7th World Congress of Veterinary Dermatology

Transcription

1 Focus o the Sciece UPDATE: 7th World Cogress of Veteriary Dermatology VANCOUVER JULY

2 NEW INSIGHTS AND SCIENTIFIC FINDINGS THE WORLD CONGRESS OF VETERINARY DERMATOLOGY orgaized uder the auspices of the World Associatio for Veteriary Dermatology, is the premier evet for discussio of ew scietific iformatio i the field. Held every 4 years, the record-settig 7th World Cogress i Vacouver assembled more tha 1,200 thought leaders from 55 coutries. The goal of this Cogress was to report ew research ad deliver advaced, comprehesive cotiuig educatio highlightig state-of-the-art cliical practices ad cuttigedge therapeutic advaces i veteriary dermatology. Global experts i dermatology, icludig several from Pfizer Aimal Health, preseted data idetifyig ewly recogized pathways of allergic ski disease i dogs. We ow uderstad that allergic ski disease is caused by a cycle of evets. Research suggests that overactivatio ad release of pruritogeic ad pro-iflammatory cytokies (secreted sigalig proteis) are at the ceter of this coditio. As our uderstadig icreases about these biochemical pathways ad how cytokie sigalig is cotrolled at a molecular level, alterative drug targets for developmet of ew pharmaceuticals ad biological approaches will provide a greater spectrum of treatmet optios i veteriary dermatology. Researchers have discovered through scietific advaces that pruritus is a multifactorial problem, which should direct the treatmet approach because o stad-aloe treatmet has yet proved effective. Marti Steihoff, MD, PhD, MSc Professor of Dermatology ad Surgery Uiversity of Califoria Sa Fracisco, USA Studies preseted at the 7th World Cogress provide evidece that will guide research ito ew therapies that target the pathobiology of allergic ski disease i various ovel ways. Valerie Fadok, DVM, PhD, DACVD Gulf Coast Veteriary Specialists, Housto, Texas, USA Dr. Cadace Sousa, Seior Veteriary Specialist at Pfizer Aimal Health, welcomes attedees to the symposium "Allergic Ski Disease: New Models, New Targets, New Tactics." The old approach to maagig AD icludes cotrol of iflammatio ad reactio to the ed process of the disease. The ew approach is a much broader, multifaceted approach that proactively corrects the actual disease pathogeesis where possible ad targets ati-iflammatory ad atipruritic therapies. Douglas DeBoer, DVM, DACVD School of Veteriary Medicie Uiversity of Wiscosi-Madiso, USA

