Search

Nodular sebaceous gland hyperplasia in the often middle-aged to old dog is a common, benign proliferation that results in exophytic, pink to yellow, alopecic, and often multilobulated nodules. Removal is usually carried out by surgical excision. As many old dogs have comorbidities that increase the risk of anesthesia, a topical treatment is warranted. We hypothesized that the application of a solution containing nitric acid, zinc, copper, and organic acids (Verrutop ® ), would be a safe and efficient way to treat these nodules. Eleven dogs with a total of 29 nodules, grossly compatible with nodular sebaceous gland hyperplasia, were included in the study. Eighteen of the nodules were treated; 11 were left untreated. No anesthesia or sedation was needed. Four weeks after one application, 17/18 treated nodules had decreased by 100% in volume. There was a statistically significant difference in percentual volume change between the treated and untreated nodules from day 0 to day 28 ( p < 0.0001). No serious side effects were noted. Sebaceous hyperplasia cannot always be distinguished grossly from sebaceous tumors. Cytological evaluation can be helpful, and in cases of deviant macroscopic features, local recurrence, or more aggressive behavior, the appropriate intervention would be to biopsy or excise the nodule for histopathology. Topical application of Verrutop ® is an easy, low-cost, and efficient way to remove canine sebaceous gland hyperplasia with minimal side effects in cases where surgery and anesthesia are not desired.

Clipping hair on animals can produce microtraumas of the skin and the dislodgement of microorganisms to the clipper blade. This study evaluates if clipper blades in animal hospitals in Sweden are contaminated with bacteria and/or dermatophytes after disinfection. Eleven clipper blades from three veterinary referral hospitals, including one with a small animal department and an equine department, were sampled for bacteria and dermatophytes. All the hospitals had disinfection routines in accordance with the national recommendations for hygiene in veterinary medicine. The sampled clipper blades were supposed to be disinfected and they were considered to be ready for use by staff. Five sterilized clipper blades were used as controls. The results showed that 64-100% of the disinfected clipper blades, from all three hospitals, were contaminated with bacteria, whereas all the sterilized clipper blades were negative for bacterial growth ( p < 0.05). One clipper blade from the equine department was contaminated with dermatophytes. The results indicate that the disinfection routines were not sufficient for removing bacteria from used clipper blades, and that sterilization would be a more reliable way to minimize the risk of contamination.

Insect bite hypersensitivity (IBH) associated with Culicoides biting midges is a common allergic skin disease in horses, reducing the welfare of affected horses. This study investigated the effect of IBH on animal welfare and behaviour and assessed a new prophylactic insect repellent. In total, 30 horses were recruited for a prospective cross-over and case-control study. Clinical signs of IBH, inflammatory markers in skin biopsies and behavioural data (direct observations, motion index) were scored longitudinally during two consecutive summers. No differences were observed in the total number of itching behaviours or motion index between IBH-affected horses and controls, but higher numbers of itching behaviours were observed in the evening. IBH-affected horses showed both clinical and histopathological signs of inflammatory skin lesions, with even short periods of scratching being associated with moderate/severe inflammatory skin lesions. In order to improve the welfare of the IBH-affected horses, they should be stabled/given extra protection in the evening and even short-term exposure to Culicoides should be avoided. Preliminary results showed that the repellent tested can be used as a safe and non-toxic prophylactic to potentially reduce allergen exposure in horses with IBH, but further studies are needed to determine its efficacy.

