1. The document discusses new treatments for veterinary dermatology including Apoquel and isoxazolines for demodicosis. 2. It provides an in-depth overview of Apoquel including its mechanism of action, indications, and clinical trial results showing its effectiveness for atopic dermatitis. 3. The document also discusses challenges posed by methicillin-resistant Staphylococcus pseudintermedius including increasing resistance, dissemination, zoonotic potential, and treatment challenges for infections.

1. What’s New in Vet Dermatology?
Small Animal Specialist Hospital
Linda Vogelnest BVSc (Hons)
MANZCVSc (Feline Medicine)
FANZCVSc (Veterinary Dermatology)
Specialist Veterinary Dermatologist

2. What’s new?
• New Meds
– Apoquel® – when and why?, compared to Atopica®
– Bravecto® & Nexgard®- demodicosis
• Update on tricky infections
– MRSP dermatitis/otitis – diagnosis & treatment options
– Malassezia dermatitis/otitis – treatments

3. Apoquel
• Oclacitinib
– New drug and class
• Janus Kinase inhibitor
– Enzymes vital to signaling & cell activation
– Found in many cell types
» Suppressing activation (i.e. immunosuppressant!)
» Lymphocytes (cell-mediated immunity)
• “allergy” cytokines e.g. IL-2/4/7/9/21
• “itch” cytokine – IL-31
• “anti-viral/anti-tumour” cytokines e.g. IL-10, IFN-γ
» Innate immunity – macrophages, neutrophils etc – IL-12/23

4. Apoquel
• Oclacitinib
– Immunosuppressant
• No metabolic effects
• No drug interactions
– Indications
• Control of pruritus from allergic dermatitis
• Control of atopic dermatitis
• In dogs ≥ 12 months old

5. IL-31
• Injected into 11 dogs (expt AD)  pruritus (lasted 4-24 hours)*
– 2 dogs – placebo; 10 dogs - itch increased 2-10 fold; 1 dog – no itch
• Detected in serum*
– in 57% of dogs with ‘natural’ AD(127/223)
– in 0% of dogs with expt AD (no itch; 0/24), normal dogs (no itch; 0/87)
– in 0% of dogs with flea allergy (itchy; 0/30)
• Detected in human AD; levels correlate with severity of AD
Gonzales et al(2013)*
Interleukin-31: its role in
canine pruritus and
naturally occurring
canine atopic dermatitis."
Vet Dermatol 24(1): 48-
53

6. • 299 dogs client-owned dogs with AD
• Enrolled at 19 Dermatology Specialty Practices in USA

7. 0
1
2
3
4
5
6
7
8
9
10
0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112
OwnerVASScore(cm)
Day of Study
OWNER VAS SCORE
Placebo (P) Oclacitinib (O) Open Label (OL)
0
10
20
30
40
50
60
70
80
90
100
0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112
MeanCADESI-02Score
Day of Study
DERMATOLOGIST CADESI-02 SCORE
Placebo (P) Oclacitinib (O) Open Label (OL)
After time 0 Oclacitinib is significantly different from Placebo
As much as (p < 0.0001)

8. More Controlled Studies - AUS
• Gadeyne C, Little PR, King VL, et al (2014)
– Efficacy of oclacitinib (Apoquel®) compared with prednisolone for the control
of pruritus and clinical signs associated with allergic dermatitis in client-owned
dogs in Australia. Vet Dermatol 25(6), 512-e586
• single-masked, randomized controlled clinical trial
• 123 client-owned dogs with allergic dermatitis in GP
0
10
20
30
40
50
60
70
80
90
100
0 7 14 21 28
MeanVASScore(mm)
Day of Study
Delta-Cortef (prednisolone)
APOQUEL (oclacitinib)
DOSE:
Pred – 0.5-1mg/kg SID up to
Day 6, then EOD to Day 28
Apoquel – 0.4-0.6mg/kg BID
up to Day 14, then SID