3 DIALOGUE WITH THE EXPERTS Followig the 7th World Cogress, Pfizer Aimal Health talked with three leadig veteriary ad huma dermatology specialists about developmets i maagig allergic dermatitis ad the itersectios of ew kowledge i each field. Valerie A. Fadok, DVM, PhD, DACVD Dermatologist, Gulf Coast Veteriary Specialists Housto, Texas, USA Q You were a co-author o a recet peer-reviewed article about caie atopic dermatitis (CAD) i the Joural of the America Veteriary Medical Associatio.* What do you believe are its key learigs for cliicias? A Our icreased uderstadig of the pathobiology is opeig aveues to ew therapeutic solutios. The pathogeesis of atopic dermatitis is very complex, but it has become clear that the best way to maage atopic dogs is a multimodal approach tailored to a dog's idividual eeds. Q What do you cosider the fudametals of maagig CAD? A I believe there are five essetial priciples of allergy maagemet: The first is avoidace of allerges wheever possible. The secod aspect is to determie the allerges that cause the disease (which vary amog idividual dogs) ad to make a allergy vaccie tailored to the idividual patiet. Third, maagemet of allergy patiets requires vigorous cotrol of cocurret ectoparasites ad ifectios. Fourth, successful maagemet of CAD relies o epidermal barrier repair, which ca be accomplished usig oral fatty acids ad topical lipids. Last, ad likely most critical if we are to keep cliets happy ad patiets comfortable, is to cotrol the itch. Key Isight: Chroic iflammatory diseases, such as atopic dermatitis (AD), affect a dog s quality of life ad also that of its ower. This is a area recetly ivestigated i veteriary dermatology, ad it is iterestig to ote that allergy maagemet ca improve the quality of life of both the pet ad the ower. But the ower s quality of life may ot be improved to the same degree as it is the ower who is resposible for keepig up with the demads of implemetig the therapeutic regime. Q Cosiderig the reports discussed at the WCVD i Vacouver, which do you thik have the most potetial to chage therapeutic models for dogs ad cats i the future? A Targetig cytokies is the "holy grail" as far as ew ways to cotrol iflammatio ad abormal immue reactios i a umber of diseases. The potetial use of ati-ige i treatig AD is excitig, ad the potetial for use of ati-ige i dogs, particularly i combiatio with immuotherapy, also holds promise. *Marsella R, Sousa C, Gozales A, Fadok V. Curret uderstadig of the pathophysiologic mechaisms of caie atopic dermatitis. J Am Vet Med Assoc. 2012;241: Marti Steihoff, MD, PhD, MSc Professor of Dermatology ad Surgery Uiversity of Califoria Sa Fracisco, USA Q You have spet your professioal career researchig itch i people. Why is itch so importat i allergic ad atopic diseases? A Itch (pruritus) is problematic because it is the most commo presetatio amog huma patiets with ski disease. I additio, a smaller umber of patiets without coexistet ski disease also demostrate sigs of itch. I these patiets, pruritus may be the iitial sig of systemic (eg, edocrie) disease. Most pruritus ivolves the brai ski axis, which ca lead to cogitive disruptios that lower quality of life. Q What recet scietific advaces have impacted how you look at AD? A Scietific advaces i eurosciece, immuology, ad dermatology have taught researchers that pruritus is a multifactorial problem. Treatmets aimed at improvig itch heavily rely o these advaces. More research is eeded to uderstad the causes of pruritus, to measure pruritus successfully, ad to develop successful treatmets. We ow kow the pathophysiology of CAD is more complex tha oce thought. Today's view of caie AD is that, as i humas, it is far more tha a IgE-mediated process. Q What is the relevace for cliicias of recet fidigs regardig the eurologic mechaisms of itch? A I 1946, histamie was idetified as the eurotrasmitter resposible for histamie-depedet pruritus i humas, as i hay fever ad urticaria. Atopic dermatitis, allergic cotact dermatitis, psoriasis, ad scabies are examples of pruritic diseases that are ot primarily due to histamie. By defiitio AD is a cliical etity that is diagosed oly if pruritus is preset alog with some other mior criteria, but the exact eurochemical basis of pruritus remais elusive. For about a decade it has bee kow that protease-activated receptors i the ski respod to protease factors that cause itch, such as trypsi, tryptase, cathepsis, ad kallikreis. Studies i our lab have show that protease-activated receptor 2 is oe of the ski receptors activated by these proteases, ad patiets with AD have icreased umbers of these receptors i their ski. Q How are the learigs beig applied i huma dermatology? A The presece of selective itch receptors i huma ski is a ew fidig that has prompted ew ways of thikig about the

