Evaluation of intestinal permeability and gluten sensitivity in Soft-Coated Wheaten Terriers with familial protein-losing enteropathy, protein-losing nephropathy, or both

OBJECTIVE: To evaluate intestinal permeability and gluten sensitivity in a family of Soft-Coated Wheaten Terriers (SCWT) affected with protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both. ANIMALS: 6 affected adult dogs. PROCEDURE: Intestinal biopsy specimens, urine protein-to-creatinine ratio, serum concentrations of albumin and globulin, and concentration of alpha1-protease inhibitor in feces were evaluated before, during, and 13 weeks after daily administration of 10 g of gluten for 7 weeks. Eosinophils and lymphocytes-plasmacytes were enumerated in intestinal biopsy specimens. Intestinal permeability was evaluated before and during the sixth week of gluten administration via cellobiose-mannitol and chromium-EDTA absorption tests. RESULTS: Serum globulin concentration decreased significantly after prolonged administration of gluten. Although not significant, there was an increase in lymphocytes-plasmacytes and a decrease in eosinophils in intestinal biopsy specimens. Furthermore, these counts were greater than those reported for clinically normal dogs. Gluten administration did not increase intestinal permeability. CONCLUSIONS AND CLINICAL RELEVANCE: Daily administration of gluten was associated with a significant decrease in serum globulin concentration in SCWT affected with PLE or PLN, but other variables remained unchanged. Although enhanced wheat-gluten sensitivity may be one factor involved in the pathogenesis of PLE or PLN in SCWT, this syndrome does not appear to be the result of a specific sensitivity to gluten.     

Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997)

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.     

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.     

Prognostic value of small intestinal dilatation in dogs with protein-losing enteropathy

To date, little is known about the prognostic significance of ultrasonographic findings in dogs with protein-losing enteropathy (PLE). The aim of this retrospective study was to examine the prognostic value of ultrasonographic findings in dogs with PLE. A total of 26 dogs with PLE were included: 20 dogs with chronic enteropathy and 6 dogs with gastrointestinal lymphoma. The presence of small intestinal dilatation was associated with shorter survival time in dogs with PLE (P=0.003). The presence of hyperechoic intestinal mucosal striations was associated with longer survival time in dogs with PLE (P=0.0085). The results of the current study indicate that the presence of small intestinal dilatation might be associated with poor prognosis in dogs with PLE.     

Serum concentrations of the third component of complement in healthy dogs and dogs with protein-losing nephropathy

OBJECTIVE: To develop a method for determining the concentration of the third component of complement (C3) in canine serum, to establish a reference range for C3 in healthy dogs, and to evaluate dogs with protein-losing nephropathy (PLN) to determine whether PLN is associated with decreased serum C3 concentrations. ANIMALS: 30 healthy dogs and 49 dogs with PLN. PROCEDURES: Serum samples were obtained from healthy dogs at the time of examination, whereas serum samples were obtained from dogs with PLN at the time of diagnosis. All samples were frozen at -70 degrees C until analyzed. Serum C3 concentrations were determined by use of a sandwich ELISA. Concentrations were expressed as the number of dilutions in which C3 could be detected. RESULTS: C3 was detectable in healthy control dogs (range, 1,920,000 to 15,400,000 dilutions; median, 9,600,000 dilutions). This represented a range of four 2-fold serum dilutions. In addition, C3 was detectable in dogs with PLN (range, 1,460,000 to 30,070,000 dilutions; median, 7,680,000 dilutions), which represented a range of six 2-fold serum dilutions. There was no significant difference in C3 concentrations between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: C3 is a critical part of the immune defense system that has not been extensively examined in veterinary medicine. An ELISA was developed for measuring C3 concentrations, and a reference range for healthy dogs was established. Significant decreases in C3 concentrations were not detected in any dog with PLN. Additional studies will be required to definitively determine the importance of serum C3 concentrations in PLN.     

Food allergen-specific serum IgG and IgE before and after elimination diets in allergic dogs

Serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for diets to diagnose adverse food reaction (AFR) in dogs with allergic skin disease. Antibody concentrations in blood samples obtained during an unsuccessful diet to help in the choice of diet changes may be influenced by the previous diet. The objective of this paper was to measure food antigen-specific IgE and IgG for the most commonly used 16 food antigens before and after an elimination diet. Levels of food-specific serum IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Dogs had detectable IgE antibodies to beef, pork, lamb and cows' milk; and detectable IgG antibodies to beef, pork, lamb, cows' milk, chicken and turkey. Of 19 dogs with complete data sets, 14 dogs showed clear improvement during diet and in 7 dogs AFR could be diagnosed by deterioration on rechallenge and subsequent improvement on refeeding the diet. Serum was obtained before and 6-8 weeks after beginning such a diet. There was no significant difference in pre- and post-diet levels for any of the individual allergens nor for the total IgE and IgG concentrations of all antigens (P=0.55 and P=0.53 respectively). In these 19 dogs in which an elimination diet was used for the diagnosis of food allergy and in which 14 were probably food allergic and 7 were proven food allergic there were no significant differences in food-specific antibodies before and after an elimination diet of 6-8 weeks.     

