n = 2). RESULTS: The Ethiopian patients and controls were genotyped for the four previously described common European FLG null mutations (R501X, 2282del4, S3247X, R2447X) and no carriers were found. In one patient with AD a novel heterozygous 2-bp deletion, 632del2, leading to a premature stop codon was revealed by direct sequencing. No additional carrier of this deletion or other mutations was found. In addition, no difference in filaggrin expression was detected in AD or IV skin compared with healthy control skin. CONCLUSIONS: Our results indicate that FLG loss-of-function-variants are less common in patients with IV and AD in the Ethiopian population, suggesting that other factors may be of importance in the pathogenesis in this ethnic group.

Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an ichthyosis-vulgaris-like disease.

The skin is the outer layer of protection against the environment. The development and formation of the skin is regulated by several genetic cascades including the bone morphogenetic protein (BMP) signaling pathway, which has been suggested to play an important role during embryonic organ development. Several skin defects and diseases are caused by genetic mutations or disorders. Ichthyosis is a common genetic skin disorder characterized by dry scaly skin. Loss-of-function mutations in the filaggrin (FLG) gene have been identified as the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct regulation of filaggrin expression in vivo is unknown. We present evidence that BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a constitutively active form of BMP-receptor-IB in the developing epidermis exhibit a phenotype resembling IV in humans, including dry flaky skin, compact hyperkeratosis, and an attenuated granular layer associated with a significantly downregulated expression of filaggrin. Regulation of filaggrin expression by BMP signaling has been further confirmed by the application of exogenous BMP2 in skin explants and by a transgenic model overexpressing Noggin in the epidermis. Our results demonstrate that aberrant BMP signaling in the epidermis causes overproliferation and hyperkeratinization, leading to an IV-like skin disease.

The content of free amino acids in the stratum corneum is increased in senile xerosis.

Xerosis is one of the characteristics of aged skin. Xerosis may be caused by a decrease in the stratum corneum free amino acids which are natural moisturizing factors derived from filaggrin. In aged skin, filaggrin is immunohistochemically decreased compared with the levels in young skin. However, the differences in stratum corneum amino acids between aged and young skin have not been analyzed quantitatively. Therefore, in this study we determined the stratum corneum amino acids per 1000 stratum corneum cells in aged and young skin by high-performance liquid chromatography. The amount of filaggrin mRNA in the epidermis was also compared between aged and young skin using RT-PCR. The total amount of amino acids in the stratum corneum was larger in aged senile xerosis skin than in young skin. Only a few amino acids were found in the stratum corneum of ichthyosis vulgaris patients (control skin). The expression of filaggrin mRNA in aged skin was, however, similar to that in young skin. These findings suggest that the immunohistochemical decrease in filaggrin in aged skin may be caused by promotion of filaggrin proteolysis in the upper layers of the stratum spinulosum.

Expression of transglutaminase 5 in normal and pathologic human epidermis.

To explore the expression and gain more information on the function of transglutaminase 5 enzyme in normal and defective human epidermis, we generated a rat antihuman transglutaminase 5 antiserum elicited against a purified active recombinant protein expressed in the baculovirus system. By use of Western blotting and immunofluorescence methods, the immunospecificity of the antibodies for transglutaminase 5 was tested; no crossreactivity with other transglutaminases (types 1, 2, and 3) was observed, thus allowing histochemistry studies. By indirect immunofluorescence analysis the antibodies decorated the upper layers of normal human epidermis, with consistent staining in the spinous and granular layers. We evaluated transglutaminase 5 expression in comparison with proliferating (keratin 14) and differentiating (transglutaminase 3) markers in different diseases, such as psoriasis, ichthyosis vulgaris, lamellar ichthyosis, and Darier's disease. We observed that transglutaminase 5 contributes, as a secondary effect, to the hyperkeratotic phenotype in ichthyosis (both vulgaris and lamellar) and in psoriasis. In Darier's disease, transglutaminase 5 expression, as well as transglutaminase 3, is completely missregulated, being overexpressed or totally absent in different areas of the same lesion.

Absence of the granular layer and keratohyalin define a morphologically distinct subset of individuals with ichthyosis vulgaris.

The clinical diagnosis of ichthyosis vulgaris (IV) can be difficult. Abnormalities in the granular layer and the ultrastructure of keratohyalin granules (KHG) suggest that morphology may be helpful. To clarify morphologic findings in IV, 41 clinically affected individuals and 21 unaffected family members or age- and sex-matched controls were studied by light microscopy. In these, the granular layer was totally absent in approximately 50% of affected individuals, while present in all controls. Forty-seven individuals in the light microscopy group were also studied by electron microscopy. Keratohyalin granules were absent in all affected individuals lacking the granular layer by light microscopy. Clinical severity usually correlated with the lack of a granular layer and KHG. Absence of the granular layer was consistent in different anatomic sites and in serial biopsies taken over a 1-3-year period. In a subset of clinically affected, unrelated subjects with moderate to severe involvement, four out of 11 (36%) had similar findings. Keratinocytes cultured from affected individuals with no KHG expressed virtually no detectable profilaggrin protein in vitro. The data suggest that a subset of individuals with moderate to severe IV have a consistently absent granular layer and KHG. Absence of the granular layer and lack of KHG correlated almost perfectly; thus light microscopy offers a convenient means of identifying this subtype of IV. However, both morphologic types of IV were observed within single families. Therefore, the relationship between granular layer abnormalities and IV is complex and requires the study of more affected families. One interpretation of the data is that IV is a multigenic disorder in which one of the genes alters profilaggrin expression. We propose this clinical and histologic phenotype as useful for identifying the gene(s) involved and also for determining whether it represents a modifier or a major locus of the disorder.

Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes.

This study demonstrates the presence of tight junction antigens in adult and developing human epidermis. Indirect immunofluorescence labeling and immunoelectron microscopy with antibodies to ZO-1 and occludin localized tight junction components ZO-1 and occludin to a narrow zone of the granular cells of adult epidermis. Double immunolabeling for tight junction components with adherens junction or desmosome proteins suggested that occludin is more specific for tight junctions than ZO-1, which may also be associated with adherens junctions. In developing skin, tight junctions interconnected the peridermal cells, and after the fetal stratification localized to the granular cell layer. Immunolabeling of psoriasis, lichen planus, and ichthyosis vulgaris, representing aberrant differentiation of the epidermis, showed that these conditions were associated with relocation of ZO-1 and occludin to the spinous cells. Cultures of epidermal keratinocytes, which offer a useful model for the formation of cellular contacts, revealed that tight junction components, ZO-1 and occludin, displayed a marked degree of colocalization relatively late during the process when the fusion zone had assumed a linear appearance. This suggests that the formation of adherens junctions and desmosomes precedes that of tight junctions. We speculate that the epidermal barrier, isolating the human body from the external environment, is in part formed by tight junctions of stratum granulosum.

Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice: an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris.

Flaky tail (gene symbol ft) is an autosomal recessive mutation in mice that results in a dry, flaky skin, and annular tail and paw constrictions in the neonatal period. Previous studies demonstrated that the ft mutation maps to the central region of mouse chromosome 3, in the vicinity of the epidermal differentiation complex, a gene locus that includes many nonkeratin genes expressed in epidermis. In this study we report a detailed characterization of the flaky tail mouse. Affected homozygous ft/ft mice exhibit large, disorganized scales on tail and paw skin, marked attenuation of the epidermal granular layer, mild acanthosis, and orthokeratotic hyperkeratosis. Biochemical analysis demonstrated that ft/ft mice lacked normal high molecular profilaggrin (approximately 500 kDa), and instead expressed a lower molecular weight form of profilaggrin (220 kDa) that is not proteolytically processed to profilaggrin intermediates or filaggrin. Mutant mice lacked the large, irregular F-type keratohyalin granules that contain profilaggrin, and filaggrin was absent from the cornified layers of ft/ft epidermis. The expression of epidermal keratins was unchanged, whereas the cornified envelope proteins involucrin and loricrin were increased in ft/ft epidermis. Cultured ft/ft keratinocytes also synthesized reduced amounts of profilaggrin mRNA and protein, demonstrating that the defect in profilaggrin expression is intrinsic to epidermal cells. These findings demonstrate that flaky tail mice express an abnormal profilaggrin polypeptide that does not form normal keratohyalin F-granules and is not proteolytically processed to filaggrin. We propose that the absence of filaggrin, and in particular the hygroscopic, filaggrin-derived amino acids that are thought to function in epidermal hydration, underlies the dry, scaly skin characteristic of ft/ft mice. This animal model provides a tool for understanding the role of filaggrin in normal epidermal function and may provide insight into the molecular basis of the filaggrin-deficient human skin disorder ichthyosis vulgaris. J Invest Dermatol 115:1072-1081 2000

Altered expression of immunoreactive involucrin in lamellar ichthyosis.

In some cases of lamellar ichthyosis, mutations in the epidermal transglutaminase gene and a reduction in the thickness of the cornified envelope have been documented. Involucrin is a major component of the cornified envelope and a substrate for epidermal transglutaminase. The aim of the present work was to analyse the expression of involucrin in lamellar ichthyosis. An ultrastructural study and/or immunohistochemical and biochemical techniques with anti-involucrin antibody were carried out on the epidermis of fifteen patients (12 families) suffering from lamellar ichthyosis. The effect of in vivo retinoid treatment on the involucrin epidermal expression was also investigated. Four cases with normal skin, seventeen cases of other ichthyoses and ten cases of psoriasis were used as controls. In all these cases of lamellar ichthyosis, a thin or absent cornified envelope, electron-dense granules inside corneocytes and a decrease of the epidermal involucrin expression were observed. In the patients receiving treatment with retinoids, western blot and ELISA revealed an increase in the involucrin expression. The decreased expression of involucrin in lamellar ichthyosis could contribute to the altered desquamation process accompanying the disease, since the clinical improvement associated with retinoid treatment is accompanied by an increase in the expression of involucrin.

