Transmission electron microscopy studies in an experimental model of canine atopic dermatitis

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.     

Interleukin‐31: its role in canine pruritus and naturally occurring canine atopic dermatitis

Background – Interleukin‐31 (IL‐31) is a member of the gp130/interleukin‐6 cytokine family that is produced by cell types such as T helper 2 lymphocytes and cutaneous lymphocyte antigen positive skin homing T cells. When overexpressed in transgenic mice, IL‐31 induces severe pruritus, alopecia and skin lesions. In humans, IL‐31 serum levels correlate with the severity of atopic dermatitis in adults and children. Hypothesis/Objective – To determine the role of IL‐31 in canine pruritus and naturally occurring canine atopic dermatitis (AD). Animals – Purpose‐bred beagle dogs were used for laboratory studies. Serum samples were obtained from laboratory animals, nondiseased client‐owned dogs and client‐owned dogs diagnosed with naturally occurring AD. Methods – Purpose‐bred beagle dogs were administered canine interleukin‐31 (cIL‐31) via several routes (intravenous, subcutaneous or intradermal), and pruritic behaviour was observed/quantified via video monitoring. Quantitative immunoassay techniques were employed to measure serum levels of cIL‐31 in dogs. Results – Injection of cIL‐31 into laboratory beagle dogs caused transient episodes of pruritic behaviour regardless of the route of administration. When evaluated over a 2 h period, dogs receiving cIL‐31 exhibited a significant increase in pruritic behaviour compared with dogs that received placebo. In addition, cIL‐31 levels were detectable in 57% of dogs with naturally occurring AD (≥13 pg/mL) but were below limits of quantification (<13 pg/mL) in normal, nondiseased laboratory or client‐owned animals. Conclusions – Canine IL‐31 induced pruritic behaviours in dogs. Canine IL‐31 was detected in the majority of dogs with naturally occurring AD, suggesting that this cytokine may play an important role in pruritic allergic skin conditions, such as atopic dermatitis, in this species.     

Breed-associated phenotypes in canine atopic dermatitis

Canine atopic dermatitis is a multifaceted disease, whose clinical presentation may be affected by numerous factors, including the genetic background of the animal, the environment, the offending allergens and flare factors. In particular, breed-associated differences have often been mentioned but never defined precisely. Using a large data set of atopic dogs, we document in this study the clinical presentation of nine often-affected breeds and demonstrate the existence of substantial differences between the clinical phenotype of each breed and the whole population. Some of the differences may be due to genetic differences while others are most likely to be associated with variations in environmental factors.     

Owner assessment of therapeutic interventions for canine atopic dermatitis: a long-term retrospective analysis

Background – Canine atopic dermatitis is a frequent diagnosis in veterinary medicine; however, the long‐term prognosis for canine atopic dermatitis has not been evaluated in a systematic fashion. Hypothesis/Objectives – To compare the relative efficacy of commonly used therapies for canine atopic dermatitis in two groups of dogs over 5 and 10 year time periods. Animals – Dogs were identified from the medical record database of a privately owned veterinary dermatology practice in the USA. Methods – Clients completed a four‐part, 28‐question, Internet‐based survey. Surveys were included in the analysis if one entire section was completed. Each question was completed independently of the answers to other questions. Results – Several respondents failed to complete all questions. Some respondents answered similar questions with contradictory answers. Each question was analysed individually. A total of 136 owner surveys were completed, 39 from the 10 year and 97 from the 5 year study dogs. Eighty‐five of 135 respondents indicated that their pet was receiving some form of medical therapy for atopic dermatitis at the time of the survey. Thirty of 90 respondents (33.3%) indicated that their dog improved during a dietary trial. Five dogs met the study’s definition for clinical cure. All five of these dogs had been treated with allergen‐specific immunotherapy. Conclusions and clinical importance – This study revealed that clients believe antihistamines can be a useful part of multimodal therapy for canine atopic dermatitis. The results also demonstrated that a significant number of canines benefited from dietary modification. In addition, allergen‐specific immunotherapy was the only treatment to induce true clinical remission of atopic dermatitis.     

