Skin Barrier Repair





Key points





  • Moisturizers help with skin barrier repair and continue to be the mainstay of maintenance treatment and prevention of flares in atopic dermatitis (AD).



  • Though greasier moisturizer delivery systems such as ointments and creams are most effective, patient compliance should be weighed in selection of an appropriate delivery system.



  • Though a tremendous variety of moisturizers at difference price points exist on the market, studies do not show that one moisturizer or moisturizer ingredient is significantly better than another in patients with AD.



  • Natural moisturizers such as sunflower seed oil and virgin coconut oil show promise in AD, whereas olive oil may increase skin penetration and promote inflammation.



  • Proactive use of moisturizers during infancy may have a protective effect on the incidence of AD.



Introduction


Moisturizers are the key to skin barrier regulation and repair and the mainstay of treatment for atopic dermatitis (AD) along with topical medications ( ). Moisturizers have been shown to reduce transepidermal water loss and improve barrier function, preventing flares and the need for topical corticosteroid use in patients with AD ( ). Daily use of moisturizer improves xerosis, resolves pruritus quicker, and lengthens the time to flare compared to no treatment ( ). Thus daily use of moisturizers to preserve barrier function is fundamental to preventing flares and maintaining quiescent periods in AD.


The skin barrier


Skin is the largest organ of the body and functions as an interface between the internal and external environment. The skin is an essential factor to human survival as a physical barrier against harmful external agents and in protecting against dehydration. The stratum corneum is a major component of the skin barrier, which plays a key role in these important functions. In the stratum corneum, keratinocytes terminally differentiate into corneocytes, which are embedded into a lipid-rich extracellular matrix ( ). Corneocytes are characterized by cornified envelopes that contain densely packed keratin filaments cemented by several proteins, particularly filaggrin molecules. Filaggrin degradation produces natural moisturizing factor, which is responsible for hydration of the stratum corneum, as well as regulation of its pH ( ). As a result, acidification by filaggrin metabolites helps to retain the skin barrier ( ). The filaggrin metabolites, which make up natural moisturizing factor, include amino acids, lactic acids, salts, and urea ( ). Natural moisturizing factors in the extracellular matrix attract and bind water to maintain moisturization and lipids. The lipids are made from breakdown products of keratinocytes and corneocyte membranes, called lamellar granules ( ). Lamellar lipids are composed of cholesterol, free fatty acids, ceramides, and other sphingolipids ( ). Disruptions and disorders of these biochemical pathways can impair the skin barrier and increase its vulnerability to environmental insults and transepidermal water loss ( ). Additional details of the skin barrier are discussed in Chapter 5, Chapter 11, Chapter 15 .


AD is a common chronic inflammatory skin disease attributed to both epidermal barrier dysfunction and chronic T helper type 2 (Th2) inflammation ( ). The impaired barrier function in AD impacts allergic sensitization to protein antigens and microbes, including staphylococcal superantigens, which further exacerbates barrier dysfunction due to altered epidermal differentiation from underlying epidermal inflammation ( ). Th2-related cytokines, such as interleukin-4 (IL4), further intensify skin barrier impairment by altering keratinocyte differentiation and lipid synthesis in the stratum corneum ( ). Elevated transepidermal water loss correlates with AD severity. Thus, for patients with AD, restoring hydration and reducing transepidermal water loss with appropriate use of moisturizers plays a key role in repairing epidermal barrier dysfunction ( ).


Moisturizers


While there is no consensus regarding the definition of moisturizer , the term was initially coined by marketers to promote its function to moisten the skin ( ). Moisturizers address the epidermal repair dysfunction by acting as an occlusive barrier, slowing transepidermal water loss, retaining hydration, and protecting the skin from external irritants ( ). The terms moisturizer and emollient are often used interchangeably; however, moisturizers encompass emollients, occlusives, and humectants. Emollient is more specific to a moisturizer that is mostly made up of lipids and their components ( ). Emollients fill in the space between desquamating corneocytes to create a smooth surface and are used to soften, hydrate, and smooth the skin ( ). Examples of emollients include soy sterols, collagen, elastin, shea butter, glycol, and glyceryl stearate ( ). Occlusive topical agents are mostly oil based and are similar to intercellular matrix lipids like ceramide, cholesterol, and free fatty acids ( ). Occlusives form a thin hydrophobic film on the stratum corneum to slow the transepidermal water loss and thus prevent drying ( ). Examples of occlusive agents include petrolatum, dimethicone, mineral oil, silicone, olive oil, and lanolins ( ). Lastly, humectants are agents that attract and hold water from the dermis and the environment to moisturize the skin ( ). Humectants include glycerin, sorbitol, and α-hydroxyl acids ( ). The efficacy of moisturizers depends not only on the ingredients of the moisturizer but also on the proper delivery system to encourage adherence.


