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)

(1) Atopic dermatitis (AD) is a chronic dermatological condition characterized by pruritus (itchiness) and rash. Topical corticosteroids are the mainstay of pharmacotherapy. (2) Tacrolimus ointment is a new topical anti-inflammatory agent available in Canada through the Special Access Program. (3) It is approved as a second line agent for short or long term intermittent treatment of moderate to severe AD. (4) Clinical trials suggest it is both effective and safe, but comparative studies with corticosteroids and long-term information are limited.
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PMID:Tacrolimus ointment for the treatment of atopic dermatitis. 1177 88

At present, the first-line drugs for treating atopic dermatitis are topical corticosteroids. They are effective when used short-term; however, long-term use of the corticosteroids is associated with suppressive effects on the connective tissue, seen as skin atrophy or resistance to therapy. Currently, two topical noncorticosteroid immunomodulators tacrolimus (FK506) and pimecrolimus (SDZ ASM 981) are under development, or already on the market in some countries for atopic dermatitis. These two compounds show structural similarity. In T lymphocytes they bind to the same cellular receptor, the FK-binding protein (FKBP) or macrophilin-12. Tacrolimus shows a 3-fold greater affinity to FKBP compared with pimecrolimus. The tacrolimus/ pimecrolimus-FKBP complex further binds to calcineurin, an enzyme vital for the early activation of T cells. The consequence of calcineurin binding is a lack of activation of both T helper cell types 1 and 2. Further effects of these compounds have been suggested on other inflammatory cells, such as Langerhans cells and mast cells/basophils. In contrast to corticosteroids, no suppressive effects on connective tissue cells have been observed. Taken together, treatment of inflammation results in healing of the barrier function of the skin. This again results in reduced bioavailability of the drug, as compared with systemic use. Placebo-controlled studies have shown the efficacy of both tacrolimus (at 0.03 and 0.1%) and pimecrolimus (at 0.6 and 1%). The main adverse event in these studies has been a burning sensation and increased pruritus at the site of application. Typically, these adverse events are observed only during the first days of treatment. Long-term safety studies, of up to one year, have not revealed any new adverse events. So far, long-term use of topical noncorticosteroid compounds has not been associated with signs of immune deficiency. Although there is currently no evidence for clinically relevant, prolonged adverse effects, some of these, such as an increased risk of photocarcinogenesis, need to be monitored. There is evidence from tacrolimus studies that monotherapy results in better long-term results when compared with combination therapy with corticosteroids. Tacrolimus and pimecrolimus could replace topical corticosteroids as the first-line treatment of atopic dermatitis.
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PMID:Topical noncorticosteroid immunomodulation in the treatment of atopic dermatitis. 1211 47

Atopic dermatitis is a chronic inflammatory skin disease characterized by severe pruritus, typical morphology and distribution of skin lesions, and personal and family history of atopy. The management of atopic dermatitis is directed at preventing the inflammation, itch, and secondary lesions. Therapy relies on general management measures, anti-inflammatory agents, antiprurites, antibiotics, and immunosuppressants. Treatment options for patients with severe or longstanding disease, extensive body surface area involvement of facial lesions are limited. Tacrolimus ointment is the first in the class of topical immunomodulators that has been formulated for the treatment of atopic dermatitis in children (2 to 15 years of age) and adult patients. The mechanism of action of tacrolimus in atopic dermatitis seems to involve T-cells, Langerhans cells, mast cells and basophiles. Experimental evidence suggests that tacrolimus inhibits T-lymphocytes activation by binding to an intracellular protein, FKBP-12. This binding phenomenon inhibits the ability of calcineurin to activate the promotor region of the gene for IL-2, IL-3, IL-4, IL-5, interferon gamma, tumor necrosis factor alpha, and granulocyte macrophage colony-stimulating factor, all of which participate in the early immune response and play a role in the pathogenesis of atopic dermatitis. Tacrolimus ointment is not atrophogenic, and is associated with minimal systemic absorption. There were no consistent changes in any laboratory variable during topical tacrolimus therapy. The most common adverse events associated with its use were transient skin burning and pruritus at the site of application. Tacrolimus ointment is safe and efficacious therapy for the treatment of pediatric and adult patients with atopic dermatitis on all skin regions including the face, neck and intertriginous areas. An overview is given of tacrolimus in atopic dermatitis.
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PMID:Tacrolimus ointment: a new therapy for atopic dermatitis--review of the literature. 1213 28