Oxidative stress markers in canine atopic dermatitis

There are no data in the veterinary literature relating to oxidative stress in canine atopic dermatitis (CAD). The study aimed to determine levels of oxidative stress markers, plasma malondialdehyde (MDA), total antioxidant capacity (TAC), whole blood glutathione peroxidase (GPX) and erythrocyte superoxide dismutase (SOD), in 15 CAD patients and 17 healthy dogs. A correlation between CADESI (Canine Atopic Dermatitis Extent and Severity Index) score and MDA was also determined. Significantly higher plasma MDA levels were found in patients than in healthy dogs. The significant, highly positive correlation determined between CADESI score and MDA in the patient group indicates an association between the severity of CAD and the extent of oxidative damage to membrane lipids. There were no significant differences in TAC, GPX and SOD between patients and healthy dogs. Our findings suggest that oxidative stress with increased lipid peroxidation could be involved in the pathogenesis of atopic dermatitis in dogs.     

Advances in our understanding of canine atopic dermatitis

Canine atopic dermatitis (cAD) is a genetically inherited clinical syndrome that encompasses a diversity of mechanisms and can have a variety of triggers. Development of clinical disease is the result of genetic factors and environmental conditions, which shape the resulting immunological response. Clinical disease becomes evident once a threshold of inflammatory response is achieved. Skin barrier impairment plays a role in promoting cutaneous dysbiosis and increased allergen penetration. Keratinocytes shape the response of dendritic cells and subsequent lymphocytic response. Thymic stromal lymphopoietin is one of the links between the damaged skin barrier and the modulation of a T-helper (Th)2 response. It is still unclear whether mutations in skin barrier genes exist in atopic dogs, as they do in humans, or whether the observed alterations are purely secondary to inflammation. A dysregulated immune response with increased Th2, Th17 and CD4+ CD25+ regulatory T cells has been reported. A variety of cytokines [interleukin(IL)-31, IL-34, Macrophage migration inhibitory factor] are proposed as potential biomarkers and treatment targets because they are increased in the serum of atopic dogs when compared to controls, although a correlation between serum levels of these factors and severity of disease is not always present. The main issue with many published studies is that atopic dogs are always only compared to normal controls. Thus, it is unclear whether the changes that we find are truly a signature of cAD or merely a manifestation of nonspecific broad inflammatory responses. Studies considering comparison with other inflammatory diseases different from cAD are urgently needed to correctly identify what is specific to this complicated syndrome.     

Characterization of pruritus in canine atopic dermatitis,flea bite hypersensitivity and flea infestation and its role in diagnosis

Background – In dogs, flea infestation (FI), flea bite hypersensitivity (FBH) and canine atopic dermatitis (CAD) have been mainly characterized by their lesions but never by their pruritus. In clinical practice, many of these dogs exhibit only pruritus. Hypothesis/Objectives – The purpose of this study was to evaluate the characteristics of pruritus in these dermatoses and their potential usefulness for diagnosis. Animals – Dogs included were selected from the Oniris clinical data. Cases were selected in which the dogs had only one of the three dermatoses diagnosed. The diagnosis of CAD was based on Prélaud’s criteria and positive intradermal tests except flea; for FBH by compatible clinical signs and a response to an intradermal test with flea allergen; and for FI by the presence of fleas. Moreover, in each group, other primary pruritic skin diseases were excluded. Methods – Location, behavioural manifestations, seasonality and quantification of the pruritus were evaluated. The statistical analysis used chi‐squared test with a P‐value <0.05. Results – Three hundred and forty‐six dogs were analysed, 91 with CAD, 110 FI and 145 FBH. The period (season) of onset was not statistically different either for each dermatosis or among the three dermatoses. Some locations were highly specific for one dermatosis as follows: ventral abdomen/medial surface of thigh (chewing) and radius/carpus/tibia/tarsus (chewing) in FI; back/dorsolumbar area (chewing) and tail (chewing) in FBH; and paws (chewing/licking) and face/neck (rubbing) in CAD. Conclusions and clinical importance – Some features of pruritus could be suggestive of the causal disease, with possible diagnostic value in pruritic dogs.     

