@article{halliwell_pucheu-haston_olivry_prost_jackson_banovic_nuttall_santoro_bizikova_mueller_2021, title={Feline allergic diseases: introduction and proposed nomenclature}, volume={32}, ISBN={1365-3164}, url={https://doi.org/10.1111/vde.12899}, DOI={10.1111/vde.12899}, abstractNote={Feline allergic diseases present as challenging problems for clinicians, not least because of the number of reaction patterns of the feline skin, none of which are specific for allergy. Furthermore, there is some controversy over the nomenclature that should be used in their description.To review the literature, assess the status of knowledge of the topic and the extent to which these diseases could be categorized as atopic in nature, and make recommendations concerning nomenclature.Atopic diseases in humans and cats were researched. A comparison then was made of the essential features in the two species.There were sufficient similarities between human atopic diseases and the manifestations of feline diseases of presumed allergic aetiology to justify the use of "atopic" to describe some of the feline conditions affecting the skin, respiratory and gastrointestinal tract. However, none of the allergic skin diseases showed features consistent with atopic dermatitis as described in man and the dog.The term "Feline Atopic Syndrome" (FAS) is proposed to encompass allergic diseases of the skin, gastrointestinal tract and respiratory tract, and "Feline atopic skin syndrome" (FASS) proposed to describe allergic skin disease associated with environmental allergies. We are not aware of any adverse food reactions in cats that are attributable to causes other than immunological reactions against the food itself. We therefore propose an aetiological definition of "Food Allergy" (FA) to describe such cases.Une nouvelle anomalie congénitale de la tige pilaire ressemblant au phénotype nu des rongeurs est décrite dans une portée de quatre chats européens (DSH). Les données relatives aux anomalies de la tige pilaire et des follicules pileux sont rares en médecine vétérinaire.Décrire et comparer les anomalies structurelles de ces chats avec d’autres dystrophies félines et d’autres mammifères.Une portée de chats DSH avec alopécie progressive non-inflammatoire. MÉTHODES: L’évaluation histopathologique, la microscopie électronique à transmission et l’analyse des éléments par rayons X définissaient les changements pilaires et cutanés des chats nés alopéciques. Les données ont été comparées aux archives de chats normaux et de souris mutantes Dsg4lahJ et Krt75tm1Der . RÉSULTATS: La microscopie électronique à lumière et à balayage des poils a révélé des défauts de forme de l’extrémité de la tige pilaire en pointe ou en lance. Les données histopathologiques consistaient en des tiges pilaires enflées, initialement au dessus de la matrice du bulbe pilaire et ensuite retrouvé dans les parties distales des follicules pileux télogènes, semblables à ceux observés chez les souris mutantes Dsg4lahJ Krt75tm1Der . La microscopie électronique à transmission de la tige pilaire et des follicules pileux a révélé une perte de la structure normale des poils de garde chez les chats alopéciques. Il y a avait une diminution statistiquement significative du contenu en sulfure juste au dessous des défauts des tiges pilaires (trichothiodystrophie). CONCLUSIONS ET IMPORTANCE CLINIQUE: une forme rare d’alopécie congénitale résultant en une dystrophie folliculaire est décrite chez le chat, comparable aux changements de la tige pilaire et du follicule pileux décrits dans plusieurs souches de souris mutantes avec une mutation génétique unique des gènes des molécules d’adhésion ou de kératine.ANTECEDENTES: se describe una nueva