eMedicine Specialties > Gastroenterology > Pancreas

Pancreatitis, Acute: Differential Diagnoses & Workup

Author: Timothy B Gardner, MD, Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of Pancreatic Disorders, Section of Gastroenterology, Dartmouth-Hitchcock Medical Center
Coauthor(s): Brian S Berk, MD, Assistant Professor, Department of Medicine, Dartmouth Medical School; Director of End Stage Liver Disease, Section of Gastroenterology, Dartmouth Hitchcock Medical Center
Contributor Information and Disclosures

Updated: Dec 29, 2009

Differential Diagnoses

Workup

Laboratory Studies

• Once a working diagnosis of acute pancreatitis is reached, laboratory tests are obtained to support the clinical impression. In addition to confirming the diagnosis, laboratory tests are helpful in defining an etiology and looking for complications.
• Amylase and lipase
  • Serum amylase and lipase levels are typically elevated in persons with acute pancreatitis. However, these elevations may only indicate pancreastasis. In research studies, amylase or lipase levels at least 3 times above the reference range are generally considered diagnostic of acute pancreatitis.
  • Serum amylase determinations are routinely available, but they are not specific for pancreatitis. Elevations can occur in anyone with small intestinal obstruction, mesenteric ischemia, tubo-ovarian disease, renal insufficiency, or macroamylasemia. Rarely, elevations may reflect parotitis.
  • The serum half-life of amylase is short, and elevations generally return to reference ranges within a few days.
  • Lipase has a slightly longer half-life and abnormalities may support the diagnosis if a delay occurs between the pain episode and the time the patient seeks medical attention. Elevated lipase levels are more specific to the pancreas than amylase levels.
  • The level of serum amylase or lipase does not indicate whether the disease is mild, moderate, or severe, and monitoring levels serially during the course of hospitalization does not offer insight into prognosis.
• Liver-associated enzymes
  • Determine alkaline phosphatase, total bilirubin, aspartate aminotransferase, and alanine aminotransferase levels to search for evidence of gallstone pancreatitis.
  • An alanine aminotransferase level greater than 150 U/L suggests gallstone pancreatitis and a more fulminant disease course.
• Calcium, magnesium, cholesterol, and triglycerides: Determine these levels to search for an etiology of pancreatitis (hypercalcemia or hyperlipidemia) or complications of pancreatitis (hypocalcemia resulting from saponification of fats in the retroperitoneum). However, be wary of the fact that baseline serum triglyceride levels can be falsely lowered during an episode of acute pancreatitis.
• Serum electrolytes, BUN, creatinine, and glucose: Measure these to look for electrolyte imbalances, renal insufficiency, and pancreatic endocrine dysfunction.
• CBC count
  • Hemoconcentration at admission (an admission hematocrit value greater than 47%) has been proposed as a sensitive measure of more severe disease. However, this has subsequently been shown to have value only as a negative predictor, that is, a lack of hemoconcentration effectively rules out severe disease.
  • Leukocytosis may represent inflammation or infection.
• C-reactive protein
  • A C-reactive protein (CRP) value can be obtained 24-48 hours after presentation to provide some indication of prognosis. Higher levels have been shown to correlate with a propensity toward organ failure.
  • A CRP value in double figures (ie, >10 mg/dL) strongly indicates severe pancreatitis. CRP is an acute-phase reactant that is not specific for pancreatitis.
• Arterial blood gases
  • Measure ABGs if a patient is dyspneic.
  • Whether tachypnea is due to acute respiratory distress syndrome or diaphragmatic irritation must be determined.
• LDH, BUN, and bicarbonate should also be measured at admission and at 48 hours in order to help determine the Ranson criteria for survival.
• IgG4 levels can be checked to evaluate for autoimmune pancreatitis.  However, this test is not specific, as IgG4 levels can be elevated in up to 10% of patients with acute pancreatitis who do not have autoimmune pancreatitis.
• Trypsin and its precursor trypsinogen-2 in both the urine and the peritoneal fluid have been evaluated as possible markers for acute pancreatitis but are not widely used. Trypsinogen activation peptide (TAP) is formed when trypsinogen is cleaved to form trypsin and can be measured commercially in the urine to diagnose acute pancreatitis and to help determine severity.
• Although not currently in use clinically, polymorphisms in the chemokine monocyte chemotactic protein 1 (MCP-1) gene may also predict severity. This is the first gene identified that plays a role strictly in predicting the severity of disease.