9. More Controlled Studies - AUS
• Little PR, King VL, Davis KR, et al (2015)
– A blinded, randomized clinical trial comparing the efficacy and safety of
oclacitinib and ciclosporin for the control of atopic dermatitis in client-owned
dogs. Vet Dermatol, 26(1), 23-e28
• blinded, randomized clinical trial, non-inferiority test at day 28
• 226 client-owned dogs with AD from eight specialty derm practices
DOSE:
Atopica – 5mg/kg SID
Apoquel – 0.4-
0.6mg/kg BID up to
Day 14, then SID
0
10
20
30
40
50
60
70
80
90
100
0 7 14 21 28 35 42 49 56 63 70 77 84
MeanVASScore(mm)
Day of Study
Owner VAS Pruritus Score
Atopica APOQUEL
Extremely severe
itching
Severe itching
Moderate itching
Mild itching
Very mild itching
Normal dog
*
*
*
*

10. Apoquel in Sydney
• Compassionate use
– 5 dogs severe AD – 1-2 years
• Not readily controlled variety other tx
– 4 dogs x 2 years (JRT, Staffie, Sharpei X, Lab)
• Owners extremely happy
• Mild intermittent dermatitis – erythema, alopecia
• Minimal pruritus
• Worsening when daily dose due/if dose late (1 dog)
• Weight gain (mild, 2 dogs)
– 1 dog (Lab) – moved to Canberra (AD signs resolved)

11. Apoquel in
Sydney
• Compassionate use
– 1 dog (choc lab)
– severe AD
• Partially controlled - pred 0.5mg/kg EOD, azathioprine, shampoo
– Couldn’t afford cyclosporin
• Responded brilliantly in trial on Apoquel (within one day)
• Severe secondary infections – yeast, bacterial
• Poor response 1yr later restarting under compassionate use
– severe infections, continued pruritus, ultimately euthenasia

12. When To Use Apoquel?
• Indicated for Atopic dermatitis
• Also FAD, Food allergy, Contact (?)

13. 13
1. Atopic Dermatitis
Multi-modal treatment plans
1. Acute flare plan
2. Long-term management plan
Strategies:
1. Minimise allergen &/or irritant exposure
2. Immunotherapy
3. Symptomatic therapy
OLIVRY, DE BOER (2010). Treatment of canine atopic dermatitis: 2010 clinical practice
guidelines from the International Task Force on Canine Atopic Dermatitis. Veterinary
Dermatology 21: 3; 233-248.

14. 14
1. Atopic Dermatitis
Multimodal Treatment
• Allergen-specific Immunotherapy (“allergy vaccines”)
– May reduce need for life-long symptomatic therapy
• Safe symptomatic options
– Antihistamines, Fatty acids
– Topicals – cleansing, soothing, potent steroids
– Manage secondary infections
• More potent options
– Glucocorticoids
– Cyclosporin
– Oclacitinib

15. 15
1. Atopic Dermatitis
Multimodal Treatment
• Allergen-specific Immunotherapy (“allergy vaccines”)
• Safe symptomatic options
• More potent options
– Glucocorticoids – flares & long-term (low regular dose e.g. 1-2X wkly)
– Cyclosporin – slow onset: long-term (2-6wks; wean gradually)
– Oclacitinib – quick onset: flares & long-term (daily for life)
• ADVANTAGES
– small, easily divided tablets
– rare, mild side effects – GIT
– quick response
– no interference with allergy testing
• DISADVANTAGES
– Flare secondary infections/otitis?
– Cost

16. 16
2. Food Allergy?
• Diagnosis
– Elimination diet x 6-8 weeks
• Novel protein – fresh (ideal) or commercial
• Hydrolysed commercial
– Rechallenge phase x 2wks (smorgasbord)
• Role for Apoquel?
– During diagnostic trial - initial relief
– Discontinue last week of diet
• Stabilise if flare before progress to rechallenge

17. 17
3. Flea Allergy?
• Diagnosis
– Flea treatment trial x 4wks
• Adulticidal: quick flea kill
• Consider environment: consider IGR
• Role for Apoquel?
– During diagnostic trial - initial relief
– Discontinue last week of trial

18. When Not To Use Apoquel
• For pruritus due to infectious causes
– Bacterial pyoderma
– Malassezia dermatitis
– Bacterial &/or malassezia otitis
– Sarcoptes, Demodicosis, Dermatophytosis etc.

