White skin - Neanderthal inheritance

White skin - Neanderthal inheritance

My younger son Daniel pointed out to me an error in my last post, the topic of which was a recent increase of the frequency of rickets in children in the UK. As would be predictable from previous experience, the incidence was higher in children of South Asian and Black ethnicity than in white children.

I mentioned in the Post that the dark skin people living in tropical parts of the world is an evolutionary adaptation to the high intensity of the sun. Daniel pointed out that strictly speaking this is not correct, as Homo sapiens originated in Africa and the vast majority of the world population is dark-skinned, living in tropical or semi-tropical zones.

It is the white-skinned population of the world that is a small minority, differing from the majority, and it is this group that is an evolutionary variant, and adapted to living only in the northern temperate area of north-west Europe. What was the origin of this small group?

Neanderthal (Neander tal) is a valley close to Dusseldorf in Germany. It is indicated by a sign on the autobahn viaduct that crosses the valley. Skeletal remains of a humanoid species were first discovered in the valley in the 18th century and have since been discovered in other parts of Europe. The humanoid became know as Neanderthal Man, scientifically Homo sapiens neanderthalensis.

Recent genetic studies have shown that the white-skinned variant of Homo sapiens has in the genome some DNA derived from the now extinct species Neanderthal Man. In other words at some time in the distant past there was a small amount of interbreeding between the new Homo sapiens spreading out of Africa and the older Neanderthals living in Europe, about 60,000 years ago. Little genetic advantage was passed on to Homo sapiens but one is a genetic factor for fair skin, an advantage when living in northern Europe. Another genetic factor is fair straight hair.

Darwin introduced the idea of “survival of the fittest”, indicating that if a new gene gives an advantage, then those with that gene will thrive. In north-west Europe a pale skin gave an advantage in the form of enhanced vitamin D synthesis.

And so, thanks to the Neanderthal humanoid, white-skinned people are genetically adapted to living very distant from the equator. Dark skin is the global norm of “pure” Homo sapiens. The Neanderthals became extinct as Homo sapiens proved to be superior, but their genetic influence lives on in white-skinned people.

 Reference:

http://www.newscientist.com/article/mg22129542.600-neanderthalhuman-sex-bred-light-skins-and-infertility.html#.U0WpP16AQpE

Rickets - a recent increase in children

Rickets is a disease of children. Formation of bone is impaired so that the bones become soft. When the child starts to walk the bones of the legs bend, giving rise to “bow-legs”. In severe cases the pelvis will contract and if in a girl it will lead to subsequent difficulty with labour. 

It is due to deficiency of vitamin D, which is essential for the process of “ossification”, the incorporation of calcium into bone. Rickets was very common in industrial cities in the 19th century. A hundred years ago it was recognised as being due to lack of sunlight, which acts on the skin to produce vitamin D. 

It was also discovered that vitamin D was present in fish oils, and this led to an opportunity to treat or prevent rickets despite lack of sunlight penetration through heavily polluted atmosphere. Cod liver oil became a standard medication for children in northern Europe, but this became out of fashion in the latter half of the 20th century when clean air legislation and holidays in the sun became effective.

Rickets became a disease of history, but in the 1960s there were medical case reports of rickets in children of immigrants from South Asia into the northern parts of the UK. This became a more widespread problem as the result of increased immigration into the UK. In the USA rickets was identified in Black children.

Dark pigmented skin is an evolutionary adaptation to tropical and sub-tropical regions where sunlight intensity at ground level would cause severe burn in non-pigmented white skin. The pigmented skin is less efficient in the synthesis of vitamin D but this is not important when sun intensity is high.  It is of great importance when the individuals move to live in north-west Europe. The northern parts of the UK are further north than anywhere in China, and sun intensity is relatively low, even in the summer.

South Asian people are adapted culturally to living in a hot hot sunny climate by dress that covers virtually all of the body. This is an important additional factor leading to vitamin D deficiency when resident in north-west Europe.  

The trickle of case reports has now reached a significant number, and among white children in addition. A study from Oxford has shown a significant increase in the incidence of rickets during the past 15 years. Incidence means the number of new cases each year. The numbers are small, one increasing to three per 100,000 children aged less than 15 years. The study includes both the incidence within Oxford and also within England.

Increase in rickets in recent years

The incidence is lower in Oxford than in England overall, probably the result of a lower immigrant population. Ethnicity is important in the development of rickets, but it has been occuring in white children in recent years.

Overall an important part of the increase in the incidence of rickets is an increase in the proportion of the ethnic minority and especially the South Asian of the UK population. During the past few years, the birth rate of the indigenous population has decreased by 2%, whereas that of the ethnic minorities has increased 19%. 

