Chronic Pancreatitis in Cats | Today's Veterinary Practice
https://todaysveterinarypractice.com/table-of-contents-may-june-2020/
Endocrinology , Management Strategies

Chronic Pancreatitis in Cats

Jörg M. Steiner med. vet., Dr. med. vet., PhD, DACVIM-SAIM, DECVIM-CA, AGAF

Dr. Steiner is Professor of Small Animal Internal Medicine at Texas A&M University. In 2016, he was named the Dr. Mark Morris Chair in Small Animal Gastroenterology and Nutrition. He is the Director of the Gastrointestinal Laboratory at Texas A&M and is involved in small animal and comparative gastroenterology research. He has authored or co-authored approximately 290 peer-reviewed articles, 90 book chapters, and 430 research abstracts. In 2019, he was selected as a Distinguished Professor at Texas A&M.

Sue Yee Lim DVM, PhD

Dr. Lim graduated with a DVM degree from Universiti Putra Malaysia in 2009 and continued her studies at Hokkaido University, Japan. She earned her PhD degree in 2014 researching on the application of contrast-enhanced ultrasound in diagnosing canine pancreatitis. Her current research at Texas A&M’s GI Laboratory is focused on pancreatic lipases.

Chronic Pancreatitis in Cats
SIGNS OF TROUBLE The clinical signs associated with feline pancreatitis can include inappetence, lethargy, and vomiting. Photo: Shutterstock.com/Natata
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Pancreatitis is common among cats, although its exact incidence is unknown. The disease can take several forms—acute, chronic (FIGURE 1), and acute on chronic (an episode of acute pancreatitis in a patient with chronic pancreatitis)—and differentiating among the forms clinically and making an antemortem diagnosis in cats remain challenging.1 According to one study, the prevalence of pancreatitis in cats that had died or had been euthanized for a variety of reasons was more than 50%.2 This article focuses on the management of chronic pancreatitis in cats: minimizing risk factors, nutritional management, treating symptoms, treating concurrent conditions, identifying and treating autoimmune components, and monitoring.

RISK REDUCTION

Although the underlying cause of chronic pancreatitis in cats often cannot be determined, possible risk factors should be eliminated. In our experience, factors that have been associated with the development of chronic pancreatitis in cats include high-fat diets, infections (i.e., feline parvovirus, Toxoplasma gondii, feline calicivirus, feline herpesvirus, and feline coronavirus), hypercalcemia, some drugs, and potentially autoimmune disease. However, most cases are idiopathic. Thus, as a first step, we recommend the following (depending on the patient): consider a diet change; test for specific infectious diseases, if suspected; identify and treat the underlying causes of hypercalcemia, if present; take a thorough drug history and discontinue any nonessential drugs or replace essential drugs with alternative medications, if possible; and consider immunosuppressants for autoimmune disease, if suspected.

NUTRITIONAL MANAGEMENT

By the time cats with chronic pancreatitis are taken to the veterinarian, most have already been hyporexic or anorexic for days to weeks.1 Prolonged undernutrition in cats can lead to weight loss or even hepatic lipidosis.

Although appetite stimulants may encourage food intake in hyporexic cats, they rarely result in attainment of caloric requirements. The only Food and Drug Administration (FDA)-approved drug that can be used as an appetite stimulant in cats is mirtazapine transdermal ointment (2 mg/cat, applied daily for 14 days) (FIGURE 2), although the drug has actually been approved for management of undesired weight loss. However, take caution when administering appetite stimulants to cats with hepatic lipidosis.3 Another drug, capromorelin (a ghrelin-receptor agonist) has been FDA-approved as an appetite stimulant for use in dogs. Also, initial studies have shown that its daily administration was well tolerated by healthy laboratory cats; mild side effects (e.g., vomiting, hypersalivation, lethargy, head shaking, and lip smacking) were associated with its administration.4 Further studies are needed before the routine use of this drug in cats can be recommended.

