DERMATOLOGY DETAILS Peer Reviewed

What is New in the Diagnosis and Management of CANINE ATOPIC DERMATITIS? Sandra N. Koch, DVM, MS, Diplomate ACVD University of Minnesota

Canine atopic dermatitis (CAD) is a prevalent, approaches for avoidance of allergen and microbial multifaceted, pruritic skin disease with a complex exposure, and development of novel therapies to etiopathogenesis (Figure 1). In recent years, restore or protect the skin barrier of atopic .6 remarkable progress in the understanding of CAD has led to new diagnostic and therapeutic strategies. Role of Secondary Infections Bacterial and yeast infections are common in atopic UPDATES ON PATHOGENESIS OF CAD dogs, and are important contributing factors in the Not Always IgE pathogenesis of AD due to:7 Although immunoglobulin E (IgE) is an important • Increased adherence to, and colonization of, component in atopic dermatitis (AD), recent studies atopic skin by staphylococci have shown that AD is not always IgE-mediated.1,2 • Evidence that staphylococcal exotoxins serve As in humans, a small subset of dogs with AD as superantigens and, thereby, augment the do not have detectable—by either serology or cutaneous inflammatory response intradermal testing—allergen-specifi c IgE. This form • Reduced production of antimicrobial peptides of AD has been recently referred to as atopic-like (eg, defensins, cathelicidins) by epidermal cells dermatitis.1,2 • Bacterial and Malassezia hypersensitivity, which indicates a probable role for allergen-specific Immune Dysregulation and JK Inhibition immunotherapy.7 Immune dysregulation in the skin of atopic dogs These fi ndings, along with the increased incidence leads to overproduction of pro-infl ammatory and of bacterial resistance, have led to new strategies in pruritogenic mediators, such as T-helper type-2 antimicrobial therapy. cytokines, including interleukins IL-4, IL-5, IL-10, and IL-13.1,2 Impact of Food Allergy More recently, IL-31 was shown to play a Food allergy, or food-induced dermatitis, can manifest signifi cant role in CAD, inducing infl ammation and pruritus in atopic dogs via activation of Janus kinase (JK) signal transduction.3 This led to the development of the JK inhibitor, oclacitinib maleate (Apoquel, zoetisus.com).4 See page 98 for further information.

Skin Barrier Abnormalities There is increasing evidence that dogs with AD have epidermal barrier abnormalities, including abnormal lipid and ceramide composition, resulting in:1,5,6 • Dry skin due to increased transepidermal water loss • Increased penetration of allergens into the skin with stimulation of the immune response • Enhanced susceptibility to irritants and infections, contributing significantly to disease severity. FIGURE 1. Willie, a 4-year-old Labrador retriever with AD, had This new understanding has led to updated severe pruritus and secondary infections at initial presentation.

