My Approach to Treatig Allergies Athoy Yu, DVM, MS, Dipl. ACVD Yu of Guelph Veteriary Dermatology Mississauga Oakville Veteriary Emergecy ad Referral Ceter Guelph Veteriary Specialty Hospital www.yuofguelphvetderm.com FAD VS Adverse Food Reactio FELINE Distributio patters Flea vs Food vs Atopy Flea HD Sigs affectig rump or tail, flak or dorsum Noflea HD (Food Allergies) Lesios o head or face Particularly with food HD Noflea ad ofood HD (Atopy) Wide spread distributio Abdome ad extremities Food ad Atopy Sometimes cliically idistiguishable Thorough workup elimiate differetial diagoses Hobi S, Like M, Marigac G et al. Vet Derm 2011; 22(5): 406-413. Adverse Food Reactio - cat + Cytology - Tips Gram stais rarely useful Roll samples across short legth of slide iclude more sites focus your search sped less time staiig save the eviromet. Black waxy exudate i ear è mieral oil prep Heat fix w/bbq lighter blue flame codesate evaporates. Sca 3D w/fie-tuig kob for Malassezia Malassezia kob Courtesy of Vero Durie VMD 1
+ Ski Scrapigs Tips Lots of mieral oil permethri (30:1) for mites Lower codeser for cotrast Demodex gatoi i cats abdome, iterscapular fecal for igested mites Demodicosis Pigmeted spots ID life stages Dorsal scaly areas for Cheyletiella. Rigworm (Dermatophyte) RealPCR Pael Microsporum gypseum, Microsporum cais ad Trichophyto metagrophytes 95% sesitivity; 99% specificity Results i 1 3 workig days Picked up 82/82 culture-positive samples + 11 samples that were missed by culture. Sample submissio Pluck hairs i a red top tube Toothbrush sample i plastic bag Affected ails or clippigs Aspirate from mycetoma + Ski Biopsy - Tips Use a DERMATOPATHOLOGIST Email cliical photos Full lesio descriptios NO mii-reports Biopsy procedure Multiple ski biopsies (3-5) from differet lesios Biopsy puch size to ecompass the lesio size o more, o less Elliptical biopsy for trasitios ormal ad abormal (e.g. ulcers, pigmet abormalities, etc) cut alog the log axis Evaluatio of patch testig with proteis, carbohydrates ad commercial foods for diagosis of caie adverse food reactios C. JOHANSEN*, C. MARIANI AND R.S. MUELLER* 2013 ESVD, 197 N=25 dogs raw ad cooked meat (=16) salmo ad carbohydrates (=11) commercial foods (=4) patches/dog = 17-30 Food Challege Other tests available form biopsy Special stais, (e.g. PAS, GMS, etc), Immuohistochemistry PCR Secod opiio at a later date. Save for later if too $$$ for cliet ow The 4-week Dietary Trial What s o the meu? Icreased ower acceptace 50% reductio of cliical sigs i 4-weeks If NOT è Chage the diet If positive respose oted è ower is more willig to cotiue for total of 8-12 weeks 100% restrictio REQUIRED 2
The Yu-ski 8 week Dietary Trial Dietary trial 8-12 weeks Symptomatics for atopy 6 weeks Steroids, CSA poor respose Jackso et al. Vet Derm 2006;17(5): 358 Atimicrobials 4 weeks R/O Sarcoptes Ivermecti/avermecti q2wks X 3 treatmets Pruritic Threshold Sarcoptes/ Fleas Ifectio Atopy Food The Yu-ski 8 week Dietary Trial 100 90 80 70 60 50 40 30 20 10 0 Day 0 2 weeks * 4 weeks 6 weeks 8 weeks 12 weeks Time HypoT4 Cushig's DM Bact HS Yeast HS Diet Ati-iflammatory Atimicrobial The Yu-ski 8 week Dietary Trial The Yu-ski 8 week Dietary Trial 100 100 90 90 80 70 60 50 40 Allergy Test OR Logterm Symptomatic Therapy Diet Ati-iflammatory Atimicrobial 80 70 60 50 40 Diet Ati-iflammatory Atimicrobial 30 20 10 30 20 10 Dietary Challege 0 Day 0 2 weeks * 4 weeks 6 weeks 8 weeks 12 weeks Time 0 Day 0 2 weeks * 4 weeks 6 weeks 8 weeks 12 weeks