4 DIALOGUE WITH THE EXPERTS eurologic mechaisms of itch. This discovery led to the idea that there are direct eural pathways to the brai from itch receptors. Future studies i our lab aim to idetify the eurochemical mediators that stimulate these receptors. Whe dysregulated, cytokies, such as IL-31, are importat cotributors to the itch associated with allergic ad atopic diseases i dogs. Q Why is curret research i huma medicie focused o fidig o-glucocorticoid treatmets for allergic ad atopic diseases? A There are umerous therapeutic optios available, which speaks to the problem of o good sigle treatmet, which i tur speaks to the problem of a kowledge gap i the pathophysiology of AD. Steroids are ot the ideal therapy for four reasos: Except i their weakest stregth, they caot be used o the face, itertrigious areas (axillae), ad uder diapers because they ihibit the productio of collage ad ca lead to atrophy of the ski. Because of reduced efficacy with log-term usage, they should ot be used at all with a patiet i remissio. They require daily applicatio durig flares, which ca be cumbersome. Their actio is multisystemic ad does ot represet targeted therapy. Possible side effects iclude decreased boe desity, blood sugar abormalities, ad glaucoma. Key Isight: For severe flares, oral steroids are acceptable therapy, but immuosuppressio ca develop if log-term therapy is idicated. Patiets receivig atibiotics ad steroids cocurretly to treat ifectios are especially at risk. The limitatios of steroids clearly show the eed for more targeted treatmets. Prof. Dr. Med. Vet. Ralf S. Müller Dermatologist, Ceter for Cliical Veteriary Medicie Ludwig-Maximilias-Uiversity Muich, Germay Q What are the most importat factors a veteriaria should address whe a pet ower presets a pet ad complais of its itchig ad scratchig? A It is importat that veteriarias develop a systematic method of workig up dogs with pruritic behavior (scratchig, rubbig, chewig, etc.) to idetify the uderlyig coditio that is causig the pruritus. Ad, maybe eve more importatly, that they use the system routiely to work up each patiet that presets. There are a few simple diagostics that are easily doe o first presetatio, ad these ca rule out a umber of uderlyig causes of itch, which ca be readily treated if idetified. Use of cytology ad tape preparatios ca quickly idetify bacterial or yeast ifectios, ad ski scrapigs ca rule out parasitic ifestatios, such as scabies or demodectic mage. The results of these examiatios combied with good history (eg, age of the patiet, oset of the itch) ad thorough cliical examiatio, icludig ispectio of the lesios, also helps rule out may of the most commo causes of pruritus. Adverse food reactios, scabies, bacterial or yeast ifectios secodary to other diseases or to atopic dermatitis, fleabite hypersesitivity, ad demodicosis are the most frequet diagoses. Addressig itch therapeutically differs for each patiet depedig o the uderlyig coditios ucovered ad ca ivolve rehydratig dry ski, dow-regulatig the iflammatio i the ski, treatmet of secodary ifectios or ifestatios - ad, of course, stoppig the pruritus. Differetial stimulatio of caie peripheral blood moouclear cells ad aalysis by immuoassay suggest T cells, specifically T helper cells (Th2), are the source of IL-31. Q What is the most importat cliical skill whe treatig ski disease? A Commuicatio skills are by far the most importat skills i veteriary dermatology. May patiets are chroically afflicted, ad the pet ower ca become very frustrated. So it is essetial that o first presetatio the veteriaria explais to the pet ower that some ski diseases ca be treated, but ot cured, ad that successful maagemet of allergic ski disease ca ivolve a multimodal approach that is tailored to miimize the pet's disease ad maage flares. Successfully helpig pet owers deal with a chroic ski coditio i their dog ca require a great deal of empathy o the part of a veteriaria, keepig i mid the owers' usually limited medical kowledge ad the eed to fully iform them ad equip them to maage the coditio log-term without overchallegig them. This is the art of practicig veteriary medicie! Q Whe should a allergic/atopic dog be referred to a veteriary dermatologist? A Referral is a good optio for allergic or atopic aimals whe a uderlyig cause or flare factor caot be idetified. I additio, referral ca be a effective ad ecouragig step whe owers become fatigued ad frustrated with the active maagemet required by a pet's chroic disease coditio.

