In the dog, diarrhoea represents a significant proportion of all visits to veterinary clinics. Acute-onset diarrhoea usually responds well to treatment against intestinal parasites, dietary modification and/ or symptomatic therapy; however, successful management of chronic diarrhoea is usually more challenging.

Chronic diarrhoea is a change in the frequency, consistency and volume of the dog’s faeces for more than three weeks. Starting in the small or large intestine, diarrhoea can be due to various reasons, 90% are primary intestinal (termed chronic enteropathy- CE) and the remaining 10% are secondary to another cause beyond the intestine such as EPI [1].

CEs are categorised according to response to treatments, here we shall consider the most common CEs: food responsive (FRE), antibiotic responsive (ARE) and immunosuppressant responsive enteropathy (IRE). The distribution is reported as FRE 64%, ARE 16.2% and IRE 19.2% [2]. It is always worth bearing this distribution incidence in mind when faced with cases of chronic enteropathy, as it forms the basis of diagnosis.

Terminology

The term immunosuppressant responsive enteropathy (IRE) is used interchangeably with steroid responsive enteropathy (SRE). This the closest entity to human Crohn’s disease (a variant of inflammatory bowel disease, IBD). Idiopathic IBD has also been used interchangeably with IRE, where inflammation is present on histology. Dogs not responding to treatment are categorized as having non-responsive enteropathy, NRE [3]. In addition to categorisation according to treatment response, dogs losing protein across the gut are typically grouped as protein losing enteropathies (PLE), highlighting the more guarded prognosis this type of CE holds [4].

Parasite infestation

Before embarking on further treatments, it is essential to rule out the presence of intestinal parasites. Fecal shedding of parasite ova or cysts is not continuous, three successive negative samples are needed to confirm the absence of parasites. Moreover, several protozoan parasites such as Giardia, may be difficult to detect. A “practical” approach is systematically administering a broad-spectrum anthelminthic drug to treat locally prevalent endoparasites (e.g., fenbendazole 50 mg/kg p.o. daily for 5 days).

Food responsive enteropathy

FRE is the most frequent cause of chronic diarrhoea in dogs [2]. An adverse reaction to food (AFR) is defined as “reactions to an otherwise harmless dietary component, which are experienced by certain individuals upon ingestion” [5]. AFR can be either food allergy (FA) or food intolerance (FI). FRE cases are typically younger than SRE cases and often present with large bowel signs [4].

• Food allergy FA

Not all FA experience diarrhoea- non seasonal cutaneous pruritus is the most common clinical sign of FA [6]. However, of the non-cutaneous signs, diarrhoea is the most commonly reported, with an incidence of 70-88% [7]. In true FA, an immunological reaction against one of the dietary components (allergen) is at the origin of the problem. This is usually the protein in the diet, 10-70kDa in size and heat, acid, protease stable [8]. Food allergy is IgE mediated [9]; despite this, investigation has found that serum IgE testing is a completely unreliable method of diagnosis of food allergy [10].

• Food intolerance

FI is an abnormal physiological response to a food or food additive. This is not due to an immunological phenomenon. Clinical signs reduce or disappear within 7-10 days after being fed exclusively a hypoallergenic diet. Often, when challenged with the original diet, symptoms do not recur [6]. Cutaneous signs are not seen with FI.

In all cases of suspected AFR, it is recommended to feed the dog with a hypoallergenic diet. This can either be a novel protein diet, or a hydrolysed protein diet. Here the proteins are broken down to a molecular level unrecognised by the host’s immune system. This novel diet should be maintained for at least 5 weeks, but more usually 8 weeks until full response can be assessed.

To confirm the diagnosis of FA and find out what exactly the dog is allergic to, it is necessary to perform a dietary challenge after 8 weeks with components of the original diet, and to wait for the recurrence of clinical signs. If pruritus was seen as a clinical sign, recurrence happens within 3-6hrs (23.9%) or 12hrs (60.9%) of the original food being fed [11]. Recent studies [10] have suggested that treatment with a short course of prednisolone at the beginning of an elimination diet trial can shorted then time period until rechallenge, and thus hasten the confirmation of diagnosis. Not many owners are keen to undergo the rechallenge aspect of diagnosis, and the true allergen often remains unidentified.

