Diagnostic techniques in dermatology: The investigation and diagnosis of adverse food reactions in dogs and cats

Most veterinary clinicians recognize a population of patients in which dermatologic and/or gastrointestinal signs are related to the feeding of particular dietary components. This article briefly reviews the clinical signs associated with adverse food reactions in dogs and cats, and discusses the practical issues associated with confirming a diagnosis.     

A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions

Several hydrolysate-based diets have been commercialized for helping diagnose or treat dogs with cutaneous adverse food reactions (CAFR). This systematic review was performed to examine the evidence in favour of reduced immunological and clinical allergenicity of hydrolysates in dogs with CAFR. Citation databases, meeting abstracts and article bibliographies were scanned for relevant citations, and companies were contacted to provide unpublished reports. Eleven studies relevant to this study were identified. Some evidence of reduced serum IgE binding to a soy hydrolysate (1 study) and decreased intradermal test reactivity to hydrolysed proteins (three studies) was found. In four reports, the feeding of dogs suspected of having CAFR with hydrolysate-based diets reduced or eliminated clinical signs in a variable proportion of subjects. The percentage of dogs with CAFR that still reacted to these hydrolysate-based diets could not be assessed, however. Importantly, up to 50% of dogs with CAFR enrolled in three controlled studies exhibited increases in clinical signs after ingesting partial hydrolysates derived from foods to which they were hypersensitive. In conclusion, the limited number of studies undertaken point to reduced – but not eliminated – immunological and clinical allergenicity of hydrolysate-based commercial diets. A variable proportion of dogs with CAFR will exhibit a worsening of clinical signs when fed partial hydrolysates. Clinicians must weigh the clinical benefit of these diets versus their high cost and low risk of reduced appetence or gastrointestinal sign development. At this time, hydrolysate-containing diets are probably best used in dogs suspected not to be hypersensitive to their individual components.     

Evaluation of serum allergen-specific IgE for the diagnosis of food adverse reactions in the dog

A new monoclonal enzyme-linked immunoassay (ELISA; CMG IMMUNODOT, Fribourg, Switzerland) measuring food antigen-specific serum IgE was used in an attempt to investigate food allergen-specific IgE in dogs. The serum of eight dogs with clinically proven adverse reactions to specific proteins was tested for beef, cow's milk, pork, lamb, hen's egg, soybean, fish mix (cod/sole), peanut, maize and wheat flour. The control group consisted of three healthy dogs, three dogs with nonallergic skin disease, two dogs with atopy, a cat and a horse. Only three mild positive reactions to beef, lamb and peanut, respectively, were found in this study; the sera were from two control dogs with the clinical diagnosis of dermatophytosis and atopy. None of the animals with confirmed food adverse reactions showed positive reactions. This study indicates that the diagnosis of food adverse reactions in the dog by measuring allergen-specific IgE with the used mononuclear ELISA is unreliable.     

Comparison of a commercial limited-antigen diet versus home-prepared diets in the diagnosis of canine adverse food reaction

The objective of the present study was to compare the efficacy of a commercial limited-antigen diet (Eukanuba Veterinary Diets Response Formula FP/Canine, The Iams Company) with home-prepared diets in the diagnosis of adverse food reaction in dogs. The study was conducted in two phases. The first phase utilized 28 dogs fed a home-prepared diet to enable a diagnosis of adverse food reaction. Dogs diagnosed from this phase were entered into the second phase in which these dogs were fed the commercial limited-antigen diet. Owners of 10 of the 28 dogs quit Phase 1 before it could be completed, and one case was eliminated because extended treatment with steroids was required. Eight of the remaining 17 (47 %) dogs were diagnosed with an adverse food reaction. A reaction occurred in four of eight dogs fed the test diet in Phase 2. These results demonstrated the difficulties encountered by owners and veterinarians attempting to feed dogs home-prepared diets. In addition, the results of the study suggest that the occurrence of adverse reactions to fish could make it a less desirable ingredient as a limited antigenin canine diets.     

