1. The Role of Topical Moisturizers in Managing Compromised Skin
This presentation will look at the differences between infant and adult skin, provide an overview of the skin barrier and the importance of lipids and proper pH to maintaining a healthy skin barrier in skin diseases such as eczema – one of the primary skin conditions you see in your practice. We’ll then look at the role topical moisturizers can play in managing compromised skin through an example of the effectiveness of a product with oat lipids and ceramides in managing eczema symptoms.

2. Skin Function Natural protective barrier from physical injury
pathogenic microbes
chemical agents
UV radiation
extreme temperatures
Helps to restrict fluid and water loss
Sensory perception: temperature, pressure, touch and pain
Temperature regulation of the body
Skin protects everything that lies beneath it.  It acts as a cushion against insult to the body. 
It alerts the body of danger (through sensation) and provides a barrier which prevents infection, the loss of water from the body, and penetration of irritants and allergens.
Skin barrier function resides primarily within the stratum corneum (SC), the top layer of the epidermis. 
1. Irving V: Caring for and protecting the skin of pre-term neonates. J Wound Care 2001, 10:253-6.
2. Nikolovski J, Stamatas GN, Kollias N, Wiegand BC: Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life. J Invest Dermatol 2008, 128:

3. Bricks & Mortar
The skin is a complex active organ. One way to understand the barrier function of the stratum corneum is to think of it as a brick wall. The corneocytes (made of tough protein) form the bricks and between these a double layer of lipids (fatty materials) and water make up the mortar. Some lipids have a hard crystal-like structure and are impermeable to water. Others lipids do not have this structure and they allow water to percolate through. So, the barrier is semi-permeable.

4. Infant vs Adult Skin
Infant skin is different from adult in structure, function, and composition.  The stratum corneum (SC) of infant skin (on the left) and adult skin (on the right) is hydrated (small blue spheres) under normal conditions. Infant SC is more hydrated but also loses water at higher rates than adult SC.
The Infant Skin Barrier: Can We Preserve, Protect, and Enhance the Barrier? Lorena S. Telofski, A. PeterMorello III, M. CatherineMack Correa, and Georgios N. Stamatas; Dermatology Research and Practice Volume 2012, Article ID , 18 pages doi: /2012/198789

5. Structure SKIN PARAMETER ADULT INFANT Surface Microrelief lines
Less dense
More dense
Cell size
Corneocytes (SC)
Larger
Smaller
Granular Keratinocytes
Larger Less dense
More densely packed
Thickness
Stratum corneum
Thicker
~ 10µm
Thinner
~ 7µm
Epidermis
Thinner (-20% vs adult)
Dermal structure
Dermal papillae (density, size, morphology)
Less homogenous
More homogenous
Distinction between papillary and reticular dermis
Present
Absent
↗ water retention
↗ permeability
When we look at the structure of infant skin, the differences in the skin surface, cell size, thickness of the stratum corneum and dermal structure contribute to increased water retention and increased permeability in infant skin.
L.S Telosfski et al. Dermatology Research and Practice, vol 2012
G.N. Stamatas et al. International Journal of Cosmetic Science, 2011, 33, 17-24

6. Higher (in older infants)
Composition
SKIN PARAMETER
ADULT
INFANT
Water content
Stratum corneum
Lower
Higher (in older infants)
Drier at birth
Inter-personal variability
Higher
NMF
Natural moisturizing factor concentration
Surface lipids
Sebum
(7-10 month-old infant)
Collagen
Fiber density
Higher (young adult)
Melanin
Density
↗ skin hydration
↗ dryness
↘ hydro-lipid film protection
↘ UV protection
NMF: Natural moisturizing factor
However, the composition of infant skin including lower levels of natural moisturizing factor, and surface lipids contribute to dryness and decreased hydro-lipid protection and lower melanin levels lead to decreased UV protection.
L.S Telosfski et al. Dermatology Research and Practice, vol 2012
G.N. Stamatas et al. International Journal of Cosmetic Science, 2011, 33, 17-24