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While these guidelines may streamline diagnosis of TABLE 1. suspected CAD, diagnosis should still be based on:1,2 Favrot’s Criteria* for Canine Atopic 1. Patient’s signalment, history, and clinical signs Dermatitis (Favrot et al 2010) characteristic of AD Atopic dermatitis is very likely if ≥ 5 of the 2. Exclusion of other similar pruritic skin conditions, following criteria are present and other differentials have been ruled out: including secondary infections. Most important, allergen-specifi c IgE serologic Affected ear pinnae (but not pinnal margins) Affected front feet and/or intradermal tests should not be used as Age of onset < 3 years primary diagnostic criteria.1,2 Chronic or recurrent yeast infections Corticosteroid-responsive pruritus UPDATES ON TREATMENT OF CAD Mostly indoor lifestyle Nonaffected dorsolumbar area Therapeutic Approach & Evidence of Ef cacy Pruritus without skin lesions at onset CAD is a noncurable disease that has a detrimental * At least 5 positives = 85% sensitivity (miss 15%); 79% impact on the quality of life of affected animals speci city (falsely diagnose 21%) and their owners. There is no universal treatment; therefore, it is crucial to establish an effective 2,6 clinically in some dogs as AD. For this reason, it was and safe individualized multimodal treatment recently proposed to subdivide CAD into food-induced plan (Figure 2), as early as possible, based on AD and nonfood-induced AD, supporting investigation the patient’s quality of life, response to therapy, of potential food allergens in atopic dogs, particularly potential adverse effects, owner compliance, and 2,6 those with year-round signs. medication costs (Figure 3). Recent systematic evidence-based effi cacy reviews NEW DIAGNOSTIC CRITERIA FOR CAD (Table 2)9,10 and published guidelines from the Recently, a new set of diagnostic criteria, named International Task Force on Canine AD2 provide Favrot’s criteria (Table 1), was published, providing recommendations for, and new approaches to, a framework to assist in the diagnosis of CAD.8 therapeutic interventions, based on whether the However, these criteria have several limitations: patient is experiencing an acute fl are or has chronic • Not all atopic dogs fit within these criteria skin lesions. • Using the criteria alone can lead to misdiagnosis of AD Approach to Acute Flares • The criteria do not differentiate between patients Acute fl ares usually occur when allergens to which with and without food allergies. the dogs are sensitized are most prevalent. These fl are factors include environmental (eg, house dust mites, pollens), food, and/or fl ea allergens, and can be exacerbated by secondary infections. Make an effort to identify, avoid, and/or eliminate these triggering and contributing factors. When identifying fl are factors:2 • Look for evidence of fleas or flea dirt, especially in endemic areas • Investigate possible ingestion of diet triggers to which the is known to be sensitive • Investigate possible aeroallergen prevalence and exposure (eg, consultation of pollen count) • Perform cytology (+/- bacterial skin culture and susceptibility, if indicated) to confirm the presence of bacterial and/or yeast skin and ear infections. These fl ares can be addressed with a combination of:2 FIGURE 2. After treating secondary infections and testing • Frequent baths with mild, nonirritating many therapeutic interventions to assess his individual antipruritic and/or antimicrobial shampoos and response, Willie’s allergies became well controlled with moisturizers allergen-specifi c immunotherapy, frequent medicated baths, • Short course of oral and/or topical glucocorticoids and oral ciclosporin. • Control of exposure to fleas and food allergens.

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FIGURE 3. Integrated treatment approach to canine atopic dermatitis.

Approach to Chronic Disease TABLE 2. Similar to the approach to acute fl ares, triggering Evidence-Based Review: Various Therapies factors of chronic disease need to be identifi ed and for Treatment of Canine Atopic Dermatitis corrected. Focus management of chronic signs on (Olivry and Mueller 2003, Olivry et al 2010) identifying the safest and most effi cacious long- term therapeutic modalities and managing chronic GOOD EVIDENCE FOR USE recurrent secondary infections, which can be done Ciclosporin with a combination of interventions, including:2 Oral glucocorticoids • Frequent baths with mild, nonirritating FAIR EVIDENCE FOR USE antipruritic and/or antimicrobial shampoos and Misoprostol moisturizers Pentoxifylline • Anti-inflammatory and antipruritic systemic Subcutaneous recombinant gamma-interferon medications Topical hydrocortisone aceponate Topical tacrolimus • Allergen-specific immunotherapy (ASIT). Topical triamcinolone INSUFFICIENT EVIDENCE FOR OR AGAINST USE THERAPEUTIC MANAGEMENT: Anti-In ammatory & Antipruritic Medications Ascorbic acid Aspirin (Table 3, page 99) Chinese herbal therapy Topical Glucocorticoids This form of therapy is best suited for short-term Gabapentin use, particularly in