Background: A rebound of pruritus occasionally occurs after oclacitinib dose reduction in dogs with atopic dermatitis (AD)., Objectives: To determine whether an initial 4-day course of prednisolone decreases the probability of a pruritus rebound after reducing the frequency of oclacitinib administration., Animals: Forty dogs with mild-to-moderate AD lesions and moderate-to-severe pruritus., Materials and Methods: Dogs were randomised to receive oclacitinib at 0.4-0.6 mg/kg twice daily for 14 days then once daily, alone or with prednisolone at 0.5 mg/kg, orally, twice daily for the first 4 days. Clinicians graded the Canine Atopic Dermatitis Extent and Severity Index (CADESI)4 and 2D-investigator global assessment (IGA) before and after 28 days; owners assessed the pruritis Visual Analog Scale (PVAS)10 and Owner Global Assessment of Treatment Efficacy (OGATE) on Day (D)0, D4, D14, D21 and D28. We considered a rebound any increase greater than one PVAS10 grade at D21 compared to D14., Results: On D21, there were significantly fewer rebounds in the dogs receiving prednisolone (three of 20, 15%) compared to those given oclacitinib alone (nine of 20, 45%; Fisher's test, p = 0.041). Compared to oclacitinib monotherapy, the concurrent administration of prednisolone for the first 4 days led to significantly lower PVAS10 on D4 and D28, CADESI4 and 2D-IGA on D28, and OGATE on D21 and D28 (Wilcoxon-Mann-Whitney U-tests). Adverse effects of therapy were minor, intermittent and self-resolving., Conclusions and Clinical Relevance: The initial addition of 4 days of prednisolone significantly decreased the probability of a rebound of pruritus 1 week after oclacitinib dose reduction. This short concomitant glucocorticoid administration led to a higher skin lesion improvement and improved perception of treatment efficacy with minimal adverse effects., (© 2022 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Pug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflammation have been described. PDM has a late onset and affects more male than female dogs. The breed-specific presentation of the disorder suggests that genetic risk factors are involved in the disease development. To perform a genome-wide search for PDM-associated loci, we applied a Bayesian model adapted for mapping complex traits (BayesR) and a cross-population extended haplotype homozygosity test (XP-EHH) in 51 affected and 38 control pugs. Nineteen associated loci (harboring 67 genes in total, including 34 potential candidate genes) and three candidate regions under selection (with four genes within or next to the signal) were identified. The multiple candidate genes identified have implicated functions in bone homeostasis, fibrotic scar tissue, inflammatory responses, or the formation, regulation, and differentiation of cartilage, suggesting the potential relevance of these processes to the pathogenesis of PDM.

Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus (Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated., (© 2022. The Author(s).)

Glucocorticoids are widely used to treat canine allergic disorders, but they frequently cause polyuria and polydipsia (PUPD). At equipotent dosages, oral methylprednisolone is believed to cause less PUPD than prednisolone. We performed a pilot randomized, open, parallel trial with 22 dogs with nonseasonal AD receiving either prednisolone or methylprednisolone at equipotent dosages, once daily for 14 days during the first phase of a restriction-provocation dietary trial. Before and on days 3, 7, and 14 after starting the glucocorticoids, owners estimated water consumption for 24 h. On the same days and before the glucocorticoid was given, owners collected the first-morning urine to determine the urine specific gravity (USG). There were no significant differences between the prednisolone and methylprednisolone groups on days 3, 7, and 14 when comparing the changes in water intake from baseline. Most dogs from both groups exhibited a slight reduction in USG during the study. Still, there was no significant difference in USG changes between the groups on any of these three reevaluation days. In conclusion, the administration of two weeks of oral prednisolone and methylprednisolone at equipotent anti-inflammatory dosages at the beginning of an elimination diet did not lead to significant differences in water intake and USG.

