3. Racial/ethnic differences affecting the skin barrier include ethnicity-related variations in ceramide levels and filaggrin null mutations. Certain alterations in skin barrier lipid content correlate with increased trans-epidermal water loss (TEWL) and enhanced barrier permeability.
Filaggrin (filament-aggregating protein) is encoded by the filaggrin (FLG) gene and is first synthesized as a precursor, profilaggrin. It is expressed in the SC where it plays a significant role in barrier function and skin hydration. Loss of function (LOF) mutations in filaggrin are associated with atopic dermatitis (AD) and ichthyosis. Specifically, null mutations in FLG have been associated with epidermal barrier abnormalities, the abnormal architecture of the lamellar bilayer, and increased transepidermal water loss. However, the prevalence of LOF mutations in FLG varies by population, with lower frequencies reported in AD patients of East Asian and African descent. Two LOF mutations were initially discovered in the Northern European Caucasian population with a frequency of 7%–10%.25 In populations with AD, 27.5% of Caucasian children in the United States, 31.4% of Han Chinese, 20% of Japanese, and 0.6% to 0.9% of Italians have been shown to have FLG mutations.26-29 Few studies have found FLG mutations in individuals of African descent. Early studies found as little as 0% of patients having an FLG mutation, with subsequent studies ranging from 1.3% to 3.2%.25,30-32 More recently, Margolis et al evaluated 370 African Americans with AD and found FLG mutations in only 8.1% of subjects.26 It is important to note that the FLG mutations in different ethnic/ racial populations are different mutations in the FLG gene.
Water content in the skin can be measured by capacitance, conductance, impedance, and resistance; however, few studies use these methods to compare water content between racial and ethnic groups.
Seven studies examined Black and White skin, with four of these studies showing no significant differences.12,13,33,34 One study showed increased water content in Black skin while another suggested decreased water content in Black skin.11,35 Another study showed no statistical difference in skin hydration between African subjects and White subjects except on the palms, which demonstrated a greater level of SC hydration in Caucasians.15
The data on water content amongst various ethnic groups remains contradictory and inconclusive.
Transepidermal Water Loss
Transepidermal water loss (TEWL) is one measure of SC barrier function. Five studies of TEWL in Black skin indicate that TEWL is greater in Black skin than White skin.14, 33,36-38 However, there are nine studies that contradict these findings. Variations in methodology, including the anatomic site of measurement, may account for some of the differences observed between studies. Seven reported no difference in baseline TEWL between the Black and White subjects 5,13,15,34,39-41 and two reported decreased TEWL in Black patients.9,11 There has been no difference demonstrated in TEWL between Hispanic and White skin.33,40 Further research is required before any conclusions can be made regarding TEWL in Black skin compared to White skin. Differences in TEWL for Asian skin have also been studied (vide infra).
Lipid Content and Ceramides
The skin lipids play a particularly significant role in barrier function and are produced in the lamellar bodies of the stratum granulosum during keratinocyte differentiation. The intercellular lamellar lipid membrane is primarily composed of roughly equimolar concentrations of ceramides, cholesterol, and free fatty acids, which play a vital role in the physiological maintenance of SC hydration. The physiologic SC lipids comprise approximately twenty percent of the volume of the SC and are composed of ceramides (CERs) (40–50%), cholesterols (25%), and free fatty acids (10–15%).42,43 Optimal lipid composition is essential for ideal barrier function within the stratum corneum.
Studies have suggested that there is greater lipid content in Black SC when compared to White SC.42,43 Controversial findings have been reported regarding the lipid levels found in the SC of varying ethnic groups. Although greater overall lipid content has been reported in Black SC, subsequent studies have shown that ceramide levels were lowest in Black skin. Sugino et al found ceramide levels existed in decreasing order in Hispanic and Asian, White, and Black skin. Ceramide levels were inversely correlated with TEWL. Additionally, the ceramide levels are directly correlated with water content of the SC.37 This was again demonstrated by Hellemans et al, who quantified ceramide levels using hydrolysis and found the lowest level of lipid in the SC in Black skin.44 In the largest study of its kind, involving 341 healthy subjects in the U.S., Muizzuddin et al found African Americans to have significantly fewer ceramides compared to Caucasian and Asian American subjects.9
In a study of 71 healthy student volunteers residing in Denmark, SC lipid profiles in Asian, Black, and White subjects were evaluated by high-performance thin-layer chromatography. The highest ceramide/cholesterol ratio was seen in the Asian group, while the lowest was seen in Africans. However, no significant differences were found in the amount of individual ceramide subgroups.45
Based on the various studies discussed, the data regarding racial differences in lipid content consistently point to reduced ceramide levels in Black skin, which has implications for the presence of xerosis. Abnormalities in ceramide composition alter the stratum corneum's physiologic properties and