Tests to investigate gastrointestinal diseases in dogs ‐ which markers are actually useful for the practitioner?
Year: 2007
Type: editorial
Abstract: Chronic enteropathies in dogs are frequently encountered in practice and can result in long standing clinical signs of diarrhoea, vomiting and weight loss. The clinician faced with an animal presenting with a chronic enteropathy is usually forced to perform an extensive workup to exclude diseases such as intestinal parasites, bacterial infections, metabolic disease and pancreatic diseases. This includes routinely testing the faeces for endoparasites and enteropathogenic bacteria, performing a complete blood count, chemistry screen and urinalysis to exclude renal and hepatic disease and, lastly, to run a TLI test to check for the presence of exocrine pancreatic insufficiency. However, even if a potentially pathogenic organism (such as Campylobacter) is identified in the faeces, it can be difficult to decide if the organism is the sole cause of the diarrhoea or if it is simply a complicating factor of an underlying disease, such as inflammatory bowel disease (IBD). This is demonstrated elegantly in the study by Guest and others (2007) which shows that organisms such as Campylobacter sp., Isospora sp., Uncinaria spp., and Toxocara spp can be found equally frequently in healthy dogs as well as in dogs with diarrhoea. At the end of the workup for chronic diarrhoea in most cases stands a relatively invasive procedure (endoscopy or laparotomy) to obtain biopsies from the intestine. Food allergies, idiopathic IBD and antibiotic-responsive diarrhoea are the diseases most commonly diagnosed in dogs. Frustratingly, they all appear similar histologically, with some degree of lymphoplasmacellular and/or eosinophilic infiltration most commonly reported. Therefore, these diseases are actually often diagnosed retrospectively by their response to a sequential treatment trial involving several weeks of an elimination diet, several weeks of antibiotic treatment and, finally, trial therapy with several weeks of immunosuppressive treatment such as prednisolone. Unfortunately, very little information is available on potential markers that may help distinguish between cases that respond to diet alone and those that require treatment with antibiotics or corticosteroids. Despite recent advances in our knowledge of the pathogenesis of IBD in humans, we still don’t know very much about the development of IBD in dogs. Specifically, it would be very convenient for the clinician to know which dogs will be likely to respond to diet, antibiotics or steroids before having to undergo treatment trials. Several papers in this issue of JSAP assess the clinical usefulness of serum markers in gastrointestinal (GI) diseases of dogs. Cytokines, especially pro-inflammatory Th1-type cytokines such as TNF, seemed to be a promising marker based on human studies. In human patients with IBD, high levels of intestinal mucosal TNF have been shown to correlate with the severity of disease and antibodies against TNF are a useful rescue therapy if all other treatments fail. Several recent studies aimed to investigate the cytokine mRNA pattern in intestinal biopsies in dogs with chronic enteropathies. In an earlier study, the authors measured cytokine expression in the mucosa semi-quantitatively and found increased levels of IFN-γ, TNF, IL-2, IL-5, IL-12 and TGF-β suggesting a similar Th1-biased cytokine profile in dogs with IBD as can be seen in humans with IBD (German and others 2000). However, newer studies in which real-time RT-PCR was used to measure cytokine expression profiles in biopsies found no distinct cytokine profile towards either a Th1 or Th2 pattern (Peters and others 2005, Sauter and others 2006). Furthermore, when cytokine mRNA levels were compared with total number of infiltrating cells and CD3 cells as well as clinical activity indices, no significant correlations of cytokines levels with any of these parameters were detected (Sauter and others 2006). Obviously, it would be even easier and less invasive to be able to look for elevated cytokine levels in the serum of dogs with IBD. In one paper in this issue (McCann and others 2007), the authors hypothesised that serum levels of TNF are elevated in dogs with IBD and that the levels would correlate with clinical severity of disease. Unfortunately, serum TNF levels were normal in all dogs with IBD in this study (16/16). In chronic diseases such as IBD, elevations in cytokine levels seem to be a predominantly local response which influences the microenvironment in the gut, but systemically, inflammatory cytokine levels are rarely detectable. To the contrary, serum levels of TNF are elevated in many diseases causing sepsis, as has been shown in several studies, including the paper by Yilmaz and Senturk (2007) in this issue. The authors prove that TNF