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1.
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2.
Background – Antimicrobial peptides (AMPs) are small immunomodulatory peptides produced by epithelial and immune cells. β‐Defensins (BDs) and cathelicidins (Caths) are the most studied AMPs. Recently, increased cutaneous expression of AMPs was reported in atopic humans and in beagles with experimentally induced atopy. Hypothesis/Objectives – Our goal was to analyse mRNA expression and protein levels of canine (c)BD1‐like, cBD2‐like/122, cBD3‐like, cBD103 and cCath in healthy and naturally affected atopic dogs, with and without active skin infection, along with their distribution in the epidermis using indirect immunofluorescence. Animals – Skin biopsies were taken from 14 healthy and 11 atopic privately owned dogs. Methods – The mRNA levels of cBD1‐like, cBD2‐like/122, cBD3‐like, cBD103 and cCath were quantified using quantitative real‐time PCR. The protein levels of cBD3‐like and cCath were analysed by relative competitive inhibition enzyme‐linked immunosorbent assay, while the distributions of cBD2‐like/122, cBD3‐like and cCath were detected by indirect immunofluorescence. Results – Dogs with atopic dermatitis had significantly greater mRNA expression of cBD103 (P = 0.04) than control dogs. Furthermore, atopic skin with active infection had a higher cBD103 mRNA expression (P = 0.01) and a lower cBD1‐like mRNA expression (P = 0.04) than atopic skin without infection. No significant differences in protein levels (cBD3‐like and cCath) or epidermal distribution of AMPs (cBD2‐like/122, cBD3‐like and cCath) were seen between healthy and atopic dogs. Conclusions and clinical importance – Expression of cBD103 mRNA was greater, while expression of cBD1‐like mRNA was lower in dogs with atopic dermatitis that had active infections. Work is needed to clarify the biological mechanisms and possible therapeutic options to maintain a healthy canine skin.  相似文献   

3.
Background – Cutaneous impairment plays a crucial role in atopic dermatitis (AD). Transepidermal water loss (TEWL) measurement is an indirect assessment of skin barrier function and correlates with disease severity in humans. Skin impairment also exists in canine AD; however, concerns exist regarding variability and reliability of TEWL measurements in dogs. Hypothesis/Objectives – The purposes of this retrospective study were twofold: first, to investigate the correlation between severity of dermatitis [measured by Canine Atopic Dermatitis Extent and Severity Index (CADESI)] and TEWL; and second, to evaluate whether increased TEWL at a young age correlates with disease severity later in life. Methods – Data from atopic beagles and dogs with natural AD were analysed. Transepidermal water loss was measured in atopic beagles (n = 24) with an open chamber and in dogs with naturally occurring AD with a closed chamber device (two studies, with n = 14 and n = 18). Pearson product–moment correlation was used for analyses. Transepidermal water loss of the inguinal region, axilla, antebrachial flexure and pinna was analysed. Correlations were investigated for each study, separately first and then jointly. They included CADESI and TEWL of individual regions, total CADESI and total TEWL of all measured regions, and total CADESI and TEWL of key regions. Results – In atopic beagles, TEWL measured at 1 year of age pre‐ and post‐allergen challenge was correlated with CADESI at 1, 3 and 6 years of age. Overall, low correlation coefficients were found; therefore, a biologically relevant connection could not be demonstrated. The main significant positive correlation was found between TEWL in the pinna and total CADESI. Conclusions and clinical importance – It is concluded that TEWL does not correlate with disease severity.  相似文献   

