Beyond Celiac Disease
Dr. Rodney Ford M.D.
Dr. Rodney Ford is a Pediatric Gastroenterologist. He was Professor of Pediatrics at the Christchurch School of Medicine. He runs the Children's Gastroenterology and Allergy Clinic in New Zealand. He has written a series of 7 books on gluten (www.DrRodneyFord.com). His main theory is that symptoms from gluten reactions arise from brain and nerve damage. His latest book is "The Gluten Syndrome" which encapsulates current ideas and concepts of gluten and the harm that it does.View all articles by Dr. Rodney Ford M.D.
This article originally appeared in the Spring 2013 edition of Celiac.com's Journal of Gluten-Sensitivity.
Celiac.com 03/04/2014 - The question. What is the spectrum of gluten related disorders?
“Experience is that marvelous thing that enables you to recognize a mistake when you make it again” – Franklin P Jones.
The chilling news is that gluten-harm reaches far beyond the concept of celiac disease. Gluten has now been recognized to cause a widespread spectrum of illness, over and above celiac disease. The two questions to answer in this context are:
- How many other diseases does gluten cause?
- How many people are adversely affected by gluten over their lifetime?
Last century, gluten-illness was synonymous with celiac disease. But, by the turn on the millennium, this concept radically changed. It was discovered that gluten intolerance was not limited to celiac disease.
Disturbingly, celiac disease is only just the beginning of the scourge of gluten. Most people with any of these symptoms will not have celiac disease, but are likely to have an illness caused by gluten-harm. A gluten-related disorder.
A Typical Story
Heidi, in her blog, writes about her life-long struggle to get a meaningful diagnosis for herself and for her family. She says that testing for celiac disease and gluten sensitivity should be the first diagnosis to think about—not the last! http://www.adventuresofaglutenfreemom.com/2011/05/dermatitis-herpetiformis-and-other-atypical-symptoms-of-gluten-sensitivity/.
“I also believe that the “atypical” symptoms are one of the major reasons why 95% of the estimated 3 million Americans living with celiac disease are undiagnosed. Add to that, the fact that you can go into any medical specialist’s office in this country and no doubt find patients whose underlying health problem is gluten, whether in the form of celiac disease or non-celiac gluten sensitivity. If doctors would stop being so eager to treat any of the 300+ signs, symptoms and conditions caused by gluten sensitivity (often with dangerous medications that will only perpetuate the problem), and take the time to practice medicine by seeking out the underlying root cause of the symptom, what a different world it could be!”
The Gluten Syndrome
The eating of gluten-grains is definitely associated with a lot of other serious illnesses. Collectively, I call this “The Gluten Syndrome”. This includes:
- Brain and nerve damage
- Auto immune disease
- Mental illness
- Skin disease
- Gastroenterological disorders
A number of names are now in use for identifying gluten-related illnesses. These include:
- Non-celiac gluten sensitivity (NCGS)
- Gluten intolerance
- Gluten sensitivity
- Gluten Syndrome
- Gluten-related disorders
Gluten-related disorders diseases are being indentified by more and more research groups. The realization of this widespread gluten-harm is so recent that adequate clinical studies have yet to be done. Therefore, the true extent of the problem remains unknown, although meaningful estimates can be calculated.
The Spectrum of Gluten-related Disorders
With the publication of a landmark paper of “Spectrum of gluten-related disorders (http://www.biomedcentral.com/content/pdf/1741-7015-10-13.pdf), perhaps it is time for the Health Guidelines (or medical protocols) of celiac disease and gluten sensitivity to be revised.
There have been many developments over the last few 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:
a) 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:
- allergic (wheat allergy)
- autoimmune (celiac disease, dermatitis herpetiformis, and gluten ataxia)
- 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%
- headache (35%)
- ‘foggy mind’ (34%)
- fatigue (33%)
- diarrhea (33%)
- depression (22%)
- anemia (20%)
- numbness in the legs, arms or fingers 20%
- joint pain (11%).”
“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.”
b) 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 http://www.ncbi.nlm.nih.gov/pubmed/21181303.
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.
c) gluten sensitivity a common illness
Dr. Fasano estimates that 6% of the population has gluten sensitivity, compared to 1% with celiac disease. http://celiacdisease.about.com/b/2011/03/11/u-of-md-study-identifies-differences-between-celiac-gluten-sensitivity.htm.
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.
d) 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.
e) 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), http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(09)70290-X/abstract
“Gluten sensitivity is a systemic autoimmune disease with diverse manifestations ... celiac 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.”
“To improve diagnosis rates, the perception of physicians that gluten sensitivity is solely a disease of the gut must be changed.”
f) 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.
g) 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.
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-celiac gluten intolerance, why it occurs and whether low levels of gluten can be eaten safely. http://www.smh.com.au/lifestyle/diet-and-fitness/gluten-intolerance-possible-without-celiac-disease-study-finds-20110117-19u5b.html
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. For the year ending 2012, the sales of gluten-free products were up 19%. Also, nearly 20% of the population are actually buying.Gluten-free products, for whatever the reason.
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 wide 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 10% of the total community (and obviously it therefore affects a much higher proportion of the unwell-community).
Surely it is time for gluten-related-disorders to be part of the medical main-stream differential diagnosis.
This is a chapter from Dr Rodney Ford’s new book “Gluten: ZERO Global” which is available as an ebook at http://www.glutenZEROglobal.com
As always, Celiac.com welcomes your comments (see below).