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.     

Feline inflammatory bowel disease: a review

Inflammatory bowel disease (IBD), while a popular diagnosis, may not occur as commonly as it is diagnosed. It is a diagnosis of exclusion, meaning that it is important to eliminate diseases that mimick it. Dietary intolerance or allergy in particular, can have the same clinical and histologic appearance as IBD. Likewise, well-differentiated alimentary lymphosarcoma can also be confused with it. Intestinal biopsies are useful, but must be taken carefully and then evaluated by someone with interest and expertise in alimentary tract pathology. Therefore, it behoves the clinician to carefully consider the diagnosis instead of starting multiple drug therapy in a cavalier fashion. Well constructed dietary therapy can often be beneficial for both dietary problems and IBD.     

Food hypersensitivity dermatitis in the dog: diagnostic possibilities

Dogs with food hypersensitivity usually develop chronic pruritic dermatoses virtually indistinguishable from atopic dermatitis. These reactions are often called food allergy but the pathogenesis is poorly characterized. Several studies have addressed the incidence of canine adverse reactions to food but the outcomes were conflicting. The gold standard for the diagnosis of such a condition is the restricted dietary trial and the subsequent provocation challenge. Some attempts have been made to develop serological tests but none of these tests accurately predicted canine food sensitivity. The aim of the present study was to determine the incidence of food hypersensitivity dermatitis and to evaluate a newly developed serological test for the diagnosis of food allergy in dogs. Only 9% of 55 dogs with dermatological signs compatible with food hypersensitivity or atopic dermatitis have been diagnosed as food hypersensitive dogs.The repeatability of the serological test has shown to be insufficient.     

Diagnosis and management of food allergy and intolerance in dogs and cats

SUMMARY This paper reviews food allergy and intolerance in dogs and cats. Adverse reactions to ingested food components can affect many systems and can produce signs involving the skin, gastrointestinal tract, respiratory tract and central nervous system, and these clinical signs are reviewed. Most basic food ingredients have the potential to induce an allergic response, although most reactions are caused by proteins. In particular, dogs and cats can become sensitive to cow's milk, beef, fish or cereal. Food allergy and intolerance is rare in dogs and cats, although the incidence in practice is difficult to establish. Clinical signs are quite variable, depending on the individual response, although the major clinical sign is pruritus. Diagnosis can be difficult, as there is no single test available to help the clinician to confirm or refute the presence of food sensitivity. Diagnosis is based on dietary investigation in the form of elimination diets and test meals. Elimination diets for dogs include lamb, chicken, rabbit, horse meat and fish as sources of protein, with rice or potatoes. Successful elimination diets for cats include lamb, chicken, rabbit or venison, with rice. Improvement in clinical signs while on the elimination diet is suggestive of food allergy. The diagnosis should be confirmed by feeding the original diet, with the development of clinical signs within 7 to 14 days of feeding.     

Allergy diagnosis in companion animals: clinical experience with the basophil activation model

Animal allergy diagnosis is based mainly on clinical history, skin tests and, at least for dogs, specific IgE antibodies. The quality of anti-canine IgE antibodies is variable and monoclonal antibodies have been recently characterized. The allergen panel tested in humans and in dogs is similar except for flea and for Staphylococcus. Allergen-induced basophil activation may be measured by the release of mediators such as histamine and leukotriene C4 and by the expression of the CD63 marker on basophil membrane. This latter method is based on the flow cytometric analysis of leukocyte suspensions after double anti-IgE FITC, anti-CD63 PE labelling of human basophils, and has been validated for aero-allergens, food allergens, venoms and several drugs for human allergy diagnosis. After having demonstrated that, in the dog, anaphylactic anti- bodies were capable of binding to human basophil high-affinity receptors for IgE, we went up a flow cytometric method for animal allergy diagnosis based on passive sensitization of human basophils. Prelim- inary results obtained by this method for allergens such as house dust mite or pollen were very encouraging. This method is faster and less expensive than the methods based on mediator release but is still dependent on the availability of fresh human leukocytes. This method may represent a new sensitive and specific method for animal allergy diagnosis.     