4.
Atopic dermatitis (AD) is a chronic, life‐long disease. In humans, immunotherapy (IT) is the only treatment that can alter the course of AD. Oral IT is appealing owing to the ease of administration and the potential for increased compliance. The purposes of this study were to investigate the tolerability, clinical efficacy and effects on allergen‐specific IgE of oral IT using a canine AD model. Thirteen atopic beagles sensitized to house dust mites (HDMs) were randomly divided into two groups. One group received daily oral doses of HDMs while the other group received vehicle only for 7 months. The investigator evaluating the dogs was blinded to the allocation of treatments. Prior to and after 2 and 7 months of IT, dogs were challenged daily with HDMs for 3 days concurrently, and clinical signs were scored using a modified Canine Atopic Dermatitis Extent and Severity Index (CADESI). Prior to and at completion of oral IT, serum was collected for measurement of allergen‐specific IgE. Oral IT was well tolerated, and no adverse effects were noted. Analysis of variance showed no significant effect of time, group and group × time interaction for CADESI scores. In addition, there were no significant differences in allergen‐specific IgE levels. In conclusion, it appears that oral administration of HDMs is well tolerated in these atopic beagles but that this protocol was not sufficient to induce clinical improvement. Further, longer‐term studies will be necessary to explore the potential of oral IT in veterinary medicine.  相似文献   

5.
Impairment of skin barrier function has been hypothesized in canine atopic dermatitis (AD). In this prospective, controlled study, the ultrastructure of the upper epidermal layers was investigated using an experimental model of canine AD. Seven atopic Beagles sensitized to Dermatophagoides farinae and four healthy Beagles were used as controls. Both normal and atopic dogs were challenged with D. farinae for 3 days. Clinical signs were scored and skin biopsies were taken from the inguinal area before and 3 days after allergen exposure. Samples were processed to enhance lipid visibility and evaluated by Transmission Electron Microscopy. Emphasis was placed on evaluation of the lipid lamellae (LL), and lamellar bodies (LB) of the stratum corneum.
After allergen challenge, atopic Beagles developed severe pruritic dermatitis while no skin lesions were noted in the controls. Ultrastructurally, before allergen challenge, atopic Beagles displayed focally severe abnormalities in LL organization and wider intercellular spaces containing abnormal lipid material. In atopic Beagles, LBs were frequently found inside corneocytes while this finding was not observed in the controls. After allergen challenge, further increase of intercellular spaces was observed in the stratum corneum of atopic Beagles while no appreciable changes were observed in the normal dogs. Intercellular spaces in atopic Beagles were filled with abundant amounts of abnormal lipid material and highly disorganized LL. It is concluded that baseline differences in the ultrastructure of the skin exist between normal and experimentally sensitized atopic Beagles and that these changes are aggravated by allergen challenge and the resulting flare-up of dermatitis.  相似文献   

6.
Epidermal tight junctions (TJ) have been well-described in human medicine and are involved in many skin diseases such as atopic dermatitis (AD). In dogs, there are no data regarding the implication of TJ in skin diseases including canine AD.The aim of this study was to compare the expression and the distribution of ZO-1, occludin and claudin-1 in the epidermis of healthy and atopic dogs.Skin biopsies from 6 high IgE-producing beagles sensitized to house dust mite (atopic group) were used. Skin specimens from nine healthy dogs without skin issues were sampled (healthy group).Immunoperoxydase staining was used to study the staining pattern of zonula occludens-1 (ZO-1), occludin and claudin-1 in the epidermis of healthy and atopic dogs. Positive controls were healthy human skin samples.Labeling patterns were assessed by 2 examiners blinded to the identities of the specimens. Comparisons between groups were performed using an exact Wilcoxon-Mann-Whitney test.The mean total expression score of claudin-1 was lower in atopic dogs as compared to healthy subjects. Occludin and ZO-1 expression remained unchanged within each group.These results suggest a defect in claudin-1 expression in the nonlesional epidermis of atopic dogs.  相似文献   

