Gluten sensitivity, wheat intolerance or celiac disease: Confusing names, confusing diagnosis

wheat-bread

In recent years there has been a lot of interest in “non-celiac gluten sensitivity” (NGCS), first described in in a study in 1978. This concept now applies to patients who don’t meet all the criteria for celiac disease or wheat allergy, but who do have a number of GI symptoms after eating food containing gluten.

But is it really gluten that causes NCGS?

Even after a patients go through a double blind placebo-controlled challenge to test for NGCS, there is no proof that gluten is responsible for symptoms. Such challenges give patients food either containing gluten or not, but they commonly use wheat rather than chemically purified gluten. It’s possible that they may be reacting to components of wheat that have nothing to do with gluten, like starch and other carbohydrates known as FODMAPs, or other proteins that are known to cause inflammation.

Figure 1

Figure 1

Research on NGCS

In a survey conducted in Italy on 486 patients with suspected NCGS, patients suffered from the symptoms seen in figures 1 and 2. The most common GI symptoms were bloating, abdominal pain, diarrhea and/or constipation, nausea, and acid reflux, though they also showed fatigue, headache, ‘foggy mind,’ fibromyalgia-like joint and muscle pain, leg or arm numbness, skin rash, depression, anxiety, and anemia. In this study, 95 percent of patients reported symptoms almost every time they ingested gluten.

In another trial, 34 patients on a gluten-free diet who had irritable bowel syndrome but not celiac showed GI symptoms and fatigue more frequently after reintroducing gluten than those in the control group. These patients also showed other symptoms like attention deficit and hyperactivity, sleep problems, loss of coordination, autism, depression, bipolar disorder, schizophrenia, muscular problems and even autoimmune diseases such as psoriasis.

But how common is NCGS? Given how difficult it is to diagnose, it’s impossible to say. As a result, estimates range widely, from 0.6 percent to a whopping 50 percent on some popular–but likely inaccurate–websites. NCGS appears to be more prevalent in women than men, in first degree relatives of celiac patients, and in adults rather than children. In fact, there is only limited evidence of its existence in children.

Figure 2

Figure 2

Diagnosing NCGS

In spite of the uncertainty about the exact definition of NCGS, the following diagnostic criteria have been proposed:

  1. The patient does not have celiac disease
  2. The patient does not have a wheat allergy
  3. The patient does show rapid onset of symptoms after eating foods containing gluten, but no signs of intestinal damage as in celiac disease

It is essential to rule out celiac before labeling a patient with NCGS. In fact, patients who begin a gluten-free diet prior to an adequate diagnostic work-up for celiac disease risk a missed or at least delayed celiac diagnosis. People who believe they are affected by a gluten-related disorder should be screened for celiac disease first, which will include a blood test, and in most cases, an intestinal biopsy while still on a normal, gluten-containing diet. About 60 percent of patients with NCGS have a completely normal intestinal lining–the remaining 40 percent may have “lymphocytic enteritis”, or an increase in immune system cells in the intestine that is common in many other conditions besides celiac. Still, it is part of the spectrum of celiac disease and it is important to differentiate between celiac and NGCS when patients have it.

Gluten challenge for NCGS diagnosis

Because there is no specific biomarker or genetic component for NCGS, the only reliable standard for diagnosis would be a double blind, placebo-controlled challenge. However, there is no agreement yet on what would constitute a proper gluten challenge. Clearly, there is an urgent need to standardize a diagnostic tool for clinical trials. In clinical practice, the diagnosis is usually made based on the patient’s report and often even without having properly excluded celiac, a major obstacle toward understanding NGCS.

False positives

It is possible that at least a subset of NCGS patients may have a food allergy instead. Studies have shown that about one-third of IBS patients improved on an elimination diet and worsened after a challenge with wheat and cow’s milk, suggesting that a percentage of them could be suffering from a food allergy. There are also cases in the early development where the disease cannot yet be detected by a blood test of intestinal biopsy.

There is also a well-known placebo effect in a variety of GI disorders. Even in severe conditions such as Crohn’s disease, about 15 percent of patients see improvement on placebo, so the likelihood of a placebo effect of gluten withdrawal has been suggested. In a study on patients with IBS-like symptoms claiming to suffer from various food intolerances, only 38 percent of patients with symptoms improved on an elimination diet and reacted to food challenges. Thus, it is quite possible that a portion of NCGS patients, and arguably a substantial one, fall in this category.

Conclusions

Until more is known, it is questionable whether gluten is causing NCGS and whether NCGS involves the immune system. In the absence of more research, the term “non-celiac gluten sensitivity” is misleading, and should be replaced with “wheat intolerance syndrome,” since wheat, rather than gluten, seems to be the cause.

At some point, research will tease out the various components of wheat intolerance syndrome and clarify it as possibly several more specific conditions. Until then, let’s all humbly take a step back, and go back to the drawing board to design rigorous studies to answer the many outstanding questions.

About Stefano Guandalini, MD (1 Article)
Stefano Guandalini, MD, is the founder and medical director of the University of Chicago Celiac Disease Center, and Section Chief of Pediatric Gastroenterology, Hepatology, and Nutrition at the University of Chicago Medicine.
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