The ACVD task force on canine atopic dermatitis (XXIV): allergen-specific immunotherapy.

Allergen-specific immunotherapy (ASIT) has been used for years to treat dogs with atopic dermatitis (AD) and humans with atopic diseases. The efficacy of ASIT has been well documented for humans with respiratory atopic diseases and stinging insect allergy, but its effectiveness seems more controversial for patients with AD. In spite of insufficient evidence derived from randomized controlled trials, multiple open studies and a large body of clinical observations suggest that ASIT is effective in controlling the clinical signs of dogs with AD. As a result of the scarcity of evidence from controlled trials, the true efficacy of ASIT, and the optimal protocols for allergen dose and frequency of injection are currently unknown. Allergen-specific immunotherapy nevertheless may be included in the treatment of canine AD because of its potential advantages and limited disadvantages compared to other forms of therapy. There is no evidence, however, for the preference of any specific treatment protocol. The predictive value of historical, clinical and immunologic features related to the efficacy of ASIT in dogs with AD are discussed in this paper. Adverse reactions, and the requirements for monitoring of patients receiving ASIT, then are reviewed and detailed. Finally, this review highlights aspects of ASIT where further research and controlled studies are needed.     

The ACVD task force on canine atopic dermatitis (XXI): antihistamine pharmacotherapy.

Antihistamines frequently are recommended by veterinary dermatologists for symptomatic treatment of pruritus associated with canine atopic dermatitis (AD), perhaps because of their moderate success in some human patients with AD. A critical review of the literature describing antihistamine use in canine AD reveals that the majority of published, peer-reviewed studies are open, uncontrolled or partially-controlled trials. Such studies vary widely in reported efficacy, from perhaps 0 to 75% of patients, even using the same drug. The few blinded placebo-controlled trials available have failed to confirm efficacy of these drugs to relieve the pruritus of canine AD. Some studies indicate that synergistic effects could occur with concurrent use of essential fatty acid supplements. Consequently, at the time of this writing, there is insufficient evidence to conclude for or against the efficacy of antihistamines for treatment of canine AD. Additional blinded, randomized and controlled trials with larger numbers of patients are necessary to establish which of the antihistamine drugs currently available, if any, are truly efficacious for canine AD. Nevertheless, present clinician consensus suggests that several different antihistamine drugs should be evaluated in sequence, for 7-14 days each, in canine patients with AD.     

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.     

The ACVD task force on canine atopic dermatitis (XVII): intradermal testing.

Intradermal testing has been practiced for decades in human and veterinary medicine. The primary utility of intradermal testing is in the demonstration of IgE-mediated allergen hypersensitivity. The presence of a positive reaction on an intradermal test is not always indicative of allergy, as it may sometimes be an indication of sub-clinical hypersensitivity. Despite its widespread use by veterinary dermatologists, the usefulness of the intradermal test would be greatly enhanced by the use of standardized allergen extracts and homogeneous criteria for the interpretation of results. Irrespective of these shortcomings, intradermal testing is regarded as a valuable tool in the demonstration of allergen-specific hypersensitivity when performed according to accepted guidelines.     

The ACVD task force on canine atopic dermatitis (XX): glucocorticoid pharmacotherapy.

Glucocorticoids (GCs) have been the most commonly prescribed drugs for treatment of canine atopic dermatitis (AD) during the last decades. In spite of this widespread usage, there are a few studies documenting their efficacy. Fortunately, recently completed clinical trials were designed with oral GCs used as "standard of care" for treatment of canine AD. These studies provided high quality evidence in favor of the strong efficacy of oral low-dose glucocorticoid formulations to control skin lesions and pruritus in dogs with AD. Consequently, there is good evidence to support the recommendation of use of oral glucocorticoids for treatment of canine AD.     

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.     

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.     

The ACVD task force on canine atopic dermatitis (I): incidence and prevalence.

