Top Questions From General Practitioners About Pancreatitis in Dogs

Pancreatitis is a common but challenging disorder in dogs, often leaving many general practitioners with questions regarding optimal diagnostic and treatment options. This article will address some of the most frequently asked questions specialists receive from general practitioners about pancreatitis in canine patients.

What is the pathogenesis of pancreatitis?

Development of pancreatitis in a dog requires an underlying risk factor, inciting cause, or a combination of both. The inciting causes or underlying risk factors then trigger a sequence of events, including colocalization of zymogens and lysosomes that occur inside the acinar cell and cause trypsinogen-dependent or trypsinogen-independent pathways of pancreatic inflammation.^1,2 The degree of inflammation and necrosis then determines whether clinically evident disease develops and, potentially, its severity.^3,4 Additional specific information can be found in a recent review article.⁴

How should I approach the diagnosis of pancreatitis?

The diagnosis of pancreatitis is challenging. Historically, biopsies were recommended; however, they are costly, invasive, and challenging to interpret.⁵ Therefore, most clinicians now base a “clinical diagnosis” on integration of all available data.⁵ Doing so places the clinician at the center of the diagnosis and emphasizes their value, but it is important that the clinician understands each test and its limitations in order to provide an optimal diagnosis.

To diagnose pancreatitis, a patient’s history and physical examination findings should be integrated with diagnostic imaging and the results of a pancreatic lipase assay.⁵ Although radiography is useful for ruling out foreign bodies or other diseases that may require alternate or surgical intervention, it is neither sensitive nor specific for pancreatitis. Ruling out alternate diagnoses is, however, an integral part of the diagnostic approach to pancreatitis as false-positive pancreatic lipase results (especially cage-side assays) are possible for dogs with abdominal disease.⁶

Abdominal ultrasonography is currently the imaging modality of choice for dogs with suspected pancreatitis. Ultrasonographic evidence of acute pancreatitis includes an enlarged hypoechoic (dark) pancreas with a hyperechoic (bright) surrounding mesentery (FIGURE 1).⁷ In some dogs, ultrasonographic evidence of pancreatitis lags behind clinical signs, and repeat ultrasonography may be indicated for dogs with a high clinical suspicion for pancreatitis but “normal” ultrasonography results at hospital presentation.⁸ Conversely, ultrasonographic evidence of pancreatitis can persist well beyond the initial injury.⁹ These factors mean that the diagnostic approach to pancreatitis cannot rely on ultrasonography alone.

Figure 1. Ultrasonographic evidence of pancreatitis in a 3-year-old spayed female mixed-breed dog. The right limb of the pancreas (white arrow) is enlarged and hypoechoic, and the surrounding mesentery is hyperechoic (orange arrow). A clinical diagnosis of pancreatitis was confirmed by evaluation of the history, physical examination findings, and a specific canine pancreatic lipase immunoassay (Spec cPL; IDEXX, idexx.com) concentration of > 2000 μg/L.

Are all lipase assays equal?

Each lipase assay available has its own advantages and disadvantages. It is beyond the scope of this article to discuss each commercially available assay, but assay type can provide some general information about potential advantages and disadvantages. Pancreatic lipase assays can be divided into 2 categories: catalytic and immunologic (TABLE 1).

Catalytic assays (e.g., DGGR [1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin)]) measure lipase activity by determining the rate at which hydrolytic products are formed, often linked to a colored reaction.¹⁰ Catalytic assays may detect extrapancreatic sources of lipase¹¹; however, optimization of catalytic lipase assay conditions can reduce the detection of nonpancreatic lipases, and using 2 to 3 times the upper reference interval cutoffs may be helpful when relying on catalytic lipase assays in practice. Catalytic assays may also be more cost-efficient. Analytical specificity of DGGR assays may depend on the manufacturer.

Immunologic assays (e.g., specific canine pancreatic lipase immunoassay [Spec cPL; IDEXX, idexx.com]) measure the concentration of pancreatic lipase by using specific antibodies targeted against pancreatic lipase.¹⁰ In general, immunologic assays are more analytically specific for lipase of pancreatic origin than catalytic assays and can be more heavily relied on for confirmation of pancreatic inflammation.^10,11

Analytical specificity of an assay for pancreatic lipase can be tested in 2 general ways, and these data may be reported by the manufacturers or sales representatives. One technique is to measure the concentration/activity of pancreatic lipase in a dog for which concentrations of pancreatic lipase are expected to be negligible (e.g., a dog with exocrine pancreatic insufficiency).¹² Detection of significant concentrations of lipase in these dogs suggests that the assay is detecting extrapancreatic lipases. Another technique is to measure lipase concentration/activity before and after administering a bolus of intravenous heparin.¹¹ Because heparin causes the release of extrapancreatic lipases into the circulation, increased concentration/activity after heparin administration suggests detection of newly released extrapancreatic lipases.^10,11

What are common pitfalls in the diagnosis of pancreatitis?

