BACKGROUND
Pancreatic exocrine insufficiency (PEI) is said to be associated with numerous conditions both within and outside the gastrointestinal (GI) system. The majority of research has been concerned with conditions that reduce the volume of functioning pancreatic tissue or prevent adequate drainage to the small bowel, such as chronic pancreatitis, cystic fibrosis, pancreatic cancer and pancreatic resection. However, the evidence base supporting an association with extra-pancreatic conditions, such as coeliac disease, diabetes mellitus and congestive cardiac failure, is heterogeneous.
AIM
To strengthen the evidence base by studying all previously reported associations with PEI in a large cohort of outpatients.
METHODS
A single-centre retrospective study was performed. General gastroenterology outpatients tested for PEI with faecal elastase-1 (FE1) were identified and information retrieved from the electronic patient record. PEI was defined as FE1 < 200 μg/g. Patients already taking pancreatic enzyme replacement therapy were excluded. Multiple imputation was used to handle missing data. Univariable logistic regression was used to study which presenting symptoms predicted PEI. Multivariable logistic regression was used to explore the relationship between all previously reported associations and PEI.
RESULTS
Of 1027 patients were included. 182 patients (17.7%) were diagnosed with PEI. Steatorrhoea [odds ratios (OR): 2.51, 95% confidence intervals (CI): 1.58-3.98] and weight loss (OR: 1.49, 95%CI: 1.08-2.06) were the only presenting symptoms that predicted PEI. Chronic pancreatitis (OR: 7.98, 95%CI: 3.95-16.15), pancreatic cancer (OR: 6.58, 95%CI: 1.67-25.98), upper GI surgery (OR: 2.62, 95%CI: 1.32-5.19), type 2 diabetes (OR: 1.84, 95%CI: 1.18-2.87), proton pump inhibitor therapy (OR: 1.87, 95%CI: 1.25-2.80) and Asian ethnicity (OR: 2.11, 95%CI: 1.30-3.42) were significantly associated with PEI in the multivariable analysis. None of the other historically reported associations with PEI were significant after adjustment for the other variables included in our multivariable analysis.
CONCLUSION
PEI is common in patients with chronic pancreatitis, pancreatic cancer, upper GI surgery and type 2 diabetes. Proton pump inhibitor therapy may also be associated with PEI or a false positive FE1.
Results All cases considered not IgG4-RD in the MDM (n=52) similarly did not meet ACR/EULAR criteria. Of those considered definite IgG4-RD (n=63) in the MDM, only half (33;52%) met ACR/EULAR criteria. In those with definite HPB involvement (n=48) in the MDM, just over half (27;56%) met ACR-EULAR criteria. Most of the IgG4-HPB patients not meeting ACR/EULAR criteria scored insufficient diagnostic points (n=17) due to reliance on pancreatic imaging characteristics; diffuse swelling and pseudocapsule, with no points awarded for cholangiopathy without pancreatic involvement, atrophy, or focal enlargement of the gland. Small and unrepresentative biopsies were an additional challenge. Specific exclusions were absence of glucocorticoid response in advanced (fibrotic) cholangiopathy, and Crohn's disease or ulcerative colitis in isolated HPB involvement. Conclusions The ACR-EULAR classification demonstrated excellent specificity (100%) and will be an invaluable tool for clinical trials. Disparity between diagnosis according to our IgG4-RD MDM and the ACR/EULAR criteria are explained by specific pancreatic imaging characteristics, absence of cholangiopathy/hepatopathy as a unique entity, and the necessity for steroid responsiveness even if presenting with advanced cholangiopathy.
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