Alcohol use syndrome is one of the most common causes of both acute and chronic pancreatitis.
Acute pancreatitis (AP) is a necro-inflammatory disease resulting from exocrine cell destruction by infiltrating inflammatory cells. The diagnostic criteria are typically when a patient presents with characteristic symptoms, elevated lipase levels, and distinct imaging findings. Treatment is mostly supportive as there is no specific pharmacotherapy for this disease. Acute pancreatitis will either resolve with the pancreas fully regenerating, lead to transient organ failure, or progress to cause systemic inflammation and multi-organ failure. In these severe cases, treatment may require antibiotics and more invasive therapies.
Chronic pancreatitis (CP) is believed to result from recurrent attacks of acute pancreatitis, leading to the development of pancreatic insufficiency, steatorrhea, diabetes, pancreatic calcification, and fibrosis. While alcohol and its by-products alone do not directly cause this disease, they can predispose the pancreas to damage from otherwise benign agents. As a result, one of the main strategies to prevent recurrent attacks involve providing alcohol (and smoking) cessation counseling and strategies to patients.
Chronic alcohol consumption causes 17to 25% of acute pancreatitis cases worldwide and is the second most common cause of AP after gallstones. It usually manifests in patients with over five years of ongoing, substantial alcohol use (~4-5 drinks daily) and only rarely occurs from isolated binge drinking. The type of alcohol ingested does not affect the risk of developing pancreatitis. Interestingly, while alcohol may sensitize the pancreas to damage by external and environmental factors such as genetics, high-fat diet, cigarette use, and infectious agents, relatively few people with alcohol use syndrome will develop pancreatitis (less than 5%). Heavy smokers who drink more than 400g of alcohol per month are four times more likely to develop acute pancreatitis.
Chronic alcohol consumption is the single most common cause of chronic pancreatitis, resulting in ~40 to 70% of all cases, and increases an individual's risk of developing pancreatic cancer by 20 times. Recurrent bouts of acute pancreatitis are associated with progression to chronic pancreatitis and are more common in chronic abusers of alcohol. Furthermore, most analyses suggest that some degree of chronic pancreatic injury already exists at the time of onset of an AP episode.
Acute pancreatitis is the number one cause of gastrointestinal related hospitalization in the United States and accounts for 2.6 billion dollars in healthcare spending and 279,000 annual admissions. Eighty percent of these patients present with mild, self-limited disease. Alcohol-related pancreatitis is more common in western countries and Japan. The annual incidence of acute pancreatitis is in the range of 13 to 45 per 100,000 people and chronic pancreatitis from 5 to 12 per 100,000 people and is proportionally highest in males between 35 and 54 years old. The overall mortality is now about 2% and usually associated with severe episodes of AP.
The complete pathophysiology of this disease is not entirely understood, but likely results from alcohol’s effects on the small pancreatic ducts and acinar cells. Alcohol is believed to cause precipitation and increases the viscosity of pancreatic secretions, which leads to the development of protein plugs in the small ducts, which then form calculi causing ulceration, scarring, and eventual acinar atrophy and fibrosis.
The pancreas uses oxidative and non-oxidative metabolism to process alcohol. The oxidative pathway leads to the formation of acetaldehyde, a reactive metabolite that causes detrimental effects in acinar cells through activation of stellate cells, increased expression of proinflammatory cytokines, and a decrease in NAD+/NADH ratios. The non-oxidative pathway requires the formation of fatty acid ethyl ester (FAEE) synthase, which leads to activation of key transcription factors, sustained increases in intracellular calcium, and inhibition of extracellular matrix proteins, ultimately leading to further cell injury.
Alcohol also leads to premature activation of trypsinogen and other digestive and lysosomal enzymes within the acinar cells themselves; this causes the pancreatic tissue to auto-digest and leads to further inflammation. Another contributing mechanism is intra-acinar activation of factor-kB (NF-kB), a transcriptional activator, which further drives the inflammatory response, which can cause up to 50% of pancreatic tissue damage and lead to severe, fatal inflammatory responses.
Alcohol-induced pancreatitis occurs in the setting of prolonged, chronic alcohol use and its clinical features are similar to those of acute and chronic pancreatitis. Symptoms include nausea or vomiting and constant epigastric pain, which may also radiate to the mid-back or flanks. On examination, the abdomen may be normal or distended. In severe cases, alcohol-induced pancreatitis may be classically associated with periumbilical or flank ecchymosis, also known as Cullen’s or Grey Turner’s signs, respectively, and represent significant peritoneal or retroperitoneal hemorrhage. Of note, pain may be less abrupt and poorly localized in alcoholic pancreatitis versus gallstone induced AP. Severe presentations of AP may include peritonitis, sepsis, acute respiratory distress syndrome (ARDS), and/or shock. Chronic pancreatitis may display the additional features of pancreatic insufficiency, including steatorrhea secondary to fat malabsorption, and pancreatic diabetes secondary to endocrine cell destruction.