acute fl ares, once to twice Homeopathy daily, to prevent potential adverse effects, such as Immunomodulating antibiotics (doxycycline) Maropitant (Cerenia, cerenia.com) 2,9,10 cutaneous atrophy and calcinosis cutis. Masitinib maleate (Kinavet-CA1, kinavet.com) There is fair evidence of effi cacy of 0.015% Oral/topical fi rst- or second-generation triamcinolone acetonide and hydrocortisone aceponate spray for the treatment of CAD.9-11 Other Papaverine Topical capsaicin topical glucocorticoids commonly used include Topical pramoxine betamethasone valerate and mometasone furoate Tranilast cream. Tricyclic antidepressants (doxepin, amitriptyline) FAIR EVIDENCE AGAINST USE Oral Glucocorticoids Arofylline Good evidence exists that demonstrates high effi cacy Cysteinyl leukotriene receptor antagonists of oral glucocorticoids for treatment of CAD.9,10 Leukotriene synthesis inhibitors (zafi rlukast, zeleuton)

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• They are fast acting and, for many years, have Recombinant Interferons been the mainstay treatment of CAD, particularly This form of therapy has some reported effi cacy, during acute flares. however, dosage and protocols for optimal benefi t • They are a less ideal treatment option for long- and safety are currently unknown.9-11 term management of chronic disease due to their broad, nonspecific anti-inflammatory response Antihistamines & EFAs and many potential adverse effects. Despite their extensive use in practice, there is • It is important to recognize, though, that insuffi cient evidence for or against the use of 2,9-11 some atopic dogs may require long-term antihistamines and EFAs for treatment of CAD. glucocorticoids when other therapies fail, induce While antihistamines and EFAs are not suited for 2,9,10 adverse effects, or cannot be attempted due to acute fl ares, they may have some effi cacy: client financial limitations. • In patients with mild pruritus If long-term systemic glucocorticoids are • As part of combination therapy required, it is crucial to attempt identifi cation • In a preventive role of the safest and lowest dose and frequency that • As sparing agents for glucocorticoids. remains effi cacious (eg, a target dose for prednisone Oral antihistamines that may be used include: 14 is 0.25–0.5 mg/kg PO Q 48 H). Injectable • Fexofenadine (18 mg/kg PO Q 24 H) 11 formulations should be avoided to minimize adrenal • (2 mg/kg PO Q 12 H) • Combination of hydroxyzine (20.9 mg/10 kg) suppression.2,9-11 and chlorpheniramine (0.7 mg/10 kg) (divided) PO Q 12 H15 Ciclosporin • Cetirizine (0.5–1 mg/kg PO Q 12 H).11 Good evidence exists that demonstrates high There is no current evidence of superior effi cacy of ciclosporin, a calcineurin inhibitor, for effi cacy of any EFA combination, dosage, ratio, or treatment of CAD. Oral ciclosporin is approved formulation, including enriched diets, to improve for long-term management of CAD at 5 mg/kg skin and coat quality and reduce pruritus in dogs PO Q 24 H, and adverse effects are uncommon with AD.2,9,10 I recommend high-quality fi sh oil with at this dose. Ciclosporin can require 4 to 6 weeks omega-3 EFAs—eicosapentaenoic acid (EPA) and to achieve satisfactory clinical improvement; docosahexaenoic acid (DHA)—at 300 mg (180 mg therefore, it is not suitable for treatment of acute of EPA and 120 mg of DHA) per 4.5 kg (10 lb) per fl ares.2,9-11 day PO.11

Tacrolimus 0.1% Cream Oclacitinib Maleate Tacrolimus, another calcineurin inhibitor, has good Oclacitinib maleate, a JK inhibitor, is a new and 9-10 evidence of effi cacy. It is best suited for localized unique oral targeted therapy that selectively inhibits 2,9-11 lesions and appears to be safe for short-term use. JAK-1-dependent cytokines involved in allergic infl ammation and pruritus, particularly IL-31.4 It Misoprostol is approved for treatment of allergic dermatitis or Misoprostol, a prostaglandin E1 analogue, has atopic dermatitis in dogs older than 12 months of good evidence of modest efficacy at 5 mcg/kg age. 9,10,12 PO Q 8 H. Studies. Several controlled studies have indicated an effi cacy rate comparable to glucocorticoids and Pentoxifylline ciclosporin, with a fast onset of action (within 24 Pentoxifylline, a phosphodiesterase inhibitor, has fair H) for control of pruritus.16-18 It is suitable for evidence of effi cacy at 10 mg/kg PO Q 12 H.2,9-11 the treatment of acute fl ares as well as long-term However, a more recent study using higher doses—20 management.17,19 mg/kg PO Q 8 H—in combination with oral essential Drug interactions. The safety of oclacitinib in fatty acids (EFAs) showed more benefi t.13 combination with systemic immunosuppressive Pentoxifylline has a good safety profi le but is not agents, such as glucocorticoids or ciclosporin, is suited for acute fl ares due to its slow onset of action unknown. It can be used safely with other common (4–6 weeks). It may be best suited as adjunctive medications, such as antibiotics, nonsteroidal anti- therapy with medications, such as glucocorticoids, infl ammatory drugs, parasiticides, vaccinations, and in chronic conditions.2,9 allergy shots.

