From intestinal parasites to irritable bowel disease (IBD), dietary indiscretion to food allergies, gastrointestinal issues are among the most common problems veterinarians see. While they might seem straightforward, they can be difficult to diagnose and treat for a number of reasons.
Chronic diarrhea and vomiting may not be brought to your attention until it has been going on for a while without improving or begins to worsen in severity. And, of course, diarrhea and vomiting can be seen with diseases unrelated to the GI tract. Once the GI tract is pinpointed as the source of the problem, the signs can still have many potential causes. Radiographs show only faint shadows of the intestines, making interpretation difficult.
Gastrointestinal problems can resolve on their own in three to five days, but when they don’t, additional diagnostics, therapeutic trials, and medication can be the next step. Fortunately for pets, owners, and veterinarians, more companies are beginning to develop drugs and run clinical trials specifically for cats and dogs with GI disease, says M. Katherine Tolbert, DVM, PhD, DACVIM, clinical associate professor of medicine at Texas A&M University College of Veterinary Medicine & Biomedical Sciences.
“There are a lot of new drugs that can help manage clinical signs associated with GI disease, such as dysrexia and vomiting,” she says. “This is relatively new for us in the veterinary profession. In the past, we have had to use drugs developed for humans and hope they work in cats and dogs. As you can imagine, this can be fraught with error, especially since their metabolism of drugs can vary dramatically from humans.”
Drug treatments are influenced by a variety of factors, such as severity of disease, whether it is progressive or intermittent, and where in the intestinal tract it is taking place. Potential side effects, patient factors, cost, and veterinarian preference based on experience must be considered as well.
For chronic disease, steroids are often prescribed, ideally after histologic confirmation of disease, but many veterinarians prefer not to use them until less aggressive therapies have been exhausted. Gastroenterologists are moving toward more conservative doses of steroids in certain cases, particularly in dogs, says Sara Wennogle, DVM, DACVIM, at Colorado State University Veterinary Teaching Hospital.
“I think that’s partially due to the concern for the gut barrier being quite abnormal in many of these cases and the concern for over-immunosuppressing these patients and potentially creating an environment for secondary infections.”
In cases of inflammatory bowel disease and certain types of colitis, an alternative to prednisone is budesonide. The steroid has a high affinity for the steroid receptor and is rapidly metabolized. Dr. Wennogle describes it as a drug that can provide the benefits of a steroid with potentially fewer adverse effects in some patients.
Several immunosuppressive drugs not commonly used for GI disease are being used more readily but it is too early to justify their use globally, says Douglas Palma, DVM, DACVIM (SAIM), staff doctor at Animal Medical Center in New York City. They include chlorambucil, tacrolimus, mycophenolate, and leflunomide.
Steroids have their uses, but use caution when prescribing them. It’s not unusual for patients to arrive at a specialist on multiple immunosuppressive drugs that are creating more catabolic effects than beneficial effects. These catabolic effects can have a profound impact on morbidity and potentially could be associated with thromboembolic complications. That’s not uncommon in dogs with severe protein-losing enteropathies, Dr. Palma says, adding that if chronic high doses of steroids are prescribed and the patient is refractory, maintaining those doses could be doing more harm than good.
“There are certainly times where ‘refractory’ cases receive more and more immunosuppressive drugs rather than considering other variables that may be having a synergistic effect, including the microbiome and dietary factors,” he says. “It’s a complicated issue and every patient is slightly different. Oftentimes, manipulation of diet may be the primary change that results in dramatic clinical improvement. In other words, all factors may work in concert with one another in a unique way within a given patient to achieve success. The role for each aspect and its contribution to disease cannot be emphasized enough.”
Clients may request a course of antibiotics to treat a pet’s diarrhea or other gastrointestinal signs, but use of antimicrobials is not risk-free. Sometimes infectious GI conditions respond to antibiotics, but they are best reserved for cases in which the patient has compatible clinical signs and, ideally, positive results from culture and sensitivity testing for the infectious organism. Antibiotics can cause side effects, such as vomiting, diarrhea, and inappetence, worsening or prolonging intestinal upset. It can be better to withhold them unless they are specifically indicated.
Even when antibiotics work, it’s not always clear why.
“Metronidazole is commonly administered to dogs with acute diarrhea, and many cases respond,” says Michael Stone, DVM, DACVIM, at Tufts University’s Cummings Veterinary Medical Center in North Grafton, Mass. “Why this antibiotic works is a little bit of a mystery. The antibiotic is not killing all the bacteria in the intestine, but instead altering the types of bacteria back to a healthy mix. At least that’s our current theory.”
In an example of antibiotic usage gone wrong, Dr. Stone notes use of antibiotics in research studies for patients with salmonellosis. Instead of speeding resolution of disease, antibiotic use prolonged the period that patients shed salmonella bacteria in the stool.
