Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of topical calcineurin inhibitors resulted in a significant improvement in the treatment of inflammatory skin diseases such as atopic dermatitis. In addition, an excellent amelioration of pruritus could be observed. Other itchy dermatoses such as chronic irritative hand dermatitis, rosacea, graft-versus-host-disease, renal pruritus, lichen sclerosus, prurigo simplex, prurigo nodularis, scrotal eczema, and inverse psoriasis also have been treated successfully with pimecrolimus and tacrolimus. The antipruritic effect currently is believed to be related to the inhibition of inflammatory cytokines. Furthermore, recent investigations indicate a release of neuropeptides from sensory nerve fibers and degranulation of mast cells mediated by pimecrolimus and tacrolimus. Similar effects have been observed during capsaicin treatment. These findings may provide a possible explanation for initially observed calcineurin inhibitors related side-effects such as burning and pruritus. Moreover, the antipruritic potency may be related to a direct effect on nerve fibers leading to suppression of itch mediated by unknown mechanisms.
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PMID:[Antipruritic effects of pimecrolimus and tacrolimus]. 1271 60

In about 60% of cases, atopic eczema can persist in adulthood with distinctive clinical features and disease course. The introduction of the topical calcineurin inhibitors pimecrolimus 1% cream and tacrolimus 0.03 and 0.1% ointment clearly improves the long-term management of atopic eczema in adult patients; this has been shown in several large clinical studies and is confirmed by the growing practical experience with these substances. Topical calcineurin inhibitors are, even when applied for weeks and months, safe, well tolerated and efficient; they have a rapid and positive effect on pruritus and the potential--as shown in clinical studies with pimecrolimus 1% cream--to reduce the number of eczema flares, to significantly prolong the time to a first flare and to reduce or even eliminate the need for topical corticosteroids.
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PMID:[The treatment of atopic dermatitis in adults with topical calcineurin inhibitors]. 1271 62

The clinical experience with topical calcineurin inhibitors in the field is still rudimentary, if compared to our knowledge of topical corticosteroids. This is especially true for the long-term effects. The systemic transcutaneous absorption that occurs during the therapy of atopic dermatitis is quantitatively irrelevant. However, in the setting of permanent disruption of the skin barrier, as may be encountered in rare Genodermatoses, but as well in cases that do not respond to therapy, continued treatment my result in clinically relevant blood levels. Side effects of topical calcineurin inhibitors may be separated into two groups, i.e. local intolerance reactions, and skin infections. While the typical burning sensation of the newly treated skin is ephemeral, local alcohol intolerance, albeit less frequent, will persist throughout the treatment period. Regarding skin infections, Eczema herpeticatum seems to be the only serious complication; adequate preventive will further reduce the risk of this rare complication.
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PMID:[Practice experience with topical calcineurin inhibitors]. 1271 63

The aim of this study was to evaluate the ability of topical tacrolimus 0.1% under occlusion for 48 h to suppress nickel-elicited allergic contact dermatitis in a randomized, petrolatum- and mometasone furoate 0.1% ointment-controlled double-blind, intra-individual study which included 28 women volunteers. 3 closed patch tests (Finn Chambers on Scanpor, Epitest Ltd Oy, Tuusula, Finland) containing 0.1 ml of 5% nickel sulfate in petrolatum were applied on day 0. After removal on day 2, the study compounds were applied under occlusion for 48 h. The eczema reaction and the degree of erythema were evaluated clinically and by reflectance spectrophotometry at days 4 and 7, respectively. Mean visual scores corresponding to petrolatum-treated sites were significantly higher than those corresponding to both mometasone furoate and tacrolimus at days 4 (P < 0.001) and 7 (P < 0.001). In both tacrolimus- and mometasone furoate-treated sites, there was a significant decrease in visual scores with time (P < 0.001) from day 2 to day 7, and the corresponding mean decreases in scores were 0.73 and 1.04, respectively. The difference between both was 0.30 in favour of tacrolimus (95% confidence intervals, -0.04 and 0.65), although this did not reach statistical significance (P = 0.084). Mean erythema index values were similar at day 2. Significant differences among treatment sites were seen at days 4 (P < 0.001) and 7 (P < 0.001). The decrease was significantly more pronounced on day 7 in patches where tacrolimus had been supplied (P < 0.5). This method might provide useful means to compare different concentrations and/or presentations of tacrolimus or other calcineurin inhibitors and topical anti-inflammatory agents.
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PMID:Topical tacrolimus 0.1% ointment (protopic) reverses nickel contact dermatitis elicited by allergen challenge to a similar degree to mometasone furoate 0.1% with greater suppression of late erythema. 1499 65

