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CONTENTS
Introduction: the chicken or the egg?
. ............................................................................................................
P.3
Unraveling the importance of the epidermal barrier
P.4
A. The permeability barrier in healthy skin
B. Barrier dysfunction in skin disease
C. Therapeutic implications
P.4
P.8
P.10
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Allerderm® spot-on:
a new lipid-replacement therapeutic option
................................................................................
P.12
A. A triple topical combination of skin identical lipids
1. Composition and Mode of action
2. Evidence-based efficacy
Material and methods
Results
Conclusion
P.12
P.12
P.13
P.13
P.13
P.15
B. An easy-to-use spot-on formulation
1. Product presentation
2. Application of the product on skin
Directions for use
P.16
P.16
P.17
P.17
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Clinical benefits delivered by Allerderm® spot-on
P.18
A. Indications for use
1. Allerderm® spot-on value in skin disorders
2. Allerderm® spot-on and aged skin
P.18
P.18
P.18
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B. Dermatologists’ opinions
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P.19
Introduction: the chicken or the egg?
This is the era of immunology in canine dermatology.
Canine atopic dermatitis is defined as “a genetically-predisposed inflammatory and pruritic
allergic skin disease…most commonly associated with IgE antibodies to environmental
allergens” (Olivry et al., 2001). Derangements in immunological responses to allergens have
been extensively studied in connection with their role in generating dermal inflammation
and pruritus. By contrast, changes in the epidermal barrier that accompany inflammatory
dermatoses have long been considered downstream participants in the disease pathogenesis.
Consequently, specific or nonspecific anti-inflammatory therapy has been the focus of the
treatment of canine atopic dermatitis.
The concept is emerging in human medicine that skin barrier abnormality is not just a
secondary phenomenon, but rather a critical - if not primary - triggering factor in inflammatory
skin disease (Elias & Feingold, 2001). The outer layer of the epidermis (stratum corneum),
the defense barrier between the outside world and the inside of the body, is not just an inert
end product, but rather a sophisticated biosensor that responds to external perturbations.
When the skin surface is injured or the skin barrier is compromised, a variety of signals
are produced (cytokines, growth factors, lipid mediators) that stimulate metabolic responses
in the underlying living epidermis. The responses are aimed at normalizing the stratum
corneum function. Over stimulation of this process stimulates signal cascades that initiate
inflammatory events in deeper skin layers. The best-known example of this sequence is
the so-called cytokine cascade, which has been proposed to provoke or sustain several
important inflammatory dermatoses. According to this new outside-inside paradigm, it is
the faulty barrier that drives and sustains inflammation in underlying skin layers.
It seems reasonable to think that both primary epidermal barrier dysfunction and inappropriate
immunologic response contribute to the full expression of atopic dermatitis in dogs. Therefore,
therapies aimed at normalizing epidermal barrier function should not be seen as secondary
or inconsequential, and management of allergic skin disease should consider treatment of
inflammation along with selection of an appropriate barrier repair strategy.
This very good idea has driven the development of a new topical lipid replacement therapy
by Virbac Animal Health. We invite you to discover the Allerderm® Spot On in the following
pages.
Nancy Bathurst, DVM
Christophe A. Rème, DVM
Research & Development
Hugues Gatto, PhD
Virbac Corporation
Medical Department
Virbac SA
introduction
Unraveling the importance
of the epidermal barrier
1
A. The permeability barrier in healthy skin
The skin serves the vital function of providing the protective barrier between the hostile, dry, terrestrial
world and the internal environment of the body. This defensive function is localized to the outer part (stratum
corneum) of the most superficial skin layer (the epidermis). The structure of the stratum corneum can
be compared with a brick wall, in which the bricks represent dead cells (corneocytes) and the mortar an
intercellular matrix made of lipid lamellar sheets [Mason & Lloyd, 1993]. Adjacent layers of densely-packed
living cells (keratinocytes) maintain stratum corneum integrity. In the epidermis, keratinocytes are associated
with immune cells (Langerhans cells), pigmentary cells (melanocytes) and cells involved in sensory perception
(Merkel cells). The epidermis does not contain blood vessels and therefore receives its nutrients by diffusion
from the adjacent skin layer, the dermis.
