ArticlePDF Available

Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself

Open AccessResearch Article
Allergy & Therapy
Eberting et al., J Allergy Ther 2014, 5:5
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
Keywords: Skin barrier repair; Ceramide; Phytosphingosine;
Cholesterol ester; 18-β Glycyrrhetinic acid; Niacinamide; pH; Calcium
chelation; Silicone; Paran
Abbreviations: ACD: Allergic Contact Dermatitis; AD: Atopic
Dermatitis; AHAs: Alpha Hydroxy Acids; GLU: Gluconolactone; ICD:
Irritant Contact Dermatitis; PPAR: Peroxisome Proliferator Activated
Receptor; TEWL: Transepidermal Water Loss
A compromised skin barrier plays a major role in many dermatoses
including irritant and allergic contact dermatitis, atopic dermatitis,
dry skin, aged skin, xerosis, rosacea, and acne [1–5]. Many of these
conditions share common defects in the skin barrier and an association
with inammation [4,6]. e knowledge we have regarding specic
lipid deciencies, pH aberration, inammation, irregular calcium
gradients, and susceptibility to contact sensitization can be leveraged to
address many aspects of the disrupted skin barrier. By addressing these
major points of vulnerability the skin’s inherent ability to heal itself can
be optimized for skin barrier repair.
Dermatitis is a term that includes irritant and allergic contact
dermatitis, atopic dermatitis and many other conditions that are
explained by skin barrier disruption and dysfunction. An association
with inammation and, in many cases, exacerbation from chemical
irritants and allergens is common (Figure 1). We will discuss the
commonalities of skin barrier compromise in dermatitis and other
forms of skin barrier disruption. We will discuss the role that skin
barrier dysfunction plays in these conditions, how to leverage the
strengths of the skin’s barrier repair pathways to stimulate skin barrier
repair, and the optimal features of skin barrier repair products.
ACD and ICD are associated with skin barrier defects that may be
a result of exogenous (the nature of an irritant or allergen, exposure
concentration, duration, chronicity, and other mechanical factors) and
endogenous factors [7]. In atopic dermatitis, there are several known
inherent skin barrier defects including specic lipid deciencies
and llagrin null mutations [8–10]. ough the specic etiology of
ACD, ICD and AD may be variable, all three conditions have similar
deciencies that drive the disease state. All three conditions are
initiated as a result of skin barrier defects that lead to the activation of
inammatory mediators such as IL-1 and TNFα [5,11,12]. ese pro-
inammatory mediators set into motion inammatory cascades in an
eort to induce reparative processes and restore skin barrier function
[13]. Unfortunately, the role of inammation may overshoot the skin
barrier repair mechanisms and result in dry, scaly, inamed, and
irritated skin.
For protection, the skin utilizes the following types of barriers:
physical, biochemical, redox, and immune [4]. e epidermis makes
up the physical barrier that is the rst line of defense, mostly attributed
to the protective eects of the stratum corneum which includes the
lipid bilayer, the acid mantle (one contributor to the acidic pH of the
epidermis), a calcium gradient which inuences desquamation and
cellular turnover and dierentiation of the epidermis, and the many
aspects of the cutaneous immune system [14]. e epidermis is able to
provide protection from solids, liquids, and gases in addition to warding
o attacks from viruses, bacteria, fungi, and other microbes [15].
Points of Vulnerability
A disrupted skin barrier has many points of vulnerability including
excessive water loss, slow/decient lipid production, an imbalance in
content and ratio of skin lipids, a dry skin barrier, an elevation of pH,
susceptibility to infection and inammation, and susceptibility to contact
sensitization [16–19]. ere have been many approaches to induce and
enhance skin barrier repair in chronic dermatitis. Some products have
focus on skin barrier protection or physiologic skin lipid replacement
or inammation. To eectively heal the skin barrier, trans-epidermal
water loss (TEWL) must be minimized and the skin must be protected
*Corresponding author: Cheryl Lee Eberting, 144 South Main St. Suite
300, Alpine, Utah 84004, USA Tel: 8017637107; Fax: 8017637607; E-mail:
Received May 16, 2013; Accepted August 11, 2014; Published August 18, 2014
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised
Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself. J Allergy Ther
5: 187. doi:10.4172/2155-6121.1000187
Copyright: © 2014 Eberting CL, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Skin barrier defects play a major role in many dermatoses including irritant and allergic contact dermatitis, atopic
dermatitis, dry skin, aged skin, xerosis, rosacea, acne and more. Skin barrier repair technology has heretofore
focused on physiologic skin lipid replacement and skin protection without addressing the myriad other areas of
compromise such as an elevated pH, balance of the microbiome, inammation, succeptibility to infection, aberrant
calcium gradients and the proclivity for contact sensitization. By changing the paradigm from physiologic skin lipid
supplementation to that of supplementing the epidermis with lipids that have recently been found to be particularly
decient from the disrupted skin barrier, and by simultaneously addressing the many facets of vulnerability, the skin
barrier can be effectively repaired. This model of advanced skin barrier repair wherein physiologic deciencies are
supplemented and/or augmented may be an effective method for restoring the ability of xerotic and dermatitic skin
to heal itself.
Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the
Skins Ability to Heal Itself
Cheryl Lee Eberting1*, Garrett Coman2 and Nicholas Blickenstaff2,3
1CherylLeeMD, Sensitive Skin Care, Alpine, Utah, USA
2,3University of Utah School of Medicine, Salt Lake City, Utah, USA
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 2 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
from further contact with irritants, allergens, and infectious organisms
[20]. Ideally, the skin pH would be optimized to encourage natural
ceramide production and to discourage the growth of pathogens while
encouraging the growth of a healthy microbiome [21,22]. Modulation
of the disrupted calcium gradient may restore appropriate levels of
desquamation [23]. Inammation must also be minimized while all
sensitizers, irritants and proinammatory mediators should be avoided
[24]. By addressing all of these points of vulnerability simultaneously,
the skin’s ability to itself may be optimized.
Skin Barrier Heal
Current medical and scientic literature provides insight to the
characteristics, features, and classes of ingredients able to address the
aforementioned vulnerabilities of the disrupted epidermis in chronic
Lipid Replacement
Close examination has revealed that much of the barrier protection
from the epidermis comes from stratum corneum lipids. e lipids are
arranged in a highly organized structure with controlled ratios. When
these ratios or structure are interrupted or unbalanced, barrier function
is compromised which gives microbes and allergens unencumbered
entrance to the deeper layers of the skin where inammatory pathways
are triggered [15,25].
Current therapeutic options include products which address skin
barrier repair by supplementing the skin with lipids in physiologic
ratios, while other products have employed behentrimonium
methosulfate, a cationic surfactant quaternary ammonium salt, as
part of a dynamic lipid delivery system [20,26]. Several specic lipid
deciencies have been elucidated in many forms of chronic dermatitis.
Phytosphingosine-containing ceramides such as ceramide 3 [27–29],
and possibly phytosphingosine itself are decient in conditions such
as dry skin, aged skin, and in atopic skin. In fact, as dryness levels of
the skin increase, so does the degree of phytosphingosine-containing
ceramide deciency [27,30,31]. Marked deciency in ceramide 3
(N-Acyl phytosphingosine) has also been well-documented in atopic
skin and correlated to increased TEWL [32].
Cholesterol esters are decient relative to cholesterol in xerotic skin
[33] and in SDS-induced dry skin (Figure 2). e overall sterol content
is preserved, but the ratio of cholesterol to cholesterol esters is increased
with an excess relative concentration of cholesterol [27,33]. When
SDS-induced dry skin treated with 1% cholesterol base was compared
to 1% cholesterol ester base, the cholesterol ester treated skin showed
improved conductance values while the cholesterol-treated skin did
not [34]. Atopic skin has also been shown to have abnormally elevated
levels of cholesterol [32]. Cholesterol esters are esteried to short,
medium, long, and very long chain fatty acids. Based on these studies
of chronic dermatitis conditions where the cholesterol:cholesterol ester
ratio has been shown to be elevated as compared to normal skin, it may
be optimal to supplement the skin with cholesterol esters rather than
with cholesterol as has traditionally been done by many physiologic
skin lipid replacement products. Indeed, it may not be necessary
and may possibly be less ecacious, to supplement, xerotic, atopic,
and SDS-induced dry skin with unesteried cholesterol, because the
cholesterol:cholesterol ester ratios in these conditions have been shown
to be abnormally elevated. (Figures 2-5) Of note however, cholesterol
itself was shown to aid barrier recovery in a tape stripping model in
aged skin, but not in young skin [35]. e aged skin in this study was
not controlled for ingestion of cholesterol lowering medications. Of
note, a disease of unknown etiology in aged skin, Grover’s disease, is
Figure 1: The epidermal barrier plays an important role in many dermatoses. Copyright of Cheryl Lee Eberting, M.D.
