Topical tacrolimus (Protopic)
by Kevin McElwee, MD
University of British Columbia
Tacrolimus given systemically has long been used to avert organ rejection after organ transplants. Tacrolimus acts directly on the T-cells and stalls the transcription or copying of the IL-2. This retards the growth and the multiplying capacity of the T lymphocytes, which would otherwise assume abnormal proportions in order to counteract the foreign antigens. Tacrolimus also holds back other cytokines (such as TNF-alpha and IFN-gamma) from activating the T-cells.
Oral tacrolimus, like all systemic immunosuppressants, leads to such fatal consequences as kidney and liver impairment and high blood pressure. Topical formulations of tacrolimus in the form of ointments have been found to be as effective as oral tacrolimus (yet devoid of the negative side-effects). Presently, topical tacrolimus is one of the safest and result-oriented (hence FDA-approved) treatments for both dermatitis and psoriasis.
Clinical trials of alopecia areata patients, however, do not present the ointment formulation in so favorable a light. A study conducted by the Department of Dermatology, University of California, involving alopecia areata patients highlighted the ineffectiveness of topical tacrolimus. Seventeen alopecia areata patients with varying percentages of scalp area affected – between 25% and 75% – and persisting for over a period of 12 months, were treated with 0.1% of tacrolimus ointment twice daily for 24 weeks. A six-week observation period showed no noticeable changes in the alopecia areata condition and hair loss continued. Yet, another study in which five patients with long-term Alopecia Universalis were recommended a one-time application of 0.1% tacrolimus ointment also proved the inefficacy of the treatment.
These failures, however, have not completely deterred scientists and they are continuing with their experiments with tacrolimus. Instead, the fact that the topical application of tacrolimus induces anagen during the telogen phase and stimulates hair growth (especially in the absence of T-cells) has given a new impetus to their research work.
The ongoing research studies are aimed at determining the effectiveness of tacrolimus in treating early alopecia areata. In the early, active phases of alopecia areata, the dermal T-cell infiltrate is comparatively dense. It is a phase, the scholars opine, which is more treatment-receptive. Though the results are yet awaited, the scientists are working hard engaging in large placebo-controlled trials. They have even come up with a far less greasy formulation of Tacrolimus, which in itself is easy to apply and hopefully more effective.
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