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)

Alterations of skin and hair pigmentation are important features that have warranted treatment from ancient history on up to modern time. In some cultures, even today patients with vitiligo are regarded as social outcasts and are affected considerably both emotionally and physically. This article presents current options and future directions for the treatment of hypopigmentary disorders. Whereas with congenital disorders, such as albinism and phenylketonuria, no causal therapy has been established up to now, several treatment options for acquired hypopigmentary disorders have been investigated. In particular, in vitiligo, one of the most prevalent hypopigmentary disorders, a number of treatment modalities have been employed in the past 30 years. However, most of them are only able to palliate, not cure, the disease. Depending on the distribution of the hypopigmented lesions (localised or generalised) and the state of the disease (active or stable), several therapeutic options, for example phototherapy, surgical skin grafts, autologous melanocyte transplantation and immunomodulators, can be applied alone or in combination. For phototherapy, because of unfavourable results and adverse effects, ultraviolet (UV) A has been largely replaced by narrow-band UVB for repigmentation of generalised vitiligo. Although immunomodulators, such as corticosteroids, have been used both topically and systemically over the past 3 decades for the treatment of disseminated vitiligo, they are only suitable for the treatment of acrofacial and localised forms because of adverse effects. Hence, new immunomodulatory agents, such as calcineurin antagonists, have recently been introduced as new promising tools to treat acquired hypopigmentary disorders. However, all therapeutic approaches are hampered by the fact that the pathophysiology of hypopigmentary disorders is still poorly understood.
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PMID:Hypopigmentary skin disorders: current treatment options and future directions. 1472 60

The development of effective treatment modalities for vitiligo is dependent on an understanding of the events leading to depigmentation. However, the exact pathogenesis of vitiligo is still mostly unknown. Abnormalities in both humoral and cell-mediated immunity have been documented in vitiligo patients and they present a basis for using immunomodulating agents, such as corticosteroids and macrolide immunomodulators, in the treatment of vitiligo. Macrolide immunomodulators, such as tacrolimus and pimecrolimus, which can be used topically, are known as topical immunomodulators (TIMs). TIMs inhibit the action of calcineurin, and consequently inhibit T-cell activation and the production of various cytokines; this is considered the working mechanism of action of TIMs in vitiligo. Several small studies and case reports on the use of TIMs in vitiligo have been published so far. Tacrolimus achieves better results on the face and neck than on other body areas. Particular advantages of TIMs are safety in treating these areas because of lack of skin atrophy and good tolerability. The incidence of application site adverse events in vitiligo seems to be lower than in the treatment of atopic dermatitis. On the face and neck, TIMs may become a useful tool in the treatment of adults and children with vitiligo despite possibly lower efficacy than topical corticosteroids. Further, larger, controlled clinical studies are warranted to determine the definite role of TIMs as monotherapy or in combination with other modalities in the treatment of vitiligo.
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PMID:New treatment modalities for vitiligo: focus on topical immunomodulators. 1573 9

Vitiligo is a common skin condition resulting from loss of normal melanin pigments in the skin which produces white patches. Topical corticosteroids are indicated for the treatment of limited areas of vitiligo. Pimecrolimus, which inhibits calcineurin, has recently been shown to be effective for the treatment of vitiligo. We performed a prospective study to evaluate the efficacy of the 0.05% clobetasol propionate and 1% pimecrolimus in the treatment of vitiligo. Ten patients with virtually bilateral symmetrical lesions of vitiligo were included. 0.05% clobetasol propionate was applied twice daily over the lesion on right side of the body, and topical 1% pimecrolimus was applied twice daily over the lesion on left side of the body. It was determined that both treatment modalities resulted in a comparable rate of repigmentation. Response to treatment was varied according to the anatomical location of the lesions where better results were seen on the trunk and extremities. Results from this pilot study indicate that topical 1% pimecrolimus is as effective as clobetasol propionate in restoring skin disfiguring due to vitiligo. For a better conclusive statement further studies involving larger groups of patients should be performed.
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PMID:Topical 0.05% clobetasol propionate versus 1% pimecrolimus ointment in vitiligo. 1670 11

