Chronic Diseases of the Intestinal Tract Causing Diarrhea

6. Chronic Diseases of the Intestinal Tract Causing Diarrhea

Diseases that affect the intestinal tract can cause a range of clinical signs (Table 20). Diarrhea is the most common clinical signs and is defined as an increase in fecal water content with an accompanying increase in the frequency, fluidity or volume of feces.

Diarrhea may be due to SI, large intestinal (LI) or diffuse disease. Chronic diarrhea is rarely self-limiting and, in order to administer rational therapy, a definitive diagnosis is required. Diarrhea may be the result of a number of pathogenetic mechanisms (Table 21).

Diagnosis of Chronic Intestinal Diseases

A staged approach to diagnosis is usually recommended (Table 22).

• First, the diarrhea is defined as either small or large intestinal (Table 23)
• Intestinal parasitism is excluded (with fecal analyses)
• Empirical therapies are often used.

When a definitive cause has not been established, or cases do not respond, further diagnostics are justified (Table 22) including laboratory analyses (hematology, serum biochemistry, multiple fecal samples), diagnostic imaging and ultimately biopsy procurement.

Specific Small Intestinal Conditions

Small Intestinal Bacterial Overgrowth (SIBO) and Antibiotic-Responsive Diarrhea (ARD)

SIBO is defined as an increased number of bacteria in the upper small intestine, and is the cause of much recent controversy. SIBO is well documented in humans and almost invariably develops secondary to an underlying cause.

Therefore, it should be viewed more as a sign than a specific diagnosis. Recently, the term secondary SIBO has been used for cases which arise as a result of an underlying disorder e.g., partial obstruction, EPI, motility disorder, reduced gastric acid production (gastric surgery, gastric achlorhydria or drug therapy with antacids), and possibly, IBD. The previously described "idiopathic SIBO" is now more commonly referred to as "antibiotic-responsive diarrhea", given the uncertainty as to the underlying pathogenesis. This occurs in young dogs (especially German Shepherds) with a predominance of small intestinal diarrhea and weight loss/stunting. The clinical signs are antibiotic responsive.

Diagnosis for secondary SIBO involves identifying the underlying cause; none of the currently available tests are ideal for the diagnosis of idiopathic ARD, and diagnosis is based upon exclusion of all other causes and response to antibacterial therapy. Secondary SIBO is best controlled by treating the underlying cause (if possible), though antibacterials may be required if response is suboptimal. Long courses (and some times lifelong) antibacterials is the mainstay of treatment for ARD. Other medical therapies include parenteral cobalaminsupplementation, if cobalamin deficiency is identified.

German Shepherds show a breed predisposition for idiopathic antibiotic-responsive diarrhea. (© Hermeline).

Dietary Management of SIBO/ARD

In light of the unknown etiology of the disease, dietary treatment should be considered adjunctive rather than definitive therapy. The diet should have a high digestibility, so that can be effectively absorbed and utilized by the dog. High digestibility supports the patient by providing available nutrients, and reduces the potential load of antigenic material. By providing highly digestible diets, the flux of nutrients into the colon is reduced. These nutrients would be utilized by the colonic microflora with negative effects as gas formation, flatulence and diarrhea. In cases where dietary sensitivity or allergy cannot be excluded, an antigen-limited hypoallergenic diet is recommended. The diet can either contain a highly digestible protein source (e.g., chicken, fish, and wheat gluten) or any other highly digestible meats not normally used in commercial diets (e.g., rabbit, venison). Alternatively, a hydrolyzed protein diet may be suitable. Even in cases that are not etiologically linked with allergy or sensitivity a high digestible diet can be expected to support the patient.

Psyllium grains are a source of non fermentable, soluble fiber with a strong hygroscopic power. These benefits are very useful for regulating intestinal transit in diarrhea or constipation.

Diets for patients with small intestinal bacterial overgrowth should contain carbohydrate sources that are highly digestible in the small intestine. Most carbohydrate sources will fulfill the requirements as long as the starch is adequately processed by thermal treatment (cooking, extrusion). Rice is the cereal that contains the lowest level of fiber and it is considered as the most digestible starch source (Figure 9).

