Thursday, March 8, 2012

Who endorses gluten syndrome?

Three years ago I asked the question "Who endorses the Gluten Syndrome?"

At that time, the “HealthPathways” website (which is a collection of medical guidance) of my local hospital board acknowledged the entity of gluten-sensitivity under the pathway of coeliac disease. Gluten sensitivity is a condition that presents with similar symptoms to celiac disease, but without the intestinal damage, and is treated with a gluten-free diet.

However, all references to gluten-sensitivity have been subsequently removed. This decision was made by the members of the ‘Child Health Team’ (of the Canterbury District Health Board, CDHB), which included 3 paediatricians and 7 General practitioners.  This section was reviewed by all the Child Health specialists and accepted by the Department of Paediatrics. It was also reviewed by many general practitioners particularly the Clinical Practice Education Committee of Pegasus Health.   

But, with the publication of a landmark paper of “Spectrum of gluten-related disorders (, perhaps it is time for the Health Pathway of coeliac disease and gluten sensitivity to be revised.

There have been many developments over the last 3 years: the diagnosis of gluten sensitivity has come of age.  The concept of gluten-related-disorders has gathered momentum with a number of converging influences: the boundary between celiac disease and gluten sensitivity has become blurred; the “gold-standard” small bowel biopsy for the tissue diagnosis of celiac disease is no longer regarded as mandatory; there has been recognition of a wide range of gluten-related disorders without intestinal damage; the extensive neurological effects of gluten have been well documented; and there has been a widespread adoption of gluten-free diets and lifestyle in the community.

Here is the background of these statements:
1) Spectrum of gluten-related disorders
A group of 15 international celiac experts, who up until a few years ago were skeptical of gluten causing any illness other than celiac disease, have now defined a much wider group of illnesses which they have called “gluten-related disorders”.  This landmark paper “Spectrum of gluten-related disorders: consensus on new nomenclature and classification” places celiac disease in context of other gluten-illness.  Celiac disease no longer dominates the gluten sensitive picture (Sapone et al. BMC Medicine 2012, 10:13, published 7 February 2012).

The abstract reads:
“A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten free diet appears much higher than the projected number of celiac disease patients, fueling a global market of gluten free products approaching the $2.5 billion in global sales in 2010. This trend is supported by the notion that along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions:

1) allergic (wheat allergy)
2) autoimmune (celiac disease, dermatitis herpetiformis, and gluten ataxia)
3) possibly immune-mediated (gluten sensitivity)”

Regarding gluten sensitivity, they say: “there are cases of gluten reactions in which neither allergic nor autoimmune mechanisms can be identified. These are generally defined as non-celiac GS or more simply, GS. Some individuals who experience distress when eating gluten-containing products and show improvement when following a GFD may have GS instead of CD. GS is a condition distinct from CD and is not accompanied by the concurrence of anti-tTG autoantibodies or other autoimmune comorbidities.”

They go on to say: “the two conditions cannot be distinguished clinically, since the symptoms experienced by GS patients are often seen in CD … their symptoms included abdominal pain (68%); eczema and/or rash (40%); head- ache (35%); foggy mind(34%); fatigue (33%); diarrhea (33%); depression (22%); anemia (20%); numbness in the legs, arms or fingers 20%; and joint pain (11%).”
They conclude: “All individuals, even those with a low degree of risk, are therefore susceptible to some form of gluten reaction during their life span. Therefore, it is not surprising that during the past 50 years we have witnessed an epidemicof CD and the surging of new gluten-related disorders, including the most recently described GS.”

2) No definitive test yet for gluten sensitivity.
Unfortunately, there is no accurate or reliable test for gluten sensitivity.  However, the IgG-gliadin antibody (also know as AGA, anti-gliadin antibody) has been widely used as the best-available-marker, particularly in the identification of neurological and psychiatric gluten-disorders. Between 40-50% of gluten sensitivity patients may have IgG or IgA anti-gliadin antibodies (AGA Sapone A et al. (2010). Differential mucosal IL-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy celiac disease. International Archives of Allergy & Immunology; 152: 75-80;
Bizzaro N et al. (2010) Cutting edge issues in celiac disease and in gluten intolerance. Clinical Reviews in Allergy & immunology

Therefore, if the IgG-gliadin antibody is not elevated, this cannot rule out a diagnosis of gluten sensitivity.  But, if elevated it can contribute to the diagnosis.
Research laboratories are actively seeking specific test.  Until such a test is available, elimination and challenge with gluten remains the most effective option.

3) gluten sensitivity a common illness
Dr. Fasano estimates that 6% of the population has gluten sensitivity, compared to 1% with celiac disease.

Gluten sensitive now has its own Wikipedia page ( which also cites this figure.  The problem of estimating the incidence of gluten-related-disorders is that there is not yet a diagnostic test.  Current estimates are likely to be conservative.

It is now known that no one can successfully digest gluten, and that we all have the potential to get unwell from gluten, and that it can cause illness in many different ways.  Celiac disease has increased five-fold over the last 40 years, ( and it is likely that gluten sensitivity has increased at the same rate.   

