Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disorders of cornification are a group of diseases that share abnormalities in the manufacture or desquamation of corneocytes. This paper reviews the major and a few of the rarer ones with a concentration on their therapy. Ichthyosis vulgaris is probably a post-translational defect in pro-filaggrin expression. It shows fine white flaky scales of the extensor surfaces, trunk, flank, lower legs but spares the folds and wet areas. Treatment is with aggressive moisturization. Hydrocortisone creams may be needed to control itch. Recessive X-linked ichthyosis is due to a deficiency of cholesterol sulfatase. Boys with this condition show small dark scales around the ears, sides of the neck, extensor surfaces of the arms and legs, and the peri-umbilical region. It spares the folds and face. Treatment is with moisturizers, topical retinoid creams or with topical cholesterol-based creams. Checking for signs of contiguous gene disorders (Kallman or Conradi-Hunermann syndromes) is necessary. Bullous congenital ichthyosiform erythroderma is caused by mutations in keratins 1 and/or 10. These patients are born as bright red babies with large blisters and erosions. Slowly, a porcupine quill-like waxy scaling develops. Blistering continues throughout life. Secondary infections of the skin cause pain, debility, and a very foul odor. Treatment is difficult. Topical moisturizers, descalers and retinoid creams help a little. Oral retinoids help a lot but can cause increased blistering. Controlling the odor is an ongoing issue using antibacterial washes, absorbing powders, and masking fragrances. Autosomal recessive ichthyosis is a term for both lamellar ichthyosis and congenital ishthysosiform erythroderma. They are caused by various mutations in transglutaminase-1 gene. In both instances patients are born as 'collodion babies'. Lamella ichthyosis has the very recognizable plate-like scale over the entire body. Children with congenital ishthysosiform erythroderma are red all over with a finer scale in some places and plate-like scales in others. Treatment is with topical moisturizers, retinoid creams, descalers, and in some cases oral retinoids. Palmar plantar keratodermas occur in conjunction with some ichthyoses, but also by themselves. Some are diffuse and others have discrete, corn-like hardenings. Treatment with topical acids, propylene glycol and retinoid creams help to some extent.Throughout the article pearls from my practice are included to assist the clinician in the day-to-day handling of these patients. A short section on genetic counseling concludes this article.
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PMID:Disorders of keratinization: diagnosis and management. 1497 40

The structure, composition, formation and function of the stratum corneum have been the subject of intense research over the last few decades. As has become apparent, stratum corneum barrier function is not only dependent on one single component but also on its total architecture. Recent developments in understanding lipid composition have led to a new ceramide nomenclature system, a new proposal for a molecular model of the interactions between ceramides, cholesterol and fatty acids, and the demonstration of the presence of crystalline orthorhombic and gel hexagonal lipid phases in the stratum corneum. Linoleate-containing ceramide one, now known as CER EOS, have been shown to be essential for the formation of the 13 nm long periodicity phase (LPP) observed by electron microscopy and X-ray diffraction studies, whereas long-chain fatty acids are important for the formation of the crystalline lipid phases essential for barrier function. The role of the corneocyte envelope, its constituent proteins and its transglutaminase-mediated maturation processes have been shown to be essential for good skin condition. Several proteases may have a role in corneodesmolysis, particularly serine and cathepsin-like enzymes. Novel filaggrin polymorphisms have been identified that may be involved in the expression of a dry skin phenotype. Disturbances in lipid packing states, reduction in ceramide levels (particularly the phytosphingosine-containing ceramides), reductions in the levels of long-chain fatty acids and loss of the LPP largely account for the perturbations in lipid structure that occur in dry skin. The reduced corneodesmolysis that occurs in this xerotic skin disorder is now well accepted and is caused by reductions in the levels and activities of stratum corneum proteases together with elevated levels of corneodesmosomal glycoproteins in the superficial layers of the stratum corneum. Additionally, increased levels of fragile corneocytes are associated with reduced transglutaminase activity and corneocyte envelope cross-linking events. However, in comparison with the advances in our understanding of the textural changes that occur in dry skin, the somatosensory changes are poorly understood and the itching associated with dry skin is still an under-researched area. The unique biosensor role of the stratum corneum essential for a competent natural moisturizing barrier may also have a role to play in the action of anti-ageing technologies by controlling the expression and secretion of epidermal cytokines and growth factors. Technologies to treat the surface textural skin problems, enhance the differentiation process, particularly lipid biosynthesis, and to control the somatosensory problems in dry skin have received much attention in the last decade. This paper will review the state of the art of stratum corneum biology and the trends in the management of dry skin.
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PMID:Trends in stratum corneum research and the management of dry skin conditions. 1849 84