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 3 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
frequently beneted from cholesterol ester-containing skin barrier
repair products. Author’s experience, CLE (Figure 6).
Fatty acid deciency also contributes to a disrupted skin barrier.
Long chain fatty acids like palmitic (C16) and stearic acids (C18) are
known to be decient in atopic skin [36], but more recent studies have
shown a particular deciency in the very long chain fatty acids cerotic
(C26) montanic, (C28), and melissic (C30) acids [37]. Very long chain
fatty acids are naturally occuring in candelilla wax. Candelilla wax
is accessible, aordable, and has only one reported case of contact
sensitization [38].
e use of molecules with inherent anti-inammatory qualities has
been shown to be eective in many forms of skin barrier disruption
[39]. Glucocorticoids are most commonly prescribed for this purpose,
but non-glucocorticoid molecules also show anti-inammatory
qualities [40]. An over the counter petrolatum and lanolin-based
product that employs bisabolol as an anti-inammatory agent has
shown comparable ecacy to a prescription medical device cream [41].
Increasing numbers of contact sensitization to this product are being
reported in patients who are using it to treat dermatitis. ose who
are sensitized to bisabolol should be counseled to avoid any bisabolol-
containing products [42–44].
18β-Glycyrrhetinic acid exhibits corticosteroid-like anti-
inammatory, anti-allergic activity, and many other benets in
contact dermatitis. In vitro, glycyrrhetic acid is known to inhibit Δ4β-
reductase, an enzyme that competitively inactivates steroid hormones,
and 11β-hydroxysteroid dehydrogenase, an enzyme that deactivates
cortisol [45]. Inhibiting the metabolism of naturally occurring cortisol
enhances the body’s natural anti-inammatory capacity by potentiating
the activity of endogenous (and possibly even exogenously applied)
corticosteroids. When used in formulation by it or with a glucocorticoid,
glycyrrhetinic acid may augment and extend the eectiveness of
glucocorticoids, allowing the use of less-potent glucocorticoids and/or
a shorter course of treatment. is could limit overall glucocorticoid
exposure and associated side eects. When a metabolic precursor to
18β-glycyrrhetinic acid was given intraperitoneally, it suppressed
contact dermatitis in mice with higher ecacy than prednisolone.
When administered orally, it was ineective [46]; possibly highlighting
the necessity to deliver the active molecule directly to the area of
contact dermatitis. is same molecule is bactericidal to MRSA and has
anti-candidal eects [47,48], a benecial characteristic when treating
disrupted skin that particularly is susceptible to these organisms.
is molecule has skin brightening and lightening eects [49] and
thus may have additional benets for dermatitis associated with
Figure 2: Irritant “Lip-licker’s Dermatitis” Before and eight hours after
a single application of a preservative-free ointment that contains skin
barrier lipids, isostearyl isostearate, petrolatum, parafn wax and 18-β
glycyrrhetinic acid. Photos copyright of Cheryl Lee Eberting, M.D.
Figure 3: Atopic and allergic contact dermatitis due to lanolin. R. arm was
treated with 0.1% Triamcinolone ointment and L. arm was treated with
a preservative-free ointment that contains skin barrier lipids, isostearyl
isostearate, petrolatum, parafn wax and 18-β glycyrrhetinic acid. Photos
copyright of Cheryl Lee Eberting, M.D.
Figure 4: Severe Xerosis before and 30 seconds after application of a
preservative-free ointment that contains skin barrier lipids, isostearyl
isostearate, petrolatum, parafn wax 18-β glycyrrhetinic acid. Photos
copyright of Cheryl Lee Eberting, M.D.
Figure 5: Atopic Dermatitis before and after ten days twice daily application
of a hypoallergenic skin barrier repair cream that contains skin barrier
lipids, isostearyl isostearate, petrolatum, niacinamide, gluconolactone,
18-β glycyrrhetinic acid, gluconolactone and EDTA. Photos copyright of
Cheryl Lee Eberting, M.D.
Figure 6: Grover’s Disease before and after ten days of twice daily
application of a preservative-free ointment that contains skin barrier lipids,
isostearyl isostearate, petrolatum, parafn wax and 18-β glycyrrhetinic
acid. Photos copyright of Cheryl Lee Eberting, M.D.
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 4 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
post-inammatory hyperpigmentation in light and darker-skinned
individuals [49]. is molecule also has photoprotective benets. Aer
UV exposure, it reduced ROS, NF-KB, cytochrome c, and caspase 3
levels and inhibited hyaluronidase, possibly by inhibition of MMP1
activation by modulating NF-KB signaling [50]. Feeding mice with this
molecule prior to UVB radiation caused delays in tumor appearance,
multiplicity, and size [51]. is molecule also oers protection from
UVB radiation damage in humans [52].
Niacinamide, a B vitamin and possible Peroxisome Proliferator-
Activated Receptor (PPAR) ligand, has been shown to up regulate
llagrin and involucrin synthesis [53]. It has been proven eective
in the treatment of many forms of a disrupted skin barrier [54-
56]. Niacinamide also suppresses antigen-induced lymphocytic
transformation, an added benet that may minimize rates of
contact sensitization. Niacinamide also inhibits 3'-5' cyclic AMP
phosphodiesterase, and blocks the inammatory actions of iodides
[57]. Niacinamide increases the thickness of the epidermis [58]
while inducing de novo ceramide production through up-regulated
expression of serine palmitoyltransferase, the rate-limiting enzyme in
sphingolipid synthesis [59]. Ceramides are eective in blocking the
reduction, and even stimulating the synthesis, of collagen aer UV
irradiation [60]. Niacinamide shows improved facial wrinkle appearance
and tolerability compared to tretinoin [61]. Additionally, a niacinamide-
containing moisturizer applied with tretinoin therapy enhanced the
response to tretinoin, improved the stratum corneum, and decreased
tretinoin-associated side-eects [62]. Niacinamide is well tolerated
by the skin and provided signicant improvements versus control in
ne lines/wrinkles, hyperpigmentation spots, texture, red blotchiness,
elasticity, and skin yellowing versus an oil in water moisturizer control
[63,64]. Both niacinamide and 18-β glycyrrhetinic acid are optimal
anti-inammatory molecules for optimizing repair of the compromised
skin barrier.
pH Modulation
e pH of the epidermis becomes abnormally elevated in the setting
of dermatitis, infection, or from contact with alkaline substances such
as soap, bleach, solvents and even tap water [65]. e optimal pH of
the skin is between 4.6 and 5.6 which is ideal for ceramide production.
e skin lipid-producing enzymes β-glucocerebrosidase and acid
sphingomyelinase both have optimal levels of activity within this pH
range [21,22]. When the skin is overly alkaline, both serine protease-
mediated inactivation and metabolism of the β-glucocerebrosidase
and acid sphingomyelinase enzymes take place. Ceramide and lipid
production slows or comes to a halt [66]. e disrupted and alkaline
skin barrier is unable to support a healthy microbiome. Staphylococcus
aureus, Candida, and Propionibacterium acnes all grow more
eectively in an alkaline environment. Natural skin ora also become
compromised at an elevated pH [67,68]. is shi in the microbiome
of the skin may lead to a cycle of increased alkalinity, infection, and
a disrupted epidermal barrier. Additionally, as the pH reaches and
exceeds 5.7, there is inhibition of lamellar body secretion and corneo-
desmosome-constituent proteins can be degraded [66].
Acidication and even hyper-acidication of the epidermis has
been shown to decrease TEWL [69]. In fact, a common technique for
acidifying topical skin care formulations is the addition of acidic salts,
such as citric or lactic acids. ese acids are uncommon sensitizers,
but are prone to crystallization, which can result in irritation of the
skin. Alpha Hydroxyacids (AHAs) are also used to modulate the
pH of the skin and to enhance stratum corneum desquamation and
improve skin appearance. Unfortunately, AHAs result in sunburn cell
formation and increase the risk of skin cancer. e FDA now requires
a sun-burn warning on products containing AHAs [70]. A natural
polyhydroxy acid, Gluconolactone (GLU) is a free radical scavenger
and is a superior TEWL inhibitor when compared to several other acids
[69,71]. Additionally, GLU is known to enhance stratum corneum
desquamation, improve skin appearance, prevent skin irritation, and
is protective against UV radiation-induced elastin promoter activation
[71]. GLU treatment does not result in a signicant increase in sunburn
cells. UV absorption of GLU is low, so the UV protective eect must be
due to other mechanisms, such as its ability to function as a chelating
agent and free radical scavenger [71]. Additionally, GLU does not
crystalize and become an irritant to the skin as easily as citric and
lactic acid, making it an optimal epidermal acidier (CLE, unpublished
author observation).
