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Evidence That Epidermal Immunocytes Are Direct Therapeutic Targets

Todd R. Coven, MD; Frank P. Murphy, MD; Patricia Gilleaudeau, RN, BSN; Irma Cardinale, BS; James G. Krueger, MD, PhD

Arch Dermatol. 1998;134:1263-1268.

Background  Psoriasis vulgaris can be effectively treated with trimethylpsoralen (TMP) bath PUVA therapy (psoralen plus UVA), but no data exist on the extent to which psoriatic pathology is affected by this treatment, or on its cellular mechanism of action.

Observations  Eleven patients with recalcitrant psoriasis vulgaris were treated with TMP bath PUVA therapy and observed through clinical and histological measures. Clinical resolution of psoriasis was achieved in 10 of 11 patients. Histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 90% of individuals treated with TMP bath PUVA. Epidermal acanthosis was reduced by 40% at 2 weeks and 66% by the end of treatment. Epidermal improvement correlated best with reduction in intraepidermal T lymphocytes, which were reduced by 76% at 2 weeks of treatment and 93% at the end of treatment. Furthermore, following TMP bath PUVA therapy, the numbers of epidermal CD1a⁺ Langerhans cells were markedly reduced, and CD86⁺ cells were eliminated. Through in vitro assays, TMP was found to be about 10000-fold more active as a lymphotoxic agent compared with 8-methoxypsoralen (8-MOP). Additionally, at physiologic concentrations, lymphocytes were killed more readily by TMP PUVA (TMP plus UVA) than were keratinocytes.

Conclusions  Treatment with TMP bath PUVA was effective in treating moderate to severe psoriasis, even in darker pigmented individuals. It is likely that this treatment ameliorates psoriasis through direct effects on activated leukocytes in lesional skin.

From the Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY.

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