Food allergy in the cat: a diagnosis by elimination

PRACTICAL RELEVANCE: Food allergy is recognized as a cause of non-seasonal dermatologic disease and pruritus in cats, though its exact prevalence remains unknown. Feline food allergy can also be associated with gastrointestinal, neurologic, respiratory and behavioral components. PATIENT GROUP: There are no breed, sex or age predispositions for developing food allergy, though there is some evidence that the Siamese and its crosses may be at increased risk. CLINICAL CHALLENGES: Food allergy cannot be diagnosed simply on the basis of the distribution of pruritus, and many of the dermatologic reaction patterns observed in affected cats, such as miliary dermatitis, eosinophilic granuloma complex and alopecia, may be seen in cats with flea allergy and atopy; in some cases, cats may have concurrent allergic conditions. The only way to definitively diagnose food allergy is to identify a causative food component through a food elimination trial. However, palatability and client compliance can each be a problem; specifically, many owners are unwilling to perform a provocation challenge, which is required to confirm a suspected food allergy. For cats in which the existence of a food allergy is confirmed, a suitable maintenance diet then needs to be fed for the remainder of the patient's life. EVIDENCE BASE: Recent literature has revealed that there is marked variability in the clinical picture, response to treatment and outcome in food-allergic cats. This article reviews published literature and highlights clinically relevant observations pertinent to feline food allergy.     

The ACVD task force on canine atopic dermatitis (XVI): laboratory evaluation of dogs with atopic dermatitis with serum-based "allergy" tests.

Serum-based in vitro "allergy tests" are commercially available to veterinarians, and are widely used in diagnostic evaluation of a canine atopic patient. Following initial clinical diagnosis, panels of allergen-specific IgE measurements may be performed in an attempt to identify to which allergens the atopic dog is hypersensitive. Methodology for these tests varies by laboratory; few critical studies have evaluated performance of these tests, and current inter-laboratory standardization and quality control measures are inadequate. Other areas where information is critically limited include the usefulness of these tests in diagnosis of food allergy, the effect of extrinsic factors such as season of the year on results, and the influence of corticosteroid treatment on test results. Allergen-specific IgE serological tests are never completely sensitive, nor completely specific. There is only partial correlation between the serum tests and intradermal testing; however, the significance of discrepant results is unknown and unstudied. Variation in test methodologies along with the absence of universal standardization and reporting procedures have created confusion, varying study results, and an inability to compare between studies performed by different investigators.     

Disease conditions of canine anal sacs

The literature about the anal sacs of healthy dogs and the pathogenesis, diagnosis and therapy of anal sac impaction and sacculitis are reviewed. Knowledge about the physiological role of the anal sacs is still confusing. The colour and consistency of the anal sac contents are variable in healthy dogs and there are no pathognomonic signs of anal sac impaction or sacculitis. The wide variation in macroscopic detail of anal sac secretions may give rise to misinterpretation and thus overdiagnosis of sacculitis. Other diseases such as vaginitis, flea allergy, atopy, proctitis, parasites and perianal fistulae can lead to similar signs and must be eliminated from the differential diagnosis before the anal sacs are incited as the cause of the signs. Further research is necessary on the morphological, physical and biochemical aspects of the anal sacs and their secretions to define more precise criteria for the diagnosis of impaction and sacculitis. It is imperative that controlled therapeutic trials should be performed, and such studies are indispensable for the rational therapy of anal sac disease.     

Postweaning multisystemic wasting syndrome (PMWS) in pigs. A review

Postweaning multisystemic wasting syndrome, caused by porcine circovirus type 2 (PCV2), is a recently described clinical condition which affects nursery and growing pigs. PMWS was initially recognized in Canada in 1991 and nowadays is considered to be worldwide distributed. Clinically, PMWS most representative symptoms include wasting, unthriftness, paleness of the skin, respiratory distress, diarrhea and sometimes icterus. PCV2 infection occurs in both PMWS affected and non-affected farms, and viral seroconversion shows a typical pattern, with declining of colostral antibodies during the lactating and nursery periods, with the lowest levels at the end of the nursery period, and active seroconversion of almost all pigs during the grower period. Although antibodies to PCV2 have been detected as early as 1969, no explanation for the emergence of this disease in the 90s has been established. Macroscopic lesions associated with PMWS are quite unspecific, but histopathological lesions in lymphoid tissues (lymphocyte depletion with histiocytic infiltration) are almost unique for this disease. These lesions together with other clinical and laboratorial findings suggest that severely affected pigs may be immunosuppressed. The criteria used for the diagnosis of PMWS include the existence of compatible clinical signs, presence of characteristic microscopic lesions and detection of PCV2 within these lesions. Because of the lack of appropriate treatment or vaccination against PCV2, zootechnical changes have been proposed in affected farms to reduce the so-called "infection pressure" due to PCV2 as well as to any other pathogen.     

