Cytological evaluation, culture and genomics to evaluate the microbiome in healthy rabbit external ear canals.

BACKGROUND: Lop-eared rabbits may be predisposed to otitis externa (OE) as a consequence of their ear conformation. Although otoscopy, otic cytological evaluation and culture are valuable tools in dogs and cats, published data on rabbits remain lacking. HYPOTHESIS/OBJECTIVES: This study aimed to assess the utility of otoscopy and cytological results in evaluating healthy rabbit external ear canals (EECs) and to characterise ear cytological and microbiological findings through culture techniques and metagenomic sequencing. ANIMALS: Sixty-three otitis-free client-owned rabbits. MATERIALS AND METHODS: All rabbits underwent otoscopy and ear cytological evaluation. In a subset of 12 rabbits, further bacterial and fungal culture, fungal DNA assessment and metagenomic sequencing were performed. RESULTS: Otic cytological results revealed yeast in 73%, cocci in 42.9% and rods in 28.6% of healthy rabbit EECs. Compared to upright-eared rabbits, lop-eared rabbits had more discharge and more bacteria per oil immersion field. Culture isolated eight different species yet metagenomic sequencing identified 36, belonging to the Bacillota (Firmicutes), Pseudomonadota and Actinomycetota phyla. Staphylococcus were the most commonly observed species with both methods. Ten of 12 rabbits were yeast-positive on cytological evaluation with only three yielding fungal growth identified as Yarrowia (Candida) lipolytica, Eurotium echinulatum and Cystofilobasidium infirmominiatum. CONCLUSIONS AND CLINICAL RELEVANCE: Healthy rabbit EECs lack inflammatory cells yet can host yeast and bacteria, emphasising the need to evaluate cytological results alongside the clinical signs. Lop-ear anatomy may predispose to bacterial overgrowth and OE. Notably, yeasts may be present despite a negative culture.

Clinical Techniques: When and how to do a myringotomy - a practical guide.

A myringotomy is a surgical incision made in the tympanic membrane (TM). This gives access to the middle ear for sampling, flushing and instilling topical therapy. It should be considered whenever the TM is intact and there is clinical evidence of otitis media, abnormal TMs and/or abnormal diagnostic imaging. Samples should be collected for cytological investigation and culture, and then the external ear should be cleaned and dried (if required). Myringotomies should be performed under general anaesthesia and, wherever possible, using a video otoscope; the enhanced view and instrument ports facilitate the technique and reduce the risk of complications. The myringotomy incision should be made in the caudoventral quadrant of the TM using an appropriately sized urinary catheter to collect samples and flush the middle ear cavity. A thorough understanding of the anatomy, technique and potential ototoxicity of topical therapy is needed to minimize the risk of neurological and other complications. The TM usually heals within 35 days if kept free of infection.

Une myringotomie est une incision chirurgicale de la membrane tympanique (TM). Elle donne accès à l'oreille moyenne pour prélèvement, flushing et traitement topique. Elle doit être envisagée même si la TM est intacte et si il y a des signes cliniques évocateurs d'otite moyenne, de TM anormale et/ou un diagnostic anormal d'imagerie. Les échantillons devraient être collectés pour cytologie et culture, et ainsi l'oreille externe devrait être nettoyée et séchée (si besoin). Les myringotomies devraient être réalisées sous anesthésie générale et si possible à l'aide d'un vidéo-otoscope; l'amélioration de la visualisation et du port des instruments facilitent la technique et réduit le risque de complications. L'incision de myringotomie devrait être réalisée dans le cadrant caudo-ventral de la TM à l'aide d'une sonde urinaire de diamètre approprié pour la collecte des échantillons et le nettoyage de la bulle tympanique. Une meilleure connaissance de l'anatomie, la technique et la potentielle ototoxicité du traitement topique est nécessaire pour minimiser le risque de complications, notamment, neurologiques. La Tm cicatrise habituellement en 35 jours si aucune infection n'est présente.