Figure 9. Comparison of starch and dietary fiber contents in cereals used in dog food. The minimum indispensable fiber for good transit and to avoid prolonged stasis in the large intestine is provided by the combination of corn, purified cellulose and beet pulp.

The concentration of dietary fiber has to be adjusted according to the requirements of the patient. Usually it is recommended to start with a low fiber type of diet (<3% crude fiber or 6% total dietary fiber DMB). Depending on the clinical outcome, it may be necessary to increase the fiber concentration by adding small amounts of insoluble or soluble fiber sources. Adequate feedstuffs are small amounts of cellulose, carrots, beet pulp or psyllium. (See Chapter 1 for more on dietary fiber.)

It may be advisable to adjust energy intake according to the needs of the patient. Many patients with small intestinal digestive problems suffer from malabsorption and resulting deficiencies. Weight loss and poor coat and skin quality are major problems that must be treated by increasing the density of certain nutrients in the diet. Fat concentration in a diet for patients with small intestinal disease has to be considered from two sides.

• On the one hand, fat can be used effectively to increase dietary energy density.
• On the other hand fat can induce problems (due to the bacterial conversion of non absorbed fatty acids and bile acids into hydroxylated fatty acids and deconjugated bile acids, respectively) that may cause hypersecretion and aggravate clinical signs of diarrhea.

Therefore, the level of fat tolerated by dogs with SIBO/ARD needs to be evaluated according to individual needs. In cases that have experienced severe weight loss, it is justified to test increased intakes of dietary fat as long as the clinical condition is not negatively affected. In many chronic intestinal diseases, a high level of fat (20% of crude fat in a dry diet, supplying more than 40% of the calories) is very well tolerated by the dogs. This may be explained by the presence or absence of bacteria that are able to metabolize fatty acids and bile acids.

Role of Probiotics and Prebiotics

Probiotics and prebiotics have been suggested as treatment options for patients with intestinal problems.
A probiotic is a living organism that is administered orally, and exerts health benefits beyond those of inherent basic nutrition. In theory they are "beneficial" bacteria that colonize the intestine at the expense of harmful bacteria. Their exact mechanism of action is not known and the identification of suitable bacteria for dogs is still in progress. However, two strains have been recently approved by the European authorities as feed additives in complete dog food: Lactobacillus acidophilus and Enterococcus faecium. A probiotic containing a strain of Lactobacillus acidophilus was successfully incorporated into canine diets, and improved recovery from clinical Campylobacter infection (Baillon et al., 2004). More work would be required to determine whether there would be similar effects in SIBO/ARD.

Prebiotics are substrates for "beneficial" bacterial species, which cause alterations in the luminal microflora. The aim is to offer a substrate to certain beneficial members of the gut flora and by this to achieve a shift in the composition of the gut bacteria in favor of a "healthy" flora. Therefore, they work in a similar or supportive way to probiotics. Prebiotics are non-digestible carbohydrates that can be used by several gut bacteria. Lactulose and certain types of dietary fiber with moderate bacterial fermentability can be used. Examples include several carbohydrates with different chain length: inulin and different oligosaccharides (fructo-oligosaccharides, galacto-oligosaccharides, mannan-oligosaccharides). There is currently no convincing evidence that such feed additives and feed compounds are beneficial in dogs with SIBO/ARD, and further work is required before their use can be recommended (Willard et al., 1994; Zentek et al., 2002; Guilford & Matz, 2003).

Adverse Reactions to Food

Adverse food reactions are an extremely common cause of chronic gastrointestinal disease and can be divided into non-immunologically mediated "food intolerance" and immunologically mediated "food allergy" (or hypersensitivity) (Table 24). Clinical signs may effect more than one body system, but most common are dermatological signs (e.g., pruritus) (See Chapter 2), and gastrointestinal signs (e.g., vomiting and diarrhea ). The gold standard of diagnosis involves response to exclusion diet and subsequent challenge (See Chapter 2).

