For such reasons, atopic dermatitis remains the only FDA-approved indication for the macrolactams.
One recent study shows that in a pig model involving dinitrofluorobenzene-induced allergic contact dermatitis (ACD), 0.1 percent pimecrolimus outperformed betamethasone-17-valerate in inhibiting gross lesions (55 percent versus 38 percent, respectively; Meingassner JG et al. Br J Dermatol. 1997 Oct;137(4):568-576.). The same trial showed 0.1 percent pimecrolimus (the marketed concentration is 1.0 percent) to be as effective as 0.05 percent fluticasone propionate and 0.05 percent clobetasol-17-propionate.
Similarly, a randomized, controlled, multicenter human trial tested pimecrolimus at 0.2 percent and 0.6 percent for treating nickel allergy.
Other research has shown 0.1 percent tacrolimus to be approximately equivalent to mometasone furoate in treating nickel allergy as measured by patch test responses and colorimetric assessment (Alomar A et al. Contact Dermatitis. 2003 Oct;49(4):185-188.). A double blinded, vehicle-controlled study performed in part by Dr. Belsito, furthermore, has shown that in treating chronic ACD in the form of nickel allergy, 0.1 percent tacrolimus works fairly quickly.
In this study, "the tacrolimus achieved improvement of the dermatitis as early as seven days and cleared the eruption in the vast majority of patients within two weeks of use," he says. More specifically, the 20-patient study found that at day seven, about 35 percent of patients had achieved clear or almost clear status (p=0.28). At day 14, this proportion was nearly 80 percent (p=0.0004; Saripalli YVet al. J Am Acad Dermatol. 2003 Sep;49(3):477-482.).
The efficacy of tacrolimus in treating dyshidrotic eczema, however, depends largely on what body area is treated. In this regard, a recent study evaluated responses of 16 volunteers with bilaterally symmetric, moderate-to-severe, chronic dyshidrosis of the hands to tacrolimus and mometasone furoate.
"For dyshidrotic eczema of the palms," Dr. Belsito says, "the tacrolimus seemed to give significant benefit and again was equivalent to mometasone furoate 0.1 percent (Schnopp C et al. J Am Acad Dermatol. 2002 Jan;46(1):73-77.). "However, on the plantar surface neither drug really seemed to create much of a benefit. The thicker the skin, the less likely these large molecules are to penetrate."
This issue also can impact the efficacy of pimecrolimus in treating chronic hand dermatitis, according to one recent study involving nearly 300 patients who were treated for up to three weeks with either this drug (in a PM application followed by at least six hours' occlusion) or a vehicle.
"The conclusion of that study essentially is that occlusion of the pimecrolimus overnight enhances efficacy (Belsito DV et al. Cutis. 2004 Jan;73(1):31-38.)," he says. "Irritant contact dermatitis and allergic dermatitis seem to be more responsive than dyshidrotic endogenous disease. But if you excluded individuals in the analysis who had significant palmar involvement, then all types of diseases responded. So the bottom line is that when the skin is very thick or hyperkeratotic, as with the tacrolimus in the plantar dyshidrosis, pimecrolimus also doesn't work as well, particularly in that short a period of time."