Over-the-counter Options and Clinical Studies
Petrolatum – a mixture of long-chain hydrocarbons that is pale yellow in color, translucent, odorless, and hydrophobic – has been used for over 100 years as a healing ointment. Originally thought to be an occlusive moisturizer that forms a hydrophobic layer on the skin surface, petrolatum can penetrate and restore the stratum corneum by filling the spaces between desquamating corneocytes. This can reduce the appearance of fine lines and impart a soft, silky feel to the skin. Increased skin hydration is a consequence of epidermal lipogenesis and production of free sterols, sphingolipids, and free fatty acids.[30–32] Occlusives are generally not appealing to patients, due to their greasy feel, but can be very beneficial directly as a moisturizer and indirectly by reducing TEWL. A recently published study demonstrated the clinical efficacy and cost-effectiveness of a petrolatum-based moisturizer (Aquaphor® Healing) in treating mild-to-moderate AD as compared to two commonly prescribed medical device creams; one glycyrrhetinic acid-containing barrier repair cream (Atopiclair™) and another a ceramide-dominant barrier repair cream (EpiCeram®). Some barrier repair creams contain petrolatum as their primary ingredient (Eletone®) and one study demonstrated comparable efficacy to a TCI (i.e., Elidel®) in the treatment of AD.
Dimethicone – a mixture of polydimethylsiloxanes and silicon dioxide sometimes called simethicone – is another occlusive (insoluble in water) used in many OTC moisturizers and found to be safe and effective at skin moisturizing, though it is not as effective as petrolatum at reducing TEWL.[35,36] Dimethicone is the first ingredient in a foam formulated for the relief of irritation from inflammatory dermatoses such as AD and allergic contact dermatitis (Neosalus™). A combination of cyclomethicone (a cyclic higher-viscosity silicone) and dimethicone are used in barrier creams designed to prevent skin sensitization to allergens and can be useful in patients with itching and burning associated with contact dermatitis (Tetrix™).[37,38] Additionally, a recent study showed significant reduction in the incidence of incontinenceassociated dermatitis in patients using dimethicone-impregnated clothes.
Colloidal oatmeal has a long-standing history of benefit in dermatologic conditions associated with itch and irritation because of the ability to soothe and protect inflamed skin. It contains a variety of active components including polysaccharides, proteins, lipids, saponins, enzymes, flavonoids, vitamins and avenanthramides (polyphenol). In 2003, colloidal oatmeal became an approved OTC monograph ingredient. Current, ready-to-use oatmeal preparations are the concentrated starch-protein fraction of the oat grain mixed with emollient. Fine particles disperse on the skin and form a protective, occlusive barrier that retards water loss and moisturizes to improve the epidermal barrier. Further, oatmeal saponins help to solubilize dirt, oil and sebaceous secretions, which may normalize the skin pH. Oats have important antioxidant, ultraviolet (UV) absorbent and anti-inflammatory properties attributed to the ferulic, caffeic and coumaric acids, as well as flavonoids and α-tocopherol (vitamin E) components.[43,44] Recent research has identified avenanthramides (phenolic compounds) as a minor component of oat grains and in vitro work has demonstrated anti-inflammatory and anti-pruritic properties by decreased production of Nuclear Factor-kappaB (NF-κB) in keratinocytes and reduced pro-inflammatory cytokine (such as IL-8) production. Avenanthramides have also been reported to inhibit prostaglandin synthesis. As a result, many studies have substantiated the anti-inflammatory, hydrating and anti-pruritic properties of colloidal oatmeal and their use in the management of common inflammatory dermatoses.
As discussed previously the ceramides – which are a family of lipid molecules composed of sphingosine and a fatty acid, and found in high concentrations within the membrane of cells in the stratum corneum – are an essential component of the normal stratum corneum and function to help maintain the integrity of the skin barrier. They serve as important water-holding molecules in the extracellular space, linking corneocytes and creating a waterproof barrier. In ceraminde-deficient skin there is enhanced TEWL, dryness, and increased permeability to environmental irritants and allergens. A recent study found that the mechanisms of ceramide changes in atopic skin are due to both Th1 (accentuate) and Th2 (attenuate) cytokines, as both IL-4 and IL-6, as well as interferon (IFN)-γ and tumor necrosis factor (TNF)-α influenced ceramide content in the stratum corneum. This further solidifies that immune dysregulation in AD has a multitude of pathophysiological effects on the skin.