Moisturizer delivery systems


Choosing an ideal delivery system for a patient is critical to delivering the most efficacious treatment while also encouraging adherence to treatment. Various delivery systems include ointments, creams, lotions, gels, and oils. A summary of these moisturizer vehicles can be found in Table 22.1 .



Table 22.1

Moisturizer delivery systems




























Vehicle name Composition Notes
Ointments Emulsion of <20% water and volatiles >50% hydrocarbons, waxes, or polyethylene glycols Most greasy, least spreadable; prevent dehydration and transepidermal water loss (TEWL); do not evaporate
Creams Emulsion of >20% water and volatiles <50% hydrocarbons, waxes, or polyethylene glycolsEmulsion of either water in oil or oil in water Less greasy, more spreadable than ointments; evaporate and/or absorbed
Lotions Aqueous vehicle and >50% water and volatiles Nongreasy, spreadable; evaporate rapidly thus poorer at slowing TEWL
Gels Colloidal dispersion of water, acetone, alcohol or propylene glycol, thickened with cellulose derivativeOily gel: nonalcoholic, lipophilic gel formulation (oil or organic solvents, gelled with an organogelator) Liquefy on contact with skin and dry as nonocclusive film; easily removed with water and perspiration (except the oily gel); oily gel could slow TEWL
Oils Mainly triglycerides; also contain fatty acids, phosphatides, sterols, tocopherols, stanols, waxes, and more Some oils may have skin barrier benefits, but not all oils are created equally


Ointments


Ointments are made of an emulsion of semisolid containing less than 20% water and volatiles and more than 50% hydrocarbons, waxes, or polyethylene glycols ( ). They contain a greasy base, which often forms an occlusive layer over the skin to prevent dehydration and transepidermal water loss ( ). Ointments are translucent, greasy, do not evaporate, and are the least spreadable compared to the other delivery systems ( ). They are the most effective and tolerable in drier areas such as the trunk, nonhair-bearing regions, and extremities, including the palms and soles ( ). The greasy nature may limit patient adherence, especially on hair-bearing skin ( ).


Creams


Creams are made of an emulsion of semisolid containing more than 20% water and less than 50% hydrocarbons, waxes, or polyethylene glycols ( ). Creams are opaque, viscous, range from nongreasy to mildly greasy, and are made of an emulsion of either water in oil or oil in water ( ). They are less greasy, less viscous, more spreadable than ointments, and usually evaporate or are absorbed when rubbed onto the skin ( ). Creams are effective all over the body, especially in flexural and genital areas and in those areas with both dry and weepy skin conditions ( ). Creams are preferred when an occlusive effect is not as important ( ). Though creams are less hydrating, patients may be more adherent to creams compared to ointments due to the ease of spread and the less greasy texture ( ).


Lotions


Lotions are solutions containing an aqueous vehicle and more than 50% water and volatiles ( ). Lotions are thin, opaque, nongreasy, and evaporate rapidly ( ). Lotions are easier to spread, are beneficial for exudative conditions, and are effective in large hair-bearing areas ( ). Lotions evaporate quickly, which is not as beneficial for slowing transepidermal water loss.


Gels


Gels are transparent lattices of organic macromolecules in a semisolid dosage form containing a gelling agent to provide stiffness to a solution or colloidal dispersion for application to the skin ( ). Gels are formulated as a colloidal dispersion of water, acetone, alcohol, or propylene glycol thickened with a cellulose derivative ( ). Gels are usually clear or translucent in a single phase, but opaque in a two-phase system ( ). They are typically thick and nongreasy, except the oily gel, which is a nonalcoholic, lipophilic gel formulation ( ). Gels liquefy upon contact with the skin and then dry as a nonocclusive film ( ). Gels are advantageous and could promote adherence given their cosmetic advantage and ease of use as they are easy to apply to hair-bearing areas and are nongreasy ( ). However, gels are easily removed with water or perspiration and tend to lack emolliating and skin protective properties ( ). An exception is the oily gel, which is characterized by a nonpolar dispersion medium such as oil or organic solvents, gelled with an organogelator ( ). These oily gels are advantageous and could slow transepidermal water loss as they are resistant to water and perspiration ( ).


