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The ACVD task force on canine atopic dermatitis (XIV): clinical manifestations of canine atopic dermatitis.

Canine atopic diseases, including those with skin lesions, have been described for many years. Unfortunately, early descriptions often failed to establish definitive guidelines for considering a patient atopic, and criteria for diagnosing atopic dermatitis (AD) have varied from author to author. Larger case-series published from the 1960s to the 1980s suggested that the most common clinical manifestation of AD was pruritus, particularly of the face, ears, paws, extremities, and/or ventrum. It is not always clear that testing to eliminate other differential diagnoses was always carefully performed on patients in early reports; therefore, some descriptions could include patients affected with diseases other than or in addition to AD. Points of consensus regarding clinical manifestations of AD in case-series include the presence of pruritus beginning at a young age, possibly seasonally; and a prominent lesional involvement of the face, extremities, axillae or ventrum. Conflicting information on breed and sex predispositions is present, perhaps representing regional or temporal variability. Clinical reports vary, in regard to the description of lesions seen in dogs with AD. This reflects a possible confusion with lesions of secondary complications, and highlights the fact that the existence and nature of primary lesions of canine AD are not truly known.

Age of Onset↗

The ACVD task force on canine atopic dermatitis (X): is there a relationship between canine atopic dermatitis and cutaneous adverse food reactions?

In humans, allergies to foods are known to induce skin lesions in some patients with atopic dermatitis. This is particularly evident in infants with severe atopic dermatitis. Food allergy in humans is an IgE-mediated hypersensitivity in most cases, and thus has the same (or very similar) pathogenic mechanism of disease induction as environmental allergen-induced atopic dermatitis. Cutaneous adverse food reactions and atopic dermatitis in dogs are often indistinguishable from each other on historical and clinical grounds alone. Limited current evidence suggests that dogs with cutaneous adverse food reactions may be predisposed to developing atopic dermatitis. However, confirmation of any association between these two diseases in dogs awaits further elucidation of the pathogenic mechanism of cutaneous adverse food reactions, and epidemiological studies of the relative prevalence of these diseases in relation to each other and the general population.

Animals↗

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.

Allergens↗

The ACVD task force on canine atopic dermatitis (IX): the controversy surrounding the route of allergen challenge in canine atopic dermatitis.

For decades, the dogma that environmental allergens trigger cutaneous inflammation led to the denomination of canine atopic dermatitis as "allergic inhalant dermatitis". Definitive proof for a respiratory route of allergen challenge is lacking, however. Recent observations suggest, in fact, that skin inflammation could occur because of epidermal allergenic contact. The aim of this paper is to review the evidence published in favor and against the two suspected routes of allergen provocation.

Allergens↗

The ACVD task force on canine atopic dermatitis (XII): the relationship of cutaneous infections to the pathogenesis and clinical course of canine atopic dermatitis.

Dogs and human beings with atopic dermatitis (AD) frequently exhibit concurrent skin infections with Staphylococcus sp. bacteria or Malassezia yeast, and treatment of such infections is an important facet of managing these patients. Staphylococci appear to colonize atopic skin readily, and bacterial products on the skin could augment cutaneous inflammation via immediate hypersensitivity responses to the bacteria, by superantigen-mediated lymphocyte activation, or other non-specific mechanisms. Similarly, skin colonization by Malassezia yeast could contribute to clinical signs of AD; yeast components could induce inflammation via non-specific mechanisms, such as alteration in mediator release, or via antigen-specific hypersensitivity reactions. Clinical and experimental evidence exists that secondary microbial infections can both initiate and perpetuate episodes of AD in dogs and humans, and could even participate in promotion of pro-allergic immunologic responses. Mechanistic details of these complex interactions are under extensive investigation in human beings; only a few observations have been extended to include dog with AD.

Animals↗

The ACVD task force on canine atopic dermatitis (II): genetic factors.