19. When Not To Use Apoquel
• For pruritus due to infectious causes
• For AD with effective, safe, affordable control plans
– Allergen-specific immunotherapy
– Safer symptomatic treatment plans
– Cyclosporin (EOD or less)
• For FAD, Food allergy in long-term
– Diagnose and avoid allergens
• In dogs under one year age
• In dogs with history of demodicosis?

20. Using Apoquel
Dose:
• 0.4-0.6mg/kg BID x 2wks, then SID long term
• Poor response – reconsider infections/diagnosis

21. Expectations:
• Quick response
• Pruritus flares common when reduce to SID
– Not severe
– Usually settle over next ~2-4 weeks
• What if SID not sufficiently effective?
– Consider timing of administration – AM vs PM
– Can dose be raised?
– Remember the dose range
– Consider off-label BID dosing (low dose)
Using Apoquel

22. 22
Vet Dermatol 2015; 26: 235–e52
5/12 Cats - AD

23. What’s new?
• New Meds
– Apoquel® – when and why?, compared to Atopica®
–Bravecto® & Nexgard®- demodicosis
• Update on tricky infections
– MRSP dermatitis/otitis – diagnosis & treatment options
– Malassezia dermatitis/otitis – treatments

24. Squeeze Tape Impression
for Demodicosis

25.  30 dogs – demodicosis
 21 generalised; 9 localised
 27 positive deep scrape (single)
 30 positive tape squeeze (one squeeze)
 Advantages
 Simple, less invasive
 Sensitivity comparable
(greater?) than deep scraping

26. 26
40 dogs – demodicosis
 23 generalised; 17 localised
 40 positive deep scrape
 30 positive tape squeeze (one
squeeze per site)
 29 positive trichogram
Advantage
 Simple, less invasive first test
Disadvantage
 Deep skin scraping more sensitive

27. 16 dogs Demodicosis
15 dogs – normal skin
15 dogs – inflamed skin
- Multiple squeezes per site
100% specificity – no mites
in normal/inflamed skin
(120 samples)
100% sensitivity – mites in
each lesional sample 16
dogs (16 samples)
Deep skin scraping – 90%
sensitivity
Mites in 14/16 samples

29. Squeeze Tape Impression
• Simple, minimally invasive test
– Less patient discomfort
– No skin trauma
– Readily sample multiple sites
• High specificity
• Apparent high sensitivity

30. Isoxazolines
• Bravecto® - fluralaner
– 8 dogs generalised
demodicosis
– No mites Days 56, 84

31. Isoxazolines
• Nexgard® - afoxolaner
– Twice monthly
– 8 dogs generalised
demodicosis; no mites day 84
– Anecdotal: monthly very
effective

32. Isoxazolines
• Simparica® - sarolaner
– Zoetis
– Monthly flea/tick control

33. What’s new?
• New Meds
– Apoquel® – when and why?, compared to Atopica®
– Bravecto® & Nexgard®- demodicosis
• Update on tricky infections
– MRSP dermatitis/otitis – diagnosis & treatment options
– Malassezia dermatitis/otitis – treatments

34. • Superficial - pyoderma, folliculitis, impetigo, mucocutaneous pyoderma
• Deep
• 2° to
– 1° Skin disease/defects
– Systemic immune suppression
34
Bacterial Pyoderma

35. 35
Bacterial Pyoderma
• Causal Bacteria
– Staphylococcus pseudintermedius
• Normal flora – esp. moist sites: nares, mouth, perianal
• Virulence factors
– Staphylococcus aureus
– Staphylococcus schleiferi schleiferi
• Other normal flora – many
– Gram +ve - coagulase negative Staph, α-haem. Streptococci,
Propionibacterium acnes
– Gram –ve - Clostridium spp., Acinetobacter spp.
• Transients – many
– Proteus mirabilis, Pseudomonas spp., Corynebacterium spp.

