Successful topical adapalene treatment for the facial lesions of an adolescent case of epidermolytic ichthyosis
Authors: Mariko Ogawa, Masashi Akiyama
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Epidermolytic ichthyosis (EI) is a keratinopathic ichthyosis that is characterized by generalized multiple blisters and erosions with erythroderma at birth. EI is caused by autosomal dominant rarely recessive mutations in the keratin 1 gene (KRT1) or the keratin 10 gene (KRT10). Their mutations lead to cytoskeletal fragility in the upper epidermis. Here we report the successful use of topical adapalene for treating a patient with EI. A 16-year-old Japanese male adolescent was given the diagnosis of EI at birth. He was born with erythrodermic skin, blisters, and erosions on the whole body. As previously reported,1Ishiko A. Akiyama M. Takizawa Y. Nishikawa T. Shimizu Y. Shimizu H. A novel leucine to valine mutation in residue 7 of the helix initiation motif of keratin 10 leads to bullous congenital ichthyosiform erythroderma.J Invest Dermatol. 2001; 116: 991-992Crossref PubMed Google Scholar mutation analysis using the patient's genomic DNA samples revealed the heterozygous missense mutation c.457C>G (p.Leu153Val) in KRT10. During the first year of life, blister formation became less frequent, and the erosions and blisters were replaced with diffuse hyperkeratosis on almost the entire body surface. The palms and soles were spared, as is often the case with patients whose EI is caused by KRT10 mutations. He experienced diffuse pruritus on the whole body. During his course, various treatments implemented with modest efficacy included topical vitamin D3, urea, steroids, and sulfadiazine. When he was 14 years old, he began applying topical adapalene gel 0.1% to his face. After 6 months of treatment, his facial skin, mainly on the forehead, became smoother and his facial appearance greatly improved. He was satisfied with the results, and he has continued to use topical adapalene. The skin changes have persisted (Fig 1). For hyperkeratotic lesions in EI, topical emollients containing glycerin, lactic acid, urea, and white petrolatum, along with topical vitamin D3 analogues are often used. Systemic retinoids are a beneficial treatment, despite their several adverse effects, for example, cheilitis, conjunctivitis, and liver dysfunction. For pediatric cases, we sometimes hesitate to use systemic retinoids because long-term administration carries the risk of bone hypoplasia. In light of this, topical application of retinoids is a beneficial treatment for EI, especially for pediatric patients, because a topical retinoid leads to less systemic exposure to the agent than a systemic treatment. A tretinoin derivative, adapalene is a third-generation retinoid. To our knowledge, there are no case reports in which ichthyosis was treated with topical adapalene, although tazarotene, another third-generation retinoid, was reported to be effective for several types of ichthyosis, including X-linked ichthyosis, lamellar ichthyosis, and ichthyosis vulgaris.2Hofmann B. Stege H. Ruzicka T. Lehmann P. Effect of topical tazarotene in the treatment of congenital ichthyoses.Br J Dermatol. 1999; 141: 642-646Crossref PubMed Scopus (66) Google Scholar, 3Cotellessa C. Cuevas-Covarrubias S.A. Valeri P. Fargnoli M.C. Peris K. Topical tazarotene 0.05% versus glycolic acid 70% treatment in X-linked ichthyosis due to extensive deletion of the STS gene.Acta Derm Venereol. 2005; 85: 346-348PubMed Google Scholar In the current case, we used topical adapalene because topical adapalene causes less irritation than topical tazarotene, and adapalene is the only topical retinoid available in Japan. Adapalene works to suppress the proliferation of keratinocytes. Unlike tretinoin, adapalene does not bind to the cytosolic retinoic acid binding proteins, but selectively binds to the nuclear retinoic acid receptors β and γ. The retinoic acid receptor γ subtype is predominantly expressed in the epidermis.4Shroot B. Michel S. Pharmacology and chemistry of adapalene.J Am Acad Dermatol. 1997; 36: S96-S103Abstract Full Text Full Text PDF PubMed Google Scholar Several studies have suggested that, because of this selectivity, adapalene may demonstrate greater suppressive effect against hyperkeratosis with milder side effects than other retinoids demonstrate.5Verschoore M. Poncet M. Czernielewski J. Sorba V. Clucas A. Adapalene 0.1% gel has low skin-irritation potential.J Am Acad Dermatol. 1997; 36: S104-S109Abstract Full Text Full Text PDF PubMed Google Scholar For pediatric patients with EI, instead of systemic retinoids, topical adapalene might be a useful and powerful tool for improving facial lesions and quality of life.