VIENNA — The topical calcineurin inhibitors constitute the most important advance in topical therapy of inflammatory dermatoses in half a century, Thomas A. Luger, M.D., said at a satellite symposium held in conjunction with the annual meeting of the European Society for Dermatological Research.
Topical tacrolimus (Protopic) and pimecrolimus (Elidil) are approved only for the treatment of atopic dermatitis. But investigations are underway for their use in a wide range of other inflammatory skin diseases. These agents are attractive alternatives to corticosteroids because they exhibit efficacy akin to that of mid- to high-potency topical steroids, but without the classic steroid side effects of skin atrophy and suppression of the hypothalamic-pituitary-adrenal axis. Pimecrolimus is marketed by Novartis, sponsor of the satellite symposium.
Here are some of the skin diseases where the early off-label clinical experience with the topical calcineurin inhibitors appears to be favorable, although it must be stressed that randomized controlled trials will be required to establish which patients are best treated with these agents, added Dr. Luger, professor and chair of dermatology at the University of Münster (Germany);
▸ Cutaneous lupus erythematosus. A recent 11-patient series reported by investigators at Ruhr University in Bochum, Germany, concluded that 3 weeks of twice-daily 1% pimecrolimus cream, with the second application followed by overnight occlusion, resulted in excellent results in all patients, with the benefits being sustained in most patients during 8 weeks of follow-up off treatment (J. Am. Acad. Dermatol. 2004;51:407–10). The investigators found that the skin lesions of systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (LE) responded better than those of long-standing discoid LE, which tend to be more hyperkeratotic and therefore resistant to transdermal drug penetration.
Topical tacrolimus appears to be effective as well. Investigators at St. Thomas' Hospital, London, have reported that 6 of 11 LE patients with resistant cutaneous lesions showed clear improvement in their skin lesions in response to a minimum of 6 weeks of 0.1% tacrolimus ointment. Among the responders were patients with discoid LE, subacute cutaneous LE, and SLE (Rheumatology 2004;43:1383–5).
Dr. Luger added that he, too, has had favorable clinical experiences using topical tacrolimus, particularly in patients with cutaneous LE of the face.
▸ Netherton syndrome. Dr. Luger and colleagues have obtained gratifying results using 1% pimecrolimus cream to treat a series of patients with this disorder. Systemic absorption wasn't a problem with pimecrolimus cream, unlike topical tacrolimus, which permeates skin more efficiently. Other investigators have reported that topical tacrolimus therapy in Netherton syndrome patients often results in therapeutic blood levels.
“We treated 99% of the body surface area with pimecrolimus in some of our patients with Netherton syndrome, yet their blood levels after 3 weeks of therapy were still only one-tenth of what's needed for a systemic effect,” Dr. Luger said.
▸ Psoriasis. The topical calcineurin inhibitors are quite effective for facial lesions and for the intertriginous lesions of psoriasis inversa. These are sites where the skin is relatively thin. In contrast, neither topical agent is effective in chronic plaque-type psoriasis because the drugs can't penetrate the thick hyperkeratotic skin.
▸ Lichen sclerosus. Dr. Luger and his associates have reported complete resolution of anogenital lichen sclerosus with once-daily tacrolimus ointment in three prepubertal girls and three adults, with remissions lasting for up to 1 year and no noteworthy adverse effects (Arch. Dermatol. 2003;139:922–4). The pain and itching prominent in the disorder resolved completely in the first 2–3 weeks; fissuring, erythema, and other physical changes responded more slowly.
Other investigators recently reported that 3–4 months of pimecrolimus cream resulted in almost complete remission of severe anogenital lichen sclerosus in four prepubertal girls (BMC Dermatol. 2004;4:4).
▸ Other applications. Promising results have been reported with use of topical calcineurin inhibitors are perioral dermatitis; the skin lesions of dermatomyositis, vitiligo, steroid-induced rosacea, alopecia areata; and seborrheic dermatitis.