36. • Historically – predictable antibiotic sensitivity
– ~98% isolates sensitive to β-lactams
• cephalexin, amoxyclav
• Methicillin-resistance (MRSP, MRSA)
– Small mobile gene (mecA), transferred amongst Staph spp.; alters PBP
– MRSP - first report France – mid 1980’s; first dz USA – 1999
– Alarming  MRSP since 2006 – clonal spread of small number isolates
• ST71 (Europe, Japan), ST68 (USA)
• ST45 (Israel, Thailand)
36
Staphylococcus pseudintermedius

37. • Colonisation/transient carriage (dogs, cats)
– 0-10% worldwide; 30% in Japan (2006)
• Pyoderma (dogs)
– 15-17% (USA 2001-4); 0.8% (Germany 2007); 10% (Spain 2009)
– ~30% (USA 2008); 55-67% (Japan 2007-9)
– Australia – Sydney, Brisbane, Melbourne, Adelaide, Perth
• Perth - 12 isolates/19 dogs 2011/12: some potentially related ST45
(Thailand); some new lineage Canada
• Sydney – 1/29 dogs 2010/12
– 55 dogs 2013 - ~ 20%
37
MRSP
Siak M, Burrows AK, Coombs GW et al. Journal of Medical Microbiology 2014; 63 (9): 1228-1233
Ravens PA, Vogelnest LJ, Ewen E et al.
AVJ 2014; 92(5): 149-155.

38. • Concurrent transfer of resistance to multiple antibiotics: MDR
• Resistance to
– Β-lactams: cephalexin, amoxyclav, cefovecin
– Macrolides: clindamycin
– Fluoroquinolones: enro, marbo
– Tetracyclines: doxy
– TMS
– Chloramphenicol (European isolates)
• Sensitive to
– Rifampicin, amikacin
– Topicals: fusicid acid, mupirocin
– Restricted: vancomycin, linezolid, teicoplanin
38
MRSP Challenges

39. • Dissemination
–  risk MRSP infections – hospitalisation, prior antibiotic therapy
– Positive cultures hospital environment/staff
– Hospital outbreaks
• Zoonosis
– Rare
–  concern – hospital staff, pet owners
• Survival 6mnth (environ)
• Ready transmission household pets
39
MRSP Challenges

40. • Dogs, Cats, (Horses)
• Skin/ears
– Pyoderma – superficial, deep
– Otitis
– Surgical wound infections
• Urinary tract infections
• Septicaemia
40
MRSP Infections

41. • Clinical clues?
– None – looks like ‘normal’ pyoderma
• Historical clues?
– Poorly responsive to antibiotics
• Inadequate antibiotics dose/duration/poor owner compliance
• Concurrent GC therapy
• Active underlying disease (rare)
• MRSP
41
MRSP Pyoderma

42. • Diagnosis?
– Cytology
• Neutrophils, i/c bacterial cocci
– Exclude other causes for poor response to empirical ab’s
– Bacterial C&S (cytologically confirmed pyoderma sites)
• Pustule - puncture sterile 25g needle, culture swab
• Other lesions - dry swab rubbed vigorously 5 sec
• Avoid moist sites/cytology confirms mixed microbes
42
MRSP Pyoderma

43. • Skin cytology
– Adhesive tape impression (all lesions)
• Diff-Quik stain (no fixative)
43
Diagnosis

44. • Skin cytology
– Adhesive tape impression (all lesions)
– Glass slide impression/FNA (moist/nodular lesions)
44
Diagnosis

45. 45
Tape Impression - Normal skin - 4X lens (40x magnification)
 Keratinocytes dominate; normal flora very sparse

46. 46
Tape Impression – Pyoderma 4X lens (40x magnification)
 Clumped keratinocytes; Neutrophil rims/clusters

47. 47
4X lens (40x magnification)