Skin Barrier Protection
Eective transepidermal water loss inhibition
TEWL measurements can be used as a marker for skin barrier
integrity. Improvements in TEWL have been tied to improvements
in SCORAD scores in atopic dermatitis and are considered a marker
for stratum corneum integrity and hydration [20]. In addition to the
TEWL lowering benets of sphingolipid and cholesterol ester fractions,
TEWL inhibitors like petrolatum, dimethicone and other lipid fractions
are commonly used as skin protectants. Petrolatum is considered to be
the gold standard TEWL inhibitor [72]. In an eort to explore possible
alternatives to petrolatum, the author subjectively tested countless
plant-based petrolatum substitutes and was unable to nd one that
matched the characteristics of petrolatum including: hypoallergenicity,
hydration, taste, viscosity, melting temperature, and non-desiccating
eects on palmar and lip skin (as these areas tend to become most-
easily irritated/tight when they are desiccated). Petrolatum is a complex
semi-solid combination of paran wax, microcrystalline wax and
white mineral oil. Paran wax is even more impermeable to water than
petrolatum and when combined with petrolatum, is also an extremely
ecient TEWL inhibitor.
Dimethicone, a man-made polymer of the naturally occurring
element silica or silicon, is a very common skin protectant. Silicon
is naturally present in very small amounts in the human body and
may be associated with bone health [73]. Silicone and dimethicone
are manufactured by polymerizing silicon with carbon, hydrogen
and oxygen. e human body does not have the ability to metabolize
these polymers and in fact, when human monocytes were incubated
on dimethicone, they secreted variable levels of IL-1 beta, IL-6 and
TNF-alpha [24]. Furthermore, dimethicone has the potential to cause
an inammatory reaction when implanted [74]. When ve dierent
silicone materials were tested for skin sensitization potential, the murine
local lymph node assay showed weak to moderate skin sensitization
potential for four of the ve materials. Sensitization via cutaneous
contact or via injection or implantation is increasingly reported in the
literature. Reactions include allergic contact dermatitis, granuloma
formation, systemic sclerosis, and a psoriasiform eruption, among
others [75-78]. Rates of sensitization to silicone and silicone polymers
are increasing in both topical and implanted exposures [79-81].
While it is technically dicult to objectively study a skin protectant’s
ability to prevent penetration of allergens, irritants, and microbes
into the skin, there are three objective measures that may be used to
determine a product's or ingredient’s eectiveness in these areas: 1)
if a product or molecule has superior hydrophobicity; 2) lower water
solubility; and 3) a higher melting point than another, it may be more
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 5 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
dicult to wash o and therefore more ecient at preventing contact
with irritants, allergens and pathogens. Solvent permeability and
penetration characteristics are also to be considered.
Hydrophobicity is the measure of a product or ingredient’s degree of
repellency from a mass of water. Hydrophobic molecules are non-polar
and prefer other neutral molecules. e hydrophobicity of a skin barrier
product or ingredient can be objectively measured by determining the
contact angle, or the angle measured through the liquid where a liquid/
vapor interface meets a solid surface, of a drop of water applied to the
product in question. e contact angle is also directly correlated with a
molecule’s ability to adhere to a surface. While there are many variables
that can alter the contact angle of a molecule, hydrophobicity can be
subjectively measured by observing how easily water will bead and
roll o of the skin. A product that is very hydrophobic will have a high
contact angle, causing water to bead more eciently [82]. e higher
the contact angle, the more hydrophobic and adherent to the skin the
molecule is. e largest contact angles measured between water and
a smooth surface are with paran. Paran is a mixture of saturated
aliphatic hydrocarbons and is considered to be the most hydrophobic
water-repelling agent [83]. By comparison, to reach this range of
hydrophobicity, dimethicone must be applied to a smooth surface such
as glass and then must be baked on [84]. e contact angle of paran
is between 106 and 112 degrees and is dependent on the texture of
the surface and the purity of the paran [83]. Paran is composed of
non-polar alkane chains that, like the methyl groups in silicone uid,
have hydrophobic properties. ey interact very weakly with water
molecules so water stays in a drop and does not wet the paran wax.
Melting point
e melting points of skin protectant molecules may be another
indicator of their persistence on the skin aer washing and eectiveness.
e melting point of paran wax ranges from 47°C up to 65°C
depending on which grade of wax is used [85]. e melting point of
dimethicone is generally below 50°C (depending on which polymer is
used) [86].
Water solubility
Water solubility is an objective variable that can be used to assess the
eectiveness of a skin protectant. e water solubility of an ingredient
is an important indicator of its ability to protect the skin from water,
allergens and irritants. e water solubility of dimethicone is 33-77 g/l,
while paran wax is insoluble in water [87].
In addition to petrolatum, paran wax, and dimethicone, many
lipid-based TEWL inhibitors have also been investigated. ese lipids
include glyceryl monoisostearate, isopropyl isostearate, isostearyl
isostearate, cetyl alcohol, potassium cetyl phosphate, cetyl behenate and
behenic acid [88,89]. Isostearyl Isostearate has been proven to be the
most eective lipid-based TEWL inhibitor in these studies [88].
Calcium chelation
Forslin et al. were able to use a scanning nuclear microprobe to map
calcium distribution in cross sections of normal, atopic, and psoriatic
skin. In normal skin, calcium localizes to the uppermost granular layer
of the epidermis as well as to the basal and spinous layers. Forslind et
al. found that psoriatic and dry atopic skin had an epidermal calcium
gradient higher than normal skin [90]. Calcium is a necessary part of
the apoptotic process, and increased intracellular calcium may induce
the activation of endonuclease, transglutaminase, and morphological
changes [90]. Lee et. al., showed that removal of extracellular calcium
stimulates both lamellar body secretion and lipid synthesis, while also
blunting those responses when extracellular calcium concentration
was raised for hairless mice [91]. Calcium also seems to impair
corneodesmin hydrolysis with incomplete desquamation at alkaline pH
and without the presence of EDTA [23]. e nal step appears to be
inhibited by calcium, resulting in incomplete desquamation and residual
intercorneocyte cohesion in cases of skin barrier disruption. e skin’s
naturally occurring chelating agent is unknown, but calcium chelation
in a lower pH environment and in the presence of EDTA allows this
step to proceed [92]. erefore, weak calcium chelation may benet
a disrupted skin barrier by improving desquamation. Gluconolactone
and EDTA are both mild chelating agents that can safely be used in skin
barrier repair formulations to help optimize desquamation.
Susceptibility to contact sensitization
ose with llagrin null mutations have been found to have
increased rates of ACD particularly to lanolin and p-tert-butylphenol-
formaldehyde resin [93]. Research regarding the relevance of ACD in
atopic dermatitis is emerging [17,94,95]. ose with atopic dermatitis are
more likely to develop contact sensitization to certain chemicals relative
to non-atopics. Formaldehyde-releasers [18], cocamidopropylbetaine
[96] nickel, cobalt, chromium [16], Kathon CG, fragrance, neomycin
[97], and propolis (from beeswax but found in cough syrup, pills,
cosmetics, and vitamins) are advisably avoided in atopic dermatitis in
the setting of contact dermatitis as atopics are possibly more likely to
develop contact dermatitis [96].
Techniques that optimize skin barrier repair include skin
lipid replacement, pH modulation/optimization, the use of anti-
inammatory molecules, the use of mild calcium chelation, and the
overt avoidance of known skin irritants and allergens in formulation.
e eectiveness of a skin barrier repair and protectant product may
also be determined by its ability to adhere to the skin and its ability
to prevent the contact of water, irritants, allergens, and solvents from
coming in contact with the skin. ese qualities may be a function of a
product’s hydrophobicity, melting point, and water solubility.