7.
Although canine atopic dermatitis (cAD) is common, few models are available. The aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were environmentally challenged with HDM using various doses and protocols. Similar challenge protocols were used in positive and negative control dogs: three dogs with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and three normal dogs without history of skin disease and negative IDT to HDM. All high-IgE beagles and all atopic dogs developed severe cutaneous lesions and pruritus after challenge. Lesions were erythematous papules and macules in contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They were first visible after 6 h and increased in severity over time. No normal dog developed pruritus or lesions. Biopsies of representative lesions in the high-IgE beagles were taken for histopathology and immunohistochemistry. There was superficial perivascular dermatitis with mononuclear infiltrates and spongiosis. Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that this colony of high-IgE beagles develops a dermatitis that clinically, histopathologically and immunologically resembles the naturally occurring canine disease. It is also concluded that this modality of challenge is not irritating to normal dogs but induces flare-ups in hypersensitive atopic dogs.  相似文献   

8.
Seven dogs with atopic dermatitis and six normal dogs were treated with a spot-on product containing essential oils and unsaturated fatty acids q 7 days for 8 wk. Seven additional atopic dogs received a daily spray containing similar ingredients to the spot-on. In all dogs, transepidermal water loss (TEWL) was measured before and after treatment using a closed chamber device. In atopic dogs, a validated lesion score (canine atopic dermatitis extent and severity index, CADESI) was determined and pruritus was assessed with a visual analog scale before and after treatment. The mean CADESI scores in atopic dogs decreased with the spot-on (P=0.0043) and with the spray (P=0.0366). Similarly, the pruritus scores decreased with the spot-on (P=0.266) and with the spray (P=0.0177). There was a significant difference between the TEWL values of healthy and atopic dogs on the abdomen (P=0.0181) and back (P=0.0123). TEWL decreased significantly on the back after treatment with the spray (P=0.016), but not on the abdomen (P=0.078). Adverse effects were not observed. The results of this pilot study indicate that topical fatty acids and essential oils are a useful treatment option for canine atopic dermatitis.  相似文献   

9.
This study evaluated the efficacy of PhytopicaTM, a proprietary blend of standardised plant extracts, in canine atopic dermatitis (AD). One hundred twenty dogs with perennial AD were recruited on the basis of history and clinical signs, and a positive intradermal allergen test or rFcεRIα serology to perennial allergens. Other pruritic dermatoses were eliminated by antimicrobial treatment, skin scrapings, Sarcoptes serology, flea control and a 6-week food trial. Exclusion criteria included antimicrobial therapy within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or cyclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days of entry into the study. Dogs [minimum Canine Atopic Dermatitis Extent and Severity Index (CADESI) = 25] were randomly allocated to receive placebo, 100, 200 or 400 mg/kg PhytopicaTM daily for 12 weeks. Their CADESI was assessed every 4 weeks. A modified intention-to-treat population was analysed. The mean reductions in CADESI scores at the end of treatment compared to baseline were 4.4% (100 mg/kg; n  = 30), 23.4% (200 mg/kg; n  = 29, P  < 0.01), 8.5% (400 mg/kg; n  = 29) and 3.9% (placebo; n  = 29). For more severely affected dogs (minimum CADESI ≥ 50 at baseline), there was significant reduction in mean CADESI score (29.3%, P  = 0.038) only in the 200 mg/kg treatment group ( n  = 14). In conclusion, this study demonstrates that PhytopicaTM is an effective nonsteroidal treatment for canine AD.
Funding: Phytopharm plc.  相似文献   

10.
This study evaluated the efficacy of PhytopicaTM, a proprietary blend of standardised plant extracts, in canine atopic dermatitis (AD). One hundred twenty dogs with perennial AD were recruited on the basis of history and clinical signs, and a positive intradermal allergen test or rFcεRIα serology to perennial allergens. Other pruritic dermatoses were eliminated by antimicrobial treatment, skin scrapings, Sarcoptes serology, flea control and a 6‐week food trial. Exclusion criteria included antimicrobial therapy within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or cyclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days of entry into the study. Dogs [minimum Canine Atopic Dermatitis Extent and Severity Index (CADESI) = 25] were randomly allocated to receive placebo, 100, 200 or 400 mg/kg PhytopicaTM daily for 12 weeks. Their CADESI was assessed every 4 weeks. A modified intention‐to‐treat population was analysed. The mean reductions in CADESI scores at the end of treatment compared to baseline were 4.4% (100 mg/kg; n = 30), 23.4% (200 mg/kg; n = 29, P < 0.01), 8.5% (400 mg/kg; n = 29) and 3.9% (placebo; n = 29). For more severely affected dogs (minimum CADESI ≥ 50 at baseline), there was significant reduction in mean CADESI score (29.3%, P = 0.038) only in the 200 mg/kg treatment group (n = 14). In conclusion, this study demonstrates that PhytopicaTM is an effective nonsteroidal treatment for canine AD. Funding: Phytopharm plc.  相似文献   

