Alitretinoin as a treatment modality for ichthyosis in women of childbearing age - a case series and review of the literature

Background: Acitretin, a synthetic vitamin A derivative, is the most studied and widely used oral retinoid for ichthyoses. Its major disadvantage is the need for contraceptive measures during three years after discontinuation. An alternative is needed for women of childbearing age. With alitretinoin, another retinoid, pregnancy is considered safe one month after discontinuation. Objectives: To provide evidence for alitretinoin as an alternative for acitretin for ichthyosis in women of childbearing age. Our experience is shared in a case series combined with an overview of the current literature. Methods: Nine women of childbearing age (19-31 years, median 21) with different subtypes of ichthyosis (autosomal recessive congenital ichthyosis, (superficial) epidermolytic ichthyosis, erythrokeratoderma variabilis, and epidermolytic epidermal nevi, a mosaic form of epidermolytic ichthyosis) were included and treated with 30mg alitretinoin during 2-28 months. Severity was measured by Ichthyosis Area Severity Index (IASI) and Investigator Global Assessment (IGA). A literature search in Pubmed using the Mesh terms "alitretinoin", "skin diseases, genetic" and "ichthyosis" was performed.Results: Significant reduction in the mean scores of IGA, IASI-erythema, IASI-scaling and IASI-total was seen. Seven patients are still being treated, one patient stopped to become pregnant, one patient discontinued due to financial reasons. Observed side effects were reversible headache (n=6), asteatotic eczema (n=1), 'not feeling well' temporarily (n=1) and easier blistering of the feet (n=1). The literature search resulted in six case reports and case series about alitretinoin in ichthyosis and ichthyosis syndromes with in total 29 patients. The vast majority (21/29) reported significant improvement or even complete remission of skin symptoms. However, validated outcome measures to support these results were lacking. Side effects (n=16) were relatively mild, except for benign intracranial hypertension (n=1) and autoimmune hypothyroidism (n=1).Conclusion: Our study shows, with validated outcome measures, that alitretinoin is effective to mitigate the symptoms of ichthyosis in women of childbearing age and a suitable alternative to acitretin.