Numerous similarities exist between canine AD and the human counterpart suggesting the canine AD might be used as a model for the human disease. Dogs have been used in the past as model for human disease.

A task force of the American College of Veterinary Dermatology has recently revised the definition of atopy and AD in dogs. According to the latest definition canine atopy has been described as a genetically predisposed tendency to develop IgE-mediated allergy to environmental allergens (syn. atopic state). In the dog, atopic dermatitis is considered the most commonly diagnosed atopic disease and AD was defined as a genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features. Canine AD is associated most commonly with IgE antibodies to environmental allergens.

In humans, the prevalence of AD in developed countries is approximately 15%, with a steady increase over the past decades. In dogs there are no reliable epidemiological data of the true incidence and prevalence of AD in the general canine population but it has been reported that canine AD affects up to 10% of the population. The typical age of onset of canine AD is between six months and three years (young adults). Various factors have been evaluated as risk factors for canine AD. Strong breed predilection and familial history suggest that genetics play an important role in canine AD.

No clear association has been demonstrated between atopy and dog leukocyte antigen typing although the combination of haplotypes DL-A3 and R15 seemed to be more common in dogs with AD. No significant differences existed in the IgE levels between normal and atopic dogs and a relationship between serum IgE and Dl-A was not observed.

Unsuccessful attempts have been done in the past to establish colonies of dogs with AD. In one study atopic dogs were bred to establish a colony of progeny predisposed to develop type I hypersensitivity. In a 2-year period, 72 pups were born and were monitored for clinical evidence and immunologic "markers" of atopic disease. Thirteen dogs in the colony, belonging to the oldest age group, manifested clinical signs compatible with AD. No correlation was found between the seasonal dermatitis and measurements for specific IgE to airborne allergens and no indicators could be found to predict the development of the atopic state in those dogs.

In humans most patients with AD exhibit elevated total IgE and allergen specific IgE to both environmental and food antigens to the extent and anti-IgE have been successfully used to reduce clinical signs in affected individuals. A so-called intrinsic type of AD has also been described in which normal serum IgE levels and negative immediate-type skin reactions towards environmental allergens are reported. The recently characterized human autoantigen Hom S 1 has been proposed to play a part in the pathogenesis of intrinsic AD.

In canine AD, the role of IgE is not clear, in that disease expression does not correlate as closely with the presence of allergen-specific IgE, and allergen exposure. Most dogs with canine AD have allergen specific IgE demonstrable either by intradermal testing (IDT), or by the use of serological assays such as the enzyme-linked immunosorbent assay (ELISA) although the agreement between these two tests is only 10 times greater than that expected by chance alone.

Experimental sensitization in dogs has revealed that the capacity to produce high levels of IgE against a variety of allergens (high IgE responders), an essential characteristic of the atopic state, is a genetic trait inherited in a dominant manner. In high IgE responder dogs spontaneous development of IgE to inhaled allergens, such as house dust mites, on the other hand, represents an apparent phenotype very similar to that observed in human atopic families. It is important to note, though, that increased allergen specific IgE does not necessarily cause disease and that additional factors influencing mediator release may be involved as well as IgE heterogeneity. In canine AD abnormalities in T-lymphocyte function are also demonstrable, and it is possible that a number of other immunological pathways besides IgE synthesis could be involved in the pathogenesis of this disease.

In human AD various environmental allergens have been implicated in the pathogenesis of the disease and IgE have been suggested to increase the efficiency in capturing and presenting allergens. In a subgroup of patients with atopic eczema, exacerbations of itching and eczematous skin lesions have been described after contact with aeroallergens and atopy epicutaneous patch test (atopy patch test) with allergens has been reported to be useful and results in 30-70% of patients.

In canine AD numerous environmental allergens have been incriminated. These include dust and storage mite antigens; house dust; pollens from grasses, trees and weeds; mould spores; epidermal antigens; insect antigens; and miscellaneous antigens such as kapok. In canine AD, an epidermal route of allergen contact has been hypothesized based on a combination of clinical and histological observations. Most dogs with AD benefit from frequent bathing, which decreases allergen exposure and penetration.

e. Relationship with food allergy

Although the relationship between food allergy and AD in humans was debated in years past, recent information has clearly established a link between these two diseases and measurement of IgE in atopic patients with food allergy has been reported to be useful. The role of cutaneous adverse food reactions in dogs has not been fully elucidated. Reports of experimental models of induced food allergy and a few reports of spontaneous IgE-mediated food allergy suggest that at least some dogs with cutaneous adverse food reactions have IgE-mediated disease. In addition, cutaneous adverse food reactions and AD share a number of very similar historical and clinical features. In dogs with a nonseasonal presentation of clinical signs, it is practically impossible to distinguish between the two diseases on a clinical basis alone.

