Table 2 –
Differential diagnosis for exocrine pancreatic dysfunction along with diagnostic testing strategies and treatment alternatives or complements to pancreatic enzyme replacement therapy.
| Evaluation | Treatments to consider other than PERT | |
|---|---|---|
| Decreased pancreas exocrine function or drainage | ||
| Acute pancreatitis | History | |
| Chronic pancreatitis | History, imaging | |
| Pancreatic cancer | History, imaging | |
| Pancreatic resection | History, imaging | |
| Genetic and congenital disorders: | History, genetic testing | |
| Cystic fibrosis, CFTR-related disorders | Genetic testing | Exocrine function may improve with CFTR modulators |
| Schwachman-Diamond syndrome | Genetic testing | |
| Johanson-Blizzard syndrome | Genetic testing | |
| Pancreatic agenesis | Imaging | |
| Wilson’s disease | Serum ceruloplasmin, 24-hour urine copper | Chelation therapy |
| Hemochromatosis | Iron studies, genetic testing | Therapeutic phlebotomy |
| Post-cibal asynchrony (disordered mixing and/or altered hormone secretion) | ||
| Gastric resections and other foregut surgery | Surgical history, imaging | Dietary changes, open-capsule or uncoated PERT |
| Crohn’s disease with enteritis | Imaging, endoscopy | Treat underlying cause |
| Celiac disease | Serology and small intestine biopsy | Gluten free diet |
| Diabetes mellitus | History and glucose lab values | |
| Other disorders with maldigestion or malabsorption of fats | ||
| Gastrinoma (Zollinger-Ellison Syndrome) | Fasting gastrin level | Treat underlying cause |
| Cholestatic disorders (e.g., primary sclerosing cholangitis) | Liver function tests and imaging | Fat soluble vitamin supplementation |
| Medications (orlistat, purgative use to facilitate eating disorder) | History | Discontinue use |
| Short bowel syndrome | History, imaging | Dietary changes, treat underlying cause |
| Intestinal lymphangiectasia | Cardiac and/or lymphatic imaging | Treat underlying cause |
| Genetic and congenital disorders | ||
| Abetalipoproteinemia | Genetic testing | Dietary changes |
| Hypobetalipoproteinemia | Genetic testing | Dietary changes |
| Infections | ||
| Giardia | Stool assay | Antibiotics (e.g., metronidazole) |
| Whipple’s disease (Trophyerma whipplei) | Small bowel biopsy | Antibiotics (e.g., ceftriaxone then TMP-SMX) |
| Bacterial overgrowth | Breath testing or empiric therapy | Antibiotics (e.g., rifaximin) |
Abbreviations: exocrine pancreatic insufficiency (EPI), pancreas enzyme replacement therapy (PERT),