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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis and treatment of psoriasis are reviewed. Psoriasis is characterized by defects in the normal cycle of epidermal development that lead to epidermal hyperproliferation, altered maturation of skin cells, and vascular changes and inflammation. The condition typically manifests as areas of thickened, flaky, silvery white and reddened skin that may hurt, itch, and bleed. Biochemical markers of psoriasis are changes in levels of keratins, keratinocyte transglutamase, migration inhibitory factor-related protein, skin-derived antileukoproteinase, involucrin, small protein rich protein 2, filaggrin, and cytokines. Types of psoriasis that may be clinically encountered include plaque psoriasis, guttate psoriasis, erythrodermic psoriasis, and pustular psoriasis. Psoriasis is believed to be genetically linked but can also be triggered by mechanical, ultraviolet, and chemical injury; various infections; prescription drug use; psychological stress; smoking; and other factors. Topical treatment of psoriasis is usually the first line of therapy. Topical treatments consist of emollients and keratolytic agents, anthralin, coal tar, corticosteroids, vitamin D3 analogues, topical retinoids, and topical psoralens plus ultraviolet A (UVA) light. In patients who do not respond adequately to topical therapy, oral or injectable therapy, such as oral retinoids, methotrexate, cyclosporine, tacrolimus, and oral psoralens plus UVA light, may be warranted. Patients receiving systemic treatments should be carefully monitored for adverse effects and drug-drug interactions. Drug therapy is the mainstay of the treatment of psoriasis. The potential adverse effects and interactions necessitate vigilant monitoring.
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PMID:Pathophysiology and treatment of psoriasis. 1076 19

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

Atopic dermatitis (AD) is a pruritic inflammatory skin disease associated with a personal or family history of allergy. The prevalence of AD is on the rise and estimated at approximately 17% in the USA. The fundamental lesion in AD is a defective skin barrier that results in dry itchy skin, and is aggravated by mechanical injury inflicted by scratching. This allows entry of antigens via the skin and creates a milieu that shapes the immune response to these antigens. This review discusses recent advances in our understanding of the abnormal skin barrier in AD, namely abnormalities in epidermal structural proteins, such as filaggrin, mutated in approximately 15% of patients with AD, epidermal lipids, and epidermal proteases and protease inhibitors. The review also dissects, based on information from mouse models of AD, the contributions of the innate and adaptive immune system to the pathogenesis of AD, including the effect of mechanical skin injury on the polarization of skin dendritic cells, mediated by keratinocyte-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-6, and IL-1, that results in a Th2-dominated immune response with a Th17 component in acute AD skin lesions and the progressive conversion to a Th1-dominated response in chronic AD skin lesions. Finally, we discuss the mechanisms of susceptibility of AD skin lesions to microbial infections and the role of microbial products in exacerbating skin inflammation in AD. Based on this information, we discuss current and future therapy of this common disease.
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PMID:Cellular and molecular mechanisms in atopic dermatitis. 1947 21

The skin protects us from water loss and mechanical damage. The surface-exposed epidermis, a self-renewing stratified squamous epithelium composed of several layers of keratinocytes, is most important in the barrier defense against these challenges. Endogenous and exogenous proteases such as kallikreins, matriptase, caspases, cathepsins, and proteases derived from microorganisms are important in the desquamation process of the stratum corneum and are able to activate and inactivate defense molecules in human epidermis. Protease inhibitors such as like LEKTI, elafin, SLPI, SERPINs, and cystatins regulate their proteolytic activity and contribute to the integrity and protective barrier function of the skin. Changes in the proteolytic balance of the skin can result in inflammation, which leads to the typical clinical signs of redness, scaling, and itching. This review summarizes the current knowledge of how proteases, their inhibitors, and their target proteins, including filaggrin, protease-activated receptors, and corneodesmosin, contribute to the pathophysiology of inflammation of the skin and highlight their role in common inflammatory skin diseases such as atopic dermatitis, rosacea, and psoriasis.
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PMID:Reddish, scaly, and itchy: how proteases and their inhibitors contribute to inflammatory skin diseases. 1968 85

Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL-31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation-regulated chemokine (TARC) and proliferating-inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside-outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen-specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.
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PMID:Atopic eczema or atopiform dermatitis. 2010 Jan 92

Atopic dermatitis, commonly known as eczema, is a common chronic, relapsing skin disease characterized by pruritus, disrupted epidermal barrier function, and immunoglobulin E-mediated sensitization to food and environmental allergens. Atopic dermatitis is a complex disease that arises from interactions between genes and the environment. Loci on several chromosomes have been identified, including a family of epithelium-related genes called the epidermal differentiation complex on chromosome 1q21. Mutations in filaggrin, a key protein in epidermal differentiation, have also been identified in early-onset and severe atopic dermatitis. There are 3 classical stages of eczema: infantile, childhood, and adulthood. The spectrum of eczema presentation varies widely from a variant that only affect the hand to major forms where a patient presents with erythroderma. The acute and subacute lesions of atopic dermatitis are often characterized by intensely pruritic, erythematous papules and vesicles with excoriations and a serous exudate. Chronic atopic dermatitis is exemplified by lichenified plaques and papules with excoriations. Atopic dermatitis patients are also at higher risk for skin infections, including bacterial and viral superinfections. Conventional therapy includes avoidance of irritants and potential allergens, as well as continued hydration of the skin with thick emollients. Topical corticosteroids and topical immunomodulators are often used primarily. Other therapies including phototherapy, antimicrobials, antihistamines, and systemic immunosuppressives are also options in certain situations.
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PMID:Eczema. 2191 2