Una miringotomía es una incisión quirúrgica realizada en la membrana timpánica (TM). Esto da acceso al oído medio para tomar muestras, lavar e introducir la terapia tópica. Se debe considerar siempre que la TM esté intacta y haya evidencia clínica de otitis media, TM anormales y/o imágenes de diagnóstico anormales. Se deben obtener muestras para investigación citológica y cultivo, y luego se debe limpiar y secar el oído externo (si es necesario). Las miringotomías deben realizarse bajo anestesia general y, siempre que sea posible, utilizando un video otoscopio; la mejor visualización y los enlaces para instrumentos facilitan la técnica y reducen el riesgo de complicaciones. La incisión de miringotomía debe realizarse en el cuadrante caudoventral de la TM utilizando un catéter urinario de tamaño apropiado para recolectar muestras y lavar la cavidad del oído medio. Se necesita un conocimiento profundo de la anatomía, la técnica y la posible ototoxicidad de la terapia tópica para minimizar el riesgo de complicaciones neurológicas y de otro tipo. La TM generalmente cicatriza en 35 días si se mantiene libre de infección.

A miringotomia é uma incisão cirúrgica realizada na membrana timpânica (MT) que dá acesso ao ouvido médio para coleta de amostras, limpeza e instilação de terapia tópica. A miringotomia deve ser considerada sempre que a MT está intacta e há evidência clínica de otite média, MTs anormais e/ou exame de imagem anormal. As amostras devem ser coletadas para investigação citológica e cultura, e depois o ouvido médio deve ser limpo e seco (se necessário). Miringotomias devem ser realizadas sob anestesia geral e, sempre que possível, utilizando um vídeo otoscópio; a visão ampliada e as portas para instrumentos facilitam a técnica e reduzem o risco de complicações. A incisão da miringotomia deve ser realizada no quadrante caudoventral da MT utilizando um cateter urinário de tamanho apropriado para coletar amostras e lavar a cavidade do ouvido médio. Um conhecimento aprofundado da anatomia, técnica e potencial ototoxicidade de produtos tópicos é necessário para minimizar o risco de complicações neurológicas e de outra natureza. A MT geralmente cicatriza em 35 dias se for mantida sem infecção.

Treatment of the feline atopic syndrome - a systematic review.

BACKGROUND: Feline allergic skin disease and asthma occur regularly in small animal practice. OBJECTIVES: To provide evidence-based recommendations for small animal practitioners on the treatment of feline atopic syndrome (FAS). METHODS AND MATERIALS: The authors reviewed the literature available before February 2020, prepared a detailed evidence-based literature review and made recommendations based on the evaluated evidence. RESULTS: Sixty-six papers and abstracts were identified describing treatment interventions for FAS and evaluated to establish treatment recommendations. For many treatment options, the papers were retrospective, open studies or case reports. CONCLUSION AND CLINICAL RELEVANCE: In this review, there was good evidence for the efficacy of systemic glucocorticoids and ciclosporin, and limited evidence for the efficacy of topical glucocorticoids, oclacitinib and allergen-specific immunotherapy in feline atopic skin syndrome. Evidence pointed to low-to-moderate efficacy for antihistamines, fatty acids and palmitoyl ethanolamide. In feline asthma, there was good evidence for the efficacy of oral and inhaled glucocorticoids, and limited evidence of moderate efficacy for allergen-specific immunotherapy. Evidence supported low-to-moderate efficacy of mesenchymal stem cells, inhaled lidocaine and oclacitinib as treatments for feline asthma. For almost all therapeutic options (with the exception of glucocorticoids and ciclosporin), more randomised controlled trials are needed.

Feline allergic diseases: introduction and proposed nomenclature.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: Atopic diseases in humans and cats were researched. A comparison then was made of the essential features in the two species. RESULTS: 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. CONCLUSIONS AND CLINICAL IMPORTANCE: 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.

Measurement of serum Interleukin 34 (IL-34) and correlation with severity and pruritus scores in client-owned dogs with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of dogs. Interleukin (IL)-34 is a monocyte/macrophage growth factor, produced mainly by keratinocytes, that has been implicated in several human inflammatory conditions including human AD. HYPOTHESIS: Canine serum IL-34 concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores. ANIMALS: Forty seven client-owned dogs diagnosed with AD and 25 healthy, unaffected control dogs. METHODS AND MATERIALS: A commercially available IL-34 ELISA was optimized for the measurement of IL-34 in canine serum samples. Information regarding treatment, clinical lesion scores [Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04)] and pruritus Visual Analog Score (pVAS) were recorded for each dog at the time of serum collection. RESULTS: Dogs with AD had significantly increased serum IL-34 concentrations compared to controls. There was a significant positive correlation between IL-34 concentrations and CADESI-04 and pVAS scores. Concentrations of IL-34 remained increased in dogs with AD receiving steroids or the JAK1 inhibitor, oclacitinib, compared to unaffected control dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum IL-34 concentrations are increased in dogs with AD and are correlated with clinical severity and pruritus. IL-34 may be a suitable candidate therapeutic target for canine AD.