A healthy skin barrier protects from pathogens, allergens, toxins,
and irritants. When the skin’s leading physical barrier, the stratum
corneum, is damaged as a result of disease or acute destruction, the
deeper layers of the epidermis and dermis are vulnerable to further
irritation and sensitization. Finding ways to protect the skin and repair
its natural barrier qualities is a major goal in reducing the incidence of
chronic dermatitis. Utilizing the large amount of existing and recent
data on dierent chemicals’ interaction with the stratum corneum
and the skin barrier to create novel products based on evidence-
based medicine is essential to improving treatment outcomes. Further
research and investigation into the skin’s barrier function and our
ability to enhance its protective qualities is paramount to the future
treatment of these patients.
1. Jarmuda S, McMahon F, Zaba R (2014) Correlation between serum reactivity
to Demodex-associated Bacillus oleronius proteins, and altered sebum levels
and Demodex populations in erythematotelangiectatic rosacea patients. J Med
Microbiol 63: 258-262. doi:10.1099/jmm.0.065136-0.
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 6 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
2. Purohit P, Chandar P, Vilinska A, Ananthapadmanabhan KP, Somasundaran
P (2014) Effect of mixed surfactants on stratum corneum: a drying stress and
Raman spectroscopy study. Int J Cosmet Sci .
3. Zouboulis CC, Jourdan E, Picardo M (2014) Acne is an inammatory disease
and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol
Venereol 28: 527-532.
4. Proksch E, Brasch J (2012) Abnormal epidermal barrier in the pathogenesis of
contact dermatitis. Clin Dermatol 30: 335-344.
5. Czarnowicki T, Krueger JG, Guttman-Yassky E2 (2014) Skin barrier and
immune dysregulation in atopic dermatitis: an evolving story with important
clinical implications. J Allergy Clin Immunol Pract 2: 371-379.
6. Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier.
Exp Dermatol 17: 1063-1072.
7. Lee HY, Stieger M, Yawalkar N, Kakeda M (2013) Cytokines and chemokines in
irritant contact dermatitis. Mediators Inamm 2013: 916497.
8. Kezic S, O'Regan GM, Lutter R, Jakasa I, Koster ES, et al. (2012) 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 laggrin deciency. J Allergy Clin Immunol 129: 1031-1039.
9. Vávrová K, Henkes D, Strüver K, Sochorová M, Skolová B, et al. (2014)
Filaggrin deciency leads to impaired lipid prole and altered acidication
pathways in a 3D skin construct. J Invest Dermatol 134: 746-753.
10. Agrawal R, Woodfolk JA (2014) Skin barrier defects in atopic dermatitis. Curr
Allergy Asthma Rep 14: 433.
11. Lisby S, Baadsgaard O (2006) Mechanisms of Irritant Contact Dermatitis. In:
Frosch P, Menné T, Lepoittevin J-P (Eds.) Contact Dermatitis. Springer Berlin-
Heidelberg, Germany
12. Smith HR, Basketter DA, McFadden JP (2002) Irritant dermatitis, irritancy and
its role in allergic contact dermatitis. Clin Exp Dermatol 27: 138-146.
13. Feingold KR, Schmuth M, Elias PM (2007) The regulation of permeability
barrier homeostasis. J Invest Dermatol 127: 1574-1576.
14. Watt FM (1989) Terminal differentiation of epidermal keratinocytes. Curr Opin
Cell Biol 1: 1107-1115.
15. Madison KC (2003) Barrier function of the skin: "la raison d'être" of the
epidermis. J Invest Dermatol 121: 231-241.
16. Malajian D, Belsito DV (2013) Cutaneous delayed-type hypersensitivity in
patients with atopic dermatitis. J Am Acad Dermatol 69: 232-237.
17. Fonacier LS, Aquino MR (2010) The role of contact allergy in atopic dermatitis.
Immunol Allergy Clin North Am 30: 337-350.
18. Shaughnessy CN, Malajian D, Belsito DV3 (2014) Cutaneous delayed-
type hypersensitivity in patients with atopic dermatitis: reactivity to topical
preservatives. J Am Acad Dermatol 70: 102-107.
19. Herro EM, Matiz C, Sullivan K, Hamann C, Jacob SE (2011) Frequency of
contact allergens in pediatric patients with atopic dermatitis. J Clin Aesthetic
Dermatol 4: 39-41
20. Chamlin SL, Kao J, Frieden IJ, Sheu MY, Fowler AJ, et al. (2002) Ceramide-
dominant barrier repair lipids alleviate childhood atopic dermatitis: changes
in barrier function provide a sensitive indicator of disease activity. J Am Acad
Dermatol 47: 198-208.
21. Holleran WM, Takagi Y, Imokawa G, Jackson S, Lee JM, et al. (1992) beta-
Glucocerebrosidase activity in murine epidermis: characterization and
localization in relation to differentiation. J Lipid Res 33: 1201-1209.
22. Bowser PA, Gray GM (1978) Sphingomyelinase in pig and human epidermis. J
Invest Dermatol 70: 331-335.
23. Egelrud T, Lundström A (1990) The dependence of detergent-induced cell
dissociation in non-palmo-plantar stratum corneum on endogenous proteolysis.
J Invest Dermatol 95: 456-459.
24. Anderson JM, Ziats NP, Azeez A, Brunstedt MR, Stack S, et al. (1995) Protein
adsorption and macrophage activation on polydimethylsiloxane and silicone
rubber. J Biomater Sci Polym Ed 7: 159-169.
25. Wollenberg A, Kraft S, Hanau D, Bieber T (1996) Immunomorphological and
ultrastructural characterization of Langerhans cells and a novel, inammatory
dendritic epidermal cell (IDEC) population in lesional skin of atopic eczema. J
Invest Dermatol 106: 446-453
26. Draelos ZD (2008) The effect of ceramide-containing skin care products on
eczema resolution duration. Cutis 81: 87-91.
27. Fulmer AW, Kramer GJ (1986) Stratum corneum lipid abnormalities in
surfactant-induced dry scaly skin. J Invest Dermatol 86: 598-602.
28. Wu JQ, Kilpatrick-Liverman L (2011) Characterizing the composition of
underarm and forearm skin using confocal raman spectroscopy. Int J Cosmet
Sci 33: 257-262.
29. Macheleidt O, Kaiser HW, Sandhoff K (2002) Deciency of epidermal protein-
bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol 119:
30. Van Overloop L, Declercq L, Maes D (2001) JOURNAL OF INVESTIGATIVE
DERMATOLOGY. In: Visual scaliness of human skin correlates to decreased
ceramide levels and decreased stratum corneum protease activity. (Edn.),
31. Chopart M, Castiel-Higounenc I, Arbey E (2001) Quantitative and qualitative
analysis of ceramides in the stratum corneum of normal and dry skin. Poster
Strat Corneum III Bâ
32. Di Nardo A, Wertz P, Giannetti A, Seidenari S (1998) Ceramide and cholesterol
composition of the skin of patients with atopic dermatitis. Acta Derm Venereol
78: 27-30.
33. Saint-Léger D, François AM, Lévêque JL, Stoudemayer TJ, Kligman AM, et al.
(1989) Stratum corneum lipids in skin xerosis. Dermatologica 178: 151-155.
34. Imokawa G, Akasaki S, Minematsu Y, Kawai M (1989) Importance of intercellular
lipids in water-retention properties of the stratum corneum: induction and
recovery study of surfactant dry skin. Arch Dermatol Res 281: 45-51.
35. Hamanaka S, Asagami C, Suzuki M, Inagaki F, Suzuki A (1989) Structure
determination of glucosyl beta 1-N-(omega-O-linoleoyl)-acylsphingosines of
human epidermis. J Biochem 105: 684-690.
36. Yamamoto A, Serizawa S, Ito M, Sato Y (1991) Stratum corneum lipid
abnormalities in atopic dermatitis. Arch Dermatol Res 283: 219-223.
37. van Smeden J, Janssens M, Kaye EC, Caspers PJ, Lavrijsen AP, et al. (2014)
The importance of free fatty acid chain length for the skin barrier function in
atopic eczema patients. Exp Dermatol 23: 45-52.
38. Barrientos N, Abajo P, Moreno de Vega M, Domínguez J (2013) Contact cheilitis
caused by candelilla wax contained in lipstick. Contact Dermatitis 69: 126-127.
39. Hoare C, Li Wan Po A, Williams H (2000) Systematic review of treatments for
atopic eczema. Health Technol Assess 4: 1-191.
