Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of topical immunomodulators in pediatric patients is an important topic in the clinical practice. Their prescription for chronic diseases suggests the necessity of evaluating their efficacy and safety profile in a long term period. In children they can develop systemic adverse events after their application, though sometimes they are useful to reduce the long consumption of other drugs, as topical steroids, or to have influence in the critical aspects of immunomodulation. Pimecrolimus and tacrolimus are two topical calcineurin inhibitors, from which there are several reports that support their efficacy in pediatric patients with atopic dermatitis. Recently, the FDA issued a recommendation for their topical use in a sporadic way in two years old children or older that have moderate to serious atopic dermatitis and that have not responded to other treatments. This article shows the results of several studies in which these drugs have been applied for a long time in children with atopic dermatitis. The more frequent adverse effects were: infections, pyrexia, burning, pruritus, erythema, and papules in the application area. In suckling babies they were: dry skin, pruritus, infections, constipation, erythema, and papules. Even when these adverse effects have been reported with relative frequency, their controlled use in concrete clinical conditions is still a therapeutic option and they should be considered particularly useful in the treatment of atopic dermatitis without positive reaction to other treatments in children older than two years, during short periods and in cases in which immunocompromised situations have been ruled out.
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PMID:[Safety of topical tacrolimus and pimecrolimus in children with atopic dermatitis]. 1626 86

Atopic dermatitis is a chronic, relapsing inflammatory skin disease that frequently affects infants and children. The worldwide prevalence of atopic dermatitis is estimated to be 5-20% of the pediatric population. Studies have shown that atopic dermatitis is associated with considerable economic costs and decreased quality of life. There is no proven curative therapy at present for atopic dermatitis; first-line therapy has generally consisted of dry skin care, avoidance of triggers, application of topical corticosteroids, and administration of histamine H1 receptor antagonists (antihistamines) and oral antibacterials as appropriate. Topical corticosteroids, while effective in many patients, carry the concern of local and systemic adverse effects. As a result, physicians and patients are reluctant to utilize stronger topical corticosteroids in certain areas of the body and for prolonged periods of time. The purpose of this article is to review the efficacy and economics of topical calcineurin inhibitors in the treatment of atopic dermatitis. This new class of agents (specifically tacrolimus ointment and pimecrolimus cream) represents an exciting advance in the treatment of atopic dermatitis. Clinical data show that topical calcineurin inhibitors are effective and do not cause the adverse effects associated with topical corticosteroids. Several studies have provided evidence that topical calcineurin inhibitors positively affect the quality of life of patients and their caregivers. Compared with branded topical corticosteroids and previous standards of care, topical calcineurin inhibitors appear to be a cost-effective treatment option. Drawing comparisons between tacrolimus and pimecrolimus is difficult because definitive head-to-head comparative studies involving these drugs have not been conducted.
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PMID:Efficacy and economics of topical calcineurin inhibitors for the treatment of atopic dermatitis. 1690 Nov 81

EpiCeram consists of a specific combination of ceramides, cholesterol and fatty acids that mimics those naturally found in the skin. EpiCeram was approved by the FDA in April 2006 for use as a nonsteroidal lipid barrier emulsion to manage symptoms of burning and itching associated with dry skin conditions such as atopic dermatitis, irritant contact dermatitis, radiation dermatitis and other dermatoses. EpiCeram has shown comparable efficacy to a mid-strength topical corticosteroid in a clinical study involving 113 children with moderate to severe atopic dermatitis. Unlike topical steroids and immunomodulators such as calcineurin inhibitors that have clinically well-recognized undesirable side effects and usage restrictions (including FDA black box warning for the latter), current data suggests that EpiCeram has a favorable safety profile. Additionally, EpiCeram does not appear to have substantial restrictions associated with its use, especially with regards to the duration of use or patient age, compared to the other classes of prescription products.
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PMID:Epiceram for the treatment of atopic dermatitis. 1913 28

