Abstract

Chronic pancreatitis is a progressive inflammatory condition characterised by irreversible fibrosis of the pancreatic parenchyma, accompanied by calcification and dilatation of the main pancreatic duct and its branches. There are multiple aetiologies including excessive alcohol consumption, smoking, autoimmune disease and post acute severe pancreatitis. However, excessive alcohol consumption is the most common cause. The prevalence of chronic pancreatitis is variable, with estimates between 4 and 52.4 per 100,000. A mismatch exists between reported incidence and prevalence in many studies suggesting chronic pancreatitis is under recognised. One cause for this mismatch is that once diagnosed many patients are lost to secondary care follow-up. Therefore, although a GP may only see two new cases during their career they are likely to encounter patients requiring recurrent consultations. Chronic pancreatitis presents with relapsing, remitting upper abdominal pain accompanied by features of malabsorption and malnutrition due to pancreatic exocrine insufficiency and diabetes due to endocrine deficiency. Diabetes is more likely to occur as the duration of chronic pancreatitis increases, where pancreatic exocrine insufficiency has developed after pancreatic resection and in those with early onset calcification. Patients with suspected chronic pancreatitis should be referred to gastroenterology or a specialist pancreatic centre for confirmation of the diagnosis.

Chronic pancreatitis is an irreversible, progressive condition where scarring of the pancreas occurs in response to inflammation from many aetiologies including excessive alcohol consumption, smoking, autoimmune disease and post acute severe pancreatitis (see table 1).

It presents with relapsing, remitting upper abdominal pain accompanied by features of malabsorption and malnutrition due to pancreatic exocrine insufficiency and endocrine deficiency with diabetes.

Recognising chronic pancreatitis can be challenging especially in its early stages and patients require multidisciplinary management. GPs, in conjunction with secondary care colleagues, have a crucial role in managing the often complex needs of these individuals.

Causes and risk factors

Chronic pancreatitis is a progressive condition characterised by irreversible fibrosis of  the pancreatic parenchyma, accompanied by calcification and dilatation of the main pancreatic duct and its branches.¹  The prevalence of chronic pancreatitis is variable, with estimates between 4 per 100,000 population (in a UK study) and 52.4 per 100,000.^2-5 A mismatch exists between reported incidence and prevalence in many secondary care studies suggesting chronic pancreatitis is under recognised, especially with historical post-mortem series reporting prevalence rates up to 13%.

One cause for this mismatch is that once diagnosed many patients are lost to secondary care follow-up. Therefore, although a GP may only see two new cases during their career they are likely to encounter patients requiring recurrent consultations.^3,5,6

Fibrotic changes in the pancreas develop following multiple inflammatory insults and can be due to a variety of causes, see table 1. However, excessive alcohol consumption is the most common cause and studies have estimated it to account for 45-84% of cases in the Western world.^3,7 Smoking has also been shown to be a major independent, dose-related risk factor for chronic pancreatitis.^5,7

Presentation

Patients with chronic pancreatitis can present insidiously and are challenging to diagnose especially in the early phases. Symptoms including upper abdominal pain, weight loss and loose stools are non specific and can be attributed to other conditions, see table 2.⁸ 

Classically the pain is localised to the epigastrium, radiates to the back or flanks and is described as dull in nature. Duration and frequency of pain episodes vary but as the disease progresses attacks can intensify and lengthen.⁹

The timing of the development of symptoms from pancreatic exocrine insufficiency (diarrhoea and malnutrition) and endocrine failure (diabetes) can vary significantly, either preceding the onset of pain or taking many years to manifest.¹⁰ Diabetes is more likely to develop as the duration of chronic pancreatitis increases, where pancreatic exocrine insufficiency has developed after pancreatic resection and in those with early onset calcification.¹¹

Rarely, chronic pancreatitis can present with jaundice from biliary obstruction or cholangitis due to inflammation of the pancreas around the bile duct. Clinical distinction between chronic pancreatitis and pancreatic cancer can be difficult. Urgent referral for investigation should be made where the possibility of underlying pancreatic cancer exists.¹²

Assessment and screening for complications

When first assessing patients with symptoms of chronic pancreatitis it is helpful to start by excluding other differential diagnoses, see table 2. Clinical suspicion of chronic pancreatitis alone is insufficient for diagnosis and a composite assessment is necessary. Symptoms and clinical history, cross-sectional imaging, computed tomography (CT), and assessment of nutritional status is recommended, see table 3,¹³ with referral to secondary care for confirmation of diagnosis, see table 4.