 Proportion is the the proportion of children who have rickets

But the incidence of rickets has increased in white children, and this requires an explanation. There is no suggestion of a decrease in the intensity of the sun and so we must for behavioural factors. 

http://www.drdavidgrimes.com/2013/10/vitamin-d-supplements-when-and-what-to.html

http://www.drdavidgrimes.com/2013/09/the-benefits-of-vitamin-d-and-sun.html

Should there be population screening for coeliac disease ?

Should there be population screening for coeliac disease ?

This Post follows two previous posts on the subject of Coeliac Disease

http://www.drdavidgrimes.com/2013/12/is-there-really-epidemic-of-coeliac.html

http://www.drdavidgrimes.com/2014/02/how-common-is-coeliac-disease.html

Anaemia is one of the classical features of coeliac disease and so it follows logically that if someone is found to be anaemic, that person might have coeliac disease. It is suggested that 5% of people with iron deficiency anaemia have coeliac disease.

Anaemia, low haemoglobin concentration in the blood, has many causes. In most cases there is an impairment of the production of red blood cells. This can be the result of specific disease of the bone marrow, where red blood cels are produced. Anaemia can also be due to the absence of an essential factor in the synthesis of haemoglobin, the oxygen-carrying complex that is within the red cells. The three essential factors are iron, folic acid and vitamin B12. Shortage of iron is usually due to blood loss, occasionally dietary shortage of iron, and rarely the malabsorption of iron from food through the intestinal wall into the blood-stream. This is what happens in coeliac disease.

Causes of iron deficiency anaemia:

                   Menstruation        20%

                       Cancer colon       5–10%

            Cancer stomach     5%

             Coeliac disease      5%

            Poor diet                 5%

Pregnancy

Not all people diagnosed with coeliac disease develop anaemia. The coeliac disease blood test is so commonly positive with the condition being unrecognised, and so it does not follow that coeliac disease when diagnosed will necessarily be the cause of anaemia.  

It is simple to treat deficiency of iron or folic acid with a course of tablets. It then follows that additional life-long gluten free diet might not give an advantage. 

A 86 year old man was found to have anaemia. His family doctor referred him for a gastroscopy, wondering quite rightly whether or not he had a bleeding lesion in the stomach. He did not, but the endoscopist rather enthusiastically took a biopsy from the duodenum, knowing that coeliac disease might cause anaemia. The biopsy showed partial villous atrophy, the typical appearance of coeliac disease, and the man was sent to my outpatient clinic for further evaluation. His anaemia had been treated and he felt as well as he could expect for his age. Should he be advised to take a gluten free diet? The answer was clearly “No”. It is important to treat a person and not just a biopsy specimen. There would be nothing to gain from him taking a gluten free diet and in this particular case there would be a great deal to lose. He lived alone and he could not cook – he had depended on his wife for sustenance until her death a few years earlier. His present diet seemed to bread either as toast or sandwiches. No wonder he had developed iron deficiency anaemia. A gluten free diet would have brought about his death from starvation.

Is there a place for screening

I have noticed that paediatricians are keen on case-finding. It is known that although coeliac disease does not follow a Mendelian inheritance pattern it is more common in a family member. After diagnosing coeliac disease in a child a paediatrician might tell the family doctor to arrange screening blood test for other family members. I remember well the father of a child newly diagnosed with coeliac disease being sent to me with a positive coeliac blood test. He was a fit and healthy young man without anaemia and without symptoms. Was there are point in trying to coerce him into a life-long gluten free diet? 

This was a long time ago but it made me stop and think about case-finding among the asymptomatic. It is very simple, just a blood test. Much more simple that mammography or cervical cytology. It leads to “diagnosis” but to no more than that. There is certainly no national enthusiasm for screening for coeliac disease, but very enthusiastic individuals might emerge – they usually do and cannot be kept down.

Wheat intolerance 

Many people with intestinal disorders are classified as irritable bowel syndrome. They often find that bread makes them worse and avoidance of bread an other wheat products helps. Testing for coeliac disease will occasionally be positive but it will be negative in the majority. This might come as a disappointment as the diagnosis of coeliac disease is something very positive. Furthermore with this diagnosis will come the entitlement to certain gluten free food products on prescription.

What is happening in people with wheat intolerance but negative coeliac testing is that the intestinal tract cannot handle wheat (not just gluten), probably because of an imbalance of intestinal bacteria. They will take a gluten free diet, best called a wheat free diet and they should not be labelled as having coeliac disease.