48. 48
Neutrophils with intracellular & colonising cocci
1000X (oil)
200X (20X lens)

49. 49
Degenerate neutrophils with intracellular cocci – oif (1000x)

50. 50
Neutrophils with intracellular & colonising cocci – oif (1000x)

51. 51
Neutrophils with intracellular & colonising cocci
1000X (oil)
40X (4X lens)

52. 52
Neutrophils, colonising bacterial rods –
oif (1000x)
Yeast, and colonising cocci, rods
– oif (1000x)

53. 53
Deep Pyoderma: neutrophils with intracellular cocci (often sparse)
1000X (oil)

54. 1. Address 1° disease/cause
– Reduce immunosuppression
– Atopic Dermatitis – cyclosporin
2. Antibiotic susceptibility unpredictable
– Susceptibility testing important, in light of cytology findings!
– Methicillin (oxacillin) resistance = resistant to all β lactams
54
MRSP Pyoderma - Treatment

55. 1. Systemic Options
– Possibly doxycycline – 10mg/kg SID
– Possibly TMS – 30mg/kg BID
– Rifampicin – 5-10mg/kg SID
• Hepatotoxicity (25% dogs)
• Drug interactions – many
• Orange discolouration body fluids
• Combine with 2nd antibiotic?
55
MRSP Pyoderma - Treatment

56. 1. Systemic Options – doxy?, enro?, TMS? – based on C/S
2. Topical Options
– Antibiotics - resistance documented; colonisation MRSA (people)
• Mupirocin oint/cream (Bactroban®)
• Fusidic acid oint (Conoptal®, Fucidin® - tablet also)
– Antiseptics - act rapidly at bacterial cell walls; less susceptible to resistance?
• Chlorhexidine (more effective; less irritating/staining vs iodine)
– Effective as sole tx MRSP in dogs; daily chlorhex baths reduce MRSA (people)
– 3-4% faster antibacterial effect; leave-on solution/cream; shampoos/scrubs
– Resistance documented
• Other: acetic/boric acid; benzoyl peroxide
• Low irritant: silver sulfadiazine (Flamazine®); medical honey
• Sodium hypochlorite (household bleach) ~ 1ml per litre water
56
MRSP Pyoderma - Treatment

57. • Aggressive individual patient treatment plan
1. Minimum 3-wk treatment course
• Topicals - chlorhexidine; bleach +/- antibiotics
• Cleaning - frequent swimming (salt water), gentle shampooing
2. NO CONCURRENT GLUCOCORTICOIDS!
• Incomplete/delayed resolution of infections
• Encourages antimicrobial resistance
• Pruritus markedly reduced in 24-48 hours without steroids in most cases
57
MRSP Pyoderma – Tx Summary

58. • Aggressive individual patient treatment plan
1. Minimum 3-wk treatment course
• Topicals - chlorhexidine; bleach +/- antibiotics
• Cleaning - frequent swimming (salt water), gentle shampooing
2. NO CONCURRENT GLUCOCORTICOIDS!
3. Address underlying disease
• Atopic Dermatitis/On-going immunosuppression – active prevention plan
1. Topical antiseptics/cleaning
58
MRSP Pyoderma – Tx Summary

59. 59
Diagnosis uncertain?
• Options
1. Antibiotic (or antifungal) treatment trial (3wks; no steroids)
• Pruritic: pruritus & lesions should improve by 5-7d
• Non-pruritic: lesions should resolve by 2-3wks
2. Steroid-treatment trial (2-7 days; no antibiotics/antifungals)
• Pruritic: pruritus and lesions should improve notably by 7d
• Non-pruritic: not indicated!
3. Referral?
DON’T use pred & 5-10 days antibiotics !!
Pyoderma (& MD) - Treatment

60. 1. Prudent Antibiotic Use
1. Pruritic presentations
1. DO NOT USE pred/dex + 5-10d course cephalexin/cefovecin inj
2. Identify pyoderma (cytology or tx trial)
– 3wk cephalexin/amoxyclav AND NO concurrent GC
– Only use 2nd line drugs e.g. fluoroquinolones, clindamycin, cefovecin IF
supported by C&S
60
MRSP – Limiting Spread