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.     

Gastroscopic food sensitivity testing in 17 dogs

Seven of 17 dogs with gastrointestinal signs and suspected dietary intolerance had positive responses to gastroscopic food sensitivity testing (GFST). Five of the non-responders and six of the dogs that responded to GFST were successfully treated with dietary control alone. The seventh dog that responded to GFST had an ileal adenocarcinoma and did not survive to follow-up. Local reactions to GFST included mucosal oedema, mucosal hyperaemia and gastric hyperperistalsis and systemic reactions consisted of hyperventilation and retching. The character of the responses to GFST is consistent with a type 1 hypersensitivity reaction to the food antigen, suggesting that IgE may mediate dietary sensitivity in some dogs. Positive responses to GFST may, therefore, demonstrate gastric mucosal hypersensitivity to food antigens and be useful in formulating therapeutic diets; negative responses need to be interpreted with caution. The limitations of the procedure are that it requires a videoendoscopy system, may significantly add to general anaesthetic time and will only detect immediate reactions.     

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.     

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.     

IgE reactivity to milk components in dogs with cutaneous adverse food reactions

We investigated the IgE reactivity to crude and purified milk antigens in the sera of 112 dogs with cutaneous adverse food reactions (CAFRs). Of the 112 dogs, 33 (29%) had specific IgE for crude milk antigens. In the dogs with milk-specific IgE, IgE reactivity to casein, bovine serum albumin (BSA), α-lactalbumin, β-lactoglobulin, and bovine IgG were 81%, 85%, 39%, 27%, and 35%, respectively. Casein and BSA may be important allergens in dogs with CAFRs. Some canine vaccines contain casein hydrolysate as a stabilizer and the pooled serum with anti-casein IgE showed IgE reactivity to the vaccines containing it. Information about IgE reactivity to casein in dogs with CAFRs could be useful for predicting adverse reactions to the vaccines including casein hydrolysate.     

Intestinal crypt lesions associated with protein-losing enteropathy in the dog

Six dogs were diagnosed with protein losing enteropathy (PLE). There was no evidence of inappropriate inflammatory infiltrates or lymphangiectasia in multiple mucosal biopsies of the small intestine of 4 of the dogs. The 5th and 6th dogs had obvious lymphangiectasia and a moderate infiltrate of inflammatory cells in the intestinal mucosa. All 6 dogs had a large number of dilated intestinal crypts that were filled with mucus, sloughed epithelial cells, and/or inflammatory cells. Whether PLE occurs in these dogs because of protein lost from the dilated crypts into the intestinal lumen or whether the dilated crypts are a mucosal reaction due to another undetermined lesion that is responsible for alimentary tract protein loss is unknown. However, when large numbers of dilated intestinal crypts are present, they appear to be associated with PLE even if there are no other remarkable lesions in the intestinal mucosa.     

Hypercoagulability in dogs with protein-losing enteropathy

Background: Dogs with protein‐losing enteropathy (PLE) have previously been reported to present with thromboembolism; however, the prevalence and pathogenesis of hypercoagulability in dogs with PLE have not been investigated so far. Hypothesis: Dogs with PLE are hypercoagulable compared with healthy control dogs. Animals: Fifteen dogs with PLE. Thirty healthy dogs served as controls (HC). Methods: A prospective study was performed including 15 dogs with PLE. All dogs were scored using the canine chronic enteropathy activity index (CCECAI). Thromboelastography (TEG) and other measures of coagulation were evaluated. Recalcified, unactivated TEG was performed and reaction time (R), kinetic time (K), alpha angle (α), and maximum amplitude (M_A) values were recorded. Nine dogs were reassessed after initiation of immunosuppressive treatment. Results: All dogs with PLE in the study were hypercoagulable with decreased R (PLE: median 7.8, range [2.4–11.2]; HC: 14.1 [9.1–20.3]), decreased K (PLE: 2.5 [0.8–5.2]; HC: 8.25 [4.3–13.1]), increased α (PLE: 56.7 [38.5–78.3]; HC: 25.6 [17–42.4]), and increased M_A (PLE: 68.2 [54.1–76.7]; HC: 44.1, [33.5–49]) (all P < .001). Median antithrombin (AT) concentration was borderline low in PLE dogs; however, mean serum albumin concentration was severely decreased (mean 1.67 g/dL ± 5.1, reference range 2.8–3.5 g/dL). Despite a significant improvement in serum albumin and CCECAI, all 9 dogs with PLE were hypercoagulable at re‐examination. Conclusions and Clinical Importance: The hypercoagulable state in dogs with PLE cannot be solely attributed to loss of AT. Despite good clinical response to treatment, dogs remained hypercoagulable and could therefore be predisposed to thromboembolic complications.     

