Background: Darier's disease is an inherited genodermatosis with autosomal dominant transmission characterized by hyperkeratotic papules of seborrheic regions in the axillae, groin or submammary skin in women. Current therapeutic alternatives are poor, encouraging recourse to alternatives treatments such as topical 5-fluorouracil (Efudix) used until now for pre-epitheliomatous keratosis.
Case report: A 55-year-old man presenting severe Darier's disease refractory to therapy for more than twenty years was treated with topical 5-fluorouracil. The cream was applied at a concentration of 1% every second day for five months, alternating with clobetasol ointment in order to improve tolerability. After one month of treatment, clinical signs of hyperkeratosis had virtually disappeared from the patient's face and neck. This dramatic improvement persisted for 2 months after the end of the treatment with 5-fluorouracil. No local or systemic side-effects have been observed to date.
Discussion: Darier's disease is caused by mutations of the ATP2A2 gene, which codes for the SERCA2 endoplasmic reticulum calcium pump. This pump is rendered non-functional through decreased ATP and calcium affinity and blockade of phosphorylation-dephosphorylation. We propose a new hypothesis according to which the action of 5-fluorouracil results from restoration of normal intracytoplasmic calcium concentrations, leading to renewed keratinization. Thanks to its mode of activation, this prodrug can compensate for failure of the ATP phosphorylation-dephosphorylation mechanisms necessary for calcium pump activity by releasing phosphoric acids. Thus, topical 5-fluorouracil appears to constitute an effective alternative therapy. Long-term studies in a larger population are needed to clarify the optimal dosage and identify potential side effects.