p.1

Diagnostic Approach
to the Pruritic Dog

Candace A. Sousa, DVM
Diplomate (Emeritus) American Board of Veterinary Practitioners,
Canine and Feline Practice
Diplomate (Emeritus) American College of Veterinary Dermatology

p.2

Its All About the Diagnosis
- With a diagnosis you can discuss the best therapies with the owner and let them know about the cause of the condition and the prognosis. - Too many veterinarians try to “fix the pet without knowing what theyre treating
- Would you do that with other clinical signs? - Seizures - PU / PD
- How do you make a diagnosis? - Test results – positive or as a “rule out - Response to therapy – or no response

p.3

Canine Pruritus
“Infectious Diseases
1. Sarcoptes scabiei
2. Malassezia colonization
3. Staphylococcal pyoderma
Demodex Hypothyroidism
Conformation (obesity)
4. Other (dermatophytosis, Cheyletiella, lice, etc)

Allergic Diseases
1. Flea allergy dermatitis
2. Atopic dermatitis
Food Non IgE (atopic-like)
Environmental allergens
3. Other allergic diseases (Drug eruptions, contact
allergy, etc)

p.4

Diagnosis Begins with Relief
- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.5

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.6

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.7

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.8

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.9

Canine Pruritus
“Infectious Diseases
1. Sarcoptes scabiei
2. Malassezia colonization
3. Staphylococcal pyoderma
Demodex Hypothyroidism
Conformation (obesity)
4. Other (dermatophytosis, Cheyletiella, lice, etc)

Allergic Diseases
1. Flea allergy dermatitis
2. Atopic dermatitis
Food Non IgE (atopic-like)
Environmental allergens
3. Other allergic diseases (Drug eruptions, contact
allergy, etc)

p.10

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.11

Canine Pruritus
“Infectious Diseases
1. Sarcoptes scabiei
2. Malassezia colonization
3. Staphylococcal pyoderma
Demodex Hypothyroidism
Conformation (obesity)
4. Other (dermatophytosis, Cheyletiella, lice, etc)

Allergic Diseases
1. Flea allergy dermatitis
2. Atopic dermatitis
Food Non IgE (atopic-like)
Environmental allergens
3. Other allergic diseases (Drug eruptions, contact
allergy, etc)

p.12

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.13

Canine Pruritus
“Infectious Diseases
1. Sarcoptes scabiei
2. Malassezia colonization
3. Staphylococcal pyoderma
Demodex Hypothyroidism
Conformation (obesity)
4. Other (dermatophytosis, Cheyletiella, lice, etc)

Allergic Diseases
1. Flea allergy dermatitis
2. Atopic dermatitis
Food Non IgE (atopic-like)
Environmental allergens
3. Other allergic diseases (Drug eruptions, contact
allergy, etc)

p.14

Diagnosis Begins with Relief

- Stop the Itch
- Rule out Parasites
- Treat Skin Infection
- Conduct Diet Trial
- Confirm Atopic Dermatitis

p.15

Food Allergy
- Actual allergic reactions (types I, III, or IV hypersensitivity reactions) have not been documented in the majority of dogs that have a pruritic disease that has improved after a change in diet
- Should be called a “Cutaneous Adverse Food Reaction [CAFR]

p.16

Food allergic Springer Spaniel
Image

p.17

Food allergic Springer Spaniel
Image

p.18

Food allergic Springer Spaniel
Image

p.19

Food Allergy - Testing
- No correlation between results of intradermal testing for food allergens and clinical hypersensitivity
- No correlation between results of allergen-specific IgE serology for food allergens and clinical hypersensitivity
- An in vitro allergy panel for food allergens run on 29 dogs after they were fed a 2 ingredient home-cooked diet for a minimum of 3 weeks
- No correlation

p.20

Test Diet
- A novel protein +/- carbohydrate
- Home cooked preferred
- 6 cups carbohydrate + 1 lb “meat = 4 lbs food
- 20 lb dog eats 1 lb / day
- Novel protein / CHO commercial diet
- Hydrolyzed protein diet
- Minimum of 4 weeks / maximum of 8 weeks - This will diagnose >90% of dogs with CAFR
- Rechallenge

p.21

Food allergic Springer Spaniel – 6 week post diet change

p.22

Food allergic Springer Spaniel – 6 week post diet change

p.23

Food allergic Springer Spaniel – 6 week post diet change

p.24

Canine Pruritus
“Infectious Diseases
1. Sarcoptes scabiei
2. Malassezia colonization
3. Staphylococcal pyoderma
Demodex Hypothyroidism
Conformation (obesity)
4. Other (dermatophytosis, Cheyletiella, lice, etc)

