A strong association has been found between use of proton pump inhibitors and microscopic colitis, particularly for lansoprazole.
Findings from a Danish observational study of 10,652 patients diagnosed with microscopic colitis showed the risk of the condition was up to a 16-fold higher among current users of lansoprazole compared to people who never used a PPI.
Current use of any proton pump inhibitor had a strong association with collagenous colitis (adjusted Odds Ratio 6.98) and also increased risk of lymphocytic colitis (adjusted OR 3.95).
The association seen with lansoprazole was especially strong, with an OR of 15.74 for collagenous colitis with current use of the PPI and 6.87 for lymphocytic colitis. In contrast, the association was weaker for other PPIs such as esomeprazole (OR 3.75 for collagenous colitis and 2.93 for lymphocytic colitis).
In respect to timing of PPI use, the association with microscopic colitis was weaker among former users, perhaps because the effect of PPIs on microscopic colitis is reversible. The Odds Ratio for collagenous colitis among recent users (within 90 days) of PPIs was 5.16 and for past users (within the last year) the OR was 1.52.
No obvious dose-response relationship could be seen between PPI use and microscopic colitis, but this might be due to the lack of verifiable data on the daily dose of PPI consumed by patients, the study authors say.
Writing in Alimentary Pharmacology and Therapeutics, they say microscopic colitis causes watery diarrhoea and rising rates of diagnosis of the condition over the last two decades have coincided with the rise in use of PPIs.
It is not clear by what mechanism PPIs might have a causal link to microscopic colitis, but it is unlikely to be due entirely to an acid supressing effect, they say.
Given the stronger association seen with lansoprazole, the mechanism might be related to a direct effect on proton pump in the colon triggering an immune response, they suggest.
And while the risk to an individual patient using a PPI is low, the widespread use of the agents may be responsible for a large population burden of microscopic colitis, they add.
Extrapolating the figures to the general population, they estimate that PPIs may have been responsible for 2105 cases of collagenous colitis and 969 cases of lymphocytic colitis over the 10-year study period for a population of five million people.
“There is currently insufficient evidence to recommend specific strategies for PPI use in patients with microscopic colitis [but] as always, an inappropriately prescribed PPI should be discontinued,” they conclude.