Restored epidermal CD44 expression in lichen sclerosus et atrophicus and clinical improvement with topical application of retinaldehyde

Sir, CD44 is a widely distributed polymorphic transmembrane glycoprotein which is expressed as multiple isoforms resulting from alternative splicing and post‐translational modifications.1 CD44 is currently thought to be the principal cell surface receptor for hyaluronate (HA).2 CD44‐targeted deficiency in mouse epidermis results in a lichen sclerosus et atrophicus (LSA)‐like histological picture.3 In human genital and extragenital LSA lesions, the epidermal expression of CD44 is decreased or absent, both at the protein and mRNA levels, which is correlated with an accumulation of HA in the superficial dermis. This suggests that LSA might result from an epidermal damage of unknown origin, responsible for a progressive decrease in keratinocyte CD44, subsequently leading to dermal changes in which HA accumulation is a conspicuous feature.4 We thus hypothesized that restoring epidermal CD44 expression might be a therapeutic target in LSA. Recently we found that topical application of retinoids dramatically increases epidermal CD44 expression at both the protein and mRNA levels in murine and human skin.5 As the application of retinoic acid on female genital skin might not be well tolerated, we tried retinaldehyde (RAL), the immediate precursor of RA.6 RAL has been chosen because (i) it strongly induces CD44 when applied on murine and human skin,5, 7 and (ii) it has been previously used for 6 months in association with mometasone furoate in 20 adult patients with biopsy‐proven vulvar LSA.8