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TABLE 3. Selected Canine Atopic Dermatitis Therapeutic Agents ACTIVE INGREDIENT BRAND NAME DOSAGE KEY POINTS TOPICAL GLUCOCORTICOIDS 0.015% Triamcinolone Genesis spray Topically Q 12–24 H • Indicated for acute fl ares and localized lesions acetonide (virbacvet.com) • Best suited for short-term use (7–14 days) Hydrocortisone Cortavance spray Topically Q 12–24 H • Adverse effects include cutaneous atrophy and calcinosis aceponate (virbac.ca) cutis Betamethasone Otomax (merck-animal- Topically Q 12–24 H valerate health-usa.com) Mometasone furoate Mometamax (merck- Topically Q 12–24 H animal-health-usa.com) ORAL GLUCOCORTICOIDS Prednisone or Generic formulations Induction or initial dose: • Indicated for acute fl ares prednisolone 0.5–1 mg/kg PO Q 24 H • Fast acting and taper • Broad, nonspecifi c anti-infl ammatory response Target dose: 0.25–0.5 mg/kg • Many potential adverse effects PO Q 48 H CALCINEURIN INHIBITORS Ciclosporin Atopica 5 mg/kg PO Q 24 H • Indicated for long-term management (us.atopica.com) Initial dose: Can be tapered • Can take 4–6 weeks to achieve clinical improvement to the lowest dose that • Not suitable for treatment of acute fl ares controls the disease • Most common adverse effects are gastrointestinal signs Tacrolimus 0.1% cream Protopic Apply topically Q 12–24 H • Indicated for localized lesions (protopic.com) • Appears to be safe for short-term use PROSTAGLANDIN E1 ANALOGUE Misoprostol Cytotec (pfi zer.com) 5 mcg/kg PO Q 8 H • Modest effi cacy PHOSPHODIESTERASE INHIBITOR Pentoxifylline Trental 10 mg/kg PO Q 12 H or • May be best suited as adjunctive therapy for chronic (products.sanofi .us) 20 mg/kg PO Q 8 H conditions • Slow onset of action (4–6 weeks) • Not suited for acute fl ares • Good safety profi le ANTIHISTAMINES Fexofenadine Allegra (allegra.com) 18 mg/kg PO Q 24 H • Helpful for mild pruritus Hydroxyzine Generic formulations 2 mg/kg PO Q 12 H • Best as part of combination therapy • Preventive role Hydroxyzine + Histacalmine (virbac. (20.9 mg + 0.7 mg)/10 kg • Sparing agents for glucocorticoids chlorpheniramine com) (divided) PO Q 12 H • Not suitable for acute fl ares Cetirizine Zyrtec (zyrtec.com) 0.5–1 mg/kg PO Q 12 H ESSENTIAL FATTY ACIDS High-quality fi sh oil Generic formulations 300 mg/4.5 kg (10 lb) PO Q • No current evidence of superior effi cacy of any EFA (with EPA and DHA) 24 H combination, dosage, ratio, or formulation, to improve skin and coat quality and reduce pruritus JANUS KINASE INHIBITOR Oclacitinib maleate Apoquel (zoetisus.com) 0.4–0.6 mg/kg PO Q 12 H • Indicated for acute fl ares and long-term management for 2 weeks; then Q 24 H • Fast onset of action (within 24 H) for pruritus control • Most common adverse effects are gastrointestinal signs • Contraindicated in dogs with serious infections or neoplasia • May increase susceptibility to infections, demodicosis, and neoplastic conditions IMMUNOTHERAPY Subcutaneous Various protocols exist • Very specifi c targeted effect allergen-specifi c Adjust dosage and schedule • Slow onset of action (up to 12 months) immunotherapy for each patient • Not useful for acute fl ares • Most common adverse reaction is worsening of pruritus Sublingual Heska Allercept Pump dispenser directly • Most common adverse reactions are face rubbing, transient immunotherapy Therapy Drops onto oral mucosa, under and worsening of pruritus, and gastrointestinal signs (heska.com) around the tongue, Q 12 H