A histological diagnosis is possible for chronic pancreatitis but a biopsy is rarely performed because of its invasive nature, risk of complications and poor intra-observer agreement of chronic pancreatitis features.¹⁴

NICE guidance on the management of chronic pancreatitis in primary care advocates blood tests and supports abdominal ultrasound to exclude gallstones as a cause.

CT is the preferred first-line diagnostic investigation especially where there is a history of alcohol misuse.¹⁵ The sensitivity of CT exceeds that of ultrasound, (75-90% vs 60-70%) although the specificity is similar 85% vs 80-90%.¹⁶ Magnetic resonance imaging (MRI) is used for detailed ductal assessment in secondary care.¹⁷

Full blood count (FBC) and biochemistry may be normal, but liver function can be affected if there is concomitant liver disease, or in the instance of common bile duct compression by strictures or pseudocysts. HbA1c or fasting glucose should be checked to screen for diabetes.^11,18 Serum tumour markers and amylase testing are not helpful in the diagnosis of chronic pancreatitis and should not be performed, although amylase remains useful in diagnosing acute pancreatitis.¹⁵

Malnutrition is a major complication resulting from fat and protein malabsorption in addition to deficiencies of vitamins A, D, E and K.¹⁹ Up to 63% of chronic pancreatitis patients have fat soluble vitamin deficiencies.19,20 Vitamin D deficiency occurs in many patients, and also in the general population, and although its presence is not diagnostic, deficiencies should be corrected.²¹ Several serum markers have been associated with pancreatic exocrine insufficiency including magnesium, haemoglobin, albumin, pre albumin and retinol binding protein A.²² Vitamin E has been shown to be the single most useful parameter to check as a marker of malnutrition,²² see table 3.

Osteoporosis and a high prevalence of low trauma fracture are seen in patients with chronic pancreatitis with one meta-analysis reporting 65% of chronic pancreatitis patients affected by osteoporosis or osteopenia.²³ In addition to the reduction in bone mass, patients with chronic pancreatitis have been shown to have significant reductions in lean body mass and fat mass despite normal body mass index scores,²⁰ see figure 1.

Exocrine function can be assessed with faecal elastase-1 (FEL-1). This is an indirect test of pancreatic function using FEL-1 as a surrogate. Other methods to assess pancreatic function directly have been described but are highly invasive and not widely available.

FEL-1 measurement is easily performed; patients collect a pea-sized amount of faeces for analysis.  It is highly specific and sensitive in severe disease but less sensitive and specific in mild to moderate disease.²⁴ It is felt to be the most appropriate first-line investigation for screening for pancreatic exocrine insufficiency in at-risk patients.²⁵

Patients with chronic pancreatitis are at high risk of pancreatic cancer26 and have increased mortality largely due to cardiovascular complications.²⁷

A reduction of 20-30% in ten-year survival is seen in chronic pancreatitis compared with the general population,28 so continued follow-up is required.

Management

NICE recommendations for management of patients with alcohol-related chronic pancreatitis as well as international guidelines advocate a multidisciplinary approach.^13,17,29

The treatment of chronic pancreatitis is the same regardless of aetiology.

Aims of therapy include pain control, management of exocrine and endocrine insufficiency and management of complications.³⁰ Input from chronic pain teams, dietetics and diabetologists can be beneficial for complex pain and management of exocrine and endocrine insufficiency respectively. Surgery may be indicated for selected patients. 

Complete abstinence from alcohol and smoking cessation is essential for all patients to slow disease progression31 and improve pain.^7,32

Chronic pain and the burden of incurable disease may affect relationships and social interactions and patients with chronic pancreatitis are prone to social isolation. Support groups may be of benefit where knowledge and experiences can be shared to boost coping strategies.8 Patients with psychosocial problems  may struggle to attend clinics and comply with treatment; often presenting as emergencies which adds to the management challenges.²⁹

Pain can initially be managed with simple analgesia with the addition of a weak opioid if necessary. It is not uncommon for patients with chronic pancreatitis to require rapidly increasing doses of strong opioids risking the development of tolerance and hyperalgesic side effects. Adjuncts such as gabapentin tricyclic antidepressants have been shown to be beneficial.³³

Care should be taken when prescribing to avoid polypharmacy and opioid dependence. Strong opioid prescribing should be avoided in primary care if possible but, if considered, it should prompt a referral to secondary care to review alternatives. Many patients with chronic pancreatitis with a history of alcohol misuse could be at high risk for rapid development of dependence symptoms.

