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)

Topical tacrolimus (FK506, Protopic) has been developed and marketed for the treatment of atopic dermatitis (AD). Tacrolimus works as an inhibitor of calcineurin, which creates a downregulation of the inflammatory cascade. Numerous trials have shown the efficacy and safety of tacrolimus in treating AD in both adults and children. Additionally, comparison data with other medications commonly used for AD, such as topical steroids and pimecrolimus, show improved efficacy of tacrolimus. A comprehensive review of the off-label uses of tacrolimus in other dermatoses, including psoriasis, lichen planus and seborrhoeic dermatitis, is provided. The efficacy of tacrolimus in treating these diseases is based on Phase IV clinical trials and on case reports or series in the literature. Overall, tacrolimus has proven to be a safe and useful topical therapy for many inflammatory dermatological conditions, with AD being the principal indication.
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PMID:Tacrolimus ointment: the treatment of atopic dermatitis and other inflammatory cutaneous disease. 1546 48

Bullous pemphigoid (BP) is a cutaneous autoimmune disease predominantly affecting older patients which can cause death either due to severe clinical manifestations or due to the side effects of systemic immunosuppressive treatment. Topical treatment with corticosteroids is an established alternative to systemic treatment. However, prolonged application is accompanied by side effects such as skin atrophy. Recently, the immunomodulatory calcineurin antagonists tacrolimus and pimecrolimus have been introduced for topical treatment of skin diseases. Tacrolimus has been reported to be effective in several inflammatory skin disorders such as atopic dermatitis, psoriasis, lichen planus, lupus erythematosus and pyoderma gangraenosum. Efficacy has also been described in the topical treatment of BP in some cases. Here we present the case of a 89 year old patient with BP. He was treated with 0.1% tacrolimus ointment, which was able to control the disease. We briefly review the literature and discuss the potential role of tacrolimus as a novel option for the topical treatment of BP.
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PMID:[Topical treatment of bullous pemphigoid with tacrolimus. Case report with brief literature review]. 1637 15

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

Ciclosporin and tacrolimus are calcineurin inhibiting immunosuppressant agents useful in the treatment of immune-mediated inflammatory dermatoses. Available data and clinical experience demonstrate ciclosporin's efficacy in treating psoriasis, atopic dermatitis, pyoderma gangrenosum, lichen planus, autoimmune bullous disease (in combination with corticosteroids), recalcitrant chronic idiopathic urticaria, and chronic dermatitis of the hands and feet. Although the role of topical tacrolimus in atopic dermatitis is well established, such experience with the oral formulation of tacrolimus has been limited. However, there are several case studies and anecdotal reports of the successful use of oral tacrolimus in various dermatoses. In this article we discuss the utility of systemic ciclosporin and tacrolimus in dermatology.
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PMID:Systemic ciclosporin and tacrolimus in dermatology. 1797 Aug 89

The topical calcineurin inhibitors pimecrolimus (Elidel) and tacrolimus (Protopic) were initially developed for the treatment of atopic eczema (atopic dermatitis), a chronic or chronically relapsing skin condition most prevalent in infants and children. Their main advantages compared with conventional topical corticosteroid therapy are that they are more selective in their mode of action, do not induce skin atrophy and are not associated with significant systemic absorption. In addition, topical calcineurin inhibitors may represent a useful alternative to topical corticosteroids for the treatment of a number of other inflammatory skin diseases. Preferred sites for the use of topical calcineurin inhibitors are areas such as the face, neck, flexures, and genital areas, which are more susceptible to topical corticosteroid side effects. The efficacy of topical calcineurin inhibitors has been demonstrated for flexural psoriasis, seborrhoeic, contact and hand eczema. Preliminary data also support the efficacy of topical calcineurin inhibitors in lichen planus, facial lupus erythematosus, autoimmune bullous dermatosis, and vitiligo. In these latter indications, controlled studies are needed to better understand the efficacy and safety of topical calcineurin inhibitors and their role in disease management.
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PMID:Potential new indications of topical calcineurin inhibitors. 1817 92