“Given this phenomenon, we only treat patients that have salmonellosis with antibiotics if the bacteria have migrated from the intestine into the blood,” Stone says. “Otherwise we allow the infection to run its course, with resolution of illness within three to seven days.”
While antibiotics have their place, they are generally not a good long-term solution for most dogs, Wennogle says. Extensive antibiotic use can lead to resistance, causing dogs to experience relapses after first being initially responsive to the drugs.
Shift in focus
One of the changes in treatment for gastrointestinal problems is a move toward addressing bacterial populations in the gut. Currently, there isn’t yet a lot of strong science supporting prebiotics, probiotics, or symbiotics, but the premise for using them is strong, Palma says. Some data that has been presented shows promise in certain models and disease states, he says.
“A relatively recent publication looking at a human probiotic called VSL #3 showed, in an IBD model in dogs, improvements when compared to traditional therapy with prednisone and metronidazole. There is a slight benefit in patients that receive the medication versus standard therapy, which is kind of unheard of. While studies are oftentimes underpowered and may not be repeatable, this is a well-designed study that certainly suggests further investigation.”
Symptomatic therapies, such as clay- or resin-based absorbent compounds, are becoming more commonplace in management of patients with diarrhea. In addition, some drugs are in development with the goal of blocking common mechanisms in secretory diarrhea.
Although they are not a medication per se, fecal microbiome transfers (FMTs) also show promise. They have the potential to normalize microbiota and levels of secondary bile acids, and replenish bacterial species in the gut.
The effect can depend on the underlying disease, according to Texas A&M University College of Veterinary Medicine associate professor Jan Suchodolski, DrMedVet, DACVM (immunology), who spoke on the microbiome at VMX in 2018. If the initial trigger is gone, there can be lasting improvement of microbiota, but dogs with chronic enteropathies may need repeated FMTs.
Food is medicine, too
There is renewed interest in the importance of diet in treating gastrointestinal upset. While diet is not considered medication, it is a mainstay of therapy for gastrointestinal problems. Changing a patient’s diet can be helpful in treating underlying disease.
“Diet and medications are not necessarily mutually exclusive,” Wennogle says. “Manipulation of the diet has a lot of value in treating underlying diseases and potentially sparing the use of more medications.”
Conversely, a patient’s diet may be a potential cause of illness. Dietary constituents may contribute to gut inflammation, for instance. A consultation with a veterinary nutritionist can be a form of “medication” to suggest for patients with chronic problems, Stone says.
Anyone who has suffered stomach upset knows gastrointestinal problems can be painful. Treating that pain is another aspect of managing GI problems in pets. A few classes of pain medication are available for veterinary use, and the choice of which to use varies depending on the condition.
Appetite stimulants can be a supportive therapy for patients that have nutritional deficiencies because they are reluctant to eat. Antiemetics (maropitant citrate) can help vomiting patients, and may alleviate visceral pain to some extent, Wennogle says. When it’s not cost-prohibitive, such as in smaller dogs and cats, buprenorphine may help with patients with spasmodic or visceral pain.
“Because many of these animals end up perhaps being treated with steroids, we don’t necessarily want to encounter a situation where we have to get them off a nonsteroidal anti-inflammatory drug and then wait a while to start a steroid,” she says. “We tend to lean more on the opioid-type medication and maybe trying [a maropitant citrate] for pain. I think another drug to consider would be gabapentin.”
Gastroprotectant drugs that may seem appropriate don’t always have a place in treatment of GI disease.
“Much like in human medicine, there is a huge problem with the overuse of gastroprotectant drugs, such as famotidine or omeprazole in dogs and cats with GI signs,” Tolbert says. “Many veterinarians use these drugs for the adjunctive treatment of chronic kidney disease (CKD), pancreatitis, and vomiting. The use of these drugs for those conditions is inappropriate because CKD and pancreatitis are not causes of GI ulceration. When vomiting or dysrexia is a concern, veterinarians should reach for antiemetics and appetite stimulants, respectively, rather than gastroprotectants.”
Clients may expect medication to provide a quick resolution to their pet’s problem, but that’s not always possible. Tolbert spends a good part of the first appointment educating clients about the possible extent of diagnostics, along with first-, second-, and third-tier options. Not every patient needs a $2,000-plus workup, but in some cases, a number of conditions must be excluded before arriving at a diagnosis.
“Clients often want quick and inexpensive options,” she says. “This is often not possible with the diagnosis and treatment of GI diseases, especially those that are chronic.”
Successfully managing a complicated or refractory chronic enteropathy calls for attention to detail and manipulation of variables, including medications and dietary factors over time. It may take months of constant tweaking of the diet and/or a combination of medications.
“It’s critical our clients who want a quick or easy fix know that it’s not there yet,” Palma says. “As we learn more and more about the molecular mechanisms of things, there will no doubt be lots of different and potential avenues for treatment. It’s hoped we will gain more understanding about gastrointestinal disease over time, but we’re still learning those things.”