7. Function SKIN PARAMETER ADULT INFANT Protective barrier
Skin barrier function
Competent
Competent – still maturing
TEWL
Trans-epidermal water loss
Lower
Higher
Water handling
Rate of water absorption
Rate of water desorption
Cell proliferation
Turnover rate pH
Surface pH
More alkaline
(newborn only)
↗ water evaporation
↗ potential infections
TEWL: Trans-epidermal water loss
As a result, the rate of transepidermal water loss, water absorption, water desorption and cell turnover rate are higher in infants than in adults.
In summary, a baby's skin has a less developed epidermal barrier than adults and thus is more prone to damage. Recent research suggests that the stratum corneum of infants becomes 'adult-like' only after one year of life organ.
L.S Telosfski et al. Dermatology Research and Practice, vol 2012
G.N. Stamatas et al. International Journal of Cosmetic Science, 2011, 33, 17-24

8. Role of skin lipids
Now let’s look at the role of lipids. The lipid barrier is our first line of defense against the outside world. There are three types of lipids that combine to form the lipid barrier. They are ceramides, cholesterol and fatty acid esters. Each of these lipids has the ability to both attract and repel water. When working together these lipids alternate between bringing moisture in and keeping moisture out of the skin.
During childhood, skin disorders that are characterized by skin barrier dysfunction are common. Compromised skin barrier integrity is thought to be critical to the early onset and severity of AD, which is often accompanied by dry, scaly skin that is lipid deficient.

9. Importance of proper pH
Babies are born with skin pH close to neutral:
Adults have a much more acidic skin with pH values:
Acidic skin pH affects several activities:
Maturation and maintenance of the epidermal permeability barrier
Control of the desquamation process
Regulation of bacterial proliferation on the skin
Another factor to consider is the pH of the skin.
Babies are born with skin pH close to neutral: Adults have a much more acidic skin with pH values: Acidic skin pH affects several activities including
Maturation and maintenance of the epidermal permeability barrier
Control of the desquamation process
Regulation of bacterial proliferation on the skin
Eczema can cause skin surface pH to shift from normal to 7.3 to 7.4. This is a 1,000- fold increase in the pH shift, as pH is measured in logarithmic function. The entire skin surface pH is increased on skin of people with atopic dermatitis. An increased skin pH contributes to Staphylococcus aureus colonization, which can play a role in the genesis of atopic dermatitis.
 Gil Yosipovitch, M.D., and Judy Hu, M.D., The Importance of Skin pH. The Dermatologist, Vol 11, Issue 3, March 2003.
G.N. Stamatas et al. International Journal of Cosmetic Science, 2011, 33, 17-24

10. The clinical outcome of this type of response is atopy and asthma.
Now let’s look at the defective epidermal barrier in individuals with atopic dermatitis.
The epidermal barrier is found in the lower layers of the stratum corneum, and is composed of differentiated keratinocytes, termed corneocytes (beige rectangles), held together with corneodesmosomes (purple spheres). The hyperactivity of degradatory proteases (red hexagons) found within the epidermis, and contributed to by exogenous proteases (red hexagons), from house dust mites and Staphylococcus aureus, for example, facilitate the cleavage of the corneodesmosome junctions. This is just one event in the breakdown of the epidermal barrier that permits the penetration of allergens. Dendritic cells (DC) (green) found in the dermis take up and present these allergens (red stars) to helper T (TH) cells and recruit CD4 þ T cells (blue). Activated DC and IL-4, expressed by CD4 þ T cells, promote TH1 to TH2 switching with the subsequent release of pro-inflammatory cytokines and elevation of IgE levels
The clinical outcome of this type of response is atopy and asthma.
Epidermal Barrier Dysfunction in Atopic Dermatitis. Michael J. Cork, et al., Journal of Investigative Dermatology (2009) Vol 129

