@article{eisenschenk_hensel_saridomichelakis_tamamoto-mochizuki_pucheu-haston_santoro_2023, title={Introduction to the ICADA 2023 canine atopic dermatitis pathogenesis review articles and updated definition}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13183}, abstractNote={The International Committee on Allergic Diseases of Animals (ICADA) considers recent literature to coordinate reviews of important advances in atopic and allergic diseases over time. These review articles and translations can be found on the website www.icada.org and include the following: feline atopic syndrome—pathogenesis,1 diagnosis2 and treatment3; canine atopic dermatitis—pathogenesis,4-8 diagnosis,9, 10 research guidelines11, 12 and treatments.13, 14 The purpose of the following papers is to include new information since the last ICADA review papers pathogenesis of canine atopic dermatitis were published in 2015. These updated reviews were prepared by searching for articles and meeting abstracts from 2015 to 2022, and the manuscripts were submitted to the ICADA membership for review before submission to this journal. This new definition is useful in that it includes our current broader understanding of the pathogenesis of this condition beyond allergy. This new definition highlights the multiple factors involved in this disease, which supports the recommendation that the management of canine atopic dermatitis must be multimodal (as seen in the former14 and soon-to-be updated Canine Atopic Dermatitis Practice Guidelines). The first paper includes multiple studies showing the importance of environmental factors in the development of atopy, including lifestyle, diet and parasite exposure. Although atopy is unquestionably a hereditary condition and large atopy prevalence studies continue to show strong breed predispositions, unfortunately no consistent genetic markers have yet been found. The next paper reviews skin barrier measurement (which continues to be difficult and controversial), as well as updates on ceramides, filaggrins and other skin proteins, and interesting studies on the cutaneous microbiome and dysbiosis, and cutaneous host defence peptides. Most new knowledge on the pathogenesis of cAD is in the last paper, which examines the role of cytokines and chemokines. However, many studies are conflicting. Several consistently show upregulation of many T-helper (Th) cell cytokines that is not restricted to certain groups (such as only Th2 cytokines, for example). There also is a consistently strong central role for interleukin (IL)-31 in pruritus, in line with successful therapies targeting this cytokine for relief of clinical signs of AD. Certain topics were not included in the updated pathogenesis papers (e.g. the role of eosinophils, basophils, IgE and dendritic cells) because there is a lack of new information in these areas in dogs. In conclusion, these articles summarise the most important studies on cAD since 2015. Our knowledge of the pathogenesis and the definition of cAD will continue to evolve over the years. Hopefully these review papers will be useful to help direct future research endeavours to better understand the multifactorial complexity of cAD. Melissa Eisenschenk on behalf of the group of authors. Self-funded. The International Committee of Allergic Diseases of Animals (ICADA) should be acknowledged as they reviewed all of these review articles including this introduction and coming to a consensus on the new definition of atopic dermatitis. ICADA was also listed as an author, but the system would not accept it, perhaps acknowledgement would be more appropriate. No conflicts of interest have been declared.}, journal={VETERINARY DERMATOLOGY}, author={Eisenschenk, Melissa C. and Hensel, Patrick and Saridomichelakis, Manolis N. and Tamamoto-Mochizuki, Chie and Pucheu-Haston, Cherie M. and Santoro, Domenico}, year={2023}, month={Dec} }
 @article{tamamoto-mochizuki_santoro_saridomikelakis_eisenschenk_hensel_pucheu-haston_icada_2023, title={Update on the role of cytokines and chemokines in canine atopic dermatitis}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13192}, abstractNote={AbstractBackgroundCytokines and chemokines play central roles in the pathogenesis of canine atopic dermatitis (cAD). Numerous studies have been published and provide new insights into their roles in cAD.ObjectivesTo summarise the research updates on the role of cytokines and chemokines in the pathogenesis of cAD since the last review by the International Committee on Allergic Diseases of Animals in 2015.Material and MethodsOnline citation databases, abstracts and proceedings from international meetings on cytokines and chemokines relevant to cAD that had been published between 2015 and 2022 were reviewed.ResultsAdvances in technologies have allowed the simultaneous analysis of a broader range of cytokines and chemokines, which revealed an upregulation of a multipolar immunological axis (Th1, Th2, Th17 and Th22) in cAD. Most studies focused on specific cytokines, which were proposed as potential novel biomarkers and/or therapeutic targets for cAD, such as interleukin‐31. Most other cytokines and chemokines had inconsistent results, perhaps as a consequence of their varied involvement in the pathogenesis of different endotypes of cAD.Conclusions and Clinical RelevanceInconsistent results for many cytokines and chemokines illustrate the difficulty of studying the complex cytokine and chemokine networks in cAD, and highlight the need for more comprehensive and structured studies in the future.}, journal={VETERINARY DERMATOLOGY}, author={Tamamoto-Mochizuki, Chie and Santoro, Domenico N. and Saridomikelakis, Manolis and Eisenschenk, Melissa N. C. and Hensel, Patrick and Pucheu-Haston, Cherie and ICADA, Int Comm Allergic Dis Anim}, year={2023}, month={Jul} }