The pH gradient over the stratum corneum differs in X-linked recessive and autosomal dominant ichthyosis: a clue to the molecular origin of the "acid skin mantle"?

In a search for pathogenetic mechanisms underlying retention hyperkeratosis, we examined the pH gradient over the stratum corneum in 13 male patients suffering from either x-linked recessive (XRI) or autosomal dominant ichthyosis vulgaris. For recording pH values, a flat glass electrode was repeatedly applied to the skin during tape stripping of mildly involved forearm skin. Before stripping, surface pH was higher in ichthyosis vulgaris (5.3 +/- 0.7; n = 7) than in XRI (4.6 +/- 0.4; n = 6; p < 0.05) and healthy control men (4.5 +/- 0.2; n = 7; p < 0.01). Removal of stratum corneum, which required 100-240 strippings in ichthyotic skin and 80-120 strippings in healthy control skin, disclosed markedly different pH variations in the two types of ichthyosis. The major abnormality in ichthyosis vulgaris skin was that a neutral pH was attained already halfway through the horny layer, possibly reflecting a congenital lack of acidic breakdown products from keratohyaline. By contrast, stripping of XRI skin revealed a shallow pH gradient that plateaued at 6.2-6.6, instead of about 7 as in normal and ichthyosis vulgaris skin. A likely explanation is the XRI-associated accumulation of cholesterol sulfate in lower stratum corneum. Our results suggest that the "acid mantle" of normal skin, which penetrates deep into the stratum corneum, is the combined result of cornification-associated organic acids and back-diffusion of acid material from the surface. Because corneocyte desquamation involves many pH-dependent enzymes, abnormalities in the transcorneal pH gradient might play a role in the pathogenesis of ichthyosis.

Decreased profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control.

Ichthyosis vulgaris is an autosomal dominant disorder of keratinization characterized by mild hyperkeratosis and reduced or absent keratohyalin granules in the epidermis. Profilaggrin, a major component of keratohyalin granules, is reduced or absent from the skin of individuals with ichthyosis vulgaris. In this report, we have further characterized the molecular basis of low profilaggrin expression, which occurs in this disease. In situ hybridization revealed little profilaggrin mRNA in ichthyosis vulgaris-affected epidermis. In keratinocytes cultured from the epidermis of affected individuals, the abundance of profilaggrin was reduced to less than 10% of normal controls, while the mRNA level was decreased to 30-60% of controls. Expression of K1 and loricrin, other markers of epidermal differentiation, were not affected. Nuclear run-on assays indicated that the decrease in mRNA levels was not caused by aberrant transcription. Nucleotide sequencing of 5'-upstream, 3'-non-coding, and flanking regions of the profilaggrin gene from ichthyosis vulgaris-affected individuals revealed only minor changes, probably due to genetic polymorphisms. Our results indicate that defective profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control.

Expression of tenascin, biglycan and decorin in disorders of keratinization.

The distribution of three (recently discovered) extracellular matrix components (tenascin, biglycan and decorin) was studied in normal adult human skin and in a number of monogenic disorders of keratinization, using immunohistology. The expression of tenascin, which is sparsely distributed in normal human dermis, was found to be grossly increased in epidermolytic hyperkeratoses and in Darier's disease. Tenascin expression in three types of ichthyosis (X-linked recessive ichthyosis, autosomal dominant ichthyosis vulgaris, non-erythrodermic lamellar ichthyosis) was similar to that of normal skin. The presence of biglycan and decorin did not show a marked variation between the different disorders studied, suggesting that their expression is subject to regulatory mechanisms distinct from those of tenascin. The increased expression of tenascin in two disorders of keratinization with a hyperproliferative phenotype, lends further support to the hypothesis that dermal tenascin expression is increased as a result of epidermal hyperproliferation.

A statistical study on in vivo sorption and desorption of water in ichthyosis vulgaris.

Experiments on the variation of electrical conductance on sorption and desorption of water were performed on the skin of 34 subjects: 17 ichthyosis vulgaris patients and 17 normal subjects, matched for age and gender, under different ambient conditions. An exponential model of the form ft = theta oe theta t, where ft denotes fractional conductance at time t, describes the process of desorption with high accuracy. The parameter theta, identifiable as the rate of desorption, is significantly different between the ichthyotic and normal populations. The study discusses the impaired barrier function of the ichthyotic skin.

The quantification of free sphingosine in the stratum corneum of patients with hereditary ichthyosis.

Sphingosine is a long-chain base which provides the back-bone of all sphingolipid molecules. Free sphingosine is found in normal epidermis, especially in the stratum corneum. As a free molecule it may modify epidermal cell proliferation and differentiation through its inhibition of protein kinase C. Using a thin-layer chromatography technique we have demonstrated in vitro that the erythrodermic ichthyoses show significantly lower levels of stratum corneum sphingosine than the non-erythrodermic types. The exact in vivo significance of this finding is unclear, but free sphingosine may have an important role in determining the inflammatory component of the hereditary ichthyoses.