Do Food Allergies Cause PLE/PLN in Soft Coated Wheaten Terriers?  Shelly Vaden, DVM, PhD  North Carolina State University

Summary:

A familial syndrome of protein-losing enteropathy (PLE) and/or protein-losing nephropathy (PLN) has been reported in Soft Coated Wheaten Terriers (SCWT) where PLE is associated with inflammatory bowel disease of varying morphology and/or lymphangiectasia and PLN is the result of glomerulonephritis. PLE develops at an earlier mean age than does PLN (4.7 years vs. 6.3 years). We have established a colony of SCWT and SCWT x Beagles that are at risk for developing PLE/PLN. This has enabled us to make advances towards a better understanding of this syndrome.

Description of Colony Dogs: Currently, we have seventeen dogs in our research colony. Colony I SCWT were born to affected female x male SCWT (one male, DOB 7/94. two male, two female, DOB 2/95). Colony 2 SCWT were born to brother x sister mating of two colony I SCWT (one male, three females, DOB 7/97). The SCWT x beagle were born to affected Colony I SCWT x normal beagle (four males, four females, DOB 10/96). We have conducted sequential clinical evaluations of all dogs of our colony throughout their life. Overt clinical signs of PLN have developed in 3/6 of the Colony I SCWT; I of these dogs also has overt clinical signs of PLE. Overt signs of PLE/PLN are not yet present in any Colony 2 or SCWT x Beagle dogs; however, subclinical PLE is pervasive in these groups of dogs. More time is needed to determine if the disease is inherited as a dominant trait or if we are detecting the carrier state of a recessive trait in the SCWT x Beagle dogs.

Studies of Food Hypersensitivities: We have shown that PLE/PLN of SCWT is not the result of a specific gluten sensitivity, as was once suspected by SCWT breeders and owners, and that intestinal permeability, as measured by the chromium-EDTA and cellobiose/mannitol absorption tests, is normal in affected SCWT early in the course of the disease. We demonstrated that Colony I SCWT have food hypersensitivities to multiple food allergens as demonstrated by gastroscopic food sensitivity testing, provocative dietary trials and fecal IgE determinations conducted at a time when the dogs had only mild disease. Using similar methods, we have demonstrated that all of our Colony 2 and some of the SCWT x beagle have food hypersensitivities.

Studies of Mast Cell Function: We believe enhanced mast cell degranulation is involved in the pathogenesis of this disorder because of the following: 1) Increased circulating and intestinal eosinophil numbers are some of the earliest abnormalities detected in our affected dogs. 2) Eosinophil chernotactic factor is released from activated mast cells. 3) Enhanced mast cell degranulation can contribute to the pathogenesis of allergies. To test this hypothesis, we harvested mast cells from gastric and jejunal biopsies obtained from Colony I SCWT and normal control dogs. When the mast cell high affinity receptor for IgE (Fc-R1) is stimulated with IgE or concanavalin A, the percent histamine released from mast cells from Colony I SCWT is significantly lower than that obtained from control dogs. The most likely explanation for this is that SCWT have ongoing mast cell degranulation resulting in histamine depletion.

Treatment Trials: If mast cells are unstable in affected SCWT and this instability leads to food hypersensitivities which in turn leads to the development of PLE/PLN, affected SCWT should benefit from therapeutic measures aimed at mast cell stabilization (e.g., sodium cromoglycate, hydrolysate diets). A Colony I SCWT had an increased fecal alpha1-protease concentration (fecal API, marker of enteric protein loss) before treatment with sodium cromoglycate (9.73 ug/g, normal <6 ug/g), which decreased to within the normal range after treatment (0.90 ug/g). Another Colony 2 dog had a reduction in fecal API concentration from 7.13 ug/g to 4.3 ug/g after feeding a hydrolysate diet for 6 weeks. Sodium cromoglycate treatment did not appear to provide any additional benefit beyond that obtained with the hydrolysate diet in the latter dog. Reductions in urinary protein losses were not seen in either dog. A client owned SCWT had complete resolution of anorexia, severe diarrhea, and ascites following two weeks of sodium cromoglycate administration. Unfortunately, this dog was lost to follow-up evaluation. Several owners of affected SCWT are reporting clinical improvement associated with feeding a hydrolysate diet. There has not been a controlled therapeutic trial of either therapeutic measure in SCWT affected with PLE/PLN.

In summary, food allergies do occur in SCWT with PLE/PLN. It is not possible to state if they are a cause or an effect of the primary pathologic abnormality that occurs in affected dogs. However, preliminary findings suggest that some resolution of the clinical manifestations of disease may be obtained through therapeutic interventions aimed at mast cell stabilization.

Dr. Vaden's work is supported by the following grants from the AKC Canine Health Foundation:

No. 1285: Mode of Inheritance and Method for Early Detection of Protein-Losing Enteropathy (PLE) and Protein-Losing Nephropathy in Soft Coated Wheaten Terriers (Sponsored in part by the Soft Coated Wheaten Terrier Club of America) No. 1873 (Pending): Sequential Clinical Evaluation, Mode of Inheritance, and Therapeutic Trial of Protein-Losing Enteropathy and Nephropathy in Soft Coated Wheaten Terriers

Biographical Profile

Dr. Shelly Vaden graduated from the University of Georgia, College of Veterinary Medicine. She completed a Small Animal Internship at the New York State College of Veterinary Medicine at Cornell University. She completed a Small Animal Internal Medicine Residency program and received her PhD from North Carolina State University College of Veterinary Medicine. She is a Diplomate of The American College of Veterinary Internal Medicine. Since 199 1, Dr. Vaden has been a member of the faculty at North Carolina State University College of Veterinary Medicine. Her research and clinical interests are in diseases of the urinary tract. She has been studying proteinwasting diseases of Soft Coated Wheaten Terriers since 1992.