A pilot study of the in vitro antimicrobial activity and in vivo residual activity of chlorhexidine and acetic acid/boric acid impregnated cleansing wipes.

BACKGROUND: Topical antimicrobials are recommended for first line treatment of surface and superficial infections in dogs. This is especially important given the increasing prevalence of antimicrobial resistant infections. Antimicrobial wipes have become popular, but there are a lack of controlled studies assessing their in vitro antimicrobial and in vivo residual activity. We aimed to assess the antimicrobial efficacy of two commercial antimicrobial wipes against frequently isolated pathogens. Ten clinical and one reference isolate each of meticillin-susceptible Staphylococcus pseudintermedius (MSSP), meticillin-resistant S. pseudintermedius (MRSP), Escherichia coli (EC), extended spectrum beta-lactamase (ESBL) producing E. coli (ESBL-EC), Pseudomonas aeruginosa (PA) and Malassezia pachydermatis (MP) were tested using a modified Kirby-Bauer technique. Each isolate was tested against 6 mm discs of chlorhexidine (CHX) and acetic acid/boric acid (AABA) wipes, and positive and negative controls either overnight (bacteria) or for 3 days (Malassezia). Healthy dogs were treated with the wipes and distilled water on a randomised flank (n = 5 each). Hair samples (1 cm; 0.1 g) taken at days 0, 1 and 3 were inoculated with an isolate of each organism. Zones of inhibition (ZI) were measured. RESULTS: All isolates produced confluent growth with AABA and control wipes, except for the cleansing wipes and MP (median ZI 12 mm; 95% CI 8.2-15.8). The median (95% CI) CHX wipe ZIs (mm) were: MP 48.0 (47.0-49.0), MSSP 15.6 (14.2-17.0), MRSP 14.0 (13.6-14.4), EC 13.6 (12.0-15.2) and ESBL-EC 10.0 (9.4-10.6). PA showed confluent growth. The differences between the bacterial isolates was significant (Kruskal-Wallis p < 0.0001; post-tests MSSP = MRSP = EC > EBSL-EC > PA). Confluent growth was visible with all the hair samples. CONCLUSION: CHX but not AABA showed in vitro efficacy against MSSP, MRSP, EC and MP. ESBL-EC were less susceptible and there was no activity against PA. There was no residual activity on hair. Additional studies are required to determine efficacy of these products in clinically affected patients.

Measurement of serum macrophage migration inhibitory factor (MIF) and correlation with severity and pruritus scores in client owned dogs with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of dogs. Macrophage migration inhibitory factor (MIF) initiates pro-inflammatory cytokine release in human AD and serum concentrations are correlated with disease severity. HYPOTHESIS: Canine serum MIF concentrations are increased in dogs with AD and correlate with clinical lesion and pruritus scores. ANIMALS: Client owned dogs (n = 49) diagnosed with AD and 17 healthy, unaffected control dogs were used for the study. METHODS AND MATERIALS: A commercially available MIF ELISA was optimized for the dog and serum from clinical cases used. Information regarding treatment, Canine Atopic Dermatitis Extent and Severity Index, (CADESI-4) and pruritus Visual Analog Scale (pVAS) were recorded for each dog at the time of serum collection. RESULTS: Dogs with AD which had not received steroid therapy and those treated with oclacitinib had significantly elevated serum MIF concentrations compared to controls. Concentrations of MIF were not significantly different in AD dogs receiving steroids compared to controls. There was no significant correlation between MIF concentrations and clinical scores (CADESI-4 or pVAS). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum MIF concentrations are increased in dogs with AD and MIF might be a target for therapy.