It is estimated that in the past only about ten per cent of people with coeliac disease were diagnosed. The simplicity of diagnosis since the introduction of the coeliac disease blood test makes it possible for many more to be diagnosed. These could be people with minimal “illness” such as mild anaemia, usually without symptoms but noted on routine testing. Population screening for coeliac disease would be based on people with no symptoms and no suspicion of illness. Positive testing would lead to the imposition of an unwelcome diet with no significant advantage. Although there will inevitably be enthusiasts for coeliac disease screening, the objective view is that although it would be very easy, it would be of no value.

How common is coeliac disease?

How common is coeliac disease?

This follows from the previous post “Is there really an epidemic of coeliac disease?”

The characteristic syndrome of coeliac disease is rare. It usually will develop in children when, following a milk-only diet, weaning to cereals takes place. The child will fail to gain weight, develop diarrhoea and be generally unwell. After coeliac disease is diagnosed the change to a gluten-free diet will be followed by a rapid improvement.

If coeliac disease is diagnosed in adult life it is assumed that it has been present since early childhood and has been clinically latent. It can be diagnosed at any age, even among the elderly. The presentation would be with anaemia, shortage of iron and folic acid, low weight and diarrhoea.

The new simple blood test allows the testing of people in whom there is no suspicion of coeliac disease, and this allows an estimate of its frequency in the general population. The result is quite remarkable and it now appears that about 90% of people with coeliac disease are undiagnosed. They are walking around happily and taking a normal diet.

But many of them might not be as well as they think. Some will have low-grade abdominal symptoms, often classified as an irritable bowel. If they are demonstrated as having coeliac disease, then a gluten-free diet might give them a sense of health better than they had previously experienced.

Testing for coeliac disease in adults should be considered in circumstances such as irritable bowel syndrome, symptoms being abdominal discomfort after eating, with bloating and diarrhoea.  The testing should be considered especially if there are other pointers such as low weight or weight loss, and iron deficiency anaemia. It can however be diagnosed in people who are overweight.

Irritable bowel symptoms are so common in society that many people accept them as just part of life, and indeed they are often just features of normal intestinal physiology. There comes a time when they interfere with life and this is when a visit to the doctor comes about. Hitherto undiagnosed coeliac disease might then be diagnosed by the simple blood test. 

What harm does it do?

It is vital that this is understood, otherwise justification for “treatment” will make no sense.

In the early 1970, when I was taking Crosby capsule biopsies, case reports came out in the medical journals of various gastro-intestinal cancers in adults who had been diagnosed as coeliac disease in childhood. This was thought to be a big problem, and that very strict adherence to a gluten free diet was imperative to avoid cancer. We thus entered an area of medicine by fear, and this still exists: “You must keep to a very strict gluten free diet or will develop cancer”.

Experience now tells us that these case reports were exceptional and that there is no excess of common gastro-intestinal cancers in coeliac disease. There is however an increase of a very rare form of intestinal lymphoma, but it remains rare. A large community based study of coeliac disease from Nottingham UK, as opposed to previous and biased hospital based reports, indicates a very minimal increase in deaths from intestinal lymphoma, and rather surprisingly a significant reduction of deaths from lung and breast cancers. So coeliac disease is far from being all bad news.

The risk of rare lymphoma has become far less than originally thought. In the past, without up-to-date information, we have been basing risk on only the 10% of coeliac disease patients that have been diagnosed. When we consider all people now assessed as having coeliac disease, the risk of lymphoma immediately reduces by a factor of ten, and this is a big factor.

The purpose of treatment therefore changes from cancer prevention and life prolongation to treatment of the illness, if indeed there is an illness. When coeliac disease has been diagnosed it is worth trying a gluten free diet. If it improves the abdominal symptoms then the person diagnosed will want to continue the diet. Some will find that they are extremely sensitive to gluten and that just a tiny amount will cause symptoms that might persist for several days.

On the other hand some people will notice no benefit. Although they have undoubtedly being diagnosed as having Gluten Enteropathy (disease of intestine caused by gluten), strictly speaking do they really have coeliac disease if they are coming to no harm?

Health statistics - can they be bad for your health ?

How health statistics can misinform - 

We hear of and we see many headlines concerning health issues, and most of them are both bad news and very dramatic. 

They can be very misleading and they can exaggerate what they intend to show. The methods of exaggeration always involve the use of percentages, rather than what  are usually called raw data, ordinary numbers.

Example 1:

About 800,000 people die each year in the UK.

Let us suppose that 8 of  these people die by being stung by a bee or a wasp. This would be an annual death rate of 1 in 100,000.

Let us suppose that in the following year 16 people die from the same cause. This is a death rate of 2 in 100,000.

