Should I ask about Proton Pump Inhibitor (PPI) history in all patients with diarrhea?

PPI History Should Be Routinely Obtained in All Patients with Diarrhea

Yes, you should ask about PPI history in all patients presenting with diarrhea as PPIs are an important modifiable risk factor for several causes of diarrhea, particularly C. difficile infection.

Rationale for Obtaining PPI History in Diarrhea

PPI-Associated Diarrhea Conditions

1. C. difficile-Associated Diarrhea (CDAD)

   • PPIs significantly increase the risk of hospital-acquired C. difficile infection with a pooled odds ratio of 1.81 (95% CI, 1.52-2.14) 1
   • PPI use is considered an emerging and potentially modifiable risk factor for CDAD 2
   • The mechanism involves reduced gastric acid secretion, which normally serves as a defense mechanism against ingested C. difficile spores 3

2. Small Intestinal Bacterial Overgrowth (SIBO)

   • Long-term PPI use is associated with SIBO development, which can cause chronic diarrhea 4
   • The European Society for Neurogastroenterology and Motility recommends avoiding medications that worsen gastric motility, including long-term PPIs 4

3. PPI-Responsive Esophageal Eosinophilia (PPI-REE)

   • While not directly causing diarrhea, this condition highlights how PPIs can significantly affect gastrointestinal pathophysiology 5

Clinical Practice Guidelines Support

The ESMO guidelines for diarrhea in cancer patients explicitly include PPI history in their diagnostic algorithm for chemotherapy-related diarrhea 5. This demonstrates the importance of considering PPI use in the diagnostic workup of diarrhea.

Clinical Approach to Diarrhea Evaluation

Key Questions About PPI Use

• Current or recent PPI use (type, dose, duration)
• Indication for PPI therapy
• Temporal relationship between PPI initiation and diarrhea onset
• Previous attempts to discontinue PPI and resulting symptoms

Risk Stratification

Patients with the following factors should receive particular attention regarding PPI use:

• Recent antibiotic exposure plus PPI use (highest risk for C. difficile) 2, 6
• Hospitalized patients on PPIs (increased risk of nosocomial C. difficile) 1
• Elderly patients with multiple comorbidities on PPIs 6
• Cancer patients receiving chemotherapy 5

Management Implications

When to Consider PPI De-prescribing

The American Gastroenterological Association recommends:

• All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing 5
• Most patients with nonerosive GERD can be considered for PPI discontinuation 5
• Patients on twice-daily dosing should be considered for step-down to once-daily PPI 5

Exceptions to De-prescribing

Patients with the following conditions generally should not be considered for PPI discontinuation 5:

• Complicated GERD with history of severe erosive esophagitis
• Esophageal ulcer
• Peptic stricture
• Barrett's esophagus
• High-risk patients on NSAIDs requiring gastroprotection

Common Pitfalls to Avoid

1. Overlooking PPI as a cause of diarrhea - Many clinicians focus solely on infectious causes and miss this important modifiable factor

2. Failure to document PPI indication - The AGA recommends clearly documenting an acceptable indication for PPI use and confirming that the indication is ongoing 5

3. Not considering PPI discontinuation - In patients with diarrhea on long-term PPI therapy without clear indications, consider a trial of discontinuation

4. Missing the connection between PPIs and C. difficile - Particularly in patients with recent antibiotic exposure, the additional risk from PPI use is significant 2, 1

By routinely including PPI history in your evaluation of all patients with diarrhea, you can identify potentially modifiable risk factors and improve patient outcomes through appropriate PPI management.