A retrospective analysis of case series using home-prepared and chicken hydrolysate diets in the diagnosis of adverse food reactions in 181 pruritic dogs

The purpose of this retrospective study was to compare home-prepared and chicken hydrolysate diets in the diagnosis of canine adverse food reactions (AFR). Seventy-two dogs were fed home-prepared diets and 109 were fed hydrolysate. Owners chose the type of diet at presentation, and ingredients of home-prepared diets were selected depending on each dog's dietary history. Ectoparasitic infestations and microbial infections were treated during the trials. Cutaneous and gastrointestinal signs and pruritus scores were recorded before starting the diet, 6 weeks into the trials and after provocation with the original diets. AFR was diagnosed if pruritus resolved during the trial and recurred on dietary provocation. The dropout rate was lower for home-prepared diets although not statistically significant (18.1% home prepared; 24.7% hydrolysate, P=0.377). AFR alone was diagnosed in 10 dogs (17%) using home-prepared diets and in 15 (18.3%) fed the hydrolysate. Gastrointestinal problems were more frequent in dogs with AFR than in dogs without AFR (P=0.001). Another 11 dogs (18.6%) in the home-prepared diet group and 20 (24.4%) in the hydrolysate diet group had AFR concurrent with other pruritic diseases, mainly atopy. The similar frequencies of AFR diagnosis in the two groups (P=0.837 AFR; P=0.416 concurrent AFR) indicate that the chicken hydrolysate diet may be a valuable alternative to home-prepared diets in the diagnosis of canine AFR. Prospective cross-over studies are warranted to confirm these findings.     

Prevalence of adverse food reactions in 130 dogs in Italy with dermatological signs: a retrospective study

Objectives : To determine the prevalence of adverse food reactions (AFRs) in dogs with dermatological signs presented to the referral dermatological clinic of the University of Milan. Methods : The medical records of dogs with dermatological signs were reviewed. Prevalence of AFRs was calculated. Owner and clinician pruritus scores were compared. Breed, sex and age predisposition were statistically tested, as was the association between AFR and selected clinical features. Results : The prevalence of AFRs in dogs with dermatological signs was 12% (16 of 130). AFR was diagnosed in 26% of dogs with allergic disease and 48% of those subjected to a dietary trial. There was a significant association between AFRs and early onset of clinical signs (<1 year) (OR=3·8; P=0·0221, 95% CI=1·27 to 11·16). There was a significant association between AFRs and both otitis externa (OR=5·9; P=0·0015, 95% CI=2 to 17·9) and perianal fistula (OR=26·1; P=0·0058, 95% CI=2·52 to 269·4), although all dogs with perianal fistulas were German shepherd dogs. Clinical Significance : The prevalence of AFRs in the study population was higher than most reported values. Further studies are warranted to investigate the true prevalence of AFR and its possible association with perianal fistula and other potential markers.     

Patch testing and allergen-specific serum IgE and IgG antibodies in the diagnosis of canine adverse food reactions

Adverse food reaction (AFR) is a common differential diagnosis for pruritic dogs. The only way to diagnose AFR is an elimination diet of 6-8 weeks with a protein and a carbohydrate source not previously fed. In humans, patch testing has been shown to be a useful tool to diagnose food allergies. In veterinary medicine, serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for such diets. The aim of this study was to determine sensitivity, specificity, negative and positive predictability of patch testing with and serum antibody testing for a variety of common food stuffs. Twenty-five allergic dogs underwent an elimination diet and individual rechallenge with selected food stuffs, food patch testing and serum testing for food-antigen specific IgE and IgG. Eleven clinically normal control dogs only were subjected to patch and serum testing. The sensitivity and specificity of the patch test were 96.7 and 89.0% respectively, negative and positive predictability were 99.3 and 63.0%. For IgE and IgG the sensitivity was 6.7 and 26.7%, specificity were 91.4 and 88.3%, the negative predictive values 80.7 and 83.7% and the positive predictive values were 15.4 and 34.8%. Based on these results, a positive reaction of a dog on these tests is not very helpful, but a negative result indicates that this antigen is tolerated well. We conclude that patch testing (and to a lesser degree serum testing) can be helpful in choosing ingredients for an elimination diet in a dog with suspected AFR.     

A comparison of the clinical manifestations of feeding whole and hydrolysed chicken to dogs with hypersensitivity to the native protein

Twenty‐six dogs with known adverse food reactions were fed whole chicken for 14 days. From this group, 12 dogs with cutaneous manifestations following exposure to chicken meat were selected and randomly divided into two groups (n = 6). Each group was then fed hydrolysed chicken or hydrolysed soy for 14 days in a blinded crossover design with a 17‐day washout period between each diet. Assessments of a CADESI (Canine Atopic Dermatitis Extent and Severity Index) score and pruritus were performed throughout the entire study, and combined in a global score (GS). Serum was collected weekly for the measurement of chicken‐ and soy‐specific IgG and IgE. Dogs displayed the most severe clinical response when eating whole chicken compared to baseline (P < 0.001). The GS was significantly reduced in 11 of the 12 dogs when fed hydrolysed chicken were compared to those fed whole chicken (3.58 ± 2.81 versus 20.38 ± 14.65, P < 0.01). Serum immunoglobulin G and E responses were variable and did not show relationship with specific dietary exposure.     

