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.
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).
http://www.biomedcentral.com/content/pdf/1741-7015-10-13.pdf
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 ‘epidemic’ of 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
http://www.ncbi.nlm.nih.gov/pubmed/19940509;
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
Gluten sensitive now has its own Wikipedia page (
http://en.wikipedia.org/wiki/Gluten_sensitivity#cite_ref-2)
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, (
http://www.ncbi.nlm.nih.gov/pubmed/20868314)
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
http://www.phadia.com/Laboratories/Autoimmunity/Resources/PoM/2012/No-1-2012/
, 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
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.
http://www.ncbi.nlm.nih.gov/pubmed/21224837
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
http://www.gesa.org.au/media.asp?cid=5&id=153.
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.
Conclusion
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