Some of the best options for elimination diets are made from hydrolysed protein sources. These include Royal Canin Hypoallergenic and Anallergenic. The hydrolyzation process breaks the protein molecules into shorter chains which are not recognized by the dog’s immune system and therefore do not spark an immune response. Most specialists prefer to recommend a hydrolysed diet as this lowers exposure to potential allergens (compared to a novel protein diet) which the dog may sensitise to in future.

Antibiotic responsive enteropathy

ARE is recognised as one form of CE, although the pathophysiology is not well understood. It is associated with intestinal microbiota dysbiosis, responds wonderfully to administration of antibiotics and recurs after they are withdrawn [12]. More common causes of CE should be ruled out (parasitic treatment and elimination diet) prior to instigating antibiotic therapy. This approach goes some way to helping to reduce the unnecessary overuse of antibtiotics, remembering ARE accounts for only 8% of CE cases [1]. The exact role of the antibiotic remains unclear, work is ongoing in studying possible local immunomodulatory effects of metronidazole [13]. However, the use of antimicrobials for non-antimicrobial effects is questionable and should be discouraged. There is ongoing concern of the unnecessary use of antibiotics leading to increases in resistant strains of bacteria emerging.

Younger large breed and GSDs are over-represented [2, 14]. GSDs may be predisposed to ARE due to insufficient production of immunoglobulin A [15]. French Bulldogs and Boxers can suffer from granulomatous colitis; this is the only CE in which bacterial invasion of the gut wall is seen and clinical signs resolve with the clearance of the bacteria using antibiotic therapy [16].

Metronidazole, oxytetracycline and tylosine are commonly used in cases of ARE [2, 17]. There is no data published determining the optimum duration of treatment, but 4-6 weeks is typically recommended. The dose or duration of treatment does not seem to correlate with time to relapse [17], which raises questions to the role the antibiotic actually plays in resolution. Interestingly, prednisolone has been found to be as effective as prednisolone combined with metronidazole in induction therapy of IBD [18] adding to the debate over the efficacy or necessity of antibiotics in these cases.

Antibiotic administration affects the diversity of the intestinal microbiota which may be detrimental and can take many weeks to be restored to normal [19]. The importance of the microbiota is being increasingly recognised in intestinal health and CE and strategies to alter the microbiota are of increasing interest. These include probiotics, prebiotics and faecal microbiota transplantation.

Immunosuppressant responsive enteropathy

Dogs which have failed to respond to either diet or antibiotic therapy are usually moved to immunosuppressive therapy. Initially prednisolone, with increasing dose or change to other immunosuppressants if no response is seen [17]. Other drugs used include azathioprine, budesonide and cyclosporin; remission rates are usually over 60% irrespective of treatment [17]. This response is short-term; long-term control with prednisolone is inadequate and not fully elucidated with other agents.

Dietary options

Irrespective of the nature of the enteropathy, all dogs will benefit from a specialised Gastro Intestinal diet. Royal Canin provides a full range. In cases of FRE a hydrolysed diet is recommended, such as Anallergenic or Hypoallergenic. Other CE cases benefit from the highly digestible ingredients used in RC GI diets, enabling optimal absorption in the inflamed intestine. Royal Canin GI diets contain a balance of soluble and insoluble fibre, including psyllium husk. Psyllium husk has been found to be effective in improving stool consistency, reducing frequency of defecation and weight gain in working dogs with chronic large bowel diarrhoea [21]. For cases of EPI Royal Canin GI low fat is recommended.

Conclusion

CE cases are classified according to their response to treatments. Trial treatments should be given in order of prevalence: FRE, ARE then IRE. Around 65% of CE cases will respond to dietary modification, thus this should always be the first treatment option before antibiotics or immunosuppressants are used.