The skin's permeability barrier protects against extensive water loss and prevents the entry into the skin of harmful substances like irritants, allergens and microorganisms. The permeability barrier is mainly located in the stratum corneum and consists of corneocytes and a lipid-enriched intercellular domain. The barrier is formed during epidermal differentiation. In atopic dermatitis the skin barrier is disturbed already in non-lesional skin. The disturbed skin barrier allows the entry of environmental allergens from house dust mites, animal dander and grass pollen into the skin. In predisposed individuals these allergens may trigger via immunologic pathways the inflammation of atopy. The causes for the disturbed epidermal skin barrier are changes in skin lipids and in epidermal differentiation, in particular filaggrin mutations. Filaggrin mutations lead to a disturbed skin barrier and dry skin which are hallmarks in atopic dermatitis. Therapeutic agents influence the skin barrier differently; topical therapy with potent corticosteroids does not lead to the repair of the barrier in atopic dermatitis, whereas therapy with the calcineurin inhibitors and lipid-containing emulsions support barrier repair.
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PMID:Role of the epidermal barrier in atopic dermatitis. 1968 76

This viewpoint presents a unifying concept for the treatment of atopic dermatitis (AD) that is based on the improvement of deficient Notch signalling, which appears to represent the fundamental epithelial defect of AD resulting in epidermal and immunological barrier dysfunction. One study of AD patients demonstrated a marked epidermal deficiency of Notch receptors and several mouse models with genetically suppressed Notch signalling exhibit dry skin, signs of scratching, skin barrier abnormalities, increased transepidermal water loss and Th2 cell-mediated immunological changes closely resembling human AD. Notch signalling is critically involved in the differentiation of regulatory T cells, in the feedback inhibition of activated innate immunity, in the repression of activating protein-1 (AP-1), the regulation of late epidermal differentiation associated with filaggrin- and stratum corneum barrier lipid processing, in aquaporin 3- and claudin-1 expression and in keratinocyte-mediated release of thymic stromal lymphopoietin (TSLP), which promotes Th2-driven immune responses with TSLP- and IL-31-mediated stimulation of cutaneous sensory neurons involved in the induction of itch. Translational evidence will be provided that all major therapeutic regimens employed for the treatment of AD such as glucocorticoids, calcineurin inhibitors and UV radiation may converge in the upregulation of impaired Notch signalling, the proposed pathogenic defect of AD.
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PMID:Does therapeutic intervention in atopic dermatitis normalize epidermal Notch deficiency? 2488 7

Atopic dermatitis is a chronic inflammatory disease characterized by recurrent flares, intense itching, erythema, dry skin resulting from skin barrier defects, and staphylococcal infections. Multiple factors may affect the skin`s normal barrier function, including filaggrin gene mutations, immune dysregulation, altered skin microbiome, altered lipids in stratum corneum, or deficiency of antimicrobial peptides AMPs. The disease mainly affects children, causing a considerable impact on the quality of their life; its first manifestations occur with up to 90% of cases before the age of 5. For years emollients have been known as oily substances used to treat rough, scaling, xerotic conditions to make skin flexible and soft. Recently, we have learned that emollients can also moisten and hydrate dry skin, so the terms "emollient" and "moisturizer" are often used interchangeably. According to current management guidelines on atopic dermatitis prepared by dermatological societies, long-term emollient application direct to the skin and as bath additives are the basic therapy of atopic dermatitis. Emollients may be used in monotherapy or - in the flares - in conjunction with topical corticosteroids or calcineurin inhibitors. Clinical trials proved that regular emollient application moistens and hydrates the skin and helps the skin maintain a defensive barrier effect as well as reduces the amount of topical corticosteroids needed for atopic eczema in infants, children and adult patients. The results of trials and long clinical experience proved that emollients are safe and effective in patients with atopic dermatitis. This paper presents information based on recent knowledge concerning emollients: an overview of emollient components, their properties, mechanism of action, and the role they play in atopic eczema, as well as the results of clinical trials performed in children with atopic dermatitis.
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PMID:[The role of emollients in atopic dermatitis in children]. 3063 40