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Recurrent acute pancreatitis (RAP): Causes & Diagnosis

By Dr. Vikas Singla in Gastroenterology, Hepatology & Endoscopy

May 30 , 2022 | 4 min read

Recurrent acute pancreatitis (RAP) is a condition in which there are 2 or more episodes of acute pancreatitis. In patients with no signs of chronic pancreatitis, complete resolution of symptoms occur between episodes.

Up to 22% of patients have at least one recurrence. It is important to prevent recurrent attacks of pancreatitis because continued recurrence can lead to chronic pancreatitis or even Pancreatic Cancer.

Causes and Diagnosis of Recurrent Acute Pancreatitis

  1. Alcohol

    History sometimes reveals obscure alcohol intake as the culprit for RAP. Proper counselling to stop alcohol is the only effective way to prevent recurrent attacks of pancreatitis.

  1. Gallstones

    Gallstone disease should be strongly considered when there is no prior history of cholecystectomy, and the attacks of acute pancreatitis are associated with a greater than two-fold rise in liver enzymes. 

Transabdominal ultrasound is a reasonable initial test for gallstones but not as reliable for CBD stones. The best imaging tests for gallbladder stones and CBD stones are MRI and endoscopic ultrasound (EUS)

In patients with both CBD and Gall bladder stones, Endoscopic Retrograde Cholangiography and Pancreatography (ERCP) should be performed for removal of CBD stones, followed by cholecystectomy, preferably in the same hospital setting in cases of mild pancreatitis. 

If no gallbladder stones are documented on either or both cross-sectional imaging and EUS and liver biochemistries are normal or near-normal with attacks, the benefit of cholecystectomy to prevent recurrent bouts is controversial.

  1. If gallstones and alcohol etiologies are ruled out, less common causes should also be considered, such as
  1. Ductal obstruction (e.g., intraductal papillary mucinous neoplasm, solid pancreatic tumours, ampullary tumours)

  2. Medications (diuretics, HIV medications, and azathioprine)

  3. Smoking

  4. Hypercalcemia

  5. Hypertriglyceridemia

  6. Genetic abnormalities

  7. Autoimmune pancreatitis

Also Check: Gallbladder Stones Treatment

Detailed history, physical examination, blood tests and contrast-enhanced CT or magnetic resonance cholangiopancreatography (MRCP) helps in getting an accurate diagnosis. Mutations in PRSS1 (protease, serine, 1), CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), SPINK1 (serine protease inhibitor kazal type 1), and CTRC (chymotrypsin C) genes may be present in patients who present with RAP during adulthood, even in the absence of family history.

  1. Pancreas divisum and sphincter of Oddi dysfunction (SOD) are often missed etiologies of RAP.

  1. Pancreas divisum

With the advent of EUS and MRCP, ERCP is no more the gold standard for identifying pancreas divisum. Though the benefit of minor papilla sphincterotomy for the treatment of pancreas divisum has always been questionable, there are now sufficient compelling evidences suggesting its benefit. Endoscopic interventions are designed in patients with pancraeatic divsum and no other identifiable cause of RAP. This is done to reduce minor papilla tone, leading to increased dorsal duct drainage and decreased pressure.

Sphincter of Oddi Dysfunction(SOD)

Sphincter of Oddi dysfunction (SOD) is classically defined as a pathologic elevation in basal sphincter pressure >40 mmHg, commonly seen in post cholecystectomy leading to dilation of the pancreatic and/or biliary ducts, pain, and enzyme abnormalities. 

Though SOD may trigger acute pancreatitis by causing an increase in pancreatic intraductal pressure, there are little data supporting the practice of pancreatic sphincterotomy for the treatment of RAP. A trial evaluated the effects of endoscopic sphincterotomy in patients with RAP. It reported that among patients with sphincter of Oddi dysfunction, a combination of biliary and pancreatic sphincterotomy vs only biliary sphincterotomy has similar effects in preventing pancreatitis recurrence.

Rule out occult pancreatic tumours, particularly in older adults with recent-onset diabetes mellitus

Pancreatic cancer should be suspected in patients of age >50 years with a history of recent-onset diabetes mellitus. For small tumours <2 cm in size, EUS is superior to MRI, and CT scans in terms of diagnosis and acquiring tissue for histopathologic evaluation.

Unknown aetiology in some cases

Ten to twenty percent of cases of RAP have no identifiable cause; these patients should be routinely evaluated with EUS. EUS and MRCP are less invasive alternatives for identifying chronic pancreatitis, ductal abnormalities (e.g., strictures), and occult obstructive etiologies. Endoscopic sphincterotomy is most widely accepted when there is discrete aetiology of RAP like concomitant duct dilation or obstructing pathology (e.g., stone or stricture). While biliary sphincterotomy is safer than pancreatic sphincterotomy, the benefit of empiric biliary sphincterotomy for the treatment of occult choledocholithiasis or microlithiasis is still unproven, and its impact on the natural history of RAP also remains unclear. 


  1. Often the aetiology of RAP is not easily identifiable. Common etiologies missed on antecedent evaluation like obscure choledocholithiasis or microlithiasis need to be ruled out using advanced imaging modalities such as MRI and EUS.
  2. Genetic testing should be considered even in patients with the adult-onset disease and no family history.
  3. Rule out occult pancreatic tumours, particularly in older adults with recent-onset diabetes mellitus.
  4. Pancreatic divisum and SOD are often missed etiologies of RAP that can be treated with endoscopic interventions. 
  5. ERCP should only be done with discrete aetiology for RAP. The benefit of empirical biliary/ pancreatic sphincterotomy and empirical cholecystectomy without any proven cause is controversial.

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