Gut Check on Gastroenterology Archive

 I have been using PPIs to manage GERD and acid-sensitive dyspepsia since omeprazole first became available in 1989. Although no drug class is absolutely safe, there is, as yet, not a single case report of a death related to this drug class, despite hundreds of millions of patient-years of exposure. Despite this remarkable safety profile, much attention has focused recently on the overall safety of PPIs, as they have been associated with enteric infections (e.g., c. difficile), decreased bone density, electrolyte abnormalities (e.g., low magnesium), etc. However, most of these risks have been described in epidemiological studies that can establish association but not causation, and we learned an important lesson about interpreting such results with caution after authors and the FDA sent a message about the so-called interaction between PPIs and clopidogrel that turned out to be clinically irrelevant.

Despite the benefits of PPIs, increased scrutiny of the safety of this drug class has led a number of my patients to question recommendations about trying or continuing PPI therapy. I think that patients are wise to ask about the relevant side effects of any drug, but I have had trouble giving much in the way of advice or information about PPI risks, given the lack of credible evidence of cause and effect.

So, what do you tell your patients about risks when you start them on a PPI therapy?

What do you tell patients on long-term PPI therapy?

Do you use drug holidays?

Do you do bone-density studies earlier or more often in patients on PPIs?

Do you monitor magnesium levels?

Do you have patients stop therapy if they at risk for enteric infections (e.g., from hospital antibiotic exposure, travel to developing nations, etc.)?

I am looking forward to your insightful comments.

All gastroenterologists are very familiar with celiac disease, including its characteristic findings on small bowel biopsy and the treatment with a gluten-free diet. But I have noticed that we as gastroenterologists approach the possibility of sprue, or those suspected of having gluten sensitivity without sprue, with extraordinary variability. For instance, a negative screening tissue transglutaminase (TTG) has greater than a 99% negative predictive value (essentially excluding celiac disease), but a positive TTG has only a 25% to 35% positive predictive value, meaning that most patients who test positive do not have celiac disease.

So, first, here are some questions:

1) Do you still take biopsies in some patients with a negative TTG, and, if so, how do you decide which patients should undergo biopsy?

2) Do you take biopsies in all patients with positive TTG screens? If not, do you put these patients on a gluten-free diet as a trial?

3) Where and how many biopsies do you take to diagnose sprue? Do you always take biopsies in the duodenal bulb?

4) If you take duodenal biopsies, how long do you want the patient on gluten prior to the exam?

Now, let’s talk about gluten sensitivity:

1) If you take biopsies in patients with symptoms suggestive of sprue, and the biopsies are normal, but the patiens are improved on a gluten-free diet, what do you tell these patients? That they are sprue-variant? That they do not have sprue, but they are gluten sensitive?

2) Do you prescribe the same diet to these patients?

Please weigh in. I look forward to seeing your responses.