A blinded randomized controlled trial evaluating the usefulness of a novel diet (aminoprotect care) in dogs with spontaneous food allergy

Aminoprotect Care (APC) is a novel diet composed of aminoacids, potato proteins and corn starch. The objectives of this study were to determine whether Maltese-Beagle atopic (MBA) dogs hypersensitive to corn exhibited clinical signs and changes in immunological markers after being fed APC. The study was designed as a blinded randomized controlled crossover experiment. Ten MBA dogs with signs of allergy within five days of ingesting corn were selected. Dogs were randomized to be fed either their maintenance diet with corn or APC for five days. After a washout of two weeks, diets were switched. Before and daily during each intervention, skin lesions were graded by an investigator while pruritus was assessed by another. Before and at the end of each intervention, the percentage of circulating CD4+CCR4+, corn-activated CD4+ T-lymphocytes and serum corn-specific IgE levels were measured and ratios of post:pre values calculated. During this trial, pruritus and skin lesions increased significantly in MBA dogs when ingesting corn while no such increase occurred when fed APC. Total, median and maximal pruritus values were significantly higher in MBA dogs ingesting corn compared to APC. There were no significant differences between interventions in the immunological parameters assessed. In summary, even though APC contains corn starch to which corn-sensitive MBA dogs often react, the ingestion of APC did not lead to significant increases in skin lesions or pruritus. Aminoprotect Care might prove valuable for management of food allergies. These experimental observations must be validated in large field studies.     

Chemotherapy‐induced diarrhoea in dogs and its management with smectite: Results of a monocentric open‐label randomized clinical trial

Chemotherapy‐induced diarrhoea (CID) is a frequent chemotherapy adverse event in dogs. Yet, there is currently no consensus regarding its management. Smectite is a natural medical clay, widely used in the treatment of acute diarrhoea in humans. The objectives of this study were to assess the efficacy of smectite in the management of CID in dogs, and to collect epidemiological data on CID. For each episode of diarrhoea, dogs were randomized into two management groups: Smectite group, receiving smectite at 0.5 g/kg PO per day divided in two to three doses initiated at the start of CID; control group, without initial medication. In both groups, rescue metronidazole was prescribed if CID progressed or was not improved within 48 hours. Sixty dogs were recruited and received 426 chemotherapy administrations between June 2017 and March 2019. The incidence rate of CID was 110/426 (25.8%, 95% CI: 21.7%‐30.2%), and significantly differed between the chemotherapeutic drugs administered (P < .001). Metronidazole was administered in 5/54 events (9.3%, 95% CI: 3.1%‐20.3%) in the smectite group and in 40/56 events (71.4%, 95% CI: 57.5%‐82.3%) in the control group (P < .001). The time to resolution of diarrhoea was shorter (P < .001) in the smectite group (median: 19.5 hours, interquartile range [IQR]: 13.5‐32 hours) compared with the control group (median: 53 hours, IQR: 31.5‐113.5 hours). The results of this study support the administration of smectite in the first‐line management of CID in dogs.     

Identification of allergens responsible for canine cutaneous adverse food reactions to lamb, beef and cow's milk

Lamb, beef and cow's milk are common causes of cutaneous adverse food reactions in dogs. The aim of this study was to identify the proteins responsible for cutaneous adverse reactions to these foods. Ten dogs with allergen-specific serum immunoglobulin (Ig)E to lamb, beef and cow's milk were included in the study. These dogs had been diagnosed with cutaneous adverse food reactions by convincing clinical history and food-elimination diet trials followed by challenge exposure. Sera were analysed by enzyme-linked immunosorbent assay with bovine proteins and SDS-PAGE immunoblots with lamb, beef and cow's milk extracts. All the dogs had specific IgE against bovine IgG, and it was the only protein in the cow's milk extract that bound IgE from the sera studied. In the lamb and beef extracts, the major allergens recognized by the specific IgE of most sera had molecular masses between 51 and 58 kDa, which were identified as phosphoglucomutase and the IgG heavy chain. Other IgE-binding proteins with molecular masses of 27, 31, 33, 37 and 42 kDa were also detected with some sera. Our results indicate that bovine IgG is a major allergen in cow's milk and hence it appears to be a source of cross-reactivity with beef and probably with lamb because of the high homology with ovine immunoglobulins. These results are similar to those found for meat allergy in humans. However, this is the first time that phosphoglucomutase has been identified as an important allergen involved in allergic reactions to lamb and beef.