Search

Background: Canine flank alopecia (CFA) is characterized by seasonally recurring noninflammatory, occasionally hyperpigmented alopecia predominantly in the thoracolumbar area. Previous studies suggest that reduced production of endogenous melatonin may play a role in the pathogenesis of this condition, and placebo‐controlled studies on the efficacy of preventative melatonin treatment are lacking. Objective: To evaluate the efficacy of subcutaneous slow‐release melatonin implants in the prevention of CFA recurrence. Animals: Twenty‐one client‐owned dogs with a history of CFA were included in the study. Materials and Methods: At time (T)0, a general physical and dermatological examination was performed on each dog, blood was collected for serum biochemistry analysis and two skin biopsies were taken from alopecic areas on the nonsedated affected dogs after subcutaneous injection with 2% lidocaine. Dogs with normal blood work and histological results compatible with CFA were included in the study. Participating dogs were randomly assigned to receive either placebo or 18 mg melatonin subcutaneously in the interscapular area, approximately 2 months before expected CFA onset (T1). CFA recurrence was scored qualitatively as complete, ≤50% recurrence, or no recurrence at 5 and 7 months after the intervention (T2 and T3, respectively). Results: At T3, in dogs treated with placebo (nine of 17), the percentages for complete recurrence, ≤50% recurrence and no recurrence were 44%, 0% and 56%, respectively. In dogs treated with melatonin (eight of 17), these percentages were 25%, 50% and 25%, respectively. There were no statistically significant differences in the scores between melatonin‐treated dogs and placebo‐treated dogs (p = 0.40). In three of eight melatonin‐treated dogs, mild transient swelling was observed at the injection site. Conclusions: This study did not provide evidence that an 18 mg melatonin implant treatment, although well‐tolerated, is efficacious in preventing recurrence of CFA in affected dogs. [ABSTRACT FROM AUTHOR]

Abstract: Canine atopic dermatitis (AD) is a chronic inflammatory and pruritic skin disease which shares several characteristics with its human counterpart. In chronic patch test lesions of human with AD mainly a Th1-type cellular response is found. Besides, non-lesional AD skin is already skewed for inflammation and therefore different from healthy skin. The goal of this study was to characterize local immune responsiveness in chronic canine AD lesions as compared to that in non-lesional AD skin by defining T cell subset relevant cytokine- and transcription factor expression profiles. The gene expression of the Th1 cytokines IL-12p35, IL-12p40 and IFN-γ and their related transcription factors STAT4, SOCS5 and T-bet, the Th2 cytokines IL-4 and IL-13 and transcription factors STAT6, SOCS3 and GATA-3 and the regulatory cytokines IL-10 and TGF-β and the transcription factor FOXP3 was evaluated in healthy control and atopic dogs. In non-lesional (NLS) and chronic lesional skin (LS) of atopic dogs and control skin (CS) from healthy dogs mRNA expression of cytokines and transcription factors were measured by quantitative real-time PCR. Significantly different values were found for the following factors: IL-12p40 mRNA was lower in LS when compared to NLS. Expression of STAT4 was higher in LS compared to CS and NLS. More IL-13 and SOCS3 were found in LS and NLS when compared to CS and also in LS compared to NLS. GATA-3 was lower in LS compared to NLS. IL-10 expression was higher in both LS and NLS compared to CS and more IL-10 was present in LS compared to NLS. These findings indicate that both Th1- and Th2-type as well as T regulatory cells are present in NLS and LS in canine atopic skin. [Copyright &y& Elsevier]

Abstract: Quantitative real time PCR (Q-PCR) is the method of choice to study mRNA expression levels. Since Q-PCR is very sensitive, normalization of the data with stably expressed reference genes if of utmost importance. The stability of reference genes depends on the tissue and the species of interest. Therefore, evaluation of the stability of reference genes must be performed for each new tissue and species under study. The stability of B2M, GAPDH, HPRT, SRPR, hnRNPH, GUSB, RPL8, RPS5, and RPS19 was analyzed with the GeNorm software in snap frozen canine skin biopsies. Healthy dogs (n =7) and dogs with confirmed atopic dermatitis (n =28) were included. Lesional and non-lesional skin was analyzed. The study indicated that the most appropriate reference genes in canine skin are the ribosomal gene products RPL8, RPS5 and RPS19 besides GUSB and HPRT. As little as three reference genes will reveal highly reliable Q-PCR calculations. [Copyright &y& Elsevier]

