Tacrolimus topical therapy

Topical therapy is the initial drug treatment strategy for patients with mild to moderate psoriasis. It is estimated that approximately 70% to 80% of all patients with psoriasis can he treated adequately with use of topical therapy.1 Topical therapies include corticosteroids, coal tar products, anthralin, vitamin D3 analogues such as calcipotriol, retinoids such as tazarotene, and topical immunomodulators such as tacrolimus and pime-crolimus.18 Vitamin D3 analogues and topical retinoids all affect keratinocyte functions and the immune response. Currently, these are in wider use than is either anthralin or coal tar preparations. 

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterised by extreme pruritus and lichenified papules and plaques that may begin in or persist in to adulthood. Topical corticosteroids are first-line prescription therapy for AD they are efficacious and have a well established safety profile. The topical calcineurin inhibitors tacrolimus and pimecrolimus have been approved as second-line topical therapy for AD. The current review evaluates the available studies on the comparative effectiveness, safety, cost, and impact on quality of life of topical corticosteroids and topical calcineurin inhibitors for the treatment of adult AD [17 ]. 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

Echinacea (Echinacea purpurea) Uses immune system stimulant prevention/Rx of colds, flu as supportive th apy for colds chronic infxns of the resp tract lower urinary tract Action Stimulates phagocytosis cytokine production T resp cellular activity topically exerts anesthetic, antimicrobial, anti-inflammatory effects Efficacy Not established may X severity duration of URI Available forms Caps w/ powdered herb equivalent to 300-500 mg, PO, tid pressed juice 6-9 mL, PO, once/d tine 2-4 mL, PO, tid (1 5 dilution) tea 2 tsp (4 g) of powdered herb in 1 cup of boiling water Noles/SE Fever, taste p -version, urticaria, angioedema Contra w/ autoimmune Dz, collagen Dz, progressive systemic Dz (TB, MS, collagen-vascular disorders), HIV, leukemia, may interfere w/ immunosuppressive therapy Interactions t Risk of disulfiram-like reaction W/ disulfiram, metronidazole T risk of exacerbation of HIV or AIDS W/ chinacea amprenavir, other protease inhibitors X effects OF azathioprine, basiliximab, corticosteroids, cyclosporine, daclizumab, econazole vag cream, muromonab-CD3, mycophenolate, prednisone, tacrolimus EMS Possible immunosuppression... 

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. 

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. 

Skin manifestations of accompanying atopic eczema require a parallel local anti-inflammatory therapy, specifically with topic corticoids, anti-itching preparations and various fatty ointments. In the future, tacrolimus and pime-crolimus preparations might play a special role because they are able to substitute the application of corticoids [18]. 

Tacrolimus, an immunosuppressant that inhibits T-cell activation, is a useful alternative in severe recalcitrant psoriasis. Although it is not FDA approved for this indication, patients have received oral doses of 0.05 mg/kg daily, with increases up to 0.15 mg/kg daily, depending on results. Adverse effects include diarrhea, nausea, paresthesias, hypertension, tremor, and insomnia. Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can he administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral fohc acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

No particular therapy is effective. It is not known whether the minute quantities of phytomenadione that are present in some foods, such as parsley, kale, brussels sprouts, spinach, cucumber, soy bean oil, and green and black tea leaves, preclude effective dietary therapy. Since the mechanism of this reaction is thought to be delayed hypersensitivity, another potential therapeutic approach is topical application of tacrolimus (FK-506), a potent inhibitor of interleukin 2 and T cell activation. Tacrohmus up to now has only been shown to suppress allergic contact dermatitis to dinitrophenol. 

The most common patient complaints with topical tacrolimus therapy are transient itching and burning at the site of application. Although no data support the practice, many clinicians recommend pretreatment with topical corticosteroids to prevent or reduce tacrolimus-induced burning and erythema. Systemic adverse effects of tacrolimus, while well documented with oral therapy, have not been observed in patients using the topical ointment for AD. Patients who receive long-term systemic immunosuppressants are prone to devel-... 

If no functional impairment is present, patients with fimited disease are not treated with systemic therapy. A variety of topical preparations may be used in patients with skin-only disease, snch as clo-betasol, tacrolimus, and pimecrofimus. Many patients with extensive chronic GVHD, if left untreated, will die of infections or become disabled. The long-term survival rate is worse in certain snbgronps of patients, such as patients with extensive skin involvement, thrombocytopenia, progressive onset of chronic GVHD, and those who fail to respond to immunosuppressive therapy. 

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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