Sensor-Based Detection of the Severity of Hyperkeratosis in the Teats of Dairy Cows.

The aim of this study was to evaluate whether the severity of hyperkeratosis (HK) in the teats of dairy cows can be assessed by a dielectric measurement. The study focused on surveying the occurrence of hyperkeratosis in a total of 241 teats of lactating dairy cows. A scoring system consisting of four categories was used to macroscopically assess the severity of HK. Additionally, the dielectric constant (DC) of all teats with milkability was measured in a double iteration with the MoistureMeterD (Delfin Technologies, Kuopio, Finland) on four different days. The Spearman rank correlation coefficient revealed a negative correlation between the DC and HK score (rs = -0.55 to -0.36). The results of the regression analysis showed that the DC values differed significantly between healthy teat ends (≤2) and teat ends with HK (≥3). Thus, the non-invasive measurement of DC provides a promising method of objectively assessing the occurrence and severity of HK.

Management of Epidermolytic Ichthyosis in the Newborn.

Epidermolytic ichthyosis (EI) is a rare autosomal dominant genodermatosis that presents at birth as a bullous disease, followed by a lifelong ichthyotic skin disorder. Essentially, it is a defective keratinization caused by mutations of keratin 1 (KRT1) or keratin 10 (KRT10) genes, which lead to skin fragility, blistering, and eventually hyperkeratosis. Successful management of EI in the newborn period can be achieved through a thoughtful, directed, and interdisciplinary or multidisciplinary approach that encompasses family support. This condition requires meticulous care to avoid associated morbidities such as infection and dehydration. A better understanding of the disrupted barrier protection of the skin in these patients provides a basis for management with daily bathing, liberal emollients, pain control, and proper nutrition as the mainstays of treatment. In addition, this case presentation will include discussions on the pathophysiology, complications, differential diagnosis, and psychosocial and ethical issues.

[Mutation analysis of KRT10 gene in a patient with bullous congenital ichthyosiform erythroderma].

OBJECTIVE: To investigate the gene mutation in one sporadic case of bullous congenital ichthyosiform erythroderma (BCIE), and to explore the relationship between the genotype and phenotype. METHODS: DNA was extracted from the blood samples of the patient with BCIE, unaffected members of the pedigree, and 50 unrelated healthy controls. PCR was used to amplify the hot spot fragment of keratin 1 (KRT1) and keratin 10 (KRT10) gene. The PCR products were directly sequenced to detect the mutations. RESULTS: A heterozygous 467G>A mutation was found in the patient, resulting in the substitution of arginine (R) by histidine (H) in codon 156 (R156H) in the 1A domain of the KRT10 protein but not in the healthy individuals from the family and the 50 unrelated individuals. CONCLUSION: The mutation of 467G>A in exon 1 of KRT10 gene identified may play a major role in the pathogenic mechanism of this case of BCIE.

Immortalized keratinocytes derived from patients with epidermolytic ichthyosis reproduce the disease phenotype: a useful in vitro model for testing new treatments.

BACKGROUND: Epidermolytic ichthyosis (EI) is a skin fragility disorder caused by mutations in genes encoding suprabasal keratins 1 and 10. While the aetiology of EI is known, model systems are needed for pathophysiological studies and development of novel therapies. OBJECTIVES: To generate immortalized keratinocyte lines from patients with EI for studies of EI cell pathology and the effects of chemical chaperones as putative therapies. METHODS: We derived keratinocytes from three patients with EI and one healthy control and established immortalized keratinocytes using human papillomavirus 16-E6/E7. Growth and differentiation characteristics, ability to regenerate organotypic epidermis, keratin expression, formation of cytoskeletal aggregates, and responses to heat shock and chemical chaperones were assessed. RESULTS: The cell lines EH11 (K1_p.Val176_Lys197del), EH21 (K10_p.156Arg>Gly), EH31 (K10_p.Leu161_Asp162del) and NKc21 (wild-type) currently exceed 160 population doublings and differentiate when exposed to calcium. At resting state, keratin aggregates were detected in 9% of calcium-differentiated EH31 cells, but not in any other cell line. Heat stress further increased this proportion to 30% and also induced aggregates in 3% of EH11 cultures. Treatment with trimethylamine N-oxide and 4-phenylbutyrate (4-PBA) reduced the fraction of aggregate-containing cells and affected the mRNA expression of keratins 1 and 10 while 4-PBA also modified heat shock protein 70 (HSP70) expression. Furthermore, in situ proximity ligation assay suggested a colocalization between HSP70 and keratins 1 and 10. Reconstituted epidermis from EI cells cornified but EH21 and EH31 cells produced suprabasal cytolysis, closely resembling the in vivo phenotype. CONCLUSIONS: These immortalized cell lines represent a useful model for studying EI biology and novel therapies.

