Natural history of pancreatitis associated with cystic fibrosis gene mutations

Abstract Background. An increased incidence of CFTR mutations has recently been reported in chronic and idiopathic pancreatitis. Aim. The aim of the study was to verify these data and describe the clinical, morphological and histological findings in 99 patients (59 males, 40 females, mean age 40±16 years), 45 suffering from idiopathic chronic pancreatitis and 54 from acute recurrent pancreatitis. Methods. Each subject was screened for the 18 CFTR mutations: DF508, DI507, R1162X, 2183AA>G, 21303K, 3849+10KbC>T, G542X, 1717-1G>A, R553X, Q552X, G85E, 711+5G>A, 3132delTG, 2789+5G>A, W1282X, R117H, R347P, R352Q), which cover 72% of cystic fibrosis chromosomes in the Italian population, plus the 5-thymidine allele in intron 8 of the CFTR gene (IVS85T). Results. Among the 99 patients, we found 14 patients with CFTR mutation (14.1%). Three idiopathic chronic pancreatitis patients had cystic fibrosis (compound mutations in two and a single mutation with a pathological sweat test in one) and 11 (11.1%) presented a single mutation (carriers) (seven idiopathic chronic pancreatitis and four acute recurrent pancreatitis). The incidence of patients with cystic fibrosis was 167.5 times higher than that observed in the general population, whereas the carrier frequency was 4.43 times higher for chronic pancreatitis and 2.11 times for acute recurrent pancreatitis than that observed in 428 unrelated partners of cystic fibrosis patients. The prevalence of IVS8-5T was similar (7.1%) to that of the general population (10%). All idiopathic chronic pancreatitis patients with one or more CFTR gene mutations had a long history of recurrent attacks of pancreatitis. The length of recurrences of pancreatitis before diagnosis of chronic pancreatitis was shorter in chronic pancreatitis patients with one or more CFTR gene mutations than in the other idiopathic chronic pancreatitis patients (7.4±5.8 vs. 2.1±2 years). In idiopathic chronic pancreatitis patients with one or more CFTR gene mutations, exocrine and endocrine insufficiency (diabetes and steatorrhoea) were rare or delayed events. Conclusions. The natural history of pancreatitis associated with CFTR gene mutations seems to be characterised by recurrences of pancreatitis which develops into chronic pancreatitis.