anomalía congénita del pelo que se asemeja al fenotipo de pelo lanceolado de los roedores en una camada de cuatro gatos domésticos de pelo corto (DSH). Los datos relacionados con los trastornos del pelo y los folículos siguen siendo escasos en medicina veterinaria. OBJETIVOS: Describir y comparar anomalías estructurales en estos gatos con otras distrofias capilares en gatos y otros mamíferos. ANIMALES: una camada de gatos DSH con alopecia no inflamatoria progresiva. MÉTODOS: evaluación histopatológica, por microscopía electrónica de barrido y de transmisión y el análisis de elementos basados en rayos X definieron los cambios en el pelo y la piel de los gatos nacidos con alopecia. Los hallazgos se compararon con datos de archivo de gatos normales y ratones mutantes de pelo lanceolado (Dsg4lahJ ) y queratina 75 (Krt75tm1Der ). RESULTADOS: la microscopía óptica y electrónica de barrido de los pelos reveló defectos en la punta del cabello en forma de lanza o punta de lanza. Los hallazgos histológicos fueron pelos hinchados, inicialmente por encima de la matriz del bulbo piloso y luego encontrados en las partes distales de los folículos pilosos telógenos, similares a los observados en ratones mutantes Dsg4lahJ Krt75tm1Der . La microscopía electrónica de transmisión del pelo y los folículos pilosos mostró una pérdida en la estructura normal de los pelos primarios en los gatos alopécicos. Hubo una disminución estadísticamente significativa en el contenido de azufre justo por debajo de los defectos en los tallos del cabello (tricotiodistrofia). CONCLUSIÓN E IMPORTANCIA CLÍNICA: en gatos se describe una forma poco común de alopecia congénita que da como resultado distrofia folicular, similar a los cambios en el folículo piloso y el tallo del pelo descritos en varias cepas de ratones mutantes con mutaciones de un solo gen en moléculas de adhesión o genes de queratina.Es wird eine neue angeborene Haarschaft Abnormalität bei einem Wurf von vier Hauskatzen (DSH) beschrieben, die dem lanzenförmigen Haar Phänotyp von Nagern gleicht. Daten über Haarschaft- und Follikelstörungen bleiben in der Veterinärmedizin rar.Eine Beschreibung der Strukturabnormalitäten bei diesen Katzen und ein Vergleich mit anderen Haardystrophien bei Katzen und anderen Säugern.Ein Wurf von Hauskatzen mit einer progressiven nichtentzündlichen Alopezie.Mittels histopathologischer Evaluierung, Raster- und Transmissionselektronenmikroskopie, und Röntgen-basierter Elementanalyse wurden die Haar- und Hautveränderungen bei Katzen, die mit einer Alopezie geboren worden waren, definiert. Die Befunde wurden mit archivierten Daten von normalen Katzen und lanzenförmigen Haaren (Dsg4lahJ ) und Keratin 75 (Krt75tm1Der ) von mutanten Mäusen verglichen.Die Licht- und Rasterelektronenmikroskopie der Haare zeigte Lanzen- oder Speer-Kopf geformte Defekte der Haarspitzen. Die histologischen Befunde zeigten geschwollene Haarschäfte, ursprünglich oberhalb der Haarwurzelmatrix und später auch in den distalen Teilen der telogenen Haarfollikel, ähnlich denen bei Dsg4lahJ Krt75tm1Der mutanten Mäusen. Die Transelektronenmikroskopie von Haarschaft und Haarfollikeln zeigte ein Verschwinden der normalen Struktur der Deckhaare bei haarlosen Katzen. Es bestand eine statistisch signifikante Abnahme des Schwefelgehaltes unmittelbar unter den Defekten in den Haarschäften (Trichothiodystrophie).Eine seltene Form einer angeborenen Alopezie, resultierend aus einer follikulären Dystrophie wird bei Katzen in einer ähnlichen Form beschrieben, wie es bereits bei einigen mutanten Mausstämmen mit einer Einzelgenmutation in Adhäsionsmolekülen oder Keratingenen publiziert worden war.背景: げっ歯類の槍状の毛の表現型に似た新しい先天性毛幹異常が4頭のドメスティック・ショートヘア（DSH）の同腹子で記述されている。