The diagnosis of acute pancreatitis requires that at least two of the following three criteria are met, based on the Revised Atlanta Classification system:
Clinical features include constant upper abdominal pain, with or without radiation to the back, and tenderness of the abdomen with palpation. Laboratory criteria include a serum lipase of at least three times the upper limit of normal. Lipase peaks more rapidly, remains elevated for a more extended period, and has a higher sensitivity and specificity than amylase. Testing for both enzymes does not improve sensitivity or specificity. A hepatic panel, calcium level, and triglyceride level may help differentiate alcoholic from other causes of AP. Finally, CT with IV contrast is the imaging modality of choice and findings may include pancreatic enlargement, loss of pancreatic borders, surrounding fluid, and/or fat stranding. Areas of no enhancement indicate pancreatic necrosis. Imaging is normal in 15-30% of cases of mild pancreatitis and is not routinely indicated or needed for diagnosis. An exception to this rule is in cases where the patient does not respond to treatment after 48 hours, and further imaging can rule out other abdominal pathology or complications. Endoscopic retrograde cholangiopancreatography (ERCP) is not beneficial in alcohol-induced pancreatitis unless there are signs of comorbid biliary etiology.
Treatment and management of alcohol-induced pancreatitis follow the same principles as that for other causes of pancreatitis with the addition of alcohol cessation intervention during or after admission. Namely, these principles include accurate diagnosis, high-quality supportive care, recognizing and avoiding complications, and prevention of recurrence. To accomplish this, clinicians employ goal-directed fluid therapy with either normal saline or lactated Ringers, give timely analgesics and antiemetics, and replete electrolyte as needed. The current recommendations are also to initiate feeding trials within 24 hours of disease onset instead of keeping the patient NPO. There are no clear indications for the type of diet, but typically small low-fat, soft or solid meals correlate with shorter hospital stays than starting a clear liquid diet with slow advancement to solid meals. Enteral feeds via a feeding tube is preferred to total parenteral nutrition in patients unable to tolerate PO. The AGA currently recommends against the use of prophylactic antibiotics in predicted severe AP and necrotizing pancreatitis. Additionally, providing brief alcohol intervention during admission or repeated counseling regularly at a primary care or gastrointestinal clinic appointments has been shown to decrease alcohol use, hospital admissions for recurrent attacks, and development of chronic pancreatitis.
Chronic pancreatitis pain can be managed with analgesics (avoiding high-potency opioids) and/or pancreatic enzyme replacement therapy. Antioxidants may be helpful in cases where other pharmaceutical options fail. Endoscopic therapy or surgery are other options when pain is refractory to medical management.
The differential diagnoses include, but are not limited to:
There is a broad differential diagnosis for this condition, as conditions affecting the gallbladder, stomach, or upper GI tract may present with a similar pain pattern. A history of frequent alcohol use, in combination with the characteristic abdominal pain patterns, elevated lipase, and imaging findings can help narrow down the differential.
Also, sickle cell crisis or diabetic ketoacidosis should also merit consideration in patients with a corresponding past medical history.
Various scoring systems have been created to predict the severity of acute pancreatitis based on clinical, laboratory, and radiology findings; however, they have largely demonstrated low specificity and low positive predictive values. These include Ranson’s criteria, the APACHE II score, BISAP, and the CT severity index, among others. Further, the American Pancreatic Association and the American College of Gastroenterology differ in their criteria for prognosticating a severe disease course. While the number of hospital admissions for acute pancreatitis is increasing and 15 to 25% of cases categorize as severe acute pancreatitis, the mortality rate has significantly decreased to 1 to 2% throughout the last ten years. A recent report showed that following an initial episode of acute alcoholic pancreatitis, there was a 24% chance for a recurrent AP episode and a 16% chance of developing chronic pancreatitis.
Complications from this disease can have both localized and systemic effects including:
Systemic complications include sepsis, bacteremia from the migration of intestinal flora, pleural effusions, ARDS, and shock.
Chronic pancreatitis patients are also at increased risk of developing pancreatic cancer, pancreatic diabetes, bile duct obstruction, and splenic vein thrombosis.
Consultations from the following specialties may be necessary:
As mentioned above, patients with acute pancreatitis or chronic pancreatitis secondary to alcohol use should receive brief alcohol intervention when admitted to the hospital or receive alcohol counseling during their primary care or gastroenterology outpatient visits.
Alcohol use syndrome is one of the most common causes of both acute and chronic pancreatitis, but likely requires other factors such as smoking and diet to manifest.
Alcohol counseling has shown benefits to patients as it decreases total hospital admissions for acute pancreatitis. One randomized controlled trial showed that repeated counseling during gastroenterology clinic visits decreases the risk of hospitalization for recurrent pancreatitis attacks. Alcohol intervention strategies have also been shown to reduce alcohol consumption in men significantly. Smoking cessation and dietary modifications are also recommendations, as these are risk factors when combined with alcohol. Reducing both alcohol and tobacco consumption was shown to reduce the risk of recurrent attacks, the progression to chronic pancreatitis, and the development of secondary pancreatic malignancy. [Level I]
For patients with uncomplicated chronic pancreatitis, medical management remains the first line of therapy. Behavior modification counseling for the cessation of alcohol consumption and smoking is also in order; therefore, certified therapists play a large role in patient outcomes. [Level 2b]
Since extraneous factors such as diet may play a synergistic role in leading to initial and recurrent episodes of pancreatitis, consultation with a nutritionist would benefit such patients. Endoscopic, surgical, or radiology guided interventions may be required for cases of pancreatic pain refractory to medical therapy and conservative measures or used to treat the complications associated with acute pancreatitis such as pancreatic necrosis.
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