Treatment vs non-treatment of helminth infections in cattle: defining the threshold

Helminth infections are an important cause of lost productivity in livestock world-wide, often necessitating anthelmintic treatment. However, a large part of the anthelmintics are used indiscriminately because the parasite levels are too low to justify treatment or because the treatments are not correctly programmed, resulting in undertreatment or overtreatment. The objective of this paper is to discuss possible thresholds for anthelmintic treatment of some of the more important helminth infections in livestock, i.e. gastrointestinal nematodes, lungworms and liver fluke, to promote a more appropriate use of anthelmintics. When possible, a distinction is made between therapeutic thresholds, production-based thresholds and preventive thresholds. A "therapeutic threshold" is intended to identify (an) animal(s) with parasite levels that necessitate immediate treatment. The therapeutic threshold is basically the diagnosis of clinical disease, and can be determined relatively easily for the parasites discussed in this paper. A "production-based threshold" is intended to measure the effects of sub-clinical parasitism on productivity parameters, such as weight gain and milk yield, before clinical disease occurs. Finally, a "preventive threshold" is meant to predict future infection levels, to enable the application of appropriate control measures.     

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.     

A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis

Canine atopic dermatitis (CAD) is a multifaceted disease associated with exposure to various offending agents such as environmental and food allergens. The diagnosis of this condition is difficult because none of the typical signs are pathognomonic. Sets of criteria have been proposed but are mainly used to include dogs in clinical studies. The goals of the present study were to characterize the clinical features and signs of a large population of dogs with CAD, to identify which of these characteristics could be different in food-induced atopic dermatitis (FIAD) and non–food-induced atopic dermatitis (NFIAD) and to develop criteria for the diagnosis of this condition. Using simulated annealing, selected criteria were tested on a large and geographically widespread population of pruritic dogs. The study first described the signalment, history and clinical features of a large population of CAD dogs, compared FIAD and NFIAD dogs and confirmed that both conditions are clinically indistinguishable. Correlations of numerous clinical features with the diagnosis of CAD are subsequently calculated, and two sets of criteria associated with sensitivity and specificity ranging from 80% to 85% and from 79% to 85%, respectively, are proposed. It is finally demonstrated that these new sets of criteria provide better sensitivity and specificity, when compared to Willemse and Prélaud criteria. These criteria can be applied to both FIAD and NFIAD dogs.     

Determination of CADESI-03 thresholds for increasing severity levels of canine atopic dermatitis

To evaluate the extent and severity of skin lesions in clinical trials enrolling dogs with atopic dermatitis (AD), the International Task Force on Canine Atopic Dermatitis recently recommended the use of the third version of the CADESI. This version of the CADESI was found to exhibit acceptable content, construct, criterion, inter- and intraobserver reliability and sensitivity to change. The current study was aimed at determining optimal CADESI-03 cut-off points to separate AD severity categories for future clinical trials. One hundred and eight dogs with AD were selected based on current diagnosis standards. At one or more visits, clinicians subjectively rated the severity of AD as 'in remission', 'mild', 'moderate' or 'severe', and a CADESI-03 score was then determined. In all, 158 CADESI-03 values were recorded and divided among the four disease severity categories. Receiver-operating characteristics (ROC) curves were generated at increasing cut-off values to determine the benchmark that would offer optimal sensitivity and specificity between adjacent categories. Cut-offs of 16, 60 and 120 are proposed at the interface of remission, mild, moderate and severe categories, respectively. Proposed intervals therefore are: remission: 0-15; mild AD: 16-59; moderate AD: 60-119; and severe AD: >/= 120. This Task Force recommends that, whenever applicable and relevant, subgroup analyses of outcome measures, based on disease severity as determined with these cut-off CADESI-03 values, be preplanned for clinical trials enrolling dogs with AD. Such subgroup analyses could help determine whether specific interventions might be more effective in a particular subset of atopic dogs.     

