Mutations in the filaggrin gene (FLG) are among the most com-mon and profound single-gene defects identified to date in thecausation and modification of disease. FLG encodes an importantepidermal ...protein abundantly expressed in the outer layers of theepidermis 1. Approximately 10% of persons of European ances-try are heterozygous carriers of a loss-of-function mutation in FLG,resulting in a 50% reduction in expressed protein 2. The criticalrole of filaggrin in epidermal function underlies the pathogenicimportance of this gene in common dermatologic and allergicdiseases. The spectrum of such diseases encompasses monogenicdisorders of keratinization through complex abnormalities of epi-dermal transport of lipids and allergens. FLG mutation carriershave a greatly increased risk of common complex traits, includingatopic dermatitis (which affects 42% of all mutation carriers), con-tact allergy, asthma, hay fever, and peanut allergy. These geneticvariants also influence the severity of asthma and alopecia areataand susceptibility to herpetic infection.
In the stratum granulosum of mammalian epidermis, keratohyalin contains the histidine-rich protein filagrin which determines the aggregation of keratin bundles in terminally differentiating ...keratinocytes. Among reptiles, the lizard epidermis possesses keratohyalin-like granules during a period preceding molting. Tritiated histidine is taken up at 3-22 h post-injection mainly in keratohyalin-like granules of the clear layer, and less intensely in oberhautchen cells, in pre-keratinizing cells of wound epidermis and in the alpha-layer. No labelling was observed in beta-cells and mesos cells. Single and double immunogold localization of filagrin and keratin, using mammalian antibodies, show that some filagrin-like immunoreactivity is localized in 0.15-0.40 microm diameter roundish keratohyalin-like granules in cells of wound epidermis, and lacunar and clear layers (soft alpha-layers). Pro-filagrin was not immuno-localized in these layers with the mammalian antibodies. The small granules merge with keratin bundles into mature keratinocytes where immunopositive keratin filaments predominate and the filagrin-like immunolabelling rapidly disappears. Little or no labelling is observed in the large keratohyaline-like granules of the clear layer. This may be due to lack of filagrin-like immunoreactivity but may also be due to epitope-masking or chemical degradation of filagrin-like molecules. No immunoreactivity is present in the beta-layer and mesos-layer but the immunolabelling reappears in the maturing alpha-layer and lacunar layer. This study suggests that histidin-rich protein with some filagrin-like immunoreactivity is initially present in those alpha-layers of lizard epidermis where keratohyalin-like granules are present, such as lacunar and clear cells, and that a filagrin-like molecule is degraded or altered in mature keratinocytes.
The aromatic retinoids etretinate and acitretin are widely used in the systemic treatment of severe psoriasis. The purpose of the present investigation was to further elucidate the mode of action of ...acitretin on abnormal keratinization and epidermal hyperproliferation in an in vivo model. Studies on the interference of acitretin with epidermal hyperproliferation and abnormal keratinization in psoriatic plaques are difficult to interpret, as acitretin-induced changes might be due to direct effects of acitretin or be the indirect effect of retinoid-induced modulation of cutaneous inflammation. Using an immunohistochemical assessment, we examined the in vivo effect of systemic acitretin ( > 35 mg daily) on the expression of filaggrin, involucrin, and on the recruitment of cycling epidermal cells, in the tape-stripped uninvolved skin of psoriatic patients, a model which provides the opportunity to study epidermal regeneration in the absence of significant accumulation of T-lymphocytes. During acitretin therapy and 3 weeks after withdrawal of acitretin, we took biopsies from uninvolved skin following tape-stripping in 6 patients with psoriasis. Six patients with psoriasis who had never used acitretin served as controls. We did not observe a Koebner response in our patients after tape stripping. Filaggrin expression was decreased, while the recruitment of cycling epidermal cells and the involucrin expression were increased in the biopsies taken from patients who did not use acitretin. During acitretin treatment, however, the filaggrin expression was similar, whereas the Ki-67 positive nuclei and the involucrin expression showed a statistically significant decrease compared to those parameters in the patients who did not use acitretin. Our findings indicate that epidermal hyperproliferation and abnormal keratinization are modulated directly by acitretin.
La Dermatitis Atópica es una enfermedad crónica e inflamatoria de la piel, se transmite genéticamente y se caracteriza por placas de eritema, descamación y prurito intenso que puede afectar la ...calidad de vida de los individuos comprometidos. Rev.cienc. biomed.2010; 1 (2): 271 - 277
La dermatite atopique (DA), ou eczéma atopique (EA), est sans contexte la pathologie chronique la plus fréquente de l’enfant. La signification clinique de l’hypersensibilité aux aliments dans la DA a ...fait l’objet d’un débat ancien. L’amélioration très nette de la qualité des études récentes a permis que soit désormais reconnu le rôle, au moins partiel, de l’allergie alimentaire (AA) au cours de la DA. Actuellement, on distingue la forme de la DA allergique IgE-dépendante, qui touche environ 70 à 80 % des patients chez lesquels on retrouve des sensibilisations aux allergènes alimentaires et/ou de l’environnement et la forme non allergique non IgE-dépendante, qui affecte une minorité de patients (20–30 %, dont 15 à 20 % d’enfants). Des études actuelles montrent que la DA qui débute souvent chez le nourrisson est loin d’être associée à un taux élevé d’IgE et que les sensibilisations apparaissant beaucoup plus tard suggèrent que l’EA peut débuter sous une forme non allergique (intrinsèque) et évoluer ensuite vers une forme allergique (extrinsèque). Les actuels travaux insistent sur la perte de l’intégrité de la barrière épidermique et sur le rôle crucial d’une protéine la filagrine dont le déficit serait en partie responsable. En ce qui concerne le rapport DA et AA, il est raisonnable de suivre les conclusions de l’Académie européenne d’immunologie et d’allergologie clinique en 2007, qui considère que 50 % des enfants atteints de DA présentent une aggravation de leurs lésions cutanées après ingestion de certains aliments, confirmées par la présence des tests cutanés positifs ou d’anticorps spécifiques IgE ou par l’existence des patch-tests positifs qui signifieraient l’existence d’un autre mode sensibilisation de type retardée. Dans cet article, nous attirons l’attention sur le rôle des allergènes alimentaires aéroportés et sur l’association souvent méconnue d’une DA et d’un reflux gastro-œsophagien. Enfin, la prise en charge d’une DA demande un contrôle de l’environnement et du mode alimentaire ainsi que des approches thérapeutiques locales et générales ainsi qu’un soutien psychologique de la famille.
