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 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.
J Dtsch Dermatol Ges 2009 Oct
PMID:Role of the epidermal barrier in atopic dermatitis. 1968 76

The management of chronic hand eczema is often inadequate. There are currently no evidence-based guidelines specifically for the management of chronic hand eczema, and evidence for established treatments for hand eczema is not of sufficient quality to guide clinical practice. This consensus statement, based on a review of published data and clinical practice in both primary and secondary care, is intended to guide the management of chronic hand eczema. It describes the epidemiology and pathogenesis of hand eczema, its diagnosis and its effect on patients' quality of life. Management strategies include a skin education programme, lifestyle changes, and the use of emollients, barriers and soap substitutes. Topical drug therapy includes topical steroids and calcineurin inhibitors. Treatment with psoralen ultraviolet A and systemic therapies may then be appropriate, although there is no strong evidence of efficacy. Alitretinoin has been shown to be effective in a randomized controlled trial, and is currently the only treatment specifically licensed for the treatment of hand eczema. Recommendations for management are summarized in a treatment algorithm.
Clin Exp Dermatol 2009 Oct
PMID:Consensus statement on the management of chronic hand eczema. 1974 39

Cutaneous lupus erythematosus (LE) may present in a variety of clinical forms. Three recognized subtypes of cutaneous LE are acute cutaneous LE (ACLE), subacute cutaneous LE (SCLE), and chronic cutaneous LE (CCLE). ACLE may be localized (most often as a malar or 'butterfly' rash) or generalized. Multisystem involvement as a component of systemic LE (SLE) is common, with prominent musculoskeletal symptoms. SCLE is highly photosensitive, with predominant distribution on the upper back, shoulders, neck, and anterior chest. SCLE is frequently associated with positive anti-Ro antibodies and may be induced by a variety of medications. Classic discoid LE is the most common form of CCLE, with indurated scaly plaques on the scalp, face, and ears, with characteristic scarring and pigmentary change. Less common forms of CCLE include hyperkeratotic LE, lupus tumidus, lupus profundus, and chilblain lupus. Common cutaneous disease associated with, but not specific for, LE includes vasculitis, livedo reticularis, alopecia, digital manifestations such as periungual telangiectasia and Raynaud phenomenon, photosensitivity, and bullous lesions. The clinical presentation of each of these forms, their diagnosis, and the inter-relationships between cutaneous LE and SLE are discussed. Common systemic findings in SLE are reviewed, as are diagnostic strategies, including histopathology, immunopathology, serology, and other laboratory findings. Treatments for cutaneous LE initially include preventive (e.g. photoprotective) strategies and topical therapies (corticosteroids and topical calcineurin inhibitors). For skin disease not controlled with these interventions, oral antimalarial agents (most commonly hydroxychloroquine) are often beneficial. Additional systemic therapies may be subdivided into conventional treatments (including corticosteroids, methotrexate, thalidomide, retinoids, dapsone, and azathioprine) and newer immunomodulatory therapies (including efalizumab, anti-tumor necrosis factor agents, intravenous immunoglobulin, and rituximab). We review evidence for the use of these medications in the treatment of cutaneous LE.
Am J Clin Dermatol 2009
PMID:Cutaneous lupus erythematosus: issues in diagnosis and treatment. 1982 38

Allergic and irritant contact dermatitis are important dermatological problems. Although the frequencies of positive reactions to a number of allergens have decreased during last 30 years because of better avoidance (and at least in part due to improved legislation), contact allergy to other agents is rising. The medical treatment starts from a correct identification of triggers of contact dermatitis which could allow patients to reduce or avoid exposure to these agents in future. A good clinical history, examination and immunological tests including patch testing are of crucial importance at this stage. Further management includes emollients, topical and oral corticosteroids, topical calcineurin inhibitors, azathioprine and ciclosporin. Methotrexate and alitretinoin are recent additions to the armamentarium of dermatologists who manage contact dermatitis.
G Ital Dermatol Venereol 2009 Oct
PMID:Medical management of contact dermatitis. 1983 32

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.
J Am Acad Dermatol 2009 Nov
PMID:Calcineurin inhibitors in oral medicine. 1983 43

Topical calcineurin inhibitors have developed a bad connotation because of a black-box warning that was based on safety concerns of hypothetic systemic absorption and because systemic treatment with calcineurin inhibitors in patients who receive organ transplants is associated with an increased cancer risk. A few case reports of lymphoma and skin cancer in patients treated with topical calcineurin inhibitors initiated the discussion. These drugs were recommended for use as second-line therapy for the short-term and noncontinuous treatment of atopic dermatitis in patients who do not respond adequately to topical corticosteroids or in whom they are contraindicated. According to the latest knowledge, there is no scientific evidence of an increased risk for malignancy due to a topical treatment with calcineurin inhibitors.
Clin Dermatol
PMID:Malignancy concerns of topical calcineurin inhibitors for atopic dermatitis: facts and controversies. 2008 51