Fig.1 Epidermis location & structure
New keratinocytes are constantly produced in the germinative layer of the epidermis (stratum basale) and
gradually migrate upwards to the surface layer undergoing differentiation and maturation into corneocytes.
In the granular layer (stratum granulosum), lipids are produced by the keratinocytes and stored inside a
unique intra-cellular organelle, the lamellar body. At the interface between the stratum granulosum and
the stratum corneum, lipids are extruded from the cells into the inter-corneocyte space. Along with the
lipids, lamellar bodies release enzymes that transform polar lipids into nonpolar lipids arranged in highly
organized, multilamellar bilayers preventing transcutaneous water loss [Elias, 2008]. After loosing their
nuclei, keratinocytes become flattened dead cells (the corneocytes), full of keratin filaments aggregated by
a protein called filaggrin. Filaggrin is subsequently degraded into metabolites that act as osmolytes drawing
water into corneocytes [Elias, 2008]. The healthy stratum corneum thus has relatively high water content
and is elastic and pliable. At the skin surface, cells are continuously shed at a rate proportional to synthesis,
so that epidermal thickness (0.1 to 0.5 mm on average in the dog) is maintained constant [Kwochka, 1993]
[Scott, 2001]. Corneocyte desquamation also serves the purpose of mechanical elimination of pathogens
4
and allergens from the skin surface [Downing, 1992]. Epidermis turn-over is relatively rapid in the dog
(22 days) [Scott, 2001].
> The stratum corneum thus serves as a water permeability barrier, which also prevents the
transcutaneous penetration of allergens and irritants.
Keratinocytes play also an important role
in local immune function, as they produce
interleukins and cytokines aimed at preserving
barrier homeostasis. Antimicrobial peptides
(cathelicidin, β-defensins) of the innate
immune system produced in the skin
are stored in the lamellar bodies and
subsequently delivered to the stratum
corneum [Sugarman, 2008]. Permeability and
antimicrobial functions are coregulated and
interdependent. Failure of the permeability
barrier in itself favors secondary infection
and conversely pathogen colonization/
infection further aggravates any abnormality
of the permeability barrier [Elias et al., 2008]
resulting in a vicious cycle.
The lipids of the extra-cellular matrix of
the stratum corneum are composed
of approximately 50% ceramides, 25%
cholesterol and 10 to 20% long-chain free
fatty acids arranged in repeated arrays of
lamellar sheets [Downing, 1992] [Wertz,
2000] [Madison, 2003] [Jungersted et al.,
2008]. These lipids are critical to normal
permeability barrier function [Sugarman,
2008].
Fig.2 Stratum corneum synthesis and structure
Fig.3 Lamellar lipid sheets organization
in the stratum corneum
Ceramides are complex sphingolipids formed from the amide linkage of a sphingoid base (sphingosine,
phytosphingosine, 6-hydroxysphingosine) with a variety of nonhydroxylated, α-hydroxylated or ω-hydroxylated
fatty acids. Nine ceramides (numbered from 1 to 9 according to polarity) have been identified in human
stratum corneum, that differ from one another based on the type of sphingoid base they include as well as the
length and hydroxylation (position of -OH groups) of the carbon chain of the fatty acids [Coderch et al., 2003].
Recent thin-layer chromatography studies have confirmed that canine epidermis contains ceramide species
similar to that of humans, based on the same 3 sphingoid bases coupled to long-chain fatty acids (especially
ω-hydroxylated fatty acids, which are found in Ceramide 1 and 4 in humans) [Segiguchi et al., 2003; Pin et
al., 2008].
Fig.4 General chemical formula of a ceramide
5
A. The permeability barrier in healthy skin
Ceramides located in the intercellular spaces of the stratum corneum are not able to form bilayer configurations
by themselves. However, in conjunction with cholesterol sulfate and free fatty acids, which are ionized at
physiological pH, they form ordered structures. These arrays of hydrophobic chains construct lipid bilayers
with closely packed interiors which dramatically reduce their permeability to water and solutes. At physiological
temperature, the lipid chains are mostly in a solid crystalline or gel state. Each ceramide species in the stratum
corneum has unique properties that contribute to the extracellular lipid matrix organization and cohesion
[Coderch et al., 2003].