Allergic Diseases
1. Flea allergy dermatitis
2. Atopic dermatitis
Food Non IgE (atopic-like)
Environmental allergens
3. Other allergic diseases (Drug eruptions, contact
allergy, etc)

p.25

Canine Atopic Dermatitis
- A common pruritic dermatosis of dogs that is believed to be related to the presence of allergen-specific IgE antibodies
- 2 to 15% of the canine population
- Develops from 6 months to 7 years (70% between 1 and 3 years)

p.26

Scratching
Inflammatory process
Neuronal Itch Stimulation

Langerhans Cell
Th Cell
Sensory Nerve
Dendritic cell
Th, Cell
Eosinophil
Th, Cell
Monocyte
Neutrophil
Mast cell
Blood Vessel

p.27

Diagnosis of Canine Atopic Dermatitis
- History
- Breed
- Age at onset of clinical signs
- Physical examination
- Distribution of pruritus / lesions
- Rule out other pruritic dermatoses
- A diagnosis of exclusion!

p.28

Atopic dermatitis – Bull Terrier

p.29

Atopic dermatitis – Bull Terrier

p.30

Atopic dermatitis – Bull Terrier

p.31

Atopic dermatitis – caudal carpus

p.32

Atopic dermatitis – caudal tarsus

p.33

Use the intradermal test (IDT) or
allergen-specific IgE serology (ASIgES)
as a means of selecting allergens for
hyposensitization,
not to diagnose canine AD

p.34

Evaluation of Response to Immunotherapy
- Approximately 60% of dogs will show improvement in clinical signs after 10 months of maintenance concentration of allergens used weekly (meaning that 40% will not show any improvement) - Based on reports from several sources when allergen selection was done in a variety of ways
- This may manifest as a decrease in pruritus, lessened need for other therapies, etc.

p.35

BMC Veterinary Research
Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Disease of Animals (ICADA)

p.36

Therapy
- Treat / control the infections
- Avoidance (?)
- Topical therapy
- Allergen-specific immunotherapy

p.37

Therapy
- Medical therapy
- Antihistamines
- Corticosteroids
- Omega3 fatty acid supplements
- Cyclosporine
- Apoquel
- Cytopoint

p.38

Therapy
- Medical therapy
- Antihistamines
- Corticosteroids
- Omega3 fatty acid supplements
- Cyclosporine
- Apoquel
- Cytopoint

p.39

Antihistamines
- No antihistamine approved for use in veterinary medicine to treat pruritus or allergic skin disease since they cant show efficacy
- Target histamine that is released from mast cells after degranulation
- Research shows that atopic dermatitis is mediated by lymphocytes and
the cytokines they release
- Other research shows that histamine doesnt make dogs itch!

Carr MN, Torres SMF, Koch SN, Reiter LV. Investigation of the pruritogenic effects of histamine, serotonin, tryptase, substance P and interleukin-2 in healthy dogs. Vet Dermatol 2009; 20(2): 105-10.

p.40

Corticosteroids to Manage Allergic Dermatoses
- Prednisone or prednisolone
- 1-2 mg/kg SID, lowered to 0.25 - 0.5 mg/kg q 48 hrs
- Methylprednisolone (Medrol®)
- 4 mg = 5 mg prednisone
- Less PU/PD

p.41

Canine Organs Affected by Corticosteroids
CNS
- Polydipsia / Polyuria
- Mood Changes

LIVER
- Fat accumulation
- Elevated liver enzymes

ADRENAL GLANDS
- Suppression or iatrogenic hyperadrenocorticism (Cushings disease)

KIDNEYS
- Polyuria
- Altered electrolyte balance
- Protein losing glomerulonephropathy

PANCREAS
- Predisposed for type II diabetes
- Predisposed for pancreatitis

BLADDER
- Increase susceptibility to infection

SKIN & FUR
- Hair loss
- Thinning of the skin
- Increased susceptibility to infection
- Calcinosis cutis

LYMPH NODE
- Suppression of the immune system
- Lymphopenia

HEART & BLOOD VESSELS
- Water retention
- Muscle weakening

MUSCLE
- Thinning
- Weakness
- Pendulous abdomen
- Temporal muscle atrophy

p.42

Oclacitinib and Prednisolone Provide Similar Itch Control

Reference: Study A161R-AU-12-096

LS-mean (±SE) Pruritus VAS Scores Assessed by Owners

Delta-Cortef (prednisolone)
APOQUEL (oclacitinib)