11. Healthy Barrier Function
Appropriately formulated emollients can preserve, protect, and enhance the skin barrier by supplying the SC with water and lipids and by helping to inhibit water loss. Emollients also supply lipids to epidermal keratinocytes, where they can be transported through the cell membrane and metabolized within the cell. Keratinocytes can then use lipids (including linoleic acid) as components to build a functional epidermal barrier.
L.S Telosfski et al. Dermatology Research and Practice, vol 2012
G.N. Stamatas et al. International Journal of Cosmetic Science, 2011, 33, 17-24

12. Oats in Skincare

13. Attributes of Oats in Skin Care
Let’s take a look at the attributes of colloidal oatmeal in the benefits they provide in helping to replenish and maintain barrier integrity.
Colloidal oatmeal is produced as a fine powder from the grinding and processing of whole oat grains. In addition to polysaccharides, which comprise the largest portion (60%–64%), colloidal oatmeal contains approximately 12.5% to 18% proteins and 3% to 9% lipids. Colloidal oatmeal also contains vitamins A, E, and B; antioxidants (phenolic compounds), anti-inflammatories (prostaglandin inhibitors), saponins, which serve as cleansers and preservatives; and enzymes (superoxide dismutase).
Kurtz ES, WalloW. Colloidal oatmeal: history, chemistry and clinical properties. J Drugs Dermatol ;6(2):
Cerio R, Dohil M, Jeanine D, Magina S, Mahé E, Stratigos AJ. Mechanism of action and clinical benefits of colloidal oatmeal for dermatologic practice. J Drugs Dermatol. 2010;(9):
Zhou M, Robards K, Glennie-Holmes M, Helliwell S. Oat lipids. J Am Oil Chem Soc. 1999;76:

14. pH LEVEL BEFORE TREATMENT
Buffering Capacity of Colloidal Oatmeal Restores the pH of Damaged Skin to Within the Normal Range
ECZEMA (N=33)
(N=33)
WINTER ITCH
SENILE PRURITUS
pH LEVEL IMMEDIATELY AFTER TREATMENT WITH COLLOIDAL OATMEAL
(N=16)
SENILE SKIN
(N=14) PH
pH LEVEL BEFORE TREATMENT
pH measured on forearm
NORMAL pH RANGE
The buffering capacity of colloidal oatmeal restores the pH of damaged skin to within the normal range.
Grais ML. Role of colloidal oatmeal in dermatologic treatment of the aged. AMA Arch Derm Syphilol. 1953;68(4):
Grais M. AMA Arch Derm Syphilol.1953;68(4):

15. Avenanthramides
We will focus on 2 main components—avenanthramides and oat lipids.
Much of the recognized benefit of oats results from its phenolic components. The most active of these compounds are the avenanthramides.
Dimberg LH, Theander O, Lingert H. Avenanthramides – a group of phenolic antioxidants in oats. Cereal Chemistry. 1993;70:

16. Avenanthramides vs other oat fractions
The avenanthramide fraction is the most effective oat component in reducing UV-induced redness 24 hours after dermal application
Avenanthramides
Flavonoids
Saponins 50
100
150
200
250
Avenanthramides may be of particular value in restoring the cutaneous barrier and helping reduce symptoms of atopic dermatitis.
In a skin erythema model, separated oat fractions were tested to further explore the functional properties of various oat components. Compared to saponins, flavonoids, sugars and amino acids, ash, proteins, and lipids, the avenanthramide fraction most effectively reduce UV-induced erythema 24 hours after skin application.
Vollhardt J, Fielder DA, Redmont MJ. Identification and cosmetic application of powerful anti-irritant constituents of oat grain. XXI IFSCC International Congress 2000, Berlin. Proceedings;
% of redness attenuation per gram after UV irradiation. Measure 24h after application
Separated oat fractions tested in a skin erythema model/Patients received 1.5 MED of UVB/Products applied 24 hours after irradiation/Clinical erythema evaluation 24 hours after product application
Vollhardt J, Fielder DA, Redmont MJ. Identification and cosmetic application of powerful anti-irritant constituents of oat grain. XXI IFSCC International Congress 2000, Berlin. Proceedings;

