The Mount Sinai School of Medicine, Department of Dermatology, New York, NY, US A
Conflict of interest: No conflicts of interest
Topical corticosteroids (TCS) and topical calcineurin inhibitors (TCIs) are very effective treatments in inflammatory dermatoses, but carry risks with long-term use. TCS are associated with cutaneous atrophy and tachyphylaxis and TCIs can be irritating and contain a black box warning of an increased risk of cancers including lymphoma and non-melanomatous skin cancers. Nevertheless, they are appropriate treatments for inflammatory conditions such as psoriasis and atopic dermatitis (AD) and should be used more often with disease flares and less as maintenance therapy. Given the associated risks of long-term continuous use with these pharmacologic agents, alternatives are needed with similar anti-inflammatory and barrier repair properties that can be used indefinitely without risk. Some over-the-counter (OTC) ingredients such as colloidal oatmeal and petrolatum, as well as anti-inflammatory prescription moisturizers (medical device creams), have demonstrated efficacy with little complications in skin barrier repair and symptom relief in steroid-responsive conditions. With regimented application, these non-drug options are safe and effective and can limit the long-term continuous use of TCS or TCIs.
atopic dermatitis, emollients, eczema, skin barrier repair, moisturizers, topical corticosteroids, topical calcineurin inhibitors
Topical corticosteroids (TCS) are the cornerstone of treatment for inflammatory dermatoses, particularly for the swift resolution of acute flares, as TCS can calm inflamed and irritated skin due to rapid absorption and action.1 A wide range of potencies and vehicles enables tailoring of therapy to be site-specific and considerate of patient preference. Long-term continuous therapy with TCS can lead to localized side effects such as cutaneous atrophy, telangiectasias, acne and rosacea exacerbation, and tachyphylaxis, as well as systemic absorption if used on large surface areas causing hypothalamic-pituitary-adrenal (HPA) axis suppression, growth retardation in children, and cataract and glaucoma formation in adults.2-6 Thus, intermittent therapy should be supplemented with alternative treatments that can help limit localized side effects and provide epidermal barrier dysfunction improvement.7
Topical calcineurin inhibitors (TCIs; tacrolimus ointment/ Protopic®; pimecrolimus cream/Elidel®) represent secondline therapies for the short-term and non-continuous chronic treatment of moderate-to-severe atopic dermatitis (AD) in non-immunocompromised adults and children who have failed to respond adequately to or are not suitable for other topical prescription AD treatments.8,9 TCIs inhibit calcineurin in T-cells, reducing the production of interleukin (IL)-2 and related proinflammatory cytokines. Clinical studies have demonstrated longterm efficacy, minimal systemic absorption, and few transient side effects, such as localized irritation, with the use of these agents.10-12 TCIs do not induce skin atrophy or inhibit collagen synthesis, enabling their use on the face, neck and intertriginous areas.13 In 2006 the United States Food and Drug Administration (USFDA) placed a black box warning on TCIs based on safety concerns over the possible risk of systemic absorption and on data from transplantation research reporting systemic immune suppression with oral calcineurin inhibitors (tacrolimus and cyclosporine) is associated with an increased cancer risk.14 To date, this risk remains theoretical and is based mainly on the drug’s mechanism of action, data from animal studies and a few single case reports of lymphoma and skin cancer in patients treated with TCIs.
Recently, medical device creams (Table 1), which are nonsteroidal agents with emollient, anti-inflammatory and antipruritic properties, have entered the marketplace for the treatment of inflammatory dermatoses to help treat epidermal barrier dysfunction as well as limit potential long-term use of TCS and TCIs. Atopiclair® is a hydrolipidic cream containing Butyrospermum parkii (shea tree), glycyrrhetinic acid (licorice), Vitis vinifera (grapevine) extract, bisabolol (German chamomile), hyaluronic acid and tocopheryl acetate (vitamin E), and is thought to have moisturizing, anti-inflammatory and antioxidant properties.15 It also contains telmesteine, which inhibits elastase, collagenase and matrix metalloproteinases, helping to prevent epidermal breakdown. MimyX™ contains lipid components that mimic the normal skin barrier (triglycerides, phospholipids, and squalene) along with the anti-inflammatory cannabinoid N-palmitoylethanolamine (N-PEA), an endogenous fatty acid amide thought to target the peroxisome proliferator-activated receptor-alpha (PPAR-α).16 Other added ingredients such as purified water, olive oil, glycerin, pentylene glycol, vegetable oil, and hydrogenated lecithin have humectant and emollient effects. EpiCeram® is a microencapsulation system emulsion of ceramide, conjugated linoleic acid, cholesterol and palmitic acid formulated with Euphorbia cerifera (candelilla) wax, corn syrup solids, squalene, glycerin, petrolatum, and dimethicone.17,18 Eletone® has a high lipid content dispersed in an outer aqueous phase (Hydrolipid Technology™) in petrolatum, purified water, and mineral oil.19 Hylatopic Plus® is an emollient cream and foam containing Theobroma grandiflorum seed butter (a skin conditioning butter made from the fruit of a the Cupuaçu tree that is native to Brazil), hyaluronic acid, glycerin, dimethicone, petrolatum, and tocopheryl acetate (vitamin E).20 All of the medical device creams are indicated for the treatment of various dermatoses such as AD, allergic contact dermatitis, and radiation dermatitis, which are associated with symptoms of itching, burning, and pain.