Oils


Oils include mineral, almond, jojoba, soybean, avocado, coconut, olive, and cannabinoid oils as well as various other vegetable oils. Oils can act as a protective barrier to the skin via the occlusive effect, allowing moisture retention, and thus may decrease transepidermal water loss ( ). Plant oils are classified into essential oils and fixed oils, where the latter is not volatile at room temperature ( ). Fixed plant oils are composed of triglycerides, free fatty acids, squalene tocopherols, sterols, stanols, phospholipids, waxes, and other components ( ). Certain oils are enriched in these various components and have been shown to improve barrier function, reduce inflammation via activation of peroxisome proliferator-activated receptors (PPARs), and/or provide nutritional benefits ( ). Plant oils vary by types of free fatty acids, including straight-chain saturated fatty acids (SFAs) and unsaturated fatty acids (UFAs), which have been shown to have differences in slowing transepidermal water loss and irritant skin response ( ). For example, linoleic acid, a long-chain fatty acid and a major lipid in sunflower seed oil, has been shown to maintain the water permeability barrier of the skin, and its metabolite has antiproliferative properties ( ). On the other hand, oleic acid, a short-chain fatty acid, causes barrier disruption and could induce dermatitis under continuous application ( ). Patients often choose these treatments given perceived lower risk of natural products ( ). Some studies have shown skin barrier benefits with sunflower seed oil and virgin coconut oil ( ). Additional natural oils for skin moisturization and barrier repair are discussed later in Alternative and Natural Moisturizers and in Chapter 26 .


Moisturizer ingredients


It is well established that moisturizers are the mainstay of treatment for AD and, as such, a tremendous variety of moisturizers at difference price points exist on the market. Increased understanding of the pathophysiology of AD has also led to newer moisturizers, which claim to replenish ceramides or natural moisturizing factor among other claims, though, for the most part, these claims have not been substantiated. Here we review the evidence behind a few of the primary ingredients in moisturizers. A summary of these moisturizer ingredients can be found in Table 22.2 .



Table 22.2

Moisturizer ingredients
































































Ingredient Mechanism of action in AD Summary of clinical data Notes
Lanolin Blocks transepidermal water loss (TEWL)


  • Few studies



  • Appears efficacious

Allergic contact dermatitis in patients with AD (2%–10%)
Petrolatum Blocks TEWL, increases stratum corneum thickness, reduces T-cell infiltrate, and upregulates antimicrobial peptides Improves overall disease severity and pruritus Cost-effective moisturizer
Ceramides Help replace lowered levels of epidermal ceramides found in AD to maintain skin integrity and prevent water loss


  • Effective steroid-sparing moisturizer



  • Unclear if significantly more beneficial than other moisturizer ingredients

Prescription version, EpiCeram, can be costly
Urea Absorbs water from the atmosphere to help hydrate the superficial layers of the stratum corneum Preparations with concentrations of 4%–10% may improve erythema, dryness, induration, and papules in AD Can cause stinging and irritation
Glycerol Absorbs water from the atmosphere to help hydrate the superficial layers of the stratum corneum


  • Improves xerosis, dryness, skin hydration, and scaling compared to vehicle



  • Decreased TEWL

Glycyrrhetinic acid Exerts antiinflammatory and antibacterial properties Improves erythema, edema, pruritus, and overall disease severity Found in licorice root
PEA, cannabinoids Exerts antiinflammatory and antipruritic properties by binding cannabinoid receptors in the skin (CB1/CB2) Improves erythema, pruritus, excoriation, scaling, lichenification dryness, and sleep quality PEA and cannabinoids tested for treatment of AD have minimal to no psychoactive properties
Sunflower seed oil


  • Rich in linoleic acid, which helps maintain barrier function in epidermis and modulates inflammation through its conversion to arachidonic acid



  • Improved stratum corneum integrity

Improves dryness, hydration, flaking, lichenification, and overall SCORAD Good alternative for parents/patients who would like a natural emollient option
Olive oil Causes reduction in stratum corneum integrity and induces irritation Increases skin hydration, but shown to cause erythema and irritation Not recommended as an emollient in AD
Virgin coconut oil


  • Improves skin barrier



  • Rich in lauric acid, which has antibacterial and antiinflammatory properties

Improves SCORAD, decreases TEWL and lower rates of colonization with Staphylococcus aureas Good alternative for parents/patients who would like a natural emollient option
Almond oil Antioxidant and antibacterial properties


  • Improves moisture and lipid content of skin



  • Reduces itch

Can lead to percutaneous sensitization

AD , Atopic dermatitis; PEA , palmitoylethanolamide.