Routine antibiotic therapy in dogs increases the detection of antimicrobial-resistant faecal Escherichia coli.

Background: Antimicrobial resistance (AMR) is a critical health problem, with systemic antimicrobial therapy driving development of AMR across the host spectrum. Objectives: This study compares longitudinal carriage, at multiple timepoints, of AMR faecal Escherichia coli in dogs undergoing routine antimicrobial treatment. Methods: Faecal samples (n = 457) from dogs (n = 127) were examined pretreatment, immediately after treatment and 1 month and 3 months post-treatment with one of five antimicrobials. Isolates were tested for susceptibility to a range of antimicrobials using disc diffusion for each treatment group at different timepoints; the presence/absence of corresponding resistance genes was investigated using PCR assays. The impact of treatment group/timepoint and other risk factors on the presence of resistance [MDR, fluoroquinolone resistance, third-generation cephalosporin resistance (3GCR) and ESBL and AmpC production] was investigated using multilevel modelling. Samples with at least one AMR E. coli from selective/non-selective agar were classed as positive. Resistance was also assessed at the isolate level, determining the abundance of AMR from non-selective culture. Results: Treatment with ß-lactams or fluoroquinolones was significantly associated with the detection of 3GCR, AmpC-producing, MDR and/or fluoroquinolone-resistant E. coli, but not ESBL-producing E. coli, immediately after treatment. However, 1 month post-treatment, only amoxicillin/clavulanate was significantly associated with the detection of 3GCR; there was no significant difference at 3 months post-treatment for any antimicrobial compared with pretreatment samples. Conclusions: Our findings demonstrated that ß-lactam and fluoroquinolone antibiotic usage is associated with increased detection of important phenotypic and genotypic AMR faecal E. coli following routine therapy in vet-visiting dogs. This has important implications for veterinary and public health in terms of antimicrobial prescribing and biosecurity protocols, and dog waste disposal.

Impact of systemic antimicrobial therapy on mucosal staphylococci in a population of dogs in Northwest England.

BACKGROUND: Antimicrobial-resistant bacteria are increasingly isolated from veterinary patients. OBJECTIVES: To determine risk factors for antimicrobial resistance (AMR) among canine mucosal staphylococci following routine antimicrobial treatment with cefalexin (CFX), clavulanate-amoxicillin (AC), cefovecin (CVN), clindamycin (CD) or a fluoroquinolone (FQ). ANIMALS: Mucosal swab samples (n = 463) were collected from 127 dogs pre-treatment, immediately, and at one- and three-months post-treatment. METHODS: Staphylococci were identified phenotypically and biochemically as coagulase negative (CoNS) or coagulase positive (CoPS); CoPS were speciated by nuc gene PCR. Antimicrobial susceptibility was determined using disc diffusion and mecA gene carriage by PCR. Multilevel, multivariable models examined associations between risk factors and presence/absence of CoPS, meticillin resistance (MR), multidrug-resistance (MDR) and fluoroquinolone resistance (FQR). RESULTS: The percentage of samples with CoNS increased and with CoPS (including S. pseudintermedius) decreased immediately post-treatment with CFX, CVN and CD (P ≤ 0.001) and one month post-treatment with CD (P = 0.003). By three months post-treatment, there was no significant difference compared to pre-treatment samples. Immediately post-treatment with FQs there was significantly increased risk of isolating MRS (P = 0.002), MDR (P = 0.002) or FQR (P = 0.013) staphylococci and of MDR following CFX treatment (P = 0.019). The percentage of samples with AMR staphylococci declined from immediately to three months post-treatment and there was no significant difference between resistance prevalence at one or three months post-treatment for most AMR traits and treatment groups. Exceptions include increased MDR following FQ (P = 0.048) or CFX (P = 0.021), at one and three months post-treatment, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic antimicrobials impact on mucosal staphylococci. Immediately after therapy, the mucosa may be a reservoir for AMR staphylococci that are a source of mobile genetic elements carrying AMR genes.

TREATMENT SUCCESS IN THREE ANDEAN BEARS (TREMARCTOS ORNATUS) WITH ALOPECIA SYNDROME USING OCLACITINIB MALEATE (APOQUEL®).