The gut mucosa is exposed to numerous exogenous factors and has differentiated regulatory mechanisms which enable selective permeability for nutrients and certain macromolecules but also exclusion of potentially harmful dietary, environmental or bacterial antigens. Discrimination of absorption and exclusion, tolerance and reactivity results from complex regulatory processes that depend on the age of the individual, the functional and regulatory mechanisms of the immune system and the influence of exogenous factors. The interaction between luminal factors of dietary or bacterial origin and the gut wall is of particular importance. Exogenous food antigens, e.g., peptides, glycoproteins and lectins, but also microorganisms have the ability of interacting with the gut wall and to induce reactions and regulatory and counter regulatory processes. The interaction of luminal factors with the gut wall influences digestion (secretion, absorption, motility), immunological mechanisms (exclusion of antigens, regulation of the GI immune system, antigen processing, sensitivity, allergy), and neuro-endocrine processes.

Nutrition has a significant impact on the gastrointestinal tract of puppies and is of special importance for the function of the gut and the associated immune system during the early growth phase and later in adulthood. If animals are sensitized, reducing the exposure to potential allergens seems to be an important prerequisite for clinical improvement.

Dietary Management of Adverse Reactions to Food

Dietary management of adverse reactions to food can be difficult in practice because clinical signs can be slow to respond, and the animal will remain at risk of recurrence if dietary indiscretion occurs. Therefore, good owner compliance is essential if long-term success is to be ensured. Because of the difficulties in deciding whether the underlying reason is a dietary allergy or unspecified dietary intolerance without allergic etiology, dietary protocols should follow a standard model. In this regard, the diet should have a balanced nutrient composition, high digestibility in the small intestine and a restricted number of ingredients. Such a diet will support the patient because it facilitates the digestion and absorption of essential nutrients and helps to reduce the amount of potential antigens in the GIT. These goals can be achieved by using:
- Home prepared diets;
- Commercial diets with single or a limited number of protein sources; or
- Hydrolyzed protein diets.

Even in those cases where the dietary intolerance is not linked to a specific protein or ingredient, a dietary change can be helpful because the new diet may have a beneficial impact on the intestinal digestive processes and it may also influence the intestinal microflora. Such a change may limit growth of potentially harmful microorganisms, and reduce the concentration of microbial metabolites in the gut. Although it has not yet been proven that microbial metabolites can have negative impact on the health of dogs with dietary intolerance, this concept seems to work in practice.

In all cases of dietary intolerance, veterinarians should obtain a complete overview of the dietary history of the patient. In this regard, the clinician should ask detailed questions on the dietary history, including information on the usual diet(s) fed and on all treats or table scraps that are fed. In some cases it is possible to identify problematic food components which can then help when formulating an elimination diet or selecting adequate diets from a commercial source. When it is not possible to identify the offending compound, the choice of initial elimination diet will depend upon the history of ingredients fed to that individual.

When a diet has been selected, it should be fed as the sole source of nutrition for sufficient time to determine whether a positive response will occur. The ideal duration of such a diet trial has not been determined. Some recommend up to 3 months, especially for dermatological cases. However, GI signs will often resolve more quickly, and owners of patients with diarrhea rarely have that degree of patience. Therefore a trial length of ~3 - 4 weeks seems appropriate for most GI cases.

If a positive response is documented, food provocation trials can be performed to identify the exact causal protein(s) i.e., single proteins are added sequentially to the diet for 7 days at a time. If no response occurs the ingredient can be deemed safe; however, if signs recur the ingredient should be avoided in the future. However, this is laborious and many owners elect not to pursue provocation if the elimination diet works (Willard et al., 1994; Zentek et al., 2002; Guilford & Matz, 2003).

Diets Containing Single Sources of Protein and Carbohydrate

Choice of Protein

Meat, poultry and fish are usually used as a source of protein in exclusion diets. Suitable foods include chicken, turkey, venison, rabbit, duck or lamb. Although lamb has commonly been used, the widespread use of lamb protein in commercial diets would make this choice less suitable. Fish is an excellent choice because it is an uncommon ingredient in commercial diets. Vegetable protein sources may be used in as long as they are properly processed (e.g., isolated soy protein).

Many foodstuffs that are used as a source of carbohydrates also include significant amounts of protein, and this could complicate the elimination test.

Gluten proteins from cereals (e.g., wheat - Figure 10 - and barley) have been investigated extensively because they can cause dietary allergy (including celiac disease) in humans, and have the potential to cause similar problems in companion animals. Therefore, this carbohydrate source may be unsuitable for some patients with dietary intolerance. However, given their high digestibility, it may be worth considering their use in patients that are not specifically sensitive to them.

