Use of Topical Glycolic Acid Plus a Lovastatin-Cholesterol Combination Cream for the Treatment of Autosomal Recessive Congenital Ichthyoses

Abstract

IMPORTANCE Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders caused by defects in signaling pathways involved in epidermal proliferation and differentiation, leading to a wide range of skin manifestations. Therapeutic options are limited and often unsatisfactory. Topical cholesterol and statin as a combined formulation has proven successful in the treatment of patients with CHILD syndrome (congenital hemidysplasia ichthyosis and limb defects).OBJECTIVE To assess change in disease severity score after a 3-month therapeutic regimen consisting of a glycolic acid, 10% to 20%, cream and a combination cream of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. DESIGN, SETTING, AND PARTICIPANTSThis case series of 15 patients with ARCI was conducted at the American University of Beirut, a referral center in the Middle East region for genodermatoses, between May 2017 and January 2018. No age groups were excluded; all patients were from the Middle East area; and all were initially not responsive to treatment with hydrating creams in combination with urea creams, 30% to 40%, or glycolic acid, 10% to 20%. Excluded were patients who had been taking systemic retinoids within 3 months before the start of the study.INTERVENTIONS A 3-month therapeutic regimen of glycolic acid, 10% to 20%, cream and a combination of lovastatin, 2%, with cholesterol, 2%, cream. MAIN OUTCOMES AND MEASURESPercentage change in disease severity scores following 2 and 3 months of study treatment. RESULTSOf the 15 patients included in the study, 10 were male (mean age, 11.2 years; age range, 2-38 years). The average percentage reduction in the disease severity score was 33.7% at 2 months (from 60.8 to 40.2) and 57.5% at 3 months (from 60.8 to 21.9). Adverse effects were mild and consisted mainly of irritation and burning.CONCLUSIONS AND RELEVANCE These findings suggest a benefit from a treatment regimen consisting of glycolic acid, 10% to 20%, and a combination of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. This combination of creams might also prove to be beneficial in other types of ichthyoses and other dermatological diseases with a defective skin barrier.

Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research

“…Hydroxyacids are inherently irritating to the skin when applied at high concentrations or after repeated exposure [ 10 ]. In order to examine whether the ex vivo porcine skin model could be used to evaluate the safety of cosmetic ingredients, hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days as follows: AHA, 5–10% (0.66–1.32 mM); BHA, 1–2% (0.08–0.15 mM); and PHA, 6–12% (0.17–0.34 mM), based on the generally used concentrations in chemical peels.…”

Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis

“…There is no radical therapeutic regimen for ARCI at present, and affected individuals could only undergo limited symptomatic treatment to relieve symptoms. One potentially effective therapeutic strategy including glycolic acid, 10%-20%, cream and a combination cream of lovastatin, 2%, with cholesterol, 2%, has been suggested to yield a satisfactory curative effect with improvement of the cutaneous condition of patients with ARCI (Khalil et al, 2018).…”

The Efficacy of Cholesterol-Based Carriers in Drug Delivery

“…Since the replacement of cholesterol alone without blocking the metabolite production is not effective, the combination of cholesterol with lovastatin showed improved results [ 129 ]. This is because lovastatin inhibits endogenous cholesterol production, thereby preventing the accumulation of toxic metabolites that may disrupt skin differentiation [ 130 ].…”

“…The right side significantly improved compared to the left side, probably because of the role played by glycolic acid in allowing better skin penetration of the lovastatin-cholesterol cream. The results showed the potential of topical application of glycolic acid, 10–20% cream and a combination of 2% lovastatin and 2% cholesterol in treating patients with ARCI [ 130 ].…”