What We Will Cover Today - Wheat Ridge Animal Hospital

Transcription

9/30/2014
Wheat Ridge
Veterinary Specialists
EXPERTISE YOU CAN TRUST.
2014 Symposium at Coors Field
What We Will Cover Today
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Wheat Ridge
Pathogenesis : Genetic Factors
Pathogenesis : Skin Barrier Function
Pathogenesis : Immune Dysfunction
Pathogenesis : T Cells and Cytokines
Therapy : Client Education
Therapy : Topical Therapy
Therapy : Immunotherapy
Therapy : Antihistamines
Therapy : Oclacitinib
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Wheat Ridge
Pathogenesis
Pathogenesis – Genetic Factors
Wheat Ridge
1. Genetic factors play a large role in AD.
a. Changes on chromosome 5, 7 and 11.
Izuka 2002
b. Down-regulation of cornified envelope
genes. Vasilopoulos 2004
c. Up-regulation of genes for alternative
keratinization pathways.
d. Loss-of-function mutations in the filaggrin
gene. Zirwas 2007
e. Abnormalities in genes related to lipid
formation.
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Wheat Ridge
1. Veterinary focus has been on genes responsible
2.
3.
4.
5.
for IgE production. Halliwell 1972
Increased IgE production does not always lead to
clinical disease. Schwartzman 1984
20% of dogs with AD do not have elevations in
IgE.
AD cannot be induced in dogs with high IgE
production. Egli 2002
No one specific gene encodes for AD and there
may be variance between different breeds.
Stensham 2006, Wood 2010
Wheat Ridge
Affected Breeds:
German shepherd dogs, Shar Pei, Akita, Golden
retriever, Labrador retriever, Dalmatian, Boxer,
Shih Tzu, Beagle, Schnauzer, Bulldog, Bichon,
Rottweiler, Newfoundland, Chihuahua, Poodle,
West Highland White Terrier, Scottish Terrier,
Wirehaired Fox Terrier, Irish Setter, Beauceron,
Boston Terrier, Cairn Terrier, Sealyham Terrier,
English Setter, Labrit, Yorkshire Terrier, Cocker
Spaniel, Mixed Breed Dogs………………………
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Labrit : Pyrenean Sheep Dog
Wheat Ridge
Pathogenesis-Barrier Function
Wheat Ridge
1. Skin barrier dysfunction shown in dogs and
people with AD.
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Wheat Ridge
1. Mutations in proteins of the corneocytes, specifically
2.
3.
4.
5.
6.
filaggrin. Hightower 2008, Marsella 2012
There are abnormal and disorganized lipid lamellae.
Inman 2001
Decreased ceramide content in stratum corneum. Popa
2010 and 2011, Chervet 2010
Decrease antimicrobial peptides (defensins).
Increased adherence of bacteria to the epithelium.
Bacteria, yeast and pollens secrete enzymes that
degrade the stratum corneum and decrease ceramides.
Wheat Ridge
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Wheat Ridge
Filaggrin
Filaggrin is a filament-associated-protein that
binds keratin fibers in epithelial cells.
Wheat Ridge
1. Widened intracellular spaces, abnormal lipids
and impaired local immunity allows for water to
escape and bacteria, pollen antigens and
malassezia to enter the skin.
2. Barrier dysfunction leads to transepidermal
water loss (TEWL) which
leads to dry skin.
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Tewameter or Vapometer
Pathogenesis: T Cells and
Cytokines
Wheat Ridge
1. Acute skin lesions in AD are associated with
CD4+ TH 2 which produce more proinflammatory
cytokines including IL-4 and IL-13.
2. IL-4 and 13 also help in development of IgE
levels and eosinophil survival.
3. Drugs targeted at cytokines are the wave of the
future.
4. Apoquel inhibits ILs 2,4,6,13 and 31
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Wheat Ridge
Pathogenesis: Role of Histamine
Wheat Ridge
1. Serum histamine levels in AD dogs are the
same or lower than normal dogs. Wilkie 1990,
Rhodes 1987
2. Histamine release does not correlate with IgE
levels. Small 1994, Vaughn 1994
3. One study showed histamine in skin mast cells
to be higher than normal animals. Demora
1996
4. Leukotrienes are thought to play a role in AD in
people. Not shown yet in dogs.
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Pathogenesis: Vasoactive
Substances
Wheat Ridge
1. Serotonin
2. Substance P
3. Neuropeptide Y
4. VIP
5. Beta-endorphin
6. Somatostatin
7. Number and size of cutaneous free nerve
endings is increased.
Diagnosis
Wheat Ridge
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Wheat Ridge
Diagnosis
1. Atopy is diagnosed clinically based on history,
clinical signs and lesional distribution.
2. There is no specific test for allergies.
3. Intradermal or serum allergy tests are used to
identify to what the pet is allergic and to chose
antigens for allergy immunotherapy once the
diagnosis has been made.
Role of Allergens
Wheat Ridge
1. Originally antigen entrance was thought to be
via inhalation. As early as 1941.
2. Epicutaneous entrance is the predominant rout
allergens enter the skin. Popa 2010, Olivry
2002
3. Oral and inhalant routes are also involved.
4. Food allergens cause a flare of symptoms in
dogs with AD in 2-5% of cases. Carlotti 1994,