Andean bear (Tremarctos ornatus) alopecia syndrome (ABAS) commonly affects captive bears, particularly sexually mature females. ABAS is characterized by bilaterally symmetrical predominantly flank alopecia with or without profound pruritus and secondary bacterial and Malassezia infections. There is no effective treatment and severely affected bears have been euthanized. This paper describes the successful management of ABAS in three female Andean bears. Skin biopsies and cytology revealed a mixed dermal inflammatory infiltrate, alopecia, hyperkeratosis, and Malassezia dermatitis. Allergen specific serology was positive for environmental allergens in one case. Hematology, serum biochemistry, and thyroid and adrenal function were normal in all cases. There was no consistent response to novel diet trials, antifungals, antihistamines, allergen specific immunotherapy, or topical antimicrobials. There was a partial response to ciclosporin (Atopica® cat, Novartis Animal Health; 5 mg/kg po, sid) in one case and oral glucocorticoids in all cases (dexamethasone sodium phosphate, [Colvasone 0.2%, Norbrook], 0.15 mg/kg po, sid or prednisolone [Deltacortene, Bruno Farmaceutici, and Megasolone 20, Coophavet], 0.3-1.2 mg/kg po, sid), but treatment was withdrawn following adverse effects. Treatment with oclacitinib maleate (Apoquel®, Zoetis; 0.46-0.5 mg/kg po, bid) resulted in rapid and complete resolution of the pruritus with subsequent improvement in demeanor and fur regrowth. After 5 mo, the bears were almost fully furred and off all other medication. Treatment was tapered to the lowest dose that prevented relapse of the pruritus (0.23-0.4 mg/kg po, sid). No adverse effects have been noted. ABAS is usually an intractable condition, and, to our knowledge, oclacitinib is the first treatment shown to result in sustained clinical improvement. Further studies on the etiology of ABAS, and on efficacy and long-term safety of oclacitinib are needed.

Efficacy of proactive long-term maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study.

BACKGROUND: Long-term remission between flares of canine atopic dermatitis (CAD) can be difficult to achieve. Therefore, additional strategic forms of treatment are needed in order to target flare prevention. The concept of proactive therapy is recommended in the European guidelines for the treatment of human atopic eczema. OBJECTIVES: To evaluate the efficacy of a proactive treatment regimen with a 0.0584% hydrocortisone aceponate (HCA) spray for CAD. ANIMALS: Client-owned dogs with spontaneous atopic dermatitis (AD) (n = 41). METHODS: This pilot study was conducted as a randomised, placebo-controlled, double-blinded clinical trial with an end-point of treatment failure. Dogs were treated once daily to remission, then randomly assigned to receive either the HCA spray (n = 21) or a placebo (n = 20) spray on two consecutive days each week. All dogs were on appropriate flea control. No topical or systemic anti-inflammatory or antimicrobial agents were permitted. Intention-to-treat analysis was used. RESULTS: At Day 0, all the dogs were in remission or had mild AD based on their Canine Atopic Dermatitis Extent and Severity Index, version 3 (CADESI-03) scores. The time to relapse was significantly higher in the HCA group (median 115 d; range 31-260 d) compared to the placebo group (median 33 d; range 15-61 d) (P < 0.0001). No adverse events were attributable to the HCA spray. Four dogs were lost to follow-up and four were withdrawn after receiving prohibited medication. CONCLUSIONS AND CLINICAL IMPORTANCE: These results indicate that proactive long-term therapy of CAD with an HCA spray administered on two consecutive days each week is effective and well-tolerated.

Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA).

BACKGROUND: In 2010, the International Task Force on Canine Atopic Dermatitis (now International Committee on Allergic Diseases of Animals, ICADA) published the first consensus guidelines for the treatment of atopic dermatitis (AD) in dogs. This is the first 5-year minor update of this document. RESULTS: The treatment of acute flares of AD should involve the search for, and then elimination of, the cause of the flares, bathing with mild shampoos, and controlling pruritus and skin lesions with interventions that include topical and/or oral glucocorticoids or oclacitinib. For chronic canine AD, the first steps in management are the identification and avoidance of flare factors, as well as ensuring that there is adequate skin and coat hygiene and care; this might include more frequent bathing and possibly increasing essential fatty acid intake. The medications currently most effective in reducing chronic pruritus and skin lesions are topical and oral glucocorticoids, oral ciclosporin, oral oclacitinib, and, where available, injectable recombinant interferons. Allergen-specific immunotherapy and proactive intermittent topical glucocorticoid applications are the only interventions likely to prevent or delay the recurrence of flares of AD. CONCLUSIONS: This first 5-year minor update of the international consensus guidelines for treatment of AD in dogs further establishes that the treatment of this disease is multifaceted, and that interventions should be combined for a proven (or likely) optimal benefit. Importantly, treatment plans are likely to vary between dogs and, for the same dog, between times when the disease is at different stages.