Imaging Studies

• Although unnecessary in most cases of pancreatitis, visualization of inflammatory changes within the pancreas provides morphologic confirmation of the diagnosis. Obtain imaging tests when the diagnosis is in doubt, when severe pancreatitis is present, or when a given imaging study might provide specific information needed to answer a clinical question.
• Abdominal radiography
  • This modality has a limited role in acute pancreatitis.
  • These radiographs are primarily used to detect free air in the abdomen, indicating a perforated viscus, as would be the case in a penetrating, perforated duodenal ulcer.
  • In some cases, the inflammatory process may damage peripancreatic structures, resulting in a colon cut-off sign, a sentinel loop, or an ileus.
  • The presence of calcifications within the pancreas may indicate chronic pancreatitis.
• Abdominal ultrasonography
  • This is the most useful initial test in determining the etiology of pancreatitis and is the technique of choice for detecting gallstones.
  • In the setting of acute pancreatitis, sensitivity is reduced to 70-80%. In addition, the ability to identify choledocholithiasis is limited.
  • Ultrasonography cannot measure the severity of disease.
• Abdominal CT scanning
  • This is generally not indicated for patients with mild pancreatitis unless a pancreatic tumor is suspected (usually in elderly patients).
  • CT scanning is always indicated in patients with severe acute pancreatitis and is the imaging study of choice for assessing complications. Scans are seldom needed within the first 72 hours after symptom onset unless the diagnosis is uncertain, because inflammatory changes are often not radiographically present until this time.⁴
  • Abdominal CT scans, like the one shown below, also provide prognostic information based on the following grading scale developed by Balthazar^5,6 :
    • A - Normal
    • B - Enlargement (as seen in the image below)
    • C - Peripancreatic inflammation
    • D - Single fluid collection
    • E - Multiple fluid collections
    • 
      

      

      Abdominal CT scan showing pancreatic enlargement and peripancreatic fat stranding. The gallstones are not visible.

      [ CLOSE WINDOW ]

      

      Abdominal CT scan showing pancreatic enlargement and peripancreatic fat stranding. The gallstones are not visible.

  • The chances of infection and death are virtually nil in grades A and B but steadily increase in grades C through E. Patients with grade E pancreatitis have a 50% chance of developing an infection and a 15% chance of dying.
  • Dynamic spiral CT scanning is used to determine the presence and extent of pancreatic necrosis. After the administration of an oral agent to define bowel structures, a study of the upper abdomen is performed twice, before and after administration of an intravenous bolus of iodine contrast agent. A healthy pancreas shows density numbers of 30-40 Hounsfield units on an unenhanced study, increasing to 100-150 Hounsfield units on an enhanced study. When pancreatic necrosis is present, focal or diffuse areas of unenhanced parenchyma on the second study suggest pancreatic necrosis. Pancreatic necrosis for research purposes is defined as loss of enhancement in at least 30% of the pancreatic parenchyma.
• Magnetic resonance cholangiopancreatography
  • Magnetic resonance cholangiopancreatography (MRCP) has an emerging role in the diagnosis of suspected biliary and pancreatic duct obstruction in the setting of pancreatitis.
  • Heavily T-2–weighted images provide a noninvasive image of the biliary and pancreatic ducts.⁷
  • Although not as sensitive as ERCP, MRCP is safer, noninvasive, and fast, and it provides images useful in guiding clinical care decisions. This modality should be used if choledocholithiasis is suspected, but there is concern of worsening pancreatitis is ERCP is performed.
• Endoscopic ultrasonography
  • Endoscopic ultrasonography (EUS) is an endoscopic procedure that allows a high-frequency ultrasound transducer to be inserted into the gastrointestinal tract to visualize the pancreas and the biliary tract. This study allows a more detailed image to be obtained than with transcutaneous ultrasonography because the high-frequency transducer can be introduced directly adjacent to the pancreas.
  • EUS is often helpful in evaluating the cause of severe pancreatitis, particularly microlithiasis and biliary sludge, and can help identify periampullary lesions better than other imaging modalities.
  • Its principal role in the evaluation of acute pancreatitis is the detection of microlithiasis and periampullary lesions not easily revealed by other methods. This modality should not be used to help identify chronic pancreatitis until several months after the episode of acute pancreatitis has been completed.
  • In specialized centers with highly trained medical staff, a secretin-stimulated EUS study may reveal resistance to ductal outflow at the level of the papilla, as evidenced by dilatation of the pancreatic duct to a greater extent and longer duration than in a healthy population. This can be helpful in evaluating patients with recurrent idiopathic pancreatitis.