Lanolin, a wax derived from the sebaceous glands of sheep, is a common ingredient that is either used as moisturizer alone or as an ingredient in many moisturizers. However, there are surprisingly few trials that have investigated the efficacy of lanolin as an emollient. In one study, 173 preterm infants who were treated with a 30% olive oil and 70% lanolin product twice daily for 4 weeks had improvement in their skin condition compared to a water-in-oil emollient cream ( ). The results of this study support the efficacy of lanolin as a moisturizer in AD. Allergic contact dermatitis to lanolin can occur in patients with AD. Contact allergy to lanolin occurs in approximately 2% to 10% of patients ( ).


Petrolatum is a semisolid hydrocarbon that is also found in many moisturizers and is often used as a moisturizer alone. In one trial, patients with AD were randomized to apply either Aquaphor healing ointment, for which the active ingredient is 41% petrolatum, EpiCeram, or Atopiclair three times daily for 3 weeks. Atopiclair contains glycyrrhetinic acid, which has antiinflammatory and antibacterial properties likely beneficial in the treatment of AD ( ). Glycyrrhetinic acid is further discussed in Alternative and Natural Moisturizers, later. EpiCeram is a prescription-only cream rich in ceramides used to treat AD ( ). EpiCeram is discussed in more detail in Prescription Emollients, later. In this study, application of Aquaphor healing ointment showed improvement in itch and disease severity that was comparable to the other moisturizers, leading the authors to not only conclude that the over-the-counter petrolatum-based moisturizer was as effective as the other moisturizers, but also 47 times more cost effective ( ). In another study, occlusion with petrolatum was compared with occlusion alone for 48 hours in nonlesional skin of 13 patients with AD and 39 healthy patients to investigate changes in the cutaneous molecular makeup and structure of the skin in AD. Skin biopsies of occluded areas obtained after 72 hours demonstrated a significant upregulation in antimicrobial peptides, as well as an increased stratum corneum thickness, and significantly reduced T-cell infiltrates in petrolatum-occluded skin compared to both control and occluded-only skin ( ). These results confirm that petrolatum is an effective treatment for AD. Studies also show that petrolatum is a far more cost-effective moisturizer compared to other common moisturizers, further supporting its use in the treatment of AD ( ).


Ceramides are lipids found in high concentration in cell membranes in the stratum corneum. Ceramides help to maintain the integrity of skin and prevent water loss ( ). Individuals with AD have been found to have lower epidermal levels of ceramides and pseudoceramides, thus ceramide precursor containing emollients have been developed to treat AD ( ). There have been several studies investigating the efficacy of such moisturizers in treating AD. In one study, investigators compared a 6-week course of twice-daily application of a nonprescription ceramide containing cream, Atobarrier cream, to a control nonceramide-containing cream. Patients also applied beclomethasone dipropionate 0.025% cream throughout the study. Those randomized to ceramide-containing cream used on average less topical steroid cream compared to the group randomized to apply a nonceramide-containing cream. As a result the investigators concluded that the ceramide-containing cream was a more effective steroid-sparing moisturizer ( ).


Urea is another ingredient frequently added to moisturizers. As mentioned earlier, it is a natural moisturizing factor that is produced by the degradation of filaggrin in the skin and absorbs water from the atmosphere to help hydrate the superficial layers of the stratum corneum ( ). Urea cream is available in different concentrations ranging from 1% to 50%. It acts as a humectant in lower concentrations but can be irritating at higher concentrations (>20%) where it is keratolytic ( ). In one study, researchers compared application of a 4% urea cream to a 20% glycerin cream and placebo (the vehicle of the glycerin cream) in patients with AD. Patients were instructed to use their designated cream as often as desired, with a minimum of once daily for 1 month. Investigators found that improvement in dryness was equivalent between the glycerin and urea cream, though there were no significant differences in the patients’ perception of dryness at the end of study between the three creams ( ). In another study, subjects preferred a 10% urea-containing cream to a vehicle cream in terms of improvement of erythema, dryness, induration, and papules ( ). Additionally, 5% urea cream has been shown to prolong the time between AD flares compared to no moisturizer ( ). However, it should be noted that in the studies mentioned, each moisturizer contained other ingredients, such as petrolatum in the glycerin cream, paraffinum liquidum in the 4% urea cream, and coconut oil and propylene glycol in the latter study, which confounds whether the results are due to the individual ingredients alone ( ).