Fine self-regulating mechanisms control the synthesis of ceramides by keratinocytes, depending on needs of
the epidermis at any given time.
The free fatty acids in the stratum corneum are not enriched in essential fatty acids. They are predominantly
saturated and range from 14-28 carbons in length (eg palmitic, stearic, oleic, behenic, lignoceric acids) and
markedly differ from that found in the serum or sebum, as they derive from de novo synthesis in the epidermis.
The essential fatty acid linoleic acid plays an important role in barrier function as a component of Ceramide
1. The linoleic tail, ester linked to the ω-hydroxyl group of the very long fatty acid chain of Ceramide 1, inserts
into adjacent regions of the lipid bilayer and acts as a molecular rivet joining two leaflets together [Wertz, 2000]
[Downing, 1992].
Fig.5 Structure of ceramide 1
Cholesterol in the intercellular lipid domain of the horny layer is roughly perpendicular to the bilayer surface,
and is thought to improve both plasticity and rigidity of the membranes. Cholesterol sulfate is important for
cell to cell cohesion in the stratum corneum. Any alteration of cholesterol metabolism in the epidermis may
lead to alterations of the normal desquamation process [Coderch et al., 2003].
B. Barrier dysfunction in skin disease
Loss of normal barrier function plays an important role in several skin conditions including atopic dermatitis
and keratoseborrheic disorders.
In human atopic dermatitis, abnormal maturation and secretion of lamellar bodies have been demonstrated
[Fartasch, 1997]. Abnormal lamellar body secretion results in decreased intercellular lipids in the stratum
corneum, and in particular a reduction of ceramides [Di Nardo et al., 1998] [Macheleidt et al., 2002].
Analysis of the lipid content in the skin of atopic individuals has revealed a significant decrease in the levels
of ceramides 1 and 3 [Yamamoto et al., 1991] [Di Nardo et al., 1998] [Jungersted et al., 2008].
Two electron microscopy studies report similar findings of defective epidermal lipid barrier in atopic dogs
[Inman et al., 2003; Piekutowska et al., 2008]. The deposition of lipid lamellae is markedly heterogeneous in
the stratum corneum of non-lesional skin of atopic dogs as compared to healthy controls. Many areas in the
inter-corneocyte spaces are devoid of lipids. When present, lipid lamellae often exhibit an abnormal and/or
incomplete structure. This contrasts with lipid matrix organization in the healthy canine stratum corneum,
6
where lamellar lipids are well arranged in compact sheets and almost entirely fill the space between
corneocyte layers. Quantitative evaluation demonstrates a significant difference in the continuity and
thickness of lipid lamellae in the skin of dogs with atopic dermatitis as compared to normal dogs. In the
lower stratum corneum of healthy dogs, lamellar lipids fill around 90% of the total intercellular space,
while this figure falls to 32% in the non-lesional skin of atopic dogs. The biochemical defects in the
skin of atopic dogs have been further evaluated by HPLC analysis [Pin et al., 2008]. Canine stratum
corneum can be collected using adhesive tape strips and the different classes of lipids can be purified
and analyzed individually. The findings confirm that the horny layer of atopic dogs has much lower lipid
content with a marked deficit in ceramides as compared to normal dogs.
Fig.6 E lectron microscopy comparison of non-lesional skin of atopic dogs and healthy
canine skin [from Piekutowska et al., 2008]
7
B.Barrier dysfunction in skin disease
The net result of lipid barrier deficiency is increased transepidermal water loss (TEWL) and penetration of
foreign allergens. A significant increase in TEWL is found on atopic predilection sites (axilla, antecubital fossa,
chin, periocular area, pinna, thorax) in sensitized dogs as compared to normal dogs, and TEWL is further
increased after allergen challenge [Hightower et al., 2008].
A compromised barrier facilitates penetration of antigens, pathogens, and nonspecific irritants, that stimulates
a cytokine cascade initiated by keratinocytes. If prolonged, this will lead to recruitment of an inflammatory
infiltrate. The inflammatory response in atopic dogs favors Th2 cytokines and production of IgE. The ensuing
immunologic events that are characteristics of atopic dermatitis lead to further epidermal barrier compromise
[Sugarman, 2008].