In contrast to its effect in dogs, the effect of dietary fat content on pancreatitis in cats is still controversial. However, anecdotal evidence suggests that chronic pancreatitis does develop in some cats that are fed high-fat diets (e.g., diets for the management of chronic kidney disease or low-carbohydrate diets). Thus, if a cat with chronic pancreatitis is being fed a high-fat diet, the cat should be transitioned to a lower-fat diet. However, commercial ultra–low-fat diets are not available for cats and are probably unnecessary for this species.

To prevent food aversion in cats, forced oral feeding is strongly discouraged. For cats with chronic pancreatitis that do not consume adequate amounts of food despite antinausea therapy and appetite stimulants, consider tube feeding. For short-term caloric support, a nasogastric tube (5- to 8-French flexible polyurethane feeding tube) can be placed. However, these tubes can be very disturbing to cats, who are obligate nasal breathers, and an Elizabethan collar will probably be needed to keep the cat from removing the tube. Persistently anorexic patients who need longer periods of supplemental nutrition may do better with an esophageal or gastric tube. These tubes also facilitate administration of oral medications, which can be challenging in any cat. The initial goal of nutritional management is to provide 25% to 50% of target caloric intake. Over the next 2 to 4 days, gradually increase the volume to reach the target caloric intake.

The selection of diet should take into account concurrent conditions. Cats with secondary hepatic lipidosis require a high-protein (30% to 40% of metabolizable energy, while taking caution not to feed excessive amounts of fat), calorie-dense diet. Cats with concurrent inflammatory bowel disease (IBD) may benefit from a novel or hydrolyzed protein diet.

By the time cats with chronic pancreatitis are taken to the veterinarian, most have already been hyporexic or anorexic for days to weeks.1

SYMPTOMATIC THERAPY

Antiemetic/Antinausea Drugs

Although not all cats with pancreatitis vomit, it is suspected that they often experience nausea. Cats >4 months of age can be given maropitant at 1 mg/kg SC or PO q24h. Maropitant is a neurokinin-1 receptor antagonist that has both central and peripheral effects. It has been speculated that maropitant may provide analgesia through inhibition of visceral neurokinin-1 receptors. There is evidence that ondansetron (a serotonin [5-HT3] antagonist) has poor oral bioavailability and a short half-life; therefore, the preferred route of administration for this drug may be subcutaneous.5 Another 5-HT3 antagonist that can be given either subcutaneously or orally and may decrease nausea, and in turn increase appetite, is dolasetron.

Pain Management

Cats are extremely good at hiding pain. Cats with chronic pancreatitis rarely display signs of abdominal pain.1 Outpatient analgesia can be provided by buprenorphine at 0.01 to 0.03 mg/kg sublingually q4h to q12h or butorphanol at 0.5 to 1.0 mg/kg PO q6h to q8h. For more severe pain, the only feasible modality is a transdermal fentanyl patch q72h to q120h (12 µg/hour for small cats and 25 µg/hour for large cats).6 For cats with chronic pancreatitis, nonsteroidal anti-inflammatory drugs are contraindicated because of the risk for nephrotoxicity, gastroduodenal erosion and ulceration, and because they are considered risk factors for pancreatitis in humans.

Antimicrobial Drugs

Chronic pancreatitis in cats is usually sterile.2 One study suggested that bacterial DNA was present in pancreatic biopsy samples from cats with pancreatitis, but it is unclear whether these findings have any clinical relevance.7 Therefore, antimicrobial therapy is rarely indicated unless patients have evidence of a concurrent bacterial infection (i.e, septic fluid within the pancreas [sometimes referred to as a pancreatic abscess], neutrophilic cholangitis, or severe neutropenia).

Gastrointestinal Protectants

Gastrointestinal protectants (e.g., H2 antagonists, proton-pump inhibitors, or sucralfate) are sometimes given to cats with chronic pancreatitis, but they are rarely, if ever, indicated. Even in cats with severe acute pancreatitis, gastric ulceration is extremely rare. Gastroprotectants may dramatically shift the gastrointestinal microbiota, which may have detrimental effects on the patient.

