Atopic dermatitis tacrolimus

The evidence of the safety and efficacy of pimecrolimus was derived from studies primarily in patients with mild-to-moderate atopic dermatitis tacrolimus data was derived from moderate-to-severe patients. 

The topical immunomodulators tacrolimus (Protopic) and pimecrolimus (Elidel) inhibit calcineurin, which normally initiatives T-cell activation. These agents can be used on all parts of the body for prolonged periods without producing corticosteroid-induced adverse effects. Tacrolimus ointment 0.03% and 0.1% is applied twice daily the lower strength is preferred in children with moderate to severe atopic dermatitis. The most common adverse effect is transient itching and burning at the site of application. Pimecrolimus cream 1% is applied twice daily for mild to moderate atopic dermatitis in adults and children older than age 2. 

T Cells May Contribute to the Defects in Innate Immune Response in Atopic Dermatitis Most patients with atopic dermatitis are colonized with S. aureus and experience exacerbation of their skin disease after infection with this organism [2]. In patients with S. aureus infection, treatment with anti-staphylococcal substances can result in the reduction of skin disease. Binding of S. aureus to the epidermis is enhanced by atopic skin inflammation. This is supported by clinical studies demonstrating that treatment with topical corticosteroids or tacrolimus reduces S. aureus counts in atopic dermatitis. 

Nghiem P, Pearson Q Langley RG. (2002) Tacrolimus and pimecrolimus From clever prokaryotes to inhibiting calcineurin and treating atopic dermatitis. J Am Acad Dermatol 46 228-241. 

Tacrolimus also is available as a cream for moderate to severe atopic dermatitis refer to the Dermatologies chapter. 

Pharmacology Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis. The mechanism of action of tacrolimus in atopic dermatitis is not known. It has been demonstrated that tacrolimus inhibits T-lymphocyte activation by first binding to an intracellular protein, FKBP-12. Pharmacokinetics ... 

Absorption/Distribution - In atopic dermatitis patients, tacrolimus is absorbed after topical application of 0.1% tacrolimus ointment. 

Infected atopic dermatitis Before commencing treatment with tacrolimus ointment, clear clinical infections at treatment sites. 

Tacrolimus is used in situations where cyclosporine has been shown to be ineffective or cannot be used because of toxicity or otherwise. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants and in vitiligo. 

Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimns and tacrolimus in the treatment of atopic dermatitis meta-analysis of randomised controlled trials. BMJ 2005 330 516-21. 

Pimecrolimus (SDZ ASM 981, Elidel) is another recently approved macrolide immunosuppressant that acts by inhibiting calcineurin and blocking the release of proinflammatory cytokines from T lymphocytes. The parent compound, ascomycin, was originally isolated from Streptomyces hygroscopicus var ascomyceticus. Like tacrolimus, pimecrolimus is approved for the topical treatment of moderate to severe atopic dermatitis that is refractory to other therapies. Transient local irritation is a common side effect. 

It is an immunosuppressant macrolide antibiotic produced by Streptomyces tsukubaensis. Like cyclosporine, tacrolimus binds to a cytoplasmic immunophylin and the complex inhibits the activity of the calcium dependent phosphatase known as calcineurin. This in turn, inhibits the translocation of the transcription factor NF-AT into the cell nucleus, blocking the initiation of NF-AT dependent T-cell responses. It is indicated in atopic dermatitis. 

Because of the effectiveness of systemic tacrolimus in some dermatologic diseases, a topical preparation is now available. Tacrolimus ointment is currently used in the therapy of atopic dermatitis and psoriasis. 

Ruzicka, T., Bieber, T., Schopf, E. et al. A short-term trial of tacrolimus ointment for atopic dermatitis. European tacrolimus multicenter atopic dermatitis study group. N. Engl. J. Med. 1998 339 1788-89. 

Tacrolimus is a macrolide antibiotic from Streptomyces tsukubaensis. In principle, it acts like ciclosporin. At the molecular level, however, its receptor is not cyclophilin but a so-called FK-binding protein. Tacrolimus is likewise used to prevent allograft rejection. Its epithelial penetrability is superior to that of ciclosporin, allowing topical application in atopic dermatitis. 

Topical calcineurin inhibitors are also used to treat atopic dermatitis and include pimecrolimus (Elidel) and tacrolimus (Protopic).Treatment effects are seen in 1 to 3 weeks. Adverse reactions most commonly include burning. Although a causal relation has not been established, rare skin malignancy and lymphoma have been reported. 

A 31-year-old woman with a long history of presumed atopic dermatitis actually had contact dermatitis due to the soft white paraffin that was present in the several medicaments (glucocorticoids, tacrolimus, pimecroli-mus, and ciclosporin) that she had used to treat the skin (30). 