Diagnostic testing of dogs for food hypersensitivity

Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercially available egg and rice diet, intradermal skin testing, and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Feeding of a home-cooked whole lamb meat and rice diet for 3 weeks, followed by challenge with each dog's regular diet, served as the standard for diagnosing food hypersensitivity. Each dog underwent provocative testing with 6 individual ingredients to determine as many of its dietary allergens as possible. Prior to skin testing and serologic testing by ELISA, most dogs had been recently exposed to the offending diet and subsequently manifested clinical signs of allergy. All dogs that tolerated the aforementioned commercial diet were exposed to it for at least 7 weeks; 84.6% of food-hypersensitive dogs ate the commercial diet with impunity. Of the 2 reactors to the commercial diet, only 1 became pruritic in response to provocation testing with chicken eggs. Low sensitivity and high specificity were found for skin testing and the ELISA, indicating a lack of true- and false-positive reactions. Neither the positive nor negative predictive values adequately predicted positive and negative reactions, respectively, for either test. On the basis of these results, the commercial diet, skin testing, and anti-IgE ELISA cannot replace an owner-prepared food elimination diet for food hypersensitivity testing in dogs.     

Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy

Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5- to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (P<0.05), suggesting that lymphocytes against food allergens may be involved in the pathogenesis of canine FA.     

Development of Gastroscopic Food Sensitivity Testing in Dogs

The aims of this study were to develop a gastroscopic food sensitivity testing (GFST) technique for clinical use in dogs and to determine if the results of GFST were influenced by the feeding of a hypoallergenic diet immediately before the testing period ("unmasking"). The technical requirements for GFST were devised during a total of eight endoscopies performed in four healthy dogs. GFST was performed in anesthetized dogs in sternal recumbency. Food extracts were dripped onto the dependent aspect of the body of the stomach via plastic tubing passed through the endoscope. Changes were observed within 2 to 3 minutes of application, and included localized mucosal swelling and erythema, generalized mucosal erythema, and hyperperistalsis. The influence of "unmasking" was then examined in 6 atopic and 2 healthy dogs, which underwent GFST on three occasions, 4 weeks apart. Before the first and third testing periods, the dogs consumed a commercial dry dog food. For 5 days before the second testing period the dogs were fed a hypoallergenic elemental diet. Oral challenges were performed to identify which of the dogs had clinically overt immediate food sensitivity. Localized swelling was most frequently correlated with positive challenge PO. No positive reactions occurred in response to the negative control extract (lamb). The number of positive GFST results increased after feeding the hypoallergenic diet. In conclusion, these preliminary results indicate that GFST holds substantial promise for the diagnosis of immediate food sensitivities affecting the gastrointestinal tract. The sensitivity of the procedure appears to be enhanced by preceding testing with a hypoallergenic diet.     

Changes in the coagulation parameters in dogs with protein-losing enteropathy between before and after treatment

Protein-losing enteropathy (PLE) is known to induce hypercoagulability and resultant thromboembolism in dogs. We hypothesized that hypercoagulability would improve if remission was obtained in dogs with PLE after treatment. This study aimed to evaluate the changes in the coagulation parameters after treatment in dogs diagnosed with PLE. As coagulation parameters, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, thrombin-antithrombin complex (TAT), D-dimer, and antithrombin (AT) were measured. In addition to these parameters, rotational thromboelastometry (ROTEM), which evaluates the comprehensive coagulation and fibrinolysis reactions of whole blood, was conducted and the data of clotting time (CT), clot formation time (CFT), α angle (α), maximum clot firmness (MCF) and lysis index at 60 min (LI60) were obtained. Eleven of the 14 dogs diagnosed with PLE were classified as responders to the treatment based on the changes in their plasma albumin (ALB) concentration after treatment. Significant increase in CFT and decrease of α and MCF indicating the resolution of hypercoagulability were found after treatment in responder dogs; however, there was no significant change in the coagulation and fibrinolysis parameters other than those measured by ROTEM. This study demonstrated that the hypercoagulability detected by ROTEM was significantly improved after treatment in dogs with PLE.     