Chronic pancreatitis can be associated with concurrent cholangitis and IBD, sometimes referred to as triaditis.8

CONCURRENT CONDITIONS

Diagnosis and management of concurrent conditions are paramount for the care of cats with chronic pancreatitis. Chronic pancreatitis can be associated with concurrent cholangitis and IBD, sometimes referred to as triaditis.8 According to one prospective study of cats, concurrent pancreatic, hepatic, and/or intestinal inflammation was more common (27/47) than isolated pancreatic inflammation (1/47).9 Also, chronic pancreatitis is often associated with diabetes mellitus. However, some evidence also indicates that hyperglycemia may lead to pancreatic inflammation in cats.10

Cholangitis

Cholangitis is a common liver disease in cats and can take on several forms: neutrophilic, lymphocytic, mixed, or liver fluke associated. Studies have led to different conclusions about the prevalence of each form of cholangitis, resulting in discrepancies regarding which is most common.9,11 Because the clinical presentations of cats with these different forms may be similar, it is important to determine which kind of cholangitis is present before instituting treatment.

The most common route for development of neutrophilic cholangitis is thought to be an enteric bacterial infection ascending via the biliary tree. Cytology and bacterial culture (aerobic and anaerobic) and sensitivity testing should be performed on bile and/or liver biopsy samples.12 If neither of these samples can be safely obtained, culture can be attempted from a fine-needle aspirate of the liver or gall bladder. If infection is established, antibiotics should be administered. Antibiotics can be selected before culture susceptibility results are available; appropriate choices for gram-positive and gram-negative aerobes and anaerobes include fluoroquinolones, penicillin and metronidazole, or a fluoroquinolone and a potentiated penicillin.12-14 Given the difficulty of achieving adequate concentrations of the antibiotic in hepatic and biliary tissue, prolonged courses of treatment are recommended. Although duration of treatment should be guided by follow-up sampling, collecting the samples can be risky and costly. If no culture and sensitivity testing can be obtained, empiric antibiotic therapy for 4 to 6 weeks is suggested.13

Lymphocytic cholangitis is thought to be immune mediated. Given this assumption, treatment usually involves the administration of prednisolone (1 to 2 mg/kg q12h starting dose).15 However, prednisolone should not be initiated until active bacterial infections have been ruled out or treated with empiric administration of antibiotics.6

Inflammatory Bowel Disease

Cats with pancreatitis often have concurrent inflammatory infiltrates (e.g., lymphocytes, plasma cells) of the intestines.9 With better understanding of chronic enteropathies in cats, therapeutic options have become more refined. Most of these cats will respond to dietary therapy (e.g., food-responsive enteropathy); some may respond to modification of the intestinal microbiota (suggesting an underlying dysbiosis), but others may require immunosuppressive therapy (i.e, they have idiopathic IBD).16 Many cats with idiopathic IBD are deficient in cobalamin and require oral or parenteral supplementation with cyanocobalamin.

Diabetes Mellitus

Many cats with chronic pancreatitis have concurrent diabetes mellitus. Some of these cats are undergoing dietary management with a low-carbohydrate diet. We believe that these patients may benefit from being switched to a diet with a lower fat content.

IMMUNOSUPPRESSIVE THERAPY

Although immune-mediated chronic pancreatitis is well described for humans, it has not been definitively proven whether this condition occurs in cats. Anecdotally, however, cats with chronic pancreatitis may respond to treatment with prednisolone (the dosing varies, but we use 2 mg/kg q12h for 10 days, then 1 mg/kg q12h for 6 weeks, followed by a decreasing dose at 6-week intervals) or cyclosporine (5 mg/kg q12h to q24h for 6 weeks followed by a decreasing dose at 6-week intervals). To determine whether treatment is effective, re-evaluate the patient after the first 2 to 3 weeks of therapy. Therapeutic trials are under way to study the efficacy of these drugs in cats with chronic pancreatitis (vetmed.tamu.edu/gilab/research/feline-chronic-pancreatitis).

MONITORING

With appropriate management and symptomatic care, cats with pancreatitis should show clinical improvement (e.g., increased activity, appetite, and body condition score). It is imperative to educate clients about the potential long-term sequelae of chronic pancreatitis, such as diabetes mellitus, exocrine pancreatic insufficiency, or acute exacerbation of this chronic disease. The management of cats with concurrent chronic pancreatitis and diabetes mellitus is more complex.

