Calcineurin inhibitors

1.2.1. Tacrolimus (FK506) Previously known under its experimental name, FK506, tacrolimus is a hydrophobic macrolide, which was extracted from the fermentation broth of Streptomyces tsukuba, a soil microbe found in Tsukuba, Japan. Initially, tacrolimus was administered to prevent graft rejection in a liver-transplant patient and is currently used both intravenously and orally as an immunosuppressive agent in many kinds of organ transplantations (Starzl et al., 1989; Wong et al., 2005). However, the experience with the systemic use of tacrolimus in autoimmune diseases is limited to some severe cases in which 'all other medications' have been tried unsuccessfully. In the 1990s, tacrolimus was also introduced as a topical agent producing favourable results in various skin disorders (Ruzicka et al., 1999). Meanwhile, safety and efficacy data of the topical formulation are available for more than 10 years from at least 20,000 cases worldwide (Assmann et al., 2001; Gupta et al., 2002). Tacro-limus ointment is generally well tolerated and all studies have shown a very good safety profile. The most common side effects are the sensation of skin burning and pruritus at the site of application, which are mostly of short duration and of mild or moderate severity. Sometimes, its application also leads to local erythema, skin infections, and, in rare cases, to flu-like symptoms and headache. In contrast to topical steroids, tacrolimus does not cause skin atrophy despite prolonged application (Cheer and Plosker, 2001). The cutaneous absorption of tacrolimus depends on the extent of the treated body surface and the skin barrier damage. Due to the low or even not detectable blood levels, there is only a very low risk of systemic toxicity. In Febuary 2005, the American Food and Drug Administration (FDA) advised physicians urging caution in prescribing tacrolimus and pimecrolimus because few cases of lymphoma have been reported in adults and children who were treated with one of these topical immunosuppressive agents (Luger and Gollnick, 2005). However, there were no recommendations from the FDA Advisory Committee that the appropriate use of topical cal-cineurin inhibitors should be discontinued.

Topical tacrolimus is licensed for the treatment of moderate and severe atopic eczema in children (0.03%) and adults (0.1%) and, more recently, it has also been applied to other inflammatory dermatoses such as contact dermatitis, erosive lichen ruber planus, steroid-induced rosacea, pyoderma gangrenosum, vitiligo, and psoriasis (Assmann and Ruzicka, 2002; Gupta et al., 2002; Nasr, 2000). In single case reports, topical tacrolimus has also been shown to be effective in treating cutaneous lupus erythematosus (CLE). According to

Lampropoulos et al. (2004) more than 50% of the 12 investigated patients mainly suffering from resistant lesions showed improvement after 6 weeks of treatment with tacrolimus 0.1% as monothe-rapy twice daily. Similar results for various subtypes of CLE have been reported by several other groups showing marked improvement especially for initial skin lesions within 4-8 weeks of application (Yoshimasu et al., 2002; Walker et al., 2002; Bacman et al., 2003; Bohm et al., 2003; Druke et al., 2004). Further studies also described that tacrolimus may be useful for treating the malar rash of patients with SLE (Kanekura et al., 2003). Actually, a phase II multicentre clinical trial is ongoing to analyse the efficacy of topical ta-crolimus in patients with various cutaneous manifestations of this disease.

Treatment with topical tacrolimus of other connective tissue diseases is rarely mentioned in the literature. Recently, Hollar and Jorizzo (2004) reported some degree of improvement in all six investigated patients with dermatomyositis following 6-8 weeks of treatment with tacrolimus 0.1%. Yoshimasu et al. (2002) further demonstrated a therapeutic effect in three of four patients with facial lesions of dermatomyositis. In two patients with localized scleroderma, Mancuso and Berdon-dini (2003) described significant improvement of the skin lesions after using tacrolimus 0.1% under occlusion twice daily.

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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