So Why Do Celiacs Still Need Biopsy?

Celiac.com 01/11/2006 - For many years, biopsy of the small bowel demonstrating villous atrophy has been fundamental to the diagnosis of celiac disease. Older celiacs will remember, fondly or otherwise, the Crosby suction biopsy device which was swallowed attached to a long tube and made its way down to the small bowel where, position confirmed by x-rays, it guillotined a small portion of tissue. The procedure was tedious and technical failures common—only identified when the device was hauled up after several hours. Later it became clear that biopsies from the duodenum obtained during endoscopy were just as good, and the biopsy process became a five minute job with no need for X-rays. Nevertheless, many celiacs are reluctant to undergo biopsy and its necessity is increasingly questioned, particularly now that blood tests for celiac-related antibodies are highly sensitive and specific. There are a number of reasons why, in my own practice, biopsies continue to be helpful in celiacs diagnosed in adulthood.

• Biopsies are necessary when blood tests are negative. While endomysial (EmA) and tissue transglutaminase (TTGA) antibodies are detectable in most cases where villous atrophy is present, 5-10% of patients lack these antibodies¹. In this situation, where the story is suggestive of celiac, perhaps with a family history or strongly suggestive symptoms, biopsy is the only way to make the diagnosis. Increasingly, physicians recognize that many patients with gluten sensitivity do not have villous atrophy (Grade III of the Marsh classification) of "classic" celiac disease, but have milder abnormalities such as crypt hyperplasia (Marsh II) or an excess of the inflammatory cells called lymphocytes (Marsh I). Patients in these categories are less likely to have positive serology².
• Biopsies are necessary where false positive blood tests may occur. TTGA, particularly where levels are low, may be associated with diseases other than celiac: ulcerative colitis, Crohns disease, arthritis and liver diseases without any evidence of celiac disease have been linked³. Newer TTGA tests have steadily improved in this regard but I still would be reluctant to diagnose celiac on a TTGA test alone. "False positive" EmA is a different issue which I will return to.
• Biopsies give a baseline for comparison. Suppose a patient starts a gluten-free diet without biopsy—we dont know whether she or he had Marsh I, II or III or even normal histology. A year later, same patient develops new symptoms of diarrhea, weight loss, whatever. Well get a duodenal biopsy as part of the workup, but its going to be difficult to interpret without knowing what things were like before going gluten-free. Specifically, a baseline to look back at tells us whether the small bowel is better, worse or no different, and helps us decide whether we need to focus on celiac disease as the most likely cause of new problems or explore other possibilities involving the rest of the gut. The biggest diagnostic disaster of all, of course, is the gluten-free diet started without any sort of baseline investigation including antibodies, raising the specter of the infamous gluten challenge if a definitive diagnosis is needed.
• Biopsies provide a "gold standard" assessment of the state of the bowel. There has been much excitement recently about capsule endoscopy, a wireless device the size of a large pill (not to be confused with the Crosby capsule!) which makes its own way down the small bowel taking pictures as it goes. Characteristic abnormalities can be seen in celiac disease, raising the possibility that this device might be useful in diagnosis. If experience with conventional endoscopes is any guide, however, these abnormalities are missing in a sizeable minority of celiacs particularly with mild disease⁴ (Capsule endoscopy in its present state of development can not take biopsies). Certainly the capsule allows assessment of the bowel beyond the reach of conventional "anaconda-style" endoscopes, but I am not convinced at present that it can replace biopsy.
• A follow-up biopsy gives an indicator of progress. I offer my patients a repeat biopsy after two years gluten-free and perhaps surprisingly most take up the offer and are keen to hear how things have improved. Ive increased the biopsy interval from one to two years because only 40% of people had complete recovery after 12 months gluten-free⁵. EmA and TTGA disappearance is only a marker of how successful gluten exclusion has been and is not a reliable indicator of bowel recovery. Does persisting villous atrophy matter if the patient is doing well on a gluten-free diet? Intuitively, one might like to keep a closer eye on the patient with persistently flat biopsies, who could be at greater risk of complications in the future⁶.
• The endoscopy not only allows examination and biopsy of the duodenum but also a look at the esophagus and stomach. Sad fact of the ageing process is that you start to collect diseases like trading cards, and just because youre celiac doesnt mean you cant have something else. Its important to have a good look for bleeding lesions in the upper gut even if the blood work for a seventy year old with anemia says celiac (and check out the colon too, but thats a topic for another day).