[Show abstract][Hide abstract] ABSTRACT: Atopic Dermatitis (AD) is a prevalent disease that affects both humans and animals. Dogs share similar environments with the owners and spontaneously develop a disease that is clinically and immunologically identical to AD in humans. In past decades AD has become more and more common in both dogs and humans, possibly due to the increased exposure to indoor allergens and decreased exposure to parasites and beneficial bacteria. The allergic component plays an important role in both species. Allergen specific immunotherapy (ASIT) has been used with great success in veterinary medicine for decades for the treatment of AD and traditionally has been accomplished with subcutaneous injections. In human medicine, ASIT has been traditionally used for respiratory manifestations of atopic disease and only recently considered for the therapy of AD. Interestingly, dogs primarily express cutaneous manifestations of atopic disease and only rarely progress from cutaneous into respiratory disease, a process referred in human medicine as “atopic march”. Recently, sublingual immunotherapy has been replacing subcutaneous immunotherapy both in human and veterinary medicine due to its ease and safety, leading to increased compliance. The purpose of this mini review is to focus on the use of sublingual immunotherapy for AD highlighting similarities and differences between humans and dogs.
[Show abstract][Hide abstract] ABSTRACT: Atopic dermatitis (AD) is a common skin disease that affects humans and animals. Skin impairment has been described in human and canine AD. Equine AD is recognized in practice but little is known about its pathogenesis. As remarkable similarities exist across species in terms of cutaneous manifestations of AD, it was speculated that skin abnormalities may also exist in atopic horses. This case report describes the ultrastructure of the stratum corneum of two normal and two atopic horses. Biopsies were taken from sites predisposed to AD and examined using electron microscopy. Stratum corneum in normal samples was compacted with organized lipid lamellae while in atopic samples disorganized lipid lamellae, retained lamellar bodies and amorphous lipids were found. These changes are very similar to what reported in AD in other species. It is currently unknown whether these abnormalities in atopic horses are primary or secondary and their importance in allergen penetration.
Research in Veterinary Science 10/2014; · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allergies are common in horses. It is important to identify and correct as many factors as possible to control pruritus and make the patient comfortable. Culicoides hypersensitivity is a common component in allergic horses. The main treatment continues to be rigorous fly control and avoidance of insect bites. Environmental allergies are best addressed by early identification of the offending allergens and formulation of allergen-specific immunotherapy to decrease the need for rescue medications. Food allergy is best managed with food avoidance. Urticaria is one of the manifestations of allergic disease wherein detection of the triggering cause is essential for management.
The Veterinary clinics of North America. Equine practice 12/2013; 29(3):551-557. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Filaggrin is a structural protein that has attracted increasing interest over the past decade for its role in the pathogenesis of human atopic dermatitis (AD). Null mutations in its sequence are considered risk factors in the development of AD.
To investigate canine filaggrin mRNA and protein expression in the skin of atopic beagles with experimentally induced AD compared with breed-matched healthy control dogs.
All dogs were environmentally challenged for 3 days consecutively with allergens to which the atopic dogs had been sensitized. Skin biopsy specimens were taken from six healthy and seven atopic beagles before and after allergen challenge. Canine filaggrin mRNA was measured using quantitative real-time PCR. Indirect immunofluorescence was used to localize the filaggrin protein in canine skin. Analysis of variance with Tukey's multiple comparison test (over-time effect) and unpaired Student's t-test (treatment effect) were used. Values of P ≤ 0.05 were considered significant.
Analysis of variance showed a significantly higher expression of filaggrin mRNA in atopic dogs compared with healthy control dogs (P = 0.004 on day 3 and P = 0.01 on day 10) and a decreased mRNA expression on day 3 in healthy control dogs (effect of time, P = 0.006). On blinded evaluation, filaggrin immunofluorescence was distributed homogeneously in the stratum granulosum and the stratum corneum in healthy dogs. Atopic dogs showed a patchy immunofluorescence pattern, which was exacerbated after environmental challenge.
Altered epidermal filaggrin mRNA expression and protein distribution was detected in this experimental model.