Dogs and human beings with AD frequently exhibit concurrent infections with Staphylococcus bacteria or Malassezia yeast. Canine AD is also commonly associated with superficial infections with Staphylococcus intermedius bacteria. This organism is harbored on the skin, haircoat, anal area, or nasal passages of many healthy dogs, at least transiently. Allergic dogs have higher skin surface counts of S. intermedius than healthy dogs, and adherence of the bacteria to keratinocytes is greater in allergic dogs. This may explain in part why allergic dogs have recurrent staphylococcal infections.

In human AD skin-seeking T cells, secreting Interleukin 4 (IL-4), IL-5 and IL-13 play an important role in the development of high IgE levels and eosinophilia. In the chronic skin lesion, there is conversion to a Th1-like response with evidence for increased gamma-interferon, IL-12 and GM-CSF.

Cytokine production in dogs with AD has been recently investigated. One-fourth of atopic samples exhibited clear type-2 cytokine profiles; the remainder did not demonstrate polarized repertoires. Conversely, type-1 cytokine profiles were characterized in one-fourth of normal control specimens.

Reduced skin reactivity to intradermal injections of substance P (SP) was reported dogs with AD when compared to healthy controls. Wheal diameters for histamine and SP injections were significantly smaller in dogs with AD compared with clinically normal dogs. The results of this study are similar to those reported in human medicine, where a role for SP in AD is proposed and desensitization of receptors to both SP and histamine is hypothesized. Leukocytes of atopic dogs also have a greater tendency to release histamine than those of normal and artificially sensitized dogs and that this is independent of the concentration of total serum IgE or antigen-specific IgE, suggesting that there may be immunoregulatory abnormalities in atopic dogs intrinsic to the atopic state as is described in man. Other features of canine AD analogous to the human disease include blunted cyclic adenosine monophosphate (cAMP) responsiveness to beta adrenergic agents and in vivo release of histamine and slow-reacting substance of anaphylaxis in response to antigen aerosol challenge.

Atopic dermatitis in dogs has many histopathological features that are similar to the human disease. In humans skin T-lymphocytes from AD patients consist of a heterogenous population of Th1 and Th2 or Th0 cells. In humans both CD4+ and CD8+ memory/effector T cells with skin-homing property play a specific and decisive role in the pathogenesis and exacerbation of AD.

In dogs, increased numbers of CD4+ and CD8+ T-cells are found in canine lesional atopic skin, with a predominance of CD4+ T-cells in the epidermis. In non-lesional atopic skin there is also an infiltration with CD4+ and CD8+ T-cells, but without predominance of CD4+ T-cells.

l. Clinical signs and criteria for diagnosis

In both humans and dogs AD is most consistently characterized by pruritus. In dogs with AD, clinical lesions affect most commonly ventral hairless areas (axillae, inguinal region, interdigital areas) similarly to the lesions seen in allergic contact dermatitis. Similarly, lesions in flexure areas (e.g. anterior elbows) or zones of friction (e.g. axillae) might reflect a chronic abrasion of the epidermal barrier, thus facilitating the rubbing of allergens onto the epidermis. Typical clinical signs in dogs include pruritus of the face, ears, paws, extremities, and/or ventrum. Generalized pruritus is reported in 40% or more of dogs. Secondary skin lesions are common and reflect chronic pruritus and trauma, chronic inflammation. Secondary lesions include red-brown "salivary" staining, excoriations, self-induced alopecia, dry lusterless hair, hyperpigmentation, scaling and lichenification. These lesions are observed principally at sites of pruritus, such as the face (muzzle, periocular skin), concave ears, dorsal and ventral aspect of the paws, flexural aspects of joints on the extremities, axillae, abdomen, groin and medial thighs. Otitis externa or aural pruritus is very common, occurring at least historically in as many as 86% of dogs. Conjunctivitis is present in as many as 50% of patients. Respiratory signs associated with canine AD are reportedly uncommon.