|Product Name||Main Active Ingredients||Other Important Ingredients||Year of Approval||Indication||Dosage Forms (grams)|
|Atopiclair® (Sinclair Pharma)||Glycyrrhetinic acid (licorice), hyaluronic acid||Butyrospermum parkii (shea tree), glycine, bisabolol, tocopheryl acetate, Vitis vinifera (grape vine)||2003||Relieve the burning, itching and pain experienced with various types of dermatoses including atopic and allergic contact dermatitis; relief of dry skin||100 cream|
|MimyX™ (Stiefel Laboratories)||Palmitoyl ethanolamide, olive oil, glycerin, vegetable oil||Palm glycerides, hydrogenated lecithin, squalane||2005||Manage the burning and itching experienced with various types of dermatoses including atopic dermatitis, allergic contact dermatitis and radiation dermatitis||70, 140 cream|
|EpiCeram® (PuraCap Pharmaceutical)||Ceramide, capric acid, conjugated linolenic acid, cholesterol||Purified water, Euphorbia cerifera (candelilla) wax, glyceryl stearate, squalane, glycerin, hydroxypropyl bispalmitamide MEA (ceramide), petrolatum, dimethicone, cholesterol, conjugated linoleic acid, palmitic acid||2005||To treat dry skin conditions and to manage and relieve the burning and itching associated with various types of dermatoses including atopic dermatitis, irritant contact dermatitis and radiation dermatitis; relief of dry and waxy skin||50, 90 cream|
|Eletone® (Mission Pharmacal)||Petrolatum||Mineral oil||2009||Management and relief of burning, itching and redness associated with atopic dermatitis||100 cream|
|Hyaluronic acid||Glycerin, ethylhexyl palmitate, propylene glycol, Theobroma grandiflorum seed butter, petrolatum, dimethicone, tocopheryl acetate||2009||To manage and relieve the burning, itching and pain experienced with various types of dermatoses including atopic dermatitis, allergic contact dermatitis and radiation dermatitis; relief of dry and waxy skin||100, 450 cream; 100, 150 foam|
|Promiseb™ (Promius Pharma)||Piroctone olamine||Butyrospermum parkii, ethylhexyl palmitate, cera alba (beeswax), bisabolol, tocopheryl acetate, hydrogenated castor oil, acifructol complex, Vitis vinifera, glycyrrhetinic acid (licorice), telmesteine||2009||To manage and relieve the signs and symptoms of seborrhea and seborrheic dermatitis such as itching, erythema, scaling and pain; helps to relieve dry waxy skin||30 cream|
|Tetrix™ (Coria Laboratories/ Valeant Pharmaceuticals)||Cyclomethicone, dimethicone||Aluminum magnesium hydroxide stearate||2008||To manage the burning and itching experienced with various types of dermatoses including atopic dermatitis, allergic contact dermatitis and irritant contact dermatitis; helps to relieve dry waxy skin||56.7 cream|
|Bionect® (Innocutis Holdings)||Hyaluronic acid||Oleic acid, emulsifying wax, sorbitol||2012||Dressing and management of partial to full thickness dermal ulcers (pressure sores, venous stasis ulcers, arterial ulcers, diabetic ulcers) and wounds including cuts, abrasions, donor sites, and post-operative incisions, irritations of the skin, and first and second degree burns||25, 50, 100 cream; 30, 60, 100 gel; 20 ml spray|
|Biafine® (Valeant Pharmaceuticals)||Paraffin||Stearic acid, squalane, avacado oil, trolamine/ sodium alginate, cetyl palmitate, sorbic acid||2006||Full thickness wounds, pressure sores, dermal ulcers including lower leg ulcers, superficial wounds, first and second degree burns including sunburns, dermal donor and graft site management, radiation dermatitis and minor abrasions||45, 90 cream|
|Neosalus™ (Quinnova Pharmaceuticals)||Dimethicone||Carbomer, glycerin, polysorbate 20, povidone, propylene glycol, sodium hydroxide, stearic acid, trolamine||2009||For the management of various types of dermatoses including atopic dermatitis and allergic contact dermatitis||60, 100 cream; 70, 200 foam; 236 ml bottle|
|Table 1. Prescription medical device creams on the market
*Emollient foam formulation has glycerin (humectant), dimethicone (occlusive) and petrolatum (occlusive)
Epidermal Barrier Dysfunction
Defects in skin barrier function and stratum corneum hydration have been identified in a variety of inflammatory dermatoses.21 A functioning stratum corneum consists of corneocytes surrounded by ceramides, cholesterol, and free fatty acids – the so-called “bricks and mortar” model.22 Topical balms containing lipids and lipid-like substances have been shown to restore the barrier function of an impaired stratum corneum by replacing the deficient lipids, thereby improving skin hydration through decreasing transepidermal water loss (TEWL).23 Further, epidermal barrier disruption results in greater density of epidermal Langerhans cells (antigen-presenting immune cells), enhanced inflammatory responses by increased foreign antigen presentation, and decreased anti-microbial proteins (AMPs), which play a role in innate skin defense (first-line skin protection).24