Other Tests

• With the advent of molecular medicine, various genetic abnormalities have been associated with pancreatitis. Although effective treatments for these conditions have yet to be discovered, it is sometimes reasonable to begin testing for these mutations in patients with otherwise idiopathic pancreatitis, rather than subjecting the entire group to the risks of endoscopic sphincterotomy or stent placement for presumptive SOD. As more is learned about molecular mechanisms and therapy, logical novel treatments can eventually be offered to these patients as part of clinical trials. Of course, as with any type of genetic testing, expert genetic counseling that addresses social, familial, insurance, and financial issues is essential for all persons prior to being tested. In fact, it is the author’s policy not to perform any genetic testing unless patients are first counseled by a qualified genetic counselor.
• Hereditary pancreatitis has been associated with a mutation of cationic trypsinogen (PRSS1). At least 4 mutations have thus far been identified. These mutations appear to render the protein resistant to second-line proteolytic defense mechanisms. Patients with PRSS1 mutations typically develop their first episode of pancreatitis by the time they are in their mid teens. Most often, there is a strong family history of pancreatic disease (eg, acute or chronic pancreatitis, pancreatic malignancy). It should be noted that the PRSS1 -induced disease is very rare.
• Some patients with idiopathic pancreatitis have atypical mutations in the CFTR gene. This gene follows an autosomal recessive pattern of inheritance. This is a fascinating advance in understanding the spectrum of cystic fibrosis in which phenotypic expression depends on the degree to which the genetic mutation affects the activity of the CFTR enzyme's function. Relatively minor mutations that do not affect pulmonary function may influence chloride transport in the pancreas enough to predispose individuals to development of recurrent idiopathic pancreatitis.
• Mutations in the SPINK1 gene can predispose patients to acute pancreatitis. The SPINK1 protein blocks the active binding site of trypsin, rendering it inactive. However, approximately 1 in 100 persons in the United States are at least heterozygotes for SPINK1. It is an autosomal recessive gene pattern of inheritance. Therefore, although this is not usually enough to cause pancreatitis, mutations of the SPINK1 gene are likely a cofactor responsible for pancreatitis in some individuals.

Procedures

• Endoscopic retrograde cholangiopancreatography
  • ERCP is an endoscopic procedure used to evaluate the biliary and pancreatic ductal system and is indicated in a subset of patients with acute pancreatitis. However, ERCP should be used with extreme caution in patients with acute pancreatitis and should never be used as a first-line diagnostic tool in this disease.⁷
  • ERCP should only be used in the following situations: (1) if a patient has severe acute pancreatitis that is believed, and is seen on other radiographic studies, to be secondary to choledocholithiasis, and (2) if a patient has biliary pancreatitis and is experiencing worsening jaundice and clinical deterioration despite maximal supportive therapy. When combined with sphincterotomy and stone extraction, it may reduce the length of hospital stay, the complication rate, and, possibly, the mortality rate.
  • Occasionally, ERCP with sphincter of Oddi manometry reveals SOD as the cause of recurrent idiopathic pancreatitis (see the diagram below). However, in the setting of suspected SOD, the risk of the procedure inducing pancreatitis is at least 30%.
• CT-guided needle aspiration
  • This procedure is used to differentiate infected necrosis and sterile necrosis in patients with severe necrotizing pancreatitis.
  • The needle is placed into an area of low attenuation in or around the pancreas of a patient with fever and tachycardia or other signs of a systemic inflammatory response syndrome, generally following the first week of severe pancreatitis. The procedure may be repeated weekly if clinically indicated.
  • The specimen should be delivered to the laboratory within an hour and interpreted promptly. The specimen should always be evaluated for Gram stain, culture, and sensitivity.
  • If the Gram stain shows bacteria or fungi, surgical debridement of the infected necrosis is generally indicated. An exception would be if the patient could not tolerate surgery; in this case, CT-guided catheter drainage may be more effective.
• EUS-guided needle aspiration: EUS can often be used to differentiate infected versus noninfected necrosis as per the CT scan (see Imaging Studies).
• EUS-guided fluid collection drainage
  • EUS can be used to drain pancreatic and peripancreatic fluid collections that have complicated an episode of acute pancreatitis. These procedures should only be carried out once the pseudocyst has had the opportunity to mature.
  • A complete description of these procedures is beyond the scope of this article.

