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)

For more than five decades, topical corticosteroids and emollients have been the mainstay of therapy for atopic dermatitis. However, the potential for side-effects limits the clinical utility of corticosteroids in providing long-term disease control. With a unique mode of action that differs from that of corticosteroids, the steroid-free topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, provide skin-selective treatment that targets key factors involved in the pathogenesis of this chronic disease. An extensive series of clinical trials involving more than 16,000 patients with predominantly moderate to severe atopic dermatitis in tacrolimus studies and over 2000 patients with primarily mild to moderate disease in pimecrolimus studies has shown that both TCIs provide effective and well-tolerated treatment for atopic dermatitis. Randomized controlled trials have demonstrated that tacrolimus is superior to conventional hydrocortisone-based regimens and does not cause skin atrophy or other steroidal side-effects. Both tacrolimus and pimecrolimus prevent disease flares and provide progressive and sustained disease improvement with long-term therapy. These and other clinical benefits of TCIs are discussed, together with the safety profiles of tacrolimus and pimecrolimus and their use in clinical practice. In addition, this review summarizes findings from the many trials carried out with these agents and outlines how TCIs can provide long-term treatment and control of a chronic skin disease that may persist for years.
Br J Dermatol 2004 Dec
PMID:The role of topical calcineurin inhibitors in atopic dermatitis. 1554 71

Pimecrolimus is the most recent member of calcineurin inhibitors available for the therapy for inflammatory skin diseases. It targets T-cells and mast cells and inhibits the production and release of cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus and much less than corticosteroids. It, thus, has a lower potential for transcutaneous resorption after topical administration, resulting in a lower risk of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal models of skin inflammation, including a model reflecting neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than tacrolimus. Pimecrolimus does not affect sensitization in a murine model of allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to tacrolimus. In conclusion, the results of preclinical studies show that pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory skin diseases.
Exp Dermatol 2004 Dec
PMID:Pimecrolimus -- an anti-inflammatory drug targeting the skin. 1556 Jul 55

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.
Eur J Dermatol
PMID:Topical 0.05% clobetasol propionate versus 1% pimecrolimus ointment in vitiligo. 1670 11

Approximately 10-20% of infants in industrialized countries experience atopic dermatitis. In recent decades topical corticosteroids have been the first-choice therapy for treatment of flares. However, this form of therapy may induce skin atrophy, especially after application to facial lesions or with long-term use. Thus, development of new anti-inflammatory topical agents for the treatment of childhood atopic dermatitis was needed. The topical calcineurin inhibitors tacrolimus and pimecrolimus have an effect on various cells of the cutaneous immune system, specifically on T cells, by inhibiting the phosphatase calcineurin and preventing the transcription of proinflammatory cytokines. In several clinical studies of children and adults with atopic dermatitis, topical calcineurin inhibitors were found to be effective both on the face and the trunk and extremities, in both short- and long-term treatment regimens. Tachyphylaxis or rebound were not observed. In most patients an improvement of their eczema occurred during the first week of treatment, as measured by subjective and objective clinical signs of atopic dermatitis. Treatment significantly reduced the incidence of flares and the need for corticosteroids in children and adults. Treatment success, commonly defined as 'excellent improvement' or 'clearing of all lesions', was observed in more than one-third of all children treated with 0.03% or 0.1% tacrolimus or 1% pimecrolimus. Topical application of pimecrolimus and tacrolimus does not lead to significant blood concentrations of these agents in the majority of children with atopic dermatitis, and any increase in blood concentrations decreases after a few days of therapy. No changes in laboratory parameters were observed in short- and long-term studies in patients with atopic dermatitis. The most common adverse effect following the application of topical calcineurin inhibitors is mild to moderate symptoms of irritation such as burning, erythema and pruritus, which occurred in up to 20% of all children treated with tacrolimus and 10% of children treated with pimecrolimus, and usually faded after a few days. In contrast to topical corticosteroids, calcineurin inhibitors do not induce skin atrophy, even after long-term use. Topical calcineurin inhibitors have been proven to be effective and have a good safety profile during short-term and long-term use for up to 1 year with pimecrolimus and up to 4 years with tacrolimus. Given the lack of extensive experience with use of topical calcineurin inhibitors over longer periods, regular use of these agents, particularly in children, should be undertaken only after careful consideration of individual cases. Sun protection should also be advised.
Am J Clin Dermatol 2005
PMID:Safety and efficacy of topical calcineurin inhibitors in the treatment of childhood atopic dermatitis. 1579 78

Further understanding of the pathogenesis of dermatologic conditions at a molecular level has led to targeted therapies. The topical immune response modifiers have contributed significantly to the treatment of cutaneous diseases. New topical remedies, particularly the Toll-like receptor agonists and calcineurin inhibitors, have added to the clinical armamentarium and have further advanced clinicians' ability to treat a wide variety of benign, premalignant, and malignant conditions. Furthermore, these agents have contributed to the understanding of the disease process. The next decade will witness even greater advances in targeted immunotherapies for dermatologic disease.
Dermatol Clin 2005 Apr
PMID:Topical immunotherapy: what's new. 1583 54

