Review
Idiopathic recurrent acute pancreatitis

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Summary

Idiopathic recurrent acute pancreatitis is clinically challenging and has substantial socioeconomic consequences. Investigations are expensive and often reveal little about the cause of the disease. Little is known about the interaction between genetic, environmental, anatomical, and other factors that contribute to the disease. Data on the efficacy, safety, and long-term outcomes of endoscopic therapies are scarce. The effect of idiopathic recurrent pancreatitis on quality of life is often underestimated. A more thorough examination of the causes of the disease and the roles of other associated risk factors is needed, as are well designed clinical studies with robust and objectively measurable outcomes. Ideally, evaluation of the causes of disease and therapy should be done only in specialised centres, should follow a protocol, and all outcomes should be formally assessed.

Introduction

Acute pancreatitis is one of the most common causes of acute hospital admission, and substantially contributes to morbidity, mortality, and health-care costs.1, 2 Recurrent acute pancreatitis (also known as relapsing acute pancreatitis) is defined as two or more discrete episodes of acute pancreatitis, and has an estimated annual incidence of 8–10 per 100 000 and a prevalence of 110–140 per 100 000 worldwide.3

Acute pancreatitis has several aetiological factors, some of which are readily recognised as causative, whereas others are not. Most cases of acute pancreatitis are caused by either gallstones or alcohol.1 When biliary factors and alcohol are ruled out, 25% of patients with acute pancreatitis subsequently develop recurrent acute pancreatitis.4 Routine investigations identify a cause in up to 80% of cases; however, in up to 20% of cases, the cause of disease remains unclear—this is known as idiopathic recurrent acute pancreatitis. Both the sequence of testing and treatment options for patients with idiopathic recurrent acute pancreatitis are not clear, and have been subject to debate.1, 5 In at least 7% of cases, more than one causative factor can be identified (eg, in an individual who is genetically predisposed to recurrent acute pancreatitis, a toxic or obstructive cause can be an additional contributing factor).6 Although some causes are obvious, data on the role of genetic or environmental factors are scarce, and, more importantly, the interplay between the factors that contribute to pancreatitis is not well understood. If the underlying cause is not corrected, recurrences of acute pancreatitis or chronic pancreatitis could occur.7 However, invasive techniques such as endoscopic retrograde cholangiopancreatography (ERCP) can cause complications, including further episodes of pancreatitis.8 In this Review, we address the issues associated with idiopathic recurrent acute pancreatitis; management of acute pancreatitis and chronic pancreatitis are beyond the scope of this Review.

Section snippets

Defining acute pancreatitis and recurrent acute pancreatitis

Acute pancreatitis is defined as a condition in which at least two of the following three criteria are present: abdominal pain, elevations in serum amylase and lipase concentrations that are equal to or greater than three times the upper limit of normal, and cross-sectional imaging (typically CT or MRI) or ultrasound findings that suggest pancreatitis.9 Recurrent acute pancreatitis is generally defined as a condition in which at least two well documented episodes of acute pancreatitis have

Does idiopathic recurrent acute pancreatitis represent early chronic pancreatitis?

In acute pancreatitis, once inflammation resolves, the pancreas is expected to return to normal function and morphology. However, available data suggest that recovery might not necessarily be complete, and ductal changes can persist without any signs or symptoms of acute or chronic pancreatitis.13, 14 In some cases, pain persists with inflammatory changes that are apparent on imaging; this type of pancreatitis is often referred to as smouldering pancreatitis. Smouldering pancreatitis is thought

Aetiological considerations

As mentioned previously, some of the aetiological factors associated with recurrent acute pancreatitis are widely accepted to be causative, whereas others are debated, and some of the invasive testing techniques that are used for the assessment of the cause, and even the treatments themselves, pose an additional risk of pancreatitis. The problem is compounded by the fact that there is often more than one causative factor, and correction of an apparent cause might not lead to an alteration in

Evaluation

As with any illness, a proper history and physical examination are needed to assess recurrent acute pancreatitis. A review of medications and assessment of risk factors including smoking and alcohol use are important. Family history of pancreatic disease and congenital hyperlipidaemia should be obtained. Routine serum chemistries are useful, including obtaining serum calcium and fasting triglyceride concentrations. Alanine aminotransferase concentrations that are two-to-three times greater than

Genetic testing

Whether gene mutations in themselves cause acute recurrent pancreatitis is unclear. Some gene mutations are common in patients with acute recurrent pancreatitis, and whether these gene mutations act in the presence of other factors such as pancreas divisum to modify disease severity or treatment response remains unclear. Many hypotheses about the role of gene mutations in acute recurrent pancreatitis are speculative. Data clearly indicate that pathogenic genetic variants of PRSS1, SPINK1, CTFR,

Role of laparoscopic cholecystectomy

In clinical practice, empirical laparoscopic cholecystectomy has been done in patients with recurrent acute pancreatitis to treat presumptive microlithiasis not detected on conventional imaging. Although this technique is commonly used, no evidence supports its use. A retrospective study has shown a decrease in recurrence of pancreatitis after cholecystectomy in patients with idiopathic recurrent acute pancreatitis.62 However the authors of the study did not have any information on the

Disease management

Every episode of acute pancreatitis should be managed, irrespective of the cause, with supportive measures, including aggressive hydration, adequate analgaesia, and other interventions as appropriate.61 Metabolic abnormalities should be corrected. CT scanning is recommended, typically at least 48–72 h after presentation, for severe episodes, to allow any necrosis to develop. Transabdominal ultrasound should be considered when no CT abnormalities or laboratory testing point to a diagnosis.

Current problems and future trends

Recurrent acute pancreatitis represents an important problem with respect to patient disability and health-care burden. Recurrent acute pancreatitis generally presents with abdominal pain and elevations in lipase or amylase concentrations that are more than three times the upper limit of normal. Clinically, these problems are compounded when patients do not have a classic clinical presentation. Understanding of the disease is impaired by scarcity of natural history data and knowledge of the

Search strategy and selection criteria

We searched PubMed from Jan 1, 2008, to March 1, 2018, for the term “acute recurrent pancreatitis”. We included all clinical trials and all clinical studies, consensus development conferences, and reviews. We limited our search to core clinical journals in English. Any older publications that were cross-referenced were reviewed and included.

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