Fig.7 T he vicious cycle of epidermal barrier dysfunction and inappropriate immune
response in atopic dermatitis [after Sugarrman, 2008]
In addition to the disease itself, some of the agents used to treat atopic dermatitis may further disturb the
permeability barrier homeostasis. Oral and topical glucocorticoids, which are often necessary to control
acute flares, are known to be detrimental to the epidermal barrier due to multiple mechanisms including
decreased lipid synthesis and decreased epidermal proliferation and differentiation. The implementation of
therapeutic measures to correct barrier deficits should be considered in conjunction with anti-inflammatory
therapy.
8
Other dermatological conditions are associated with lipid barrier perturbation in humans. Decreased
levels of ceramide 1 and 6 are related to a lower threshold to irritant contact dermatitis [Di Nardo et al.,
1996]. The relative ceramide content of intercellular lipids also is reduced in dry scaly conditions like
ichthyosis [Lavrijsen et al., 1995] and xerosis [Akimoto et al., 1993].
Determination of lipid profiles in keratoseborrheic conditions is lacking in dogs, although there is evidence
that topical application of linoleic acid, a key component of ceramide 1, reduces TEWL in dogs with
seborrhea sicca [Campbell & Kirkwood, 1993]. In seborrheic disease, overall epidermal differentiation
is disturbed and thus there are secondary effects on corneocyte structure as well as on the composition
and function of the intercellular lipids that ultimately result in scaling [Madison, 2003].
C. Therapeutic implications
The recent advances in our understanding of the pathophysiology of the epidermal barrier and its
relation to disease expression, particularly in atopic dermatitis, logically leads to renewed interest in
barrier repair therapy.
The use of moisturizers (agents that aim at normalizing epidermal barrier function by reducing TEWL
and improving hydration in the stratum corneum) in addition to anti-inflammatory therapy has long been
advocated for the management of allergic skin disease.
Traditional occlusive moisturizers (eg petrolatum) act as exogenous barriers to water loss, forming a
film on the skin surface. Humectants (eg urea, propylene glycol, glycerin, lactic acid) are water holding
substances that trap water in the epidermis. None of these agents however correct the underlying lipid
biochemical abnormality in the stratum corneum.
There is a strong rationale for the deployment of a lipid-replacement strategy, which aims at rebuilding
an effective epidermal barrier through the topical delivery of lipid precursors.
Lipid-based topical products composed of the lipids found in skin penetrate the horny layer and are
taken up by keratinocytes, packaged into lamellar bodies, and then re-secreted to form lamellar bilayers
[Madison, 2003]. In various human and animal models, mixtures of the 3 stratum corneum lipids:
ceramides, cholesterol and free fatty acids are shown to be most effective for barrier recovery, while
the use of unbalanced lipid formulations containing only one or two ingredients is less effective and even
can be detrimental [Mao-Quiang et al., 1996] [Cordech et al., 2003] [Sugarman, 2008].
This new barrier repair strategy opens new avenues in the management of various skin diseases,
notably canine atopic dermatitis, with a medium term goal of minimizing chronic disease exacerbation
by reducing ”stress” generated by epidermal barrier disruption.
9
C Therapeutic implications
Fig.8 Treatment options in inflammatory skin disease
10
Allerderm® spot-on:
a new lipid-replacement therapeutic option
1
A. A Triple topical combination of skin identical lipids
1 - Composition and Mode of action
The lipid formula in Allerderm® spot-on (skin lipid complex) is a nano-emulsion that mimics the
composition and structure of intercellular lipids in the stratum corneum.
All 3 types of lipids found in the epidermal barrier are included:
u Ceramides (Ceramide 1, Ceramide 3 & Ceramide 6 II)
u Cholesterol
u Fatty acids (Polyglyceryl-4 Laurate, Dilauryl Citrate)
These lipids are organized in multi-lamellar layers similar to that found in the skin (liquid crystalline
structure). When applied topically, they permeate through the horny layer to be incorporated in the
nucleated cell layers of the epidermis and enhance its lipid synthetic capabilities (Fig. 9).
