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)

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

Immune response modifiers (IRMs) are agents that target the body's immune system (i.e., cytokines, receptors, and inflammatory cells) to combat disease. Topical IRM therapies, which encompass both proinflammatory and immunosuppressive therapeutics, have been used to successfully treat a number of dermatologic conditions. Proinflammatory treatments include Toll-like receptor agonists (e.g., imiquimod 5% cream) and interferon (e.g., interferon-alpha) therapies, which have been used in the treatment of external genital warts, basal cell carcinoma, and other dermatologic diseases. Immunosuppressive therapies include topical and intralesional corticosteroids, anti-tumor necrosis factor agents (e.g., infliximab and etanercept), and anti-CD4+ T-cell agents, including calcineurin inhibitors and mycophenolate. These agents have been used to treat a number of conditions, including atopic and seborrheic dermatitis and psoriasis. This article reviews the mechanism of action of IRMs and the application of IRMs in several dermatologic diseases.
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PMID:Mechanism of action and emerging role of immune response modifier therapy in dermatologic conditions. 1564 61

Seborrheic dermatitis affects the scalp, central face, and anterior chest. In adolescents and adults, it often presents as scalp scaling (dandruff). Seborrheic dermatitis also may cause mild to marked erythema of the nasolabial fold, often with scaling. Stress can cause flare-ups. The scales are greasy, not dry, as commonly thought. An uncommon generalized form in infants may be linked to immunodeficiencies. Topical therapy primarily consists of antifungal agents and low-potency steroids. New topical calcineurin inhibitors (immunomodulators) sometimes are administered.
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PMID:Seborrheic dermatitis: an overview. 1739 May 92

Pimecrolimus is an ascomycin macrolactam. It is a specific calcineurin inhibitor that allows topical application. The highly lipophilic nature of this compound reduces the risk of systemic absorption through normal and inflammed skin. Pimecrolimus shows activity not only against T-cell activation, but also against mast cells and pruritus. Pimecrolimus 1% cream is approved for atopic dermatitis, and also has a great potential in other inflammatory skin diseases. Clinical trials have been performed in contact- and seborrhoeic dermatitis, genital lichen sclerosus, intertriginous psoriasis and cutaneous lupus erythematosus. In other diseases, the available data are limited to small case series, or individual cases of graft-versus-host disease or Netherton's disease. Although the use of calcineurin inhibitors in the treatment of vitiligo is promising, detailed studies with pimecrolimus and ultraviolet-irradiation are necessary and there is a need for prospective randomised, double-blind controlled trials.
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PMID:Topical pimecrolimus for skin disease other than atopic dermatitis. 1702 Apr 22

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

Tacrolimus is an ascomycin macrolactam derivative with immunomodulatory and anti-inflammatory activity that belongs to the class of calcineurin inhibitors. Tacrolimus in its topical formulation has been established as a safe and effective alternative to topical corticosteroids because of its mild side effects and its minimal systemic absorption. Topical tacrolimus has been approved for the treatment of atopic dermatitis in two concentrations, 0.03 and 0.1%. In a thorough research of literature the authors review all of the available data regarding the off-label uses of the medication in other dermatoses. It seems that compared to pimecrolimus, tacrolimus has proved to be a more effective treatment. There is no causal relationship that has been established between tacrolimus and carcinogenesis. Furthermore, the authors believe that, without any evidence, the theoretical concerns are not enough to produce warnings. Tacrolimus ointment 0.1% may be recommended as a first-line choice for seborrheic dermatitis of the face and trunk, facial and intertriginous psoriasis and probably for allergic contact dermatitis and Zoon's balanitis. It has been ineffective in numerous dermatoses such as alopecia areata, necrobiosis lipoidica, internal pruritus and in thick hyperkeratotic plaques of psoriasis when administered as the commercially available formulation without occlusion. There is yet unexploited therapeutic potential regarding the use of topical tacrolimus in dermatology. Isolated cases of successful administration of the medication in various cutaneous conditions require further large-scale studies to clarify the actual effectiveness.
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PMID:Assigning new roles to topical tacrolimus. 1768 74