11.
Pathogenesis of canine atopy has not been completely elucidated. In humans, sulphido-leukotrienes (s-LT) play a role in atopy, and increased production of s-LT occurs in the skin and peripheral leukocytes after allergen challenge. The study population included 16 clinically normal and 13 atopic dogs. All atopic dogs had in common a positive reaction (4+) to the intradermal injection of house dust mite (allergen of reference). Blood samples and skin biopsies were collected. Sulphido-LT synthesis by peripheral leukocytes after stimulation was measured, and no statistically significant difference was found between clinically normal and atopic dogs. Sulphido-LT concentrations in skin samples from stimulated and unstimulated sites were measured, and no statistically significant difference was detected between clinically normal and atopic dogs or between lesional and nonlesional skin within the atopic group. Clinical signs of atopic dogs were graded by owners and no correlation was found between their severity and cutaneous concentrations of s-LT. In this study there was no increase in s-LT synthesis in atopic dogs.  相似文献   

12.
The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen‐specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen‐specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL‐4, TNF and IL‐10 was quantitated using RT‐PCR. A mixture of allergen extract and liposome‐DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t‐test. There were significant improvements in pruritus scores (P = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL‐4 production decreased significantly (P = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen‐specific immunotherapy for the treatment of canine atopic dermatitis. Funding: Self‐funded.  相似文献   

13.
The purpose of this study was to evaluate a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis. Seven dogs with nonseasonal atopic dermatitis diagnosed by history, clinical signs and exclusion of differential diagnoses were included. All dogs had been on allergen-specific immunotherapy for at least 12 months with incomplete responses, were on additional antipruritic therapy and showed residual pruritus. Pruritus was marked by the owner on a visual analogue scale, lesions were determined by a clinician using the Canine Atopic Dermatitis Extent and Severity Index (CADESI), and concurrent medications were recorded before entering the study and after 14 weeks of treatment. Peripheral blood mononuclear cells were isolated and cultured; canine cytokine message for IFNγ, IL-4, TNF and IL-10 was quantitated using RT-PCR. A mixture of allergen extract and liposome-DNA complexes was injected intradermally at the beginning of the study and after 2, 4, 6, 10 and 14 weeks. CADESI, pruritus and medication scores, and cytokine messages at the beginning and end of the study were compared with a paired t -test. There were significant improvements in pruritus scores ( P  = 0.0277). Reductions in medication scores and CADESI were not statistically significant. IL-4 production decreased significantly ( P  = 0.0428); decreases in other cytokines were not significant. Although the number of dogs in this pilot study was small, the results warrant further investigation of a combination of immunostimulatory bacterial DNA sequences and allergen-specific immunotherapy for the treatment of canine atopic dermatitis.
Funding: Self-funded.  相似文献   

