Edward J. Hall, MA, VetMB, PhD, DECVIM-CA, MRCVS
Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford
The existence of breed-specific intestinal diseases would suggest that there is an underlying genetic cause to each disease. However, many gastrointestinal (GI) diseases have an infectious aetiology, and suspected inherited diseases can be due to infection transmitted between relatives. In humans, for example, gastric Helicobacter infection most commonly follows infection from the mother, and can lead to a spectrum of disease raging from gastritis to ulcers, mucosal lymphoma and gastric carcinoma. Gastric carcinoma is the most common gastric neoplasm of dogs, and the marked over-representation of the disease in collies, especially Rough collies, suggests a genetic predisposition. However, passage of a pathogenic strain of Helicobacter from dam to pup as the initiating cause cannot be ruled out. For whilst the pathogenicity of Helicobacter in dogs and cats is debated, there is no doubt in veterinary dermatology that the transmission of Demodex from dam to pups occurs, and similar transmission of Helicobacter is likely.
Indeed, even apparent susceptibility to infection may merely reflect opportunity. For example, intestinal pythiosis is most common in hunting dogs in the southern states of the USA, but then they are the breeds likely to be exposed to the swampy environment where the infection is acquired. Nevertheless, whilst there is little doubt that susceptibility to infections exists, certain breeds of dogs and cats are also susceptible to other noninfectious enteropathies. Awareness of breed-specific intestinal disease raises the likelihood of a specific disease in any particular breed. Whilst this may aid the formulation of a differential diagnosis, it can never be relied upon to make the diagnosis.
Any unvaccinated dog is susceptible to parvovirus infection, but breeds such as the Rottweiler, Dobermann, English Springer spaniel and American pit bull terrier have been shown to be at risk of more severe disease1. The reason is not known although inadequacies in the immune response are suggested.
Exocrine pancreatic insufficiency (EPI)
Although not strictly an intestinal disease, EPI mimics small intestinal malabsorption and should be ruled out before beginning investigations of chronic GI disease. This is simply done by the trypsin-like immunoreactivity (TLI) test. Surveys have shown that certain breeds are predisposed to EPI, and heritability has been demonstrated in German shepherd dogs and Rough collies.
Antibiotic-responsive diarrhoea (ARD)
Formerly termed small intestinal bacterial overgrowth, this syndrome is seen most commonly as an idiopathic problem in young, large-breed dogs, and especially in the German shepherd dog. Whilst controversy surrounds the issue of whether bacterial numbers are actually increased in these dogs, and how antibiotics provide effective treatment, there is no doubt there are a number of dogs with GI signs that respond to antibiotics2,3. Further discussion of this condition is the subject of another presentation.
Inflammatory bowel disease (IBD)
Although the cause of idiopathic IBD is believed to be a loss of tolerance to the normal enteric flora, which could theoretically develop in any dog or cat, there appears to be a breed predisposition that may reflect breed differences in the function of the mucosal immune system. The condition is particularly reported in the German shepherd and Shar Pei, two breeds where there is some circumstantial evidence of an immune defect. In cats, the Siamese cat is considered predisposed.
Inflammatory bowel disease is classified by histological type, i.e., lymphoplasmacytic, eosinophilic, etc. The lymphoplasmacytic is reported the more common in these breeds, but the German shepherd is also reportedly predisposed to eosinophilic enteritis, as are Boxers. A very severe form of lymphoplasmacytic enteritis is reported in Basenjis (see below).
Treatment is based on immunosuppression with corticosteroids and cytotoxic drugs such as azathioprine. Some dogs go into complete remission, but the tendency is towards chronic relapsing disease that can only be controlled but not eradicated, again suggesting there is some underlying 'genetic' abnormality.
This condition is characterized by severe lymphoplasmacytic enteritis and hypergammaglobulinaemia4. The intestinal inflammation can be so severe that spontaneous intestinal perforation has been reported and the prognosis is generally poor. Initially this condition was termed Immunoproliferative Small Intestinal Disease (IPSID) because it resembled a condition seen in humans of primarily Mediterranean origin. However the human condition is associated with alpha heavy-chain disease and a predisposition to lymphoma. Alpha heavy-chain disease is not present in affected Basenjis but they may be predisposed to lymphoma.
Signs of chronic intractable diarrhoea and emaciation are most common. Lymphoplasmacytic gastritis, with hypergastrinaemia and mucosal hyperplasia, may be seen in addition to the enteropathy. Protein-losing enteropathy (PLE) often occurs with consequent hypoalbuminaemia, although oedema and ascites are not common. Clinical signs are usually progressive, although early aggressive combination treatment with prednisolone, antibiotics and dietary modification may achieve remission in some cases.
Histiocytic ulcerative colitis (HUC)
This unusual form of IBD has been reported almost exclusively in Boxers. There are two reports of HUC in an ancestrally related breed, the French bulldog, but recently it has been recorded in a Mastiff, an Alaskan malamute, and a Dobermann pinscher.
The disease is restricted to the colon. The colitis is characterized by accumulations of periodic acid Schiff (PAS) positive macrophages, although a mixed inflammatory response with T cells and IgG plasma cells is actually present. The disease is rare and sporadic and for many years it has been hypothesized that it is infectious in nature, although attempts at disease transmission have failed. However, recently the condition has been reported to be sensitive to enrofloxacin5, suggesting an infectious aetiology.
