To the Editor: A 26-year-old woman presented with 24 hours of severe constant epigastric pain and vomiting. She had no history of similar pains, alcohol consumption or gallstones. Four days before presentation she had received her first dose of human papillomavirus (HPV) vaccine. Two days after vaccination she developed a fever and self-limiting rash of 3 days’ duration.

Examination revealed marked epigastric tenderness and temperature of 40°C. Other physical parameters were within normal limits. Biochemical investigations showed normal liver function, moderate leukocytosis, a serum amylase level of 1900 U/L (reference range [RR], 23–85 U/L) and lipase level of 3400 U/L (RR, 0–160 U/L).

An upper abdominal ultrasonography showed a non-dilated biliary tree and no evidence of gallstones. Computed tomography showed an oedematous pancreas with peripancreatic fat stranding and arterial enhancement of the pancreatic parenchyma, consistent with pancreatitis without necrosis (Box). Other investigations showed normal serum levels of calcium, triglycerides and parathyroid hormone. Serological tests were negative for acute infection with coxsackie A9, coxsackie B1–6, echo, mumps, herpes simplex, hepatitis and varicella zoster viruses.

The patient was diagnosed with pancreatitis and treated conservatively with intravenous fluids and analgesia. Pain, symptoms and biochemical abnormalities settled after 10 days. She was discharged and remains well. Magnetic resonance cholangiopancreatography performed after discharge showed no pancreatic parenchymal or ductal abnormality.

Acute pancreatitis is common, with an incidence of 5.4–80 per 100 000.1 Gallstones and alcohol use account for 70%–85% of cases; other causes include drugs, viral infections, tumours, hyperlipidaemia, hypercalcaemia, trauma, iatrogenic injury and pancreatic ductal anomalies. The cause is unidentified in up to 10% of cases.1,2

Viral pancreatitis is well recognised, with cytomegalovirus and mumps, coxsackie, hepatitis, herpes simplex, and varicella viruses all known causes.3 Vaccines have been implicated, with pancreatitis associated with measles–mumps–rubella and hepatitis A and B vaccines.4,5 To date, there has been no report linking HPV vaccination with pancreatitis.

The pathophysiology linking vaccination with pancreatitis is unclear. It has been postulated that viral replication in immunodeficient hosts receiving live attenuated viral vaccines can cause pancreatitis. Alternatively, “molecular mimicry” could stimulate production of auto-antibodies, which react with host antigens and cause autoimmunity.5 The HPV vaccine is a quadrivalent, recombinant, non-infectious formulation, eliminating viral replication as a mechanism of pancreatitis. Therefore, an autoimmune mechanism is possible.

Extensive clinical testing has demonstrated the safety of HPV vaccine in the general population. In our patient, intensive history taking and investigation failed to identify another cause for pancreatitis, and the close temporal relation of the HPV vaccination, the development of a prodromal illness, and fever without evidence of sepsis led us to postulate that pancreatitis was secondary to vaccination. A coincidental illness causing pancreatitis cannot be ruled out, but neither can HPV vaccination be excluded as a potential cause. We therefore suggest that pancreatitis be considered in cases of abdominal pain following HPV vaccination and if proven, notified to the Adverse Drug Reactions Advisory Committee.

Computed tomography scan of the abdomen in a patient with pancreatitis

Portal venous computed tomography images showing oedematous enlargement of the pancreas, with surrounding fat stranding and ascites. The pancreas (arrows) appears fully enhanced with contrast, suggesting there was no necrosis. A: Pancreatic head. B: Pancreatic body and tail.