Figure 10. Wheat gluten. Wheat gluten is a highly concentrated protein source (80 - 82% protein) with exceptional digestibility. It is used in hydrolyzed form as a milk protein substitute in neonatal food.  

Another problem may result from other ingredients that are commonly used in a complete balanced diet. For instance, fat sources may contain small amounts of proteins, either animal or plant derived. Although oils or fats may contain only traces of proteins, it cannot be excluded that this may affect the result of the feeding trial.

Wheat gluten is a complex mix of proteins from two different families: the prolamines and glutenins.
It is obtained through traditional milling methods: cleaning to eliminate wheat flour and bran, steeping to eliminate the germ, grinding and centrifugation to separate the solid non-soluble part (the gluten) from the starch and other soluble substances. The remaining solid part, without the fiber and starch, is dried to obtain a powder: gluten.

Wheat gluten has many nutritional qualities that make it an exceptional source of protein. It is a highly concentrated source of protein (80% - 82%), it is free of biogenic amines, has a very low dietary fiber level and excellent ileal digestibility (99%).

Accordingly, using significant quantities of wheat gluten helps reduce the flow of indigestible proteins into the colon by 20% to 40%.

Wheat gluten is also a rich source of glutamine (almost 40%). This amino acid has an important role in maintaining digestive integrity, in conserving muscle mass during intensive activity and in taurine homeostasis in the event of illness or stress. Glutamine is involved in protein synthesis and constitutes a precursor of nucleic acids.

These different qualities rationalize the use of wheat gluten as a dairy protein substitute (over 99% digestible) in neonatal food.

Carbohydrate Source 

A single source of carbohydrate is also recommended for the elimination diet. Suitable ingredients include corn, potato, rice and tapioca. Cereals are often avoided given the concerns over gluten proteins. However, given that such sources are often highly digestible, such a carbohydrate source may still be suitable for many cases.

Minerals and Trace Elements

Minerals and trace elements have to be added to the main ingredients to make it complete and balanced. However, some sources of mineral salts could contain small amounts of protein, which might itself provoke an adverse reaction. Supplementation of a diet with vitamins can also be problematic, since some of the commonly used vitamins are protected by encapsulation with gelatin (usually derived from beef or pork). Although the production process is rigid and most of the potentially antigenic epitopes are destroyed, traces of proteins or peptides could still be introduced into a diet. These problems are of relevance for home-prepared diets as well as for commercial prescription diets. If this is a significant concern, one option is to use a home-prepared diet that is based on a minimum of dietary ingredients. Adult dogs will tolerate this for a few weeks without developing severe nutrient deficiencies. However, diets need to be balanced and complete if they are fed for longer than a few weeks. Commercially prepared pet foods offer the advantage of being nutritionally balanced from the beginning.

Diets Containing Single Hydrolyzed Proteins

In the last few years diets with hydrolyzed protein sources have became available. In these diets the protein is treated enzymatically to alter its structure (Figure 11).

Figure 11. Acquisition of protein hydrolysate.

Given their small size, these peptides are in theory less likely to interact with the immune system, and recent work has demonstrated reduced in vitro antigenicity compared with the native molecule (Cave & Guilford, 2004). Nevertheless, more work is required to confirm that these diets are truly "hypoallergenic". Hydrolyzed protein diets have already been used successfully in the production of diets for babies with milk allergy. A hydrolyzed diet is likely to be beneficial in patients with true food allergy (especially type 1), but whether there is any benefit in non-immunological food intolerance, is less clear. Given their high digestibility, these diets are likely to benefit patients with a variety of different gastrointestinal disorders, and recent clinical trials have been encouraging (Dossin et al., 2002; Mandigers & Biourge, 2004). Therefore, hydrolyzed diets offer an alternative for patients when single protein source or restricted antigen diets do not work.

