Management of Darier disease: A review of the literature and update

Abstract

Darier disease (DD) is a rare type of inherited keratinizing disorder with no definitive therapeutic approach. The objective of this study is to provide a detailed literature review of all the available treatment modalities of Darier disease, including those that are both surgical and non surgical, to compare their efficacies and to propose a novel therapeutic approach. A complete search of the literature for all articles describing the different treatments of Darier disease, with no restrictions on patients’ ages, gender or nationalities, was performed with the use of PubMed. A total of 68 articles were included in the study: 3 prospective studies, 44 case reports/case series and 21 letters/correspondences/clinical images. The treatments described were topical, oral or physical. Retinoids (isotretinoin, tazarotene and adapalene) and fluorouracil were the two most effective topical treatments. Oral retinoids were the most effective oral therapy and were prescribed in the cases of generalized Darier disease. For localized and resistant skin lesions, physical therapies including surgical excision, dermabrasion and CO2 laser ablation were the first line choices. Limitations of this article include the inability to verify the accuracy of the published data, the relatively small sample size, the absence of randomized controlled clinical trials and possible unidentified confounding factors in various studies. In every therapeutic approach to Darier disease, consideration of patient comorbidities, disease distribution, severity and treatment accessibility is essential. Large and randomized clinical trials are necessary for the comparison of the efficacy and the safety of all the treatments of Darier disease and settling a consensus for management.

A Case of Darier’s Disease with a Novel Missense Mutation in ATP2A2 Successfully Treated with Calcipotriol/Betamethasone Dipropionate Two-Compound Ointment

“…Darier’s disease is a relatively rare autosomal dominant genodermatosis, with a prevalence of 1 in 30,000 to 100,000 people and no gender difference. 1 , 6 In addition to the manifestation of hyperkeratotic papules in seborrheic or intertriginous areas, DD manifests with warty papules on the dorsum of hands and feet, palmoplantar pits, and longitudinal red or white stripes in the fingernails. 6 These findings were not presented by the present case.…”

“…Darier’s disease is an intractable disease for which there are no proven curative treatments. 1 It was recently reported that a low dose (1–5 mg/d) of opioid receptor antagonist naltrexone improved the mild-to-moderate forms of the clinical manifestation in patients with DD 12 and may become a new treatment option by possibly affecting inflammation, desmosomal adhesion, or migration of keratinocytes. 13 According to the comprehensive review of the literature on therapeutic options for DD, 14 there was grade B evidence (weak recommendation; limited-quality, patient-oriented evidence) supporting the efficacy of topical 1,25-dihydroxyvitamin D3 analogs, whereas there was grade C evidence (weak recommendation; low-quality evidence) for the use of fluocinonide, a corticosteroid.…”

“…Although DD is known to respond well to oral etretinate therapy, 1 this treatment has teratogenic side effects and is not appropriate for patients of a reproductive age. Thus, we selected a once-daily treatment with topical calcipotriol (1,25-dihydroxyvitamin D3 analog)/betamethasone dipropionate (corticosteroid) two-compound ointment (LEO Pharma K.K., Chiyoda-ku, Tokyo, Japan).…”

“…Darier’s disease (DD) is a rare autosomal dominant genodermatosis characterized by multiple firm, greasy, and hyperkeratotic papules that coalesce into plaques, and it mainly affects the seborrheic regions. 1 Darier’s disease is caused by a heterozygous mutation in the ATP2A2 gene on chromosome 12q23-24.1. 2 The ATP2A2 gene encodes for the sarcoendoplasmic reticulum calcium ATPase type 2 isoform (SERCA2).…”

Beyond the skin involvement in Darier disease: A complicated neuropsychiatric phenotype

“…The concomitant application of topical retinoids could be useful, and in some cases, oral retinoids, either acitretin or isotretinoin, could be prescribed. The use of topical corticosteroids could reduce inflammation but do not alter the disease course 6 . The apathetic behavior and the low interest about medical condition, in association with the dysthymia, could represent a factor of poor adherence to both dermatologic and psychiatric therapy.…”