14.
In canine and human atopic patients, the intracutaneous injection of offending allergens is followed by the development of both immediate and late-phase reactions. The present study was performed to expand on the characterization and dynamics of inflammatory cell subsets during IgE-mediated late-phase reactions in canine skin. Three normal dogs and three Dermatophagoides farinae -allergic dogs were selected for this experiment. All dogs were challenged intradermally with mite allergen, purified anticanine IgE antibodies (positive control) or phosphate-buffered saline (negative control). Skin biopsies were obtained before and 6, 12 and 24 h post-injection. Sections were stained with metachromatic and eosinophil-specific histological stains. Additionally, we used an immunohistochemical method with antibodies specific for canine leukocyte antigens. This study confirmed the occurrence of a late-phase reaction in atopic skin following allergen challenge, and in normal and atopic canine skin after intradermal injection of IgE-specific antibodies. Whereas early emigrating dermal cells were composed chiefly of neutrophil and activated eosinophil granulocytes, there was an influx of αβ T-lymphocytes and dermal dendritic cells in later stages of the late-phase reactions. Because IgE-mediated late-phase reactions resemble spontaneous atopic canine skin lesions, both at macroscopic and microscopic levels, we propose the use of similar challenges to study the anti-inflammatory effects of anti-allergic drugs in a pre-clinical setting.  相似文献   

15.
In humans, skin barrier dysfunction is thought to be responsible for enhanced penetration of allergens. Similar to conditions seen in humans, canine atopic dermatitis (CAD) is characterized by derangement of corneocytes and disorganization of intercellular lipids in the stratum corenum (SC) with decreased ceramide levels. This study was designed to evaluate the effects of a moisturizer containing ceramide on dogs with CAD. Dogs (n = 20, 3~8 years old) with mild to moderate clinical signs were recruited and applied a moisturizer containing ceramide for 4 weeks. Transepidermal water loss (TEWL), skin hydration, pruritus index for canine atopic dermatitis (PICAD) scores, and canine atopic dermatitis extent and severity index (CADESI) scores of all dogs were evaluated. Skin samples from five dogs were also examined with transmission electron microscopy (TEM) using ruthenium tetroxide. TEWL, PICAD, and CADESI values decreased (p < 0.05) and skin hydration increased dramatically over time (p < 0.05). Electron micrographs showed that the skin barrier of all five dogs was partially restored (p < 0.05). In conclusion, these results demonstrated that moisturizer containing ceramide was effective for treating skin barrier dysfunction and CAD symptoms.  相似文献   

16.
During the last decade, oral cyclosporin (CsA) has proven to be effective, in randomized controlled trials, for the treatment of atopic dermatitis (AD) in human patients. The purpose of this blinded randomized controlled trial was to test the hypothesis that CsA was successful in reducing the gravity of clinical signs of AD in dogs. Thirty dogs with nonseasonal AD were randomly allocated to receive an oral solution of either NEORAL CsA (5 mg kg-1) or prednisolone (0.5 mg kg-1) once daily for 6 weeks. Before, and 3 and 6 weeks after therapy, skin lesions were graded by clinicians using the Canine AD Extent and Severity Index (CADESI). Pruritus was assessed by the owners using a visual analog scale (PVAS). In both groups, CADESI and PVAS values were significantly lower at 6 weeks post treatment than before the initiation of therapy (Friedman test, P < 0.0004). The percentage reductions in CADESI and PVAS values from baseline were not statistically different between groups (Mann-Whitney test, P > 0.3). In this experiment, the tolerability and safety of oral CsA and prednisolone appeared similar. One-fifth of dogs given oral CsA occasionally developed diarrhoea or soft stools. One dog that was given CsA developed a generalized papillomatous skin eruption during the second half of the trial. Our study provides randomized controlled trial evidence that CsA reduces the severity of clinical signs in dogs with nonseasonal AD. Moreover, the anti-allergic efficacy of CsA appears comparable with that of prednisolone. We propose that oral CsA should be considered as a valuable alternative to glucocorticoid therapy in dogs with AD.  相似文献   