Long-term follow-up of cats with pancreatitis is indicated. Based on clinical experience, we recommend monitoring feline pancreatic lipase (fPL) immunoreactivity (fPLI), as measured by a Spec fPL test (IDEXX Laboratories Inc., idexx.com) every 2 to 3 weeks until the level reaches a plateau, at which point the monitoring interval can be decreased. Although the goal of management is amelioration of clinical signs and normalization of the spec fPL concentration, some cats will improve clinically but maintain a mildly increased spec fPL serum concentration.

CONCLUSIONS

Chronic pancreatitis is a common, yet complex, disease in cats, and its management is nonspecific and multifaceted. The successful management of these patients involves management of risk factors (switching to a diet with a lower fat content, addressing hypercalcemia, minimizing exposure to unnecessary drugs), managing nutrition, symptomatic care (antinausea and analgesic therapy), diagnosing and managing concurrent conditions, administering immunosuppressive drugs, and monitoring fPLI concentration.

References

1. Ferreri JA, Hardam E, Kimmel SE, et al. Clinical differentiation of acute necrotizing from chronic nonsuppurative pancreatitis in cats: 63 cases (1996-2001). JAVMA 2003;223(4):469-474.

2. De Cock HE, Forman MA, Farver TB, Marks SL. Prevalence and histopathologic characteristics of pancreatitis in cats. Vet Pathol 2007;44(1):39-49.

3. Armstrong PJ, Blanchard G. Hepatic lipidosis in cats. Vet Clin North Am Small Anim Pract 2009;39(3):599-616.

4. Wofford JA, Zollers B, Rhodes L, et al. Evaluation of the safety of daily administration of capromorelin in cats. J Vet Pharmacol Ther 2018;41(2):324-333.

5. Quimby JM, Lake RC, Hansen RJ, et al. Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats. J Vet Pharmacol Ther 2014;37(4):348-353.

6. Simpson KW. Pancreatitis and triaditis in cats: causes and treatment.
J Small Anim Pract 2015;56(1):40-49.

7. Simpson KW, Twedt DC, McDonough SP, et al. Culture-independent detection of bacteria in feline pancreatitis. ACVIM Forum Proc 2011.

8. Xenoulis PG, Suchodolski JS, Steiner JM. Chronic pancreatitis in dogs and cats. Compend Contin Educ Vet 2008;30(3):166-180.

9. Fragkou FC, Adamama-Moraitou KK, Poutahidis T, et al. Prevalence and clinicopathological features of triaditis in a prospective case series of symptomatic and asymptomatic cats. J Vet Intern Med
2016;30(4):1031-1045.

10. Zini E, Osto M, Franchini M, et al. Role of hyperglycemia in the pathogenesis of pancreatitis in cats. ACVIM Forum Proc 2009.

11. Bayton WA, Westgarth C, Scase T, et al. Histopathological frequency of feline hepatobiliary disease in the UK. J Small Anim Pract 2018;59(7):404-410.

12. Boland L, Beatty J. Feline cholangitis. Vet Clin North Am Small Anim Pract 2017;47(3):703-724.

13. Brain PH, Barrs VR, Martin P, et al. Feline cholecystitis and acute neutrophilic cholangitis: clinical findings, bacterial isolates and response to treatment in six cases. J Feline Med Surg 2006;8(2):91-103.

14. Wagner KA, Hartmann FA, Trepanier LA. Bacterial culture results from liver, gallbladder, or bile in 248 dogs and cats evaluated for hepatobiliary disease: 1998-2003. J Vet Intern Med 2007;21(3):417-424.

15. Otte CM, Penning LC, Rothuizen J, Favier RP. Retrospective comparison of prednisolone and ursodeoxycholic acid for the treatment of feline lymphocytic cholangitis. Vet J 2013;195(2):205-209.

16. Gianella P, Pietra M, Crisi PE, et al. Evaluation of clinicopathological features in cats with chronic gastrointestinal signs. Pol J Vet Sci 2017;20(2):403-410.

17. Davison LJ. Diabetes mellitus and pancreatitis—cause or effect? J Small Anim Pract 2015;56(1):50-59.

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