Approximately 10-20% of infants in industrialized countries experience atopic dermatitis. In recent decades topical corticosteroids have been the first-choice therapy for treatment of flares. However, this form of therapy may induce skin atrophy, especially after application to facial lesions or with long-term use. Thus, development of new anti-inflammatory topical agents for the treatment of childhood atopic dermatitis was needed. The topical calcineurin inhibitors tacrolimus and pimecrolimus have an effect on various cells of the cutaneous immune system, specifically on T cells, by inhibiting the phosphatase calcineurin and preventing the transcription of proinflammatory cytokines. In several clinical studies of children and adults with atopic dermatitis, topical calcineurin inhibitors were found to be effective both on the face and the trunk and extremities, in both short- and long-term treatment regimens. Tachyphylaxis or rebound were not observed. In most patients an improvement of their eczema occurred during the first week of treatment, as measured by subjective and objective clinical signs of atopic dermatitis. Treatment significantly reduced the incidence of flares and the need for corticosteroids in children and adults. Treatment success, commonly defined as 'excellent improvement' or 'clearing of all lesions', was observed in more than one-third of all children treated with 0.03% or 0.1% tacrolimus or 1% pimecrolimus. Topical application of pimecrolimus and tacrolimus does not lead to significant blood concentrations of these agents in the majority of children with atopic dermatitis, and any increase in blood concentrations decreases after a few days of therapy. No changes in laboratory parameters were observed in short- and long-term studies in patients with atopic dermatitis. The most common adverse effect following the application of topical calcineurin inhibitors is mild to moderate symptoms of irritation such as burning, erythema and pruritus, which occurred in up to 20% of all children treated with tacrolimus and 10% of children treated with pimecrolimus, and usually faded after a few days. In contrast to topical corticosteroids, calcineurin inhibitors do not induce skin atrophy, even after long-term use. Topical calcineurin inhibitors have been proven to be effective and have a good safety profile during short-term and long-term use for up to 1 year with pimecrolimus and up to 4 years with tacrolimus. Given the lack of extensive experience with use of topical calcineurin inhibitors over longer periods, regular use of these agents, particularly in children, should be undertaken only after careful consideration of individual cases. Sun protection should also be advised.
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PMID:Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. 1579 78

The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti-inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti-inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti-inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti-inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress-induced exacerbations may make psychosomatic counselling recommendable. 'Eczema school' educational programmes have proved to be helpful.
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PMID:Position paper on diagnosis and treatment of atopic dermatitis. 1585 53

Atopic dermatitis (AD) is a chronic inflammatory skin disease which often becomes manifest in early infancy and is characterized by itchy eczematous lesions with characteristic localization. The cellular infiltrate of allergic eczematous skin diseases (i.e. AD, allergic contact dermatitis) is mainly composed of mononuclear cells. Whereas allergic contact dermatitis is always triggered by allergen-specific T cells, a number of allergic and nonallergic trigger factors appear to be relevant in AD. This article discusses data coming from immunological studies focusing on T-cell responses in AD. The concept of a switch from a T helper type 1 (Th1) to a Th2 cytokine profile in lesional skin of AD is well accepted. Besides CD4+ T lymphocytes, CD8+ cells are likely to play an important role in the pathogenesis of AD. Recent studies point to the induction of apoptosis in keratinocytes by interferon-gamma derived from skin-homing T cells as a further important mechanism for the induction and maintenance of the eczema. Recent clinical studies have confirmed the major role of food allergy and infectious microorganisms as trigger factors of AD. New therapeutic strategies for AD include topical calcineurin inhibitors which were introduced as a new therapeutic principle at the beginning of this decade.
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PMID:Allergic manifestations of skin diseases--atopic dermatitis. 1635 50