毛幹および毛包の障害に関連するデータは、獣医学ではまだ不足している。 目的: 本研究の目的は、これらの猫の構造異常を説明し、猫や他の哺乳類の他の毛髪ジストロフィーと比較することであった。 動物: 進行性の非炎症性脱毛症を伴うDSH猫の同腹子。 方法: 組織病理学的評価、走査型および透過型電子顕微鏡法、およびX線ベース元素解析により、脱毛症で生まれた猫の毛および皮膚の変化が定義された。調査結果は、健常猫と披針形の毛（Dsg4lahJ ）およびケラチン75（Krt75tm1Der ）変異マウスからのアーカイブデータと比較された。 結果: 毛髪の光学顕微鏡および走査型電子顕微鏡検査により、毛先の槍または槍の頭の形をした欠陥が明らかになった。組織学的所見は、Dsg4lahJ Krt75tm1Der 変異マウスで観察されたものと同様に、最初は毛球マトリックス上にあり、後に休止期毛包の遠位部分に見られた、膨張した毛幹であった。毛幹および毛包の透過型電子顕微鏡検査は、脱毛猫のガード毛の正常な構造の喪失を示した。毛幹の欠陥（トリコチオジストロフィー）のすぐ下で硫黄含有量の統計的に有意な減少があった。 結論と臨床的重要性: 接着分子またはケラチン遺伝子に単一遺伝子変異を有するいくつかの変異マウス系統で報告された毛包および毛幹の変化に類似した、毛包ジストロフィーを引き起こすまれな形態の先天性脱毛症が猫で説明されている。.背景: 在4只同窝家养短毛(DSH)猫中，发现了类似啮齿动物披针形毛发表型，这是一种新的先天性毛干异常。与毛干和毛囊疾病相关的数据在兽医学中仍然很少。 目的: 描述这些猫的结构异常，并与猫和其他哺乳动物的其他毛发形成不良进行比较。 动物: 患有进行性非炎性脱毛症的一窝DSH猫。 方法: 组织病理学评价、扫描和透射电子显微镜以及基于X射线的元素分析，定义了新生脱毛猫的毛发和皮肤变化。将结果与正常猫、披针形毛发(Dsg4lahJ)和角质75(Krt75tm1Der)突变小鼠的存档数据进行比较。 结果: 毛发的光学和扫描电子显微镜检查显示，毛尖存在披针形或矛头形缺陷。组织学发现毛干肿胀，最初在毛球基质上方，后来在终止期毛囊的远端部分发现，与在Dsg4lahJ Krt75tm1Der突变小鼠中观察到的相似。毛干和毛囊的透射电镜显示脱毛猫护毛的正常结构缺失。毛干缺损正下方的硫含量在统计学上显著降低（毛发硫营养不良）。 结论和临床重要性: 发现了猫的罕见先天性脱发形式，由毛囊发育不良所导致，与粘附分子或角质基因中单基因突变的几种突变小鼠品系中报告的毛囊和毛干变化类似。.Uma nova anomalia congênita da haste pilosa semelhante ao fenótipo de pelo lanceolado dos roedores foi descrita em uma ninhada de quatro gatos domésticos de pelo curto (DSH). Dados relacionados a enfermidades da haste e folículo piloso permanecem escassos na medicina veterinária.Descrever e comparar as anomalias estruturais nestes gatos com outras distrofias pilosas em gatos e outros mamíferos.Um gato DSH apresentando alopecia não inflamatória progressiva. MÉTODOS: Avaliação histopatológica, microscopia eletrônica de varredura e transmissão e análise elementar baseada em raio-X foram utilizadas para caracterizar as alterações de pele e pelos em gatos nascidos com alopecia. Os achados foram comparados a dados arquivados de gatos normais e ratos com mutação de pelo lanceolado (Dsg4lahJ ) e Queratina 75 (Krt75tm1Der ).À microscopia de varredura e óptica, observou-se pelos com defeitos nas pontas, que se apresentavam em formato de lança ou ponta de lança. Os achados histológicos foram hastes pilosas dilatadas, inicialmente acima da matriz do bulbo piloso e posteriormente nas partes distais dos folículos pilosos telógenos, similar ao observado nos ratos mutantes Dsg4lahJ Krt75tm1Der .Ao microscópio eletrônico de transmissão, as hastes pilosas e os folículos pilosos demonstraram perda na estrutura normal dos pelos guardiães nos gatos alopécicos. Houve uma redução significativa no conteúdo de enxofre imediatamente abaixo dos defeitos nas hastes pilosas (tricotiodistrofia). CONCLUSÃO E IMPORTÂNCIA CLÍNICA: Uma forma rara de alopecia congênita resultante de distrofia folicular descrita em gatos é similar às alterações nos folículos pilosos e hastes pilosas em diversas linhagens de ratos com mutações de um único gene em genes de moléculas de adesão ou queratina.}, number={1}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, author={Halliwell, Richard and Pucheu-Haston, Cherie M. and Olivry, Thierry and Prost, Christine and Jackson, Hilary and Banovic, Frane and Nuttall, Tim and Santoro, Domenico and Bizikova, Petra and Mueller, Ralf S.}, year={2021}, month={Feb}, pages={8-+} }
 @article{halliwell_banovic_mueller_olivry_2021, title={Immunopathogenesis of the feline atopic syndrome}, volume={32}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12928}, DOI={10.1111/vde.12928}, abstractNote={BACKGROUND
Feline diseases of possible allergic origin with similar clinical phenotypes can have a varied underlying pathogenesis. Clinical phenotype, precise aetiology and underlying immunopathogenesis all need to be considered if advances in this neglected area of dermatology are to be made.