[Show abstract][Hide abstract] ABSTRACT: Atopic dermatitis (AD) results from complex interactions between an impaired skin barrier and immunological stimulation. Filaggrin is a key protein for the skin barrier, and its expression is decreased in subsets of atopic dogs and can be modified by inflammation; thus, immunomodulatory approaches may alter its expression. Probiotics have been explored for the prevention and treatment of allergies, owing to their immunomodulatory properties; however, it is currently unknown whether they can modulate filaggrin expression.
The purpose of this study was to evaluate whether probiotics can modulate filaggrin expression in an experimental model of canine AD.
Eighteen atopic (11 probiotic exposed and seven control) and five normal beagles were challenged for three consecutive days with Dermatophagoides farinae. Skin biopsies were taken before (day 0), at the peak (day 3) and after the end of the allergen challenge (day 10). Immunohistochemistry for filaggrin was done using a polyclonal antibody specific for canine filaggrin, and staining was scored both subjectively (for intensity, granularity and continuity) and objectively, by tracing the stratum granulosum and calculating the percentage of filaggrin per unit traced area.
Analysis of variance of the percentage of filaggrin in the stratum granulosum showed a significant effect of group (P = 0.0414, AD < normal), time (P = 0.0066, days 3 and 10 > day 0) and marginal group × time interaction (P = 0.0606). Within the atopic group, exposure to probiotics did not change filaggrin expression. No significant differences were found in the subjective scores among groups.
It is concluded that probiotic exposure early in life does not alter filaggrin expression in this AD model.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Filaggrin expression is decreased in subsets of humans and dogs with atopic dermatitis (AD). Filaggrin expression is modulated by inflammation, but it is unknown whether expression is inversely correlated with clinical signs. HYPOTHESIS/OBJECTIVES: To investigate the correlation between filaggrin expression and the severity of clinical signs in an experimental model of canine AD. ANIMALS: Eighteen atopic research beagle dogs sensitized to house dust mite allergens. METHODS: Dogs were challenged with house dust mites for 3 days consecutively (days 1-3) and skin biopsies collected on days 1 (before allergen challenge), 3 (peak of challenge) and 10 (at resolution of lesions). Clinical signs were scored using a modified version of CADESI-03, the Canine Atopic Dermatitis Extent and Severity Index. Immunohistochemical staining was measured subjectively by three investigators who graded filaggrin staining for continuity, granularity and intensity. For objective evaluation of staining, the stratum granulosum and epidermis were traced, and the percentage of filaggrin per unit stratum granulosum and epidermal area were calculated. Correlations were investigated using Pearson's product-moment correlation (for linear correlations) and Spearman's rank correlation (for nonlinear correlations), pooling all days together and then separately on each day, using total clinical scores and either subjective or objective filaggrin scores. RESULTS: The only significant correlation was found between the subjective filaggrin scores and total clinical scores on day 1. CONCLUSIONS AND CLINICAL IMPORTANCE: No inverse correlation exists between the severity of clinical signs and filaggrin expression; the clinical relevance of filaggrin in canine AD is unknown.
[Show abstract][Hide abstract] ABSTRACT: Skin barrier dysfunction exists in both human and canine atopic dermatitis, leading to increased water loss and potentially facilitating allergen penetration and sensitization. Both lipid (e.g. ceramides) and protein (e.g. filaggrin) abnormalities have been described. Some are genetically inherited (e.g. filaggrin mutations are one of the major risk factors in humans) and some are secondary and linked to inflammation. In humans, numerous studies have shown efficacy of emollients and moisturizers in barrier restoration, and this approach has been for years the mainstay of therapy. Recently, this strategy has shown promise as a preventative function. In veterinary medicine, evidence regarding skin barrier impairment is rapidly building. Decreased ceramides and filaggrin (in some subsets of dogs) have been described. Altered metabolism of ceramides has also been proposed. Despite these preliminary data and the availability of products marketed to improve the skin barrier, evidence regarding the clinical benefit of skin repair intervention is still limited. Preliminary studies have demonstrated that topical application of fatty acids and ceramides and systemic administration of fatty acids improve lipid deficiencies in the skin of dogs with atopic dermatitis, but limited clinical evidence exists. Disease remission in humans is paralleled by an improved skin barrier, both with calcineurin inhibitors and glucocorticoids. In veterinary medicine, a preliminary study on ciclosporin and prednisone failed to detect significant improvement of water loss, while successful immunotherapy correlated with an improved skin barrier. Controlled, large studies are needed to address the question of which skin repair approach is clinically most effective and whether this can be used as a preventative strategy.