The topical calcineurin inhibitors (TCIs) pimecrolimus and tacrolimus are approved for atopic dermatitis but have additional potential in other inflammatory skin diseases. This article reviews their clinical use in non-atopic dermatitis diseases. In seborrheic dermatitis, asteatotic eczema, and contact dermatitis, TCIs are of great benefit and can compete with topical corticosteroids. In psoriasis, TCIs have shown clinical efficacy and safety in facial and intertriginous lesions. Further investigations into possible combinations of TCIs with other established treatments such as UVB irradiation in this disorder are necessary. Initial studies in cutaneous lupus erythematosus have been promising, whereas the response in rosacea and rosacea-like eruptions has been mixed. TCIs have been associated with good clinical responses in oral lichen planus and anogenital lichen sclerosus et atrophicus. In vitiligo, TCIs are associated with some degree of repigmentation, with better results being seen in children and in facial and neck areas. TCIs have a synergistic effect with UVB irradiation in vitiligo. There is a long list of small series and case reports documenting use of TCIs in various other skin conditions that warrant further validation. Although the established mode of action of TCIs is T-cell control, other effects also need to be considered. Specifically, TCIs reduce pruritus and erythema, which cannot be explained by T-cell interactions, and further investigations are needed in these fields.
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PMID:The role of topical calcineurin inhibitors for skin diseases other than atopic dermatitis. 1749 44

Since clear evidence is lacking that avoidance of exposure to inhalation or food allergens will have a favourable effect on the course of atopic dermatitis, allergological screening should be restricted to patients having acute allergic symptoms. Topical corticosteroids are the treatment of choice. The working group recommends starting with a class 2-3 corticosteroid daily followed by intermittent maintenance therapy with a corticosteroid of the same class or daily administration of a class 1 corticosteroid. When used in this way, corticosteroids are safe as far as local and systemic side effects are concerned; patients with severe atopic dermatitis have decreased serum-cortisol levels but this is due to the illness and not the corticosteroid. Serum-cortisol levels will usually return to normal following topical steroid therapy. Topical calcineurin inhibitors are a good second-line alternative for patients in whom corticosteroids are insufficiently effective or produce side effects. During such treatment, the skin should be protected against ultraviolet light. Non-sedating antihistamines have no place in the treatment of atopic dermatitis. Cyclosporin is the agent of choice for the systemic treatment of severe atopic dermatitis. The attending physician should also pay attention to psychosocial factors, since severe eczema in children, their parents and adults has a serious impact on the quality of life. Patients with severe atopic dermatitis should be discouraged from working in a wet environment. Patients with moderately active atopic dermatitis without eczema of the hands should avoid exposure to water and other irritating factors.
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PMID:[The practice guideline 'atopic dermatitis']. 1816 Dec 67

Today, many therapies are available for the treatment of psoriasis and eczema. One of the oldest topical therapies is coal tar. Coal tar has been used for decades, but over the past years, the use of coal tar has decreased for several reasons, including the supposed carcinogenicity of coal tar. We investigated the current and past treatment policies for psoriasis and eczema with special emphasis on the use of tar products; a postal survey was conducted among all dermatologists in two European countries: the Netherlands (n = 360) and the Flemish speaking part of Belgium (Flanders) (n = 328). This study was conducted as part of the ongoing LATER-study ("Late effects of coal tar treatment in eczema and psoriasis; the Radboud study"). All practising dermatologists received a questionnaire. Dermatologists were asked to describe their treatment policies in mild/moderate psoriasis, severe psoriasis, mild/moderate eczema and severe eczema. The response rate to the questionnaire was 62.5% for the Dutch dermatologists and 45.7% for the Flemish dermatologists. Almost all dermatologists prescribe topical corticosteroids. In eczema, most of the dermatologists prescribe the recently introduced calcineurin inhibitors (95%). Coal tar is a second choice topical therapy. Dutch dermatologists mainly use tar in the treatment of eczema (72% vs. 48% in Flanders), whereas in Flanders, tar is mainly prescribed in psoriasis (60% vs. 41% in Holland). Flemish dermatologists very frequently prescribe PUVA in psoriasis (93% vs. 63%). Topical treatment, especially topical corticosteroids, is the mainstay in psoriasis and eczema. Coal tar still is an important (second choice) therapy for the topical treatment of psoriasis and eczema, but its use varies from country to country. Despite the carcinogenicity of PUVA, this photochemotherapy is frequently prescribed by dermatologists, mainly in Flanders.
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PMID:Treatment policy for psoriasis and eczema: a survey among dermatologists in the Netherlands and Belgian Flanders. 1767 86


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