5 NEW SCIENTIFIC FINDINGS: SUMMARIES OF REPORTED RESEARCH The followig summaries highlight cetral poits of talks give durig the symposium "Allergic Ski Disease: New Models, New Targets, New Tactics" preseted at the 7th World Cogress. Every patiet is differet ad will require a differet treatmet pla ad a differet combiatio of 'tools' to provide effective, affordable, coveiet, ad safe treatmet over a log period." Douglas DeBoer, DVM, DACVD EXPERIMENTAL MODELS Preseted Wedesday, July 25, 2012 / 10:30 AM Adrea J. Gozales, PhD Associate Research Fellow, Pfizer Aimal Health Kalamazoo, Michiga, USA Caie IL-31 ca iduce pruritic behaviors i dogs. This biological property was used to establish a caie model of pruritus ad to evaluate potetial atipruritic properties of ivestigatioal therapeutic compouds. The resultig model is a potetial protocol to future evaluatio of atipruritic activity of ew therapies. NEW TARGETS FOR THERAPY Preseted Wedesday, July 25, 2012 / 9:30 AM Valerie A. Fadok, DVM, PhD, DACVD Dermatologist, Gulf Coast Veteriary Specialists Housto, Texas, USA Most ivestigators ad cliicias uderstad that atopic dermatitis is a complex disorder ivolvig multiple geetic abormalities associated with umerous evirometal triggers. Three major areas are likely targets of future treatmets: immuologic abormalities, eurologic abormalities, ad physicochemical abormalities associated with the dysfuctioal ski barrier. Our kowledge of CAD has grow eormously over the past 15 years. The Iteratioal Task Force o Caie Atopic Dermatitis recetly published curret recommedatios for therapy of both acute ad chroic forms. (See doi/ /j x/pdf.) Aligig caie AD with huma AD eables veteriary dermatology to make use of the relative plethora of basic huma disease research that is so readily available. The complexity of the disease suggests mootherapy is rarely effective. Multiple modalities are required to maage dogs with CAD. Primary Fidigs Itch is a key compoet of CAD. Icreasig evidece suggests a syergistic iteractio betwee the ervous system ad the immue system withi the ski. T-cell cytokie imbalace exists i the ski of atopic dogs. Several Th2 cytokies have bee associated with pruritus based o pheotypes observed via geetically modified models i mice. IL-31 is a recetly discovered cytokie secreted from Th2 lymphocytes ad ski-homig T cells ad has bee implicated i pruritic ski coditios i humas. IL-31 ca be secreted by Th2-polarized PBMCs isolated from allerge-sesitized dogs. Ijectio of caie IL-31 was show to iduce pruritus i dogs. Th2 polarizatio combied with microbial presece likely leads to IL-31 mediated effects through the iductio of sigalig i macrophages ad direct euroal iteractio.

6 New Isights ad Scietific Fidigs THE SCIENCE OF ITCH: PATHOBIOLOGY OF CAD The scietific studies reported at WCVD support ew uderstadig of CAD. At the ceter of these ew isights is the fidig that cytokies, chemical messegers that trasmit sigals from cell to cell, play a sigificat role i causig itch sesatios associated with dermatologic coditios, such as allergic ad atopic diseases i dogs, as they do i humas. Based o these isights, researchers are ow focusig o cytokies as ew therapeutic targets for future treatmets. Curret uderstadig of the pathology of itch is illustrated i the itch cycle diagram, above. (1) Iitiatio of CAD occurs whe the dog is exposed to allerges, such as house dust mites. (2) These allerges cross the epidermal barrier ad preset to the immue system (residet Lagerhas cells or LC) as foreig proteis. Dogs with preexistig defects i ski barrier fuctio will be more at risk. (3) The LC fuctio as atige-presetig cells ad activate the adaptive immue system, leadig to T-helper type 2 (Th2) cells to produce cytokies, such as iterleuki 4 (IL-4), IL-5, IL-13, ad IL-31. These cytokies create a microeviromet that perpetuates ski barrier dysfuctio ad promotes allergespecific IgE (ASIgE) productio. (4) ASIgEs the bid to cells, icludig mast cells ad basophils, via cell-surface receptors. (5) Whe the dog is subsequetly exposed to the allerge, the IgE-primed cells release a variety of substaces, such as histamie, europeptide, cytokies, ad chemokies. (6) Cliical sigs of dermatitis occur whe the cytokies stimulate the euros i the ski to sed a sigal that is trasmitted to the dorsal root gaglia i the spial cord to the brai creatig the itch sesatio - ad i respose the dog begis to scratch, gaw, ad chew amog other pruritic behaviors. (7) Additioally, these substaces activate ad polarize T lymphocytes toward a Th2 pheotype that cause vasodilatatio (causig redess of the ski), ad also recruit additioal immue cells ito the ski that create chroic iflammatio ad perpetuate the CYCLE OF ITCH. Fid a copy of the SYMPOSIUM PROCEEDINGS at