17.
The kinetics of cytokine expression was evaluated in whole blood from high-IgE beagles previously sensitized to house dust mites (HDM) and known to develop clinical signs compatible with atopic dermatitis (AD) upon allergen exposure. Six high-IgE beagles were environmentally challenged daily for 3 h on three consecutive days with a HDM solution. Clinical signs were evaluated before, during, and after the conclusion of the challenge (days 0, 2, 4 and 17) and expression analyses of Th2 (IL-4 and IL-13) and regulatory (IL-10 and TGF-beta) cytokine mRNA were undertaken on blood samples at each time point using real-time polymerase chain reaction. Multiple comparison used to detect significant differences in clinical scores and expression levels of cytokine mRNA revealed that the clinical scores on days 2 and 4 were higher than those on days 0 and 17 (P < 0.05) but no temporal differences in the expression levels of IL-4 and IL-13 mRNA. Expression of TGF-beta mRNA was, however, significantly lower on day 4 (P < 0.05) and the expression of IL-10 mRNA on days 4 and 17 was significantly lower than those on days 0 and 2 (P < 0.05). The results indicate that allergen challenge decreases mRNA expression of regulatory cytokines in whole blood without enhanced mRNA expression of Th2 cytokines and suggest aberrant regulatory T-cell function in the immunopathogenesis of AD in high-IgE beagles.  相似文献   

18.
Human and canine atopic dermatitis (AD) share an association with IgE specific to environmental allergens, but few studies have evaluated serum allergen‐specific IgE in nonatopic dogs. This study compared serum allergen‐specific IgE levels in 30 atopic and 18 nonatopic West Highland white terriers. Atopic dermatitis was confirmed using standard criteria. Nonatopic dogs were over 5 years of age and had no clinical signs or history of AD. Serum allergen‐specific IgE levels were measured with Allercept® IgE ELISAs using a 48‐allergen Australian panel. Positive reactions were defined as ≥150 ELISA absorbance units. Intradermal tests were performed in 16 atopic dogs, either at the time of or at various times prior to serum collection. In atopic dogs, the most common positive ELISA and intradermal test results were to Dermatophagoides farinae (11 of 30 dogs), but there were no statistically significant correlations between results from the two methods for any allergen. In nonatopic dogs, multiple high‐positive ELISA reactions were reported to 45 of 48 allergens, most commonly D. farinae and Tyrophagus putrescentiae (17 of 18 dogs each). Positive ELISA results in nonatopic dogs were statistically significantly higher than those in atopic dogs for 44 of 48 allergens, including two allergens (D. farinae and Dermatophagoides pteronyssinus) commonly regarded as significant in canine AD. In conclusion, positive allergen‐specific IgE ELISAs were not specific for canine AD, and high allergen‐specific IgE levels were seen in nonatopic dogs. The clinical significance of this and whether it characterizes a protective phenotype is unclear.  相似文献   

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20.
Evidence suggests that high-quality diets enriched with essential fatty acids (EFA) and other nutrients can ameliorate canine atopic dermatitis (AD). This study compared such a diet (Eukanuba Veterinary Diets Dermatosis FP) with a home-cooked equivalent (fish and potato) in a randomised, single-blinded, cross-over trial. Twenty dogs with perennial AD were randomly assigned to receive either the test (group A) or the control diet (group B) for 1 month, followed by the contrasting diet for a further month. Canine Atopic Dermatitis Extent and Severity Index (CADESI version 2) and pruritus (visual analogue scale) scores were recorded at days 0, 30 and 60. Eight dogs in each group completed the study. CADESI scores significantly declined when dogs were fed the test diet (group A P < 0.01; group B P < 0.001), and increased (group A P < 0.05) or remained steady (group B) on the control diet. CADESI scores decreased in 15 of 16 dogs fed the test diet, but this was less than 50% in all cases. Pruritus scores also declined when dogs were fed the test diet compared to the control diet, but this was only significant for group A (P = 0.027). Pruritus was reduced in 11 of 16 dogs fed the test diet, but this was 50% or more in only two dogs. This trial provides evidence for the efficacy of Eukanuba Veterinary Diets Dermatosis FP in canine AD, although it is likely that most cases will require adjunct therapy. The mechanism is unclear, but may involve increased and balanced EFA levels.  相似文献   

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