In AD, the disturbed epidermal barrier is explained by nonsense mutations in the gene encoding filaggrin (FLG) and subsequent affect on the pro-inflammatory cascade, such as abnormal elevation in IL-1 cytokine profile in the stratum corneum.25,26 FLG is a structural protein essential in the cornified envelope and is expressed as pro-FLG, which functions to secure keratinocytes together in the stratum corneum. Dysfunction or loss of FLG heavily influences keratinocyte adhesion, enhances TEWL, and causes dysregulation of skin pH, resulting in increased skin permeability.27 Overall, this can induce persistent, recalcitrant and/or severe disease, increase the risk of cutaneous infections caused by microbes such as herpesvirus (eczema herpeticum) and Staphylococcus aureus, as well as increase the risk of sensitization to allergens and asthma.28 Thus, the importance of an uncompromised skin barrier in improving inflammatory conditions cannot be over-emphasized and should be a major consideration in the treatment of acute flares as well as in longterm disease management.
It is important to note that despite the acknowledged contributions of a defective epidermal permeability barrier [i.e., FLG mutations, decreased AMPs such as human tissue kallikreins and cathelicidins (LL-37)] and dryness of eczematous skin, immunologic abnormalities such as T-helper type 2 (Th2) cytokines [i.e., IL-4 and IL-13 that influence immunoglobulin E (IgE) synthesis and adhesion molecule expression] also contribute to the pathogenesis of AD.29 This suggests the development of inflammatory disorders is likely due to underlying immune dysregulation as the primary cause and epidermal dysfunction may be a secondary consequence.
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®).33 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.34
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.39
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.40 It contains a variety of active components including polysaccharides, proteins, lipids, saponins, enzymes, flavonoids, vitamins and avenanthramides (polyphenol).41 In 2003, colloidal oatmeal became an approved OTC monograph ingredient.40 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.42 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.45 Avenanthramides have also been reported to inhibit prostaglandin synthesis.46 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.47 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.48 This further solidifies that immune dysregulation in AD has a multitude of pathophysiological effects on the skin.
Newer moisturizers/topical skin care products (Table 2) 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.49 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.50 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.51 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.17 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.54 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.57 Similarly, once daily betamethasone diproprionate cream with Eucerin® Creme was equally efficacious as twice daily betamethasone diproprionate cream in patients with plaque psoriasis.58 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).59
Prescription Alternatives: Medical Device Creams
Prescription medical device creams are not classified as drugs, but rather as medical devices that have received 510(k) FDA clearance based on a demonstrated reduction in TEWL, which is a less extensive regulatory process that focuses on safety and less on efficacy. Each device cream has ingredients with proposed moisturizing, anti-inflammatory and anti-pruritic properties that may be useful as adjunctive or maintenance therapy in inflammatory dermatoses and, thereby, may help to limit the use of TCS or TCIs. Whether these device creams are equivalent in efficacy and long-term maintenance as compared to their OTC counterparts remains to be seen. Financial burden and supply limitation (insurance approval required in the US) may create difficulty in initiating and continuing therapy, especially in cases of severe disease.
