Navigating the Differential: When EPI Looks Like Something Else

With diagnosis in sight, this episode addresses the important challenge of differential diagnosis and the conditions that can masquerade as or coexist with EPI. The panelists approach this from two angles: conditions that may be concomitant with EPI, and conditions that may be the true primary diagnosis in a patient with EPI-like symptoms.

Jennifer Geremia distinguishes between new patients presenting with postprandial symptoms—where the differential is broad and may require blood testing, stool testing, and endoscopy—and patients with known EPI-associated conditions (e.g., well-controlled celiac disease still symptomatic, IBD, post-gastric bypass) where EPI is one of several conditions potentially at play. Sarah Enslin highlights irritable bowel syndrome (diarrhea-predominant), small bowel Crohn's disease, and any condition involving abdominal bloating and diarrhea as key mimickers that require careful differentiation.

The panel recommends a personalized, stepwise diagnostic strategy. For patients with alarm features or family history warranting endoscopic evaluation, appropriate endoscopy should be prioritized. However, unnecessary testing should be avoided—if symptoms are not postprandial or clearly linked to meals, ordering a fecal elastase in a patient with likely IBS may yield low utility. The key is tailoring the diagnostic sequence to the individual presentation.

A particularly important clinical pearl is raised about prior testing: in referral center practice, patients often arrive having already undergone multiple scopes, CT scans, and bloodwork. Systematically reviewing prior testing avoids unnecessary duplication, saves costs, and ensures meaningful incremental workup rather than repeated baseline evaluation. This 'chronology first' approach is presented as a practical strategy for experienced clinicians and trainees alike.

In the next episode, "Putting PROs to Work: The PEIQ and Symptom Scores in EPI Management," the discussion examines how validated patient-reported outcome tools like the PEIQ can be integrated into clinical practice to guide diagnosis, treatment adjustment, and monitoring.