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.
J Eur Acad Dermatol Venereol 2005 May
PMID:Position paper on diagnosis and treatment of atopic dermatitis. 1585 53

The advent of new topical agents such as topical calcineurin inhibitors, as well as the reformulations of older agents in new vehicles, has broadened the treatment approaches to psoriasis and atopic dermatitis. The clinician must now consider additional novel physiologic pathways and mechanisms of action as well as expanding options for combination therapy. Combination therapy is especially beneficial when the selected agents possess differing mechanisms of action that provide additive or synergistic efficacy, reducing the required doses of the individual agents compared with monotherapy and potentially limiting side effects. Therapeutic approaches also can be rotated or used in various sequences for maintenance therapy. In psoriasis, a number of trials have demonstrated the effectiveness of combination therapy. Although combination therapy has not been extensively studied in atopic dermatitis, many practitioners combine topical corticosteroids and topical calcineurin inhibitors in their clinical practice because the two drug classes have different and possibly complementary mechanisms of action. For both diseases, the decision as to what agents are combined must also be tempered by patient type, disease presentation or severity, and patient preferences.
J Am Acad Dermatol 2005 Jul
PMID:Mechanisms of action of topical therapies and the rationale for combination therapy. 1596 60

A variety of therapeutic options are available to treat psoriasis and atopic dermatitis (AD). Local agents typically are used to treat localized and milder forms of disease, whereas phototherapy and systemic agents are used for more generalized and severe disease. Various combinations and sequences of topical or systemic therapies, or both, have been utilized in the treatment of psoriasis and, less frequently, of AD. Conventional systemic therapies for psoriasis, such as corticosteroids, oral calcineurin inhibitors, antimetabolites, and retinoids, are limited by their propensity to cause serious side effects. More recently, a number of immunobiologic agents, such as monoclonal antibodies, recombinant cytokines, and fusion proteins, have been approved by the Food and Drug Administration or are undergoing development as systemic antipsoriatic treatments. In many of these categories, a number of exciting new therapies are in development that may augment the existing armamentarium available to clinicians for the treatment of inflammatory skin diseases.
J Am Acad Dermatol 2005 Jul
PMID:Therapeutic options in the treatment of psoriasis and atopic dermatitis. 1596 62

Topical corticosteroids remain the most commonly used topical treatments for inflammatory dermatoses, including psoriasis and atopic dermatitis. Topical corticosteroids are available in a variety of vehicles-creams, ointments, lotions, gels, and, more recently, foam. The vehicle used can substantially affect the individual agent's clinical action, potency, and acceptability to the patient. Moreover, some vehicles are better suited for specific body areas. Selection of the appropriate product should be determined by area of usage, physician experience, cost, and patient preference, particularly regarding vehicle. Although topical corticosteroids are associated with several side effects, including skin atrophy, telangiectases, purpura, and striae formation, appropriate usage can minimize these occurrences. Judicious use includes short-term, appropriate application as initial monotherapy or in combination strategies with other therapeutic agents that ideally possess complementing mechanisms of action. Examples include pulsing with high-potency topical corticosteroids and combination regimens with other topical agents such as topical calcineurin inhibitors, calcipotriene, or tazarotene. Appropriate education of patients and caregivers alike will facilitate the optimal use of these medications.
J Am Acad Dermatol 2005 Jul
PMID:Corticosteroids: options in the era of steroid-sparing therapy. 1596 64

Successful management of atopic dermatitis requires a multipronged approach that includes skin barrier function care, use of topical or systemic agents, and identification and elimination of precipitating or exacerbating factors. Because the origin of atopic dermatitis is multifactorial and trigger factors differ among patients, treatment plans must be specific to the individual patient. This article offers an example of a permutational, or flexible, treatment paradigm. The approach utilizes 4 topical regimens--high-potency topical corticosteroids, lowest effective potency topical corticosteroids, topical calcineurin inhibitors (TCIs), or topical corticosteroid/TCI combinations--as initial therapy in a variety of induction protocols, as determined by the severity of a patient's condition and history. The paradigm permits treatment to progress from a chosen induction therapy to maintenance therapy. During the patient's induction therapy, as soon as an acceptable level of clearance is achieved, therapy should be adjusted to a maintenance regimen, such as monotherapy with either a TCI or a lowest effective potency topical corticosteroid (the latter used intermittently) or an alternation of the two agents. If there is no clearance or positive response with the initial induction protocol, the clinician should move to one of the alternative regimens.
J Am Acad Dermatol 2005 Jul
PMID:A clinician's paradigm in the treatment of atopic dermatitis. 1596 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>