Diagnostic Challenges and Clinical Nuance of EPI, With Adam Kichler, DO

Greasy, foul-smelling stools and persistent bloating are often dismissed as routine gastrointestinal complaints, but they can signal a more overlooked issue. Exocrine pancreatic insufficiency (EPI) remains a frequently missed contributor to gastrointestinal symptom burden, in part because its clinical presentation so often overlaps with more commonly diagnosed conditions.

As Adam Kichler, DO, a gastroenterologist and advanced endoscopist at Allegheny Health Network, emphasized in an interview with HCPLive, hallmark features like bloating, loose stools, and particularly greasy, foul-smelling stools should prompt consideration of EPI, especially in patients with known pancreatic disease such as chronic pancreatitis. He also calls attention to the more clinically challenging and arguably more underrecognized population of those with so-called “secondary EPI,” particularly individuals with inflammatory or malabsorptive disorders.

The overlap with conditions like Crohn's disease and celiac disease is especially important. Both are independently associated with diarrhea and malabsorption, which can obscure a concurrent diagnosis of EPI. Kichler highlights that up to 20% of patients with these conditions may also have EPI, not due to intrinsic pancreatic failure, but rather impaired signaling from the inflamed small intestine.

“In addition to providing pancreatic enzymes as a kind of bridge to get people feeling better, the mainstay of treatment is to address the underlying small bowel disease, and then the EPI should rectify itself afterwards,” he explained.

From a diagnostic standpoint, the field has largely coalesced around indirect testing strategies. Stool-based assessments, particularly fecal elastase and spot fecal fat, offer a practical and noninvasive approach that aligns with real-world clinical workflows. Although direct pancreatic function testing remains the gold standard, its invasiveness and logistical complexity limit widespread use. In practice, Kichler says the emphasis is on balancing diagnostic accuracy with feasibility, an area where indirect testing has proven sufficient for most patients.

Treatment, however, introduces its own set of challenges. Pancreatic enzyme replacement therapy remains the cornerstone of management, most commonly with pancrelipase capsules like Creon, Zenpep, Pancreaze, Pertzye, and Viokace.

However, underdosing is a pervasive issue. As Kichler notes, appropriate initiation—typically around 40,000 to 50,000 units of lipase per meal, with titration based on response—is critical to achieving symptom control.

Equally important is proper administration timing and ensuring coverage for snacks, both of which can significantly impact therapeutic efficacy. Beyond enzyme replacement, comprehensive care requires attention to nutritional deficiencies, particularly fat-soluble vitamins, and longitudinal monitoring to ensure adequacy of repletion.

Kichler additionally underscores premature initiation of PERT without adequate evaluation as a key clinical pitfall. In patients without clear pancreatic pathology, he says alternative causes of malabsorption must be excluded before committing to lifelong enzyme therapy.

Ultimately, Kichler notes improving outcomes in EPI requires a more deliberate approach prioritizing accurate diagnosis, avoiding premature treatment, and recognizing its overlap with other GI disorders. While pancreatic enzyme replacement therapy is effective, he emphasizes that its success hinges on proper dosing, monitoring, and addressing underlying causes, particularly in secondary EPI.

Editors’ Note: Kichler reports no relevant disclosures.

References

1. Cleveland Clinic. Exocrine Pancreatic Insufficiency (EPI). June 10, 2021. Accessed March 19, 2026. https://my.clevelandclinic.org/health/diseases/21577-exocrine-pancreatic-insufficiency-epi

2. NIDDK. Definition & Facts for Exocrine Pancreatic Insufficiency. January 2023. Accessed March 19, 2026. https://www.niddk.nih.gov/health-information/digestive-diseases/exocrine-pancreatic-insufficiency/definition-facts

3. Drugs.com. Medications for Pancreatic Exocrine Dysfunction. March 19, 2026. https://www.drugs.com/condition/pancreatic-exocrine-dysfunction.html