Seborrheic dermatitis (SD) is characterized by erythematous pruritic patches and plaques with greasy scale that occur in sebaceous areas. It is common, affecting up to 3% of the population. Past treatments have relied on a wide variety of anti-inflammatory and antifungal agents, but corticosteroids have limited use because of long-term adverse effects. Topical calcineurin inhibitors provide a safe alternative for the treatment of SD, as these drugs block the inflammatory cascade involved in the disease process and pose no risk of skin atrophy. Studies of topical pimecrolimus and tacrolimus in the treatment of SD have found that improvement occurred within 2 weeks, and if SD recurred after stopping treatment, it was significantly less severe. There have been no studies of the comparative efficacy of pimecrolimus versus tacrolimus for the treatment of SD. Common adverse effects of mild burning and irritation have been associated with the use of both of these agents. Safety profile studies are limited to studies of atopic dermatitis, which show no increase in infection rate, photocarcinogenicity, or signs of immunosuppression in patients using topical calcineurin inhibitors for long-term treatment. This article reviews the clinical trials of pimecrolimus and tacrolimus in the treatment of SD, focusing on efficacy and safety.
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PMID:Role of topical calcineurin inhibitors in the treatment of seborrheic dermatitis: a review of pathophysiology, safety, and efficacy. 1922 50

Seborrheic dermatitis is a common chronic-recurrent inflammatory disorder that most commonly affects adults; however, a more transient infantile form also occurs. The definitive cause of seborrheic dermatitis is unknown. However, proliferation of Malassezia species has been described as a contributing factor. The adult form of seborrheic dermatitis affects up to approximately five percent of the general population. The disorder commonly affects the scalp, face, and periauricular region, with the central chest, axillae, and genital region also involved in some cases. Pruritus is not always present and is relatively common, especially with scalp disease. A variety of treatments are available including topical corticosteroids, topical antifungal agents, topical calcineurin inhibitors, and more recently, a nonsteroidal "device "cream. This article reviews the practical topical management of seborrheic dermatitis in the United States, focusing on the adult population.
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PMID:Adult seborrheic dermatitis: a status report on practical topical management. 2160 92

Seborrheic dermatitis is a chronic relapsing inflammatory skin disorder clinically characterized by scaling and poorly defined erythematous patches. The prevalence of adult seborrheic dermatitis is estimated at 5%. Although the exact cause of seborrheic dermatitis has yet to be understood, Malassezia yeasts, hormones (androgens), sebum levels and immune response are known to play important roles in its development. Additional factors including drugs, winter temperatures and stress may exacerbate seborrheic dermatitis. A variety of treatment modalities are available, including antifungal agents, topical low-potency steroids and calcineurin inhibitors (immunomodulators). This review summarizes current knowledge on the etiopathogenesis and therapy of adult seborrheic dermatitis.
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PMID:Seborrheic dermatitis: an update. 2272 83

Seborrheic dermatitis is a chronic, recurring, cutaneous condition that causes erythema and flaking, sometimes appearing as macules or plaques with dry white or moist oily scales. In adults, it commonly occurs in areas with high concentrations of sebaceous glands. The face and scalp are the most frequently affected areas, and involvement of multiple sites is common. Dandruff is regarded as a mild noninflammatory form of seborrheic dermatitis. There is a high incidence of seborrheic dermatitis among persons with human immunodeficiency virus infection or Parkinson's disease. The cause of seborrheic dermatitis is not well understood, but appears to be related to the composition of the sebaceous gland secretions, the proliferation of Malessezia yeasts, and the host immune response. Treatment options for nonscalp and scalp seborrheic dermatitis include topical agents and shampoos containing antifungal agents, anti-inflammatory agents, keratolytic agents, and calcineurin inhibitors. Because multiple body sites are usually involved, the physician should examine all commonly affected areas. Patients should be made aware that seborrheic dermatitis is a chronic condition that will probably recur even after successful treatment.
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PMID:Optimizing treatment approaches in seborrheic dermatitis. 2344 Dec 40


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