Dermatitis herpetiformis (DH) or Duhring-Brocq disease is a chronic bullous disease characterized by intense itching and burning sensation in the erythematous papules and urticarial plaques, grouped vesicles with centrifuge growth, and tense blisters. There is an association with the genotypes HLA DR3, HLA DQw2, found in 80-90% of cases. It is an IgA-mediated cutaneous disease, with immunoglobulin A deposits appearing in a granular pattern at the top of the dermal papilla in the sublamina densa area of the basement membrane, which is present both in affected skin and healthy skin. The same protein IgA1 with J chain is found in the small intestinal mucosa in patients with adult celiac disease, suggesting a strong association with DH. Specific antibodies such as antiendomysium, antireticulina, antigliadin and, recently identified, the epidermal and tissue transglutaminase subtypes, as well as increased zonulin production, are common to both conditions, along with gluten-sensitive enteropathy and DH. Autoimmune diseases present higher levels of prevalence, such as thyroid (5-11%), pernicious anemia (1-3%), type 1 diabetes (1-2%) and collagen tissue disease. The chosen treatment is dapsone and a gluten-free diet.
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PMID:Review: dermatitis herpetiformis. 2406 31

Dermatitis herpetiformis (DH) is an autoimmune bullous disease, which represents the cutaneous manifestation of gluten sensitivity, in the setting of celiac disease. Although classical DH is characterized clinically by grouped, vesicles on an erythematous base, primary lesions often are absent owing to the intense, associated pruritus. Instead, many cases present only with erythematous erosions with numerous overlying excoriations. As in celiac disease, the core pathogenic mechanisms of DH are likely mediated by immunoglobulin A class autoantibodies against one of several transglutaminase enzymes. As the production of these autoantibodies is directly correlated with gastrointestinal exposure to gliadin, which is an alcohol-soluble fraction of gluten, a gluten-free diet represents the cornerstone of a DH management regimen. In cases refractory to dietary management alone, dapsone is the first-line agent for the treatment of DH, although many other agents have been anecdotally reported as effective.
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PMID:Dermatitis herpetiformis. 2552 42

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease (CD), which causes an itching and blistering rash, typically on the elbows, knees and buttocks. DH and CD share a similar genetic background, small bowel mucosal alterations, and an autoimmune response against tissue transglutaminase in the serum and small bowel. DH is typically diagnosed during adulthood, and it is slightly more common among males than females. The incidence of DH seems to be decreasing, in contrast to the detected four-fold increase in the incidence of CD. In addition to typical clinical picture, diagnosis of DH relies on the demonstration by direct immunofluorescence of pathognomonic granular IgA deposits in the papillary dermis. Circulating tissue transglutaminase antibodies support the diagnosis, but their absence does not exclude DH. Obtainment of small bowel mucosal biopsies is not necessary when DH is diagnosed, but if performed, the majority of patients are found to have villous atrophy, and even those with normal villous architecture evince CD-type inflammation. The treatment of choice in DH is a strict, life-long adherence to a gluten-free diet (GFD). In addition to alleviating the symptoms of DH and healing the small bowel mucosal damage, a GFD increases the quality of life for patients, and decreases the risk for lymphoma in DH. Further, the mortality rate of patients with DH treated with a GFD seems to be lower than that of the general population. However, as changing to a GFD has a rather slow effect on the DH rash, patients with severe skin symptoms should additionally be treated with dapsone medication. This review article is based on a presentation given at the British Society for Medical Dermatology blistering skin diseases meeting 2019.
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PMID:Dermatitis herpetiformis. 3109 98

Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.
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PMID:Dermatitis Herpetiformis: Novel Perspectives. 3124 41