Atopic dermatitis is a common problem affecting up to 10 percent of all children. The mainstays of therapy have been oral antihistamines, topical emollients, topical doxepin, and topical corticosteroids. Side effects associated with higher potency topical corticosteroids have limited their use in children and for facial areas. Tacrolimus (Protopic) is an immunosuppressive agent typically used systemically in transplant patients. Used topically, it has been found to be effective in treating moderate to severe atopic dermatitis without causing the atrophy that might occur with prolonged use of topical corticosteroids. Tacrolimus works equally well in children and adults, with more than two thirds of both groups having an improvement of greater than 50 percent. Despite its potency, very little of the medication is systemically absorbed, and absorption decreases as the atopic dermatitis resolves. The main side effects are burning and itching, but these also decrease with improvement of the atopic dermatitis.
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PMID:Topical tacrolimus: a new therapy for atopic dermatitis. 1275 51

Tacrolimus ointment is the first of a new class of non-steroidal topical immunomodulators indicated for the treatment of atopic dermatitis. Topical tacrolimus has been subject to an extensive clinical development program involving more than 16,000 patients. A clinical trial program, including vehicle-controlled studies, short- and long-term comparative studies and long-term safety studies, has investigated tacrolimus 0.1% and 0.03% ointment for the treatment of atopic dermatitis in adults and children aged 24 months and older. Tacrolimus monotherapy is rapidly effective, resulting in clinical improvements within three days of starting therapy, and produces a progressive increase in efficacy that is sustained during long-term treatment. Tacrolimus treats the signs and symptoms of atopic dermatitis, reduces the incidence of flares, and offers the potential for long-term disease control. No major safety concerns have been reported to date. Tacrolimus ointment is generally well tolerated, the primary adverse events being mild to moderate and transient application-site reactions: skin burning, pruritus and erythema. Tacrolimus ointment is a significant advance in dermatology and provides physicians with an alternative to conventional topical corticosteroid therapy.
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PMID:Atopic dermatitis management with tacrolimus ointment (Protopic). 1452 34

(1) Drug therapy for exacerbations of atopic dermatitis (atopic eczema) should only be considered when simple measures and emollients are inadequate. The first-line option is a topical corticosteroid with a level of potency appropriate for the affected site and the patient's age. (2) Tacrolimus, an immunosuppressant used orally or parenterally to prevent graft rejection, is now marketed in France as an ointment, in two dose strengths, for the treatment of atopic dermatitis. It is approved for use when topical corticosteroids fail, in patients aged at least two years. (3) According to a comparative trial in adults, tacrolimus, when used as a first-line treatment, is no more effective than a class II (strong) topical corticosteroid. Several clinical trials show that it is better than the excipient in both adults and children. The 0.1% strength seems to be slightly more active than the 0.03% strength in adults. (4) It is not known whether tacrolimus is effective after topical corticosteroid failure. (5) In comparative trials the main systemic adverse events in patients using tacrolimus ointment were flu-like syndromes and headache. Local adverse events included burning or pruritus at the site of application in about 50% of patients. These local effects are due to both the excipient and tacrolimus. (6) Severe skin infections and skin cancer cannot be ruled out as serious side effects. (7) Tacrolimus uptake through the skin exposes patients to systemic adverse effects and drug interactions. (8) In practice, patients with atopic dermatitis, however severe, have no reason to use tacrolimus, at least pending studies showing it is effective after topical corticosteroid failure.
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PMID:Tacrolimus ointment: new preparation. Too many unknowns. 1523 41

We herein report a case of tinea capitis initially showing a couple of nodular lesions. The patient was a 66-year-old woman who had seen a nearby dermatologist for itching on her head and had been treated with a topical steroid followed by tacrolimus application for one month. Because pseudolymphoma-like erythematous nodules developed at two sites, she visited us. Two weeks after stopping all medication, some slight scaling was found around these nodules. On KOH direct microscopic examination, many filamentous elements around hair shafts were observed. Biopsy of the nodules confirmed the destruction of hair follicles surrounded by granulomatous inflammation histologically. Grocott staining of the same specimen revealed a few short fungal hyphae as well as spores. She was also diagnosed as tinea pedis by direct microscopic examination of her feet. Trichophyton rubrum was isolated from scales of both her head and feet on Sabouraud's dextrose agar at 25 degrees C. Kerion celsi (KC) is usually clinically preceded by a gray patch or black dots. Such a typical course of KC, however, was not observed in our patient. Tacrolimus was thought to have possibly played an important role in modifying tinea capitis.
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PMID:[A case of tinea capitis with a couple of nodular lesions possibly resulting from topical application of tacrolimus]. 1528 31