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Effect on allergy testing. It was shown to New topical therapies include: not interfere with allergy test results after 30 days • Oxychlorine (Vetericyn spray, vetericyn.com) of administration.17-21 More studies need to be • Chlorhexidine preparations (eg, Douxo conducted to demonstrate if longer use of Apoquel Chlorhexidine + Climbazole mousse and spray, would affect the results of allergy testing. douxo.us) Contraindications & Adverse Effects. Apoquel • Baths with sodium hypochlorite (1–2 tablespoons is contraindicated in dogs with serious infections of bleach per quart of water). and may increase susceptibility to infections, demodicosis, and neoplastic conditions. The Medicated Bathing most common adverse effects are gastrointestinal Frequent soothing and/or antimicrobial, signs. Lethargy, unspecifi ed benign cutaneous and nonirritating shampoos and moisturizers may subcutaneous masses, histiocytomas, papillomas, be helpful to minimize or control pruritus and urinary tract infections/cystitis, pyoderma, and infections in acute fl ares and chronic disease.9 otitis have also been reported.16,19 Bone marrow However, no evidence currently exists that suppression may be of concern, particularly if extra- demonstrates any benefi t from shampoos or label doses are used.18-21 conditioners containing lipids, oatmeal, pramoxine, Dosage & Monitoring. The dose range antihistamines, or glucocorticoids.9 recommended is 0.4 to 0.6 mg/kg PO Q 12 H, with Ten-minute, weekly baths with a shampoo or without food, for the fi rst 2 weeks; then Q 24 H containing antiseptics, lipids, and complex sugars thereafter for maintenance.16,21 (Allermyl, virbacvet.com) were shown to reduce Although the manufacturer of Apoquel does pruritus within 24 hours in 25% of dogs.22 not recommend specifi c laboratory monitoring, I recommend frequent recheck visits to evaluate THERAPEUTIC MANAGEMENT: laboratory results, until more long term safety Improving the Cutaneous Barrier studies become available. Oral EFAs, nonirritating and moisturizing • Baseline: Complete blood cell count (CBC), shampoos and sprays, and other topicals containing serum biochemical profile, urinalysis (+/-) urine lipids, such as cholesterol, EFAs, and/or ceramide culture complexes, may be of benefi t as adjunctive therapy • 1 month and 3 months post-treatment: CBC to protect or improve the epidermal barrier.2,9 • Every 6 months post-treatment: CBC, serum Recent controlled studies suggest that ceramide- biochemical profile, urinalysis, and urine culture based topical products, such as Allerderm Spot-On (virbac.ca) and Dermoscent Essential-6 Spot-On THERAPEUTIC MANAGEMENT: (dermoscent.com), may help reduce clinical signs of Antimicrobial Products AD in dogs.23,24 Antimicrobial Therapy If infection is not addressed, allergy management will fail completely. Due to the high incidence of multidrug resistance, minimize antibiotic use by favoring topical antimicrobials and narrow-spectrum antibiotics. Milder and localized bacterial and yeast infections may be treated with topical antimicrobials, such as ointments, creams, gels, sprays, mousse, or wipes containing antiseptics, antibiotics, and/or antifungals. More severe or generalized cases may require systemic antimicrobials. To identify and minimize antibiotic resistance in recurrent and unresponsive cases, choose the antibiotic based on culture and susceptibility testing. Proper duration and FIGURE 4. Use of sublingual immunotherapy, appropriate doses are important to minimize which is applied via a pump dispenser directly treatment failures and relapses and help prevent to the mucosa, under and around the tongue. resistance.2,9

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A shampoo and spray that contains the ceramide precursor phytosphingosine (Douxocalm, douxo. The Importance of Flea Control us) and a shampoo containing antiseptics, fatty Evidence exists that atopic dogs are predisposed to hypersensitivity acids, and complex sugars (Allermyl, virbacvet.com) reactions when exposed to fl ea salivary antigens. Therefore, all dogs with demonstrated similar clinical improvements.6 AD should receive year-round fl ea preventives. Identify fl ea infestations Further studies are needed to determine the true and fl ea-allergy dermatitis and consider them potential triggering factors 2,9 benefi ts of various therapies on cutaneous barrier of