40. Saeedi M, Morteza-Semnani K, Ghoreishi MR (2003) The treatment of atopic
dermatitis with licorice gel. J Dermatolog Treat 14: 153-157.
41. Miller DW, Koch SB, Yentzer BA (2011) 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 JDD 10: 531-537
42. Jacob SE, Matiz C, Herro EM (2011) Compositae-associated allergic contact
dermatitis from bisabolol. Dermatitis 22: 102-105.
43. Jacob SE, Hsu JW (2010) Reactions to Aquaphor: is bisabolol the culprit?
Pediatr Dermatol 27: 103-104.
44. Russell K, Jacob SE (2010) Bisabolol. Dermatitis 21: 57-58.
45. Hikino H (1985) Recent research on oriental medicinal plants. Econ Med Plant
Res H Wagner Hiroshi Hikino Norman R Farnsworth
46. Bradley PR (1992) British Herbal Compendium. Volume 1. A Handbook of
Scientic Information on Widely Used Plant Drugs. Companion to Volume 1 of
the British Herbal Pharmacopoeia. British Herbal Medicine Association
47. Messier C, Grenier D (2011) Effect of licorice compounds licochalcone A,
glabridin and glycyrrhizic acid on growth and virulence properties of Candida
albicans. Mycoses 54: e801-806.
48. Long DR, Mead J, Hendricks JM, Hardy ME, Voyich JM (2013) 18ß-Glycyrrhetinic
acid inhibits methicillin-resistant Staphylococcus aureus survival and
attenuates virulence gene expression. Antimicrob Agents Chemother 57: 241-
247. doi:10.1128/AAC.01023-12.
49. Fisk WA, Agbai O2, Lev-Tov HA3, Sivamani RK4 (2014) The use of botanically
derived agents for hyperpigmentation: a systematic review. J Am Acad
Dermatol 70: 352-365.
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 7 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
50. Afnan Q, Adil MD, Nissar-Ul A (2012) Glycyrrhizic acid (GA), a triterpenoid
saponin glycoside alleviates ultraviolet-B irradiation-induced photoaging in
human dermal broblasts. Phytomedicine Int J Phytother Phytopharm 19: 658-
664. doi:10.1016/j.phymed.2012.03.007.
51. Cherng J-M, Tsai K-D, Yu Y-W, Lin J-C (2011) Molecular mechanisms underlying
chemopreventive activities of glycyrrhizic acid against UVB-radiation-induced
carcinogenesis in SKH-1 hairless mouse epidermis. Radiat Res 176: 177-186
52. Rossi T, Benassi L, Magnoni C, Ruberto AI, Coppi A, et al. (2005) Effects of
glycyrrhizin on UVB-irradiated melanoma cells. In Vivo 19: 319-322.
53. Oblong J, Bissett D, Ritter J, Kurtz K, Schnicker M (2001) Niacinamide
stimulates collagen synthesis from human dermal broblasts and differentiation
marker in normal human epidermal keratinocytes: potential of niacinamide
to normalize aged skin cells to correct homeostatic balance. In: 59th Annual
Meeting American Academy of Dermatology, Washington
54. Soma Y, Kashima M, Imaizumi A, Takahama H, Kawakami T, et al. (2005)
Moisturizing effects of topical nicotinamide on atopic dry skin. Int J Dermatol
44: 197-202.
55. Niren NM, Torok HM (2006) The Nicomide Improvement in Clinical Outcomes
Study (NICOS): results of an 8-week trial. Cutis 77: 17-28.
56. Draelos ZD, Ertel K, Berge C (2005) Niacinamide-containing facial moisturizer
improves skin barrier and benets subjects with rosacea. Cutis 76: 135-141.
57. Shalita AR, Smith JG, Parish LC, Sofman MS, Chalker DK (1995) Topical
nicotinamide compared with clindamycin gel in the treatment of inammatory
acne vulgaris. Int J Dermatol 34: 434-437.
58. Mohammed D, Crowther JM, Matts PJ, Hadgraft J, Lane ME. Inuence
of niacinamide containing formulations on the molecular and biophysical
properties of the stratum corneum. Int J Pharm 441: 192-201. doi:10.1016/j.
59. Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S (2000) Nicotinamide increases
biosynthesis of ceramides as well as other stratum corneum lipids to improve
the epidermal permeability barrier. Br J Dermatol 143: 524-531.
60. Grether-Beck S, Mühlberg K, Brenden H, Krutmann J. [Topical application of
vitamins, phytosterols and ceramides. Protection against increased expression
of interstital collagenase and reduced collagen-I expression after single
exposure to UVA irradiation]. Hautarzt Z Für Dermatol Venerol Verwandte Geb.
2008;59(7):557-562. doi:10.1007/s00105-008-1554-7.
61. Fu JJJ, Hillebrand GG, Raleigh P, et al. A randomized, controlled comparative
study of the wrinkle reduction benets of a cosmetic niacinamide/peptide/retinyl
propionate product regimen vs. a prescription 0.02% tretinoin product regimen.
Br J Dermatol. 2010;162(3):647-654. doi:10.1111/j.1365-2133.2009.09436.x.
62. Draelos ZD, Ertel KD, Berge CA (2006) Facilitating facial retinization through
barrier improvement. Cutis 78: 275-281.
63. Bissett DL, Miyamoto K, Sun P, Li J, Berge CA (2004) Topical niacinamide
reduces yellowing, wrinkling, red blotchiness, and hyperpigmented spots in
aging facial skin. Int J Cosmet Sci 26: 231-238.
64. Bissett DL, Oblong JE, Berge CA (2005) Niacinamide: A B vitamin that improves
aging facial skin appearance. Dermatol Surg 31: 860-865.
65. Kawai E, Kohno Y, Ogawa K, Sakuma K, Yoshikawa N, Aso D (2005) Can
inorganic powders provide any biological benet in stratum corneum, while
residing on skin surface. IFSCC Mag 5: 269–275
66. Hachem J-P, Roelandt T, Schürer N (2010) Acute acidication of stratum
corneum membrane domains using polyhydroxyl acids improves lipid
processing and inhibits degradation of corneodesmosomes. J Invest Dermatol
130: 500-510. doi:10.1038/jid.2009.249.
67. Korting HC, Kober M, Mueller M, Braun-Falco O (1987) Inuence of repeated
washings with soap and synthetic detergents on pH and resident ora of the skin
of forehead and forearm. Results of a cross-over trial in health probationers.
Acta Derm Venereol 67: 41-47.
68. Korting H, Greiner K, Hubner K, Hamm G (1991) Changes in skin pH and
resident ora by washing with synthetic detergent preparations at pH 5.5 and
8.5. J Soc Cosmet Chem 42: 147–158
69. Berardesca E, Distante F, Vignoli GP, Oresajo C, Green B (1997) Alpha
hydroxyacids modulate stratum corneum barrier function. Br J Dermatol 137:
70. US Food and Drug Administration. Guidance for Industry: Labeling for
Cosmetics Containing Alpha Hydroxy Acids.
71. Bernstein EF, Brown DB, Schwartz MD, Kaidbey K, Ksenzenko SM (2004) The
polyhydroxy acid gluconolactone protects against ultraviolet radiation in an in
vitro model of cutaneous photoaging. Dermatol Surg Off Publ Am Soc Dermatol
Surg Al. 30: 189-195
72. Patzelt A, Lademann J, Richter H (2012) In vivo investigations on the penetration
of various oils and their inuence on the skin barrier. Skin Res Technol Off J Int
Soc Bioeng Skin ISBS Int Soc Digit Imaging Skin ISDIS Int Soc Skin Imaging
ISSI 18: 364-369. doi:10.1111/j.1600-0846.2011.00578.x.
73. Jugdaohsingh R (2007) Silicon and bone health. J Nutr Health Aging 11: 99-
74. Bélanger MC, Marois Y (2001) Hemocompatibility, biocompatibility, inammatory
and in vivo studies of primary reference materials low-density polyethylene and
polydimethylsiloxane: a review. J Biomed Mater Res 58: 467-477
75. Dospinescu P, Jones GT, Basu N (2013) Environmental risk factors in systemic
sclerosis. Curr Opin Rheumatol 25: 179-183.
76. Schmutz JL, Trechot P (2013) [Psoriaform eruption and silicone injection in a
male HIV patient]. Ann Dermatol Venereol 140: 494.
77. Petry T, Bosch A, Coste X, Dupuis V, Eigler D et al. (2012) An assessment
of the skin sensitisation hazard of a group of polyfunctional silicones using
a weight of evidence approach. Regul Toxicol Pharmacol RTP 64: 305-314.
