Dr. John Hart gave a lecture about the pathology of celiac disease during the celiac preceptorship that I attended at the University of Chicago last month. Dr. Hart is one of the world’s experts in this field. Pathology encompasses the abnormal findings that can be seen on duodenal (small bowel) biopsy in patients with celiac disease. As a disclaimer, I have not really studied pathology since my first two years of medical school (1999-2001). Nor did I ever imagine that I’d be writing about it…
Dr. Hart started his lecture by describing the difference between the “classical” biopsy findings v. the “new” biopsy findings in celiac disease.
Classic celiac disease findings on biopsy include total villous atrophy (flattening, or blunting, of the villi throughout entire duodenum), inflammatory cells, increased intraepithelial lymphocytes (IELs), and elongated crypts.
But, it has been shown in recent years that patients with celiac disease can have totally normal looking bowel mucosa (no villous atrophy) with increased IELs only (Marsh stage 1). In the past, these Marsh stage 1 patients would not have been diagnosed with celiac disease.
Dr. Hart stated that patients with abnormally high celiac antibodies (TTG IgA) and Marsh Stage 1 findings (increased IELs) have either celiac disease or Crohn’s disease. The anti-endomysial antibody can be used to differentiate between the two–it will be elevated in cases of celiac and normal in Crohn’s. There are no other diseases that would cause an elevated TTG IgA and a Marsh 1 picture on small bowel biopsy.
Many biopsies for celiac disease are done incorrectly. At least 5 tissue samples must be obtained during biopsy. One biopsy should be from the duodenal bulb and 4 should be from the distal duodenum. In 2% of cases, the damage from celiac disease is in the duodenal bulb only (so if this location is not biopsied, the diagnosis of celiac can be missed).
Increased IELs, by themselves, can be seen in many diseases in addition to celiac disease. The differential diagnosis for increased IELs includes Crohn’s Disease, Giardia infection, small bowel bacterial overgrowth (SIBO), H pylori duodenitis, and use of NSAIDS (class of drugs that includes ibuprofen and naproxen).
In addition, certain medication and other diseases can cause villous blunting that mimics “classic” celiac disease. The main culprit is olmesartan, a blood pressure medication. Losartan and mycophenolate are others. Diseases that cause villous blunting include common variable immunodeficiency (CVID) and autoimmune enteropathy. Dr. Hart suspects that many cases of seronegative celiac disease (normal celiac antibody levels but abnormal biopsy with villous blunting) are related to medications. He point blank stated that seronegative celiac disease should be a diagnosis of last resort.
At the end of the lecture I asked Dr. Hart if there is any window of time that an accurate biopsy can be obtained after a patient starts on a gluten-free diet, without having to undergo a gluten challenge. His answer was that is probably okay to do a biopsy within 2 weeks, with the caveat that the waters can still be “muddied” at this point. This is the best answer that I have ever received to this question and I appreciated that he took the time to answer it.
The take-home message is that there are many patients with celiac disease who may have mild findings on biopsy and that villous blunting is no longer needed for diagnosis of celiac. It is also important to make sure that one’s biopsy is done correctly, as, sadly, many are not. As an aside, before I had my daughter’s biopsy performed in June, I confirmed that her GI doctor was going to take enough samples and include the duodenal bulb. He did not mind me asking this at all. At this point he had no idea that I was a doctor, nor did he know that I had this page.
As always, feel free to ask questions, comment, share your story, etc. I am a bit backlogged on my email right now, so if you do email (which you are welcome to), it may take up to 2 weeks to hear back from me. Thanks for understanding.