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Penetration enhancers improve therapeutic effectiveness of topical immunomodulators

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Penetration enhancers improve therapeutic effectiveness of topical immunomodulators
Craig G Burkhart MPH MD1, Craig N Burkhart MSBS MD2
Dermatology Online Journal 11 (3): 39

1. Medical University of Ohio at Toledo.
2. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Recently Carroll et al.[1] found that topical tacrolimus ointment combined with 6% salicylic acid gel was beneficial for plaque psoriasis treatment. We also have experienced more effective therapeutic response with topical immunomodulators when used in conjunction with penetration enhancers.

Specifically, in the case of actinic keratoses, we have used topical immunomodulators once daily to decrease the irritation from fluorouracil topical chemotherapy [2]. The inflammation associated with topical 5-fluorouracil increases the penetration of pimecrolimus and tacrolimus. In this scenario, the topical immunomodulators act by suppressing antigen-specific T-cell activation and inhibiting inflammatory cytokine release, without diminishing the effectiveness of 5-fluorouracil [2].

Additionally in alopecia areata, the use of a topical retinoid or adapalene applied with pimecrolimus has resulted in total hair regrowth in 17 of 26 patients after three months of therapy. Six of the remaining nine patients showed significant improvement during that time period. As expected, patients with long-standing alopecia areata and/or extensive scalp involvement proved the least likely to achieve hair regrowth. These results are not totally unexpected as oral cyclosporin has been shown previously to offer remarkable success for this condition [3]. Of note, cyclosporin in lipid vesicles has been shown to have promising potential as a topical treatment for AA in humans, especially when used with penetration enhancers [4].

On passing, we have had moderate success in using this combination as well for vitiligo, lichen planus, and photoallergy.

Indeed, there are a host of dermatologic states in which the autoimmune T-cell-mediated response and inhibition of the inflammatory cytokine release is important and in which a potent topical immunosuppressive drug may be therapeutic. Certainly more clinical studies in the use of topical immunomodulators with agents which improve their absorption are warranted.


1. Carroll CL, Clarke J, Camacho F, Balkrishman R, Feldman SR. Topical tacrolimus ointment combined with 6% salicylic acid gel for plaque psoriasis treatment. J Am Acad Dermatol 2005;141:43-6.

2. Burkhart CN, Burkhart CG. Use of topical immunomodulators with 5-fluorouracil. J Drugs in Dermatol 2002;1:122-123.

3. Brown MD, Gupta AK, Ellis CN, Rocher LL, Voorhees JJ. Therapy of dermatologic disease with cyclosporine A. Adv Dermatol 1989;4:3-27.

4. Verma DD, Verma S, McElwee KJ, Freyschmidt-Paul P, Hoffman R, Fahr A. Treatment of alopecia areata in the DEBR model using cyclosporin A lipid vesicles. Europ J Dermatol 2004;14:332-8.

© 2005 Dermatology Online Journal