OBJECTIVES
To document the status of research into the immunopathogenesis of the diseases that fall within the spectrum of the feline atopic syndrome (FAS ), to summarize the conclusions, identify the limitations and recommend future research directions.


METHODS AND MATERIALS
A search of the literature was undertaken. The strengths and validity of the data and the contributions to our current understanding of the immunopathogenesis were analysed. Skin diseases of presumed allergic aetiology and asthma were assessed separately, as was the role of antibodies, cells and cytokines in each.


RESULTS
The research varied in its quality and its impact often was limited by a failure to employ strict criteria in case selection. This reflected the difficulties of skin reaction patterns associated with a number of inciting causes. Research into feline asthma was handicapped by the difficulties of investigating clinical material, and much of the useful information was derived from experimental models.


CONCLUSIONS AND CLINICAL IMPORTANCE
The evidence reviewed was supportive of a role for immunoglobulin (Ig)E in the pathogenesis of both feline atopic skin syndrome (FASS) and asthma, albeit not strongly so. The inflammation noted in both FASS and asthma is accompanied by eosinophils and lymphocytes, and these findings, together with the cytokine expression, are suggestive in some (not all) cats of T-helper type 2 immune dysregulation.}, number={1}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, author={Halliwell, Richard and Banovic, Frane and Mueller, Ralf S. and Olivry, Thierry}, year={2021}, month={Feb}, pages={13-+} }
 @article{leeb_leuthard_jagannathan_kiener_letko_roosje_welle_gailbreath_cannon_linek_et al._2020, title={A Missense Variant Affecting the C-Terminal Tail of UNC93B1 in Dogs with Exfoliative Cutaneous Lupus Erythematosus (ECLE)}, volume={11}, ISSN={["2073-4425"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85079084533&partnerID=MN8TOARS}, DOI={10.3390/genes11020159}, abstractNote={Cutaneous lupus erythematosus (CLE) in humans encompasses multiple subtypes that exhibit a wide array of skin lesions and, in some cases, are associated with the development of systemic lupus erythematosus (SLE). We investigated dogs with exfoliative cutaneous lupus erythematosus (ECLE), a dog-specific form of chronic CLE that is inherited as a monogenic autosomal recessive trait. A genome-wide association study (GWAS) with 14 cases and 29 controls confirmed a previously published result that the causative variant maps to chromosome 18. Autozygosity mapping refined the ECLE locus to a 493 kb critical interval. Filtering of whole genome sequence data from two cases against 654 controls revealed a single private protein-changing variant in this critical interval, UNC93B1:c.1438C>A or p.Pro480Thr. The homozygous mutant genotype was exclusively observed in 23 ECLE affected German Shorthaired Pointers and an ECLE affected Vizsla, but absent from 845 controls. UNC93B1 is a transmembrane protein located in the endoplasmic reticulum and endolysosomes, which is required for correct trafficking of several Toll-like receptors (TLRs). The p.Pro480Thr variant is predicted to affect the C-terminal tail of the UNC93B1 that has recently been shown to restrict TLR7 mediated autoimmunity via an interaction with syndecan binding protein (SDCBP). The functional knowledge on UNC93B1 strongly suggests that p.Pro480Thr is causing ECLE in dogs. These dogs therefore represent an interesting spontaneous model for human lupus erythematosus. Our results warrant further investigations of whether genetic variants affecting the C-terminus of UNC93B1 might be involved in specific subsets of CLE or SLE cases in humans and other species.}, number={2}, journal={GENES}, author={Leeb, Tosso and Leuthard, Fabienne and Jagannathan, Vidhya and Kiener, Sarah and Letko, Anna and Roosje, Petra and Welle, Monika M. and Gailbreath, Katherine L. and Cannon, Andrea and Linek, Monika and et al.}, year={2020}, month={Feb} }
 @article{banovic_denley_blubaugh_scheibe_lemo_papich_2020, title={Effect of diphenhydramine and cetirizine on immediate and late-phase cutaneous allergic reactions in healthy dogs: a randomized, double-blinded crossover study}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12840}, abstractNote={BACKGROUND
Currently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs.


HYPOTHESIS/OBJECTIVE
To determine and compare the effects oral of DPH and cetirizine on the immediate- and late-phase cutaneous allergic reactions in healthy dogs.


ANIMALS
Twelve healthy laboratory beagles.


MATERIALS AND METHODS
The study was designed as a randomized, double-blinded crossover study in which each dog served as its own control; twice-daily oral DPH (2.2 mg/kg) or cetirizine (2 mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10 days before drug administration (baseline), during oral antihistamine administration on day 6 and 10 days after last medication dosage. Global wheal scores (GWS) at 20 min and late-phase reactions (LPR) at 6h post-injection were evaluated by an investigator blinded to the drug and the interventions.


RESULTS
Treatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. Oral DPH and cetirizine reached plasma concentrations considered therapeutic in people in all dogs. No adverse effect or behavioural changes were observed during the study.