78. Chen Y-C, Chen M-L, Chiu Y-M (2011) A case of mimicking angioedema: chin
silicone granulomatous reaction spreading all over the face after receiving liquid
silicone injection forty years previously. Chin Med J (Engl) 124: 1747-1750
79. Oprea ML, Schnöring H, Sachweh JS, Ott H, Biertz J, et al. (2009) Allergy to
pacemaker silicone compounds: recognition and surgical management. Ann
Thorac Surg 87: 1275-1277.
80. Rubio A, Ponvert C, Goulet O, Scheinmann P, de Blic J (2009) Allergic and
nonallergic hypersensitivity reactions to silicone: a report of one case. Allergy
64: 1555.
81. Williams PJ, King C, Arslanian V (2012) Allergic contact dermatitis caused by a
cell phone cover. Australas J Dermatol 53: 76-77.
82. Yuan Y, Lee TR. Contact angle and wetting properties. In: Surface Science
Techniques. Springer; 2013:3–34
83. Ray BR, Bartell FE (1953) Hysteresis of contact angle of water on parafn.
Effect of surface roughness and of purity of parafn. J Colloid Sci 8: 214-223.
84. Noll W. Chemistry and Technology of Silicones. Elsevier; 1968.
85. Parafn wax (8002-74-2).
86. Material: PDMS (polydimethylsiloxane)
87. Seager SL, Slabaugh M. Alkane reactions. Chem Today Gen Org Biochem.364.
88. Pennick G, Harrison S, Jones D, Rawlings AV (2010) Superior effect of
isostearyl isostearate on improvement in stratum corneum water permeability
barrier function as examined by the plastic occlusion stress test. Int J Cosmet
Sci 32: 304-312. doi:10.1111/j.1468-2494.2010.00604.x.
89. Pennick G, Chavan B, Summers B, Rawlings AV (2012) The effect of an
amphiphilic self-assembled lipid lamellar phase on the relief of dry skin. Int J
Cosmet Sci 34: 567-574.
90. Forslind B, Werner-Linde Y, Lindberg M, Pallon J (1999) Elemental analysis
mirrors epidermal differentiation. Acta Derm Venereol 79: 12-17.
91. Lee SH, Elias PM, Feingold KR, Mauro T (1994) A role for ions in barrier
recovery after acute perturbation. J Invest Dermatol 102: 976-979.
92. Simon M, Jonca N, Guerrin M, Haftek M, Bernard D, et al. (2001) Rened
characterization of corneodesmosin proteolysis during terminal differentiation
of human epidermis and its relationship to desquamation. J Biol Chem 276:
93. Landeck L, Visser M, Skudlik C, Brans R, Kezic S, et al. (2014) No remarkable
differences in rates of sensitization to common type I and IV allergens between
FLG loss-of-function mutation carriers and wild-type subjects. Contact
Dermatitis 70: 27-34.
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal Itself.
J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Page 8 of 8
J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 • Issue 5 • 1000187
94. Landeck L, Schalock P, Baden L, González E (2011) Contact sensitization
pattern in 172 atopic subjects. Int J Dermatol 50: 806-810.
95. Heine G, Schnuch A, Uter W, Worm M, Information Network of Departments
of Dermatology (IVDK), German Contact Dermatitis Research Group (DKG)
(2006) Type-IV sensitization prole of individuals with atopic eczema: results
from the Information Network of Departments of Dermatology (IVDK) and the
German Contact Dermatitis Research Group (DKG). Allergy. 61: 611-616.
96. Czarnobilska E, Obtulowicz K, Dyga W, Spiewak R (2011) The most important
contact sensitizers in Polish children and adolescents with atopy and chronic
recurrent eczema as detected with the extended European Baseline Series.
Pediatr Allergy Immunol Off Publ Eur Soc Pediatr Allergy Immunol. 22: 252-
256. doi:10.1111/j.1399-3038.2010.01075.x.
97. Schena D, Papagrigoraki A, Tessari G, Peroni A, Sabbadini C, et al. (2012)
Allergic contact dermatitis in children with and without atopic dermatitis.
Dermatitis 23: 275-280.
Citation: Eberting CL, Coman G, Blickenstaff N (2014) Repairing a
Compromised Skin Barrier in Dermatitis: Leveraging the Skin’s Ability to Heal
Itself. J Allergy Ther 5: 187. doi:10.4172/2155-6121.1000187
Submit your next manuscript and get advantages of OMICS
Group submissions
Unique features:
User friendly/feasible website-translation of your paper to 50 world’s leading languages
Audio Version of published paper
Digital articles to share and explore
Special features:
350 Open Access Journals
30,000 editorial team
21 days rapid review process
Quality and quick editorial, review and publication processing
Indexing at PubMed (partial), Scopus, EBSCO, Index Copernicus and Google Scholar etc
Sharing Option: Social Networking Enabled
Authors, Reviewers and Editors rewarded with online Scientic Credits
Better discount for your subsequent articles
Submit your manuscript at:
... Нарушения барьерной функции кожи могут быть связаны с: действием экзогенных факторов -механических, химических и физических, что обычно соответствует диагнозу «простой ирритантный контактный дерматит»; алиментарных, таких как недостаток в пище незаменимых жирных кислот омега-3 и омега-6, которые необходимы для синтеза «защитных» липидов; ятрогенных (глюкокортикостероиды, цитостатики, ингибиторы кальциневрина и косметические процедуры) [20,23,26]; действием эндогенных факторов -приобретенные иммунологические нарушения в организме, приводящие как к резкому снижению реактивности организма, так и к дисрегуляции различных ее звеньев [27]; соматические заболевания (сахарный диабет, гипотиреоз); возрастные периоды (новорожденные и лица старше 60 лет) [3,[28][29][30]; генетическими факторами, например, при псориазе, ихтиозах и атопическом дерматите [2,5,28,30]. Основные патогенетические звенья нарушений барьерной функции кожи включают нарушения защитных механизмов: ...
... физических -разрушение межклеточных контактов; снижение пролиферации клеток эпидермиса и дермы; нарушение терминальной дифференцировки кератиноцитов; уменьшение количества НУФ; изменение состава и структуры компонентов внеклеточного матрикса дермы; проблемы кровоснабжения дермы [2,3,5,28,30]; химико-биологических -медленная или недостаточная выработка липидов, дисбаланс в их содержании и соотношении, повышение рН, уменьшение количества НУФ; уменьшение выработки АМП; изменение активности эндогенных протеаз [7,11]; защиты от УФ -снижение НУФ; уменьшение содержания 7-дегидрохолестерола в кератиноцитах [2, 3, 6]; иммунологических -иммуносупрессия; аутоиммунные реакции; нарушения врожденного и адаптивного звеньев иммунного ответа; изменения в микробиоме кожи [12,27]. Следствием действия данных патогенетических механизмов является нарушение проницаемости кожи, проявляющееся как в трансэпидермальной потере воды (ТЭПВ), так и в восприимчивости кожи к инфекции, воспалению и контактной сенсибилизации [26,28]. ...
Full-text available
The main function of the skin is to protect the body from negative environmental influences. The physical barrier permeability is mainly represented by the stratum corneum; however, other layers of the epidermis and the dermis are its important components. The mechanical strength of the skin is provided by intercellular contacts in the epidermis and structural proteins of the dermis. The chemical-biological barrier includes lipids, acids, natural moisturizing factor and antimicrobial peptides. Mucosal immunity system creates a barrier against infection. The microflora of healthy skin counteracts its colonization by pathogens and is vital for its immune functions. Physiological processes in the skin are closely related. A violation in one of them often leads to the formation of a whole cascade of pathological reactions affecting all the links of its protection. Vitamins A, D and E are used to correct impaired barrier function of the skin. The most pronounced effect of vitamin A (retinol palmitate) is the proliferation of epidermal cells and synthesis of extracellular matrix structures of the dermis; vitamin D (cholecalciferol) regulation of differentiation and suppression of excessive proliferation of keratinocytes; vitamin E (tocopherol acetate) antioxidant effect. The combined use of these vitamins in the composition of RadevitActive ointment affects all the main elements of the protection of the epidermis and dermis: strengthens the mechanical strength of the stratum corneum and dermis, stabilizes chemical and physical protection, including prevents the penetration of foreign substances and microorganisms, reduces transepidermal loss of water and electrolytes, reduces the damaging effect of UV, increases antimicrobial and antioxidant protection.