Gluten-sensitive Enteropathy (GSE)

GSE is a specialized type of food sensitivity caused by an adverse reaction to gluten (wheat protein). It has been described in certain lines of Irish setters, although it is an extremely uncommon diagnosis in clinical practice. The pathogenesis has been better defined in recent years (Garden et al., 2000), although it is unclear whether an aberrant immune response to gluten, a direct toxic effect of the gluten, or both is involved. The clinical condition has similarities with human celiac disease, but the pathogenesis is different. Diagnosis can be made in a similar manner to other dietary sensitivities, and treatment involves feeding a gluten-free diet (i.e., avoid wheat, rye, barley, oats and tritical which is a wheat-rye hybrid). Rice and corn do not contain gluten. Interestingly, many Irish setters that are affected when young grow out of the condition in adulthood. The extent to which gluten is a potential allergen in other breeds is not known. Given that the frequency of adverse reactions to food are usually related to the frequency with which the protein is fed in com-mercial diets, there is no reason to suspect that dogs are especially sensitive to wheat proteins. Therefore, the need to avoid gluten in every case with an adverse food reaction is questionable.

Irish Setter with gluten enteropathy.

Inflammatory Bowel Disease (IBD)

IBD defines a diverse group of intestinal disorders, which are characterized by inflammatory mucosal changes (both architectural abnormalities and cellular infiltrates) without a known inciting cause. Therefore, diagnosis requires that there is histological evidence of inflammation, and that all potential causes for inflammation be excluded e.g., endoparasites, dietary sensitivity, ARD. IBD is usually classified on the basis of the predominant infiltrating cell type; lymphocytes and plasma cells are most commonly seen (lymphocytic-plasmacytic enteritis; LPE), whilst eosinophilic pre-dominance (eosinophilic enteritis; EE) is noted in a few cases. Many cases have a generalized increase in many immune cell subsets and cannot easily be classified into one histological group.

Gluten Enteropathy in the Irish Setter

This is not a gluten "allergy". Although often used by owners this term is inaccurate.

The disease manifests itself in clinical signs generally associated with chronic small intestinal pathology including diarrhea, wasting and delayed growth. It is a rare hereditary disease that primarily affects certain lines of Irish Setters.

Humans suffering from celiac disease are said to be gluten-intolerant, but in reality they are gliadin-intolerant. This is a chronic disease whose symptoms vary from light, non-specific digestive complaints to severe malabsorption (severe diarrhea).

Celiac disease depends on the exposure of genetically sensitive individuals to one specific gluten protein, gliadin. The cause is a defect in intestinal permeability that allows antigens in the intestinal lumen to traverse the mucosa.

Clinical symptoms:
- Intermittent or chronic diarrhea at an early age, between 4 and 7 months
- Weight loss
- Malabsorption

Treatment: a gliadin-free diet (wheat, barley, oats, rye, triticale, which is a wheat-rye hybrid).

Such classification is often arbitrary, and depends upon the opinion of the pathologist concerned. Other types of IBD (e.g., granulomatous enteritis) are rare in dogs. Moderate to severe changes are often associated with protein-losing enteropathy (PLE) (see below).

The underlying etiology of canine IBD is unknown, and comparisons have been made with the human counterparts where a breakdown of immunological tolerance to luminal antigens (bacteria and dietary components) is thought to be critical. Antigens derived from the endogenous microflora and (possibly) dietary antigens are likely to be important in disease pathogenesis, whilst a potential role for diet-related factors is suggested by the clinical benefit of dietary therapy in some cases of canine IBD.

Alterations in immune cell populations in canine LPE have been documented, including increases in lamina propria T cells (especially CD4+ cells), IgG+ plasma cells, macrophages and granulo-cytes (German et al., 2001). Marked increases in mucosal cytokines have also been documented in canine LPE, with increased expression of Th1 (IL-2, IL-12 and IFNγ), Th2 (IL-5), proinflammatory (TNF-α) and immunoregulatory (TGF-β) cytokines (German et al., 2000). This suggests immune system dysregulation in dogs with IBD, but does not confirm how this has arisen. The pathogenesis of eosinophilic enteritis (EE) has not been studied in detail, but similar mechanisms may exist to those suggested for LPE. EE must be differentiated from other diseases that can cause increases in eosinophil number such as endoparasitism and dietary hypersensitivity.

In dogs, the most common clinical sign is chronic small bowel diarrhea, which can be accompanied by weight loss and vomiting. Owners often mention that the gastroenteritis symptomatic periods become more and more frequent, month after month. If PLE is severe, there may be signs of ascites and/or subcutaneous edema (especially if total serum/plasma protein and albumin concentrations are low), whilst other clinical sequelae can occur including systemic immune-mediated disorders and, exceptionally, thromboembolism. Diagnosis is usually made by histopathological assessment of intestinal tissue by endoscopic or exploratory laparotomy, after having eliminated other potential causes with a thorough diagnostic work up (Table 22) (Figure 12a and Figure 12b).