 @article{hensel_saridomichelakis_eisenschenk_tamamoto-mochizuki_pucheu-haston_santoro_idada_2023, title={Update on the role of genetic factors, environmental factors and allergens in canine atopic dermatitis}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13210}, abstractNote={AbstractBackgroundCanine atopic dermatitis (cAD) is a common, complex and multifactorial disease involving, among others, genetic predisposition, environmental factors and allergic sensitisation.ObjectiveThis review summarises the current evidence on the role of genetic and environmental factors and allergic sensitisation in the pathogenesis of cAD since the last review by ICADA in 2015.Materials and MethodsOnline citation databases and proceedings from international meetings on genetic factors, environmental factors and allergens relevant to cAD that had been published between 2015 and 2022 were reviewed.ResultsDespite intensive research efforts, the detailed genetic background predisposing to cAD and the effect of a wide range of environmental factors still need more clarification. Genome‐wide association studies and investigations on genetic biomarkers, such as microRNAs, have provided some new information. Environmental factors appear to play a major role. Lifestyle, especially during puppyhood, appears to have an important impact on the developing immune system. Factors such as growing up in a rural environment, large size of family, contact with other animals, and a nonprocessed meat‐based diet may reduce the risk for subsequent development of cAD. It appears that Toxocara canis infection may have a protective effect against Dermatophagoides farinae‐induced cAD. House dust mites (D. farinae and D. pteronyssinus) remain the most common allergen group to which atopic dogs react. Currently, the major allergens related to D. farinae in dogs include Der f 2, Der f 15, Der f 18 and Zen 1.Conclusions and Clinical RelevanceCanine atopic dermatitis remains a complex, genetically heterogeneous disease that is influenced by multiple environmental factors. Further, well‐designed studies are necessary to shed more light on the role of genetics, environmental factors and major allergens in the pathogenesis of cAD.}, journal={VETERINARY DERMATOLOGY}, author={Hensel, Patrick and Saridomichelakis, Manolis and Eisenschenk, Melissa and Tamamoto-Mochizuki, Chie and Pucheu-Haston, Cherie and Santoro, Domenico and IDADA}, year={2023}, month={Oct} }
 @article{santoro_saridomichelakis_eisenschenk_tamamoto-mochizuki_hensel_pucheu-haston_2023, title={Update on the skin barrier, cutaneous microbiome and host defence peptides in canine atopic dermatitis}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13215}, abstractNote={AbstractBackgroundCanine atopic dermatitis (AD) is a complex inflammatory skin disease associated with cutaneous microbiome, immunological and skin barrier alterations. This review summarises the current evidence on skin barrier defects and on cutaneous microbiome dysfunction in canine AD.ObjectiveTo this aim, online citation databases, abstracts and proceedings from international meetings on skin barrier and cutaneous microbiome published between 2015 and 2023 were reviewed.ResultsSince the last update on the pathogenesis of canine AD, published by the International Committee on Allergic Diseases of Animals in 2015, 49 articles have been published on skin barrier function, cutaneous/aural innate immunity and the cutaneous/aural microbiome in atopic dogs. Skin barrier dysfunction and cutaneous microbial dysbiosis are essential players in the pathogenesis of canine AD. It is still unclear if such alterations are primary or secondary to cutaneous inflammation, although some evidence supports their primary involvement in the pathogenesis of canine AD.Conclusion and Clinical RelevanceAlthough many studies have been published since 2015, the understanding of the cutaneous host–microbe interaction is still unclear, as is the role that cutaneous dysbiosis plays in the development and/or worsening of canine AD. More studies are needed aiming to design new therapeutic approaches to restore the skin barrier, to increase and optimise the cutaneous natural defences, and to rebalance the cutaneous microbiome.}, journal={VETERINARY DERMATOLOGY}, author={Santoro, Domenico and Saridomichelakis, Manolis and Eisenschenk, Melissa and Tamamoto-Mochizuki, Chie and Hensel, Patrick and Pucheu-Haston, Cherie}, year={2023}, month={Nov} }
 @misc{tamamoto-mochizuki_olivry_2021, title={IL-31 and IL-31 receptor expression in acute experimental canine atopic dermatitis skin lesions}, volume={32}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.13034}, DOI={10.1111/vde.13034}, abstractNote={BackgroundTo optimise the interleukin (IL)‐31‐blocking therapy in atopic dermatitis (AD), an understanding of the chronology in the expression of IL‐31 and its receptor (IL‐31RA) is needed.Hypothesis/Objectives(i) To assess the chronological expression of IL‐31 in canine AD skin lesions, (ii) to compare it with serum IL‐31 levels and macroscopic skin lesion scores, and (iii) to determine the identity of IL‐31‐ and IL‐31RA‐positive cells.AnimalsFour atopic dogs sensitised to house dust mites.Methods and materialsSkin and blood samples were obtained 0 h, 24 h, 48 and 96 h after allergen provocation. IL‐31 and IL‐31RA single‐staining immunofluorescence (IF), as