Background: Allergens targeted by serum-specific immunoglobulin E (sIgE) in dogs clinically allergic to chicken have not been reported., Objectives: To characterise the allergens targeted by sIgE in dogs sensitised and allergic to chicken., Animals: Sera from three dogs not sensitised to chicken, from 10 chicken sensitised dogs and from 12 chicken allergic dogs., Methods and Materials: Enzyme-linked immunosorbent assay (ELISA) and immunoblotting with a commercial chicken extract were utilized. The bands identified on immunoblotting were sequenced by mass spectrometry for allergen characterization., Results: Using ELISA, we detected chicken-sIgE above the positive threshold in zero of three (0%) nonsensitised dogs, five of five (100%) chicken-sensitised dogs (a selection criterion), and in seven of 12 (58%) chicken-allergic dogs. Immunoblotting performed with the same extract revealed IgE-bound protein bands in 100% of all chicken-sensitised and -allergic dogs, respectively. To identify the allergens, we excised the corresponding bands on the electrophoretic gel, and submitted them for sequencing by mass spectrometry. We conclusively identified seven major allergens (serum albumin, pyruvate kinase M, enolase 3, creatine kinase M, lactate dehydrogenase A, glyceraldehyde-3-phosphate dehydrogenase and triose-phosphate isomerase) and one minor allergen (troponin C), which are relevant to dogs., Conclusions and Clinical Relevance: We identified herein seven major chicken allergens for dogs, several of which are known to be cross-reactive allergens for humans. Based on their degree of sequence identity, these allergens exhibit the theoretical potential to be cross-reactive between poultry and mammalian meats; six of these allergens already are known to be cross-reactive between chicken and fish species. Future studies should address the clinical relevance and cross-reactivity potential of these chicken allergens in dogs., (© 2021 ESVD and ACVD.)

Background: Equine sarcoids are the most prevalent skin neoplasm in horses worldwide. Although several treatments are available, none are consistently effective and recurrence is common., Objectives: To evaluate the efficacy and safety of topical imiquimod 5% cream and Sanguinaria canadensis + zinc chloride for treatment of equine sarcoids and investigate possible systemic effects on distant untreated sarcoids., Animals/tumours: Twenty-five client-owned horses with a total of 164 tumours were included in the study. Fifty-seven tumours were treated and 107 tumours were left untreated., Methods and Materials: Skin biopsy samples were collected from a minimum of one tumour per horse and the rest were diagnosed based on clinical appearance as likely sarcoids. Imiquimod 5% (A) was applied three times weekly, while Sanguinaria canadensis + zinc chloride (X) was applied every fourth day after a six day daily initiation phase. Treatment continued until clinical remission or for a maximum of 45 weeks, with a long follow-up period (mean 34 months). Skin biopsy samples of sarcoid lesions were re-taken before treatment termination and at follow-up if the owner gave consent., Results: Complete remission was recorded in 84.4% (A) and 75.0% (X) of the tumours. Relapse was recorded in 7.3% (A) and 21.4% (X). Spontaneous remission was observed in 1.9% of untreated tumours. No systemic effect on untreated tumours was detected. During treatment varying degrees of local inflammatory reaction were common., Conclusions and Clinical Relevance: Both treatments were considered effective and safe. Smaller tumours responded more favourably to treatment. Relapse rate was low and not observed in sarcoids with repeat biopsies before treatment termination., (© 2020 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the European Society of Veterinary Dermatology and the American College of Veterinary Dermatology.)

Background: Malassezia yeast overgrowth on the skin is a common and often recurrent cause of dermatitis in dogs; it can be an exacerbating factor of atopic dermatitis. Anti-fungal drugs have been a standard treatment, but there is some concern that resistance may be evolving in a spectrum of Malassezia species. Safe, efficient and easy-to-use alternatives are needed., Objectives: To assess if a commercially available topical non-azole solution applied to paws affected by Malassezia-associated dermatitis (MAD), could ameliorate Malassezia numbers and associated signs over a short term (14 day) trial., Animals: Eighteen dogs with MAD affecting at least two paws., Methods: The study design was prospective, randomized, blinded and placebo-controlled, using a split-body protocol. Dogs were treated once daily with the test solution on one paw and placebo on the other. Dogs were examined at days 0 and 14 ± 3. The primary end-point was Malassezia numbers assessed cytologically. Secondary end-points were clinical scores for lesion severity and pruritus as assessed by a pruritus Visual Analog Scale (PVAS). Owner compliance and adverse effects were assessed., Results: There was a statistically significant reduction in Malassezia numbers and clinical scores for paws treated with the test solution versus placebo. No statistical difference in PVAS was found., Conclusion: Daily topical application of the test solution was effective in reducing the Malassezia burden, as well as improving clinical scores in dogs with MAD of the paws. No adverse effects were reported and owners described the product as either "easy" or "very easy" to use., (© 2017 ESVD and ACVD.)

