Canine EPI: Concurrent and secondary diseases
Concurrent conditions frequently diagnosed in dogs with EPI include small intestinal bacterial overgrowth, hypocobalaminemia, mesenteric torsion, and a handful of others.
Small intestinal bacterial overgrowth
Several factors favor intestinal microbe overpopulation in dogs with EPI, including an abundance of luminal substrate for bacterial consumption, altered intestinal motility and immune function, and a lack of bacteriostatic pancreatic juices.1 Small intestinal bacterial overgrowth (SIBO) is sometimes referred to as antibiotic-responsive diarrhea. As expected, SIBO does not appear to be common in dogs with subclinical EPI.2The presence of SIBO is supported by a concurrent elevation in serum folate concentration and a decrease in cobalamin concentration, which was reported in 47% of dogs with EPI in one study.3 In the same study, 60% of dogs with EPI had elevated serum folate concentrations, which is a byproduct of intestinal bacteria, and 82% had hypocobalaminemia, which is partially due to bacterial sequestration.3 The population of bacteria within the intestines has a large effect on the mucosal integrity. Anaerobic bacterial overgrowth results in partial villous atrophy and decreased activity of brush border enzymes, whereas aerobic bacterial overgrowth is not associated with mucosal changes.4
Still, the clinical impact of SIBO, whether aerobic or anaerobic, on patients with EPI is uncertain. In many cases, enzyme supplementation alone leads to resolution of clinical signs.4 The existence of SIBO with or without villous atrophy may have the potential to differentiate patients that will respond well to enzyme supplementation vs. those that will not, but this remains unproved.
If necessary, SIBO can be treated with tylosin (20 mg/kg orally every eight or 12 hours), metronidazole (10 to 20 mg/kg orally every eight hours), or oxytetracycline (10 to 20 mg/kg orally every eight hours) for one to three weeks.1,5 Once EPI is controlled with enzyme supplementation, specific therapy for SIBO should no longer be necessary. In addition to controlling the underlying condition, enzyme supplementation has antibacterial effects.5
Even when dogs with EPI do not concurrently have SIBO, they may still have severe hypocobalaminemia. This condition is due to a deficiency in the production of intrinsic factor by pancreatic acinar cells.3 Cobalamin binds to intrinsic factor, which acts as a ligand, permitting cobalamin absorption by endocytosis into the ileal enterocyte. Intrinsic factor is species-specific, so it is not replaced by pancreatic enzyme supplements.6
Parenteral cyancobalamin (vitamin ±2) supplementation is recommended at subcutaneous doses of 250 to 500 µg/dog initially, given weekly for four to six weeks, then every two weeks for four to six weeks, and then monthly. The frequency of further treatment can be tailored based on reassessment of serum cobalamin concentrations.1 The median survival time in patients with cobalamin concentrations > 100 ng/L is twice as long as in unsupplemented patients with concentrations < 100 ng/L.3
Another condition that has been documented in dogs with EPI is mesenteric torsion; however, a causal relationship has not been proved. In one study, 21 of 255 dogs with EPI developed mesenteric torsion, and 18 of the affected dogs were undergoing treatment with pancreatic enzyme supplements.7 Eight of the dogs were euthanized, four dogs died at home before treatment for torsion was instituted, and nine of the dogs underwent surgery to correct the torsion but died during recovery from anesthesia. All the dogs that developed mesenteric torsion were German shepherds, which represent 10% of the German shepherds studied. Forty-two collies with EPI were in the study, and none of them developed mesenteric torsion.7