Fig.9 Action of the Skin Lipid Complex in the epidermis
11
A. triple topical combination
of skin identical lipids
The composition of the skin lipid complex in Allerderm® Spot On is based on the developing understanding
of:
- the exact lipid defects identified in the skin of patients with atopic or contact dermatitis
(reductions in Ceramides 1, 3 and 6)
- the appropriate balance of the different types of lipids required (ceramides, cholesterol & free fatty
acids) to accelerate barrier repair and recovery.
The excipient (vehicle) in the product has been specifically developed to preserve the liquid crystal structure
of the emulsion.
Application of the skin lipid complex onto the skin ultimately results in an enhanced epidermal barrier
(increased moisturization and protection), leading to a less sensitive and less dry skin.
2 - Evidence-based efficacy
A study was performed to evaluate quantitatively, by means of electron microscopy and ruthenium tetroxide
post-fixation, the impact of the topical application of the skin lipid complex on lipid structural deficits in the
skin of dogs with AD [Piekutowska et al., 2008].
Materials and methods
Ten dogs were included in the study:
- Test group: five dogs clinically diagnosed with atopic dermatitis (AD): three males and two
females from different breeds,
- Control group: five healthy female Beagle dogs.
All dogs in the test group were treated every 3 days over 15 days with topical applications of the skin lipid
complex. Fifty micro-litters of the lipid emulsion were applied over a 4 cm2 area on the lateral side of the
thorax and gently massaged into the skin for 15 seconds. The lipid mixture was applied on non-lesional
skin on one side of the body only (treated side), the symmetrical non-lesional site on the other side of the
body remained untreated (control side). The healthy, non-atopic dogs served to provide reference normal
values. Punch skin biopsies (6 mm) were taken from the symmetric treated and untreated areas on the
lateral thorax, after local subcutaneous xylocain anesthesia, one day after topical treatment cessation.
The specimens were cut into 5-6 smaller pieces and fixed overnight in phosphate-buffered saline (PBS)
containing paraformaldehyde 4% and glutaraldehyde 1%, and then post-fixed either with osmium tetroxide
(OsO4) 1% in 0.4 M cacodylate buffer (2h) or with ruthenium tetroxide (RuO4) 0.25% in PBS (1h), in a dark
chamber at room temperature.
The dehydrated tissue blocks embedded in Epon were sectioned perpendicularly to the skin surface and
ultrathin sections (86 nm) were stained with uranyl acetate 7% in methanol, and lead citrate.
The samples were examined by transmission electron microscopy (EM) and photographs taken with a
digital camera at magnifications of 28 000x, 60 000x, 125 000x, and 260 000x. The ultrastructure of atopic
skin was compared between treated and untreated sites, as well as to that of healthy skin. Cross-sectional
surface of intercellular spaces between corneocyte strata and the surface of visible lipid lamella structures
stained by ruthenium tetroxyde within the intercellular spaces were measured with a computer-assisted
imaging system.
Results
On electron microscopy examination of untreated non-lesional skin of atopic dogs, very long and thin
corneocytes are observed. The inter-corneocyte interstices are almost empty. Rare lamellar lipids can be
observed from time to time but they are poorly organized and have a wavy “fragile” appearance.
12
The stratum corneum cells of healthy dogs also are very long and flat, but in the lower half of the horny
layer they coalesce. In this location, the lamellar lipids are well-organized in compact sheets and almost
entirely fill the space between corneocytes.
Comparison between treated and untreated sites in the atopic dogs shows marked improvement in nonlesional skin ultrastructure after application of the lipid preparation. The intercorneocyte spaces become
flat and are almost entirely filled with lamellar lipids. Numerous voluminous lamellar bodies are observed
in the apical parts of keratinocytes of the stratum granulosum. Some of these lamellar bodies have
merged with cell membranes forming extracellular conglomerates of short multi-directional lamellar lipids.
In the deeper inter-corneocyte spaces, these short lamellar discs coalesce and well-organized sheets of
lamellar lipids can be observed upwards.
Fig.10 E lectron microscopy comparison of non-lesional skin of atopic dogs before
and after treatment with the skin lipid complex
13
A. triple topical combination
of skin identical lipids
Quantitative evaluation demonstrates a significant difference (P≤ 0.05) in lamellar lipids expression between
treated and control sites. In the lower stratum corneum of healthy dogs, lamellar lipids occupy 89.5% ±6.8
(mean ± SD) of the total intercellular space. This figure falls to 31.8% ±16.7 at untreated sites in dogs with
AD. By contrast, lamellar lipids represent 74% ±10.9 of the inter-corneocyte space in treated skin areas of the
same dogs after application of the skin lipid complex, a value not significantly different from healthy controls.
