A functional mechanistic study of the effect of emollients on the structure and function of the skin barrier.

BACKGROUND: Preventing relapses of atopic dermatitis (AD) through the regular use of topical products to repair the skin barrier defect is an emerging concept. It is still unclear if some commonly used emollients exert a positive effect on the skin barrier. OBJECTIVES: To determine the skin barrier effects of emollients commonly prescribed in the U.K. MATERIALS AND METHODS: Two cohorts of volunteers with quiescent AD undertook observer-blind forearm-controlled studies. The first cohort (18 volunteers) treated the volar side of one forearm with two fingertip units of Doublebase™ gel twice daily for 4 weeks. The second cohort (19 volunteers) undertook the same regimen using Diprobase® cream. Transepidermal water loss (TEWL), stratum corneum integrity and hydration, skin surface pH and redness were determined at the test sites before and after treatment. RESULTS: Neither Diprobase® cream nor Doublebase™ gel significantly affected the underlying skin barrier function. Both emollients were associated with significantly increased skin surface pH immediately after application (by 0·8 ± 0·19 and 1·0 ± 0·18 units, respectively), and no erythema. Diprobase® cream artificially and transiently (6 h) improved permeability barrier function by 2·9-3·1 g m-2  h-1 TEWL and increased skin hydration by 6·0-6·2 units. Doublebase™ gel, containing humectants, was associated with a greater (between 10·1 and 13·0 units during the first 6 h) and more sustained increase in hydration, lasting more than 12 h following repeated use. CONCLUSIONS: Diprobase® cream and Doublebase™ gel are not associated with skin barrier harm and appear to be appropriate for AD treatment. While displaying emollient properties, neither formulation displayed an ability to actively improve sustained skin barrier function.

Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults.

BACKGROUND: From birth, the functional properties of the neonatal epidermal barrier mature whereby the stratum corneum (SC) hydrates and the skin surface acidifies. The identification of a thinner infant SC compared with adults suggests underdeveloped mechanisms underlying differentiation and desquamation. OBJECTIVES: To assess the functional properties of the neonatal SC from birth, in conjunction with the quantification of superficial chymotrypsin-like protease activity [kallikrein-7 (KLK-7)] and filaggrin-derived natural moisturizing factors (NMF). METHODS: A total of 115 neonates recruited to the Oil in Baby SkincaRE (OBSeRvE) randomized controlled trial underwent a full evaluation of the SC at birth (< 72 h old) and at 4 weeks of age (n = 39, no oil control group) using minimally invasive instrumentation and methodology. A cohort of 20 unrelated adults was recruited for comparison. RESULTS: At birth NMF levels correlated with SC hydration (r = 0·50) and skin-surface pH (r = -0·54). From birth to 4 weeks, transepidermal water loss (TEWL), superficial KLK-7 activity and filaggrin-derived NMF significantly elevated. Impaired epidermal barrier function at birth (> 75th percentile TEWL) was accompanied by significantly elevated chymotrypsin-like protease activity and reduced levels of NMF. CONCLUSIONS: The biophysical, biological and functional properties of the developing neonatal SC are transitional from birth to 4 weeks of age and differ significantly from adults. The presence of impaired barrier function with elevated protease activity and reduced NMF at birth suggests why certain infants are predisposed to epidermal barrier breakdown and the development of atopic dermatitis.

The effect of tacrolimus compared with betamethasone valerate on the skin barrier in volunteers with quiescent atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease arising as a result of immune system and skin barrier defects. Topical corticosteroids are safe and effective treatments for AD, when used in short courses. Prolonged use is associated with skin barrier damage. Topical calcineurin inhibitors are alternative immune-modulating treatments for AD purported to have no negative effects on the skin barrier. OBJECTIVES: To compare the effects of betamethasone valerate 0·1% cream (BMVc) and tacrolimus 0·1% ointment (TACo) on the skin barrier. METHODS: Twenty volunteers with quiescent AD (no active signs for 6 months) participated in a randomized observer-blind study, wherein BMVc was applied to one forearm and TACo to the other, twice daily for 4 weeks. The biophysical/biological properties of the stratum corneum were assessed before and after treatment. Nine volunteers with active disease and 10 with healthy skin were assessed at untreated sites. RESULTS: BMVc significantly reduced skin barrier function, integrity and cohesion, and the levels of pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA) towards the subclinical barrier defect observed in patients with AD (nonlesional sites). TACo preserved skin barrier function, integrity, cohesion and PCA and UCA levels, while significantly increasing skin hydration to levels comparable with healthy skin. Both treatments reduced skin surface pH and trypsin-like protease activity, with TACo doing so to a significantly greater degree. CONCLUSION: In quiescent AD, 4 weeks of BMVc treatment adversely affected the biophysical properties of the skin and reduced the levels of natural moisturizing factor, whereas TACo improved the condition of the skin barrier.

The effect of aqueous cream BP on the skin barrier in volunteers with a previous history of atopic dermatitis.

BACKGROUND: The emollient aqueous cream BP is frequently used for the treatment of atopic dermatitis (AD), yet it is associated with a high rate of adverse cutaneous reactions. It contains the harsh anionic surfactant sodium lauryl sulphate, a known negative environmental factor associated with the exacerbation of AD. OBJECTIVES: To investigate the effect of aqueous cream BP on stratum corneum (SC) integrity and skin barrier function in volunteers with a predisposition to a defective skin barrier. METHODS: Thirteen volunteers with a previous history of AD (no symptoms for 6 months) applied aqueous cream BP twice daily to the volar side of one forearm for 4 weeks. The other forearm was left untreated as a control. Permeability barrier function and SC integrity were determined before and after treatment by measuring transepidermal water loss (TEWL) in conjunction with tape-stripping. For comparison, 13 volunteers with current AD were recruited for assessment, without treatment, of SC integrity and skin barrier function at unaffected sites. RESULTS: Topical application of aqueous cream BP resulted in significant elevation of baseline TEWL and a concomitant decrease in SC integrity. Measurements made after no treatment in volunteers with current AD, at unaffected sites, suggest that application of aqueous cream BP negatively affects the skin barrier towards the damaged state associated with onset of flares of the disease. CONCLUSIONS: Aqueous cream BP used as a leave-on emollient caused severe damage to the skin barrier in volunteers with a previous history of AD. Aqueous cream BP should not be used as a leave-on emollient in patients with AD.