[Show abstract][Hide abstract] ABSTRACT: This study investigated the effects of a skin protectant solution (dimethicone 2%) on clinical signs and skin barrier function in canine atopic dermatitis (AD). Eighteen dogs with AD were randomly divided into two groups, one received dimethicone and the other received the vehicle (cyclomethicone) on selected areas (pinnae, groin, and axillae) daily for 4 weeks. Owners and investigators were blinded regarding group allocation. Clinical efficacy was evaluated using a scoring system and skin barrier by measuring the transepidermal water loss. Twelve dogs completed the study (50% drop rate in the vehicle and 20% in the dimethicone). For clinical signs, analysis of variance showed an effect of time (P < 0.005; day 0 > day 28) and region (axillae < groin < pinnae) but no effect of group or group × time interaction. For transepidermal water loss, analysis of variance showed only a main effect of region (axillae > pinnae > groin). Pearson found no correlation between transepidermal water loss and clinical scores. In this pilot study dimethicone had no significant effect on clinical signs and transepidermal water loss in canine atopic dermatitis.
Veterinary medicine international. 01/2013; 2013:239186.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
It is concluded that TEWL does not correlate with disease severity.
[Show abstract][Hide abstract] ABSTRACT: Probiotics modulate the immune response and may have protective effects against atopic dermatitis (AD). Clinical trials using dogs with spontaneous disease are limited by confounding factors such as different diets, environments and sensitizations while a more controlled evaluation is possible using experimental models. A validated model of canine AD showed that early exposure to Lactobacillus rhamnosus GG (LGG) significantly decreases allergen-specific IgE and partially prevents AD in the first 6 months of life. This study is a follow-up three years after discontinuation of LGG. Clinical signs were evaluated after allergen challenge with ragweed, timothy, Dermatophagoides farinae. Allergen-specific IgE, IL-10 and TGF-β were measured on the 1st day of challenge, before allergen exposure. Normal dogs were included as controls. Analyses included seven dogs in the non-probiotic and nine in the probiotic litter. For clinical scores, a 2-Group × 9-Time Analysis of Variance showed significant effects of group (p=0.0003, probiotic<controls), time (p<0.0001) and group × time interaction (p<0.0001). IL-10 for all allergens was significantly higher in the control group than probiotics-exposed dogs. Allergen-specific IgE and TGF-β did not differ between litters. Early exposure to probiotics has long-term clinical and immunological effects in this model and larger studies using dogs with spontaneous disease are needed.
Veterinary Immunology and Immunopathology 03/2012; 146(2):185-9. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antimicrobial peptides (AMPs) are small immuno-modulatory proteins important in defense against pathogenic organisms. Defensins and cathelicidin are the most frequently studied human AMPs. An increase in AMPs in atopic humans has been reported recently. Our goals were to determine the distribution of AMPs and evaluate their mRNA and protein expression in non-lesional (Day 0), acute lesional skin (Day 3) and post-challenged skin after resolution of skin lesions (Day 10) using a canine model of atopic dermatitis (AD). All dogs were environmentally challenged for three consecutive days with house dust mite. Clinical evaluation of atopic beagles was performed using a CADESI score at each time point before and after environmental challenge. Skin biopsies were taken from six healthy and seven atopic beagles before and after allergen challenge (Day 0, Day 3 and Day 10). The transcription of canine cathelicidin (cCath) and beta-defensins (cBD)-1, -2 and -3 mRNA was quantified using quantitative-RT-PCR while the protein distribution of cBD2, cBD3 and cCath was detected by indirect immunofluorescence. A significant effect, over-time, was seen in CADESI score in AD beagles with an increase score after challenge (Day 3). Quantitative analysis showed a significant difference in mRNA transcript levels between groups (with atopic dogs having more than controls) for all AMPs but cBD2. No effect over time was evident for either group. No significant differences were seen for the AMP protein patterns of distribution (homogenous distribution). Although, these results showed no differences in AMP's localization after allergen exposure in each group; atopic dogs had a higher mRNA expression of AMPs when compared with healthy dogs, a similar finding to humans.