Moreover, at treated skin sites, 57.6% of the space occupied by newly-formed lamellar lipids between the
granular layer and the stratum corneum were filled with lamellar body-derived short lipid discs – a figure not
significantly different from that found in the same area of the stratum corneum in normal dogs (51.7 %).
Fig.11 P
ercentage of total intercellular space occupied by structured lamellar lipids in the lower
stratum corneum. ** A,C significantly different from B (P≤0.05)
*
* p ≤ 0.05 with A & C
Conclusion
Treatment with the skin lipid complex contributes to the formation of an improved epidermal barrier in atopic dogs.
This activity is likely related to stimulation of the endogenous production and secretion of physiologic lipids in the
stratum corneum.
14
B. An easy-to-use spot-on formulation
1 - Product presentation
The skin lipid complex is formulated in a vehicle that preserves the stability of the emulsion, favors the
delivery of active lipids to the skin structures (penetration enhancer) and promotes product spreading on
the skin surface. Whereas electron microscopy experiments have shown that a few µLs of the emulsion
are sufficient to improve a small skin area, the solution can diffuse from the spot application of a few mLs
to cover surrounding sites.
Promoting barrier support is a long standing process that requires regular use of lipid emollients in hairy
patients. Diligence on the part of the pet owner to adhere to a complete plan, that includes barrier repair
therapy, prescribed by the veterinarian is key to achieve and maintain adequate control of chronic or
recurrent canine skin disease.
Thus, the topical delivery of the skin lipid complex emulsion on the skin surface in several spots spanning
the body surface or most affected areas is a convenient and efficient way of providing skin care.
u Allerderm® spot-on includes the skin lipid complex emulsion in 2 and 4 mL pipettes.
The product is a white fluid that is applied by breaking the top off of the applicator
and gently squeezing the pipette. Six pipettes are provided per box.
u The 2mL pipettes will be used in cats or dogs ≤ 10 kg while the 4ml pipettes are
required for dogs > 10 kg.
Allerderm® spot-on is
available in 2 pipette
sizes to be selected
according to the size
of the patient
15
B. An easy-to-use spot-on formulation
2 - Application of the product on skin
Directions for use
Allerderm® spot-on is easily applied and convenient for the
veterinarian and pet owner.
16
Clinical benefits delivered
by Allerderm® spot-on
1
A. Indications for use
The concentrated formula of Allerderm® spot-on provides complex lipid precursors that stimulate the
secretion of endogenous cement lipids in the upper skin layers, strengthening the epidermal barrier.
Because of its mode of action, the product can be used as a supportive measure in various situations.
1 -Allerderm® spot-on value in skin disorders
Conditions that are associated with a compromised epidermal barrier include allergic skin diseases
(atopic dermatitis, irritant/allergy contact dermatitis), kerato-seborrheic disorders and microbial infections.
In children with atopic dermatitis, ceramide-dominant emollients represent a safe, useful adjunct to the
standard topical glucocorticoid treatment, improving the severity scoring and reducing TEWL [Chamlin et
al., 2002]. The combined treatment (topical lipids + corticosteroids) improves erythema, pruritus, as well
as skin dryness, scaling and fissuring [Berardesca et al., 2001]. Dogs with atopic dermatitis may also
benefit from the barrier restructuring effects of Allerderm® spot-on, in association with pharmacological
therapy during the acute phases of the disease, or as a preventive maintenance measure to reduce
the risk of future flare-ups. Reduction of the frequency and dose of drug medications (steroids and/
or antimicrobials) required to control the disease, or reduction of frequency or severity of flare-ups,
are among the objectives of the barrier repair strategy. Improvement of the stratum corneum barrier
ultimately enhances skin hydration and reduces allergenic stimulation, offering a new adjunct and
supportive pathology-based approach, which is complementary to symptomatic therapy.