Xantomatosis perifolicular: hallazgo histológico clave en la enfermedad de Fox-Fordyce / Perifollicular xanthomatosis as a key histological finding in Fox-Fordyce disease

La enfermedad de Fox-Fordyce es una rara dermatosis caracterizada por la presencia de múltiples pápulas foliculares pruriginosas en áreas corporales con riqueza de glándulas apocrinas como axilas, areolas mamarias o región genital. Los hallazgos histopatológicos que definen la enfermedad de Fox-Fordyce son muy variados. Además de los hallazgos descritos como típicos de esta entidad, como la dilatación del infundíbulo y la hiperqueratosis y espongiosis del epitelio infundibular, se pueden observar otros muchos hallazgos histológicos. Presentamos el caso de una mujer de 21 años de edad afectada por esta enfermedad y recalcamos la importancia de la xantomatosis perinfundibular como hallazgo histológico clave en el diagnóstico de esta entidad (AU)

Fox-Fordyce disease is a rare skin condition characterized by the presence of multiple pruritic follicular papules in areas rich in apocrine glands, such as the axillae, mammary areolae, or genital regions. There is a high degree of variability in the histological findings seen in Fox-Fordyce disease. In addition to those described as typical of this entity, such as dilation of the infundibulum and hyperkeratosis and spongiosis of the infundibular epithelium, many other histological changes can be observed. We report the case of a 21-year-old woman with Fox-Fordyce disease and highlight the importance of perifollicular xanthomatosis as a key histological finding in the diagnosis of the disease (AU)

Queratosis folicular y mieloma múltiple / Follicular keratosis and multiple myeloma

La queratosis folicular puede ser una rara enfermedad paraneoplásica de etiopatogenia desconocida, a veces asociada a mieloma, cuyo diagnóstico y evolución siguen un curso paralelo. Describimos el caso de una paciente de 57 años diagnosticada de mieloma múltiple 8 años antes, que desarrolló espículas hiperqueratósicas foliculares generalizadas coincidiendo con la leucemización del mieloma

Follicular keratosis may be a rare paraneoplastic disease having unknown etiopathogeny that is sometimes associated to myeloma whose diagnosis and evolution follow a parallel course. We describe the case of a 57-year-old female patient diagnosed of multiple myeloma 8 years ago. She developed generalized follicular hyperkeratotic spicules coinciding with leukemization of the myeloma

Acroqueratosis paraneoplásica con lesiones ampollosas asociada a carcinoma epidermoide esofágico / Acrokeratosis paraneoplastica with bullous lesions associated with esophageal squamous cell carcinoma

La acroqueratosis paraneoplásica de Bazex se caracteriza por una erupción acral de aspecto psoriasiforme que suele presentarse de forma simultánea a una neoplasia subyacente. Describimos el caso de un varón de 64 años que presentaba una historia de 2 meses de evolución de lesiones pruriginosas eritematosas y descamativas en las palmas, el dorso de los dedos de las manos y los pies y en los pabellones auriculares, acompañadas de lesiones ampollosas. Refería también en los últimos 6 meses disfagia progresiva y síndrome general con pérdida de 15 kg. La endoscopia digestiva reveló la existencia de un carcinoma epidermoide en el esófago proximal. El estudio histopatológico de las lesiones ampollosas mostró la presencia de una ampolla subepidérmica, y la inmunofluorescencia directa demostró la existencia de depósitos granulares de IgG, IgA y C3 en la membrana basal de la piel sana perilesional. Estos hechos clinicopatológicos apoyan la existencia de un mecanismo patogénico inmunológico en relación con dicha entidad

Acrokeratosis paraneoplastica (Bazex syndrome) is characterized by an acral eruption with a psoriasiform appearance, which usually presents simultaneously with an underlying neoplasm. We describe the case of a 64-year-old male who presented with a two-month history of pruritic, flaky, erythematous lesions on the palms, backs of the fingers and toes and pinnae, accompanied by bullous lesions. The patient also reported progressive dysphagia in the last six months, and general wasting with a loss of 15 kg. The digestive endoscopy revealed a squamous cell carcinoma in the proximal esophagus. The histopathological study of the bullous lesions showed the presence of a subepidermal bulla, and direct immunofluorescence revealed granular deposits of IgG, IgA and C3 in the basal membrane of the healthy perilesional skin. These clinical/pathological findings support the existence of an immunological pathogenic mechanism related to this entity

[Pathophysiology of acne]. / Pathophysiologie der Akne.

Several pathogenic factors contribute to the development of acne, among them, seborrhea, follicular hyperkeratosis, propionibacteria, and inflammatory events. This article reviews current knowledge of these pathogenic factors.