allergy fl ares. impairment of atopic dogs. Currently, several SLIT suppliers offer their own THERAPEUTIC MANAGEMENT: formulations with different protocols. A 1-year Immunotherapy (Table 3, page 99) therapy trial is recommended, however, the ideal Allergen-Speci c Immunotherapy total duration of treatment is currently unknown. Attempt ASIT whenever CAD is diagnosed, as early Safety & Adverse Effects. SLIT appears as possible. ASIT remains the treatment of choice to be very safe, and the most common adverse for long-term management of CAD due to its very reactions are face rubbing, transient worsening of specifi c targeted effect and safety, despite only a few pruritus, and gastrointestinal signs that can resolve controlled studies supporting its effi cacy.2,6,9 It is not spontaneously within 1 to 2 weeks. If symptoms useful for acute fl ares due to its slow onset of action persist, the schedule may be altered to help manage (up to 12 months). side effects. Crucial aspects that maximize success and Studies. There are only a few studies minimize adverse effects of treatment include: demonstrating the effi cacy of SLIT based on allergy • Careful selection of allergens correlating with testing for atopic dogs.25-28 environmental exposure • Adjustment of dosage and schedule to suit the An uncontrolled open clinical trial of SLIT needs of each patient. for CAD, which used a formulation and dosing Subcutaneous ASIT has been administered for many schedule equivalent to a commercial product years, with a 50% to 80% reported success rate.2,9-11 (Heska Allercept Therapy Drops, heska.com), demonstrated an effi cacy rate similar to injectable 25-28 Sublingual Immunotherapy immunotherapy. Interestingly, 49% of dogs Sublingual immunotherapy (SLIT), or “allergy that previously had not responded to injection drops,” is a recent form of allergen immunotherapy immunotherapy responded favorably to SLIT. that is formulated with glycerin-based extracts in Future controlled trials are needed to determine a vehicle that augments uptake through the oral the true effi cacy of SLIT and demonstrate whether mucosa and is typically customized for each patient a particular formulation, dose, or administration based on positive reactions on allergy testing. schedule is superior for control of CAD. • The aeroallergens are formulated and administered via a pump dispenser directly to the mucosa, under FUTURE THERAPEUTIC TARGETS and around the tongue (Figure 4). Further studies are needed to investigate the potential • These allergens are absorbed through the oral benefi ts of other therapies for CAD, including other mucosa with uptake and processing by specialized kinase inhibitors, monoclonal antibodies, diets, oromucosal dendritic cells. and nutraceuticals, such as probiotics. Advances in Although SLIT has been widely used in Europe for our understanding of this complex and fascinating treating human allergies, it has only recently become disease will continue to contribute to new therapeutic available for treating animals in the United States. solutions in the future. Advantages. The main advantage of SLIT is ease of administration, which is benefi cial for: • Dogs that do not tolerate injections SANDRA N. KOCH • Owners who find injections difficult to administer Sandra N. Koch, DVM, MS, Diplomate ACVD, is an associate professor of veterinary dermatology at University of Minnesota College of Veterinary or are frightened of needles. Medicine. She is primarily involved with clinical service and teaching, The glycerin imparts a slightly sweet taste that many and her special interests include allergic and infectious skin diseases, dogs view as a treat. particularly multidrug and methicillin-resistant Staphylococcus skin and ear infections and dermatologic therapies. She is the primary author of The typically recommended protocol Dosage. the Canine and Feline Dermatology Drug Handbook. includes an indefi nite twice daily dosing schedule.