Hillier 2000, Picco 2008
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Wheat Ridge
Therapy: Client Education
Wheat Ridge
1. Essential for long term successful management of
2.
3.
4.
5.
6.
AD in dogs. Owners are our eyes and ears.
Dogs are rarely cured but are almost always
successfully managed.
Client literature and internet education.
Spend time with them at each visit and listen to
their concerns and frustrations.
We often change our therapy based on client
perceptions and requests.
Clients must understand therapy is multimodal
and often life-long
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Objective 6 – Multimodal Therapy
Wheat Ridge
1. Understand that therapy for atopy is
multimodal.
2. Immunotherapy alone rarely controls atopy but
it is very important. 25 - 50 – 25
3. Repair and care of the skin barrier.
4. Systemic and topical therapy for secondary
infections
5. Control of triggering factors.
6. Control of itch sensation.
Wheat Ridge
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Therapy: Topical Therapy
Wheat Ridge
Topical Therapy : Why?
Wheat Ridge
1. Removes allergens from the hair coat.
2. Removes bacteria from the skin.
3. Removes seborrheic oils from the skin.
4. Removes yeast from the skin.
5. Rehydrates the skin.
6. Improvement/repair of epidermal barrier.
7. Delivery of anti-inflammatory ingredients.
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Wheat Ridge
Topical Therapy
1.Douxo shampoos, sprays, ear washes, gels
and lipid spot-on contain phytosphingosine
which is a lipid component of ceramide.
2. Many companies (Virbac, Dechra, Sogeval
Dermoscent) have products with ceramides.
3. Small studies have shown ceramide products
will reduce TEWL, CADESI scores and
pruritus.
4.My personal experience is that all these
products help clinically for 24-28 hours.
Therapy: Topical Therapy
Wheat Ridge
1. Topical Spray with triamcinolone and
hydrocortisone.
2. Topical conditioners with glucocorticoids,
antihistamines and local anesthetics.
3. Topical tacrolimus ointment or spray.
4. Topical steroids for the ears with steroids,
DMSO or Burrows solution with
hydrocortisone.
5. Use of these products are part of the high
maintenance regimen for allergic pets.
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Hydrocortisone Aceponate:
Cortavance
Wheat Ridge
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Therapy: Immunotherapy
Wheat Ridge
1. Successfully used for over 100 years in people
and 50 year animals to treat/control AD.
2. Mechanism of action is unknown.
3. Affects antibody production, cytokine
secretion, mast cell degranulation and T cell
activation.
4. Modulates cytokine profile from a TH 2 to TH1
response.
5. No standardization of regimes.
Therapy: Immunotherapy
Wheat Ridge
1. 60% of patients show good to excellent results.
2. 20-25% of patients fail immunotherapy
3. Do not combine mold extracts with pollens.
4. Immunotherapy trial should be for at least one
year.
5. Give Labrador Retrievers 2 years!!!
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Wheat Ridge
Therapy: Sublingual
Immunotherapy (SLIT)
Wheat Ridge
1. Used for over 50 years in humans. Widely
used in Europe.
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Therapy: Sublingual
Wheat Ridge
1. DeBoer and Morris in 2012 showed that 59%
of 77 allergic dogs had a good or excellent
response to SLIT.
2. 23% had a fair response.
3. 49% of patients that had failed injectable
immunotherapy responded favorably.
Therapy: Sublingual
Wheat Ridge
1. Oral mucosa is a “privilaged” immunologic site.
2. Mucosa allows uptake of antigens but blocks
pathogens.
3. Oral immune reaction is toward
“antiinflammatory” and “tolerance” with IL 10
and TGF Beta.
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Therapy: Sublingual
Wheat Ridge
1. Glycerinated solution allows for room
temperature storage for up to 6 months
2. OK to combine molds and pollens.
3. Dogs and cats “like” the flavor.
4. No injection is required.
5. Therapy is required BID every day.
Wheat Ridge
Antihistamines
1. 5-20% of patients receiving antihistamines
achieve a noticeable benefit.
2. Dimetinden maleate:
In 12 of 18 dogs the pruritus improved more than
25%.
3. Hydroxyzine/chlorpheniramine combination:
In 10 of 17 dogs the pruritus improved more than
25%.
4. 2 of 19 placebo patients the pruritus improved
more than 25%.
Eichenseer M Vet Rec 2013; 173 (17): 423
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Wheat Ridge
Therapy
Apoquel : Oclacitinib
Wheat Ridge
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Apoquel : Oclacitinib
Wheat Ridge
1. Janus Kinase 1 inhibitor
2. Interferes with formation of IL 2, 4, 6, 13 and
31.
3. IL 2, 4, 6 and 13 are proinflammatory
cytokines.
4. IL 31 mediates pruritus
5. Zoetis made an error that is a lose-lose-lose.
6. Should be available mid-2015; win-win-win.
Wheat Ridge
21

What We Will Cover Today - Wheat Ridge Animal Hospital

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