17. IL-8 Release (pg/mL) from Keratinocytes Avenanthramide (μg/mL)
Avenanthramides: Inhibition of Markers Related to Topical Skin Irritation
IL-8 Release (pg/mL) from Keratinocytes
150
180
210
240
270
Unstimulated
Avenanthramide (μg/mL)
Stimulated 1 10
100
In preclinical models, avenanthramides were found to decrease the stimulated release of IL-8 from human epidermal keratinocytes. Significant reductions of IL-8 release were obtained with 1, 10, and 100 μg/mL avenanthramides (P<0.05).
Wallo W, Nebus J, Nystrand G, Southall M. Agents with adjunctive potential in atopic dermatitis. Poster presented at: 65th Annual AAD. February 2-6, 2007, Washington, DC.
IL-8=interleukin-8.
Wallo W, et al. Poster presented at: 65th annual meeting of the AAD. February 2-6, 2007; Washington, DC.

18. Oat Lipids
Now we will turn to the composition of oat lipids.

19. Composition of Oat Lipids
Total lipid content of oats: from 2%–11.8% dry weight
Triglycerides
Phospholipids
Lecithin
Glycolipids
Free fatty acids
Oleic, Linoleic, Palmitic, Stearic
Oats contain a mixture of lipids, including phospholipids that are also found in the outer bilayer of the skin. Thus, oat lipids can help to restore the lipids that are depleted in dry or eczematous skin.
Zhou M, et al. J American Oil Chem Soc. 1999;76(2):

20. Oat Oil Reduces TEWL Compared to Control Sites
Whole oat oil reduces Transepidermal Water Loss (TEWL) by as much as 56%.
Potter RC, Castro JM, Moffatt LC, inventors; Nature, Inc, assignee. Oat oil compositions with useful cosmetic and dermatological properties. US Patent April 15, 1997.
TEWL=transepidermal water loss.
Potter RC et al. US Patent April 15, 1997.

21. Whole Oat Oil Lipid Class Composition
When fractionated, whole oat oil contains a mixture of lipids, falling into 4 main lipid classes: triglycerides, diacylglycerol, phospholipids, and free fatty acids, with smaller amounts of sterols, phosphatidylethanolamine, and other compounds.
Southall M, Pappas A, Nystrand G, Nebus J. Oat oil improves the skin barrier. The Dermatologist. September 2012(suppl):1-4.
Southall M, et al. The Dermatologist. September 2012 (suppl):1-4.

22. Clinical Evidence Supporting the Use of Oat-Containing Products in Skin Care
In this section we will discuss the clinical evidence supporting the use of oat-containing products in skin care.

23. Percent Mean Reduction in Water Loss
Colloidal Oatmeal Cream vs Rx Barrier Emulsion for Improving Skin Barrier in Moderate-to-Severe Dry Skin
Colloidal Oatmeal Cream
Rx Skin Barrier Emulsion
-15
Regression Period
-20
Percent Mean Reduction in Water Loss
-25
-30
Colloidal oatmeal also improves the skin barrier in moderate-to-severe dry skin.
In a clinical study of 27 female subjects, use of colloidal oatmeal cream (blue line) showed significant improvements in TEWL values indicating an improvement in the skin barrier comparable to an prescription barrier emulsion. TEWL is a key feature of barrier dysfunction.
Nebus J, Nystrand G, Schmalenberg K, et al. Comparing the effectiveness of an oatmeal cream versus a prescription device cream in improving skin moisturization and barrier function in moderate to severe dry skin. J Am Acad Dermatol. 2011;64:AB71.
-35 1 4 7 9
Days
Nebus J, et al. J Am Acad Dermatol. 2011;64:AB71.