Comparison between an intradermal skin test and allergen-specific IgE-ELISA for canine atopic dermatitis

The aim of this study was to compare the results of an intradermal skin test (IDST) with those of an allergen-specific IgE-ELISA in 210 dogs with atopic dermatitis. All the dogs had a clinical diagnosis of atopic dermatitis and underwent an IDST. The sera of all dogs were analysed for allergen-specific IgE by ELISA using the monoclonal antibody D9 against dog IgE. IDST was used as the standard assay. In both methods, the following antigens provided a positive test result: Dermatophagoides farinae, Acarus siro, Tyrophagus putrescentiae, ragweed, mugwort and Lepidoglyphus destructor. ELISA had an overall sensitivity of 82.4% and an overall specificity of 93.8%. The overall accuracy of the ELISA was 91.3%. The evaluated monoclonal D9 ELISA was found to be a reliable tool for the diagnosis of those allergens that cause clinical atopy, and can be recommended for use in dogs when immunotherapy is a therapeutic option.     

Use of antihistamines to control pruritus in atopic dogs

In an open uncontrolled study, 30 dogs with atopy were given six different antihistamines over a period of 10 weeks. During the first six weeks the dogs were given each of the antihistamines, hydroxyzine, trimeprazine, chlorpheniramine, clemastine, promethazine and cyproheptadine for a seven-day period. The order of drug administration was randomised in each case. After assessment of clinical improvement, based on the drug's ability to control pruritus, the most successful drug was given for a further four weeks. Where several drugs performed equally well in the control of signs, the second drug was selected on cost, ease of administration and lack of side effects. More than 60 per cent of the dogs benefited from antihistamine therapy and few side effects were noted. Hydroxyzine in this trial, proved to be the most effective antihistamine in controlling pruritus, although all of the drugs were shown to have the ability to control pruritus in some dogs.     

The ACVD task force on canine atopic dermatitis (III): the role of antibodies in canine atopic dermatitis.

Although an important pathogenic role for IgE is established in the case of allergic asthma and rhinitis in man, its role in atopic dermatitis is less clear. There are many studies where allergists and immunologists have provided evidence in favour of such a role, whereas dermatologists are less than convinced.In dogs, however, there is an abundance of clinical evidence implying that atopic dermatitis is antigen driven, and recent studies suggest that there may be a role for IgE, not only in the effector pathway, but also in antigen capture. Although an IgG response often accompanies an IgE response in dogs with atopic dermatitis, there is little evidence in support of a pathogenic role in respect of the former isotype.     

Prevalence and features of canine atopic dermatitis in Hungary

Medical records of 600 dogs diagnosed with atopic dermatitis were reviewed and evaluated with reference to history, geographical distribution, breed predilection, clinical signs and positive reactions to allergens as determined by intradermal skin testing (IDT) manufactured by Artuvetrin Laboratories. In 66.6% of dogs, the age of onset of atopic dermatitis was between 4 months and 3 years. Dogs living in the garden suburb of Budapest were more sensitive to house dust mites, fleas and moulds, and dogs from the western part of Hungary were more sensitive to weeds than to other allergens (p < 0.01). Positive reactions were most common to Dermatophagoides farinae followed by human dander. The breed distribution found in the present study was consistent with that reported in the literature, except for the breeds Hungarian Vizsla, Pumi, French bulldog, Doberman Pinscher and Bobtail which were over-represented among atopic dogs compared to the breed distribution of the general dog population of a large city in Hungary. Breeds with verified adverse reaction to food were Cocker spaniels, French bulldogs, Bullmastiffs, Bull terriers, St. Bernards, Tervurens, West Highland White terriers and American Staffordshire terriers (p < 0.05). The clinical signs of atopic dermatitis and their occurrence are in accordance with the data described in the literature.