Multiple spreading epidermolytic acanthomas of the genital and perigenital skin.

Epidermolytic acanthoma is an uncommon benign tumour mainly characterized histologically by a prominent epidermolytic degeneration of the keratinocytes of the upper layers of the stratum spinosum and of the stratum granulosum. The absence of desmosome involvement allows to differentiate this condition from others such as acantholytic acanthoma. We report the first case, to our knowledge, of a 54-year-old male patient exhibiting disseminated scrotal, gluteal, inguinal and perineal epidermolytic acanthomas.

Eliminación quirúrgica de papilomas con ondas de alta frecuencia / Surgical elimination of verrucas by high frequency waves

En el presente trabajo, el autor expone una solución quirúrgica a la eliminación de los papilomas. De destacar el mínimo trauma tisular y por lo tanto mejor recuperación, sencillez del procedimiento y escasa frecuencia de recidivas (AU)

Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB).

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

Hyperproliferation, induction of c-Myc and 14-3-3sigma, but no cell fragility in keratin-10-null mice.

In the past, keratins have been established as structural proteins. Indeed, mutations in keratin 10 (K10) and other epidermal keratins lead to severe skin fragility syndromes. Here, we present adult K10-/- mice, which reveal a novel connection between the regulation of cell proliferation and K10. Unlike most keratin mutant mice, the epidermis of adult K10-/- mice showed no cytolysis but displayed hyperproliferation of basal keratinocytes and an increased cell size. BrdU labelling revealed a shortened transition time for keratinocytes migrating outwards and DAPI staining of epidermal sheets uncovered an impaired organization of epidermal proliferation units. These remarkable changes were accompanied by the induction of c-Myc, cyclin D1, 14-3-3sigma and of wound healing keratins K6 and K16. The phosphorylation of Rb remained unaltered. In line with the downregulation of K10 in squamous cell carcinomas and its absence in proliferating cells in vivo, our data suggest that the tissue-restricted expression of some members of the keratin gene family not only serves structural functions. Our results imply that the altered composition of the suprabasal cytoskeleton is able to alter the proliferation state of basal cells through the induction of c-Myc. A previous model based on transfection of K10 in immortalized human keratinocytes suggested a direct involvement of K10 in cell cycle control. While those experiments were performed in human cultured keratinocytes, our data establish, that in vivo, K10 acts by an indirect control mechanism in trans.

Focal activation of a mutant allele defines the role of stem cells in mosaic skin disorders.

Stem cells are crucial for the formation and maintenance of tissues and organs. The role of stem cells in the pathogenesis of mosaic skin disorders remains unclear. To study the molecular and cellular basis of mosaicism, we established a mouse model for the autosomal-dominant skin blistering disorder, epidermolytic hyperkeratosis (MIM 113800), which is caused by mutations in either keratin K1 or K10. This genetic model allows activation of a somatic K10 mutation in epidermal stem cells in a spatially and temporally controlled manner using an inducible Cre recombinase. Our results indicate that lack of selective pressure against certain mutations in epidermal stem cells leads to mosaic phenotypes. This finding has important implications for the development of new strategies for somatic gene therapy of dominant genodermatoses.

[Keratin diseases]. / Keratinsygdomme.

The rapid development in human genome research has resulted in a tremendous increase in our understanding of the molecular basis of many genetic skin diseases. One outstanding example of this is diseases caused by mutations in keratin genes, which comprise several disorders of the epidermis, as for example the different types of epidermolysis bullosa simplex. In this respect, the most important questions have been to 1. Define the molecular defect. 2. Unravel the pathophysiological mechanisms that lead to the characteristic phenotype and 3. Design of new therapeutic strategies. Molecular research has contributed significantly to the first two issues whereas a therapeutic break-through has yet to appear.

The relationship between hyperproliferation and epidermal thickening in a mouse model for BCIE.

Epidermal thickening is a phenomenon common to many genodermatoses but little is known about the underlying causes. We have recently created a mouse model for the human skin disease bullous congenital ichthyosiform erythroderma by gene targeting. Mice heterozygous for a truncated keratin 10 gene exhibit acanthosis and hyperkeratosis as seen in the human disease. The degree of epidermal thickening is highly variable, offering a novel opportunity to investigate how epidermal homeostasis is modulated in keratin disorders by comparing epidermis from different body regions. We have performed bromodeoxyuridine labeling experiments and detected proliferation antigens by immunohistochemical means to compare proliferation in the epidermis of wild-type and heterozygous mice. These results have been compared with the expression of epidermal differentiation markers and of the "hyperproliferation associated" keratins K6 and K16. These experiments indicated that hyperproliferation is only partly responsible for the morphologic changes and that other mechanisms such as decreased desquamation are likely to be involved.