... A compromised skin barrier frequently results in symptoms like severe itching, redness of the skin, but also in a dry skin, skin defects and pain. Because of these symptoms, adequate treatment to restore the barrier function is strongly recommended [4,5]. ...
... However, there are several age-related histological skin changes influencing skin composition and quality. These involve loss of subcutaneous fat, decrease of collagen and elastin formation with loss of dermal thickness, decrease of number and function of sweat glands, decreased sebum production, flattening of the dermal-epidermal ridges, increase of skin surface pH, increase of transepidermal water loss and reduced skin moisture [4][5][6][7]. ...
... A compromised skin barrier frequently results in symptoms like severe itching, redness of the skin, but also in a dry skin, skin defects and pain. Because of these symptoms, adequate treatment to restore the barrier function is strongly recommended [4,5]. ...
... However, there are several age-related histological skin changes influencing skin composition and quality. These involve loss of subcutaneous fat, decrease of collagen and elastin formation with loss of dermal thickness, decrease of number and function of sweat glands, decreased sebum production, flattening of the dermal-epidermal ridges, increase of skin surface pH, increase of transepidermal water loss and reduced skin moisture [4][5][6][7]. ...
... 14 The compromised skin barrier leads to excess loss of water, increased pH, susceptibility to infection, and accelerated penetration of antigens and microbes, which cause contact sensitization and inflammation. 15 Without repair to the compromised barrier, clinical signs of barrier disruption become more evident and progressive, which presents as increased desquamation, clumping of corneocytes leading to scaling, flaking, and decrease in elasticity, therefore causing cracking of the skin and hyperkeratosis as a hallmark of increased keratinocyte proliferation. 16 These can cause the skin to be cosmetically disfigured or unappealing, which creates social stigma, increased anxiety, and social distress in affected individuals. ...
... 14 The compromised skin barrier leads to excess loss of water, increased pH, susceptibility to infection, and accelerated penetration of antigens and microbes, which cause contact sensitization and inflammation. 15 Without repair to the compromised barrier, clinical signs of barrier disruption become more evident and progressive, which presents as increased desquamation, clumping of corneocytes leading to scaling, flaking, and decrease in elasticity, therefore causing cracking of the skin and hyperkeratosis as a hallmark of increased keratinocyte proliferation. 16 These can cause the skin to be cosmetically disfigured or unappealing, which creates social stigma, increased anxiety, and social distress in affected individuals. ...
Full-text available
The most important function of the stratum corneum (SC), the uppermost layer of the human epidermis, is the formation of the epidermal permeability barrier. Lipids, particularly ceramides, cholesterol, and free fatty acids, together form lamellar membranes in the extracellular spaces of the SC that limit the loss of water and electrolytes. In addition to preventing water and electrolyte loss, the SC as a permeability barrier prevents the entry of harmful irritants, allergens, and microorganisms into the skin. Disruption of the epidermal barrier leads to skin that is irritated, more reactive, and more sensitive than normal skin. SC thickness, lipid profile, and barrier function vary with different ethnic groups, which is also reflected the differences in prevalence and manifestation of diverse skin conditions related to the skin barrier function such as atopic dermatitis and sensitive skin. In addition to these compromised skin barrier related conditions, we are just now starting to understand the direct and indirect impact of COVID-19 on the skin and how current preventative measures are contributing to skin barrier disorders. Our understanding of various approaches for restoration of skin barrier, especially the role of topically applied mixtures of cholesterol, ceramides, and essential/nonessential free fatty acids (FFAs) allows for the strengthening of the compromised skin barrier and alleviation of symptoms and discomfort associated with skin barrier disorders. Ceramide containing products on the market are commonly available and offer protection and reparative benefits to the skin barrier. J Drugs Dermatol. 20(4 Suppl):17-22. doi:10.36849/JDD.S589C.
... The increase of proteolytic enzymes with the decrease of ceramide in the skin are genetic defects that lead to trans-epidermal water loss, resulting in skin dryness, and pruritus. This barrier breakdown creates a portal of entry for pathogens, allergens, and toxins causing inflammation and/or infection [31,32]. As the quality of life of patients with AD is seriously affected; it is mandatory to seek reasonable treatment options. ...
Background: Atopic dermatitis is a chronic inflammatory skin disease that remarkably affects the quality-of-life of patients. Chamomile oil is used to treat skin inflammations. We evaluated the efficacy of chamomile oil and nanoemulgel formulations as a natural alternative therapeutic option for atopic dermatitis. Research design and methods. Formulations were developed comprising chamomile oil: olive oil (1:1), Tween 20/80 or Gelucire 44/14 as surfactant-cosurfactant mixtures, propylene glycol (10%w/w), water and hydroxypropyl methylcellulose (3%w/w). In-vitro physicochemical characterization, stability testing and in-vivo assessment of inflammatory biomarkers and histopathological examination of skin lesions were conducted in rats induced with atopic dermatitis. Results: Nanoemulgels G1 and X1 which displayed the smallest particle size of 137.5±2.04 and 207.1±5.44 nm, good homogeneity and high zeta-potential values of –26.4 and –32.7 mV were selected as the optimized emulgel. Nanoemulgels were non-irritating of pH value 5.56, readily spreadable and were physically stable following 10 heating-cooling cycles. Treatment with nanoemulgels showed a two-fold decrease in duration of skin healing and no spongiosis compared to chamomile oil. Levels of biomarkers were reduced after topical application of both nanoemulgels and chamomile oil. Conclusion: Nanoemulgels are a potential cost effective, safe topical carrier system for chamomile in treating atopic dermatitis.
... The TEWL, an indicator of skin barrier function, did not show any statistically significant changes during treatment with the study cream. Research has shown that acidification of the epidermis decreases TEWL, 43 and the stability of TEWL in our study could be due to a lack of change in skin pH. Nevertheless, there was a nonsignificant decrease of TEWL after four weeks of treatment in our patients, which suggests an improvement in the barrier permeability. ...
Full-text available
Background: Contact dermatitis is a common skin condition observed by dermatologists, presenting a burden on healthcare systems. Recently, there has been a trend in producing skin-identical topical preparations for the repair of skin. However, there is a limited number of experimental studies to assess the safety and efficacy of this products. Objective: This study assessed the clinical efficacy and safety of a skin-identical ceramide complex cream (Dermalex Repair Contact Eczema; Omega Pharma, Nazareth, Belgium) in the treatment of contact dermatitis. Design: This was a Phase II, before-after trial. Setting: This study was conducted at the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL) at Tehran University of Medical Sciences in Tehran, Iran. Participants: Fifteen patients with contact dermatitis (8 men and 7 women) between the ages of 25 and 62 years (median age: 36.4 years) were enrolled in this study. Measurements: Changes were assessed using six skin biophysical parameters (transepidermal water loss [TEWL], stratum corneum [SC] hydration, melanin index, erythema index, skin pH, and skin friction), Physician Global Assessment (PGA) score, and Three-Item Severity (TIS) score at baseline, Week 2, and Week 4 of the study. Results: Skin hydration and TIS showed a statistically significant improvement after treatment with study cream (p=0.023 and p=0.007, respectively). Although the reduction in TEWL was not significant, a slight decrease was observed at Week 4. Conclusions: The skin-identical ceramide complex cream improved contact dermatitis with a decrease in TIS and an increase in skin hydration, implying a repair of the skin barrier.
... Pimecrolimus inhibits Th1 and Th2 cytokine production, reduces antigen-presenting capacity of DC's characterized by airway limitation which does not fully remit in addition to symptoms of chronic bronchitis and emphysema [87] . Subcutaneous allergen injections have been the main approach for the administration of immunotherapy, however, this has subsequently been extended to sublingual administration, which offers several advantages compared with the subcutaneous route, the treatment with the anti-IgE and omalizumab is not effective on symptoms or eosinophil counts in biopsyisease of the nasal mucosa caused by immunoglobulin-E mediated reaction to various allergens [88][89][90] . ...
Full-text available
The following study throws a light upon the inflammation causing allergies and diseases such as asthma, Allergic Rhinitis, respiratory syncytial virus, airway hyper-reactivity and their treatment for inflammation and symptoms seducing drugs and medication such as Allergen specific immunotherapy, Allergen Immunotherapy, Topical Corticosteroids, NAC anti-oxidant in left pulmonary artery ligation (LPAL), Subcutaneous immunotherapy (SIT), corticosteroid (ICS) and miraculous effects of these potential therapeutic treatments in affecting changes in metabolism of the patient etc.