Time Osuria, Elaco Osuria, Elaco FIRST LINE TREATMENT for otitis extera Adaptable gel formulatio with a flexible, soft tip Pre-measured, easy-to-use sigle-dose tube Two doses, oe week apart. Dissolves i ear wax Slowly elimiated from the ear mechaically Stored refrigerated; Room Temp up to 3 moths. Not with hypersesitivity to igrediets Not with kow tympaic perforatio Active igrediets have o kow ototoxicity cocers Florfeicol 10mg/ml Bacteriostatic - ihibitig protei sythesis Gram-positive ad Gram-egative bact Terbiafie 10mg/ml allylamie with proouced fugicidal activity. Ihibits the early sythesis of ergosterol Betamethasoe acetate 1mg/ml Diester with potet itrisic glucocorticoid activity Spectrum of activity Staphylococcus pseuditermedius Malassezia pachydermatis MIXED ifectios with Pseudomoas Pseudomoas whe fortified with Nuflor 3
Osuria, Elaco 235 dogs with otitis extera Double-masked field N=159 OSURNIA; N=76 Vehicle 63.70% vs 41.72% (p=0.0094) Trasiet loss of hearig Cosider Vitami E ~20 IU/kg TID PO esp 8y+ Oishi N et al. Ototoxicity i dogs ad cats.vcna. 2012;42(6): 1259-1271 Off label use i cats ½ tube per ear Athoy Yu PruritUs (Itch) Psychogeic Iflammatory Neurogeic DAP/Feliway Stress Reducig Pheromoe Fluoxetie Selective Serotoi Re- Uptake ihibitor (SSRI) Clomipramie, Amitriptylie Ihibit serotoi (5-HT) ad orepiephrie reuptake BLOCKS IL-2, 4, 6, 13 Atopica Calcieuri Ihibitor Iihibits T-cell activatio è Decreased IL-2, IL-3, IL-4, ad TNF-alpha Atihistamie Blocks H1 Steroids GC/GCR bids to NF-κB, GResposeElemets, ad Activator Protei-1 è alterig iflammtio Apoquel JAK 1/3 ihibitor BLOCKS IL-31 Bids capsaici receptor TrpV1 (Vailloid) Neuropathic pai Caie Atopic Dermatitis Immuotherapeutic Moocloal atibody direct at IL-31 Multi-Modal Therapy Log Term Strategies Maximum allowable steroid dose per year e.g. Apoquel Max Pred dose mg/yr = 30 X BW i kg Max Dex dose mg/yr = 4.5 X BW i kg Sousa C. Glucocorticoids i veteriary dermatology. CVT XIV 2009; 400-405. Olivry T, et al. Treatmet of caie atopic dermatitis: 2015 updated guidelies from the Iteratioal Committee o Allergic Diseases of Aimals (ICADA). BMC Veteriary Research 2015, 11:210 Calciosis Cutis due to Steroids Courtesy of Dr. Joh MacDoald Iatrogeically steroid-iduced felie ski fragility sydrome (Also watch HCM ad DM) Log Term Strategies Maximum allowable steroid dose per year Optimizig Atopica Ifectios bladder ifectios, ski ifectios, septicemia, respiratory ifectios geeralized demodecosis Alopecia, thi ski, ski fragility (cats) Calciosis cutis, atrophic remodelig of scars, Milia-like comedoes, follicular cysts, Musculoskeletal atrophy, ruptured craial cruciate Hyperlipidemia, steroid hepatopathy, colitis, Adreal suppressio/atrophy, DM, ESS, icreased PTH levels, Behavioral chages, PU/PD, polyphagia, patig QUICKEN ati-iflammatory effect with short-term steroids Cocurret short-term use of predisoloe with cyclosporie A accelerates pruritus reductio ad improvemet i cliical scorig i dogs with atopic dermatitis Dip et al. BMC Vet Res 2013, 9:173 BEST optio to promote HAIR REGROWTH Cyclospori ihibits the expressio of Protei Kiase C stimulatig hair follicle growth ad hair fibre productio Harmo et al., 1995; Takahashi, Kamimura, 2001 4