Canine atopic dermatitis is commonly diagnosed in pruritic animals. Many studies have attempted to determine the inheritance pattern of both atopic dermatitis and of elevated allergen-specific IgE production. Despite many clinical, laboratory and breeding studies, the mode of inheritance and genetic mutations underlying this disease currently remain elusive.

Animals↗

Pilot investigation of a model for canine atopic dermatitis: environmental house dust mite challenge of high-IgE-producing beagles, mite hypersensitive dogs with atopic dermatitis and normal dogs.

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.

Animals↗

The ACVD task force on canine atopic dermatitis (XXII): nonsteroidal anti-inflammatory pharmacotherapy.

The pharmacotherapy of canine atopic dermatitis has relied primarily on the use of glucocorticoids and anti-histamines. During the last decade, other anti-inflammatory drugs have been investigated in clinical trials. This paper will review the studies using misoprostol, cyclosporine, tacrolimus, phosphodiesterase inhibitors, capsaicin, leukotriene inhibitors and serotonin-reuptake inhibitors for treatment of dogs with atopic dermatitis. For each drug the mechanism of action, the rationale for use in atopic dermatitis, the clinical efficacy, reported adverse effects and strength of recommendation for treatment of canine atopic dermatitis are described. At the time of this writing, there is fair evidence to support the recommendation for using cyclosporine, misoprostol and pentoxifylline for treatment of canine atopic dermatitis. This recommendation can be strengthened by the performance of additional blinded randomized controlled trials with larger number of dogs. In contrast, there is insufficient evidence to recommend for or against treatment with tacrolimus, leukotriene inhibitors, serotonin-reuptake antagonists and capsaicin.

Animals↗

Double-blinded, placebo-controlled, cross-over pilot study on the efficacy of zileuton for canine atopic dermatitis.

Nine dogs meeting the diagnostic criteria for canine atopic dermatitis were enrolled in a double-blind, placebo-controlled, cross-over clinical trial. In this pilot study, zileuton (a 5-lipoxygenase inhibitor) given orally at 2 mg kg(-1) three times daily for 4 weeks significantly decreased erythema in dogs with atopic dermatitis but had no effect on pruritus. Zileuton was well tolerated and no adverse clinical signs were noted. However, one dog developed mild alanine aminotransaminase elevation, which resolved within 1 week of discontinuation of therapy. Monitoring of alanine aminotransaminase may be necessary in dogs receiving zileuton. Further studies with larger number of dogs are needed to evaluate the efficacy of zileuton as treatment for canine atopic dermatitis.

Administration, Oral↗

Evidence-based veterinary dermatology: a systematic review of the pharmacotherapy of canine atopic dermatitis.

The efficacy of pharmacological interventions used to treat canine atopic dermatitis, excluding fatty acid supplementation and allergen-specific immunotherapy, was evaluated based on the systematic review of prospective clinical trials published between 1980 and 2002. Studies were compared with regard to design characteristics (randomization generation and concealment, masking, intention-to-treat analyses and quality of enrolment of study subjects), benefit (improvement in skin lesions or pruritus scores) and harm (type, severity and frequency of adverse drug events) of the various interventions. Meta-analysis of pooled results was not possible because of heterogeneity of the drugs evaluated. Forty trials enrolling 1607 dogs were identified. There is good evidence for recommending the use of oral glucocorticoids and cyclosporin for the treatment of canine atopic dermatitis, and fair evidence for using topical triamcinolone spray, topical tacrolimus lotion, oral pentoxifylline or oral misoprostol. Insufficient evidence is available for or against recommending the prescription of oral first- and second-generation type-1 histamine receptor antagonists, tricyclic antidepressants, cyproheptadine, aspirin, Chinese herbal therapy, an homeopathic complex remedy, ascorbic acid, AHR-13268, papaverine, immune-modulating antibiotics or tranilast and topical pramoxine or capsaicin. Finally, there is fair evidence against recommending the use of oral arofylline, leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists.