... 1,2) Disruption of the skin barrier results in not only several pathological conditions, such as atopic dermatitis, but also cosmetic problems, such as dry skin, aged skin, and acne. 2,3) The most important skin barrier function is the physical barrier. This barrier is maintained by the lipid bilayer in the stratum corneum, the acidic pH of the epidermis, a calcium gradient that influences cellular turnover and differentiation of the epidermis, and tight junctions (TJs) formed by cells of the granular layer. ...
Tight junctions (TJs) of the epidermis play an important role in maintaining the epidermal barrier. TJ breakdown is associated with skin problems, such as wrinkles and transepidermal water loss (TEWL). Clinical studies have reported that topical nifedipine is effective in reducing the depth of wrinkles and improving TEWL. However, it remains unknown whether nifedipine influences the TJ function in the epidermis. In the present study, we investigated the effect of nifedipine on epidermal barrier dysfunction in normal human epidermal keratinocytes (NHEKs) treated with sodium caprate (C10), a TJ inhibitor. Nifedipine reversed the C10-decreased transepithelial electrical resistance values as a measure of disruption of the epidermal barrier. Immunocytochemical observations revealed that nifedipine improved the C10-induced irregular arrangement of claudin-1, a key protein in TJs. Taken together, these findings suggest that nifedipine prevents epidermal barrier dysfunction, at least in part, by reconstituting the irregular claudin-1 localization at TJs in C10-treated NHEKs.
Full-text available
The review summarizes information about the main causes and pathogenesis of xerosis cutis as one of the conditions indicating a violation of the epidermal barrier. Xerosis cutis is a clinical sign of a decrease in the amount and/or quality of lipids and/or hydrophilic substances in the stratum corneum of the epidermis. The modern approach to the treatment of dermatoses accompanied by violations of the epidermal barrier includes basic moisturizers. Urea not only moisturizes the skin. It is involved in the regulation of barrier function and antimicrobial protection. It is a low-molecular regulator of protein synthesis in keratinocytes, such as filaggrin, loricrin, involucrin and transglutaminase 1, cathelicidin, beta-defensin-2, water and urea carrier proteins into the cell, as well as proteins that promote the synthesis of intercellular matrix lipids. The main dermatotropic pharmacological effects of urea (hydration of the epidermis, strengthening of the barrier function of the skin, keratolytic effect, increased penetration of drugs into the skin) have been used in dermatological practice for many years. External agents with urea are used to treat skin diseases accompanied by dryness and excessive keratinization, to correct the deformation of nail plates of various genesis, to facilitate the local penetration of medicines. The use of topical UrocrEM5, UrocrEM10, Uroderm ointments containing 5%, 10% and 30% urea, respectively, is effective and safe.
Full-text available
Lichtgealterte Haut ist durch eine Rarefizierung dermaler Kollagenfasern charakterisiert, die Folge eines vermehrten Abbaus und einer verminderten Neusynthese ist. Der vermehrte Abbau resultiert aus einer gesteigerten Expression von Matrixmetalloproteinasen (MMPs). An der De-novo-Synthese entscheidend beteiligt sind die Kollagengene COL1A1 und COL1A2, deren Expression in lichtgealterter oder UV-bestrahlter Haut vermindert ist. In der Studie wurde untersucht, ob die topische Behandlung mit Vitaminen, Phytosterolen und Ceramiden zu einer Hemmung der UV-induzierten Aufregulation der MMP-1-Expression und zu einer Hemmung der UV-induzierten Herabregulation und/oder zu einer Aufregulation der COL1A1- und COL1A2-Expression führt. Hierzu wurden 10 hautgesunde Probanden für 10 Tage vergleichend mit einem Jojobaöl-haltigen Basispräparat, diesem Basispräparat plus Vitaminen, diesem Basispräparat plus Phytosterolen und Ceramiden und diesem Basispräparat plus Vitaminen, Phytosterolen und Ceramiden behandelt. Alle 4 Testpräparate verhinderten die UV-induzierte Aufregulation der MMP-1-Expression signifikant. Das Basispräparat hemmte weder mit noch ohne Vitaminzusatz die UV-induzierte Herabregulation der COL1A1- und COL1A2-Expression, hierfür war die Zugabe von Ceramiden und Phytosterolen erforderlich. Die Ergebnisse zeigen, dass Phytosterole und Ceramide geeignete ,,Actives“ sind, die zur Hemmung der nach UV-Bestrahlung eingeschränkten Kollagensynthese und zu ihrer Stimulation angewendet werden können. Diese Inhaltsstoffe könnten daher eine Ergänzung von Anti-Aging-Produkten darstellen.
Irritant contact dermatitis is an eczematous reaction in the skin of external origin. In contrast to allergic contact dermatitis, no eliciting allergens can be identified. The spectrum of irritant reactions is broad and includes: subjective irritant response, acute irritant contact dermatitis, chronic irritant contact dermatitis, and chemical burns (Table 4.1). Irritant contact dermatitis is in its acute form characterised by erythema, infiltration, and vesiculation. In its more chronic form, dryness, fissuring, and hyperkeratosis are more pronounced. Despite these hallmarks, the clinical manifestation of the skin lesions developing, following contact with different irritants, varies. Factors that may influence the outcome of skin contact with irritants can be divided into: (1) exogenous, such as structural and chemical properties of the irritant, exposure to other irritants, and environmental conditions (temperature, humidity); and (2) endogenous, such as the body region that is exposed (the scrotum is much more sensitive than, e.g. the upper back), age [1], race [2], and pre-existing skin disease. Moreover, in addition to the capacity of different irritants to induce clinically different reactions, it has been reported that marked interindividual variation in threshold for eliciting clinical irritant reaction in skin is present [3].
The experimental results show that when very thin films of purified paraffin were formed in vacuum by volatilization on smooth glass surfaces and water drops were placed upon them, the advancing and the receding contact angles were sensibly the same, 112[deg]; that is, hysteresis effects did not exist on these very thin and very smooth surfaces.Measurable hysteresis effects from 5[deg] to 35[deg] were found for less smooth films, and coatings of appreciable thickness formed in vacuum, in nitrogen, or in air, whether from a melt or by volatilization.The magnitude of the hysteresis effects appeared to be closely associated with the microscopic roughness of the surfaces, the roughness adding to the magnitude of the advancing angle but subtracting from the receding angle to the same degree, so that the average angle remained the same for paraffin films of different roughnesses but of the same degree of purification. The average contact angle for purified paraffin was slightly larger than the average angle for unpurified paraffin. Peer Reviewed
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance in S. aureus strains has created a need for alternative therapies to treat disease. A component of the licorice root Glycyrrhiza spp., 18β-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores the in vitro and in vivo effects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 μM. Upon exposure of S. aureus to sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, including saeR and hla. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression of saeR and hla genes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression in S. aureus both in vitro and in vivo.
Synopsis Objective Stratum corneum (SC) lipids are known to play an important role in barrier properties of skin by maintaining the optimal hydration levels. The disruption of SC lipids by cleanser surfactants is believed to lead to dry skin damage which can be a precursor to other skin disorders. The purpose of this study is to investigate the effects of commonly used anionic and zwitterionic surfactants sodium lauryl ether sulphate (SLES) and cocoamidopropyl betaine (CAPB) on the generation of drying stresses in SC and the role played by lipids. Methods Stratum corneum separated from pig skin was treated with various surfactants (SDS, SLES and CAPB) their mixtures and solvents. The tensile response to these treatments was measured by using a dynamic mechanical thermal analyzer. A Raman spectroscopy study of the treated samples was performed to investigate the effects of lipid modification (lipid chain conformational order and lipid removal) on stress generation in SC. ResultsThe effects of commonly used anionic and zwitterionic surfactants on the generation of drying stresses in SC were studied. Although known to be milder in comparison with SDS, both SLES and CAPB generated high drying stresses individually. In mixtures, SLES-CAPB at 4:1 ratio leads to lower drying stress as compared to water alone. A Raman spectroscopic study of surfactant-treated SC shows changes in lipid chain conformational order as well as a decrease in lipid-protein ratio in SC. A chloroform-methanol 2:1 treatment leads to the highest drying stress as well delipidization of SC. Conclusion The results show a correlation between generation of drying stress in SC and extent of lipid modification. We propose that the changes in lipid conformational order and removal of lipid components affect the stress relaxation properties of SC leading to high drying stresses.