Nutrition mainstay to success

Q. Could you provide an update on protein-losing enteropathies (PLE) dietary therapy for dogs?

A. Dr. Debra L. Zoran at the 2007 American College of Veterinary Internal Medicine Forum in Seattle lectured on dietary therapy of PLE and severe inflammatory bowel disease (IBD) in dogs. Some relevant points are provided here.

Protein-losing enteropathies (PLE) are a spectrum of diseases occurring primarily in dogs that manifest in non-specific protein loss through the gastrointestinal tract. Although commonly called an enteropathy, the protein loss can occur through the stomach, small intestine or large intestine.

Primary causes of protein-losing enteropathies

Protein-losing enteropathies can be primary (e.g., genetic or heritable disorders such as those that occur in Soft-Coated Wheaton Terriers or Basenjis) or secondary to another problem. From the lists of common diseases associated with protein-losing enteropathies in dogs (p.11S), particularly of note are any of the gastroenterides, lymphangiectasia and IBD. Therapy of these diseases should be aimed at treatment of the primary problem, but nutritional therapy is an essential aspect of success.

Inflammatory bowel disease (IBD)

First, remember that there are many causes of GI inflammation. Just finding lymphocytes and plasma cells or eosinophils on an intestinal biopsy does not confirm IBD, which is a chronic, idiopathic disease of the intestinal tract that has no identifiable cause.

In addition to finding inflammatory infiltrates in the GI mucosa, thorough elimination of the other causes of intestinal inflammation (e.g., dietary intolerance/allergy, bacterial enteritis) is warranted. Because a diagnosis of IBD is a concession that only symptomatic therapy remains, the long-term prognosis is more guarded than if a diagnosis and specific therapy are known.

Finally, if a specific treatment can be employed, avoidance of high doses of anti-inflammatory or immunosuppressive drugs (with substantial short-and long-term side effects), or at least the use of smaller doses for a shorter time, may be possible.

Lymphocytic plasmacytic enteritis (LPE) is primarily a disease of middle-aged to older dogs, and is uncommonly seen in young dogs. It is well-known that the gut is a massive immune organ — responding to a large number and variety of foods, bacteria, parasites and other antigens every day. Therefore, it is not surprising that the response to exposure to some of these antigens is increased numbers of lymphocytes and plasma cells, or even other cell types such as eosinophils.

At this time, it is impossible to distinguish the primary cause of these inflammatory infiltrates in the gut wall. Thus, appropriately performed food trials to eliminate adverse reactions to foods as the cause of the infiltrate are essential. An appropriate food trial may require at least six to eight weeks to achieve reversal of signs. It takes two to three weeks for the body to remove old antigens and more time is necessary for the body to resolve the inflammatory lesions. It is reasonable to use anti-inflammatory doses of prednisone during this time, but the dose should be tapered over several weeks. Use the diet response to gauge the real effect of the therapy.

Possibly the most difficult and important aspect of conducting a food trial to rule out food allergy as the cause of gut inflammation is the dietary history. Many over-the-counter pet foods contain a wide variety of protein sources, so it can be quite difficult to identify a commercial diet that is truly novel. For this reason, many veterinarians have used hydrolyzed protein diets as their trial diet in the hopes that the hydrolysates will have low immunogenicity.

Unfortunately, making the proteins smaller does not prevent the epitopes that are responsible for activating the immune reaction from being exposed. In fact, in humans, hydrolysates can be even more antigenic in some children, resulting in anaphylaxis and other hypersensitivity reactions. Further refinement of proteins (into elemental amino-acid forms) will be required to completely eliminate this problem. In addition to problems with persistent antigenicity, hydrolyzed protein diets may have changes in taste and digestibility, and as the proteins are hydrolyzed into smaller and smaller forms, the osmolarity of the diets increases, which has been blamed for causing diarrhea in humans and pets.

Finally, it is important to recognize that different commercial products contain different sources of protein hydrolysate — and it has been shown that, while not all animals known to be allergic to a protein will react to the hydrolyzed version of that protein, at least 20 percent will — thus illustrating the limitations of using these diets as the definitive means of ruling out an adverse reaction to food.

Nevertheless, because novel protein diets have been proven effective in dogs with IBD, and because hydrolyzed diets have the advantage of not sensitizing the dog to a new protein during the initial treatment phase, they are a very reasonable choice for a dog with IBD.

Many dogs with severe intestinal disease, and especially IBD, have cobalamin deficiency — which can be associated with persistent diarrhea and lack of response to therapy. Cobalamin deficiency is corrected by replacement with injectable cyanocobalamin at a dose of 25 mcg/kg once weekly for four to six weeks and then once monthly thereafter, as needed to maintain normal serum levels. In dogs with true IBD that require life-long therapy to control their signs, it is possible they will require life-long cyanocobalamin injections as well. It may take as long as three to four weeks, once starting appropriate therapy, to see any response, so it is important to be patient and not expect an immediate response.