Ligneous membranitis in Scottish Terriers is associated with a single nucleotide polymorphism in the plasminogen (PLG) gene.

Ligneous membranitis (LM) is a rare chronic inflammatory condition of the mucous membranes associated with plasminogen (encoded by PLG) deficiency in affected humans and dogs. In human, the condition is genetic in nature with numerous mutations and polymorphisms in PLG identified in affected individuals and related family members. The condition is uncommonly reported in dogs and, to date, no genetic studies have been performed. We identified related Scottish Terriers (littermates) with severe LM and unaffected relatives (sire, dam and a sibling from a previous litter). Plasma plasminogen activity was below normal in one affected dog but within normal reference intervals for the other. Sequencing of PLG from the affected dogs revealed a homozygous A>T single nucleotide polymorphism in an intron donor site (c.1256+2T>A). The related, unaffected dogs displayed heterozygous alleles at this position (c.1256+2T/A), whereas no mutation was detected in unaffected, non-related control dogs. This is the first report to identify gene polymorphisms associated with LM in dogs.

Review: Lymphocytes, cytokines, chemokines and the T-helper 1-T-helper 2 balance in canine atopic dermatitis.

BACKGROUND: The development of atopic dermatitis (AD) and other cutaneous hypersensitivities involves the activation and differentiation of allergen-specific lymphocytes. Although hypersensitivity is often considered to be a 'T-helper 2-polarized' lymphocyte response, recent evidence suggests that clinical disease is associated with the development of multiple lymphocyte phenotypes. OBJECTIVES: The purpose of this paper is to review recent advances in the understanding of the roles of lymphocytes, cytokines and noncytokine factors in the pathogenesis of canine AD. METHODS: Citation databases, abstracts and proceedings from international meetings published between 2001 and 2013 were reviewed in this update. Where necessary, older articles were included for background information. RESULTS: The development of canine AD is associated with changes in both cutaneous and circulating lymphocyte populations. These lymphocyte responses are characterized by the production of a complex variety of cytokines, including not only T-helper 2 but also T-helper 1, T-helper 17 and regulatory T-cell responses. In addition, microarray gene expression analysis has enabled the identification of a number of noncytokine factors that appear to be associated with atopic inflammation. These include the calcium-binding protein S100A8, serum amyloid A and a number of protease inhibitors, as well as genes involved in epidermal barrier formation, innate immunity receptors, cell cycle proteins and apoptosis. CONCLUSIONS: The development of AD in dogs is characterized by the development of a delicate balance between a variety of T-cell phenotypes and inflammatory mediators, including cytokines, chemokines and noncytokine factors.

Review: Innate immunity, lipid metabolism and nutrition in canine atopic dermatitis.

BACKGROUND: The pathogenesis of canine atopic dermatitis (AD) involves dysfunction of the adaptive immune system. Recent evidence suggests that nonantigen-specific inflammatory elements may play a role in the development and perpetuation of canine AD. OBJECTIVES: The objective of this review is to provide an update on recent advances in the understanding of the role of innate immune cells, keratinocytes, lipid metabolism and nutrition in the pathogenesis of AD in dogs. METHODS: Citation databases, abstracts and proceedings from international meetings published between 2001 and 2013 are reviewed in this update. Where necessary, older articles are included for background information. RESULTS: Members of the innate immune system (including dendritic cells, Langerhans cells and mast cells) and keratinocytes interact with each other and with environmental antigens during both induction and effector phases of atopic inflammation. The responses of these cells and associated noncellular factors (such as complement and protease-activated receptors) to environmental stimuli influence the entire future course of the immune response to a given agent. Abnormalities in lipid metabolism may also influence the pathogenesis of canine AD via the production of inflammatory mediators and by alteration of epidermal barrier function and antigen presentation. However, a lack of fully controlled studies precludes definitive interpretation of these data. CONCLUSIONS AND CLINICAL IMPORTANCE: Evidence indicates that the cells and noncellular components of the innate immune system and the epidermis may play critical roles during both the sensitization and the effector phases of canine AD. Derangements in lipid metabolism may be involved in the pathogenesis of AD in dogs, but additional controlled studies are required in this area.

