Changes

May to June 2021 — reviewed. A literature search was conducted in April 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has been updated in line with current evidence in the literature including the National Institute for Health and Care Excellence (NICE) guideline Pancreatitis (NICE, 2020). The topic has undergone minor restructuring to improve clarity and navigation. No major changes to recommendations have been made.

Update

Goals

To support primary healthcare professionals to:

• Be aware of when to suspect chronic pancreatitis and make a provisional diagnosis.
• Refer people with suspected chronic pancreatitis for investigation and management, the urgency depending on clinical judgement.
• Arrange follow up and appropriate management of people with confirmed chronic pancreatitis following specialist assessment.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

NICE quality standards

No NICE quality standards were found during the review of this topic.

What is it?

• Chronic pancreatitis is a chronic, irreversible, inflammation and/or fibrosis of the pancreas, often characterized by severe pain and progressive endocrine and exocrine insufficiency [Conwell, 2014] [Kleeff, 2017] [Lohr, 2017] [Beyer, 2020].
  • It usually begins as recurrent acute pancreatitis where recurrent episodes of pancreatic inflammation of variable intensity and length lead to fibrosis of pancreatic tissue, and dilatation and calcification of the pancreatic duct and branches.
  • Pancreatic endocrine insufficiency results from damage to the endocrine tissue of the pancreatic gland (islets of Langerhans), characterized by a deficiency of insulin and other hormone secretion, leading to non-diabetic hyperglycaemia and pancreatogenic diabetes mellitus.
  • Pancreatic exocrine insufficiency results from damage to the acinar cells, leading to decreased secretion of digestive enzymes and bicarbonate by the pancreas, causing maldigestion and malabsorption.

What are the causes and risk factors?

• Alcohol is the major cause of chronic pancreatitis, responsible for up to 70–80% of cases [Singh, 2019].
  • However, fewer than 10% of people dependent on alcohol develop chronic pancreatitis, which suggests that other anatomical, environmental, and/or genetic factors are involved [Lew, 2017; Lohr, 2017; Olson, 2019].
• Other risk factors for chronic pancreatitis include:
  • Smoking.
    • This acts as a risk factor for early-onset and accelerated progression of chronic alcohol-related pancreatitis, and progression from non-gallstone-related acute pancreatitis to chronic pancreatitis [Lohr, 2017; Olson, 2019; Whitcomb, 2019].
  • Hypertriglyceridaemia [Kleeff, 2017; Lohr, 2017; Whitcomb, 2019].
  • Hypercalcaemia [Kleeff, 2017; Lohr, 2017]. 
  • Autoimmune disease [Lohr, 2017; Whitcomb, 2019].
    • This differs from other forms of pancreatitis, as pancreatic insufficiency and fibrosis can revert to normal with corticosteroid treatment [Beyer, 2020].
  • Genetic abnormalities.
    • Various autosomal dominant and autosomal recessive/modifier genes have been identified. Genetic causes should be suspected if there is early-onset pancreatitis (before 35 years of age), or there is a positive family history of pancreatitis [Kleeff, 2017; Lohr, 2017; Whitcomb, 2019]. Some genetic mutations may also increase the risk of developing pancreatic cancer [Gupte, 2018].
  • Drugs.
    • These include thiazide diuretics, azathioprine, tetracyclines, oestrogens, valproic acid, cimetidine, and dipeptidylpeptidase-4 inhibitors [MHRA, 2014; Goodchild, 2019; Olson, 2019; Whitcomb, 2019].
  • Obstructive causes.
    • These include gallstones, pancreatic ductal strictures or stones, pancreatic ductal carcinoma or other localized mass [Kleeff, 2017; Whitcomb, 2019].
  • Recurrent acute pancreatitis and severe necrotizing acute pancreatitis [Kleeff, 2017; Gupte, 2018; Whitcomb, 2019]. See the CKS topic on Pancreatitis - acute for more information.
    • Recurrent acute pancreatitis describes more than one episode of acute pancreatitis, regardless of severity. This is a much stronger risk factor for chronic pancreatitis than a single episode of acute pancreatitis. The global transition rate from recurrent pancreatitis to chronic pancreatitis is about 35%. About 40% of people with chronic pancreatitis do not have a history of acute or recurrent acute pancreatitis, and multiple risk and modifying factors determine these patterns of progression [Whitcomb, 2019].
    • A meta-analysis of 14 cohort studies (n = 8492 adults) found that chronic pancreatitis developed in 10% of people after a first episode of acute pancreatitis, and in 36% of people after recurrent acute pancreatitis [Sankaran, 2015].
• Up to 20% of cases are idiopathic, where no underlying cause is found [Beyer, 2020].

How common is it?