Glycerol is an ingredient that is added to many moisturizers as a humectant. Consequently, it has been investigated as a treatment for AD. In the same study discussed earlier in which a 4% urea cream, a 20% glycerin cream, and placebo (the vehicle of the glycerin cream) were compared in patients with AD, the glycerin cream was additionally found to cause less smarting (a sharp, localized superficial sensation) on application compared to the urea cream ( ). In another study that included children ages 2 to 6 with AD, participants were randomized to apply a cream that contained glycerol and paraffin or the vehicle cream twice daily. At week 4, nonresponders were treated open-label with the emollient (the glycerol-containing cream) until week 12, whereas responders stopped treatment. Those who relapsed after stopping treatment at week 8 were then treated open-label on emollient until week 12. Treatment with the glycerol-containing cream led to a significantly greater improvement in the xerosis score of the SCORAD index, objective SCORAD, visual analogue score, and skin hydration ( ). These findings were further supported by a similar study in which a glycerol-containing cream was compared to placebo (vehicle alone) in individuals with AD in a twice-daily application for 4 weeks. Researchers found that areas treated with the glycerol cream had a greater change in SCORAD index, improvement in transepidermal water loss, and skin capacitance compared to vehicle alone ( ).


More often than looking for specific ingredients in moisturizers, parents of children with AD can be more focused on avoiding certain ingredients, the most common of which are parabens and phthalates, which are suspected to have endocrine-disrupting effects. Phthalates and parabens can be added to emollients purposefully or released from plastic containers into emollients unintentionally. In a cross-sectional study of more than 800 Danish children ages 4 to 9 years, researchers found that AD and self-reported frequent application of emollients, defined as daily or several times a week, was associated with increased urinary phthalate metabolite and paraben levels ( ). However, it is unclear whether this increase is the result of an increased exposure to phalates and paraben in children with AD or a result of their compromised skin barrier ( ). Furthermore, the difference in excretion of these ubiquitous environmental chemicals was modest, and any health implications of the increased phthalate and paraben exposure are unclear.


When selecting a moisturizer, consumers should also be cognizant of potential contact allergens commonly found in moisturizers, such as fragrances, synthetic dyes, and preservatives. These are discussed further in Chapter 7, Chapter 10 , regarding external factors.


Prescription emollients


EpiCeram is a ceramide-rich cream available by prescription only that was approved by the US Food and Drug Administration (FDA) in 2006 as a nonsteroidal lipid barrier emulsion for burning and itching associated with dry skin conditions, including AD, irritant contact dermatitis, radiation dermatitis, and other dermatoses ( ). In a pilot study, EpiCeram was found to be superior to Eucerin cream after a twice-daily 4-week application of each cream to different sites ( ). However, other studies have failed to show the superiority of EpiCeram compared to other moisturizers. In a trial in which patients with AD were randomized to receive either EpiCeram, Atopiclair, a cream containing glycyrrhetinic acid, or Aquaphor healing ointment, three times daily for 3 weeks, no significant difference was found in the improvement in itch and disease severity, as all groups showed improvement ( ). Moreover, a trial comparing the application of EpiCeram to a colloidal oatmeal–containing cream twice daily or as needed for 3 weeks in children of African descent with AD showed no significant difference in itch reduction or Eczema Area and Severity Index (EASI) score as both creams led to improvement ( ). These studies suggest that the benefit of EpiCeram compared to other nonprescription moisturizers may not outweigh its cost.