4) Change of diagnostic guidelines for celiac disease.
No longer is small bowel biopsy necessary for a diagnosis of celiac disease. In certain cases, serology is now sufficient for the diagnosis of CD. This has been discussed for the last 10 years as blood tests have been developed to accurately detect gut damage (EMA, tTG and DGP).  Added to this is the genetics that can identify those people who can sustain intestinal damage with gluten (who carry the HLA DQ2/DQ8 alleles).  Finally, the endoscopy is expensive and unreliable for the diagnosis of celiac disease.  With the rapid increase in the incidence of celiac disease, it is impractical to demand tissue diagnosis for the millions of celiac disease sufferers.

ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) has new guidelines for the diagnosis of celiac disease , they conclude: “The diagnosis of CD depends on gluten-dependent symptoms, CD-specific antibodies, the presence of HLA-DQ2 and/or HLA-DQ8, and characteristic histological changes in the duodenal biopsy. In case of high antibody levels the diagnosis of CD may be based on a combination of symptoms, antibodies, and HLA, thus omitting the duodenal biopsy.”

Their key message is: with high tissue damage markers (tTG IgA, EMA or DGP), in genetically susceptible people, celiac disease can be diagnosed without performing a duodenal biopsy.

5) Gluten can harm brains and nerves
Evidence shows that gluten does significantly affect the brain and nerves: gluten damage is not restricted to the gut.  This is elegantly documented by Marios Hadjivassiliou (Gluten sensitivity: from gut to brain. The Lancet Neurology, Volume 9, Issue 3, Pages 318 - 330, March 2010),

They write: “Gluten sensitivity is a systemic autoimmune disease with diverse manifestations ... coeliac disease, or gluten-sensitive enteropathy, is only one aspect of a range of possible manifestations of gluten sensitivity … gluten sensitivity was shown to manifest solely with neurological dysfunction.”
They conclude: “To improve diagnosis rates, the perception of physicians that gluten sensitivity is solely a disease of the gut must be changed.”

6) Double blind studies
The term “gluten sensitivity” was first used by Prof W Dicke the discoverer of gluten-related-disorders in his 1950 MD Thesis.  He worked out that gluten was the culprit causing the illness (diarrhea, poor growth and irritability).  He made his diagnosis clinically by elimination and challenge (not double blind), and with no blood tests or biopsy. He said “in the clinic, one finds many sub-acute forms of enteritis and dyspepsia which respond poorly to normal therapy but well to wheat deprivation.”

In the 1960s, with the instigation of the small bowel biopsy, the whole perspective of diagnosis became focused exclusively on the gut.  Celiac disease became a strictly gastrointestinal illness.  This focus became so intense that it led to the un-substantiated dogma that: gluten only caused celiac disease … and if the patient had a normal small bowel biopsy, then gluten could not be causing any harm.  This has now been shown to be a false doctrine.

Currently, as in Dicke’s day, to establish if someone is gluten-sensitive, still relies a clinical trial of elimination and challenge.  However, not unreasonably, there is a call for double-blind studies to establish the place of gluten-related disorders outside the framework of celiac disease.

For instance, in IBS patients, who stated that they were gluten free from self-diagnosis (and who had celiac disease excluded), were randomized to either gluten or placebo treatment groups. The finding was that symptom-severity-scores (of pain, stool consistency and tiredness) were significantly higher for gluten-eaters compared to the placebo-gluten-free group (Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR: Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol 2011, 106:508-514.

7) 10% already going gluten-free
Over the last few years there has been a widespread adoption of a gluten-free diet in the community.  Peter Gibson, professor of medicine at Monash University's Eastern Health Clinical School, estimates that in Australia, up to 10 per cent of people who are avoiding gluten because they think gluten is their problem

However, until there is a reliable way to make the diagnosis, it will remain difficult to quantify the problem. Gibson plans to investigate the prevalence of non-coeliac gluten intolerance, why it occurs and whether low levels of gluten can be eaten safely.

In America, the adoption of gluten-free diets is also increasingly common.  This can be measured by the sales of gluten-free products, which have a compound annual growth rate of 28% from 2004 to 2011.  By 2012 the market is expected to reach about $2.6 billion in sales.

Gluten was first implicated as causing disease 62 years ago by W Dicke.  Initially, it was considered a rare disease affecting only the gastrointestinal tract. But now gluten has been recognized to cause a spectrum of illnesses, with a number of different pathological and physiological mechanisms.  Celiac disease is becoming much more common, and gluten-related disorders are thought to affect at least 5% of the total community (and obviously it therefore affects a much higher proportion of the un-well-community).  It is time for gluten-related-disorders to be part of the medical main-stream differential diagnosis.

Dr Rodney Ford
9 March 2012


  1. The chairman of the "Child Health Team" has responded (and remember, that this group of medical people made their determinations on evidence 3 years ago): "Your views do not appear to be those of most of your local colleagues who have looked at the evidence."

    I find this an odd comment - what I have written in this article is not "my view" but the considered consensus of the leading 15 celiac research doctors, internationally. None-the-less, the Chairman of this local group of medical practitioners, for some reason would rather rely on local opinion of 3 years ago rather than up-to-date current knowledge on gluten-sensitivity.

    I wonder when (if ever) their HealthPathways guidance will be revised, who they will rely upon to give them accurate information, and how much more evidence they will require to add the wider spectrum of gluten-related-disorders (which includes gluten-sensitivity).

    A lot of people will suffer for longer if they are not encouraged to look at the possibility of a gluten-related-disorder.

  2. Very detailed analysis.. Thank you for sharing the valuable information.
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