Despite much research done involving elucidation of the pathogenesis of vitiligo, a precise cause is still not known. Prevalent hypotheses include the autoimmune, genetic, neural, self-destruction, growth factor deficiency, viral, and convergence theories, which have served as the basis for treatment formulation. Topical therapies have been a mainstay of vitiligo treatment, with or without phototherapy. Topical treatments used in the treatment of vitiligo include steroids, calcineurin inhibitors, vitamin D analogues, pseudocatalase, and depigmenting agents. Combination therapies are used to improve the success rate of repigmentation. In this article, we have examined randomized controlled trials utilizing topical treatments used as monotherapy or combination therapy. Although psoralen and khellin can be used as topical agents, used in conjunction with UV radiation, we have not included them in the review due to their inability to be used as monotherapy. We have also excluded less used or ineffective topical agents, such as melagenina, topical phenylalanine, topical L-DOPA, coal tar, anacarcin forte oil and topical minoxidil. According to current guidelines, a less than two month trial of potent or very potent topical corticosteroids or topical calcineurin inhibitors may be used for therapy of localized vitiligo (<20% skin surface area). Combinations of topical corticosteroids with excimer laser and UVA seem to be more effective than steroids alone. Pseudocatalase plus NB-UVB does not seem to be more effective than placebo with NB-UVB. Combinations of vitamin D analogues have varied efficacy based on which type is used and the type of UV light. Efficacy of calcineurin inhibitor combinations also vary based on the type used and UV light combined, with tacrolimus being more effective with excimer laser. Pimecrolimus has been effective with NB-UVB and excimer laser on facial lesions, and microdermabrasion on localized areas.
G Ital Dermatol Venereol 2010 Feb
PMID:Topical treatment and combination approaches for vitiligo: new insights, new developments. 2019 46

Atopic dermatitis (AD) is often treated with multiple modalities, including topical medications such as corticosteroids and topical calcineurin inhibitors (TCIs). The aim of this study was to describe the natural history of the utilization characteristics of topical treatment in those with AD. We conducted a longitudinal study of the first 4,105 children with physician-confirmed mild to moderate AD enrolled in an ongoing postmarketing safety study of pimecrolimus. Information was obtained from participants every six months using a questionnaire. Drug utilization was solely determined by the physician and patient. Over the three years of our study, an increasing number of individuals reported at least 6 months of complete control of their disease, without the continued use of a topical medication. While all study participants used pimecrolimus at the start of the study less than 40% continued to use it after 3 years of study participation. If an individual was still using a topical medication after three years of follow-up, it was most likely a topical corticosteroid. For those who continued to use pimecrolimus, the use was limited to about 60 grams of pimecrolimus in 6 months. Community-based use of topical pimecrolimus to treat AD is limited both with respect to the duration of exposure and amount or total dose of the exposure. If a topical therapy is persistent, it is most likely to a topical corticosteroid.
Pediatr Dermatol
PMID:The frequency and intensity of topical pimecrolimus treatment in children with physician-confirmed mild to moderate atopic dermatitis. 2019 41

Burning sensation at the site of application is the most common side effect of topical calcineurin inhibitors and is considered the most common reasons for premature discontinuation. Here, we analyze the possible mechanism(s) and offer a simple practical tip to mitigate this adverse effect. Simple cooling of the tube, immediately before use, does reduce the burning sensation and enable most intolerant patients to use the medication comfortably. We also discuss the possible explanation(s) for the success of this maneuver.
Dermatol Online J 2010 Apr 15
PMID:Practical tip: Precooling topical calcineurin inhibitors tube; reduces burning sensation. 2040 23

Vitiligo is a psychologically devastating condition. Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available in many forms viz. methoxsalen (solution and cream), trioxsalen (solution), corticosteroids (gel, cream, ointment and solution) and calcineurin inhibitors (ointment and cream). Although topical therapy has an important position in vitiligo treatment, side-effects or poor efficacy affect their utility and patient compliance. Novel drug delivery strategies can play a pivotal role in improving the topical delivery of various drugs by enhancing their epidermal localization with a concomitant reduction in their side-effects and improving their effectiveness. The current review emphasizes the potential of various phospholipid based carriers viz. liposomes, transferosomes, ethosomes, lipid emulsions, solid lipid nanoparticles and organogels in optimizing and enhancing the topical delivery of anti-vitiligo agents, whilst reducing the side effects of drugs commonly used in its topical treatment.
Indian J Dermatol Venereol Leprol
PMID:Topical treatment in vitiligo and the potential uses of new drug delivery systems. 2044 92


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