Lubbe J, Pournaras CC, Saurat JH. Eczema herpeticum during treatment of atopic dermatitis with 0.1% tacrolimus ointment. Dermatology 2000 201(3) 249-51. 

Soter NA, Fleischer AB Jr, Webster GF, Monroe E, Lawrence I. Tacrolimus ointment for the treatment of atopic dermatitis in adult patients part II, safety. J Am Acad Dermatol 2001 44(Suppl 1) S39 6. 

Jablonska S, Rustin M. Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with atopic dermatitis. The European Tacrolimus Ointment Study Group. Arch Dermatol 2000 136(8) 999-1006. 

In a 3-year-old African-American boy with moderate atopic dermatitis, tacrolimus caused raised transaminase and lactate dehydrogenase activities. Tacrolimus was withdrawn on day 29, but no further information was given about their liver function tests (65). 

The long-term safety of topical tacrolimus ointment 0.1% for 6-12 months has been assessed in 316 patients with atopic dermatitis (82). The most common adverse effects clearly attributed to tacrolimus were a local burning sensation (47%), pruritus (24%), and erythema (12%) the incidences fell with time. The observed incidence of infections did not exceed the expected incidence in patients with atopic dermatitis, and there were no effects on circulating cell-mediated immunity. 

In 631 adult patients with moderate to severe atopic dermatitis enrolled in a randomized, double-blind, multicenter comparison of tacrolimus (0.03% or 0.1%) with a vehicle applied twice-daily for 12 weeks, the most common adverse events were skin burning, erythema, and pruritus (83). Others were flu-like symptoms and headache. Withdrawal was required in 50 patients because of adverse events, twice as many as in the vehicle group. There was pruritus in 30 patients, skin burning in 19, skin erythema in 12, and skin infections in two. Skin burning and pruritus have consistently been observed with tacrolimus ointment, typically during the first days of treatment, reducing in incidence within the first week they tend to be mild or moderate. 

In 255 children with atopic dermatitis, tacrolimus 0.1% ointment caused transient skin burning and itching as the most common adverse events (65). Two patients required hospital admittance to control skin infections. A flu-like syndrome was the major non-topical adverse event. 

In a randomized, double-blind, placebo-controlled study at 23 centers in the USA, children with moderate to severe atopic dermatitis applied the vehicle, tacrolimus ointment 0.03%, or tacrolimus ointment 0.1% for 12 weeks (94). Burning and pruritus were the main adverse effects. Varicella infection and vesiculobullous rashes on non-application areas occurred, but with a low incidence (below 5%). Since they occurred in those who used tacrolimus 0.03%, it is likely that they were random events rather than drug-related. Regardless of dose, there were some age-related differences in the incidence of individual adverse events. For example, otitis media was more common in younger children (2-6 years). Tacrolimus ointment had no age-selective effect that was not also observed with the vehicle. Each of the adverse events resolved without sequelae. 

Pimecrolimus and tacrolimus are calcineurin inhibitors capable of exerting a local immunomodulating effect that may serve to normalize hyperproliferation of epidermis. As topical agents, tacrolimus and pimecrolimus are approved for the treatment of atopic dermatitis however, regulatory approval regarding the efficacy of these agents in psoriasis is yet to be completed. 

Topical immunomodulators, tacrolimus, and pimecrolimus provide new options for patients with mild to severe cases of atopic dermatitis. 

Boguniewicz M, Fiedler VC, Raimer S, et al. A randomized, vehicle-controlled trial of tacrolimus ointment for treatment of atopic dermatitis in children Pediatric tacrolimus study group. J Allergy Clin Immunol 1998 102(4 Pt l) 637-644. 

Hauk PJ, Leung DY Tacrolimus (FK506) new treatment approach in superantigen-associated diseases like atopic dermatitis J Allergy Clin Immunol 2001 107 391-392. 

The role of both T and B lymphocytes in a variety of disease states beyond transplantation has become increasingly important in the past decade. This is especially true of those diseases frequently referred to as autoimmune in their etiology, such as rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and so on. In addition, several other major diseases are also known to have a component of T- or B-cell-mediated pathogenesis, for example, atopic dermatitis, psoriasis, and asthma. Until very recently, the mainstay of therapy for these diseases was the corticosteroids, which were often less than satisfactory in efficacy and often associated with undesirable side effects, especially in growing children and the elderly. Thus, the search for new agents with different mechanisms of action and which did not have the same adverse event profile as conventional corticosteroids led to the subsequent evaluation of drugs such as tacrolimus and sirolimus to treat several of these diseases. 

Very recently topical tacrolimus (ointment) has been shown to be a very effective therapy for the treatment of moderate to severe atopic dermatitis, making it the first true alternative to steroids for treating this widespread disease. It seems... 

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