Figure 12a. Endoscopic lesions classically encountered in chronic intestinal inflammatory disease. Duodenitis. View from a portion of the proximal duodenum. Note the erythematous coloration and increased granularity. (© V. Freiche).

Figure 12b. Endoscopic lesions classically encountered in chronic intestinal inflammatory disease. Endoscopic appearance of the stomach mucosa illustrating a cobble-stoned appearance due to a parietal infiltration of an inflammatory nature. (© V. Freiche).

Given the variability in interpretation of pathological changes in intestinal biopsies between pathologists, a world small animal veterinary association (WSAVA) working party is currently in the process of defining standardized criteria.

Treatment often involves a combination of therapies including dietary modification, antibacterials and immunosuppressive medication. If clinical signs are stable and sequelae not too severe (e.g., PLE), treatment trials should first be instigated with dietary modification and with antibacterials (see above). Immunosuppressive medication should only be used when other treatments fail. In this way cases that are truly idiopathic in nature can be discerned from food-responsive and antibiotic-responsive conditions.

Alimentary Lymphoma

The most common malignancies in dogs are lymphoma, epithelial tumors and smooth muscle tumors. However, other types of neoplasia can occur including fibrosarcoma, haemangiosarcoma and plasma cell tumors.

Lymphoma is characterized by mucosal and submucosal infiltration with neoplastic lymphocytes, which can then lead to clinical sequel. Lymphoma can either present in a diffuse manner, infiltrating large areas of intestinal wall, or can present as a focal mass lesion. Diffuse forms affect digestive and absorptive processes and lead to malabsorption and protein losing enteropathy (PLE). In contrast, focal forms can cause complete or partial obstruction of the intestine. The etiology in dogs is not known. LPE is reported to progress to lymphoma, and lymphoma can also co-exist with LPE within adjacent regions of small intestine. However, given discrepancies in histopathological interpretation, it is not clear whether these theories are genuine or are the result of initial misdiagnosis of lymphoma.

Treatment of lymphoma involves standard combination chemotherapy protocols, based on prednisolone, cyclophosphamide and vincristine. However, the disease is usually rapidly progressive, and the majority of patients respond poorly to therapy. In the minority of cases that do respond dietary management may form a useful adjunct (See Oncology Chapter 13). If gastrointestinal signs are severe, changing to a highly digestible diet may be of benefit. The concurrence of cancer cachexia may require a diet with increased energy density.

Protein-losing Enteropathy and Lymphangiectasia

Protein-losing enteropathy (PLE) is the term used to describe an intestinal disease that is accompanied by marked loss of plasma proteins through the gastrointestinal tract. When the hepatic capacity for protein synthesis is exceeded serum protein concentrations (both albumin and globulin) fall. The situation can be confounded by the concurrence of protein malabsorption with many of these conditions. Reductions in circulating protein concentrations (especially albumin) lead to reduced plasma oncotic pressure, and severe reductions (e.g., albumin <1.5 g/dL) lead to clinical consequences (e.g., ascites, subcutaneous edema, intestinal wall edema etc).

Dietary Management of Inflammatory Bowel Disease (IBD)

An elimination diet may discriminate adverse food reactions, and benefit IBD cases because these diseases can occasionally be secondary to mucosal inflammation. Thus a dietary change might be beneficial even if there is no proven sensitivity against the current protein ingredients. Changing to a diet that is highly digestible is also beneficial.

Another relevant factor is fat restriction or modification of the fat source. The response of dogs to dietary fat cannot be predicted. Some patients may benefit from a low-fat diet because fatty acids can be hydroxylated in the GIT by certain bacteria. Hydroxylated fatty acids can induce secretory diarrhea. Conversely, fat restriction means that the diet contains higher amounts of either proteins or carbohydrates.

