Atopic Dermatitis Flashcards by Brittany Jermalovic

Pruritic think…

Allergies!

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Atopic Dermatitis

Background

Genetically predisposed inflammatory and pruritic skin disease; pruritis is a must

Tendency to develop IgE-mediated allergy vs. environmental allergens

Strong hereditary tendencies

Usually a food allergy

More exposure = more reactive

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Atopic Dermatitis

Multifactorial components

Genetic
Barrier Function
Immunologic Factors
Allergens

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Atopic Dermatitis

Cycle

Allergen
Langerhans cell stimulates T-cell
T-cell releases cytokines that stimulate sensory nerve fibers –> itch
Get local inflammation (mast cell degranulation, stimulation of other T-cells, more cytokines) –> itch
Local inflammation can also stimulate Dendritic cells which will release their own cytokines and end up contributing to inflammation

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Atopic Dermatitis

Genetic Factors

Veterinary studies still needed

Suggested to be seen in West Highland Terriers

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Atopic Dermatitis

Barrier Function

Compromise; allergens can enter, water evaporates, dry skin (may cause pruritis)

Major lipids of SC
Cholesterol
FFA’s
Ceramides (holds everything together!)

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Atopic Dermatitis

Immunologic Factors

Helper T Lymphocytes release cytokines and stimulate may ILs

Important one:
IL-4 with T-helper 2 cells
IL-4, IL-5, IL-13, IL-31

IL-31 has a targeted therapy

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Atopic Dermatitis

Presentation

1-3 years
Seasonal pruritus
Breeds: Terriers, Boxers, Labs

Sites:
Ventral hairless areas
Face
Feet
Peri-anal (licks under tail)

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Atopic Dermatitis

Diagnosis

No definitive test! 
Signalment
History (seasonality?)
Clinical Signs
Diagnosis of exclusion (rule out: ectoparasites, infections, allergies)
Must address secondary infection(s)

Allergy test in animals is not useful; can appear to have allergens to all things but what is important is what is causing the pruritis

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Atopic Dermatitis
Treatment
Symptomatic Rx

Antihistamines
Glucocorticoids
Free Fatty Acids
Topical therapy

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Atopic Dermatitis
Treatment
Specifc Rx

Immunotherapy (shot, sublingual)
Atopica
Apoquel
Cytopoint

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Antihistamines

What is the problem with these?

Does not target T-helper 2 cells which are the problem cells

Targets mast cells which do contribute to increased inflammation though

Therefore do not see a significant benefit

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Antihistamines

Examples

First generation:
Hydroxyzine (Benadryl)

Second generation:
Cetirizine (non-sedating)

Can give as a prevenative

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Glucocorticoids

Commonly used
Very effective (especially for environmental allergens)
Acts at multiple sites along atopic dermatitis cycle
Potent anti-inflammatory effects

Should NOT be used life long

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Glucocorticoids

Atopic Dermatitis Cycle

Acts on:
T-helper 2 cells
Reduces cytokines released
Mast cells 
Neutrophils
Monocytes
Eosinophils

Reduces inflammation

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Glucocorticoids

What organs does it effect?

Everything! So many side affects may be present

Most commonly: PU/PD

Lymph nodes
Heart and blood vessels
Skin and Fur
Adrenal glands
Kidneys
Pancreas (pancreatitis)
Bladder

Glucocorticoids
Oral Rx
Dose

Prednisone
Prednisolone
Methyprednisolone
Temaril-P (trimeprazine with prednisolone); anti-prurutic and anti-tussive

0.5-1.0 mg/kg/day
Try to do every other day

Glucocorticoids

Injectable

Should avoid this b/c of longevity

Greater risk of adverese effects

Glucocorticoids

Chronic use

Erythematous plaque formation (calcinotis cutis)

Free Fatty Acids

Many formulations
Topical
Enriched diets
Nutritional/herbal supplement

Not very strong by itself

Free Fatty Acids

Atopic Dermatitis Cycle

Makes tight junctions in epithelial barrier tighter; prevents allergen from entering

Some decrease in mast cell degranulation
Some action on T-Helper cells

Topical Therapy

Kinds

Shampoo
1-3x/week bathing

Sprays/wipes; once/day or can cause calcinosis cutis b/c most have steroid component

Avoid potent glucocorticoids

Allergy Immunotherapy

Intradermal Testing

Gold standard

Results in mast cell degranulation (wheals) - Type I hypersensitivity

False negatives due to:
Medications (no antihistamines on board)
Diseases (Cushing's; should be ruled out before this test)
Timing (peak season) 
Technique

In vitro serum testing

Measure IgE
Poor indicator of allergic disease
Poor reproducibility between samples

Atopic Dermatitis | Seasonal think

Grass, Trees, Weeds

Atopic Dermatitis | Year round think

Dust mites | Food allergies

Allergy Immunotherapy | Atopic Dermatitis Cycle

T-helper cells (blunts response; unsure exact mechanism) Mast cells Eosinophils

Allergy Shots

50-80% improve within 4-12 months Individualized protocols; usually once/week and hopefully shift to every other week Reactions are rare Usually treat for 1 year but can be up to 5 years Symptomatic treatment will still be necessary Goal: desensitize to allergen

Allergy drops

Sublingual Must be given every day Thought; many T-helper cells are here 50% response Not much research has been done in vet med

Cyclosporine | What is it?

Calcineurin inhibitors Targets T-lymphocytes Prevents T-cell activation and release of pro-inflammatory cytokines Inhibits histamine release Note: carcinogenic

Cyclosporine Activity | Atopic Dermatitis Cycle

Blocks pro-inflammatory cytokines such as IL-2 and pro-inflammatory pathways ``` Acts on: Langerhans cell T-cells Mast cells Eosinophils Dendritic cells ```

Cyclosporine | Drug interactions

``` Cytochrome P450 (liver and SI) Anything that blocks this will increase longevity of cyclosporine ``` Ketoconazole inhibits CYP450 and P-GP; so can give less of Cyclosporine b/c will stay in system longer

Cyclosporine | Onset

Slow onset of action (up to 2 months) Treatment can be refractory Should only use for allergies against environmental allergens => if not working most likely is not environmental issue

Oclacitinib | What is it?

Novel treatment Apoquel Allergic dermatitis and atopic dermatitis Dogs must be at least 12 months of age Can increase susceptibility to: Demodicosis Infections Neoplasia (low risk) NOT effective in cats Usually have to give daily

Oclacitnib | What does it target?

Apoquel Targets IL-31 (specific IL for pruritis) by blocking JAK-STAT signaling JAK-STAT needed to stimulate nucleus for gene transcription to make IL-31

Cytopoint | What is it?

Lokivetmab SQ injection Lasts 4-8 weeks 90% caninized mono-clonal antibody (do NOT use in cats or will cause serum sickness) Neutralizes IL-31 Inhibits binding to IL-31 receptors => do not register the pruritis b/c IL-31 never binds Does not need liver or kidney to be eliminated Promising results but there is a chance it will not work for certain patients