Graphical abstract Abstract Keratinocytes (KC) are the main cellular components of the stratum corneum that constitutes a solid physical skin barrier representing the first line of defense against pathogens. Moreover, KC are potent producers of inflammatory mediators and antimicrobial peptides (AMP) when activated through their pattern recognition receptors. In atopic dermatitis (AD) the protective skin barrier may be compromised due to barrier disruption, secondary infection and accelerated secretion of inflammatory cytokines which may also affect AMP expression in the skin. In the present study, we addressed the responses of a canine KC cell line upon exposure to Staphylococcus pseudintermedius, typically found on canine atopic skin during secondary infections, and stimulation by individual AD-associated ligands and cytokines. All stimuli induced a significant increase in expression of the pro-inflammatory cytokine genes tumor necrosis factor (TNF)-α and interleukin (IL)-8, but with different kinetics. Limited effects were observed on AMP gene expression except for K9CATH which was significantly upregulated upon bacterial infection but with none of the individual AD-associated ligands. Interestingly, K9CATH possessed antimicrobial activity towards Staphylococcus pseudintermedius, indicating that K9CATH expression is a specific defense reaction towards bacterial infection and not part of a general pro-inflammatory profile of KC. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Enzymes involved in the conversion of arachidonic acid to eicosanoids in the skin of atopic dogs. Experimental Dermatology 2010; 19: e317-e319. Abstract: Canine atopic dermatitis (AD), a chronic inflammatory skin disease, shares characteristics with its human counterpart. To get insight into the role of enzymes involved in production of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), potent inflammatory mediators originating from membrane-derived arachidonic acid (AA), expression of genes encoding these enzymes and receptors was quantified by qPCR in non-lesional and lesional skin from atopic dogs and in healthy skin. Significantly higher mRNA expression of the key enzymes 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP), leukotriene A4 hydrolase (LTA4H) and prostaglandin E synthase 1 (mPGES-1) and their receptors (PGE receptors 2 and 3) were observed. Being responsible for elevated levels of metabolites of the 3-series prostaglandins and the 5-series leukotrienes these enzymes may be interesting targets for therapy that should result in amelioration of clinical signs in canine atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Canine atopic dermatitis (cAD) is an allergic skin disease affecting approximately 10% of dogs. allergen‐specific immunotherapy (ASIT) is currently the only treatment option able to induce tolerance to the causative allergens. Objective: To retrospectively establish the efficacy of ASIT in atopic dogs. Animals: Client‐owned (n = 664) dogs with cAD presented between 2008 and 2018 to two dermatology referral clinics. Materials and Methods: Clinical records of atopic dogs were reviewed to obtain information including the results of the intradermal skin test and/or allergen‐specific immunoglobulin (Ig)E serological results, the allergens included in the ASIT, concurrent symptomatic medications, and ASIT efficacy after at least 9 months. Results: Excellent (ASIT alone controlled clinical signs), good (≥50% reduction of clinical signs) and poor (<50% improvement) responses were seen in 31.5%, 28.5% and 40.1% of the dogs, respectively. No significant differences in efficacy were associated with breed, sex, age at initiation of ASIT, type of allergens in ASIT, and between clinics. Dogs re‐examined regularly responded significantly better to ASIT than dogs that did not (>50% improvement in 69.3% and 55.4% of the dogs, respectively). Dogs treated with ASIT and concomitant systemic glucocorticoids showed a significantly poorer response (success rate of >50% improvement of 38.5%). Conclusions and clinical importance: In 59.9% of atopic dogs, subcutaneous ASIT can improve clinical signs by ≥50%. The beneficial effect of ASIT is higher if dogs are re‐examined regularly and if systemic long‐term corticosteroids are avoided, at least during the first 9 months of ASIT. [ABSTRACT FROM AUTHOR]

The immunopathogenesis of cutaneous adverse food reactions (CAFRs) in dogs is unknown. Since the clinical manifestations in the skin are like those found in canine atopic dermatitis (AD), this study investigated the similarity in T cell phenotypes and gene expression of cytokines and transcription factors in CAFRs. In addition, the influence of an elimination diet on these parameters was tested. In the skin of canine CAFRs, a predominant presence of CD8+ T cells and increased expression of the IL-4, IL-13, Foxp3 and SOTS-3 genes were observed. IFN-γ gene expression was increased in lesional compared to non-lesional skin. The predominance of CD8+ T cells indicates that the immunopathogenesis of CAFRs is different from that of canine AD. The elimination diet relieved clinical signs, but did not influence T cell phenotypes or expression of the cytokine and transcription factor genes in the skin of dogs with CAFRs, indicating a continuously pre-activated immune status in dogs sensitised to food constituents. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Bacterial (16S) and fungal (ITS) contributions to the microbiome of canine skin. • The microbiome of canine skin varies with individuality. • The most abundant bacteria observed on AD skin was Staphylococcus. • High abundance of Blumeria was observed on canine atopic skin compared to healthy skin. • Topical antimicrobial treatment significantly changed the microbiome composition. Abstract Canine atopic dermatitis is a genetically predisposed inflammatory and pruritic allergic skin disease that is often complicated by (secondary) bacterial and fungal (yeast) infections. High-throughput DNA sequencing was used to characterize the composition of the microbiome (bacteria and fungi) inhabiting specific sites of skin in healthy dogs and dogs with atopic dermatitis (AD) before and after topical antimicrobial treatment. Skin microbiome samples were collected from six healthy control dogs and three dogs spontaneously affected by AD by swabbing at (non-) predilection sites before, during and after treatment. Bacteria and fungi were profiled by Illumina sequencing of the 16S ribosomal RNA gene of bacteria (16S) and the internally transcribed spacer of the ribosomal gene cassette in fungi (ITS). The total cohort of dogs showed a high diversity of microbes on skin with a strong individual variability of both 16S and ITS profiles. The genera of Staphylococcus and Porphyromonas were dominantly present both on atopic and healthy skin and across all skin sites studied. In addition, bacterial and fungal alpha diversity were similar at the different skin sites. The topical antimicrobial treatment increased the diversity of bacterial and fungal compositions in course of time on both AD and healthy skin. [ABSTRACT FROM AUTHOR]