Mimyx cream is another moisturizer available by prescription containing palmitoylethanolamide (PEA), a synthetic cannabinoid. It was approved by the FDA in 2005 as a nonsteroidal treatment for AD as well as other skin conditions, including radiation dermatitis and allergic contact dermatitis. In a large observational, noncontrolled prospective cohort study involving 2456 participants, twice-daily application of Mimyx for 4 to 6 weeks led to significant improvement in physician assessment of symptoms (dryness, excoriation, pruritus, and erythema) and patient-reported symptoms (decreased loss of sleep related to itching), as well as decreased topical corticosteroid use ( ). In a head-to-head comparison of Mimyx and Eucerin cream applied twice daily in a split-body trial involving 74 patients with AD, more participants preferred Mimyx cream to Eucerin, and patients had a longer duration until flare at the site of Mimyx cream application compared to Eucerin cream ( ). Further studies are needed to determine efficacy of Mimyx compared to other nonprescription moisturizers.


Alternative and natural moisturizers


Many individuals and parents of children with AD seek alternative treatments for their condition ( ). As a result, knowledge of safe alternative moisturizers is essential for providers. A summary of these moisturizers can be found in Table 22.2 .


Sunflower seed oil has been proposed as a potential treatment for AD. It is rich in linoleic acid, which is needed to maintain normal barrier function in the epidermis and is thought to contribute to the modulation of inflammation through its conversion to arachidonic acid, a precursor to prostaglandin E2 ( ). In a study of 218 children with AD, twice-daily application for 30 days of a cream containing 2% sunflower oil distillate resulted in an improvement in dryness and flaking ( ). In another study, randomized 86 children with AD to receive either daily application for 21 days of desonide 0.05% cream or an every other daily application of desonide 0.05% cream alternating with an every other day application of an emollient containing 2% sunflower seed oil. Both groups had similar improvements in SCORAD, but the group treated with an emollient-containing sunflower seed oil had a greater improvement in lichenification ( ). These results indicate that sunflower seed oil may have a role as a steroid-sparing agent in AD ( ). While both were small trials, these results are promising, especially for patients and parents who prefer a natural option for a moisturizer.


Olive oil is produced by pressing olives and has also been studied as a treatment for AD. In a small study of 19 volunteers with and without a history of AD, twice-daily application of sunflower seed oil for 4 weeks preserved the stratum corneum integrity, did not cause erythema, and improved hydration ( ). In contrast, application of olive oil caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of AD ( ). Researchers randomized 115 neonates to receive either no oil, four drops of olive oil, or four drops of sunflower seed oil in a twice-daily application for 4 weeks. While there was no difference observed in transepidermal water loss, those in the olive oil group had significantly lower ordering of lipids in the stratum corneum than the no-oil group. The results of these studies demonstrate that olive oil is not a suitable emollient for the treatment of AD due to its ability to increase skin penetration and promote inflammation ( ).


Virgin coconut oil has been investigated as a potential natural plant-based emollient. It is produced by using a cold press method and retains more of its fatty acids compared to nonvirgin coconut oil, which is produced by boiling coconut meat, then heating and bleaching the oils to remove any impurities and the coconut fragrance ( ). Researchers compared the use of virgin coconut oil to mineral oil as topical emollients applied twice daily for 8 weeks in a study of 117 patients with AD; while both oils led to the improvement or decrease of SCORAD indices and decreased transepidermal water loss, virgin coconut oil was superior to mineral oil ( ). Moreover, virgin coconut oil has been shown to have antibacterial properties against Staphylococcus aureus ( ). Patients with AD treated with virgin coconut oil have lower rates of cutaneous S. aureus colonization ( ). However, these results were not corroborated in a separate study in which virgin coconut oil failed to demonstrate antibacterial activity against several bacteria, including S. aureus ( ). Regardless, virgin coconut oil can be used safely as an effective moisturizer in individuals with AD.


Almond oil is rich in phenolic acids and flavonoids and has been shown to have antioxidant and antibacterial properties ( ). As a result, almond oil has been trialed for the treatment of AD. In one study of an emollient-containing almond oil and lactic acid, researchers found that twice-daily application for 14 days in individuals with xerotic skin conditions, including AD, had significant reduction in itch and that skin moisture and lipid content were increased ( ). However, it should be noted that topical application of almond oil has been shown to lead to the percutaneous sensitization in children, so providers should be cognizant of this potential when selecting an emollient for patients ( ).