A trend towards significant pain relief from improved nutrition and pancreatic enzyme replacement therapy (PERT) has been shown in one systematic review,³⁴ although PERT is not recommended for pain alone in chronic pancreatitis.¹⁵ In selected cases, jejunal feeding has been shown to improve pain, although oral nutrition remains the preferred route.³⁵

Uncontrolled pain should trigger referral to secondary care for multidisciplinary assessment by physicians, surgeons and specialist pain clinics.¹³ Endoscopic and surgical treatments should be considered as an adjunct to medical therapy in all cases initially or if pain symptoms increase, especially before opioid escalation occurs. Endoscopic therapy to dilate strictures, remove stones or drain pseudocysts can improve pain.17 Endoscopic ultrasound-guided coeliac plexus block has been shown to reduce pain in up to 55% of patients with chronic pancreatitis so can be considered in the tertiary care setting.³⁶

Surgery can be considered in cases of main pancreatic duct dilatation to remove obstruction (pancreatic jejunostomy) providing short-term benefit in up to 80% of patients, with 60% reporting benefit for more than two years.³⁷ Pancreatic resection is indicated in the presence of pain and small duct disease or enlargement of the pancreatic head, or if previous drainage procedures have failed.⁸

Surgery for chronic pancreatitis is a significant consideration with morbidity rates of 30-60% although mortality is less than 5%.38 Recovery includes readjustment to opioid dosing and adjusting to life with insulin. Patients should be counselled extensively prior to undertaking surgery so that they are fully aware of the risks and benefits as well as the possibility that improvement is not guaranteed.⁸

Patients with evidence of malnutrition, malabsorption or pancreatic exocrine insufficiency should be treated with PERT to improve symptoms, nutritional status and quality of life,^33,39 see table 5.

The majority (80%) of chronic pancreatitis patients can be managed with a normal diet and PERT, with 10-15% requiring nutritional supplementation and 5% requiring enteral tube feeding.⁴⁰ Interventions providing balanced dietary advice have been shown to be as effective as providing supplements to optimise malnutrition in patients with chronic pancreatitis so early input from a dietitian is vital.⁴¹

The majority of patients can be managed with a normal diet (30% fat content) and PERT. However, if calorie intake is low, protein supplementation can be considered.⁴⁰

It has been suggested that baseline bone density assessment is performed in all individuals with chronic pancreatitis given the high risk of osteoporosis, fractures and the associated morbidity and cost. In addition, advice regarding weight-bearing exercise, smoking and alcohol cessation and dietary advice to maximise calcium and vitamin D intake should be provided as standard.⁴²

Follow-up

Patients should remain on at least yearly review which should include: routine blood tests, liver function tests (cholestasis or biliary obstruction), and markers of malnutrition (albumin, coagulation, FBC),⁴³ see table 3.

If the patient is not already known to have pancreatic exocrine insufficiency, stool testing for steatorrhoea with quantitative measures such as FEL-1 should be used.⁴³

Annual screening for diabetes mellitus with HbA1c should be offered.18 Additionally, osteoporosis screening, every one to two years, should be considered for those with malnutrition or high-risk indicators (previous low trauma fracture).⁴³ There is no role for routine pancreatic cancer screening, however, an urgent suspected cancer pathway referral to gastroenterology or hepatobiliary surgery should be made for patients with unexplained progressive weight loss.44 American guidelines advocate starting cancer screening only in those with hereditary pancreatitis and in chronic pancreatitis patients with a family history of pancreatic cancer. ⁴⁵

Ongoing support in primary care is vital to help with smoking cessation, abstinence from alcohol and treatment compliance. The management of this patient group is challenging especially in preventing opiate dependence.

Conclusion

Chronic pancreatitis has multiple causes, the most common of which is excessive alcohol consumption. Patients present with severe pain among other features including malnutrition and weight loss.

Early identification of chronic pancreatitis can be challenging and patients are at risk of complications such as osteoporosis, diabetes and pancreatic cancer.

Diagnosis should be confirmed in secondary care, but input from community and primary care is vital for ongoing care with a multidisciplinary team approach early on to help guide treatment and manage complications.

Competing interests: None