61. 1. Sensitivity testing SP isolates Sydney
– 27 dogs; 227 isolates - dry swab, saline-moistened swab, skin scraping
– Cephalexin, amoxyclav, TMS (96%)
– Enrofloxacin, chloramphenicol (96%)
– Less to cefovecin (90%) , clindamycin (88%), doxycycline (78%)
61
Staph Pseudintermedius - Sydney
Ravens PA, Vogelnest LJ, Ewen E et al. Canine superficial bacterial pyoderma: evaluation of skin
surface sampling methods and antimicrobial susceptibility of casual Staphylococcus isolates.
AVJ 2014; 92(5): 149-155.

62. 1. Prudent Antibiotic Use
– When clearly indicated, wise choices, complete courses (3wks), no GC
2. Adequate staff and patient hygiene
– Strict hand hygiene
• Remove gross contamination – soap/water
• Alcohol hand gel
– Patient barrier nursing – if MRSP infection confirmed
3. Hospital disinfection/maintenance
– Regular decontamination – two-step process
• Remove organic debris
• Disinfection
– Alcohol (70-90% ethanol, isopropanol) – fastest action
– Bleach 0.5% (1:10 dilution) – 10-min contact time
– Chlorhexidine 0.15% - 10-min contact time
– Quarternary ammonium compounds e.g. Trigene® – less effective
62
MRSP – Limiting Spread

63. 1. Treat the infection first
 Topicals essential
 Fusidic Acid - Canaural®
 Miconazole/Polymixin B - Surolan®/Dermotic®
2. Reduce any chronic inflammatory changes
3. Treat the underlying disease
63
Treatment – MRSP Otitis

64. What’s new?
• New Meds
– Apoquel® – when and why?, compared to Atopica®
– Bravecto® & Nexgard®- demodicosis
• Update on tricky infections
– MRSP dermatitis/otitis – diagnosis & treatment options
– Malassezia dermatitis/otitis – treatments

65. • 2° to
– Allergies – AD (can markedly  pruritus)
– Systemic immune suppression
• Immuno-suppressive therapies (e.g. pred)
• Disease (e.g. neoplasia, FIV)
– Hormonal – hypoT, hyperA (can cause pruritus)
– Keratinisation defects - primary seborrhoea, sebaceous adenitis
65
Malassezia dermatitis

66. • Skin cytology
– Adhesive tape impression (all lesions)
• Diff-Quik stain (no fixative)
66
Diagnosis

67. 67
MD – oil lens (1000X)
Dx = >1 yeast per oif

68. • Surface cytology
– Most important
– Not 100% sensitive (esp. pyoderma)
• Clinical appearance
– Rarely reliable
– Odour – variable
• Consider treatment trial
– Antifungals alone (3wks min - superficial)
68
Diagnosis

69. 1. Treat the infection first (underlying dz 2nd)
 Systemic most reliable (min. 3wk course)
 Itraconazole 5-10mg/kg SID
 Pulse tx: 2 consecutive days/wk?
69
Treatment – Malassezia Dermatitis

70. 1. Treat the infection first (underlying dz 2nd)
 Systemic most reliable (min. 3wk course)
 Topicals can be useful
 Enilconazole rinse (twice wkly), miconazole cream (BID)
 Chlorhexidine solution (2-3%) sid-bid
 Shampoos – adjunctive only (limited residual effect)
 Chlorhexidine, miconazole
 Piroctone olamine, econazole
70
Treatment – Malassezia Dermatitis

71. 1. Treat the infection first (underlying dz 2nd)
 Topicals essential
 ‘azoles’ - BID seems most effective
 Miconazole - Surolan®/Dermotic®
 Clotrimazone - Otomax®
 Nystatin – BID
 Canaural®, Topigen®
 Systemics – may be helpful, especially if otitis media?
71
Treatment - Otitis

72. 72
Questions?