well as IL‐31/CD3, IL‐31/CD4 and IL‐31RA/β3‐tubulin double‐staining IF were performed. The IL‐31‐positive cells were counted subjectively.ResultsThe peak IL‐31 expression for three of four dogs occurred 24 h or 48 h postchallenge; it started to decrease at 96 h. There was no significant correlation between the IL‐31 expression scores and the serum IL‐31 concentrations or the macroscopic skin lesion scores (P = 0.35 and P = 0.36, respectively). The majority of IL‐31‐positive cells were positive for CD3 (range 91–100%) and CD4 (range 63–100%), indicating that they were helper T (Th) cells. Unexpectedly, sebaceous glands were strongly immunolabelled with IL‐31; the extinction of this positivity after immunoabsorption with IL‐31 further supported the validity of this immunostaining. The IL‐31RA was visualised on keratinocytes and a small proportion of dermal nerves.Conclusions and clinical importanceThe early and transient production of IL‐31 by Th cells supports the concept of using IL‐31 inhibiting strategies as a proactive therapy to prevent flares of AD skin lesions.}, number={6}, journal={VETERINARY DERMATOLOGY}, publisher={Wiley}, author={Tamamoto-Mochizuki, Chie and Olivry, Thierry}, year={2021}, month={Dec}, pages={631-+} }
 @article{baeumer_jacobs_tamamoto-mochizuki_2020, title={Efficacy study of a topical treatment with a plant extract with antibiofilm activities using an in vivo model of canine superficial pyoderma}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12808}, abstractNote={BackgroundCanine pyoderma is a common skin infection caused predominantly by staphylococcal bacteria. Because of increasing rates of antimicrobial resistance in bacterial isolates, there is an urgent need for alternative or supplementary treatment options. W16P576, a Water Extract of Complex Mix of Edible Plants (WECMEP), has shown in vitro activity against a variety of bacteria, including Staphylococcus pseudintermedius. A canine model of pyoderma was developed which allows in vivo testing of antimicrobial agents in a controlled environment.ObjectiveTo evaluate the antibacterial efficacy of topical application of W16P576 in a model of canine pyoderma.AnimalsNine laboratory housed beagle dogs.Methods and materialsIn an evaluator‐blinded cross‐over study with an eight week washout period, dogs were treated topically twice daily with W16P576 WECMEP or its vehicle, starting three days before bacterial challenge. On the day of challenge, each dog was treated with two concentrations of a clinical S. pseudintermedius strain on opposite sides of the body. Topical treatment was continued for 11 days and lesions of pyoderma were evaluated and scored for 14 days.ResultsAll dogs developed lesions consistent with bacterial pyoderma. Lesion scores were generally higher on the side inoculated with a higher concentration of bacteria. Treatment with W16P576 significantly reduced lesion development and hastened resolution of lesions, compared to placebo.ConclusionTopical application of W16P576 markedly reduced lesion development in this proof of principle study. Clinical trials are warranted to estimate benefits for dogs with naturally occurring pyoderma under field conditions.}, number={2}, journal={VETERINARY DERMATOLOGY}, author={Baeumer, Wolfgang and Jacobs, Megan and Tamamoto-Mochizuki, Chie}, year={2020}, month={Apr}, pages={86–89} }
 @article{tamamoto‐mochizuki_paps_olivry_2019, title={Proactive maintenance therapy of canine atopic dermatitis with the anti‐
            IL
            ‐31 lokivetmab. Can a monoclonal antibody blocking a single cytokine prevent allergy flares?}, volume={30}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/vde.12715}, DOI={10.1111/vde.12715}, abstractNote={BackgroundOnce the signs of canine atopic dermatitis (AD) are controlled, the proactive application of topical glucocorticoids can delay disease flares.ObjectivesWe wished to determine if the proactive administration of the anti‐IL‐31 lokivetmab would prevent or delay flares of canine AD.AnimalsWe tested this strategy in four Maltese‐beagle atopic dogs before enrolling 21 dogs with spontaneous AD.Methods and materialsIn our acute AD model, house dust mite (HDM)‐sensitized dogs were injected once with lokivetmab. After seven days, an HDM suspension was applied epicutaneously, and both skin lesions and pruritus manifestations were quantified for 24 h. In a second study, 21 dogs with spontaneous AD controlled with anti‐allergic drugs were treated with lokivetmab per manufacturer's recommendations; all anti‐allergic drugs were discontinued within four weeks after the first injection. All dogs were followed prospectively for at least one year and the time‐to‐flare (TTF) of AD after the last day of anti‐allergic treatment was determined.ResultsIn the experimental study, one injection of lokivetmab prevented nearly all expected allergen‐induced pruritus manifestations but not skin lesion development. In dogs with spontaneous AD, the median TTF after lokivetmab proactive therapy was 63 days. One‐fourth of dogs did not exhibit a flare for at least one year while receiving lokivetmab monotherapy.ConclusionsAlthough lokivetmab seems more effective to prevent pruritus than skin lesions in dogs with experimental AD' it also can delay disease flares in some dogs with the spontaneous disease. Studies are needed to identify those patients most likely to respond to such a proactive regimen.}, number={2}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Tamamoto‐Mochizuki, Chie and Paps, Judy S. and Olivry, Thierry}, year={2019}, month={Jan}, pages={98–e26} }