Epidermal barrier dysfunction is a consequence of a combination of genetic factors influenced by immune dysregulation and abnormal structural proteins. Inflammatory dermatoses require treatment with TCS and/or TCIs to control acute flares, but also necessate appropriate and adequate moisturization to mitigate structural dysfunction and insufficient skin hydration. High predisposition to recurrent and recalcitrant disease, as well as infections and sensitization to allergens, makes long-term management with the goal to prolong periods of remission and reduce the severity of flares of utmost importance. As TCS can induce long-term complications and some patients are concerned with the black box warning of TCIs, non-drug options such as OTC and/or prescription medical device creams containing active ingredients known to have moisturizing, anti-inflammatory and anti-pruritic properties, are important therapeutic adjuncts that can be used daily without the risks associated with pharmacologics. Further studies are needed to determine the long-term efficacy of these products in treating chronic inflammatory dermatoses and validate their role through the development of management guidelines.
- Simpson EL. Atopic dermatitis: a review of topical treatment options. Curr Med Res Opin. 2010 Mar;26(3):633-40.
- Haeck IM, Rouwen TJ, Timmer-de Mik L, et al. Topical corticosteroids in atopic dermatitis and the risk of glaucoma and cataracts. J Am Acad Dermatol. 2010 Feb;64(2):275-81.
- Queille C, Pommarede R, Saurat JH. Efficacy versus systemic effects of six topical steroids in the treatment of atopic dermatitis of childhood. Pediatr Dermatol. 1984 Jan;1(3):246-53.
- Turpeinen M, Salo OP, Leisti S. Effect of percutaneous absorption of hydrocortisone on adrenocortical responsiveness in infants with severe skin disease. Br J Dermatol. 1986 Oct;115(4):475-84.
- Sahni D, Darley CR, Hawk JL. Glaucoma induced by periorbital topical steroid use–a rare complication. Clin Exp Dermatol. 2004 Nov;29(6):617-9.
- du Vivier A. Tachyphylaxis to topically applied steroids. Arch Dermatol. 1976 Sep;112(9):1245-8.
- Sheu HM, Lee JY, Kuo KW, et al. Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids. Br J Dermatol. 1997 Jun;136(6):884-90.
- Protopic® [prescribing information]. Astellas Pharma US, Inc., Northbrook, IL; Revised May 2012. Available at: http://www.protopic.com/pdf/protopic_ PI.pdf. Accessed November 17, 2013.
- Elidel® [prescribing information]. Manufactured by Novartis Pharma, Wehr, Germany; distributed by Valeant Pharmaceuticals, Bridgewater, NJ. Revised June 2011. Available at: http://elidel-us.com/files/Elidel_PI.pdf. Accessed November 17, 2013.
- Langley RG, Eichenfield LF, Lucky AW, et al. Sustained efficacy and safety of pimecrolimus cream 1% when used long-term (up to 26 weeks) to treat children with atopic dermatitis. Pediatr Dermatol. 2008 May-Jun;25(3):301-7.
- Eichenfield LF, Lucky AW, Boguniewicz, et al. Safety and efficacy of pimecrolimus (ASM 981) cream 1% in the treatment of mild and moderate atopic dermatitis in children and adolescents. J Am Acad Dermatol. 2002 Apr;46(4):495-504.
- Staab D, Pariser D, Gottlieb AB, et al. Low systemic absorption and good tolerability of pimecrolimus, administered as 1% cream (Elidel) in infants with atopic dermatitis–a multicenter, 3-week, open-label study. Pediatr Dermatol. 2005 Sep-Oct;22(5):465-71.
- Draelos ZD. Use of topical corticosteroids and topical calcineurin inhibitors for the treatment of atopic dermatitis in thin and sensitive skin areas. Curr Med Res Opin. 2008 Apr;24(4):985-94.
- Thaçi D, Salgo R. Malignancy concerns of topical calcineurin inhibitors for atopic dermatitis: facts and controversies. Clin Dermatol. 2010 Jan-Feb;28(1):52-6.
- Ong PY. Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs. 2009 Mar;14(1):165-79.
- Lo Verme J, Fu J, Astarita G, et al. The nuclear receptor peroxisome proliferatoractivated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol. 2005 Jan;67(1):15-9.