Gluten-sensitive enteropathy (GSE)
Small intestinal disease, induced by the presence of dietary wheat gluten and related cereal peptides, has been clearly documented in Irish setter dogs6. The condition resembles GSE (coeliac disease) in humans in whom there is an underlying genetic predisposition: there is an association with the MHC class II haplotype HLA-DQω2, and the development of anti-gliadin antibodies that cross-react with the self-antigen, tissue transglutaminase. In Irish setters it is also a familial condition with an autosomal recessive mode of inheritance. However, intestinal damage and clinical signs are less marked and, unlike human coeliac disease, there is no relationship with major histocompatibility genes DQA and DQB, nor any similarity in the pathogenesis7. The line of affected setters from which these dogs were originally bred has been eliminated but the disease may affect other dog breeds, although it has not been reported in cats.
Protein-losing enteropathy and nephropathy of the Soft Coated Wheaten terrier (SCWT)
A clinical syndrome unique to SCWTs has been characterized recently. Affected dogs present with signs of a PLE, or a protein-losing nephropathy (PLN), or both. Signs of PLE tend to develop at a younger age than PLN, and include vomiting, diarrhoea, weight loss, and pleural and peritoneal effusions. Thromboembolism may also develop.
A genetic basis is likely and, although the mode of inheritance is not yet clear, pedigree analysis has demonstrated a common male ancestor8. The disease is probably immune-mediated given the presence of inflammatory cell infiltration. A potential role for food hypersensitivity has been suggested, since affected dogs have demonstrated adverse reactions during provocative food trials, with alterations in antigen-specific faecal IgE concentrations.
Marked dilatation and dysfunction of intestinal lymphatics is the hallmark of intestinal lymphangiectasia. Leakage of protein-rich lymph from abnormal lymphatics into the intestinal lumen ultimately causes a PLE and hypoproteinaemia. Breed-specific lymphangiectasia is likely to be a primary disorder rather than secondary to lymphatic obstruction and is usually limited to the intestine although concurrent chylothorax may occur. It is usually considered a congenital abnormality, although clinical signs are not usually present from birth. The development of associated lipogranulomatous lymphangitis, superimposed on the congenital abnormalities, and is one potential explanation for it being a progressive disorder. The disease is most commonly seen in small terrier breeds (e.g., Yorkshire, Maltese), Rottweilers and the Norwegian Lundehund, suggesting a genetic predisposition.
The clinical manifestations of lymphangiectasia are largely attributable to the effects of the enteric loss of lymph. Other intestinal functions remain intact, and hypoproteinaemia may be present without diarrhoea. Signs of diarrhoea, steatorrhoea, profound weight loss and polyphagia are more typical, whilst vomiting, lethargy and anorexia are reported occasionally. Onset of signs may be insidious and signs may demonstrate an intermittent pattern. Ascites or subcutaneous oedema may develop if hypoproteinaemia is marked. Lymphangiectasia has been associated with granulomatous hepatopathy, and in Lundehunds with chronic gastritis and gastric carcinoma.
Gross findings at endoscopy include the presence of white lipid droplets or prominent mucosal blebs, which are likely the result of villus tip distension with chyle, and biopsies may be supportive of the diagnosis. However, full-thickness biopsies may be required in order to make a definitive diagnosis. At exploratory laparotomy, there is thickened small intestine, dilated lymphatics (in the mesentery and intestinal serosa), and occasionally adhesions, with scattered yellow-white lipogranulomatous masses 1-3 mm diameter. Characteristic histopathological changes include 'ballooning dilatation' of lymphatics not only in the mucosa but also the submucosa. The overall long-term prognosis is poor and patients usually eventually succumb to severe malnutrition, incapacitating effusions and intractable diarrhoea.
1. Houston DM et al. Risk factors associated with parvovirus enteritis in dogs: 283 cases (1982-1991). J Am Vet Med Assoc 1996;208:542.
2. German AJ, et al. Cytokine mRNA expression in mucosal biopsies from German shepherd dogs with small intestinal enteropathies. Digest Dis Sci 2000;45:7.
3. German AJ, et al. Immune cell populations within the duodenal mucosa of dogs with enteropathies. J Vet Intern Med 2001;15:14.
4. Lothrop Jr CD, et al. Immunological characterization of intestinal lesions in Basenji dogs with inflammatory bowel disease. Proceedings of the 15th ACVIM Forum, p. 662, 1997 (abstract).
5. Davies DR, et al. Successful management of histiocytic ulcerative colitis with enrofloxacin in two Boxer dogs. Aust Vet J 2004;82:58.
6. Hall EJ and Batt RM. Development of wheat-sensitive enteropathy in Irish setters-morphological and biochemical changes. Am J Vet Res 1990;51:978 & 983.
7. Garden OA, et al. Inheritance of gluten-sensitive enteropathy in Irish setters. Am J Vet Res 2000;61:462.
8. Littman MP, et al. Familial protein-losing enteropathy and protein-losing nephropathy in soft coated wheaten terriers: 222 cases (1983-1997). J Vet Intern Med 2000;14:68.
9. Breitschwerdt EB, et al. A hereditary diarrhetic syndrome in the Basenji characterized by malabsorption, protein losing enteropathy and hypergammaglobulinemia. JAAHA 1980;16:551.
10. Kolbjornsen O, et al. Gastropathies in the Lundehund. 1. Gastritis and gastric neoplasia associated with intestinal lymphangiectasia. APMIS 1994;102:647.