*p=0.0087

0 20 40 60 80 100
7 14 21 28
Day of study
4 Hours
*

EXTREMELY SEVERE
SEVERE

MODERATE

MILD ITCHING

VERY MILD

NORMAL

p.43

Cyclosporine
- Atopica® (veterinary), Neoral® (human)
- Inhibits interleukin-2 (IL-2)
- Suppresses T-helper and T-suppressor cells - As per PI, “Potent Immunosuppressive
- 5 mg / kg SID on an empty stomach
- After 30 – 60 days if effective can try reducing the frequency of administration or the daily dose
- Can be costly, especially in large dogs

p.44

Cyclosporine
- Side effects
- Vomiting 30%
- Diarrhea 20%
- Gingival hyperplasia 2.3%
- Excessive shedding <2%
- Papilloma-like lesions
- Most resolve with dose modification (or spontaneously)
- Contraindicated in animals with a history of neoplasia
- Killed vaccines recommended
- Unknown impact on modified live vaccines

p.45

Apoquel ® (oclacitinib maleate): Indications
Indications
- Control dermatitis of pruritus and control associated of atopic with dermatitis allergic in dogs at least 12 months of age
- Short-term control of pruritus associated with acute allergic dermatitis (flea allergy, food allergy, atopic dermatitis, contact allergy)
- Long-term control of atopic dermatitis

p.46

Apoquel for Acute Use
- 0.4 – 0.6 mg/kg twice daily for up to 14 days
- Some use it at an SID dose
- Treat any infection present
- Staphylococcal pyoderma
- Malassezia dermatitis
- Consider what caused the itch to flare
- Control fleas
- Consider other ectoparasites

p.47

Starting a diet trial

4 week diet trial
Apoquel BID 14d then SID 7d
Recheck 4 weeks

p.48

Starting a diet trial

Not pruritic – challenge with previous diet48

p.49

Starting a diet trial

Still pruritic

Apoquel BID 14d then SID 7d
Recheck 8 weeks

Continue diet trial

p.50

Atopic Dermatitis is a Diagnosis of Exclusion
Manage the Manageable

- Atopic dermatitis

p.51

Veterinary Dermatology

Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life

p.52

Apoquel Maintains Efficacy with Long Administration

0 10 20 30 40 50 60 70 80 90 100
0 90 180 270 360 450 540 630 720 810 900 990 1080

Extremely severe itching
Severe itching Moderate itching
Mild itching
Very mild itching
Normal Dog

Day of Study
n = sample size. Sample size decreases are explained by variable (rolling) enrollment dates as well as dogs withdrawn from study. Cosgrove SB, Cleaver DM, King VL, Gilmer AR, Daniels AE, Wren JA, Stegemann MR. Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life. Vet Dermatol. 2015:June;26(3):171-e35.
-

p.53

Veterinarians Noted Improvement at the First Recheck Which Remained Constant

0 10 20 30 40 50 60 70 80 90 100
0 90 180 270 360 450 540 630 720 810 900 990 1080

Extremely severe itching
Severe itching Moderate itching
Mild itching
Very mild itching
Normal Dog

Day of Study
n = sample size. Sample size decreases are explained by variable (rolling) enrollment dates as well as dogs withdrawn from study. Cosgrove SB, Cleaver DM, King VL, Gilmer AR, Daniels AE, Wren JA, Stegemann MR. Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life. Vet Dermatol. 2015:June;26(3):171-e35.

p.54

Apoquel and Neoplasia

DISPELLING THE MYTHS

- No evidence of higher risk for new neoplasms with APOQUEL treatment

- Long-term continuation study1:
- Average age of dogs 9.3 years
- Rate of neoplasia (12/239 dogs 5%, developed neoplasia) was not greater than what would be expected in the general population of dogs

- 5-year post-approval PV safety review2:
- Two most commonly reported neoplasias (papillomas and histiocytomas) each were very rare incidence rates (< 1 dog reacting out of 10,000 dogs treated)

p.55

Apoquel and Neoplasia
Comparison of malignancies and nonmalignant skin masses in 339 allergic dogs
receiving long - term (> 6 months) oclacitinib with age and breed matched control
population. B. Lancellotti, J. Angus, H. Edginton, W. Rosenkrantz. Vet Dermatol 2019; 30(4):304.
- Test Group: dogs with allergic dermatitis treated with APOQUEL (n=339) for 6-58 months (n=35.5)
- Control Group: dogs with allergic dermatitis on other treatments (n=321)
APOQUEL CONTROL (other treatments)
Developed malignancies 16.2%* 12.5%
Developed benign skin masses 57.2%* 60.1%
* Not significantly different

p.56

Inhibiting IL-31 Using a Monoclonal Antibody Approach Holds
Potential for Specificity and Low Toxicity

Cytopoint, a monoclonal antibody that binds and removes IL-31 from circulation
Effects on: IL-31, a key JAK1-dependent cytokine driving clinical signs of AD

Corticosteroids bind corticosteroid receptors present in all cells
Effects on: immune system, CNS, metabolism, homeostasis

Atopica binds cyclophilin and inhibits calcineurin function
Effects on: NFAT signaling and antigen presentation