- Sugarman JL, Parish LC. Efficacy of a lipid-based barrier repair formulation in moderate-to-severe pediatric atopic dermatitis. J Drugs Dermatol. 2009 Dec;8(12):1106-11.
- EpiCeram® [package insert]. PuraCap Pharmaceutical, LLC, South Plainfield, NJ. June 2011. Available at: http://www.epiceram-us.com/prescribing_ information.html. Accessed November 17, 2013.
- Eletone® [package insert]. Mission Pharmacal Company, San Antonio, TX. Available at: http://eletonecream.com/sites/default/files/package_inserts/ eletone_0.pdf. Accessed November 17, 2013.
- HylatopicPlus® [package insert]. Onset Dermatologics, Cumberland, RI. Available at: http://www.onsetdermatologics.com/docs/PI/HylatopicPlus-PI.pdf. Accessed November 17, 2013.
- Proksch E, Brasch J. Abnormal epidermal barrier in the pathogenesis of contact dermatitis. Clin Dermatol. 2012 May-Jun;30(3):335-44.
- Mack Correa CM, Nebus J. Management of patients with atopic dermatitis: the role of emollient therapy. Dermatol Res Pract. 2012;2012:836931.
- Lynde CW. Moisturizers: what they are and how they work. Skin Therapy Lett. 2001 Dec;6(13):3-5.
- Gallo RL, Nakatsuji T. Microbial symbiosis with the innate immune defense system of the skin. J Invest Dermatol. 2011 Oct;131(10):1974-80.
- Pellerin L, Henry J, Hsu CY, et al. Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. J Allergy Clin Immunol. 2013 Apr;131(4):1094-102.
- Kezic S, O’Regan GM, Lutter R, et al. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. J Allergy Clin Immunol. 2012 Apr;129(4):1031-9.e1
- Eichenfield LF, Ellis CN, Mancini AJ, et al. Atopic dermatitis: epidemiology and pathogenesis update. Semin Cutan Med Surg. 2012 Sep;31(3 Suppl):S3-5.
- Kubo A, Nagao K, Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest. 2012 Feb 1;122(2):440-7.
- Kuo IH, Yoshida T, De Benedetto A, et al. The cutaneous innate immune response in patients with atopic dermatitis. J Allergy Clin Immunol. 2013 Feb;131(2):266-78.
- Ghadially R, Halkier-Sorensen L, Elias PM. Effects of petrolatum on stratum corneum structure and function. J Am Acad Dermatol. 1992 Mar;26(3 Pt 2):387-96.
- Nolan K, Marmur E. Moisturizers: reality and the skin benefits. Dermatol Ther. 2012 May-Jun;25(3):229-33.
- Grubauer G, Feingold KR, Elias PM. Relationship of epidermal lipogenesis to cutaneous barrier function. J Lipid Res. 1987 Jun;28(6):746-52.
- Miller DW, Koch SB, Yentzer BA, et al. An over-the-counter moisturizer is as clinically effective as, and more cost-effective than, prescription barrier creams in the treatment of children with mild-to-moderate atopic dermatitis: a randomized, controlled trial. J Drugs Dermatol. 2011 May;10(5):531-7.
- Emer JJ, Frankel A, Sohn A, et al. A bilateral comparison study of pimecrolimus cream 1% and a topical medical device cream in the treatment of patients with atopic dermatitis. J Drugs Dermatol. 2011 Jul;10(7):735-43.
- Draelos ZD. New treatments for restoring impaired epidermal barrier permeability: skin barrier repair creams. Clin Dermatol. 2012 May-Jun;30(3):345-8.
- Nair B; Cosmetic Ingredients Review Expert Panel. Final report on the safety assessment of stearoxy dimethicone, dimethicone, methicone, amino bispropyl dimethicone, aminopropyl dimethicone, amodimethicone, amodimethicone hydroxystearate, behenoxy dimethicone, C24-28 alkyl methicone, C30-45 alkyl methicone, C30-45 alkyl dimethicone, cetearyl methicone, cetyl dimethicone, dimethoxysilyl ethylenediaminopropyl dimethicone, hexyl methicone, hydroxypropyldimethicone, stearamidopropyl dimethicone, stearyl dimethicone, stearyl methicone, and vinyldimethicone. Int J Toxicol. 2003;22(Suppl 2):11-35.