Background: Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome-wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin-2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities., Objectives: The main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD-affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location., Animals/methods: Skin biopsies were collected from nine CAD-affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology., Results: We observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding-partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed., Conclusion: Plakophilin-2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes., (© 2017 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.)

Background: Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2., Results: Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region., Conclusions: Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10-20 cases and 10-20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted resequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-of-concept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrländer dogs. To our knowledge, this is the first time this family trio WGS-approach has been used successfully to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrländer dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences, and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G > C (p.R52P) was found to be concordant in eight additional cases, and 16 healthy Kromfohrländer dogs., (Copyright © 2016 Sayyab et al.)

Immunoglobulin A deficiency (IgAD) is the most common primary immune deficiency disorder in both humans and dogs, characterized by recurrent mucosal tract infections and a predisposition for allergic and other immune mediated diseases. In several dog breeds, low IgA levels have been observed at a high frequency and with a clinical resemblance to human IgAD. In this study, we used genome-wide association studies (GWAS) to identify genomic regions associated with low IgA levels in dogs as a comparative model for human IgAD. We used a novel percentile groups-approach to establish breed-specific cut-offs and to perform analyses in a close to continuous manner. GWAS performed in four breeds prone to low IgA levels (German shepherd, Golden retriever, Labrador retriever and Shar-Pei) identified 35 genomic loci suggestively associated (p <0.0005) to IgA levels. In German shepherd, three genomic regions (candidate genes include KIRREL3 and SERPINA9) were genome-wide significantly associated (p <0.0002) with IgA levels. A ~20kb long haplotype on CFA28, significantly associated (p = 0.0005) to IgA levels in Shar-Pei, was positioned within the first intron of the gene SLIT1. Both KIRREL3 and SLIT1 are highly expressed in the central nervous system and in bone marrow and are potentially important during B-cell development. SERPINA9 expression is restricted to B-cells and peaks at the time-point when B-cells proliferate into antibody-producing plasma cells. The suggestively associated regions were enriched for genes in Gene Ontology gene sets involving inflammation and early immune cell development.

Immunoglobulin A (IgA) serves as the basis of the secretory immune system by protecting the lining of mucosal sites from pathogens. In both humans and dogs, IgA deficiency (IgAD) is associated with recurrent infections of mucosal sites and immune-mediated diseases. Low concentrations of serum IgA have previously been reported to occur in a number of dog breeds but no generally accepted cut-off value has been established for canine IgAD. The current study represents the largest screening to date of IgA in dogs in terms of both number of dogs (n=1267) and number of breeds studied (n=22). Serum IgA concentrations were quantified by using capture ELISA and were found to vary widely between breeds. We also found IgA to be positively correlated with age (p<0.0001). Apart from the two breeds previously reported as predisposed to low IgA (Shar-Pei and German shepherd), we identified six additional breeds in which ≥ 10% of all tested dogs had very low (<0.07 g/l) IgA concentrations (Hovawart, Norwegian elkhound, Nova Scotia duck tolling retriever, Bullterrier, Golden retriever and Labrador retriever). In addition, we discovered low IgA concentrations to be significantly associated with canine atopic dermatitis (CAD, p<0.0001) and pancreatic acinar atrophy (PAA, p=0.04) in German shepherds., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: A noninfectious, spontaneous, multifocal alopecia has been recognized in Norwegian puffin dogs., Hypothesis/objectives: This study aimed to report demographic information, history, clinical signs, histopathological features and follow-up information for alopecic Norwegian puffin dogs from Sweden., Material and Methods: A questionnaire was sent out to all members of the breed association. Dogs clinically diagnosed with alopecia and biopsied were allocated to Group A. Dogs reported with alopecia for which histopathology was not available were allocated to Group B., Results: Group A included 14 dogs (11.7% of the breed population in Sweden). Information regarding 72 dogs (60% of the breed population) was collected via questionnaire, and alopecia without histopathology was reported in another five dogs (Group B). Gender distribution was equal. Median age of onset was 1.5 years (range 8 months to 7 years). Multifocal or serpiginous alopecia, follicular plugging, dry skin, slight scaling and pruritus were characteristic. Extensive, widespread alopecia was not seen, and lesions were recorded only in haired skin. A lymphoplasmacytic, mural, isthmus folliculitis/perifolliculitis with follicular and perifollicular mucin was observed. Inflammation did not involve the hair bulb; atrophy was sometimes present. The inflammation sometimes extended to sebaceous glands, resulting in atrophy and absence of glands. Follow-up ranged from 6 months to 12 years (mean 3.2 years). Spontaneous remission was rare. Estrus was associated with worsening of the disease or relapse. Oral prednisolone reduced pruritus but was not effective in resolving clinical lesions. All dogs treated with ciclosporin went into remission., Conclusions and Clinical Importance: This is the first report of mural, mucinotic, isthmus folliculitis alopecia in Norwegian puffin dogs., (© 2014 ESVD and ACVD.)