When the digestive processes are impaired due to the inflammation of the gut wall, the absorption of amino acids, peptides and carbohydrates can be reduced. Low-fat diets will have reduced energy densities compared to standard products. A study on ten IBD patients demonstrated that a high-fat dry food (20% fat) can help improve fecal consistency, resolve vomiting and improve body condition (Lecoindre & Biourge, 2005). The effectiveness of the nutritional treatment is also explained by the choice of high-quality; highly-digestible proteins to minimize protein indigestion and consequently reduce the production of toxins by putrefying bacterial flora.

Suitable fat sources include vegetable oils, poultry fat and fish oil. Fish oil offers the advantage of a high percentage of long chain omega-3 fatty acids (EPA-DHA). These fatty acids may have some beneficial effects due to their anti-inflammatory activities.

Probiotics and prebiotics may be used as ingredients or additives in these patients. Many practitioners prescribe live yoghurt and other probiotic supplements, although these have not been fully evaluated in dogs and the clinical benefits in cases with IBD need to be identified. There is some evidence that probiotics and prebiotics can be helpful in managing chronic IBD in humans (Willard et al., 1994; Zentek et al., 2002; Guilford & Matz, 2003).

The causes of PLE are listed in Table 25; the three most important conditions are IBD, lymphoma and lymphangiectasia. However, there has also been a recent report of PLE associated with intestinal crypt lesions, without evidence of lymphangiectasia or inflammation in most cases (Willard et al., 2000). The underlying etiology of such lesions is not known. Response to therapy, with antibacterials and immunosuppressive medication is variable. Some dogs deteriorate suddenly and can die from thromboembolic disease. However, malnutrition is the most significant problem.

Yorkshire Terriers, soft-coated Wheaten Terriers and Rottweilers are predisposed to lymphangiectasia. (© Y. Lanceau).

A very high quality protein source is vital for patients with protein-losing enteropathy (cottage cheese, cooked chicken or turkey meat, boiled eggs). The protein intake should be adjusted to achieve if possible a normalization of the serum protein levels.

Intestinal lymphangiectasia is characterized by the abnormal dilatation and dysfunction of lymphatic vessels within the mucosa and submucosa. It may be primary (localized or generalized lymphatic abnormality) or secondary (e.g., to lymphatic obstruction). Such an obstruction can be within the intestine (i.e., neoplastic infiltration, inflammation or fibrosis) or systemic (e.g., right-sided cardiac failure, caval obstruction or hepatic disease). The lacteal dilatation is associated with exudation of protein-rich lymph into the intestine, and severe lipid malabsorption. As a result, severe hypoproteinemia or lymphatic flow disturbances result in ascites, subcutaneous edema and chylothorax.

Treatment for secondary lymphangiectasia involves rectifying (if possible) the underlying cause e.g., right-sided cardiac failure. For primary lymphangiectasia, treatment is usually supportive and symptomatic. This involves decreasing enteric protein loss (see below), resolving associated inflammation and controlling edema or effusions. Glucocorticoid therapy may benefit some cases especially if the disease is secondary to an inflammatory cause e.g., IBD. Adjunctive therapy with metronidazole or tylosin may also be of benefit. Finally, diuretics are indicated in the management of effusions and combinations of diuretics are preferred (e.g.,  furosemide and spironolactone). Intravenous administration of plasma or colloid may also help if hypoproteinemia is marked. The prognosis is most cases is guarded, and response to therapy is usually poor in most cases.

Dietary Management for Lymphangiectasia

The nutritional treatment of patients with lymphangiectasia is based on the application of foods with a low-fat concentration. Low-fat diets seem to be helpful in counteracting the pathophysiology in lymphangiectasia. However, patients with this type of intestinal disease need to be supplied with adequate amounts of essential fatty acids, e.g., linoleic acid.

Previously, medium-chain triglycerides were recommended since they were though to be absorbed directly into the portal blood circulation, therefore bypassing the lymphatic system. However, recent studies have contradicted this mechanism, and suggested that this lipid group is absorbed via lymphatics. Furthermore, high doses of medium-chain fatty acids can have negative effects in dogs and may induce vomiting and diarrhea. Therefore the use of these nutrients cannot be recommended.

Supplementation with fat-soluble vitamins is advised, and there are anecdotal reports of improvement with glutamine supplementation (Willard et al., 1994; Zentek et al., 2002; Guilford & Matz, 2003].