Repeated courses of potent topical corticosteroids and maintenance therapy with moderately potent topical corticosteroids are frequently needed to treat various forms of vulvar dermatoses, which are often characterized by an abnormal proliferation or activation of T lymphocytes. Because such therapeutic regimen is associated with an increased risk of potential side effects, particularly skin atrophy, an anti-inflammatory alternative to topical corticosteroids is desirable. The two non-steroid topical calcineurin inhibitors pimecrolimus and tacrolimus are immunomodulators that block the release of inflammatory cytokines from T lymphocytes in the skin while promoting cutaneous innate host defences. They are currently approved in Europe and in the United States of America as second-line anti-inflammatory agents for the treatment of atopic dermatitis. We provide a comprehensive summary of existing case reports, series of cases, and open-label prospective studies concerning the use of topical pimecrolimus and tacrolimus for the treatment of anogenital lichen sclerosus, genital lichen planus, vulvar lichen simplex chronicus and related pruritic vulvar dermatoses (chronic vulvar pruritus and allergic contact dermatitis of the vulva). The available data suggest that both topical calcineurin inhibitors may be effective and well tolerated in these vulvar dermatoses, although topical pimecrolimus may exhibit a better long-term tolerability profile. Being devoid of steroid-related side effects, they may represent a useful second-line therapeutic option for patients who are intolerant of, or resistant to topical corticosteroids. Controlled clinical trials and comparative studies are warranted to substantiate the promising findings summarized in this review.
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PMID:Topical calcineurin inhibitors for the treatment of vulvar dermatoses. 1963 46

Topically applied calcineurin inhibitors have been suggested to be of some benefit in the treatment of immunologically mediated oral mucosal disorders, particularly oral lichen planus. This article reviews the current evidence of the efficacy and safety of topical calcineurin inhibitor agents in the management of different oral conditions. Current evidence suggests that topical tacrolimus and pimecrolimus may be of benefit (at least in the short term) in the treatment of immunologically mediated oral mucosal disease, especially oral lichen planus that has not responded to topical corticosteroids. Both tacrolimus and pimecrolimus are minimally absorbed through the oral mucosa and give rise to few clinically significant local or systemic adverse side effects. There is little evidence to indicate that topical cyclosporine is more effective than topical corticosteroids for the treatment of immunologically mediated oral mucosal disease. Currently, there is no objective evidence suggesting that topical tacrolimus or pimecrolimus increase the risk of oral malignancy associated with oral lichen planus. There is a need for well-designed randomized controlled trials to establish the precise efficacy of topical calcineurin inhibitors for the treatment of immunologically mediated oral mucosal disease.
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PMID:Calcineurin inhibitors in oral medicine. 1983 43

Topical tacrolimus and pimecrolimus are indicated for treatment of atopic dermatitis, but they have been studied in many off-label uses. Double-blind and open studies have shown favorable results with topical tacrolimus and pimecrolimus in oral lichen planus. In 1 study of oral lichen planus, blood tacrolimus was detected in 54% of patients, but there were no signs of systemic toxicity. Double-blind and open studies of vitiligo have shown favorable results with tacrolimus in combination with excimer laser, especially for lesions over bony prominences and on extremities. Similarly, double-blind studies of vitiligo have shown favorable results when pimecrolimus is combined with narrow-band UVB, especially for facial lesions. Double-blind and open studies of psoriasis have shown favorable results for tacrolimus and pimecrolimus, especially for inverse psoriasis. Topical calcineurin inhibitors have been effective in many other cutaneous disorders, and further studies would help clarify their roles.
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PMID:Innovative use of topical calcineurin inhibitors. 2051 Jul 63

Lichen sclerosus (LS) and lichen planus (LP) are both immunologically mediated diseases with a preference for the genitalia. The basic principles of management of vulval LS and vulvovaginal LP are the same and involve explanation of the disease, emphasizing the chronic nature of the condition and outlining treatment options. The main difference between the two conditions is that LP has a propensity to involve the mucous membranes including the mouth and vagina which are rarely affected in LS. First-line treatment for LS is a super-potent topical corticosteroid ointment which has a high response rate. Erosive vulvovaginal LP is more challenging to treat. Second-line therapies include topical calcineurin inhibitors and systemic agents. There is limited evidence for systemic treatments for both conditions. The risk of vulval squamous cell carcinoma (SCC) is increased in both LP and LS, and it is not known how treatment affects this risk. We recommend teaching self-examination and longitudinal evaluation.
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PMID:Vulval lichen sclerosus and lichen planus. 2086 6

Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS.
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PMID:Anti-inflammatory treatment. 2132 40


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