The effect of CFTR modulators on a cystic fibrosis patient presenting with recurrent pancreatitis in the absence of respiratory symptoms: a case report

• Published in: BMC gastroenterology Vol. 19; no. 1; p. 123
• Main Authors: Johns, J Dixon, Rowe, Steven M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.07.2019; BioMed Central; BMC
• Subjects: Aminophenols - therapeutic use; Care and treatment; Case Report; Case studies; CAT scans; CFTR; Complications and side effects; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - drug therapy; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - drug effects; Development and progression; Diarrhea; Enzymes; Fibrosis; Gallstones; Genetic testing; Humans; Ivacaftor; Male; Medical research; Medical tests; Morbidity; Pancreatic insufficiency; Pancreatitis; Pancreatitis, Chronic - drug therapy; Pancreatitis, Chronic - genetics; Pancrelipase; Pantoprazole; Quinolones - therapeutic use; Recurrence; Recurrence (Disease); Recurrent pancreatitis; Respiratory symptoms; Treatment Outcome; Young Adult; United States; Cystic fibrosis; Ivacaftor; Pancrelipase; Recurrent pancreatitis; CFTR
• ISSN: 1471-230X; 1471-230X
• DOI: 10.1186/s12876-019-1044-7

Cystic fibrosis (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ manifestations, including pancreatic exocrine secretion. In the pancreas, CFTR abnormality results in abnormally viscous secretions that obstruct proximal ducts leading to fibrotic injury and ultimately pancreatic insufficiency in 85% of the CF population. CFTR modulators, including the potentiator ivacaftor, augment channel gating to restore 30-50% of CFTR-mediated anion transport. While CFTR modulation has been shown to alkalinize the pH of the alimentary tract and potentially augment pancreatic enzyme activity, the effect of ivacaftor on recurrent pancreatitis is emerging. Here we describe a case of a patient with CF (R117H/7 T/F508del) who presented with recurrent pancreatitis who was effectively treated with ivacaftor in the absence of respiratory symptoms. A 24-year-old white male with past medical history of recurrent acute pancreatitis presented for evaluation following a referral from an outside hospital. The patient reported a lifetime of gastrointestinal symptoms requiring over 20 hospitalizations for pancreatitis in the last 10 years. Prior U/S and CT imaging for pancreatitis ruled out gallstones or anatomical etiologies. Family history included a brother with CF carrier status who suffered from recurrent acute pancreatitis. Sweat chloride testing was suggestive of CFTR dysfunction (57 mmol/L). Genetic testing demonstrated disease causing CFTR mutations: R1117H/7 T/F508del. Patient was prescribed pancrelipase, however, he reported worsened gas and diarrhea symptoms. Pancrelipase was discontinued and the patient was prescribed ivacaftor 150 mg BID. After 6 weeks of ivacaftor treatment, patient reported improved gastrointestinal symptoms. For an additional 19 months, patient reported no episodes of pancreatitis until he discontinued ivacaftor. Over the next 3 weeks, patient experienced progressive nausea and sharp epigastric pain and laboratory studies confirmed pancreatitis. Patient was subsequently lost to follow up. These findings support a possible relationship between the use of CFTR modulators, such as ivacaftor, in the management of recurrent pancreatitis in the setting of patients with cystic fibrosis and a CFTR mutation with residual CFTR activity or otherwise known to be responsive in vitro. Ivacaftor may be useful for recurrent pancreatitis, even in the absence of respiratory morbidity.