Data on the incidence and prevalence of chronic pancreatitis are limited due to challenges in confirming a diagnosis and variable durations of longitudinal follow up in studies [Levy, 2014].

• A survey of hospital discharges in England and Wales from 1960–88 found that chronic pancreatitis accounted for 7–11.1 discharges per million population per year in 1960–64, compared with 26.8–32.4 in 1980–84 [Johnson, 1991].
• A systematic review of three population-based cohort studies of chronic pancreatitis reported a global estimate of incidence of 9.62 cases per 100,000 person-years, and men had a significantly higher incidence than women [Xiao, 2016].
• Expert opinion in a review article notes an increasing incidence of chronic pancreatitis in the past decade, with annual incidence rates worldwide ranging from 5–14 per 100,000 people, and a prevalence of approximately 30–50 per 100,000 people [Kleeff, 2017].
• The prevalence of chronic pancreatitis increases with age, with a median age of diagnosis of 51–58 years [Kleeff, 2017].

What are the complications?

Possible complications of chronic pancreatitis include:

• Maldigestion and malabsorption.
  • The likelihood of pancreatic exocrine insufficiency increases with disease duration and it is predominantly a feature of late-stage disease. It may present with steatorrhoea when there is signficantly reduced secretion of pancreatic lipase [Levy, 2014; Lohr, 2017; Petrov, 2019].
  • Pancreatic exocrine insufficiency leads to potential maldigestion of fats and proteins [Levy, 2014]. There is also an increased risk of micronutritional deficiencies, such as fat-soluble vitamins (A, D, E, and K), water-soluble vitamins (B12 and folic acid), zinc, selenium, magnesium, and iron [Lohr, 2017; Arvanitakis, 2020].
• Malnutrition.
  • This may be due to reduced oral intake due to abdominal pain, nausea or vomiting; pancreatic exocrine insufficiency; continued alcohol consumption; or diabetes mellitus [Kleeff, 2017; Lohr, 2017; Arvanitakis, 2020].
• Diabetes mellitus.
  • Diabetes mellitus secondary to pancreatic disease is classified as pancreatogenic diabetes or type 3c diabetes mellitus (T3cDM), which is distinct from type 1 and type 2 diabetes mellitus, and has an increased risk of hypoglycaemia [Kleeff, 2017]. The risk of developing diabetes increases with surgical resection, duration of disease, and with age [Lohr, 2017; Beyer, 2020].
  • Worsening insulin deficiency is induced by progressive fibrosis of exocrine tissue [Petrov, 2019].
• Chronic pain.
  • Pain in chronic pancreatitis is multifactorial, involving potential duct obstruction and tissue hypertension, active inflammation, tissue ischaemia, local nerve damage (neuropathic pain), and peripheral and central sensitization of the nervous system [Kleeff, 2017; Lohr, 2017].
• Osteoporosis, osteopenia, fracture risk. See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.
  • There is an increased risk of low-trauma fracture due to malabsorption and pancreatic exocrine insufficiency [Lohr, 2017; Petrov, 2019].
• Pancreatic cancer. See the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral.
  • Chronic pancreatitis may increase the risk of developing pancreatic cancer at least 13-fold, and people with an underlying genetic cause (hereditary pancreatitis) may be at a further increased risk [Lew, 2017; Gupte, 2018].
• Pancreatic calcification, pancreatic duct stones and strictures, fistulae.
  • The presence of pancreatic ductal calcifications is pathognomonic for chronic pancreatitis [Lohr, 2017].
  • Pancreatic duct stones and structures are a common cause of pain [Kleeff, 2017].
• Pseudocyst formation.
  • This is a cavity with a fibrous wall filled with fluid or pancreatic juice [Kleeff, 2017].
  • These occur most commonly in people with alcohol-related chronic pancreatitis, and may develop complications (infection, bleeding, rupture) or cause compression of surrounding organs (gastric, duodenal, or biliary obstruction) [Lew, 2017; Lohr, 2017].
• Pseudoaneurysm.
  • These may need treatment if they become haemorrhagic [Lohr, 2017].
• Splenic or portal vein thrombosis.
  • Obstruction of the splenic or portal vein can produce gastric or oesophageal varices, which may bleed [Gupte, 2018].

What is the prognosis?

The prognosis of chronic pancreatitis varies depending on the underlying cause, lifestyle factors, and presence of complications [Levy, 2014] [Lohr, 2017] [Singh, 2019].