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

Although the treatment of vitiligo has improved during the last decade, therapy is still not satisfactory for many patients. Recently topical calcineurin inhibitors were introduced in the treatment of atopic dermatitis. Considering the autoimmune hypothesis of vitiligo pathogenesis, the use of these topical calcineurin inhibitors seems reasonable. Most clinical vitiligo trials have been performed with tacrolimus and show beneficial effects. Concerning the value of pimecrolimus in the treatment of vitiligo only few data are available. Therefore we performed an open pilot study in 26 patients to evaluate the efficacy and safety of 1% pimecrolimus in the treatment of vitiliginous lesions in the head and neck region. In 13 of 26 (50%) evaluated target lesions, repigmentation was noted after a 6 month treatment period with a median percentage of repigmentation of 72.9% (interquartile range: 30.5-98.3%). Duration of vitiligo and total affected body surface area tended to be inversely correlated with the success rate of treatment. Side effects were mainly limited to a burning sensation at the application site. Despite the promising results of topical immunomodulators in the treatment of vitiligo, prudence is in order, as long-term follow up studies are still lacking.
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PMID:Topical pimecrolimus in the treatment of vitiligo. 1732 29

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

Treatment of vitiligo is a challenge, especially in children. Recently, topical calcineurin inhibitors have been introduced in the management of vitiligo, but significant repigmentation is not achieved except on the face. Large pretibial lesions of a 15-year-old female with progressive vitiligo were treated twice daily over six months with 0.1% tacrolimus ointment on the right and 1% pimecrolimus cream on the left side without effect. Additional overnight occlusion with polyurethane and hydrocolloid foils during the following 18 months led to substantial repigmentation on both sides (tacrolimus-treated side, 88% repigmented area; pimecrolimus-treated side, 73%). Tacrolimus serum levels measured at four different time points did not exceed 1.8 ng/ml. This case report on a direct comparison of topical tacrolimus and pimecrolimus in vitiligo shows that on the shins considerable improvement could be induced with both agents only by additional long-term occlusion and that tacrolimus was somewhat more effective than pimecrolimus.
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PMID:Repigmentation of pretibial vitiligo with calcineurin inhibitors under occlusion. 1804 49

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

This detailed and user-friendly guideline for the diagnosis and management of vitiligo in children and adults aims to give high quality clinical advice, based on the best available evidence and expert consensus, taking into account patient choice and clinical expertise. The guideline was devised by a structured process and is intended for use by dermatologists and as a resource for interested parties including patients. Recommendations and levels of evidence have been graded according to the method developed by the Scottish Inter-Collegiate Guidelines Network. Where evidence was lacking, research recommendations were made. The types of vitiligo, process of diagnosis in primary and secondary care, and investigation of vitiligo were assessed. Treatments considered include offering no treatment other than camouflage cosmetics and sunscreens, the use of topical potent or highly potent corticosteroids, of vitamin D analogues, and of topical calcineurin inhibitors, and depigmentation with p-(benzyloxy)phenol. The use of systemic treatment, e.g. corticosteroids, ciclosporin and other immunosuppressive agents was analyzed. Phototherapy was considered, including narrowband ultraviolet B (UVB), psoralen with ultraviolet A (UVA), and khellin with UVA or UVB, along with combinations of topical preparations and various forms of UV. Surgical treatments that were assessed include full-thickness and split skin grafting, mini (punch) grafts, autologous epidermal cell suspensions, and autologous skin equivalents. The effectiveness of cognitive therapy and psychological treatments was considered. Therapeutic algorithms using grades of recommendation and levels of evidence have been produced for children and for adults with vitiligo.
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PMID:Guideline for the diagnosis and management of vitiligo. 1903 36

Treatment for vitiligo is difficult and prolonged. Nevertheless, at present considerable knowledge accumulated during several decades on the pathogenic mechanisms, revealed important clues for designing new strategies to improve vitiligo depigmentation. With available medical therapies, high repigmentation percentages mostly on facial and neck lesions are achieved, although they are less effective on trunk and limbs and poor on the acral parts of the extremities. Narrow band UVB and psoralens and UVA are the two most important treatments for generalized vitiligo affecting more than 10-20% of the cutaneous surface, and topical corticosteroids, or calcineurin inhibitors are the most valuable treatments for localized vitiligo. Persistence of achieved regimentation is variable and an undefined percentage of patients may have variable recurrence. When vitiligo becomes refractory, surgical methods may improve depigmentation as effectively as with medical therapy; in segmental (unilateral) or long standing, non-segmental (bilateral) stable vitiligo, repigmentation with surgical methods is usually permanent.
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PMID:Update on skin repigmentation therapies in vitiligo. 1904 May 3


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