Exocrine pancreatic insufficiency (EPI) results from inadequate production of enzymes from the pancreatic acinar cells, leading to maldigestion, malabsorption and subsequent clinical signs, such as weight loss and diarrhea. Although EPI has previously been considered rare in the cat, it is now recognized that many cases escaped diagnosis in the past due to the lack of sensitive and specific diagnostic tests, low awareness for the disease, and its co-existence with other gastrointestinal (GI) conditions that cause similar clinical signs. Until recently, the literature on feline EPI was sparse, consisting of reports of confirmed or suspected EPI in 10 individual cats published between 1975 and 2009 1,2,3,4,5,6,7,8,9, as well as two small case series that together encompassed a total of 36 affected cats 10,11. More recently, a large retrospective study that evaluated 150 cats with EPI has been published 12, and in 2021 a small multicenter retrospective study described the ultrasonographic and clinicopathologic findings in 22 cats with EPI 13.
The true prevalence of feline EPI is unknown, and (as noted above) the condition has traditionally been regarded as being rare in the cat, with only a few published case reports. However, since the introduction of the feline trypsin-like immunoreactivity (fTLI) test in 1995 14, considerably more cases have been diagnosed. In a recent study, the Gastrointestinal Laboratory’s database at Texas A&M University was searched over an approximately 2-year period (2008-2010), and 1,094 of 46,529 serum samples (2.4%) from cats submitted for fTLI measurement had levels consistent with a diagnosis of EPI 12. Despite the fact that the population used in this study is skewed (because it reviewed cats that had GI signs and therefore a possible suspicion of EPI), it appears that EPI is a condition that is not uncommon in cats. It is uncertain if these figures reflect a true increase in prevalence, or are merely an indication that clinicians now have a greater awareness of the disease and better means for arriving at a diagnosis. Therefore, although its true prevalence is yet to be determined, EPI should be suspected in cases with a compatible clinical picture.
Etiology and pathophysiology
No studies have specifically investigated the potential causes of feline EPI, although chronic pancreatitis leading to gradual and extensive destruction of the acinar cells has almost always been traditionally cited as the sole etiology. However, this idea was based on a small number of case reports 13,15, and although chronic pancreatitis is still believed to be the most common cause of feline EPI, other etiologies may also exist. Although not proven, the belief is that a prolonged time period is necessary for chronic inflammation to cause almost complete destruction of the exocrine pancreas; however, recent studies have noted that young cats can develop EPI, making chronic pancreatitis a less likely cause, especially in this age group 12. Other potential etiologies for EPI could include pancreatic acinar atrophy (reported in a small number of cases), Eurytrema procyonis infestation (a fluke found in parts of the USA, and again reported in a small number of cases), pancreatic hypoplasia or aplasia, and pressure atrophy due to pancreatic duct obstruction 1,2,3,4,5,6,7,8,9, 13. Whilst isolated pancreatic lipase deficiency has recently been reported as a cause of canine EPI (with other pancreatic enzymes remaining within normal parameters) 16, this has not yet been reported in cats.
The exocrine pancreas is thought to have exceptional functional reserve, and clinical signs of EPI are believed to develop only when > 90% of the secretory capacity is lost 13. Regardless of the cause, insufficient production and secretion of pancreatic enzymes into the small intestine leads to maldigestion of nutrients. The large amount of undigested nutrients in the intestine may lead to osmotic diarrhea, while decreased absorption of nutrients causes weight loss.
Of major importance is the pathophysiologic association between pancreatic function and cobalamin absorption. A cobalamin-binding protein, intrinsic factor, facilitates cobalamin absorption in the ileum, but in contrast to dogs, where intrinsic factor is also produced in the stomach, in cats it is produced exclusively in the exocrine pancreas. EPI therefore leads to reduced production and secretion of intrinsic factor, resulting in decreased intestinal absorption of cobalamin, and hence hypocobalaminemia and cobalamin deficiency 17.
Where EPI is a result of chronic pancreatitis, destruction of the endocrine portion of the pancreas may lead to concurrent diabetes mellitus. Additionally, many cats with EPI may have concurrent pancreatic inflammation, a chronic enteropathy (typically inflammatory bowel disease and/or GI small cell lymphoma) and/or hepatic disease.
Signalment and clinical signs
There is no significant breed or sex predisposition for EPI 12; most affected cats are middle-aged or older, but the reported age range is from 3 months to 19 years 12. This underlines the fact that EPI should be considered in cats of any age.
The clinical signs of affected cats are nonspecific and are the same as those seen with many other more commonly diagnosed conditions (e.g., hyperthyroidism, chronic enteropathies, pancreatitis, chronic kidney disease). Weight loss is by far the most common clinical sign (Figure 1) and was present in more than 90% of 150 cats in one study, and was the only clinical sign in 5% of the cases 12. Loose stools occurred in 62% of the cats, with 2/3 of them having occasional watery diarrhea (Figures 2 and 3). This is in contrast with the typical EPI dog, where loose stools are reported in most cases (e.g., 95% in one study 18). Other clinical signs include poor haircoat (50%), polyphagia (42%), anorexia (42%), lethargy (40%), vomiting (19%), and a greasy haircoat 12. Some of the reported signs (e.g., anorexia, depression, vomiting) are not typical of EPI and are likely associated with concurrent diseases (e.g., chronic enteropathy, or inflammation of the liver and/or pancreas) than EPI per se. There is one report of a cat with EPI that developed D-lactic acidosis (presumably due to increased intestinal fermentation as a result of bacterial overgrowth) which presented with clinical signs of weakness, lethargy and ataxia 8, but this is considered to be rare.