References

1. Volkmann, M., et al., Chronic Diarrhea in Dogs – Retrospective Study in 136 Cases. J Vet Intern Med, 2017. 31(4): p. 1043-1055.
2. Allenspach, K., C. Culverwell, and D. Chan, Long-term outcome in dogs with chronic enteropathies: 203 cases. Vet Rec, 2016. 178(15): p. 368.
3. Dandrieux, J.R.S. and C.S. Mansfield, Chronic Enteropathy In Canines: Prevalence, Impact And Management Strategies. Vet Med (Auckl), 2019. 10: p. 203-214.
4. Allenspach, K., et al., Chronic enteropathies in dogs: evaluation of risk factors for negative outcome. J Vet Intern Med, 2007. 21(4): p. 700-8.
5. Cianferoni, A. and J.M. Spergel, Food allergy: review, classification and diagnosis. Allergol Int, 2009. 58(4): p. 457-66.
6. Gaschen, F.P. and S.R. Merchant, Adverse food reactions in dogs and cats. Vet Clin North Am Small Anim Pract, 2011. 41(2): p. 361-79.
7. Mueller, R.S. and T. Olivry, Critically appraised topic on adverse food reactions of companion animals (6): prevalence of noncutaneous manifestations of adverse food reactions in dogs and cats. BMC Vet Res, 2018. 14(1): p. 341.
8. Sicherer, S.H. and H.A. Sampson, Food allergy. J Allergy Clin Immunol, 2010. 125(2 Suppl 2): p. S116-25.
9. Mandigers, P. and A.J. German, Dietary hypersensitivity in cats and dogs. Tijdschr Diergeneeskd, 2010. 135(19): p. 706-10.
10. Favrot, C., et al., The usefulness of short-course prednisolone during the initial phase of an elimination diet trial in dogs with food-induced atopic dermatitis. Vet Dermatol, 2019. 30(6): p. 498-e149.
11. Shimakura, H. and K. Kawano, Results of food challenge in dogs with cutaneous adverse food reactions. Vet Dermatol, 2021.
12. Hall, E.J., Antibiotic-responsive diarrhea in small animals. Vet Clin North Am Small Anim Pract, 2011. 41(2): p. 273-86.
13. Shakir, L., et al., Metronidazole and the immune system. Pharmazie, 2011. 66(6): p. 393-8.
14. German, A.J., E.J. Hall, and M.J. Day, Immune cell populations within the duodenal mucosa of dogs with enteropathies. J Vet Intern Med, 2001. 15(1): p. 14-25.
15. Littler, R.M., R.M. Batt, and D.H. Lloyd, Total and relative deficiency of gut mucosal IgA in German shepherd dogs demonstrated by faecal analysis. Vet Rec, 2006. 158(10): p. 334-41.
16. Mansfield, C.S., et al., Remission of histiocytic ulcerative colitis in Boxer dogs correlates with eradication of invasive intramucosal Escherichia coli. J Vet Intern Med, 2009. 23(5): p. 964-9.
17. Dandrieux, J.R., Inflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same? J Small Anim Pract, 2016. 57(11): p. 589-599.
18. Jergens, A.E., et al., Comparison of oral prednisone and prednisone combined with metronidazole for induction therapy of canine inflammatory bowel disease: a randomized-controlled trial. J Vet Intern Med, 2010. 24(2): p. 269-77.
19. Manchester, A.C., et al., Long-term impact of tylosin on fecal microbiota and fecal bile acids of healthy dogs. J Vet Intern Med, 2019. 33(6): p. 2605-2617.
20. Guard, B.C., et al., Longitudinal assessment of microbial dysbiosis, fecal unconjugated bile acid concentrations, and disease activity in dogs with steroid-responsive chronic inflammatory enteropathy. J Vet Intern Med, 2019. 33(3): p. 1295-1305.
21. Alves, J.C., et al., The use of soluble fibre for the management of chronic idiopathic large-bowel diarrhoea in police working dogs. BMC Vet Res, 2021. 17(1): p. 100.
22. Lecoindre, P. and F.P. Gaschen, Chronic idiopathic large bowel diarrhea in the dog. Vet Clin North Am Small Anim Pract, 2011. 41(2): p. 447-56.
23. Kather, S., et al., Review of cobalamin status and disorders of cobalamin metabolism in dogs. J Vet Intern Med, 2020. 34(1): p. 13-28.
24. Berghoff, N., et al., Serum cobalamin and methylmalonic acid concentrations in dogs with chronic gastrointestinal disease. Am J Vet Res, 2013. 74(1): p. 84-9.
25. Werner, M., et al., Diagnostic value of fecal cultures in dogs with chronic diarrhea. J Vet Intern Med, 2021. 35(1): p. 199-208.