The biggest pitfalls in the diagnosis of pancreatitis arise from of an incomplete “clinical diagnosis” (i.e., failure to exclude alternate differentials such as a foreign body or relying on a single test to diagnose the disease). The author recognizes that client finances or other limitations may place the veterinarian in challenging circumstances, which may necessitate basing an educated judgment on a limited amount of data. In these cases, the author’s preference is to prioritize funds toward excluding differential diagnoses that require alternate/surgical intervention, thus prioritizing abdominal radiography where possible. Clients should be informed that a more complete clinical diagnosis may be required for dogs that have recurrent bouts of gastrointestinal upset or severe clinical presentations, so that the veterinarian can be confident in the diagnosis and treatment/prevention plan.

Elevated pancreatic lipase assay concentration/activity can also be seen in dogs with secondary pancreatic injury, thus necessitating integration of lipase data with imaging to ensure that the veterinarian has identified and is treating the most significant disease first.

How do you treat mild, moderate, and severe pancreatitis?

The severity of pancreatitis can vary, and mild cases of pancreatitis may be managed on an outpatient basis with regular checkups, whereas more moderate to severe cases often require intensive hospitalization and aggressive medical therapy.

Supportive Care

Supportive and symptomatic care focus on fluid therapy, nutrition, pain management, and antiemetics. Introducing food early during treatment is encouraged, is well tolerated,^13,14 and may necessitate placement of a nasogastric or nasoesophageal feeding tube. Low-fat gastrointestinal diets are frequently used in the initial management. For treatment of pain, the drugs of choice are opioids. Nonsteroidal anti-inflammatory drugs should be avoided. Full µ-opioid agonists (e.g., fentanyl, methadone) should be used for moderate to severe pain, whereas partial µ-opioid agonists may be suitable for mild pain/discomfort. Either ondansetron or maropitant citrate are suitable antiemetics and may be used together when indicated. The author prefers to use maropitant to control emesis and ondansetron to control nausea or for additional emetic control.

Anti-inflammatory corticosteroids have also been proposed as an adjunctive treatment for dogs with pancreatitis; however, data are limited and affected by study design.¹⁵ The author restricts use of anti-inflammatory corticosteroids to dogs that have been refractory to standard-of-care therapy, including fuzapladib sodium. Routine use of gastroprotectants in dogs with pancreatitis is discouraged.¹⁶

Targeted Therapeutics

Fuzapladib sodium (Panoquell-CA1; CEVA Animal Health, ceva.us) is a novel therapy that has been shown to improve the clinical signs associated with the acute onset of pancreatitis in dogs.¹⁷ The drug works by inhibiting activation of LFA-1 (leukocyte function–associated antigen 1), thereby reducing the extravasation of neutrophils into the tissues and reducing inflammation.⁴ Although additional studies are needed (and are ongoing by the manufacturer), the author uses this medication for dogs with symptomatic pancreatitis. The medication is given once daily via intravenous injection for 3 days. If clinical improvement is noted before completion of 3 doses, the remaining doses can be given on an outpatient basis. Although it may be tempting to stratify use of fuzapladib sodium based on clinical severity, dogs with pancreatitis can change quickly, and the author uses the medication when it is financially feasible. In the coming years, additional study may help provide aid for case selection.

Why do some dogs keep getting pancreatitis?

Most cases of pancreatitis are considered idiopathic, usually due to lack of diagnostic investigation into underlying causes. Underlying causes or risk factors for pancreatitis have been proposed (TABLE 2). If a potential risk factor is identified, control or avoidance of that risk factor may help prevent recurrence of disease. To try identifying a potential cause or risk factor for pancreatitis, the author recommends the following:

• Complete a drug/toxin history and a dietary history evaluating for high-fat foods (including prescription diets), table scraps, and access to trash.
• Measure ionized calcium and fasted serum triglyceride concentrations.
• Evaluate for obesity.
• Consider the potential for underlying endocrinopathies and test for them at diagnostically appropriate times (if clinically indicated).

SUMMARY

Patients with pancreatitis pose challenges for veterinarians. Diagnosis is often based on integrating data from a dog’s history, physical examination, diagnostic imaging, and a pancreatic lipase assay. Some catalytic lipase assays may detect extrapancreatic lipases, and using a 2 to 3 time upper reference interval cutoff may help mitigate the consequences of the lack of analytical specificity. One of the biggest pitfalls to an accurate diagnosis is incomplete integration of all data (e.g., failure to rule out differentials). Treatment includes supportive and targeted therapies. Prognosis and prevention of recurrence depend on identifying and eliminating underlying causes.

Disclosure

Dr. Cridge is a paid speaker and content developer for CEVA Animal Health, LLC, which markets and distributes fuzapladib sodium (Panoquell-CA1) within the United States.