Veterinary Immunology and Immunopathology 08/2011; 144(3-4):382-8. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An impaired skin barrier function is thought to be crucial for allergic sensitization. In humans, the skin barrier is assessed by noninvasive methods, such as the measurement of transepidermal water loss (TEWL). Although limitations have been reported, measurement of TEWL has been demonstrated to be a suitable method to assess barrier function indirectly in dogs. The purposes of this prospective clinical study were twofold. The first aim was to evaluate and compare TEWL in healthy and atopic dogs. The second aim was to evaluate TEWL in a population of atopic dogs and to assess TEWL in dogs whose disease was in remission after successful therapy and compare it with dogs whose disease was not controlled or receiving treatment. One hundred and fifty dogs were selected and divided into the following three groups: 50 atopic dogs before specific treatment (group A); 50 in remission (group B); and 50 control dogs (group C). The mean values for TEWL for each group were 22.47 (g/m(2) h) (group A; 95% confidence interval 20.85-24.09), 12.57 (g/m(2) h) (group B; 95% confidence interval 11.43-13.7) and 8.81 (g/m(2) h) (group C; 95% confidence interval 8.09-9.52); P-value was 0.0001 for TEWL (groups A, B and C). This study showed a significant difference of TEWL between healthy control dogs and dogs with atopic dermatitis. Additionally, TEWL was lower in atopic dogs whose disease was in remission due to treatment. These results were consistent with reports in human medicine about TEWL.
[Show abstract][Hide abstract] ABSTRACT: Atopic dermatitis (AD) is a multifaceted disease resulting from a complex interaction between environmental and genetic factors. Both of these factors can shape skin barrier function and the immunological response of predisposed patients. There is increasing evidence that an impaired skin barrier plays a role in both human and canine AD. Although many primary skin barrier defects had already been documented in the past in humans, the recent identification of the filaggrin mutations and the fact that such mutations are now considered the most important risk factor for development of AD have further emphasized the relevance of epidermal dysfunction in human AD. Much less is known in veterinary medicine, but evidence is rapidly building to support a role for skin barrier dysfunction in canine AD. Canine AD shares many clinical and immunological similarities with its human counterpart. The similar distribution of clinical lesions and the importance of the epicutaneous route of allergen exposure provided the incentive to investigate the role of skin barrier impairments in canine AD. The purpose of this comparative review is to present the current evidence of barrier dysfunction in both human and canine AD.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Tacrolimus is a nonsteroidal alternative to treat noninfectious otitis externa (OE) in people. This 21-day study investigated whether twice daily application (0.2 mL/dose) of sterile olive oil based 0.1% tacrolimus suspension in ears of atopic beagle dogs without OE was associated with adverse local reactions, development of OE, change in otic cytology, vestibular dysfunction, or hearing loss detected by brainstem auditory evoked response (BAER). The study was randomized, double-blinded, and placebo-controlled. Twenty-two dogs matched for age and sex were randomized to tacrolimus or vehicle control treatment groups. Two investigators independently evaluated dogs for signs of adverse effects including OE the first 4 days of treatment, then every 3 days. A logistic regression model was fit for each investigator's clinical scores (SAS, 9.2, 2008). Time (P = 0.0032) and group (P = 0.0167) were always significant for OE. Inter-observer reliability of clinical scores was strong, measured using Kappa coefficients and proportion of agreement. All nine exclusions (7/10 control- and 2/12 tacrolimus-treated dogs) were excluded for yeast OE. Inter-observer agreement to exclude was 100%. All dogs not excluded had normal BAER assessments before treatment, weekly during treatment, and after 21 days of treatment. None showed vestibular abnormalities at these times. Tacrolimus blood concentrations (Abbott IMx Tacrolimus II) were below detection limits (3 ng/mL) at baseline and after 21 days of treatment. Results suggest otic application of olive oil based tacrolimus suspension to canine ears with intact tympanic membranes is unlikely to result in hearing loss or vestibular dysfunction but yeast OE is a possible risk.