• A systematic review of three population-based cohort studies found the pooled mortality from an episode of chronic pancreatitis was 0.09 per 100,000 person-years [Xiao, 2016].
• An international multicentre longitudinal study of 2015 people with alcohol- and non-alcohol-related chronic pancreatitis found [Lowenfels, 1994]:
  • Overall survival was 70% at 10 years.
  • Overall survival was 45% at 20 years.
  • The standardized mortality ratio was 3.6.
  • Older people and those with alcohol-related disease had a worse prognosis.
• The natural history of chronic pancreatitis is characterized by [Levy, 2014]:
  • Episodes of acute pancreatitis, pain, hospitalizations, and surgical interventions in the first 5 years.
  • Stricture of the main biliary duct, chronic pseudocysts, pancreatic calcifications, and progressive pancreatic insufficiencies after 5–10 years.
  • Progressive pancreatic endocrine and exocrine insufficiency after 10 years onwards.

When should I suspect a diagnosis of chronic pancreatitis?

Suspect a diagnosis of chronic pancreatitis if a person has:

• Recurrent or persistent upper or generalized abdominal pain, particularly if there is a history or clinical features of alcohol misuse or other risk factors.
  • See the CKS topics on Pancreatitis - acute and Alcohol - problem drinking for more information.

How should I assess a person with suspected chronic pancreatitis?

If a person presents with a suspected diagnosis of chronic pancreatitis:

• Ask about:
  • The duration and characteristics of abdominal pain.
    • There is typically dull, deep, and severe epigastric pain, which may radiate to the back, or localize to the right or left upper quadrants. It may be relieved by sitting upright and leaning forward, and is often precipitated by eating.
    • It may be chronic and persistent, or there may be recurrent episodes of acute pain. See the CKS topic on Pancreatitis - acute for more information.
    • Note: abdominal pain may be absent in 20% of people, regardless of the cause of pancreatitis.
  • Associated symptoms, such as nausea and vomiting.
  • Symptoms of pancreatic exocrine insufficiency and malabsorption, such as steatorrhoea (foul-smelling, oily stools that are difficult to flush away), diarrhoea, bloating, abdominal cramps, excessive flatus, weight loss, and malnutrition.
  • Symptoms of pancreatic endocrine insufficiency and diabetes mellitus. See the CKS topic on Diabetes - type 1 for more information on the possible presentation of diabetes.
  • Family history of chronic pancreatitis.
• Examine the person for:
  • Signs of malnutrition — assess the body mass index (BMI).
  • Signs of chronic liver disease — may suggest chronic alcohol use. See the CKS topic on Alcohol - problem drinking for more information.
  • Jaundice — may be due to concomitant liver disease or mechanical obstruction of the extrahepatic bile duct by a mass in the head of the pancreas, or a pseudocyst. See the CKS topic on Jaundice in adults for more information.
  • Epigastric tenderness.
  • Abdominal distension — may be due to a pseudocyst, pancreatic ascites, or pancreatic cancer.
• Consider arranging investigations in primary care, depending on clinical judgement, to help clarify the diagnosis, assess for complications, or exclude other conditions:
  • Serum liver function tests (LFTs) — may be abnormal if there is coexistent liver disease or compression of the intra-pancreatic bile duct (for example by oedema or fibrosis within the head of the pancreas).
    • Note: serum amylase levels are not routinely raised in chronic pancreatitis, are not diagnostic, and should not be checked.
  • Serum HbA1c — to assess for diabetes mellitus or non-diabetic hyperglycaemia. See the CKS topic on Diabetes - type 1 for more information on the diagnosis of diabetes.
  • Faecal elastase — if low may indicate pancreatic exocrine insufficiency.
  • Abdominal ultrasound scan — can identify gallstones and some signs of chronic pancreatitis, such as pancreatic calcifications. See the CKS topic on Gallstones for more information.

What else could it be?

Alternative conditions which may present similarly to chronic pancreatitis include:

• Acute cholecystitis, biliary colic. See the CKS topics on Cholecystitis - acute and Gallstones for more information.
• Irritable bowel syndrome. See the CKS topic on Irritable bowel syndrome for more information.
• Intestinal obstruction, ischaemia, or infarction.
• Peptic ulcer disease. See the CKS topic on Dyspepsia - proven peptic ulcer for more information.
• Pancreatitic insufficiency syndromes.
• Diabetes mellitus complications including diabetic ketoacidosis and gastroparesis. See the CKS topics on Diabetes - type 1 and Diabetes - type 2 for more information.
• Pancreatic cancer and other intraductal cancers. See the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral for more information.
• Abdominal aortic aneurysm.
• Thoracic radiculopathy.
• Post-herpetic neuralgia. See the CKS topic on Post-herpetic neuralgia for more information.

Scenario: Management of chronic pancreatitis

From age 18 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of chronic pancreatitis.

Search dates

May 2016 - April 2021

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp pancreatitis, chronic /
• *Pancreatic Diseases /
• chronic adj3 pancreatitis.tw.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
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• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
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• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

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Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
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  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

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• Personal financial interests
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Competing interests declared for this topic:

None.