RESULTS
Statement 1
Studies have shown that AD-affected skin demonstrated stratum corneum (SC) barrier dysfunction and decreased ceramides and free fatty acid levels. Even the intact skin of a patient with AD that is not flaring is compromised and has impaired barrier function.
AD is characterized by compromised epidermal barrier integrity.1-5,10
Research suggests that defects in the skin barrier may be a critical factor in initiating infantile AD and other allergic diseases.11-13 It has been determined that even the intact, non-flaring skin of a patient with AD is compromised with an impaired barrier function.1-5 Barrier dysfunction causes a decrease in SC cell adhesion and increased inflammation.14 The ability of the skin to retain water is decreased, which leads to a cycle of xerosis and itching, scratching, damaged skin, and inflammation.
Filaggrin (FLG) is a filament-binding protein that is essential to the development of the skin barrier and the maintenance of epidermal homeostasis.15,16 Loss-of-function gene mutations for FLG are a significant risk factor for AD.16 Clinical studies have identified a relationship between FLG loss-of-function mutations or downregulation, increased transepidermal water loss (TEWL), and infant AD development.17-19 In a prospective cohort study in 1836 infants, Hoyer et al found an association between FLG loss-of-function mutations (n=166) and the presence of AD at age 3 months (OR 2.89, 95% CI, 1.95-4.28; P< .001).19 Significantly higher TEWL was also observed in the mutation carriers at 6 months (mean 9.68 [95% CI 8.69-10.68]) vs noncarriers (8.24 [95% CI, 7.97-8.15]; P<.01).
AD has also been associated with abnormal SC lipid levels, which disrupts lamellar matrices, diminishes skin barrier function, and increases dermal sensitivity to allergens and irritants.20 Ceramides, in particular, are lipids essential in forming the waterproof barrier of the SC, thereby retaining water in the skin and reducing TEWL.10 The chain length of very long fatty acids within ceramides is necessary for proper barrier function. Lower levels of longer-chain ceramides and higher levels of shorter-chain ceramides have been found to be expressed in the skin of patients with AD compared to healthy individuals.
Statement 2
As recommended in international guidelines, daily moisturization is an integral part of AD management. Gentle cleansers and moisturizers may improve skin barrier function in AD and reduce skin susceptibility to irritants and xerosis.
Evidence-based international guidelines recommend daily moisturization to treat skin barrier dysfunction and hydrate skin, which is the foundation of AD management.22-27 According to the US, Canadian, and European guidelines, moisturizers are integral to monotherapy, adjunctive, preventative, and maintenance treatment of AD.22,24-27 These guidelines generally support using moisturizers for skin hydration and AD symptom improvement as the primary treatment for mild disease and in conjunction with other agents for moderate-to-severe disease (Table 2).24
In treating AD, restoring skin barrier function has long been a therapeutic goal; evidence demonstrating the success of topical moisturizers in these efforts is accumulating. In a double-blind, randomized, vehicle-controlled trial, Boralevi et al investigated the effects of long-term moisturizer therapy on AD-associated xerosis in young children (n=251, age 2-6 years).6 During a 28-day period, the objective SCORAD score, xerosis score of the SCORAD index, and visual analogue score decreased, and skin hydration increased more in participants in the moisturizer group (n=124) than in the vehicle group (n=125, P<.001 for all measures).
Hebert et al conducted a systematic review of clinical trials published between 2006 and 2019 that assessed the treatment of AD with daily moisturization.23 Studies included in the systematic review evaluated the efficacy of various commercially available moisturizers using endpoints such as TEWL, corneometry, or incidence of flare. These studies showed that moisturizers (typically applied twice daily) significantly improved skin barrier function in children and adults with AD. Studies that conducted side-by-side (split body) comparisons demonstrated that skin barrier integrity was improved with moisturization vs no treatment in nearly all cases (Table 3).
Danby et al performed a randomized, observer-blinded, intra-patient-controlled study investigating a test cream containing triglycerides, ceramides, and cholesterol in a multivesicular emulsion vs a paraffin-based emollient without physiological skin lipids in adults with dry AD-prone skin.20 Skin areas on the forearm and lower leg treated with the test cream demonstrated a greater increase in skin barrier integrity (effect size for area under the TEWL curve -162, 95% CI, -206 to -118) than that observed with the reference cream. The test cream also reduced TEWL (-15.3 g/m2/h, 95% CI, -20.3 to -10.4) and skin sensitivity to sodium lauryl sulfate (-0.5 points visible redness, 97.57% CI, -1.00 to -0.25) compared to the reference cream. Furthermore, lipid chain order was enhanced and associated with skin barrier integrity (r = 0.61) in areas of skin treated with the test cream. The test cream also decreased signs of dryness and increased hydration (8.61 capacitance units, 95% CI, 6.61 to 10.6) compared to the reference. The investigators concluded that the test cream containing triglycerides, ceramides, and cholesterol facilitated skin barrier restoration and protection from irritation and dryness superior to the paraffin-based reference.