Histologic Findings

For practical purposes, the infinite spectrum of pancreatitis severity is usually subdivided into mild and severe categories.

In mild cases, the gland exhibits interstitial edema and an inflammatory infiltrate without hemorrhage or necrosis, usually with minimal or no organ dysfunction. In severe cases, extensive inflammation and necrosis of the pancreatic parenchyma are present, often associated with severe gland dysfunction and multiorgan system failure.

At surgery, peripancreatic fatty tissue is predominantly involved by necrosis, while the gland is usually less affected; hence, overestimation of the extent of pancreatic necrosis is not uncommon. In very severe cases, arterial thrombosis may lead to panlobular infarction in which the gland becomes a hemorrhagic, necrotic, gangrenous mass. The natural history of fat necrosis depends on its location and extent; small areas (<1 cm) may resolve entirely, while large areas (>5 cm) may liquefy within a fibrotic capsule.

Staging

Various strategies have been used to predict the severity and outcome of acute pancreatitis. Each has advantages and disadvantages, and none is currently recognized as a criterion standard.

Patients are diagnosed with severe acute pancreatitis if they show evidence of organ failure (ie, systolic blood pressure <90 mm Hg, PaO₂ <60 mm Hg, serum creatinine >2 mg/dL, GI bleeding >500 mL/24 h), local complications (eg, necrosis, abscess, pseudocyst), or a Ranson score of more than 3 or an APACHE score of more than 8, as described below. (See also the diagram below.)

• The Ranson criteria are perhaps best known; however, they have several drawbacks.
  • First, 11 criteria are used, some of which are evaluated on day 1 and others on day 2. The Ranson score is valid only at 48 hours after onset and not at any other time during the disease.
  • Second, the threshold for an abnormal value depends on whether the pancreatitis is caused by alcohol or gallstones.
  • Finally, the sensitivity is only 73% and the specificity is 77% to predict morality.
• Acute physiology and chronic health evaluation
  • The APACHE score has the advantage of being able to assess the patient at any point during the illness; however, it is very cumbersome for routine clinical use.
  • Attempts have been made to make this evaluation user friendly (eg, APACHE II, simplified acute physiology score, IMRIE score), but it still remains cumbersome.
  • The sensitivity is 77%, and the specificity is 84%.
• Peritoneal lavage has a high specificity (93%); however, it has a low sensitivity (54%).
• Dynamic CT scanning of the abdomen is widely available and useful in predicting the outcome of acute pancreatitis. Using the Balthazar criteria described in Imaging Studies, the sensitivity is 87%, and the specificity is 88%.
• C-reactive protein
  • CRP is a nonspecific acute-phase reactant produced by the liver in response to inflammation.
  • A CRP level greater than 6 at 24 hours, or greater than 7 at 48 hours, is consistent with severe acute pancreatitis.
  • The sensitivity of this test is 73%, and the specificity is 71%.
• Several blood tests show promise in predicting the severity of acute pancreatitis. These include trypsin activation peptide, polymorphonuclear elastase, interleukin-6, and phospholipase A₂. They are generally not used in clinical practice and are more expensive than typically used tests. Some are only slightly better than using CRP.
• For research purposes, the Atlanta classification of acute pancreatitis has been used to differentiate between severe and mild cases of acute pancreatitis.

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