Glycyrrhetinic acid is an active component of the licorice root that has antiinflammatory and antibacterial properties and a low potential to cause allergic contact dermatitis ( ). In an aforementioned study included in the petrolatum section, researchers found that three times daily application for 3 weeks of Atopiclar cream, which contains glycyrrhetinic acid cream, led to improvement in itch and disease severity comparable to the other moisturizers in the study ( ). In another trial involving 60 individuals with AD, participants were randomized to apply a gel with either 1% or 2% glycyrrhetinic acid three times daily for 2 weeks. While both formulations led to improvement, the 2% gel led to superior improvement in erythema, edema, and pruritus ( ).


Cannabinoid (CBD) oils and products have recently been postulated as a potential novel treatment for AD. Cannabinoids are a large group of compounds that are similar in structure and biochemically to the main psychoactive compound found in Cannabis sativa , delta(9)-tetrahydrocannabinol (THC) ( ). Cannabinoids have antiinflammatory and antipruritic properties by binding to receptors found in the skin, which has led to the investigation of their potential treatment for AD ( ). It is important to note that cannabinoid compounds trialed for the treatment of AD have minimal to no psychoactive properties ( ). In a small trial of 20 patients with AD, psoriasis, and scars, investigators found that twice-daily application of a CBD oil–enriched ointment for 3 months led to improvement in AD, including itch severity ( ). As mentioned, Mimyx cream, a prescription-only cream containing PEA (a synthetic cannabinoid), has been shown to be effective in the treatment of AD, and in a small clinical trial, which included twice-daily application to one side of the body, it was shown to be more effective that Eucerin cream in treating AD ( ). In a larger observational study of 2456 participants, twice-daily application of a cream containing PEA (Physiogel A.I. Cream) to affected areas for 4 to 6 weeks led to improvement in eczema with improvement in erythema, pruritus, excoriation, scaling, lichenification dryness, and sleep quality ( ). However, in both studies it is unclear if the results are due to PEA or other ingredients contained in the respective PEA creams as they were not compared to vehicle. Further research is needed before moisturizers that contain CBD oil or cannabinoids can be recommended as effective treatment for AD.


In a more recent trend, patients and parents of children with AD have turned more often to complementary and alternative medicine (CAM) due to fears regarding topical corticosteroid use ( ). It is important to note, however, that herbal creams, particularly those obtained abroad, may covertly contain topical corticosteroids ( ). Parents should also be educated that natural ingredients have risks and may not be studied as well as prescribed medications. For instance, tea-tree and lavender oils have only recently been found to cause gynecomastia in prepubescent children ( ). Consequently, patients and families should be queried on the use of CAM products and counseled on the potential risk of both CAM and prescription medications.


Role of proactive use of moisturizers in prevention of eczema in infants


Children with filaggrin mutations have an increased transepidermal water loss and an increased risk of developing AD ( ). AD has a significant negative socioeconomic impact as well as adverse effects on quality of life. Primary prevention of AD through barrier repair could significantly reduce its burden. It is well established that daily use of moisturizer can improve xerosis, resolve pruritus quicker, and lengthen time to flare compared to no treatment ( ). More recently, several studies have demonstrated that use of emollients early in life could prevent AD ( ). performed a randomized controlled trial showing a significantly reduced risk of AD in infants with daily application of moisturizer during the first 32 weeks of life compared with the control group, who occasionally received a minimum amount of petroleum jelly. also showed a statistically significant protective effect of daily emollient on incidence of AD compared to the control group that did not use any emollients.


Among infants who are at high risk for AD based on family history of atopy (first-degree relative with family history of AD, allergic rhinitis, or asthma), those who received once-daily application of a ceramide and amino acid–containing emollient had significantly lower rates of AD diagnosis at 12 and 24 months of age, compared to those who used emollients of their choice on an as-needed basis for dry skin. This study suggests a protective effect of daily emollient with ceramides and amino acids ( ).


Summary


Moisturizers continue to be the mainstay for maintenance treatment of AD and show promise in disease prevention with proactive use. Though a variety of moisturizers exist, studies do not show that one moisturizer or moisturizer ingredient, natural or synthetic, is significantly better that another in patients with AD ( ). The cost effectiveness of moisturizers in reducing physician visits, health care utilization, and overall health care costs is indisputable ( ). Delivery system and parental desire for natural or alternative options should be key considerations for physicians recommending moisturizers to increase adherence to use.



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Jun 18, 2022 | Posted by in Dermatology | Comments Off on Skin Barrier Repair
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