Protein-losing enteropathies (PLE)

Protein-losing enteropathies (PLE) comprise a complex group of gastrointestinal (GI) diseases, causing severe loss of proteins (especially albumin and similar-sized proteins) from the GI tract. PLE's common clinical signs include anorexia, weight loss and small-bowel diarrhea. PLE can be a primary disease entity, such as the disorders that occur in Yorkshire Terriers, Basenjis, Lundehunds and Soft-Coated Wheaten Terriers, but is most often secondary to a wide variety of diseases and disorders of the small bowel (e.g., lymphangiectasia, infiltrative diseases of the bowel and IBD). One of the most challenging aspects of PLE therapy is selection of an appropriate diet.

The initial treatment for dogs diagnosed with severe PLE may require aggressive intravenous therapy for correction of the hypoalbuminemia, electrolytes and mineral abnormalities. Plasma or hetastarch (or other colloid) therapy (10-20 ml/kg) often is administered to provide both plasma proteins and coagulation factors in dogs that are severely edematous or who are hypercoagulable (e.g., have significant risk of developing pulmonary/venous thromboembolism) from low antithrombin levels.

Alternatively, total parenteral nutrition (TPN) may be initiated to provide a source of protein and energy, as well as to improve oncotic pressure. Nutritional support in the form of elemental diets may be required in dogs with severe PLE no matter what the cause, because the gut may not be able to appropriately digest or absorb the nutrients in polymeric (intact) diets.

There are a variety of human enteral nutrition supplements that can be used, but a low-fat, lactose-free diet is preferred (e.g., Vivonex TEN). Most other human elementals are not low-fat, and therefore not good choices for PLE dogs. Vivonex alone should only be used as a short-term diet because it is too low in protein to support the nitrogen and amino-acid requirements of dogs (and especially cats).

For long-term nutritional support using elemental diets, amino-acid supplements and vitamins should be added to provide a more balanced diet or they must be used in combination with another diet. In these dogs, a combination of the elemental diet with a hydrolyzed diet or a homemade, ultra low-fat, highly digestible diet may be effective. The hydrolyzed diets often are reasonable choices because they are low-fat and highly digestible, but not all animals do well on them. Homemade diets frequently are chosen for severe PLE dogs because they can solve several important therapeutic goals:

1) The protein source can be novel and highly digestible (e.g., turkey, venison, egg).

2) The amount of fat can be easily controlled (no-fat to ultra low-fat) — which is extremely important for PLE management.

3) They are usually highly palatable.

Dogs with less severe hypoalbuminemia (e.g., serum albumin greater than 1.5 and less than 2.0 g/dl) often can be started on a commercial diet designed for GI disease. The key to dietary management of PLE is finding a diet that is low in fat, highly digestible and well tolerated (e.g., does not cause diarrhea), but allows the gut to absorb proteins presented.

Many of the ultra low-fat commercial diets contain increased dietary fiber, which is potentially detrimental to PLE dogs because the fiber will reduce the availability and digestion of proteins and carbohydrates in the small intestine. One ultra low-fat diet (less than 3 g/100 kcal) that does not contain high dietary fiber is Royal Canin/Waltham's Low Fat. This diet is a good choice in many dogs with mild to moderate PLE. Alternatively, two other highly digestible diets are reasonable choices because of their low-fat content (e.g., Purina EN, and Eukanuba Adult Low Residue); however, these diets may not be low enough in fat to be as effective.

The commercially available hypoallergenic diets designed for treatment of dietary intolerance or allergy may seem like reasonable options for dogs with PLE; however, the primary drawback is that they are not ultra low-fat diets. In fact, most have only modest reductions in fat content compared to normal diets. Thus, if a novel protein diet is needed for management of the disease (based on the histopathology), a homemade diet (using lean meat sources) or hydrolyzed diet is recommended, and they are highly digestible, low-fat and contain proteins in their peptide forms, which are more easily absorbed, even in the presence of significant GI disease.

In addition to dietary therapy for PLE, specific therapy is required to treat the primary cause (e.g., steroids for IBD, chemotherapy for lymphoma). In many cases of lymphangiectasia or idiopathic PLE, steroid therapy is initiated to reduce the immunologic component suspected to contribute to the ongoing clinical deterioration. Most dogs have some component of antibiotic responsive diarrhea and require metronidazole, tetracycline, tylosin or other long-term antibiotic therapy to control signs and prevent bacterial overgrowth. Supplementation with calcium, magnesium and fat-soluble vitamins often is required and should be used in cases where dietary therapy alone does not correct the imbalances.

Serum cobalamin levels should be measured, because cobalamin levels often decrease in animals with severe GI disease, and cobalamin is essential for growth and repair of the gut epithelium. However, in most cases, the most important aspect of therapy is finding an appropriate diet and providing the necessary additional supplementation.

For dogs with PLE that can be controlled with specific dietary and pharmacologic therapy, the long-term prognosis is fair to good. Nevertheless, the most severely affected dogs may not respond to therapy or relapse soon after the initial treatment and succumb to either complications or worsening PLE.

Johnny D. Hoskins

Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small-animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200 or e-mail: jdhoskins@mindspring.com