is elevated in parvovirus infections associated with sepsis, and that an elevated level of TNF is associated with a worse prognosis. This is not surprising, as many studies looking at various forms of sepsis have found similar data. On the other hand, this data also re-iterates the fact that elevated serum TNF levels are in no way specific for the underlying disease. Unfortunately, measurement of cytokine levels in serum or tissue is not an easily available test either – other markers with wide availability for practitioners would be much more useful in general practice. Albumin levels are routinely measured in most patients investigated for GI disease. Protein-losing enteropathy accounts for the loss of albumin through the gut mucosa in dogs with severe IBD, and two recent studies have confirmed that decreased albumin levels have a negative prognostic implication in dogs with IBD (Craven and others 2004, Allenspach and others 2007). One retrospective study in the UK described 12/80 (16%) dogs with hypoalbuminaemia and 4/80 (5%) dogs with panhypoproteinaemia (Craven and others 2004). Seven of these 12 dogs subsequently had to be euthanased for intractable IBD. These findings were confirmed in a prospective study performed in Switzerland, where 12/58 (21%) cases initially presented with hypoalbuminaemia (Allenspach and others 2007). Of these 12 dogs, seven were panhypoproteinaemic with severe hypoalbuminaemia (mean albumin level 11 g/l) and three of those eventually had to be euthanased. This confirms the importance of measuring albumin in cases with IBD, as it can be predictive for negative outcome, especially when it drops to lower than 15 g/l. Serum cobalamin concentration has been known to be associated with refractoriness to treatment in cats with IBD (Ruaux and others 2005), and a recent prospective study confirmed these findings for dogs with chronic enteropathies as well (Allenspach and others 2007). If the serum cobalamin concentration was lower than 200 ng/l, the odds ratio for bad outcome was ten times higher than for dogs with cobalamin concentrations above this cut-off value. Measuring cobalamin levels and supplementing vitamin B12 in cases with deficiencies therefore seems to be just as important in dogs as in cats with signs of chronic small intestinal diarrhoea. Another test that has recently become available for practitioners in the UK is canine pancreatic lipase (cPLI). Some dogs with IBD may present with signs that could be attributed to chronic pancreatitis, such as abdominal pain, changes in the ultrasonographic appearance of the pancreas, or a neutrophilia with left shift. The prevalence and characteristics of concurrent chronic pancreatitis in dogs with IBD has not been reported in the literature, however, we seem to see increasing numbers of dogs with IBD which also have elevated cPLI serum concentrations. In a recent retrospective study at the Royal Veterinary College, 50 dogs with IBD presenting either with or without concurrent chronic pancreatitis were evaluated regarding clinical signs, histopathology, management of IBD and follow-up (Kathrani and others 2007). Interestingly, dogs with IBD and concurrent chronic pancreatitis had a higher risk of a poor follow-up score and were significantly more likely to be euthanased at follow-up. In summary, we are still a long way from highly sensitive and specific non-invasive markers to help us diagnose and predict treatment response in dogs with IBD. However, some recent studies show that easily available tests such as serum albumin concentration, cobalamin measurement and cPLI could be useful prognostic indicators as to which dogs may need more aggressive treatment early on in the course of their disease. On the other hand, it is still important to “get the phenotype right”, i.e., to clinically diagnose which dogs are food-responsive, antibiotic-responsive or steroid-responsive, or which dogs have concurrent diseases or vitamin deficiencies, such as Campylobacter infections, chronic pancreatitis or cobalamin deficiency. The days of the good, diligent small animal practitioner aren’t over yet, as clinical skill is still of the utmost importance – even though we are making progress in supporting this process with evidence of which tests are least invasive and most useful for the workup of dogs with chronic diarrhoea. Karin Allenspach is a lecturer in Small Animal Internal Medicine at the Royal Veterinary College, University of London. She divides her time between seeing cases and supervising the small animal medicine service at the RVC, teaching undergraduates and postgraduates in medicine and doing clinical research. Her main research interest lies in canine gastroenterology.
Source: Journal of Small Animal Practice
Author: Karin Allenspach
Institution: Royal Veterinary College
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2008364987