Administration, Oral↗

Characterization of the cutaneous inflammatory infiltrate in canine atopic dermatitis.

Sections from lesional atopic, clinically normal atopic, and normal canine skin were investigated by light microscopy and an immunoperoxidase method using monoclonal antibodies specific for canine leukocyte antigens. We confirmed that skin-infiltrating cells of canine atopic dermatitis are constituted of mast cells, dendritic antigen-presenting cells, memory helper T-lymphocytes, low numbers of eosinophils and neutrophils, and rare B-lymphocytes. The presence of epidermal eosinophil microaggregates and clustered Langerhans' cells supports the hypothesis of epidermal allergen contact. The hyperplasia of epidermal T-cells expressing the gamma/delta T-cell receptor appears specific to canine atopic dermatitis compared with its human counterpart. This finding could be explained by an interspecies difference in skin immune systems or, alternatively, by an active participation of these epitheliotropic gamma/delta T-cells in the cutaneous allergic immune response in dogs. The paucity of dermal neutrophils in spontaneous lesions of canine atopic dermatitis is notably different from the neutrophil-rich late-phase reactions provoked by intradermal allergen injections in allergic dogs. This difference in the cellular infiltrate probably results from variations in the immune reaction between single and repeated allergen exposure as well as epidermal versus dermal antigen contact.

Allergens↗

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p&#x2009;<&#x2009;0.001), PVAS (p&#x2009;<&#x2009;0.001), TEWL (p&#x2009;=&#x2009;0.014), IgE (p&#x2009;<&#x2009;0.001) and QoL scores (p&#x2009;<&#x2009;0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p&#x2009;<&#x2009;0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals↗

House dust and forage mite allergens and their role in human and canine atopic dermatitis.

This article reviews the literature regarding the role of house dust and forage mite allergens in canine atopic dermatitis. The presence of immunoglobulin E (IgE) to these mites, especially to Dermatophagoides farinae, is common in both normal and atopic dogs. Exposure of dogs to the different mites is described both in the direct environment and in the coat of animals for house dust mites and in the food for forage mites. Allergens causing allergic disease in dogs seem to be different from those in humans. Dogs seem to react to high molecular weight allergens, compared to the low molecular weight group 1 and group 2 proteases that are commonly implicated in humans with atopic diseases. Despite numerous published studies dealing with this subject, a number of questions still need to be addressed to better understand the exact role of these mites in the pathogenesis of canine atopic dermatitis and to improve the quality of the allergens used in practice.

Allergens↗

Expression of Th1, Th2 and immunosuppressive cytokine gene transcripts in canine atopic dermatitis.

BACKGROUND: Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Human atopic dermatitis is associated with Th2-type responses, although Th1 cytokines can be identified in chronic lesions. In contrast, tolerance to environmental allergens in healthy individuals is mediated by regulatory T cells. OBJECTIVE: This study examined the expression of the immunosuppressive cytokines TGF-beta and IL-10, the Th2-type cytokines IL-4 and IL-6, and the Th1-type cytokines IFN-gamma, TNF-alpha, IL-2, IL-12p35 and IL-12p40, in canine atopic dermatitis. MATERIALS AND METHODS: RNA was isolated from lesional atopic, non-lesional atopic and healthy canine skin samples. Semi-quantitative reverse transcriptase polymerase chain reactions (RT-PCRs) were carried out using specific primers and one-way analyses of variance used to compare cytokine expression in each group. RESULTS: Canine atopic dermatitis was associated with over-expression of IL-4 mRNA and reduced transcription of TGF-beta compared with healthy skin (P < 0.05). Higher levels of IFN-gamma, TNF-alpha and IL-2 mRNA were seen in lesional compared with non-lesional and healthy skin (P < 0.05). There were no significant differences in IL-10, IL-6, IL-12p35 or IL-12p40 transcription between the three groups. CONCLUSIONS: This is the first report to demonstrate that canine atopic dermatitis is associated with over-production of IL-4. Clinical tolerance in healthy individuals appears to be associated with TGF-beta, although it is unclear if this reflects an active mechanism or simply non-responsiveness of the immune system. Th1 cytokines may be induced by subsequent self-trauma and secondary infections in atopic skin. We believe that these results better characterize spontaneously occurring canine atopic dermatitis. We further propose that this should be investigated as a possible animal model of human atopic dermatitis.

