Abstract
Background
Exocrine pancreatic insufficiency is a prominent feature of cystic fibrosis (CF). Trypsin is a measure of pancreatic function in CF patients. It was previously thought that the pancreas was irreversibly damaged in patients with CF by a certain age. However, newer modulator therapies for CF, namely ivacaftor, have shown the potential to improve pancreatic function (as demonstrated in both the KIWI and ARRIVAL study cohorts). Ivacaftor is a CFTR modulator that improves the opening of the defective CFTR channel. Another CF modulator, lumacaftor/ivacaftor combination therpay, improves trafficking of the defective CFTR channel to the membrane. Lumacaftor/ivacaftor combination therapy has not been able to demonstrate a benefit on pancreatic function in previously published work.
Aims
To describe a case of acute pancreatitis in a patient with previous pancreatic insufficient CF after lumacaftor/ivacaftor combination therapy.
Methods
We present the case of a 16-year-old female with CF (genotype: delF508/delF508) treated with lumacaftor/ivacaftor.
Results
Prior to initiation of lumacaftor/ivacaftor therapy this patient had severe pancreatic insufficiency with a serum trypsin of <5 ng/mL (reference range (RR) 19–68 ng/mL). There was no documented pre-treatment fecal elastase. After 20 months on lumacaftor/ivacaftor combination therapy, she presented with acute onset of epigastric abdominal pain radiating to her back. At this time, her total amylase was 186 U/L (RR <102 U/L), pancreatic specific amylase was 127U/L (RR 4–31 U/L), and lipase was 290U/L (RR 4-39U/L). Initial ultrasound did not visualize the pancreas, abdominal x-ray demonstrated fecal loading and she was treated as an outpatient for constipation and with pain management. Five days later her pain had worsened. At this point her amylase and lipase had normalized, but an abdominal ultrasound demonstrated increased bulkiness of her pancreas compatible with acute inflammation. Her symptoms improved after 24 hours of NPO and IV fluids. Enteral feeding was then successfully reintroduced.
Conclusions
While we are awaiting follow-up pancreatic function testing, the presentation with classic clinical symptoms, an increase in pancreas enzymes >3X the upper limit of normal and compatible ultrasound findings are consistent with a diagnosis of acute pancreatitis. This is the first reported case presentation of acute pancreatitis in a previously pancreatic insufficient CF patient occurring after treatment with lumacaftor/ivacaftor combination therapy. This case raises the question of whether her pancreatic function has normalized with lumacaftor/ivacaftor therapy or whether we are seeing the emergence of a new CF phenotype where there is some improvement in the exocrine function of the pancreas enough to cause pancreatitis.
Funding Agencies
None