Newer moisturizers/topical skin care products ( Table 1 ) targeted to improve epidermal barrier dysfunction by replenishing the amount of ceramides in the skin – with ceramide and pseudoceramide products mimicking the natural physiological skin barrier – are a mainstay of adjunctive therapy for patients with AD. Although evidence on their efficacy compared to older, less expensive traditional therapies, such as occlusives and humectants, remains to be validated. It is known that proper moisture therapy can reduce the frequency of flares and limit the need for TCS or TCIs, likely a result of barrier recovery, including restoration of proper permeability function and increased levels of AMPs. In one study, a ceramide-hyaluronic acid emollient foam (Hylatopic Plus®) and pimecrolimus both showed equivalent improvement in the signs and symptoms of AD. In another study, a ceramide-dominant, physiologic lipid-based, barrier repair emollient (TriCeram®) showed improvement when substituted for other OTC moisturizers in 24 children also receiving standard therapy (TCS or TCIs) for recalcitrant AD, thereby demonstrating the use of a ceramide-dominant moisturizer as compared to traditional agents can elicit significant improvement in symptoms of AD. TriCeram® has been discontinued by the manufacturer and is no longer available on the market.
EpiCeram® (a prescription device) consists of a specific combination of ceramides, cholesterol and fatty acids (in the ratio of 3:1:1) that mimics those naturally found in the skin and is reported to have similar efficacy to a mid-potency topical corticosteroid.[1,52,53] It contains capric acid, cholesterol, conjugated linolenic acid, candelilla and petrolatum. In a fivecenter, investigator-blinded, randomized trial, EpiCeram® was compared to fluticasone (Cutivate®) cream in 121 patients with moderate-to-severe AD and showed reduced clinical disease severity, decreased pruritus and improved sleep habits at both 14 and 28 days after initiation of therapy. The fluticasone group improved faster – greater improvement by day 14 – but by day 28, both interventions showed equal efficacy. A more recent study established improvement in clinical dryness scores and skin hydration and reduction in TEWL with the use of a new moisturizer (Cetaphil® Restoraderm® Body Moisturzier; CRM) containing FLG breakdown products [natural moisturizing factor (NMF)], a ceramide precursor pseudoceramide 5 or N-(2-hydroxyhexadecanoyl) sphinganine and niacinamide (vitamin B3), at week 4 as compared to the untreated areas. A significantly higher level of ceramide and a trend toward increased water content were observed in the stratum corneum of CRM-treated skin when compared to the control.
Additional ingredients such as glycerin or glycerol, urea, hydroxy acids and propylene glycol are common humectants added to OTC ingredients to help increase the ability of the skin to absorb water; although they are typically combined with an occlusive to prevent upward migration of water from the dermis and inadvertent increased TEWL. Glycerol or glycerin are the most effective as they have the ability to activate transglutaminase activity in the stratum corneum, accelerating the maturation of corneocytes as well as increasing water channels called aquaporins (particularly aquaporin-3) in diseased skin, which ultimately increases cutaneous hydration and reduces TEWL.[55,56]
Several studies have directly examined the steroid-sparing potential of OTC emollients in patients with AD. Daily hydrocortisone 2.5% cream in the morning combined with a once daily water-in-oil emollient cream in the evening (Eucerin® Creme) was equally efficacious as twice daily hydrocortisone 2.5% cream in children. Similarly, once daily betamethasone diproprionate cream with Eucerin® Creme was equally efficacious as twice daily betamethasone diproprionate cream in patients with plaque psoriasis. As well, in infants under 12 months of age with AD, the addition of an emollient containing water, petrolatum, shea butter, evening primrose oil, glycerin, paraffin oil, niacinamide, butylene glycol, benzoic acid, carbomer and also specific active Rhealba® oat extracts (flavonoids and saponins) (Exomega® Emolient Lotion) significantly reduced the use of topical corticosteroids (desonide 0.1% cream).
Skin Therapy Letter. 2014;19(1) © 2014 SkinCareGuide.com