Cholesterol Cream vs Urea Cream for Skin Barrier and Quality of Life in Ichthyosis (CURE-ARCI)

Autosomal recessive congenital ichthyosis (ARCI) is a rare group of inherited skin disorders caused by mutations in genes required for normal lipid metabolism and barrier lipid assembly in the stratum corneum. The resulting epidermal barrier dysfunction produces generalized dryness, scaling, elevated transepidermal water loss (TEWL), chronic pruritus, and an increased susceptibility to skin infection. These manifestations begin at or shortly after birth and persist throughout life, with substantial negative effects on physical comfort, sleep, social functioning, and psychological well-being, particularly in children.

Current standard care relies on humectant and keratolytic agents such as 10% urea cream, which improve hydration and assist desquamation but do not address the underlying lipid deficiency responsible for barrier impairment. Cholesterol is a principal lipid component of the lamellar lipid matrix that cements corneocytes together within the stratum corneum. Exogenous application of cholesterol has been proposed as a mechanism-based intervention capable of correcting the disordered lipid lamellae characteristic of ARCI, thereby improving barrier integrity and reducing transepidermal water loss. Prior open-label, half-side comparison work in recessive X-linked ichthyosis demonstrated favorable clinical responses to topical cholesterol compared with urea, although that work did not include objective barrier measurements such as TEWL or validated quality-of-life instruments. Combination cholesterol-lovastatin preparations have also shown reductions in disease severity in ARCI. To date, no study has directly compared 10% cholesterol cream with 10% urea cream in patients with ARCI using both physiological barrier measurements and quality-of-life outcomes.

This investigation uses a prospective, randomized, split-body (intraindividual, half-side) comparison design, in which each participant serves as their own control: one cream is applied to a designated body area while the comparator cream is applied to the contralateral, matched area. This design was selected because ARCI is rare and clinically heterogeneous between individuals, making between-subject comparison less efficient than a within-subject comparison.

The primary objective is to compare the efficacy of 10% cholesterol cream and 10% urea cream in restoring skin barrier function, assessed by TEWL and skin hydration. Secondary objectives include comparison of clinical dryness and pruritus severity, changes in skin surface pH, assessment of quality of life using the Dermatology Life Quality Index (DLQI) or, for pediatric participants, the Children's Dermatology Life Quality Index (CDLQI), evaluation of participant satisfaction with each cream, and documentation of clinical change through standardized clinical photography.

Sample size was calculated using a two-dependent-means (paired t-test) formula based on an expected TEWL difference of 4 g/m²/h between treatments, a standard deviation of 6 g/m²/h, a two-sided significance level of 0.05, and 80% power, yielding a minimum requirement of 18 evaluable participants. To allow for an anticipated dropout or missing-data rate of 25%, the target enrollment was set at 24 participants.

This single-center study is being conducted at the Institute of Dermatology, Bangkok, Thailand, and has received approval from the Institute's Ethics Committee