Topical liarozole in ichthyosis: a double-blind, left-right comparative study followed by a long-term open maintenance study

G.P.H.L. and C.J.V. contributed equally to this paper. Sir, Interest in liarozole, a retinoic acid metabolism blocking agent (RAMBA), has received a boost because of its recent orphan drug designation for congenital ichthyosis, approved by the European Commission. Retinoids1 are powerful substances available for modulating keratinocyte proliferation and differentiation. Side‐effects constitute a limit to the chronic use of systemic retinoids. Liarozole is an imidazole derivative developed in the late 1980s by the Janssen Research Foundation in Belgium. Extensive in vitro2–4 and in vivo5–7 pharmacological testing identified liarozole as an inhibitor of several mammalian cytochrome P450 (CYP) isozymes, among which is the one involved in the oxidative metabolism of all‐trans retinoic acid (RA), CYP 26. It represents the first drug in a new class of compounds coined RAMBAs. Oral liarozole seems at least as effective as acitretin in the treatment of hereditary ichthyosis with a rather similar side‐effect profile (1998, unpublished data). To broaden the margin between efficacy and side‐effects, a topical liarozole formulation was developed.