Sarcoids are the most common skin tumors seen in horses worldwide. The pathogenesis of sarcoids is multifactorial, including an association with bovine papillomavirus types 1 and 2 and a genetic susceptibility to tumor development. Clinical manifestations vary and include occult, verrucous, nodular, fibroblastic, mixed, and malignant (malevolent) types. The tumor is nonmetastasizing but can become very aggressive locally. Multiple tumors are common. All clinical types can be present in the same horse. No treatment protocol is universally effective. The tumor has a high risk of recurrence. Recurrent and large tumors are associated with poorer prognoses., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7), pgenome = 0.03). The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD., Competing Interests: The authors have declared that no competing interests exist.

Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4×10⁻¹⁴). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38× coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis., Competing Interests: I have read the journal's policy and have the following conflicts: A patent concerning the commercial genetic testing of HNPK in dogs has been filed. TL is the inventor on this patent.

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Cutaneous infections with bacteria and yeasts are common in small animal practice. Treatment with systemic antibiotics or antifungal agents may not be ideal, because of the increasing development of multiresistant organisms, the cost and the possible adverse effects. Topical antimicrobials may be used as adjunctive therapy to systemic treatment or as sole therapy instead of systemic treatment., Objective: This literature review evaluated studies on topical antimicrobial treatment of skin infections., Methods: In vitro and in vivo studies evaluating topical antimicrobial agents were identified using a number of electronic and manual searches of textbooks and articles. Studies were evaluated, and the evidence for or against the use of the topical agents was extracted., Results: There is good evidence for the efficacy of chlorhexidine and, to a lesser degree, benzoyl peroxide in canine bacterial skin infections. There is limited evidence for the efficacy of silver sulfadiazine and medical honey against bacterial skin infections in the dog, and for the efficacy of hydrogen peroxide and stannous fluoride in the horse. Good evidence supports the use of a combination of chlorhexidine and miconazole in dogs with cutaneous Malassezia infections. There is insufficient evidence to recommend any other topical therapy for use in cutaneous infections., Conclusions and Clinical Importance: Although many antimicrobial topicals are marketed in veterinary dermatology, the efficacy has been reported for only a minority of agents. Randomized controlled trials evaluating various topical treatments are therefore urgently needed., (© 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.)

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD., (© 2011 The Authors. Veterinary Dermatology © 2011 ESVD and ACVD.)

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

Hypersensitivity dermatitides (HD) are often suspected in cats. Cats with HD are reported to present with one or more of the following patterns: miliary dermatitis, eosinophilic dermatitis, self-induced symmetrical alopecia or head and/or neck excoriations. Previous reports on feline HD included small numbers of animals, took place in geographically restricted areas or did not compare these conditions with other causes of pruritus. The goal of the present study was to analyse 72 parameters covering signalment, clinical, laboratory and treatment characteristics from a large group of pruritic cats from different geographical areas. Of the 502 cats, the following diagnoses were made: flea HD (29% of cases), food HD (12%) nonflea/nonfood HD (20%) and other diseases in which pruritus was a feature (24%). Cats with signs consistent with a HD but which did not complete a food trial were not analysed further (15% of cases). Most cats with nonflea HD exhibited signs compatible with one or more of the four typical lesional patterns, but none of these patterns was found to be pathognomonic for any specific diagnosis. Food HD and nonflea/nonfood HD were found to be clinically undistinguishable. Young adult, purebred and female cats appeared predisposed to nonflea/nonfood HD. As many diagnoses presented with similar lesional patterns, a thorough clinical work-up is required for establishment of a specific diagnosis., (© 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.)

