Differentiating Celiac Disease From Gluten Intolerance and IBS

A presentation on October 14, 2013, at the American College of Gastroenterology Scientific Session by Joseph A. Murray, MD, FACG  (Mayo Clinic)Murray JA. Implications of gluten intolerance and celiac disease in IBS.  

A presentation on October 14, 2013, at the American College of Gastroenterology Scientific Session by Joseph A. Murray, MD, FACG  (Mayo Clinic)

Murray JA. Implications of gluten intolerance and celiac disease in IBS.
 

Joseph Murray, MD, is an international expert on celiac disease and on our developing understanding of people who report symptoms when they eat gluten but don’t have celiac disease. This is the fast-growing cohort that’s driving gluten-free food sales and primary care office visits. It’s tempting to throw up ones hands and assume there’s no science to help us sort out our current muddle. That’s just not true, but Dr Murray acknowledges that it’s still too early to accurately define gluten intolerance.

As currently formulated, “non-celiac gluten sensitivity” (NCGS) refers to the subset of persons who report improvement in GI symptoms when they discontinue gluten-containing foods. Dr Murray goes so far as to say that NCGS is “not so well defined nor certain as an entity.” Contrast that with celiac disease (CD), a well-defined autoimmune disease that causes inflammation and tissue damage in the small intestine, which can be definitively diagnosed by upper endoscopic biopsy. Its genetic predisposition is well-understood, and it reliably resolves on a strictly followed gluten-free diet.

Many studies have suggested that the irritable bowel syndrome (IBS) cohort is enriched with undiagnosed CD, and that a significant fraction of IBS patients in whom CD has been ruled out may have NCGS. CD is not predicted by IBS symptoms in population-based studies, though at least one study has shown an increased incidence of CD in secondary referrals for IBS. Dr Murray’s bottom line: “If someone has sent you a presumed IBS patient not tested for CD-test them!” IBS patients can be screened for CD serologically before they’re sent to the gastroenterologist for definitive biopsy and diagnosis (see details below). Convincing data show that CD is not being promptly diagnosed, with symptom duration ranging from 7 to 12.9 years. A prior diagnosis of IBS results in further delays-as much as 3 to 4.9 years more before diagnosis is made-so there’s a strong role for primary care to play in recognizing the problem.

Starting the workup for celiac disease: The serologic tests Dr Murray recommends are tissue transglutaminase (tTg) and antiendomysial (EMA) antibodies, not anti-gliadin IgA or IgG. The tTg is the higher-sensitivity test (96% to 98%), but it has lower specificity (88% to 100%), whereas EMA is very specific (99% to 100%) but less sensitive (75% to 98%). Note that serologies (and biopsy) can be falsely normal if the patient is already on a gluten-free diet, so you must advise patients carefully before embarking on a workup.

Adults always need a biopsy to confirm suggestive serologies, but new guidelines (European Society of Paediatric Gastroenterology, Hepatology and Nutrition [ESPGHAN]) point to a simplified diagnostic path for symptomatic children, where biopsy can be avoided if anti-tTg is greater than 10 times the upper limit of normal, EMA is positive, HLA = DQ2 or DQ8, and the patient responds to a gluten-free diet. Biopsy is still endorsed by ACG as central to diagnosis-made by endoscopic biopsy of the duodenal bulb.

What about the patient who won’t go off an established gluten-free diet to undergo testing for the first time? Dr Murray subscribes to the “why argue with success” approach-if diet is nutritionally adequate and the patient feels well, he doesn’t force the issue. Here’s the irony: only about 17% of the 1.8 million-person US celiac population actually has a diagnosis and is on a gluten-free diet. A similar number, 1.6 million, are currently on a gluten-free diet without a diagnosis of CD. What’s driving this? Persistent IBS-type symptoms-for which all of us know currently available treatments and recommendations tend to frustrate patients. They’re looking for an easier answer. Incidentally, Dr Murray’s estimates on the prevalence of gluten-free diet may be low-some food companies estimate a much higher figure, at least for short-term self-administered trials.

Dr Murray is not discounting the possibility that NCGS is a real entity, and cites many studies suggesting genetic similarities (eg, HLA-DQ2) and symptom resolution with gluten cessation in symptomatic individuals, despite negative duodenal biopsies while consuming gluten. Some studies have shown that biopsy-negative persons with serologic markers for CD have symptom resolution when off gluten, diarrhea in particular-this includes double-blind placebo-controlled trials. Indeed, small-bowel permeability markedly decreased in patients with IBS-D (diarrhea-predominant type) when they were placed on a gluten-free diet.

This may ultimately be described as a “celiac-lite” form of the disease, with similar genetic susceptibility and immunologic reaction-but without the cellular damage. The problem may not in fact be gluten, but other components of wheat, and much more study is needed.

Regardless, this is not a health-food fad likely to disappear anytime soon. Primary care physicians should familiarize themselves with the basic workup to differentiate celiac disease-from everything else.