There is an increasing incidence of atopic diseases (asthma, allergic rhinitis and atopic dermatitis) in humans, especially in developed countries. Although there is a genetic predisposition to the development of these diseases, the rapid rise in incidence is suspected to be caused by environmental rather than genetic factors. Neither the incidence nor the prevalence of atopic dermatitis in the general canine population has been studied. As many of the environmental factors associated with the increasing incidence of atopic dermatitis in humans are consistently found in the environment of dogs, it would seem likely that a similar increase in the incidence of this disease would be occurring also in dogs. Epidemiological studies of canine atopic dermatitis are needed to characterize the incidence and prevalence of atopic dermatitis, and to further study the factors that contribute to the development of this disease.     

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.     

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.     

The ACVD task force on canine atopic dermatitis (VII): mediators of cutaneous inflammation.

Controversy still exists on the role of various inflammatory mediators in the pathogenesis of canine atopic dermatitis. The objective of this article is to review the most recent information available on the inflammatory mediators that have been implicated in the pathogenesis of this disease. Studies on the role of histamine, serotonin, leukotrienes and various cytokines are presented in a comparative manner reviewing the experimental evidence for a role in the pathogenesis and the arguments against it.     

The ACVD task force on canine atopic dermatitis (XV): fundamental concepts in clinical diagnosis.

The clinical signs of atopic dermatitis (AD) in man and in dogs are variable, and there is no single physical or historical feature that, if present, indicates the presence of AD. The initial diagnosis of AD is made clinically with the fulfillment of a combination of criteria that are strongly associated with the disease. Several schemes have been proposed in an attempt to define uniform clinical criteria for diagnosing canine AD, but no system is perfect. Once AD is considered as a possible diagnosis, other important differential diagnoses must be methodically eliminated from consideration. As a final step, once the clinician is certain that AD is probable, "allergy" tests may be conducted to provide additional evidence to "substantiate" the diagnosis. It is important to understand that allergy testing, in whatever form, is not appropriately used early in the patient evaluation as a screening test. Rather, it should be reserved, after a firm clinical diagnosis of AD has been made, to implement allergen avoidance schemes or to select allergens to be incorporated in immunotherapy formulations.     

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.     

The ACVD task force on canine atopic dermatitis (XIII): threshold phenomenon and summation of effects.

The concepts of a threshold for pruritus and a threshold for canine atopic dermatitis (AD) are useful in the understanding of the development of clinical manifestations of this disease. Multiple flare factors, such as infections with bacteria and yeasts, can contribute to the severity of clinical signs in affected patients.     

The ACVD task force on canine atopic dermatitis (XXIII): are essential fatty acids effective?

Essential fatty acids (EFAs) exhibit the potential to affect allergic inflammation through the modulation of prostaglandin and leukotriene production, the inhibition of cellular activation and cytokine secretion as well as the alteration of the composition and function of the epidermal lipid barrier. Because of these multi-faceted effects, EFA have been proposed for treatment of canine atopic dermatitis (AD) since 1987. To date, more than 20 trials have been performed, reporting the efficacy of either oral EFA supplements or EFA-rich diets. Unfortunately, most of these studies were found to exhibit one or more of the following deficiencies: heterogeneity of diagnoses used as inclusion criteria, short duration of supplementation, lack of randomization of treatment allocation, lack of blinding of investigators and/or owners, lack of placebo or active controls, lack of documentation of plasma or skin EFA profiles during supplementation, as well as lack of standardization of the basal diets or supplements which could have provided additional EFA. Consequently, there is presently insufficient evidence to recommend for or against the use of EFA to control clinical signs of canine AD. Evidence of efficacy must await the performance of blinded, randomized and controlled trials of at least 3 months duration in which diets are identical for all of study subjects. In these trials, clinical efficacy should be evaluated in relation to plasma and cutaneous EFA treatment-induced alterations.     

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.     

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.     

The ACVD task force on canine atopic dermatitis (VIII): is the epidermal lipid barrier defective?

In humans with atopic dermatitis (AD), it is suspected that the epidermal lipid barrier is abnormal because of combined insufficient extrusion of lipid-containing organelles into the superficial epidermal intercellular spaces as well as skin lipid metabolic defects. To date, studies investigating skin hydration and lipids in atopic dogs are scarce and unfortunately have yielded conflicting data. Whether or not dogs with AD exhibit dry skin and an inadequate stratum corneum barrier, therefore, remains the subject of speculation.