Background: Treatment and protection of wounds in horses can be challenging; protecting bandages may be difficult to apply on the proximal extremities and the body. Unprotected wounds carry an increased risk of bacterial contamination and subsequent infection which can lead to delayed wound healing. Topical treatment with antimicrobials is one possibility to prevent bacterial colonization or infection, but the frequent use of antimicrobials ultimately leads to development of bacterial resistance which is an increasing concern in both human and veterinary medicine., Methods: Standardized wounds were created in 10 Standardbred mares. Three wounds were made in each horse. Two wounds were randomly treated with LHP® or petrolatum and the third wound served as untreated control. All wounds were assessed daily until complete epithelization. Protocol data were recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for inflammation and healing, photoplanimetry for calculating wound areas and swab cytology to assess bacterial colonization and inflammation. Bacterial cultures were obtained on day 2, 6 and 16., Results: Mean time to complete healing for LHP® treated wounds was 32 days (95%CI=26.9-37.7). Mean time to complete healing for petrolatum and untreated control wounds were 41.6 days (95%CI=36.2-47.0) and 44.0 days (95%CI=38.6-49.4) respectively. Wound healing occurred significantly faster in LHP® wounds compared to both petrolatum (p=0.0004) and untreated controls (p<0.0001). There was no significant difference in time for healing between petrolatum and untreated controls. Total scores for bacteria and neutrophils were significantly (p<0.0001) lower for LHP® treated wounds compared to petrolatum from day 16 and onwards. Staphylococcus aureus and Streptococcus zooepidemicus were only found in cultures from petrolatum treated wounds and untreated controls., Conclusions: Treatment with LHP® reduced bacterial colonization and was associated with earlier complete wound healing. LHP® cream appears to be safe and effective for topical wound treatment or wound protection.

Insect bite hypersensitivity (IBH) and atopy can both be causes of pruritus in horses and are associated with allergen-specific IgE to biting insects and environmental allergens respectively. Information with respect to differences in IgE levels in diseased and healthy animals is crucial in enabling an understanding of the clinical relevance of results of allergen-specific IgE tests. The aim of this study was (i) to evaluate and compare levels of allergen-specific IgE, using an ELISA method, in Icelandic horses, with and without IBH, from Iceland and Sweden respectively; (ii) to investigate patterns of allergen-specific IgE to insects, pollens, moulds and mites in those groups of horses; and (iii) to investigate the clinical significance of employing two different cut-off levels for the ELISA. The study compromised a total number of 99 horses from Iceland and Sweden, with and without IBH, divided in 5 groups. Sera from the horses were analysed blindly with the use of Allercept , a non-competitive, solid-phase ELISA-test, designed to detect the presence of allergen-specific IgE in sera using the recombinant alpha chain of the high-affinity IgE receptor (FcepsilonR1alpha). The distribution of the ELISA values was shown for each insect, mould, mite and pollen allergen, in the different groups using 10th, 50th and 90th percentiles. The use of two cut-off levels, 150 EA and 300 EA, did not eliminate the false positives. Horses with IBH had a higher number of positive reactions, counting all the 29 allergens, than healthy controls and this was borderline significant (P=0.053). In this study it was shown that serological testing with an ELISA that uses the high-affinity IgE receptor (FcepsilonR1alpha) is presently not suitable as a tool for establishing a diagnosis of IBH or equine atopy. The importance of establishing a correct cut-off level for the ELISA for the different allergens is emphasised.

