Characterization of Chronic Enteropathies in Dogs by Use of Fecal and Urinary N-methylhistamine Concentrations and Serum Methylmalonic Acid Concentrations

Abstract

Non-invasive markers that are clinically useful for the diagnosis and monitoring of canine chronic enteropathies are scarce. The first aim of this study was to investigate the prevalence of cobalamin deficiency on a cellular level in dogs with chronic gastrointestinal disease by measuring serum methylmalonic acid (MMA) concentrations. Hypocobalaminemia has been associated with a negative outcome in dogs with chronic enteropathies, but the prevalence of cellular cobalamin deficiency is unknown. The second aim of this study was to determine the utility of fecal and urinary concentrations of N-methylhistamine (NMH) as a marker of gastrointestinal inflammation and disease activity in dogs with chronic enteropathies.

Serum MMA concentrations were measured in healthy control dogs to establish a reference interval, which was calculated to be 415-1,193 nmol/L. Measurement of MMA concentrations in 555 serum samples from dogs with varying cobalamin concentrations showed a significant increase (p<0.05) in dogs with hypocobalaminemia. In a prospective group of 56 dogs with chronic enteropathies, 36% had decreased serum cobalamin concentrations, five of which (9% of 56 dogs) had increased serum MMA concentrations. We conclude that hypocobalaminemia is commonly seen in dogs with chronic gastrointestinal disease, but does not always appear to be associated with cellular cobalamin deficiency.

In 47 dogs with chronic enteropathies, fecal and urinary NMH concentrations were increased in 21% and 27%, respectively, indicating that mast cell degranulation plays a role in a subset of dogs with chronic enteropathies. However fecal and urinary NMH concentrations did not correlate with each other, or with the clinical activity index. Urinary NMH concentrations correlated significantly with serum CRP concentrations, and were also significantly associated with severity of duodenal mucosal inflammation (p=0.008). The lack of correlation with the clinical activity index suggests that degranulation of mast cells only plays a role in some dogs with chronic enteropathies. Also, these results suggest that NMH alone may not be a good marker for clinical disease activity in dogs with chronic enteropathies. Due to its linear association with serum CRP and severity of mucosal inflammation, urinary NMH concentrations may be a better marker of intestinal inflammation than fecal NMH concentrations.