- Slade HB, Fowler J, Draelos ZD, et al. Clinical efficacy evaluation of a novel barrier protection cream. Cutis. 2008 Oct;82(4 Suppl):21-8.
- Slade HB, Fowler J, Reece BT, et al. Clinical safety evaluation of a novel barrier protection cream. Cutis. 2008 Oct;82(4 Suppl):16-20.
- Beeckman D, Verhaeghe S, Defloor T, et al. A 3-in-1 perineal care washclothimpregnated with dimethicone 3% versus water and pH neutral soap to prevent and treat incontinence-associated dermatitis: a randomized, controlled clinical trial. J Wound Ostomy Continence Nurs. 2011 Nov-Dec;38(6):627-34.
- Cerio R, Dohil M, Jeanine D, et al. Mechanism of action and clinical benefits of colloidal oatmeal for dermatologic practice. J Drugs Dermatol. 2010 Sep;9(9):1116-20.
- Kurtz ES, Wallo W. Colloidal oatmeal: history, chemistry and clinical properties. J Drugs Dermatol. 2007 Feb;6(2):167-70.
- Baumann L, Woolery-Lloyd H, Friedman A. “Natural” ingredients in cosmetic dermatology. J Drugs Dermatol. 2009 Jun;8(6 Suppl):s5-9.
- Graf E. Antioxidant potential of ferulic acid. Free Radic Biol Med. 1992 Oct;13(4):435-48.
- Kikuzaki H, Hisamoto M, Hirose K, et al. Antioxidant properties of ferulic acid and its related compounds. J Agric Food Chem. 2002 Mar 27;50(7):2161-8.
- Sur R, Nigam A, Grote D, et al. Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity. Arch Dermatol Res. 2008 Nov;300(10):569-74.
- Guo W, Nie L, Wu D, et al. Avenanthramides inhibit proliferation of human colon cancer cell lines in vitro. Nutr Cancer. 2010;62(8):1007-16.
- Hon KL, Leung AK. Use of ceramides and related products for childhood-onset eczema. Recent Pat Inflamm Allergy Drug Discov. 2013 Jan 1;7(1):12-9.
- Sawada E, Yoshida N, Sugiura A, et al. Th1 cytokines accentuate but Th2 cytokines attenuate ceramide production in the stratum corneum of human epidermal equivalents: an implication for the disrupted barrier mechanism in atopic dermatitis. J Dermatol Sci. 2012 Oct;68(1):25-35.
- Madison KC. Barrier function of the skin: “la raison d’être” of the epidermis. J Invest Dermatol. 2003 Aug;121(2):231-41.
- Frankel A, Sohn A, Patel RV, et al. Bilateral comparison study of pimecrolimus cream 1% and a ceramide-hyaluronic acid emollient foam in the treatment of patients with atopic dermatitis. J Drugs Dermatol. 2011 Jun;10(6):666-72.
- Chamlin SL, Kao J, Frieden IJ, et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol. 2002 Aug;47(2):198-208.
- Madaan A. Epiceram for the treatment of atopic dermatitis. Drugs Today (Barc). 2008 Oct;44(10):751-5.
- Bikowski J. Case studies assessing a new skin barrier repair cream for the treatment of atopic dermatitis. J Drugs Dermatol. 2009 Nov;8(11):1037-41.
- Simpson E, Böhling A, Bielfeldt S, et al. Improvement of skin barrier function in atopic dermatitis patients with a new moisturizer containing a ceramide precursor. J Dermatolog Treat. 2013 Apr;24(2):122-5.
- Draelos Z. Aquaporins: an introduction to a key factor in the mechanism of skin hydration. J Clin Aesthet Dermatol. 2012 Jul;5(7):53-6.
- Anderson PC, Dinulos JG. Are the new moisturizers more effective? Curr Opin Pediatr. 2009 Aug;21(4):486-90.
- Lucky AW, Leach AD, Laskarzewski P, et al. Use of an emollient as a steroidsparing agent in the treatment of mild to moderate atopic dermatitis in children. Pediatr Dermatol. 1997 Jul-Aug;14(4):321-4.
- Watsky KL, Freije L, Leneveu MC, et al. Water-in-oil emollients as steroidsparing adjunctive therapy in the treatment of psoriasis. Cutis. 1992 Nov; 50(5):383-6.
- Grimalt R, Mengeaud V, Cambazard F, et al. The steroid-sparing effect of an emollient therapy in infants with atopic dermatitis: a randomized controlled study. Dermatology. 2007;214(1):61-7.