Background: Sebaceous adenitis (SA) is an uncommon, immune mediated skin disease in dogs. The aim was to retrospectively investigate SA in dogs in Sweden with respect to breed, sex and age distribution. A second aim was to retrospectively compare clinical signs in dogs with generalized SA and to estimate the survival after diagnosis in the English springer spaniel, standard poodle and the akita., Methods: In total 34 Swedish veterinarians contributed with 104 clinically and histologically verified SA cases. Breed, gender and age at diagnosis were registered for each case. The degree of clinical signs at time for diagnosis and at follow-up and information about treatments, concurrent diseases and euthanasia were recorded for the springer spaniels, standard poodles and akitas using a standardized questionnaire., Results: A total of 104 cases of SA were included; most cases were recorded for the springer spaniel (n = 25), standard poodle (n = 21) and the akita (n = 10). These three breeds, together with the lhasa apso and the chow-chow, were the most common when national registry data from the Swedish Board of Agriculture and Swedish Kennel Club were considered. The mean age at diagnosis was 4.8 years. The proportion of males was 61%. When the springer spaniels, standard poodles and the akitas with generalized signs were compared (n = 51), the spaniels showed significantly more severe clinical signs than the poodles at diagnosis regarding alopecia, seborrhoea, pyoderma and the overall severity of clinical signs. At follow-up, the degree of clinical signs for otitis externa and pyoderma differed significantly between the breeds. The estimated median survival time was 42 months. In dogs where data regarding survival was available at the end of the study (n = 44), SA was reported to be the reason for euthanasia in 14 dogs, whereof 7 within 24 months after diagnosis., Conclusion: The result of this study implicates that the English springer spaniel is a breed predisposed to SA and that it has more severe clinical signs than the standard poodle. A large proportion of the dogs (spaniel, poodle and akita) investigated regarding survival were reported to have been euthanized to great extent due to the disease.

Background: A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice., Methods: Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200-476 microg kg-1 subcutaneously 2-3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618-2185 microgkg-1) and oral ivermectin (range 616-2732 microgkg-1) administered by the owners, 3-6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2-20,0 mgkg-1, 1-3 times with an interval of 2-4 weeks. Follow-up time was 4 months-4.5 years., Results: Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively., Conclusion: All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols.

Environmental and dietary risk factors for the development of canine atopic dermatitis (CAD) in the high-risk breeds of boxer, bullterrier and West Highland white terrier were assessed in a case-control study. A logistic regression model was developed to evaluate their relative importance in 58 cases from 12 practices in Sweden and 61 unaffected controls, matched to cases by breed and year of birth. The final model included a random error term for 'examining veterinarian', as dogs from the same practice were not considered independent. No effect of gender, season of birth, environment, vaccination or de-worming practices on the odds of developing CAD was detected. The main finding was that feeding a diet including noncommercial products to the bitch during lactation had a protective effect on the development of CAD in her offspring; the odds of developing CAD were twice as high among offspring from bitches that were not exposed to home-made/noncommercial diets [95% confidence interval (CI) of the odds ratio: 1.2-3.8]. The population attributable fraction for not feeding home-made diets to the lactating bitch was estimated as 0.4 (95% CI: 0.04-0.63). Randomized controlled clinical trials are needed to further support the finding of a potential protective role of diet in CAD development.

A cross-sectional study of insured Swedish dogs with a recorded diagnosis of canine atopic dermatitis (CAD) was performed. In order to validate the correctness of this specific diagnosis in the insurance database, medical records were requested by mail from the attending veterinarians. All dogs with a reimbursed claim for the disease during 2002 were included in the original study sample (n = 373). Medical records were available for 335 individuals (response rate: 89.8%). By scrutinizing the submitted records it was determined that all dogs had been treated for dermatologic disease, and that 327 (97.6%) could be considered to have some allergic skin disease. However, as information regarding dietary trial testing was missing in many dogs the number that were truly atopic could not be determined. The clinical presentation and nature of test diet for dogs with or without response to dietary trial testing was compared for a subset of 109 individuals that had undergone such testing. The only significant difference between these two groups was that the proportion of dogs with reported gastrointestinal signs was higher in the group that subsequently responded to a diet trial. In conclusion, the agreement between the recorded diagnosis in the insurance database and the clinical manifestations recorded in the submitted medical records was considered acceptable. The concern was raised that many attending veterinarians did not exclude cutaneous adverse food reactions before making the diagnosis of CAD.