Atopic dermatitis (AD), or atopic eczema (EA), is a chronic, relapsing, inflammatory skin disease. Children with AD tend to have a higher prevalence of food allergies. AD is an early manifestation of atopy and one of the most common skin disorders seen in infants and children, usually has its onset during the first 6
months of life. Because the role and immunology of food allergy in AD remain controversial, here we review data that mainly focus on skin eczema and food allergy. Recent findings (EAACI 2007) have revealed that more than 50% of all children with AD that can be exacerbated by certain foods will react with a worsening of skin eczema alone or in addition to immediate symptoms. These symptoms include immediate reactions within minutes after ingesting food with early and late exacerbations of AD. There are two main subtypes of AE, i.e. the IgE-associated “EA” and the non-IgE associated type “non-EA” with different prognosis concerning the development of respiratory diseases “atopy march”. AD is not always associated with increased levels of serum IgE and with sensitization to food allergens. Recently, it was demonstrated that Filaggrin (filament-aggregating protein, FL) is a major gene for EA. Filaggrin binds to and aggregates the keratin cytoskeleton in the epidermis. In particular, the identification of loss of function mutations in the barrier protein filaggrin has been recently identified. The importance of skin barrier dysfunction has been highlighted in the pathogenesis of AD, particularly as it relates to allergen sensitization and eczema severity. It is important to identify clinically relevant sensitizations to foods using skin prick tests, a specific IgE blood test (ImmunoCAP
®, Phadia), patch-tests and double-blind, placebo-controlled food challenges to initiate appropriate dietary interventions and avoid unnecessary dietary restrictions. Appropriate skin care to maintain skin barrier function and dietary avoidance of highly allergenic foods during infancy may help to prevent allergen sensitization, thereby reducing the severity of AD and food allergies. The results of our studies support the evidence that the risk for development of early allergic manifestations e.g. CMA and AD can be reduced significantly by simple dietary measures for the first 4
months of life. In all infants breastfeeding should be recommended for at least 4–6
months. Food hypersensitivity and food airborne allergens may play a role in the pathogenesis of AD. The aim of this study was to evaluate the kind of food and airborne allergens which may most often induce and intensify AD lesions and also to assess the variability and the kind of allergens leading to AD. Besides other trigger factors, food allergens have been shown to play a role in the exacerbation and maintenance of eczematous lesions in patients with gastroesophageal reflux with AD, particularly in children. The management consists in reducing irritant allergens and culprit foods and in using emollient cream to deal with dryness and local corticosteroids and topic immunomodulatory drugs (tacrolimus and pimecrolimus) which have substantially improved the treatment of AE. Finally, the implementation of proper dietary avoidance can improve symptoms and provide safety from potentially severe anaphylaxis. However, if inappropriate prescribed, elimination diets can have significant negative nutritional and social consequences.
Se hizo una revisión sobre otros marcadores de diagnóstico para la artritis reumatoidea, una de las enfermedades autoinmunes sistémicas más comunes y de amplia distribución mundial, que afecta ...principalmente a las mujeres y es muy agresiva en la raza negra. Su diagnóstico precoz resulta de vital importancia para evitar las deformidades articulares características y para mejorar la calidad de vida de los pacientes. Actualmente se diagnostica siguiendo los criterios de clasificación definidos por la American Rheumatism Association, entre ellos, la detección del factor reumatoideo. Hoy día se sabe que este no es patognomónico de la enfermedad porque puede estar presente en otras entidades. Se realizó una revisión de otros marcadores sexológicos que están asociados a la artritis reumatoidea y que son mucho más específicos, de manera que podría considerarse su uso en el diagnóstico precoz de esta enfermedad.A review of other diagnostic markers for rheumatoid arthritis, one of the commonest autoimmune systemic diseases, was made. It is widely spread all over the world. It mainly affects women and it is very aggressive among black people. Its early diagnosis is of vital importance to prevent the characteristic joint deformities and to improve the patients' quality of life. At present, it is diagnosed according to the classification criteria defined by the American Rheumatism Association, among them, the detection of the rheumatoid factor. It is known that it is not pathognomonic of the disease, since it may be present in other entities. A review of other sexological markers that are associated with rheumatoid arthritis and that are much more specific was made, so that their use could be considered in the early diagnosis of this disease,