Review: The role of antibodies, autoantigens and food allergens in canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (AD) is considered to be an immunoglobulin E (IgE)-mediated hypersensitivity response to environmental allergens. The role of other antibody isotypes and nonenvironmental allergens in disease pathogenesis remains unclear. OBJECTIVES: The objective of this review is to provide an update on advances in the understanding of the relevance of specific antibody isotypes, autoallergens and nonenvironmental allergens in the pathogenesis of canine AD. METHODS: Citation databases, abstracts and proceedings from international meetings published between 2001 and 2013 were reviewed. Where necessary, older articles were included for background information. RESULTS: Neither total nor allergen-specific IgE necessarily correlates with clinical disease in canine AD. Some dogs exhibit clinical signs that are indistinguishable from AD but have no demonstrable allergen-specific IgE (atopic-like dermatitis). Allergen-specific immunoglobulin G may be demonstrated in canine AD, but there is no evidence that this isotype plays a role in disease development. Although humans with AD may develop serum IgE against autoallergens, this finding has not been substantiated in the dog. In contrast, adverse food reactions are frequently co-associated with AD in the dog. Ingestion of food and environmental allergens may trigger exacerbations of AD. CONCLUSIONS AND CLINICAL IMPORTANCE: Determination of the role of IgE in the pathogenesis of canine AD still requires clarification. Clinical trials and research studies must distinguish atopic dogs with allergen-specific IgE or skin test reactivity from those without. There is no convincing evidence demonstrating a pathogenic role for either allergen-specific immunoglobulin G or autoallergens in canine AD, but food items may be triggers for disease flares in certain individuals.

Review: Role of genetics and the environment in the pathogenesis of canine atopic dermatitis.

BACKGROUND: Multiple levels of evidence support the role of genetics and the environment in the pathogenesis of canine atopic dermatitis (AD). OBJECTIVES: This review summarizes the current evidence in genetics and the effect of environmental factors on the development and perpetuation of canine AD. METHODS: Citation databases, abstracts and proceedings from international meetings published between 2001 and 2013 were reviewed in this update. Where necessary, older articles were included for background information. RESULTS: Canine AD is a heritable disease, in which interaction with environmental factors influences disease risk and phenotype. A study of British guide dogs indicated that nearly 50% of the risk of developing AD was determined by an individual's genotype. Genomic studies performed so far in canine AD have uncovered numerous gene candidates likely to be involved in pathogenesis through their role in immunity, skin barrier formation, apoptosis and inflammation. In addition to genetics, there is evidence to suggest that exposure to certain environmental factors influences the prevalence and course of canine AD. For example, living in rural areas or feeding noncommercial diets was negatively associated with the development of AD in dogs, while exposure to high levels of smoke was associated with increased prevalence of allergic skin disease. CONCLUSIONS: It is becoming clear that canine AD is genotypically complex and influenced by a variety of environmental factors. Well-designed studies with sufficient statistical power will be critical to identify the complex genetic and environmental factors involved in disease development and progression. Recognition of such factors may help to identify new targets for therapy and enable better disease prevention and management.

Review: Pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction.