Topical tacrolimus is successfully used in people with atopic dermatitis. Preliminary studies in dogs with atopic dermatitis using tacrolimus in a compounded lotion formulation indicated that tacrolimus significantly decreased erythema and pruritus according to investigator, but no significant improvement was reported by the dog owners. The objectives of this study were to evaluate the clinical efficacy and safety of the commercially available 0.1% tacrolimus ointment (Protopic) in dogs with atopic dermatitis. The study was designed as a double-blinded, placebo-controlled, cross-over study. Selected dogs were allocated to either tacrolimus or placebo for 4 weeks. After 4 weeks there was a wash-out period of 2 weeks and treatments were switched. Twelve dogs completed the study. Clinical signs were scored. Blood samples were collected for complete blood count, chemistry panels and tacrolimus levels at week 0 and 4 of each treatment. Tacrolimus ointment significantly decreased severity of symptoms for both owners and investigators at the end of the trial. When the same dogs received the placebo, there were no differences between week 0 and week 4 scores. Dogs with localized disease responded better than dogs with generalized disease. Tacrolimus was detected in the blood of animals receiving the active ingredient. Levels were below the level of toxicity and no adverse effects were reported in any of the dogs. No changes in complete blood count and chemistry parameters were detected between groups or within groups. In conclusion, tacrolimus appears to be a safe alternative treatment in dogs with atopic dermatitis, especially in those with localized disease.
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PMID:Investigation on the clinical efficacy and safety of 0.1% tacrolimus ointment (Protopic) in canine atopic dermatitis: a randomized, double-blinded, placebo-controlled, cross-over study. 1550 Apr 81

Tacrolimus ointment (Protopic, Fujisawa) is an effective agent in a class of topical immunomodulators. Its mechanism of action is based on calcineurin inhibition, which results in decreased T-cell activation and inflammatory cytokine release. Tacrolimus ointment is safe and effective for short- and long-term treatment of atopic dermatitis (AD) in pediatric and adult patients. The most common adverse events associated with its use are a transient burning sensation and pruritus at the site of application. Unlike topical corticosteroid agents, tacrolimus ointment does not cause a reduction in collagen synthesis or skin thickness. Because tacrolimus ointment does not cause skin atrophy, it may be safely used for months or years on all skin areas, including the face and intertriginous areas.
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PMID:Tacrolimus ointment (Protopic) for atopic dermatitis. 1555 Sep 92

Topical steroids are still used suboptimally, but remain the mainstay of atopic dermatitis treatment. Topical steroid phobia is rampant in many countries, a real advantage for the entry on the market of topical immunomodulators (TIMs), which inhibit both antigen specific and non-specific T cell activation in the skin, by blockade of gene transcription of proinflammatory cytokines such as IL2 and TNF alpha. Topical tacrolimus and pimecrolimus have the most advanced clinical development. Tacrolimus, already used orally in transplantation medicine, is already available in France since 2003 as a 0.03% ointment for children (Protopic, Fujisawa). Its introduction on the market has substantially changed prescription habits in atopic dermatitis. Recalcitrant adolescent and adult head and neck lesions are the major target, but the drug is is also widely used in children, with a good safety profile. The risk of herpes virus superinfections did not increase significantly in clinical trials but needs further monitoring. Long-term prescription will need a closer look at a still much debated increased skin cancer risk. The marked efficacy on thin skin sites and absence of atrophogenic properties of the drug balance its side effects at the first applications on inflamed skin (pruritus, burning sensation). Clinical studies using pimecrolimus (Elidel, Novartis), marketed as a 1% cream, show a satisfactorily efficacy profile in adults and children including infants. The drug is better tolerated and is already widely introduced on the international market since 2002 with a pediatric positioning, but is nor available yet in 2004 in France. Besides phototherapy, systemic immunosuppressants remain useful drugs in severe disease especially in older children and adolescents, cyclosporin remaining the leading drug. Preventive immunomodulation modifying the intestinal microflora is very promising approach which deserves a large-scale assessment.
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PMID:[New treatments of atopic dermatitis]. 1580 46


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