Skin barrier disruption plays a role in the pathogenesis of atopic dermatitis (AD) in humans. However, little is known about skin barrier (dys-) function in Canine Atopic Dermatitis. The properties of lipids located in the outermost layer of the skin, the stratum corneum (SC) are considered to be important for the barrier. In the present study the lipid composition and lipid organization of the SC of AD dogs and control dogs were examined. The lipid composition of lesional AD skin as compared to control skin, showed a reduced free fatty acid level and a decreased ratio of ceramide[NS] C44/C34, in which C44 and C34 are the total numbers of carbon atoms of the sphingosine (S) and non-hydroxy (N) acyl chains. As a consequence of the observed changes in lipid composition in AD lesional skin the lamellar organization of lipids altered and a shift from orthorhombic to hexagonal lipid packing was monitored. Simultaneously an increased conformational disordering occurred. These changes are expected to compromise the integrity of the skin barrier. The C44/C34 chain length ratio of ceramide[NS] also showed a decreasing nonlinear relationship with the AD severity score (CADESI). Taken together, canine atopic skin showed alterations in SC lipid properties, similar to the changes observed in atopic dermatitis in humans, that correlated with a disruption of the skin barrier. Hence lipids play an important role in the pathogenesis of Canine Atopic Dermatitis. [ABSTRACT FROM AUTHOR]

Lipid antigens are presented to T cells by the CD1 family of proteins. In this study, we characterize the complete dog ( Canis familiaris) CD1 locus, which is located on chromosome 38. The canine locus contains eight CD1A genes (canCD1A), of which five are pseudogenes, one canCD1B, one canCD1C, one canCD1D, and one canCD1E gene. In vivo expression of canine CD1 proteins was shown for canCD1a6, canCD1a8, and canCD1b, using a panel of anti-CD1 monoclonal antibodies (mAbs). CanCD1a6 and canCD1a8 are recognized by two distinct mAbs. Furthermore, we show differential transcription of the three canCD1A genes in canine tissues. In canine skin, the transcription level of canCD1A8 was higher than that of canCD1A6, and no transcription of canCD1A2 was detected. Based on protein modeling and protein sequence alignment, we predict that both canine CD1a proteins can bind different glycolipids in their groove. Besides differences in ectodomain structure, we observed the unique presence of three types of cytoplasmic tails encoded by canCD1A genes. cDNA sequencing and expressed sequence tag sequences confirmed the existence of a short, human CD1a-like cytoplasmic tail of four amino acids, of an intermediate length form of 15 amino acids, and of a long form of 31 amino acids. [ABSTRACT FROM AUTHOR]

Background: In the Netherlands there is a lack of data regarding resistance of Staphylococcus pseudintermedius to the systemic antimicrobial drugs used for the treatment of superficial pyoderma. Objectives: To assess antimicrobial resistance, with emphasis on resistance to clindamycin and meticillin, in clinical isolates of S. pseudintermedius isolated from dogs with superficial pyoderma. Results were compared between dogs with and without a history of systemic antimicrobial therapy during the previous year. Animals: A retrospective study of 237 referral cases presented to an academic teaching hospital between 2014 and 2019, with the clinical and microbiological diagnosis of superficial pyoderma. Methods and materials: All clinical isolates were identified primarily by MALDI‐TOF mass spectrometry. Antimicrobial susceptibility was tested either by an agar diffusion method (2014–2016) or by broth microdilution. Antimicrobial history in the preceding year was obtained from medical records. Results: Meticillin‐resistant S. pseudintermedius (MRSP) was isolated from 8% of superficial pyoderma cases. Within the meticillin‐susceptible S. pseudintermedius (MSSP) population, clindamycin resistance was significantly more common in isolates derived from dogs with histories of antimicrobial treatment (37.7%) compared to dogs with no histories of exposure (21.7%; P = 0.03). Conclusions: Given the high prevalence of clindamycin resistance in MSSP isolated from dogs with prior antimicrobial exposure, it is recommended that bacterial culture and susceptibility testing be pursued before prescribing systemic antimicrobials. Clindamycin should be regarded as the preferred treatment option if susceptibility is confirmed, due to its narrow spectrum and reduced selective pressure for MRSP. [ABSTRACT FROM AUTHOR]