CONCLUSION AND CLINICAL SIGNIFICANCE
In conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Banovic, Frane and Denley, Tara and Blubaugh, Amanda and Scheibe, Ileia and Lemo, Niksa and Papich, Mark G.}, year={2020}, month={Aug}, pages={256-+} }
 @article{olivry_banovic_2019, title={Treatment of canine atopic dermatitis: time to revise our strategy?}, volume={30}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/vde.12740}, DOI={10.1111/vde.12740}, abstractNote={For decades following the recognition of atopic dermatitis (AD) as a common allergic skin disease of dogs, its treatment relied mainly on the use of oral — and more often than not injectable — glucocorticoids. When the “time was right”, allergen immunotherapy (AIT) was used to reduce the need for glucocorticoids because of their ubiquitous adverse effects. It was only in 2004 that the calcineurin inhibitor ciclosporin (Atopica, Elanco; Greenfield, IN, USA) became the first immunomodulator specifically approved for treatment of canine AD. In 2007, the hydrocortisone aceponate-containing spray Cortavance (Virbac; Carros, France) was the second pharmacological intervention approved for allergic skin diseases. More recently, in 2014, oclacitinib (Apoquel, Zoetis; Parsippany, NJ, USA) was the first-in-class Janus kinase (JAK) inhibitor available to treat AD in dogs, years before another JAKinib will be approved to treat the human disease homologue.1 Finally, 2017 saw the first monoclonal antibody (mAb) fully approved for a canine disease, the anti-interleukin (IL)-31 lokivetmab (Cytopoint, also from Zoetis) for treatment of canine AD. In 2010, the International Task Force of Canine AD published the first consensus guidelines for treatment of this disease;2 these were then updated in 2015 under the auspices of the International Committee on Allergic Diseases of Animals (ICADA).3 Both versions of these guidelines provided a framework placing various interventions in the context of three clinical situations: the treatment of acute flares of cAD, the treatment of chronic stages and, finally, the implementation of strategies to prevent the recurrence of clinical signs. In these papers, the main parameter taken into account for a drug to be proposed for treatment of acute or chronic AD was the time expected for a clinical benefit to occur. Although glucocorticoids and oclacitinib were recommended for both stages of this disease, ciclosporin was suggested only for the treatment of chronic AD.3 As shown recently in its human disease counterpart (reviewed in Czarnowicki et al.4) and by the variability of clinical presentations between breeds,5 canine AD is likely not to be a single entity, but rather a syndrome with different clinical and molecular endotypes/phenotypes. Furthermore, atopic dogs can exhibit, at the same time, both acute (e.g. erythematous macules/patches) and chronic skin lesions (e.g. plaques, lichenification, hyperpigmentation) at different body locations. As the current canine AD treatment guidelines do not recognize such a high degree of clinical heterogeneity, having both acute and chronic AD skin lesions in the same patient would lead to confusion regarding what drug to appropriately select. Nevertheless, and although it is clear that these guidelines have helped standardize the treatment of cAD, they did not consider a critical parameter in the evaluation and placement of the various pharmacological interventions: their mode of action or, within it, their breadth of inflammation targeting. The current trend in the development of small molecules or biologicals to treat human or canine AD is that of “targeted therapy”, a Holy Grail quest aimed at finding THE single molecule or receptor whose inhibition would eventually control all clinical signs. Unfortunately, this development strategy fails to consider that AD is not a disease due to the release of a single molecule or the activation of a single type of inflammatory cell! It is, in fact, the result of a complex immunological cascade that varies between lesions of different stages and that likely differs between individuals, especially if they come from different genetic origins (for example, dogs from different breeds). As a result of this complex inflammation involving at least a dozen activated cells and a myriad of mediators, the modern “narrow” targeting of a single molecule or receptor (for example by a monoclonal antibody inhibiting a cytokine) is unlikely to be effective in most patients most of the time. Indeed, the inhibited target might not be pathogenically relevant and the skin lesions or itch might be due to other mediators at the time the drug is administered! By contrast, interventions with a broad inflammation-targeting ability are likely to be beneficial most of the time in most patients, but their wide breadth of action is expected to lead to a higher risk for immunosuppression. Among the drugs currently available in our arsenal to treat canine AD, glucocorticoids and ciclosporin are those with the largest breadth of action, whereas, at the other end of the spectrum, the IL-31-blocking lokivetmab and the H1R inverse agonist antihistamines are those targeting a single mediator. Whereas oclacitinib initially prevents the signal transduction after the binding of some — but not all — AD-relevant cytokines to their respective receptors, it likely results in secondary waves of anti-inflammatory effects, because the cells downstream in the cascade are no longer activated by the blocked cytokines upstream; we would thus classify such JAKinib, at the recommended anti-allergic dosage, as having a “semi-broad” targeting capacity. Instead of using the “time-to-efficacy” of an intervention to define its place in the treatment of cAD, we propose to use instead a drug's “inflammation-targeting breadth” as the leading factor to consider in a newly revised treatment strategy that involves two distinct phases. Phase I of treatment of AD, “reactive therapy”, is the treatment of an atopic dog with