The restorative activity of Allerderm® spot-on, is also of benefit in keratinization disorders to help normalize
dry skin, regulate abnormal epidermal maturation and contribute to scale reduction, in association with
other adequate topical or systemic therapeutic measures.
Where the product is used in conjunction with soothing or keratolytic shampoos, it is advised to use the
lipid emollient after the bath, when the fur is completely dry.
2 - Allerderm® spot-on and aged skin
There is an overall decrease in total stratum corneum lipids - mostly of the ceramide content - by
approximately 30% in elderly humans [Cordech et al., 2003]. No such data are available in dogs, although
a reduction in keratinocyte and sebaceous gland activity is generally seen with age. The skin becomes
dry and less pliable, and the dog exhibits a dull, tangled hair coat. Topical lipid supplementation may help
improve the appearance of senior canine dry skin.
17
A. indications for use
B.dermatologists’ opinions
Eight veterinary dermatologists had the opportunity to sample Allerderm® spot-on under field conditions.
The objective of this sampling survey was to define the best conditions for use of the product in clinical
practice and to gather practitioners’ and owner’s opinions. All veterinarians and owners involved rated their experience with the product as positive.
Fig.12 Opinions in the field about the use of Allerderm® spot-on
18
ReFeRENCES
1.
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2.
Berardesca E, Barbareschi M, Veraldi S, Pimpinelli N. Evaluation of efficacy of a skin lipid mixture in patients with
irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multi-center study. Contact Dermatitis
2001;45:280-285.
3.
Campbell KL, Kirkwood AR. Effect of topical oils on transepidermal water loss in dogs with seborrhea sicca. In: Ihrke
PJ, Mason IS, White SD (Eds). Advances in Veterinary Dermatology vol. 2, Oxford, Pergamon Press, 1993; p157-162.
4.
Chamlin SL, Kao J, Frieden IJ, Sheu MY, Fowler AJ, Fluhr JW, Williams ML, Elias PM. Ceramide-dominant barrier
repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease
activity. J Am Acad Dermatol 2002;47:198-208. 5.
Coderch L, Lopez O, de la Maza A, Parra JL. Ceramides and skin function. Am J Clin Dermatol 2003;4: 107-129.
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Di Nardo A, Sugino K, Wertz P et al. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis: a correlation study
between ceramides and in vivo parameters of irritation. Contact Dermatitis 1996;35:86-91.
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Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic
dermatitis. Acta Derm Venereol 1998;78:27-30.
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Downing DT. Lipid and protein structures in the permeability barrier of mammalian epidermis. J Lipid Res 1992;33:301313.
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Elias PM. Skin barrier function. Current Allergy and Asthma Reports 2008;8:299-305.
10. Elias PM, Feingold KR. Does the tail wag the dog? Role of the barrier in the pathogenesis of inflammatory dermatoses
and therapeutic implications. Arch Dermatol 2001;137:1079-1081.
11. Elias PM, Hatano Y, Williams ML. Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms. J Allergy Clin Immunol 2008;121:1337-1343.
12. Fartasch M. Epidermal barrier in disorders of the skin. Microsc Res Tech 1997;38:361-372.
13. Hightower K, Marsella R, Creary E, Dutcher P. Evaluation of trans-epidermal water loss in canine atopic dermatitis:
a pilot study in beagle dogs sensitized to houst dust mites. 23rd Proceedings of the NAVDF Congress 2008, Denver,
Colorado, p183.
14. Inman AO, Olivry T, Dunston SM, Monteiro-Riviere NA, Gatto H. Electron Microscopic observations of stratum corneum
intercellular lipids in normal and atopic dogs. Vet Pathol 2001;38:720-723.
15. Jungersted JM, Hellgren LI, Jemec GB, Agner T. Lipids and skin barrier function--a clinical perspective. Contact Dermatitis 2008;58:255-62.
16. Kwochka KW. The structure and function of epidermal lipids. Vet Dermatol 1993;4: 151-159.
17. Lavrijsen APM, Bouwstra JA, Gooris GS et al. Reduced skin barrier function parallels abnormal stratum corneum lipid
organisation in patients with lamellar ichthyosis. J Invest Dermatol 1995;105:619-624.
18. Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol 2002;119:166-173.
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B. Dermatologists’ opinions
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