What are the rare causes of pancreatitis?

From the Guidelines

Rare causes of pancreatitis should be considered in patients with unexplained pancreatitis, particularly those with recurrent episodes, and may include autoimmune conditions, genetic mutations, anatomical abnormalities, certain medications, and uncommon infections. When evaluating patients with pancreatitis, it is essential to consider the etiology, as identified by 1, which recommends determining the etiology in at least three-fourths of patients. The initial history should focus on previous symptoms or documentation of gallstones, alcohol use, history of hypertriglyceridemia or hypercalcemia, family history of pancreatic disease, prescription and nonprescription drug history, history of trauma, and the presence of concomitant autoimmune diseases.

Some of the rare causes of pancreatitis include:

• Autoimmune conditions, such as IgG4-related disease, which often responds to steroid therapy
• Genetic mutations, such as those in the PRSS1, SPINK1, and CFTR genes, which may require genetic counseling for affected families
• Anatomical variants, such as pancreas divisum or annular pancreas, which can disrupt normal pancreatic drainage
• Medication-induced pancreatitis, which can occur with drugs like azathioprine, 6-mercaptopurine, didanosine, valproic acid, and tetracyclines, necessitating immediate discontinuation of the offending agent
• Rare infections, such as parasitic infections like ascariasis and viral infections like mumps, coxsackievirus, and cytomegalovirus
• Hypertriglyceridemia, hypercalcemia, and scorpion venom toxicity, which are additional uncommon causes

Diagnosis of these rare etiologies often requires specialized testing, including genetic analysis, IgG4 levels, MRCP imaging, and careful medication review, as recommended by 1. Treatment must address the underlying cause while providing supportive care for the acute pancreatitis episode. Additionally, patients with chronic pancreatitis should be considered at risk for malnutrition and osteoporosis, and preventive measures should be taken, as suggested by 1. A comprehensive approach to diagnosis and treatment is crucial to improve morbidity, mortality, and quality of life in patients with rare causes of pancreatitis.

From the FDA Drug Label

PANCREATITIS CASES OF LIFE-THREATENING PANCREATITIS HAVE BEEN REPORTED IN BOTH CHILDREN AND ADULTS RECEIVING VALPROATE Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. Acute pancreatitis, including fatalities

• Rare causes of pancreatitis associated with valproic acid include:
  • Hemorrhagic pancreatitis
  • Fatal pancreatitis
• Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation.
• If pancreatitis is diagnosed, valproate should ordinarily be discontinued 2, 2, 2.

From the Research

Rare Causes of Pancreatitis

• Valproic acid-induced pancreatitis is a rare but severe adverse effect of valproic acid use in children, with an estimated incidence of 1:40,000 3.
• The diagnosis of valproic acid-induced pancreatitis is based on clinical symptoms, laboratory tests, and imaging studies, and can be revealed by lipase levels at the time of an acute abdomen or a flulike illness in epileptic children taking valproic acid 4, 5.
• Other rare causes of acute pancreatitis include idiopathic acute pancreatitis, which accounts for 10-30% of cases, and can be diagnosed through a thorough diagnostic work-up, including endoscopic ultrasound and sophisticated radiological imaging techniques 6.
• Known factors of acute pancreatitis include pancreas divisum, hypertriglyceridemia, and complications of endoscopic retrograde cholangiopancreatography, such as post-endoscopic retrograde cholangiopancreatography acute pancreatitis 7.
• Antiepileptic drugs, especially preparations of valproic acid, can cause acute pancreatitis in children, and monitoring of pancreatic enzymes is recommended in children treated with valproate preparations who present with clinical symptoms suggesting acute pancreatitis 5.