BACKGROUND: Canine atopic dermatitis (AD) is a common, genetically predisposed, inflammatory and pruritic skin disease. The pathogenesis of canine AD is incompletely understood. OBJECTIVES: The aim of this review is to provide an in-depth update on the involvement of skin barrier and host-microbiome interaction in the pathogenesis of canine AD. METHODS: Online citation databases and abstracts from international meetings were searched for publications related to skin barrier and host-microbiome interaction (e.g. bacteria, yeast, antimicrobial peptides). RESULTS: A total of 126 publications were identified. This review article focuses on epidermal barrier dysfunction and the interaction between cutaneous microbes (bacteria and yeasts) and the host (antimicrobial peptides). Epidemiological updates on the presence of pathogenic organisms and canine AD are also provided. CONCLUSIONS AND CLINICAL IMPORTANCE: Major advances have been made in the investigation of skin barrier dysfunction in canine AD, although many questions still remain. Skin barrier dysfunction and host-microbiome interactions are emerging as primary alterations in canine AD. Based on this review, it is clear that future studies focused on the development of drugs able to restore the skin barrier and increase the natural defences against pathogenic organisms are needed.

Review: Clinical and histological manifestations of canine atopic dermatitis.

BACKGROUND: Many studies focusing on clinical and histological signs of canine atopic dermatitis (AD) have been published since its early descriptions decades ago. Findings of these studies contributed to our current knowledge about the disease pathogenesis and allowed establishment of diagnostic criteria used by clinicians and researchers. OBJECTIVES: This review serves as an update on the clinical and histological features of canine AD published by the American College of Veterinary Dermatology Task Force on Canine Atopic Dermatitis in 2001 and summarizes the recent discoveries in these fields. RESULTS: The overall findings of studies focusing on clinical features mirrored those published by the Task Force in 2001. The novelty was the larger number of animals included in these studies, which allowed establishment of a new set of diagnostic criteria that exceeded the sensitivity and specificity of the previous criteria. The same study uncovered some clinical differences between dogs with food-induced and nonfood-induced AD; however, the authors concluded that these two entities cannot be distinguished based on clinical signs only. Another study demonstrated some major breed-specific phenotypes. Several publications addressed the histological features of canine AD skin lesions in experimental models of AD, but none of those addressed naturally occurring lesions. Nevertheless, the histopathological description of the skin reactions was generally similar to that published by the Task Force in 2001. CONCLUSIONS: Considerable work has been done in recent years to provide a better definition of the clinical appearance and histopathology of canine AD. New sets of diagnostic criteria have been developed, and additional breed-associated differences in phenotypes have been demonstrated.

Antimicrobial resistance and characterisation of staphylococci isolated from healthy Labrador retrievers in the United Kingdom.

BACKGROUND: Coagulase-positive (CoPS) and coagulase-negative (CoNS) staphylococci are normal commensals of the skin and mucosa, but are also opportunist pathogens. Meticillin-resistant (MR) and multidrug-resistant (MDR) isolates are increasing in human and veterinary healthcare. Healthy humans and other animals harbour a variety of staphylococci, including MR-CoPS and MR-CoNS. The main aims of the study were to characterise the population and antimicrobial resistance profiles of staphylococci from healthy non-vet visiting and non-antimicrobial treated Labrador retrievers in the UK. RESULTS: Nasal and perineal samples were collected from 73 Labrador retrievers; staphylococci isolated and identified using phenotypic and biochemical methods. They were also confirmed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), PCR of the nuc gene and PCR and sequencing of the tuf gene. Disc diffusion and minimum inhibitory concentration (MIC) susceptibility tests were determined for a range of antimicrobials. In total, 102 CoPS (S. pseudintermedius n = 91, S. aureus n = 11) and 334 CoNS isolates were detected from 99% of dogs in this study. In 52% of dogs CoNS only were detected, with both CoNS and CoPS detected in 43% dogs and CoPS only detected in 4% of dogs. Antimicrobial resistance was not common among CoPS, but at least one MDR-CoNS isolate was detected in 34% of dogs. MR-CoNS were detected from 42% of dogs but no MR-CoPS were isolated. S. epidermidis (52% of dogs) was the most common CoNS found followed by S. warneri (30%) and S. equorum (27%), with another 15 CoNS species isolated from ≤ 15% of dogs. S. pseudintermedius and S. aureus were detected in 44% and 8% of dogs respectively. CONCLUSIONS: MR- and MDR-CoPS were rare. However a high prevalence of MR- and MDR-CoNS were found in these dogs, even though they had no prior antimicrobial treatment or admission to veterinary premises. These findings are of concern due to the potential for opportunistic infections, zoonotic transmission and transmission of antimicrobial resistant determinants from these bacteria to coagulase positive staphylococci.