Animals↗

The ACVD task force on canine atopic dermatitis (XIX): general principles of therapy.

The treatment of canine atopic dermatitis is multifaceted and consists of a combination of actions that include the use of allergen avoidance, anti-inflammatory agents, allergen-specific immunotherapy and antimicrobial drugs. The importance and order of these treatment steps vary from patient to patient. General recommendations for each of the therapeutic steps are highlighted in this paper. Specific details are covered in other papers of this issue.

Animals↗

The ACVD task force on canine atopic dermatitis (XVIII): histopathology of skin lesions.

For years, the histopathology of skin lesions of canine atopic dermatitis was deemed non-specific for this diagnosis. However, more recent studies have established that canine atopic skin lesions exhibit an inflammatory pattern characterized as a chronic, hyperplastic and spongiotic, mixed perivascular dermatitis. The nature of epidermal and dermal inflammatory cell infiltrates has now been characterized using modern immunological techniques. Epitheliotropic cells include Langerhans' cells, T-lymphocytes and rare eosinophils. Dermal cells are composed of mast cells, dermal antigen-presenting cells, T-lymphocytes and occasional intact and degranulated eosinophils. This paper provides an historical review of the landmark papers that have elucidated the pathology of canine atopic dermatitis.

Animals↗

Langerhans cell hyperplasia and IgE expression in canine atopic dermatitis.

Langerhans cells appear to be critical for IgE-mediated allergen capture and presentation in human atopic dermatitis. The present study sought to determine whether epidermal (i.e Langerhans cells) and dermal dendritic cells in the skin of dogs with atopic dermatitis are hyperplastic and expressed surface IgE. Frozen sections of lesional or non-lesional atopic and normal control canine skin were immunostained with CD1a-, CD1c-, and IgE-specific monoclonal antibodies. The enumeration of cells was performed by morphometry in both the epidermis and the dermis. Cell counts were compared with each individual's total serum IgE levels. Higher numbers of epidermal and dermal dendritic cells were present in atopic dogs than in normal control animals. Epidermal Langerhans cell counts were significantly higher in lesional than in non-lesional atopic specimens. IgE+ dendritic cells were observed in lesional atopic epidermis and dermis, and non-lesional atopic dermis, but not in normal control skin specimens. The percentages of IgE+ dendritic cells were correlated with each patient's total serum IgE levels. These results demonstrate dendritic cell hyperplasia and IgE expression in canine atopic dermatitis. Increased epidermal Langerhans cell counts in lesional specimens suggest an epidermal allergen contact in canine atopic dermatitis.

Animals↗

The ACVD task force on canine atopic dermatitis (XI): the relationship between arthropod hypersensitivity and atopic dermatitis in the dog.

The relationship between arthropod allergen hypersensitivity and the development of canine atopic dermatitis (AD) is unclear. It has been shown that dogs with AD are more likely to exhibit positive intradermal reactivity to flea allergens than non-pruritic dogs from the same flea-endemic geographic region. Also, dogs in a flea endemic region are four times more likely to suffer from flea allergy dermatitis (FAD) and AD than from FAD alone. These results provide indirect evidence to support the hypothesis that, in the canine species, atopy predisposes to the development of hypersensitivity to flea allergens and eventually to FAD. A causal relationship between insects other than fleas and canine AD has not been identified with certainty.

Animals↗