Optimizig Atopica QUICKEN ati-iflammatory effect with short-term steroids Cocurret short-term use of predisoloe with cyclosporie A accelerates pruritus reductio ad improvemet i cliical scorig i dogs with atopic dermatitis Dip et al. BMC Vet Res 2013, 9:173 BEST optio to promote HAIR REGROWTH Cyclospori ihibits the expressio of Protei Kiase C stimulatig hair follicle growth ad hair fibre productio Harmo et al., 1995; Takahashi, Kamimura, 2001 ATOPICA ad KETOCONAZOLE syergistic 2.5 mg/kg Atopica + 2.5 mg/kg ketocoazole 1.5-1.67 mg/kg Atopica + 5 mg/kg Ketocoazole Taper medicatios together Gray L, et al The effect of ketocoazole o whole blood ad ski cocetratios of cyclosporie Vet Derm 2012:23 suppl:13 Hoey Bear before ad 8-weeks after Atopica ad Ketocoazole Douxo Pyo Optimizig Atopica Atopica - a SAFE ad reliable treatmet optio Demodex, staphylococci, Malassezia, drugs Nuttall T, et al. Life-log diseases eed life-log treatmet:log-term safety of ciclospori i caie atopic dermatitis. Vet Record 2014;174(suppl 2):3-12 Freeze capsules, Refrigerate liquid Vomitig decreased to less tha 3% J. Bachtel et al. Vet Derm, 2015:26:133 159. Atopica for Cats.for Dogs TOO Switch out weight-dosed syrige for TB syrige No Gelati capsular proteis Titratable/More accurately dosed Cost savigs Miimize side effects MOA: Rapidly BLOCKS the JAK/STAT pathway, especially JAK 1&3 BLOCKS JAK receptor sigal trasductio prevetig IL-31 effect o euros stoppig NEUROGENIC itch Also some spill over effects o IL-2, 4, 6, 13 associated w/th2 cells/allergies helpig to decrease INFLAMMATORY itch Aliso Hamilto DVM Bay Cities AH Mago still iflamed post-apoquel Pharmacology 0.4-0.6mg/kg BID 14d, the sid dose q12-24h Owers ofte call with worseig of sigs day 15,16,17 TIP: Start at ONCE daily to avoid ureasoable expectatios TIP: Split SID dose to ½ BID better to have a little aroud twice daily tha a lot oce daily 3.6 mg, 5.4 mg, or 16 mg same price for all Not a PRO-drug + quickly absorbed Quickly metabolized & excreted via urie/feces Needs to be give daily; Not desiged for q48h or less 5
Apoquel product label WARNINGS APOQUEL is ot for use i dogs less tha 12 moths APOQUEL is ot for use i dogs with serious ifectios. APOQUEL may icrease susceptibility to ifectio, icludig demodicosis, ad exacerbate eoplastic coditios Figure 2 - K Ghoreschi, et al. Targetig cytokie sigalig pathways usig Jak ihibitors. Selectivity ad therapeutic ihibitio of kiases: to be or ot to be? Nature Immuology 2009;10:356-360 Apoquel is like wie Too little leaves you watig more, but too much will make your head throb. Jo Plat Off-label dosig è blocks JAK2 Ihibits hematopoietic cytokies e.g. IL-12, IL-23, EPO, GM-CSF Cosideratios Icreased aggressio, seizures Dr. Jaso McLeod Hutsville AH Maritime AH/Humae Society Icreased appetite, weight gai IIcreased risk of iterdigital cysts creased risk of ifectio, papillomas Potetial risk with eoplasia e.g. CTCL Icreased risk of demodicosis Images courtesy of Alice Jeromi Demodex after 1 moth of Apoquel NB: Ski scrapigs prior to Apoquel was egative for Demodex Moocloal IL-31 Atibody Caiized Weight depedet dosig 2mg/kg SQ q4weeks Coditioal Licese Atipruritic No ati-iflammatory effect OK to use i cacer patiets Diarrhea, lethargy, aggressio, rash at ijectio site, worseig of pyoderma Murie portio Caie portio Atige bidig site Apoquel for Cats [off label] Apoquel ad other medicatios UPDATE IN FELINE THERAPEUTICS Cliical use of 10 emergig therapies. William Whitehouse W, Viviao K. J Felie Med & Surg 2015;17:220 234 0.5 mg/kg or 1 mg/kg PO q12h for 28 days Sigificatly reduced eosiophilic airway iflammatio ad pruritus Oclacitiib Alice Jeromi DVM360 2015 Cutaeous mastocytosis 1 mg/kg oce a day 1 to 1.5 mg/kg oce a day with success i oe case of felie