existing acute and/or chronic skin lesions (and itch) with the goal of inducing clinical remission (Figure 1). During reactive therapy, as some of the clinical signs are often due to an allergen-primed self-sustaining and complex inflammation involving numerous mediators and cells, the patient should — at least theoretically — benefit most from rapidly-acting and broad-targeting drugs. For this reason, our first choice is nearly always a glucocorticoid. At the onset of treatment, using an oral short-acting glucocorticoid is more logical than that of a topical, because the normal-appearing skin of an atopic dog has been shown to be microscopically inflamed, and the lack of visible lesions would be unlikely to prompt treatment of such areas. However, topical glucocorticoids are ideal companions along with systemic formulations to treat strongly inflamed or markedly lichenified local or regional skin lesions. Once cutaneous inflammation subsides to mild levels, and to avoid the long course of oral glucocorticoids needed by dogs with generalized or severe clinical signs, one could consider substituting glucocorticoids with JAKinibs (Figure 1). A likely advantage of such glucocorticoid-to-JAKinib transition would be the prevention of the pruritus rebound that occurs after oclacitinib dose reduction. Indeed, pro-allergic cytokines continue to be secreted in atopic skin at the onset of oclacitinib therapy,6 and the transcription of such cytokines would be inhibited if glucocorticoids were given before or concurrently with the JAKinib. Of course, if the dog's lesions were mild when first needing treatment, another valid strategy would be to use oclacitinib, alone or with a topical glucocorticoid to immediately broaden its anti-inflammatory effect. Although the current treatment concept calls for the rapid tapering of glucocorticoids to reduce the risk of adverse effects, one should – in fact – consider treating “stronger and longer” to achieve the stable and complete remission of signs. This approach would ensure that only minimal residual inflammation remains in visibly-normal skin, inflammation that – if present – would rapidly flare upon treatment reduction. Once the patient has remained clear of clinical signs for several weeks, it is time to move to the second phase (i.e. Phase II) of AD treatment, “proactive therapy”, which is aimed at preventing the development of flares (Figure 2). Needless to say, the best prevention of any allergic disease will always be to avoid allergens and other factors known to trigger the recurrence of signs. This Phase II also is the time to consider allergen immunotherapy, whenever an association between allergens and AD flares is suspected. If the need were to arise for pharmacological interventions at the beginning of this second phase of canine AD treatment, proactive topical glucocorticoids and injectable biologicals such as lokivetmab could be considered (Figure 2). Proactive topical glucocorticoid therapy is defined as the treatment of previously affected areas on two consecutive days each week, whether or not lesions are visible at these sites.7 The goal of this approach is to prevent disease flares by regularly inhibiting the residual subclinical cutaneous inflammation. A recent trial confirmed the benefit of the proactive use of a topical hydrocortisone aceponate spray (Cortavance) in atopic dogs, with a nearly four-fold increase in the median time-to-flare compared to placebo without adverse events.8 This proactive topical glucocorticoid therapy, even though it does not appear to be recommended frequently, clearly deserves more attention throughout this preventive treatment phase. One could argue that the best time to use a single-target intervention, be it a monoclonal antibody or a small molecule, should be the beginning of this proactive second phase when clinical signs are in stable and full control (Figure 2). Indeed, at that time, the cutaneous inflammation is weakest and “simplest”, and the single-target intervention then would have the best chance to hit its mark as it is eventually secreted. Furthermore, if the target were upstream in the inflammation cascade, then blocking it early should prevent skin lesion and/or inflammatory itch development. If the biologicals and proactive topical glucocorticoid therapy were unable to prevent the flare of clinical signs, one should consider first “resetting” the inflammation with a short course of oral glucocorticoids to return to the complete and stable remission of signs. The failure of flare control with biologicals and topicals should then prompt treatment escalation with broader inflammation-targeting pharmacologicals such as oclacitinib or ciclosporin for their long-term use (Figure 2). In case the latter were to fail to fully control signs, or if one wishes to lower the dose or administration frequency of these drugs in fully controlled atopic dogs, then clinicians could consider adding intermittent topical glucocorticoid applications to regularly flaring areas. As new drugs or biologicals are approved for the treatment of cAD, treatment concepts should be re-evaluated periodically. It is with such periodic introspection that the best strategies will be developed, thereby ensuring that our atopic dogs will have the best quality of life possible. Now surely is the time for such periodic treatment strategy re-evaluation! The authors thank Alla Olivrī for her review of this editorial.}, number={2}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Olivry, Thierry and Banovic, Frane}, year={2019}, month={Mar}, pages={87–90} }
 @article{banovic_linder_uri_rossi_olivry_2016, title={Clinical and microscopic features of generalized discoid lupus erythematosus in dogs (10 cases)}, volume={27}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12389}, DOI={10.1111/vde.12389}, abstractNote={BACKGROUND
Generalized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic cutaneous lupus erythematosus (CLE) that is not well characterized.