Atopic dermatitis (AD), also known as atopic eczema, is a chronic relapsing inflammatory dermatosis characterized by pruritus, xerosis, and a close association with IgE-mediated sensitization to aeroallergens and foods. More than 60% of children with AD are at risk to develop allergic rhinitis or asthma (the atopic march). The distribution of lesions varies by age. Infants tend to have lesions on the cheeks and scalp, and very young children typically have involvement over the extremities cheeks, forehead, and neck. Rash in the diaper area of infants is rarely AD. Lesions in older children and adults are usually located in flexural areas, such as the antecubital and popliteal fossae, along with the head and neck. Acute lesions of AD begin as erythematous papules and serous exudates. Secondary lesions include excoriations and crusted erosions due to scratching. Subacute lesions appear as erythematous scaling papules and plaques. If the itch and rash progress uncontrolled, chronic lichenified AD develops featuring accentuated skin markings with hyperpigmentation. Trigger avoidance, skin hydration, and topical steroids are the first steps for improvement. In acute lesions of AD, the Th2 cells produce IL-4, IL-13, and IL-31, which may potentiate barrier dysfunction and contribute to pruritus. In chronic lesions, the Th1 cells predominate and secrete interferon gamma and IL-12. Barrier dysfunction from filaggrin predisposes patients to AD. Skin superinfection, particularly with Staphylococcus aureus, is common, and cultures of affected lesions help guide therapy. Eczema herpeticum from herpes simplex virus can be life-threatening in AD patients.
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PMID:Chapter 20: Atopic dermatitis. 2279 93

Atopic dermatitis is a multifactorial, chronic relapsing, inflammatory disease, characterized by xerosis, eczematous lesions, and pruritus. The latter usually leads to an "itch-scratch" cycle that may compromise the epidermal barrier. Skin barrier abnormalities in atopic dermatitis may result from mutations in the gene encoding for filaggrin, which plays an important role in the formation of cornified cytosol. Barrier abnormalities render the skin more permeable to irritants, allergens, and microorganisms. Treatment of atopic dermatitis must be directed to control the itching, suppress the inflammation, and restore the skin barrier. Emollients, both creams and ointments, improve the barrier function of stratum corneum by providing it with water and lipids. Studies on atopic dermatitis and barrier repair treatment show that adequate lipid replacement therapy reduces the inflammation and restores epidermal function. Efforts directed to develop immunomodulators that interfere with cytokine-induced skin barrier dysfunction, provide a promising strategy for treatment of atopic dermatitis. Moreover, an impressive proliferation of more than 80 clinical studies focusing on topical treatments in atopic dermatitis led to growing expectations for better therapies.
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PMID:Barrier-restoring therapies in atopic dermatitis: current approaches and future perspectives. 2295 38

Atopic eczema or dermatitis (AD) is a chronically relapsing dermatosis associated with pruritus, sleep disturbance and impaired quality of life. AD affects 10 to 20% of school-aged children. The prevalence has increased two to three folds over the past three decades in industrialized countries and there is evidence to suggest that this prevalence is increasing. AD is frustrating to both patients and caregivers and can impose considerable financial impact on the families. The pruritus and sleep disturbance can be intractable and the disease has important physical and psychological implications. Filaggrin (filament-aggregating protein) has an important function in epidermal differentiation and barrier function. Null mutations within the filaggrin gene cause ichthyosis vulgaris and are major risk factors for developing AD. The affected skin of atopic individuals is deficient in natural moisturizing factors (derived from deiminated filaggrin peptides filaggrin) or ceramides (a family of lipid molecules, composed of sphingosine and a fatty acid, found in high concentrations within the cell membrane of cells in the stratum corneum). Avoidance of triggering factors, optimal skin care and topical corticosteroids are the mainstay of therapy for AD. There are two important dermatologic facets to its management, namely, preventive and therapeutic measures. Preventive measures refer to the frequent and proper application of skin moisturizers. When these preventive measures fail to control the disease exacerbation, therapeutic measures such as topical/systemic corticosteroids, antibiotics and immunomodulating agents may be required to control the skin inflammation. Proper moisturizer therapy can reduce the frequency of flares and the demand of topical corticosteroids or topical calcineurin inhibitors. Regular topical application of a moisturizer is the key in the management of patients with AD. Moisturizer therapy of childhood-onset AD is significantly complicated by the diversity of disease manifestations and by a variety of complex immune abnormalities. Recent advances in the understanding of the pathophysiological process of AD leads to the production of new moisturizers and topical skin products targeted to correct reduced amount of ceramides in the skin with ceramide and pseudoceramide products. However, many cosmetic products claimed to have these ingredients have no or limited studies to document their clinical efficacy. Recent studies have shown the therapeutic efficacy of several new compounds. This review provides an update on recent patents that could develop into novel therapeutics available to the clinical armamentarium for the management of the disease.
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PMID:Use of ceramides and related products for childhood-onset eczema. 2308 72


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