idiopathic ulcerative dermatosis Oclacitiib i felie oflea-, ofood-iduced hypersesitivity dermatitis: results of a small prospective pilot study of cliet-owed cats. Ortalda C, et al. Vet Derm 2015;26(4):235 e52 12 cats 0.47 mg/kg p.o. twice daily (0.4-0.6mg/kg) 5/12 good improvemet i SCORFAD ad VAS pruritus Other cats were uchaged, deteriorated or dropped out due to treatmet failure Drug Class Atihistamies Systemic Glucocorticoids Topical Glucocorticoids Psycholeptics Omega 3 Fatty Acids Aalgesics No-steroidal ati-iflammatory products Prescriptio (=247) (%) 85 (34.4) 37 (15.0) 51 (20.6) 46 (18.6) 42 (17.0) 41 (16.6) 38 (15.4) 6
Apoquel ad Atopica TOGETHER Atopica AND Apoquel N = 8 dogs (4F:4M/group) Apoquel aloe (O) or Apoquel + Atopica (OC) Dosed daily at labelled doses for 3 weeks N=2 diarrhoea receivig both drugs (o BID Day 2 ad oe SID Day 17) Cliical pathology withi the referece rage Coclusios ad cliical importace No icrease umber of adverse evets or laboratory abormalities beyod those associated with oclacitiib give aloe. Cosider combiatio therapy Start Apoquel BID for 14 days, the SID for 14 days, the stop Start Atopica +/- ketocoazole every other day for 6 weeks, the taper Approach to Atopic Dermatitis Poor respose to Atopica/Steroids/Diet Sarcoptes Ski scrapigs Serologic testig False positives o allergy tests Respose to Rx Lime dip Iterceptor Revolutio Advatage-Multi Nexgard Simparica (ot yet i Caada) Bravecto Becskei, Csilla, et al. "Efficacy ad safety of a ovel oral isoxazolie, sarolaer (Simparica ), for the treatmet of sarcoptic mage i dogs." Veteriary parasitology 222 (2016): 56-61. Beuget, Frédéric, et al. "Efficacy of afoxolaer i a cliical field study i dogs aturally ifested with Sarcoptes scabiei." Parasite 23 (2016): 26. Taezler J. et al. Efficacy of fluralaer admiistered either orally or topically for the treatmet of aturally acquired Sarcoptes scabiei var. cais ifestatio i dogs. Parasites & Vectors20169:392 Bravecto for Demodex Oral isecticide ad acaricide for dogs Topical for cats soo Isoxazolie compoud Ihibit GABA-/glutamate-gated Chloride chaels Selectivity for isect euros over mammalia euros. 7
Bravecto for Demodex Fourie et al. (2015) Bravecto for Demodex Karas-Tecza J, et al (2015) Bravecto Oe dose Mite reductio 99.8% o Day 28 100% o Day 56 100% o Day 84 Statistically superior Advatage-Multi Oce mothly dosig Mite Reductio 98.0% o Day 28 96.5% o Day 56 94.7% o Day 84 Ca also bee used weekly- every other week Cliet owed dogs (=163) Geeralized demodicosis 2-18 moths (62,6%) over 2 years of age (37,4%) Fluralaer (25 mg/kg) PO 2X 3 moths apart +/- atibiotics as oly other treatmet 87.1% egative @ 4 weeks 12,9 % (all 2+ year) egative @ 2 moths Recommed: 1 tablet q2-3 moths util 2 egative ski scrapigs 4 weeks apart. Accelerated Hydroge Peroxide baths Ogeasolutios.com NexGard N=8 cliet owed 2.5mg/kg 0,14,28,56d Mite reductio 99.2% o Day 28 99.9% o Day 56 100% o Day 84 Statistically superior Advatage-Multi/Advocate N=8 cliet owed 0, 14, 28, 56d Mite Reductio 89.8% o Day 28 85.2% o Day 56 86.6% o Day 84 Efficacy @ q1wk?? Sarolaer (Simparica ; Zoetis) 8
North America Veteriary Dermatology Forum 2017 Orlado, Florida 2018 Maui, Hawaii 2019 Austi, Texas World Cogresses of Veteriary Dermatology Dijo 1989 WCVD1 Motreal 1992 WCVD2 Ediburgh 1996 WCVD3 Sa Fracisco 2000 WCVD4 Viee 2004 WCVD5 Hog-Kog 2008 WCVD6 Caadia Academy of Veteriary Dermatology www.cavd.ca - $25 membership fee Vacouver 2012 WCVD7 Bordeaux 2016 WCVD8 Sydey 2020 WCVD9 9