Allergic diseases are common in dogs and the involvement of IgE in the pathogenesis of canine atopic dermatitis (CAD) and flea allergy dermatitis (FAD) is documented. However, many dogs do not achieve sufficient control of their allergic disease, and there is a great need for new treatment strategies. In order to address this issue we first needed to obtain a better picture of IgE-levels in dogs and how plasma IgE-levels are affected by breed, age and health status. IgE is normally present at diminutive concentrations in sera and detection by diagnostic methods has been a technical challenge. Here, we present a new in vitro assay for determining absolute levels of total IgE in sera from dogs. In a panel of 76 adult dogs diagnosed either as healthy or suffering from atopic dermatitis, autoimmunity or infection by skin parasites, we show that levels of IgE range from 1 to 41 microg/ml. This is almost 100 times the level observed in non-atopic humans. However, these exceptionally high IgE-levels in the dogs could not be correlated to either breed or health status. To address the issue of novel treatment strategies, the possibility of reducing the IgE-levels in nine Beagle dogs by immunization with a new therapeutic vaccine was investigated. High levels of anti-IgE antibodies were induced in all dogs, and the IgE-levels were subsequently decreased by a mean of 65%. This shows that the allergy vaccine is potent enough to break the tolerance against IgE, even when the initial IgE-levels are as high as those observed in dogs. Thus, the vaccination treatment may have the potential to serve as a future therapy for dogs with atopic diseases.

Limited information is available on the long-term outcome of treatment of pemphigus foliaceus in dogs. The purpose of this study is to report that a prolonged remission can occur after discontinuation of immunosuppressive regimens in some animals with this disease. Six dogs were diagnosed with pemphigus foliaceus based on suggestive clinical signs and histopathology. These patients were treated either with immunosuppressive doses of oral glucocorticoids or with a combination of oral glucocorticoids and azathioprine. After clinical signs underwent complete remission, which occurred 1.5-5 months after immunosuppression was initiated, the drugs were tapered progressively and eventually withdrawn. The total duration of immunosuppressive therapy varied between 3 and 22 months. Skin lesions of pemphigus foliaceus did not recur for 1.5-6 years after treatment was stopped. These observations suggest that, in some dogs with pemphigus foliaceus, immunosuppression can lead to long-term remission of skin lesions, and that discontinuation of treatment is not necessarily followed by a recurrence of clinical signs.

A randomized, double blind, placebo-controlled multicentre clinical trial of 12 weeks' duration was undertaken in 60 dogs with atopic dermatitis to evaluate the steroid sparing effect of essential fatty acid supplementation. The dogs were randomly assigned to receive either a combination of borage seed oil and fish oil or a placebo, in addition to prednisolone tablets. All dogs received a standardized basal diet. Owners of the dogs recorded pruritus daily using a 10 cm visual analog scale and the dosage of prednisolone was established based on the pruritus score, according to written instructions. The dosage of prednisolone and the use of any concurrent treatment (shampoo and/or ear-cleanser) were recorded by the owner on a daily basis. The investigators graded the skin lesions at days 0, 42 and 84. The use of prednisolone during the test period was lower in the active group, but the difference was not statistically significant (P = 0.32). The test period was sequentially divided into 43-84, 50-84, 57-84, 64-84, 71-84 and 78-84 days. On day 64, the difference between the active group and the placebo group reached statistical significance (P = 0.04) with an increasing difference towards the end of the study. A statistically significant reduction in the pruritus scores and the total clinical scores from day 0 to day 84 was apparent in both groups (P < 0.0001). At the end of the study, both the pruritus score and the total clinical score were lower in the active group. Our findings indicate a steroid sparing effect of essential fatty acid supplementation in canine atopic dermatitis and, furthermore, that there is a time lag before the effect is attained.