Dithranol is highly effective in the treatment of
psoriasis. The
drug inhibits keratinocyte hyperproliferation, granulocyte function and, in addition, may exert an immunosuppressive effect.
Free radicals,
histamine,
eicosanoids and
platelet-activating factor have been shown to be involved in
dithranol-induced
dermatitis, and the oxidation products of the
drug are responsible for the staining. Our experimental data suggest that extracellularly generated
oxygen free radicals are responsible for both the antipsoriatic and irritative effect of the
drug. Furthermore, we could recently provide evidence that extracellularly generated
superoxide anion radical also induces an active adaptation mechanism resulting in increased tolerance to
dithranol upon repeated application. This adaptive process may explain the requirement for increasing
dithranol concentrations to maintain the antipsoriatic efficacy, and also the beneficial effect of other antipsoriatic modalities such as UV-B on
dithranol-induced
dermatitis. The recognition of this adaptive mechanism may open future prospects to overcome some limitations concerning the practical use of
dithranol.