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AD = atopic dermatitis; ASIT = 15. Eischenseer M, Johansen C, Mueller RS. allergen-specifi c immunotherapy; CAD Effi cacy of dimetinden and hydroxyzine/ chlorpheniramine in atopic dogs: A = canine atopic dermatitis; CBC = randomized, controlled, double-blinded trial. complete blood cell count; DHA = Vet Rec 2013; 173(17):423. docosahexaenoic acid; EFA = essential 16. Cosgrove SB, Wren JD, Cleaver DM, et al. A blinded, randomized, placebo-controlled fatty acid; EPA = eicosapentaenoic trial of the effi cacy and safety of the Janus acid; IgE = immunoglobulin E; JK kinase inhibitor oclacitinib (Apoquel®) in = Janus kinase; SLIT = sublingual client-owned dogs with atopic dermatitis. Vet Dermatol 2013; 24(6):587-597. immunotherapy 17. Gadeyne C, Little P, King VL, et al. Effi cacy of oclacitinib (Apoquel®) compared with References prednisolone for the control of pruritus and 1. DeBoer DJ. Canine atopic dermatitis: New clinical signs associated with allergic dermatitis targets, new therapies. J Nutr 2004; 134(8 in client-owned dogs in Australia. Vet Dermatol suppl):2056S-2061S. 2014; 25(6):512-518. 2. Olivry T, DeBoer DJ, Favrot C, et al. Treatment 18. Little PR, King VL, Davis KR, et al. A of canine atopic dermatitis: 2010 clinical practice blinded, randomized clinical trial comparing the guidelines from the International Task Force on effi cacy and safety of oclacitinib and ciclosporin Canine Atopic Dermatitis. Vet Dermatol 2010; for the control of atopic dermatitis in client- 21(3):233-248. owned dogs. Vet Dermatol 2015; 26(1):23-30. 3. Gonzales AJ, Humphrey WR, Messamore JE, et 19. Cosgrove SB, Cleaver DM, King VL, et al. al. Interleukin-31: Its role in canine pruritus and Long-term compassionate use of oclacitinib naturally occurring canine atopic dermatitis. Ve t in dogs with atopic and allergic skin disease: Dermatol 2013; 24(1):48-53. Safety, effi cacy and quality of life. Vet Dermatol 4. Gonzales AJ, Bowman JW, Fici GJ, et al. Feb 2015 [epub ahead of print]. Oclacitinib (APOQUEL) is a novel Janus kinase 20. Plumb DC. Plumb’s Veterinary Drug Handbook, inhibitor with activity against cytokines involved in 8th ed. Ames, IA: Wiley-Blackwell, 2015. allergy. J Vet Pharmacol Ther 2014; 37(4):317-324. 21. Clear V, Petersen A, Rosser EJ, Ruggiero 5. Marsella R, Olivry T, Carlotti DN. International V. Investigation of the effects of 30 day Task Force on Canine Atopic Dermatitis. Current administration of oclacitinib (Apoquel) on evidence of skin barrier dysfunction in human intradermal and allergen-specifi c IgE serology and canine atopic dermatitis. Vet Dermatol 2011; testing in atopic dogs. NAVDF proc, Nashville, 22(3):239-248. TN 2015, p 32. 