Apoquel inhibits JAK1 enzyme function
Effects on: JAK1 dependent cytokines driving clinical signs

p.57

Cytopoint
- A new option for sustained control of the clinical signs of atopic dermatitis in dogs
- An in-office injection that can improve the long-term quality of life for both the dog and the pet owner
- Cytopoint is:

Long Lasting
- Cytopoint is injected in- office, begins working within 1 day, and delivers relief for 4-8 weeks 1

Targeted
- Cytopoint is a caninized anti- cIL-31 monoclonal antibody (mAb)specifically designed to target the cytokine IL-31, a key cytokine involved in sending the itch signal to the brain

Safe
- Safe for dogs of all ages and can be used in combination with many common medications, including parasiticides, antibiotics, antifungals, corticosteroids, vaccines, immunotherapy, antihistamines, and other antipruritics, such as oclacitinib and cyclosporine 2
1. Michels GM, et al. Vet Dermatol. 2016; 27: 478–e129.
2. Michels GM, et al. Vet Dermatol. 2016; 27: 505–e136.

p.58

Apoquel
Cytokine binds receptor

APOQUEL binds JAK and works after cytokines bind receptor

Blocked pathways
IL-31 cytokine
Downstream signaling is not triggered
Cytopoint neutralizes only IL-31 cytokine before binding to receptor
Cytokines (IL-2, IL-4, IL-6, IL-13, IL-31)

JAK
Cytopoint

p.59

Mean Pruritus Scores Were Very Mild to Mild Starting on Day 1
- At day 42, owner assessment of pruritus VAS scores remained mild at 37.56 mm for dogs receiving 2 mg/kg dose of Cytopoint1

1 Michels GM, et al. Vet Dermatol. 2016; 27: 478–e129.

p.60

A Single Injection Begins Reducing Itch Within 1 Day;
Continues Working for at Least 1 Month

- At day 3, >80% of dogs treated with Cytopoint achieved treatment success, predefined as owner- assessed 20 mm reduction in pruritus as scored on the pruritus Visual Analog Scale (VAS).1

1 Michels GM, et al. Vet Dermatol. 2016; 27: 478–e129.

p.61

Cytopoint Begins to Improve Skin Lesions Within 7 Days
- Improvement in skin lesions was noted at the first visit on day 7. At day 28, there was a nearly 50% decrease in CADESI-03 dermatologist scores for dogs treated with Cytopoint1

1 Michels GM, et al. Vet Dermatol. 2016; 27: 478–e129.

p.62

Most Common Placebo Canine Atopic Dermatitis
Abnormal Health Events 0.0 mg/kg (52 dogs) Immunotherapeutic*
N (%) 2.0 mg/kg (50 dogs)
N (%)

Vomiting 1 (1.9) 4 (8.0)
Diarrhea 0 (0.0) 3 (6.0)
Pyoderma 2 (3.8) 2 (4.0)
Lethargy 0 (0.0) 2 (4.0)
Anorexia 0 (0.0) 2 (4.0)
Dermatitis 2 (3.8) 1 (2.0)
Otitis Externa 2 (3.8) 1 (2.0)

1 Michels GM, et al. Vet Dermatol. 2016; 27: 478–e129.

p.63

PRURITUS ATOPIC DERMATITIS

p.64

Tailored Treatment

Dog Presents with Allergic Signs
Pruritic Dog
Commence work-up to understand underlying allergy

Provide Immediate Relief of Itch
Protect the Bonds
APOQUEL
- Rapid, itch control for ALL allergic conditions, without many of the steroid side effects
- Comfort during Dx work-up
Other options: Oral & injectable steroids

Differential Diagnosis Completed
Other Allergic Conditions: Flea, food, contact, etc.

Tailored Treatment
Flea control, specific diets, removal contact allergens etc.
APOQUEL
Daily for allergy flares
Other options: Oral & injectable steroids

p.65

Tailored Treatment

Dog Presents with Allergic Signs
Pruritic Dog
Commence work-up to understand underlying allergy

Provide Immediate Relief of Itch
Protect the Bonds
APOQUEL
- Rapid, itch control for ALL allergic conditions, without many of the steroid side effects
- Comfort during Dx work-up
Other options: Oral & injectable steroids

Differential Diagnosis Completed
Atopic Dermatitis Confirmed
Seasonal or Chronic

Tailored Treatment
APOQUEL
- Already controlled on APOQUEL
- Owner provides daily oral tab
- Monthly visits inconvenient
- Manage intermittent flares
OR
CYTOPOINT
- < 12 months
- Comorbidities
- Poor response other Tx
- Non- drug alternative preferred
- Prefer not to pill daily
OR
APOQUEL and CYTOPOINT
- Mange flares
- Seasonal preferences

Other options include: steroids, cyclosporine, referral for allergy test + immunotherapy

p.66

QUESTIONS???