HYPOTHESIS/OBJECTIVES
We report herein the signalment, clinical signs, treatment outcome, histopathology and immunological findings of 10 dogs with GDLE.


METHODS
Inclusion criteria were: (i) a >3 month history of generalized skin lesions indicating a chronic or recurrent nature; (ii) skin lesions resembling those of human GDLE; (iii) histopathology of CLE (lymphocyte-rich interface dermatitis). Direct immunofluorescence (IF) and antinuclear antibody serology were investigated whenever possible.


RESULTS
Various breeds were affected in their mid- to late adulthood. Selection criteria of generalized multifocal, annular ("discoid") to polycyclic plaques with pigment changes, erythematous margin, adherent scaling, follicular plugging and central alopecia were shown in all dogs. In nine dogs, plaques contained mild to moderate central scarring with depigmentation and/or hyperpigmentation. There were no dogs in which the disease progressed to systemic lupus erythematosus within a median follow-up of 2.5 years. Per inclusion criteria, interface dermatitis occurred with basement membrane zone (BMZ) thickening, suprabasal apoptosis and/or dermal fibrosis in some dogs. Infundibular interface folliculitis was common; it sometimes transitioned to mural folliculitis in lower follicle segments, and occurred with follicular and sebaceous gland atrophy. The direct IF revealed patchy deposition of immunoglobulin IgG and IgM at the BMZ. Lesions responded to a variety of treatments, including ciclosporin, hydroxychloroquine, topical tacrolimus and tetracycline/niacinamide. Relapses were common after medications were tapered.


CONCLUSIONS AND CLINICAL IMPORTANCE
These observations support the existence of a canine homologue of human GDLE.}, number={6}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley-Blackwell}, author={Banovic, Frane and Linder, Keith E. and Uri, Maarja and Rossi, Michael A. and Olivry, Thierry}, year={2016}, month={Dec}, pages={488-+} }
 @article{banovic_koch_robson_jacob_olivry_2015, title={Deep pyoderma caused by Burkholderia cepacia complex associated with ciclosporin administration in dogs: a case series}, volume={26}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84955721179&partnerID=MN8TOARS}, DOI={10.1111/vde.12210}, abstractNote={BACKGROUND
Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous Gram-negative bacilli associated with fatal nosocomial infections in humans; multi-antibiotic resistance makes this organism a serious threat in hospital settings.


OBJECTIVE
To describe the historical, clinicopathological and treatment characteristics of Bcc-associated deep skin infections in dogs.


ANIMALS
Six dogs with skin infections in which skin bacterial cultures resulted in pure growth of Bcc.


METHODS
Retrospective study with review of medical records and skin biopsies.


RESULTS
All dogs were receiving oral ciclosporin at the time of skin infection development. All dogs were castrated males and four of six were West Highland white terriers. Cutaneous lesions consistent with deep pyoderma were confined mainly to the trunk. In all dogs skin cytology revealed a strong inflammatory response, with moderate to abundant numbers of intracellular (neutrophils and macrophages) and extracellular bacilli. In three dogs histopathology showed a multifocal, nodular to coalescing pyogranulomatous dermatitis associated with multifocal folliculitis and furunculosis. Tissue Giemsa and Gram stains identified numerous Gram-negative rods within macrophages. Antimicrobial susceptibility testing revealed multidrug-resistant Bcc strains with sensitivity to trimethoprim/sulfonamides in all dogs and to marbofloxacin, piperacillin and ceftazidime in three dogs. Successful treatment was achieved in all dogs using trimethoprim/sulfonamides or quinolones (marbofloxacin, ciprofloxacin) or doxycycline in conjunction with ciclosporin withdrawal.


CONCLUSIONS AND CLINICAL IMPORTANCE
Clinicians should be aware of the rare potential for Bcc-associated deep skin infections in dogs receiving oral ciclosporin. Owners should be made conscious of the potential transmission risk to humans or other animals.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Banovic, Frane and Koch, Sandra and Robson, David and Jacob, Megan and Olivry, Thierry}, year={2015}, month={Aug}, pages={287-+} }
 @article{olivry_rossi_banovic_linder_2015, title={Mucocutaneous lupus erythematosus in dogs (21 cases)}, volume={26}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84955657545&partnerID=MN8TOARS}, DOI={10.1111/vde.12217}, abstractNote={BACKGROUND
The diagnosis of dogs with chronic juxtamucosal erosive lesions and histopathology typical of cutaneous lupus erythematosus (CLE) is unclear.


HYPOTHESIS/OBJECTIVES
We report herein 21 dogs with mucocutaneous erosive lesions and lupus-specific histopathology that we propose to be affected with mucocutaneous lupus erythematosus (MCLE), another variant of chronic CLE.