6. Marsella R. An update on the treatment of 22. Löfl ath A, von Voigts-Rhetz A, Jaeger K, canine atopic dermatitis. Veterinary Medicine: et al. The effi cacy of a commercial shampoo Research and Reports 2012; 3:85-91. and whirlpooling in the treatment of canine 7. DeBoer DJ, Marsella R. The ACVD task pruritus: A double-blinded, randomized, force on canine atopic dermatitis (XII): The placebo-controlled study. Vet Dermatol 2007; relationship of cutaneous infections to the 18(6):427-431. pathogenesis and clinical course of canine atopic 23. Marsella R, Genovese D, Gilmer L, et al. dermatitis. Ve t Immunol Immunopathol 2001; Investigations on the effects of a topical 81(3-4):239-249. ceramides-containing emulsion (Allerderm Spot 8. Favrot C, Steffan J, Seewald W, Picco F. A on) on clinical signs and skin barrier function in prospective study on the clinical features dogs with topic dermatitis: A double-blinded, of chronic canine atopic dermatitis and its randomized, controlled study. Intern J Appl Res diagnosis. Vet Dermatol 2010; 21(1):23-31. Vet Med 2013; 11(2):110-116. 9. Olivry T, Mueller RS. Evidence-based veterinary 24. Blaskovic M, Rosenkrantz W, Neuber A, et al. dermatology: A systematic review of the The effect of a spot-on formulation containing pharmacotherapy of canine atopic dermatitis. Ve t polyunsaturated fatty acids and essential oils Dermatol 2003; 14(3):121-146. on dogs with atopic dermatitis. Vet J 2014; 10. Olivry T, Foster AP, Mueller RS, et al. 199(1):39-43. Interventions for atopic dermatitis in dogs: A 25. DeBoer D, Morris M. Multicentre open systematic review of randomized controlled trial demonstrates effi cacy of sublingual trials. Vet Dermatol 2010; 21(1):4-22. 11. Koch SN, Torres SMF, Plumb DC. Canine and immunotherapy in canine atopic dermatitis Feline Dermatology Drug Handbook. Oxford: (abstract). Vet Dermatol 2012; 23(Suppl 1):65. Wiley-Blackwell, 2012, 464 pages. 26. Marsella R, Ahrens K. Investigations on 12. Olivry T, Dunston SM, Rivierre C, et al. A the effects of sublingual immunotherapy on randomized controlled trial of misoprostol clinical signs and immunological parameters monotherapy for canine atopic dermatitis: using a canine model of atopic dermatitis: A Effects on dermal cellularity and cutaneous double-blinded, randomized, controlled study tumour necrosis factor-alpha. Vet Dermatol 2003; (abstract). Vet Dermatol 2012; 23(Suppl 1):66. 14(1):37-46. 27. DeBoer DJ, Verbrugge M, Morris M. Pilot trial 13. Singh SK, Dimri U, Saxena SK, Jadhav RK. of sublingual immunotherapy in mite-sensitive Therapeutic management of canine atopic atopic dogs (abstract). Vet Dermatol 2010; dermatitis by combination of pentoxifylline and 21(3):325. PUFAs. J Vet Pharm Ther 2010; 33(5):495-498. 28. DeBoer D, Verbrugge M, Morris M. Changes 14. Plevnik A, Kotnik T, Kobal S. Fexofenadine in mite-specifi c IgE and IgG levels during treatment of atopic dogs: Preliminary clinical sublingual immunotherapy (SLIT) in dust results. Acta Vet Brno, J Univ Vet Pharm Sci 2006; mite-sensitive dogs with atopic dermatitis 75:549-555. (abstract). Vet Dermatol 2010; 21(5):531-532.

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