Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tacrolimus ointment (Protopic) is a topically applied macrolide lactone immunomodulator effective in the treatment of atopic dermatitis. Its mechanism of action primarily involves calcineurin inhibition, which interrupts cytokine gene expression and leads to the downregulation of T-cell activity. Tacrolimus ointment (0.03% and 0.1% for adults and 0.03% for children) is an effective treatment for atopic dermatitis of the trunk and limbs, as well as sensitive skin areas such as the face. Its efficacy is similar to or greater than that of hydrocortisone acetate 1%, hydrocortisone butyrate 0.1% and betamethsone valerate 0.12% ointments and pimecrolimus 1% cream. Systemic absorption of tacrolimus from the ointment is minimal, and adverse events, which are mostly associated with the application site and include skin burning and pruritus, tend to resolve early in treatment. Unlike topical corticosteroids, tacrolimus ointment is not associated with skin atrophy, and it is a well tolerated treatment for adults or children with atopic dermatitis, particularly when long-term treatment is indicated or the face or skin-fold regions are involved.
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PMID:Tacrolimus ointment: a review of its use in atopic dermatitis and its clinical potential in other inflammatory skin conditions. 1581 96

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

In lymphocytes, integration of Ca2+ and other signalling pathways results in productive activation, while unopposed Ca2+ signalling leads to decreased responsiveness to subsequent stimulation (anergy). The Ca(2+)-regulated transcription factor NFAT has an integral role in both aspects of lymphocyte function. NFAT cooperates with the transcription factor AP-1 (Fos/Jun) to up-regulate genes involved in productive activation of lymphocytes. However, in the absence of AP-1, NFAT imposes an opposing genetic programme that leads to lymphocyte anergy. Anergy is implemented at least partly through proteolytic degradation of the key signalling proteins PKCtheta and PLCgamma1. Sustained Ca(2+)-calcineurin signalling increases mRNA and protein levels of the E3 ubiquitin ligases Itch, CblB and Grail and induces expression of Tsg1O1, the ubiquitin-binding component of the ESCRT1 endosomal sorting complex. Subsequent stimulation or homotypic cell adhesion promotes membrane translocation of Itch and the related protein Nedd4, resulting in PKCtheta and PLCgamma1 degradation. T cells from Itch- and CblB-deficient mice are resistant to anergy induction. Anergic T cells show impaired calcium mobilization after TCR triggering and are unable to maintain a mature immunological synapse. Thus Ca(2+)-calcineurin-NFAT signalling links gene transcription to a multi-step programme that leads to impaired signal transduction in anergic T cells.
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PMID:A molecular dissection of lymphocyte unresponsiveness induced by sustained calcium signalling. 1599 6

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 eczema (AE) is a chronic inflammatory skin disease characterized by recurrent intense pruritus and a typical age-related distribution of skin lesions. Several new aspects with regard to the pathogenetic background as well as strategies for prevention, diagnosis and treatment of AE have emerged. There are ongoing studies on genetic susceptibility loci, as well as environmental and nutritional factors associated with an increase or a decrease of AE lesions. The atopy patch test is now available for identification of allergens in aeroallergen-triggered AE. New topical therapies, such as the calcineurin inhibitors, have broadened the therapeutic armamentarium substantially. In order to increase knowledge and coping strategies, patient education programs have been launched. Learning objective Upon completing this paper, the reader should be aware of new developments in AE, especially on nomenclature, prevention strategies, diagnostic tests, as well as therapeutic options.
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PMID:Atopic eczema: what's new? 1668 75

The calcineurin inhibitors (CIs) cyclosporine A and tacrolimus are essential for graft-versus-host disease prophylaxis but are associated with adverse effects, including neurotoxicity. We report a case of irreversible CI-induced neuropathic pain following allogeneic hematopoietic stem cell transplantation. The patient developed dysesthesia, electric shock-like pain, and severe itching followed by intractable analgesic-resistant pain in the lower extremities. There were no abnormal radiographic findings, and there was no improvement with a reduction of CI dosage or with administration of a calcium channel blocker. These clinical findings are similar to but inconsistent with CI-induced musculoskeletal pain syndromes previously reported in organ transplantation.
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PMID:Calcineurin inhibitor-induced irreversible neuropathic pain after allogeneic hematopoietic stem cell transplantation. 1678 80

Atopic eczema is one of the most common diseases in dermatology. Patients suffer from both the chronic relapsing skin disease and the associated emotional stress. Itching and visible lesions on the face and hands are the most unpleasant features for many often young patients, seriously reducing their quality of life. New therapeutic approaches have changed the management of atopic eczema in recent years. Relatively potent new drugs with fewer side effects than corticosteroids help to control the disease. This review focuses on the basic principles of modern atopic eczema treatment, emphasizing basic emollient therapy and topical therapy with calcineurin inhibitors.
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PMID:[Therapy of atopic dermatitis]. 1681 54

Lichen sclerosus et atrophicus is a chronic inflammatory disorder that mainly affects girls of premenarchial age and women in their fifties. Besides the anogenital region, lichen sclerosus (LS) may also affect extragenital or mucosal areas. Symptoms include soreness and pruritus, but other less common symptoms are not rare. An increased activity of fibroblasts causes increased sclerosis of the affected skin. Latest studies have identified LS as a chronic inflammatory dermatosis. Auto-antibodies against the extracellular membrane protein-1 are present in up to 80% of the patients. Moreover, in the widely accepted therapy with potent corticosteroids promising results have been presented using calcineurin antagonists in the treatment of LS. An interdisciplinary management and a continued care of patients with LS will improve the clinical manifestations and quality of life.
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PMID:Calcineurin antagonists in vulvar lichen sclerosus. 1683 Jan 55

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

Treatment options for children with atopic dermatitis (AD) include environmental modifications, corticosteroids, calcineurin inhibitors, and some less frequently used alternative therapies. Treatment of AD is a multifaceted approach that requires avoidance of specific triggers and irritants, repair and maintenance of the stratum corneum, cessation of the itch-scratch cycle, and reduction of inflammation.
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PMID:Atopic dermatitis in children, part 2: treatment options. 1724 27


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