Food sensitivity in cats with chronic idiopathic gastrointestinal problems

The objectives of this study were to investigate the prevalence of food sensitivity in cats with chronic idiopathic gastrointestinal problems, to identify the food ingredients responsible, and to characterize the clinical features. Seventy cats that presented for chronic gastrointestinal signs underwent diagnostic investigation. Fifty-five cats had idiopathic problems and were entered into the study. Diagnosis of food sensitivity was made by dietary elimination-challenge studies by using commercial selected-protein diets as the elimination diet. Sixteen (29%) of the 55 cats with chronic idiopathic gastrointestinal problems were diagnosed as food sensitive. The clinical signs of another 11 cats (20%) resolved on the elimination diet but did not recur after challenge with their previous diet. The foods or food ingredients responsible for the clinical signs were dietary staples. Fifty percent of affected cats were sensitive to more than 1 food ingredient. The clinical feature most suggestive of food sensitivity was concurrent occurrence of gastrointestinal and dermatological signs. Weight loss occurred in 11 of the affected cats, and large-bowel diarrhea was more common than small-bowel diarrhea. Assay of serum antigen-specific immunoglobulin E (IgE) had limited value as a screening test, and gastroscopic food sensitivity testing was not helpful. In conclusion, adverse reactions to dietary staples were common in this population of cats, and they responded well to selected-protein diets. Diagnosis requires dietary elimination-challenge trials and cannot be made on the basis of clinical signs, routine clinicopathological data, serum antigen-specific IgE assay, gastroscopic food sensitivity testing, or gastrointestinal biopsy.     

Protein-losing enteropathy in dogs is associated with decreased fecal proteolytic activity

Background: Measurement of proteolytic activity in feces is a traditional method for the diagnosis of exocrine pancreatic insufficiency (EPI). A drawback of this method is the occurrence of falsely low results that may lead to a false‐positive diagnosis of EPI. We hypothesized that intestinal loss of serum proteinase inhibitors in protein‐losing enteropathy (PLE) may inhibit fecal proteolytic activity and be a potential source of false low results. Objective: The objective of this study was to determine the effect of PLE on fecal proteolytic activity in dogs. Methods: Fecal proteolytic activity was measured using a radial diffusion casein digestion assay in 12 samples from 4 clinically healthy control dogs and 30 samples from 16 dogs with PLE. Gastrointestinal protein loss was assessed using an ELISA to determine fecal canine α₁‐proteinase inhibitor concentration. The relationship between the concentration of canine α₁‐proteinase inhibitor in the feces and the diameter cleared in the casein digestion assay was determined. The mean clearing diameter was compared between control dogs and dogs with PLE. Results: A significant negative correlation was observed between fecal canine α₁‐proteinase inhibitor concentration and casein clearing diameter (P < .001, Pearson r=—.6317, r 2 =.3999). Mean clearing diameter was significantly lower in dogs with PLE than in control dogs (12.63 vs 16.83 mm, P < .001, two‐tailed Student's t‐test). Conclusion: Increased fecal loss of α₁‐proteinase inhibitor in dogs with PLE is associated with a significant decrease in fecal proteolytic activity and may result in a false positive diagnosis of EPI.     

Hypomagnesemia and hypocalcemia associated with protein-losing enteropathy in Yorkshire terriers: five cases (1992-1998)

OBJECTIVE: To determine clinical and laboratory findings associated with protein-losing enteropathy, hypomagnesemia, and hypocalcemia in Yorkshire Terriers. DESIGN: Retrospective study. ANIMALS: 5 purebred or crossbred Yorkshire Terriers with protein-losing enteropathy, hypomagnesemia, and hypocalcemia. PROCEDURE: Medical records were reviewed for dogs with protein-losing enteropathy, hypomagnesemia, and hypocalcemia. RESULTS: Of 8 dogs with these signs, 5 had Yorkshire Terrier breeding. Common findings were diarrhea, abdominal effusion, leukocytosis, neutrophilia, hypocalcemia (ionized calcium), hypomagnesemia, hypoproteinemia, hypoalbuminemia, hypocholesterolemia, and increased serum activity of aspartate aminotransferase. CONCLUSIONS AND CLINICAL RELEVANCE: Yorkshire Terriers are at increased risk for development of protein-losing enteropathy with hypomagnesemia and decreased ionized calcium concentration. Hypomagnesemia and hypocalcemia may have a related pathogenesis involving intestinal loss, malabsorption, and abnormalities of vitamin D and parathyroid hormone metabolism. Serum electrolyte replacement may be required to avoid neurologic and metabolic problems.