METHODS
Inclusion criteria were the presence of the following: (i) a >2 month history of chronic or recurrent skin lesions; (ii) erosions or ulcers predominating at mucosae or mucocutaneous junctions; (iii) microscopic lesions of CLE (i.e. a lymphocyte-rich interface dermatitis with basal keratinocyte damage); and (iv) a lack of complete remission following antimicrobials. Clinical questionnaires and skin biopsies were reviewed. Direct immunofluorescence and antinuclear antibody serology were performed whenever possible.


RESULTS
More than half of the 21 dogs were German shepherds or their crosses. The disease affected mostly dogs in their mid-adulthood and there was an over-representation of females. Erosions and ulcers predominated at genital/perigenital and anal/perianal areas, with a lower frequency of involvement of periocular, perioral and perinasal regions. In these dogs, there were no clinical signs suggestive of an associated systemic lupus erythematosus. Microscopic lesions were specific for CLE, but they were patchy and often infected with bacteria. The most common immunological finding was focal IgG deposition at the basement membrane zone. Lesions responded to varying interventions, but oral glucocorticoids led to a shorter time to complete remission. Relapses were common upon treatment tapering.


CONCLUSIONS AND CLINICAL IMPORTANCE
These observations support MCLE being another variant of canine CLE.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Olivry, Thierry and Rossi, Michael A. and Banovic, Frane and Linder, Keith E.}, year={2015}, month={Aug}, pages={256-+} }
 @article{banovic_olivry_linder_2014, title={Ciclosporin therapy for canine generalized discoid lupus erythematosus refractory to doxycycline and niacinamide}, volume={25}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911380668&partnerID=MN8TOARS}, DOI={10.1111/vde.12139}, abstractNote={BACKGROUND
Generalized discoid lupus erythematosus (DLE) is an autoimmune skin disease variant rarely reported in dogs. The antimalarial immunomodulator hydroxychloroquine has been suggested as maintenance therapy for generalized DLE in one dog, but several recurrences were noted in the 1 year follow-up of that patient.


HYPOTHESIS/OBJECTIVE
To describe the effective treatment of generalized DLE with ciclosporin in one dog.


ANIMAL
A 6-year-old, castrated male crossbred dog was presented with pruritic, well-demarcated annular to polycyclic, hyperpigmented plaques with marginal erythema on the dorsal head, neck, trunk and medial extremities; these had been nonresponsive to treatment with doxycycline and niacinamide.


METHODS
Investigation included complete blood count, serum chemistry profile, urinalysis, serum antinuclear antibody test, histopathological examination and direct immunofluorescence testing of skin biopsies.


RESULTS
The presence of lymphocyte-rich interface dermatitis on histology, together with generalized chronic recurrent hyperpigmented plaques, was consistent with the diagnosis of a generalized variant of DLE. The absence of systemic signs and unremarkable laboratory tests excluded concurrent systemic lupus erythematosus. Treatment was initiated with oral dexamethasone and ciclosporin. After 1 month, dexamethasone was discontinued and oral ketoconazole was added to the therapeutic regimen. Four months later, pruritus and erythema resolved, with most skin lesions becoming impalpable. Over the last 6 months, the patient's DLE was maintained in remission with oral ciclosporin and ketoconazole in combination every 3 days.


CONCLUSIONS AND CLINICAL IMPORTANCE
The combination of ciclosporin and ketoconazole appeared effective to induce and maintain lesion remission in this dog with generalized DLE.}, number={5}, journal={VETERINARY DERMATOLOGY}, author={Banovic, Frane and Olivry, Thierry and Linder, Keith E.}, year={2014}, month={Oct}, pages={483–E79} }
 @misc{banovic_lemo_2014, title={In vitro evaluation of the use of diluted sodium hypochlorite (bleach) against Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Malassezia pachydermatis}, volume={25}, number={3}, journal={Veterinary Dermatology}, author={Banovic, F. and Lemo, N.}, year={2014}, pages={233–234} }
 @article{banovic_olivry_linder_tobias_2014, title={Pathology in Practice}, volume={245}, ISSN={["1943-569X"]}, DOI={10.2460/javma.245.11.1237}, number={11}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Banovic, Frane and Olivry, Thierry and Linder, Keith E. and Tobias, Jeremy R.}, year={2014}, month={Dec}, pages={1237–1239} }
 @article{banovic_bozic_lemo_2013, title={In vitro comparison of the effectiveness of polihexanide and chlorhexidine against canine isolates of Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Malassezia pachydermatis}, volume={24}, number={4}, journal={Veterinary Dermatology}, author={Banovic, F. and Bozic, F. and Lemo, N.}, year={2013}, pages={409–89} }