[Show abstract][Hide abstract] ABSTRACT: A 6-year-old castrated dromedary camel (Camelus dromedarius) presented with a non-healing, severely pruritic, ulcerative fibrotic plaque located at the medial canthus. Histological examination of surgical biopsies identified degenerating nematode larvae within eosinophilic granulomas. Treatment involved repeated debridement of the lesion, injectable ivermectin and anti-inflammatory therapies, and injectable and topical antibiotics. A specially constructed mask with goggles to prevent the camel from continuing to self-traumatize the eye and lesion was also placed. Full recovery occurred approximately 1 month after diagnosis. Because of the location of the lesion, time of year, the gross and microscopic characteristics of the lesion, the presence of a likely nematode larva and the response to treatment, a diagnosis of cutaneous habronemiasis was made.
[Show abstract][Hide abstract] ABSTRACT: Stannous fluoride (SF) is an antibacterial compound that has been successfully used to treat gingivitis in people and dogs, and cutaneous bacterial infections in horses. The purpose of this prospective, double-blinded, placebo-controlled clinical trial was to investigate the efficacy of 0.2% SF spray (BacDerm; Emerald 3 Enterprises Inc., Camdenton, MO, USA) for the treatment of canine superficial pyoderma. Twenty-six privately owned dogs with bacterial skin infections diagnosed on clinical signs, cytology and aerobic culture were enrolled. Dogs were randomly assigned to vehicle only or active ingredient treatment groups. The product was applied topically to affected areas once daily for 28 days, with assessments at days 0, 14, 28 and 42. Clinical and cytological evaluations were performed by the same investigators at each visit. Owners scored the improvement of hair coat, odour, pruritus and overall improvement at each recheck. Linear mixed models showed significant effects of treatment (P < 0.0001) and time (P = 0.0037) for investigator's scores, and a significant time effect for owners' haircoat (P = 0.0077) and odour (P = 0.0170) improvement scores. Dogs in both placebo and SF groups showed some improvement over time, and the investigator's scores on days 0 and 28 were not significantly different between groups for both (t-test P > 0.05). Spearman's rho correlation coefficients revealed a significant negative correlation between investigator's scores and all categories of owners' assessment scores in dogs of both groups. Although some dogs improved on SF, this study does not support the use of 0.2% SF as sole therapy for canine superficial pyoderma.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: This study aimed to investigate whether challenge with storage mites elicited flare ups of atopic dermatitis (AD) in Dermatophagoides farinae sensitized atopic Beagles housed in a house dust and storage mite-free environment. Atopic Beagles were environmentally challenged with 50 mg of Tyrophagus putrescentiae for three days in a row. Clinical signs were scored before, 6 h after each challenge and then every 24 h for a total of 5 days using a Canine Atopic Dermatitis Extent and Severity Index. Four healthy Beagles, negative on serology and intradermal testing for both house dust and storage mites, were used as controls and similarly challenged. A month after environmental challenge, the atopic Beagles were challenged by the oral route (50 mg of T. putrescentiae for three days in a row) and evaluated as described. Analyses of variance (ANOVAs) were used for comparisons between groups and types of challenges. All atopic Beagles developed erythematous pruritic lesions clinically compatible with AD on the face, pinnae, feet and ventral abdomen after both environmental and oral challenge. Control dogs did not develop dermatitis except for mild pinnal erythema in one dog. In the environmental challenge, ANOVA showed a significant effect of time, group, and group x time interaction, with atopic Beagles showing significantly higher scores than the controls. There were no significant differences in clinical scores after oral and environmental challenge in the atopic group. Cross-reactivity between house dust and storage mites could therefore contribute to flare ups of AD in house dust mite allergic dogs.