24. Effectiveness of a colloidal oat lotion vs vehicle for the relief of dry, itchy skin
A 28 day randomized, doubleblind, bilateral controlled clinical study was conducted to
compare the efficacy of an oatmeal containing lotion against its own vehicle. Thirty (30) female subjects with bilateral moderate to severe dryness and bilateral mild to moderate itch took part in the study. Subjects were assigned two test products, one to be used on the right leg and the other on the left leg. Test sites on the lower legs of each of the subjects were graded for scaling, overall dryness and intensity, duration and frequency of itch at baseline (Visit 1, Day 0), after 21 days of treatment (Visit 2) and after a one week regression without treatment (Visit 3, Day 28).
The oatmeal containing lotion demonstrated significantly better hydration as measured by the SkiCon both at 21 days and again at 28 days (after the one week regression).
A Randomized, Double-Blind Bilateral Controlled Study to Evaluate the Effectiveness of an Oatmeal Containing Lotion vs Vehicle for the Relief of Dry, Itchy Skin, data on file.

25. Colloidal Oatmeal Bath
Colloidal Oatmeal Bath* in the Treatment of Dry and Sensitive Skin in Atopic Dermatitis
4-week, investigator-blinded, crossover study (N=25)
1.2
50%
1.0
0.8
Itching
Grading Score
0.6
Burning
0.4
67%
A colloidal oatmeal bath has been shown to reduce itching and burning in the treatment of dry and sensitive atopic skin.
In this 4-week, investigator-blinded, crossover study, 25 subjects (males and females) 12 years or older with a history of atopy and moderately dry legs. Subjects soaked legs for 20 minutes per day for 7 days with an oilated colloidal oatmeal bath. There was a 1-week washout period, followed by crossover to other treatment for 7 days.
This graph shows the 50% reduction in itching and 67% reduction in burning with the colloidal oatmeal bath.
Wallo W, Nebus J, Nystrand G, Southall M. Agents with adjunctive potential in atopic dermatitis. Poster presented at: 65th Annual AAD. February 2–6, 2007, Washington, DC.
0.2
Before
After
*Colloidal oatmeal with ceramides and dexpanthenol.
Wallo W, et al. Poster presented at: 65th annual meeting of the AAD; February 2–6, 2007; Washington DC.

26. Dermatologist Assessment: EASI Composite Score (ages 12–60 years)
Daily Oat-based Skin Care Regimen for Atopic Skin: EASI Composite Score
Dermatologist Assessment: EASI Composite Score (ages 12–60 years) 6 2 8
EASI (Mean)
Baseline
Week 8
Week 2
Week 4 4 *
In addition, dermatologist evaluations showed a statistically significant (P<0.001) improvement in EASI composite scores at Weeks 2, 4 and 8.
Fowler JF, Nebus J, Wallo W, Eichenfield LF. Colloidal oatmeal formulations as adjunct treatments in atopic dermatitis. J Drugs Dermatol. 2012;11(7):
EASI=eczema area and severity index .
*Significant improvement (P<0.001).
Fowler JF, et al. J Drugs Dermatol. 2012;11(7):

27. Evaluating the Tolerance and Safety of a Colloidal Oat and Ceramide containing Moisturizing Cream and Oatmeal containing Moisturizing Wash in Babies and Children with Atopic Dermatitis
Standardized Infant’s/Children’s Dermatology Quality of Life Indices for Dermatitis demonstrated that the improvements in skin condition after 4 weeks of using the colloidal oatmeal regimen resulted in overall improvements in Quality of Life.
Nebus J, Wallo W, Eichenfeld L, MD; Poster presented at the 34th Annual Meeting of the Society of Pediatric Dermatology. July 2008

28. Assessment of a Colloidal Oatmeal and Ceramide containing Moisturizing Cream through a multi-centric clinical study on infants, children and adults with AD*
Regular use of colloidal oatmeal cream was also shown to have a corticosteroid-sparing effect as the condition improved. After 4 weeks of using colloidal oatmeal cream, measured corticosteroid use declined by 39.4% and 63% of patients felt that they used less corticoids/ immunomodulators.
*Assessment of AVEENO® Eczema Therapy Moisturizing Cream through a multi-centric clinical study on infants, children and adults with Atopic dermatitis. (n=71 patients in total aged 6 months to adult; topical steroid data based on n=19 patients who previously used topical steroids during the washout period).

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