Serum IgE and IgG responses to food antigens in normal and atopic dogs,and dogs with gastrointestinal disease

In human food allergy, with or without concurrent atopy, there may be significant increases in serum allergen-specific IgE. Serological methods have been tried but are not currently recommended for diagnosis of suspected food allergy in dogs. The aim of this study was to investigate humoral immune responses to food antigens in dogs. Serum IgG and IgE antibodies specific for food antigens were measured by enzyme linked immunosorbent assay (ELISA) using polyclonal anti-dog IgG and IgE reagents. Antigens tested were beef, chicken, pork, lamb, chicken, turkey, white fish, whole egg, wheat, soybean, barley, rice, maize corn, potato, yeast and cow's milk. Three groups were examined: normal dogs, dogs with atopic dermatitis (AD); and dogs with one of four types of gastrointestinal (GI) disease: small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), food-responsive disease, and infectious diarrhoea. Statistically significant differences in food-specific antibodies were not detected between the GI subgroups. There were statistically significant differences in the IgE concentration between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested. There were statistically significant differences in the average IgG concentrations between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested, except egg and yeast. The relationship of antigen responses for pooled data was analysed using principle component analysis and cluster plots. Some clustering of variables was apparent for both IgE and IgG. For example, all dogs (normal and diseased) made a similar IgG antibody response to chicken and turkey. Compared with other groups, atopic dogs had more food allergen-specific IgE and this would be consistent with a Th(2) humoral response to food antigens. Dogs with GI disease had more food allergen-specific IgG compared with the other groups. This may reflect increased antigen exposure due to increased mucosal permeability which is a recognised feature of canine intestinal disease.     

Application of the log-linear and logistic regression models in the prediction of systemic lupus erythematosus in the dog

This study sought to mathematically define canine systemic lupus erythematosus (SLE) by unifying diagnostic criteria proposed by others. Thirty-one cases of canine SLE were selected for modeling when 4 different published schemes agreed on the diagnosis, and 122 controls were selected when a patient's status met no scheme's criteria. The log-linear method showed an association between SLE and polyarthritis, hematologic abnormalities, renal damage, dermatologic disorders, and antinuclear antibody test response (positive). Logistic regression was then used to derive a predictive algorithm that could identify cases and controls with which all published criteria would be in accordance. The final equation correctly classified 93.5% of the affected dogs and 98.4% of the controls. It was concluded that the log-linear and logistic regression models are useful for the diagnosis of clinically similar, but distinguishable, disease states.     

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.     

Histologic characterization of canine dilated cardiomyopathy

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.     

Ultrastructural findings of feline eosinophilic dermatoses

The objectives of this multicentre study were to describe demographics and clinical findings of a group of 63 dogs with nonseasonal atopic dermatitis (AD), where concurrent flea allergy dermatitis, ectoparasite infestation, food adverse reactions and secondary infections had been ruled out. The breed, sex, age of onset, distribution of skin lesions, prevalence of otitis externa, secondary skin infections and additional noncutaneous clinical signs were recorded. A veterinarian recorded skin lesions from 15 different body regions. Each body region was scored according to degree of erythema, alopecia, excoriations, scale, crusts, lichenification and hyperpigmentation that was present. An early age of onset (37% of the dogs being less than 1 year old) was more common in this group of dogs than described in the literature. The German shepherd breed was over-represented (21% as compared with 7–9.9% of the veterinary clinic population) and approximately half of the German shepherd dogs (46%) started showing clinical signs before 1 year of age. Erythema was the overall most common type of skin lesion, with facial erythema and conjunctivitis being less commonly reported than in other studies. Feet, ears and groin were the most common sites for skin lesions. This study indicates that it is not uncommon for dogs with nonseasonal AD to have the onset of clinical signs start at a younger age (less than 1 year of age) and have clinical lesions that vary from previously published reports. This discrepancy might be allergen-dependent or breed-related.
  The study was funded by Boehringer Ingelheim Vetmedica, Denmark.