How is it best to describe this increase in death rate?

First and most simple, there is an increase of 8 per year in the UK. 

But we need to generalise to allow comparisons between other countries, comparisons within different parts of the UK, and comparisons with other years.

And so we describe the increase as 1 in 100,000 per year, from 1 to 2  per 100,000 in this example. We can also express it as an absolute increase of 0.001% of population.

These expressions of increase would not create headlines or induce panic among the population. In order to achieve this, the increase must be presented in a much more dramatic way.

Increasing 8 to 16, or even from 1 to 2 is doubling. This sounds good, quite impressive.

“Twice as many people died from bee and wasp stings this year compared to last year”. Now we are moving into headline news. It is starting to sound dangerous.

But is it twice a big number or twice a little number? This is important in translating risk or benefit to an individual or to a community. Twice something small, like a cent or a penny, is not worth worrying about. Twice something big like £100 or $100 is worth attention!

When a number doubles, the change can be expressed as a 100% increase. 100% of one is one, added to one gives two, a 100% increase.

Once again the question must be asked (but rarely is), 100% of what? Something big or some things small?

In this example what do you think is the most useful and meaningful way of presenting the increase:
100% increase or 0.001% increase (1 in 100,000)?
You would probably agree with me that the latter expression is most useful, giving a reasonable assessment of risk.

(The real death rate from bee an wasp stings each year in the UK is 1 in 200,000, 4 per year in total)

Example 2:

We are informed that if you are admitted to a UK hospital on a Saturday or Sunday, you will have a 16% increased risk of death during the following 30 days compared to if you had been admitted on a week-day.

Dramatic and worrying. Big headlines in the national press. Questions in Parliament. “Something must be done!” “Consultants must spend more time in the hospitals at the weekends.” 

Olfactarithmetic (recent New Scientist) - does the data “smell” right, or does it smell fishy? Is it really true (as the politicians and newspaper immediately assumed) that for 100 deaths following hospital admission on Monday to Friday, there are 116 deaths for those admitted on Saturdays and Sundays?

It is indeed dramatic but it smells fishy. There appears to be a major mortality effect and it should be obvious. The important but missing information is: how many deaths are we talking about? What are the numbers?

The study that led to this identification of 16% was based on approximately 14,217,640 (14.2 million) people admitted to hospital in the UK between April 1st 2009 and March 31st 2010. By 30 days after hospital admission there had been 187,337 in-patient deaths. The proportion dying in hospital was therefore:

187,337 / 14,217,640   =  1 /  75.9  =  0.013   =  1.3%

Now we can apply the 16% because now we know the answer to “16% of what?” :  it is 1.3%.

16% of 1.3 = 0.21

So in reality the chance of dying in hospital within 30 days of admission is only 0.21% greater if admitted at a weekend compared to a weekday.

The study also reports on 30-day mortality whether dying in hospital or following discharge home. There is now a total of 284,852 deaths. 

284,852 / 14,217,640   =  1 /  49.9 =  0.02   =  2% deaths of those admitted.

An excess of deaths for those admitted at the weekend would be 16% higher, which means 0.32% greater than weekday admissions.

Another way of looking at this, is that a weekday admission gives a 98% chance of survival 30 days, compared to 97.68% following a weekend admission. Not a significant difference.

This clearly not going to make newspaper headlines or lead to a parliamentary debate.

But what is the best way of expressing this increased risk? Is it 16% increase or is it 0.32% increase? I suggest the latter, but I have no interest in headlines. The absolute increase, 0.32% is most realistic and it conveys the most useful message to the public.

(I thank Dr Steve McCabe from Portree, Skye, for drawing my attention to this) 

Data source:

Journal of the Royal Society of Medicine. 2012 February; 105: 74–84.

Weekend hospitalization and additional risk of death: An analysis of inpatient data.

N Freemantle, et al.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3284293/

What is the benefit of statins?

We have seen this in an earlier post but it is another example of how statistics can, in this case, exaggerate benefit.

A clinical trial of statin therapy was conducted in the West of Scotland and published in 1994 (is was called WOSCOPS). It studied men aged between 55 and 65, with high cholesterol levels. They had the world’s highest incidence of death from coronary heart disease (CHD, heart attack). Half were given a statin every day for 5 years and the other half acted as controls, being given a dummy placebo tablet.

The five-year death rate in the controls (untreated) was 4.2%, and in the controls it was 3.1%.

This looks like a death rate reduction of 1.1%  (ie 4.2-3.1)

This looks rather undramatic, but it means that 100 at-risk men must take a statin tablet every day for 5 years to prevent (delay) one death. Not very good.

How can we amplify the effect and make it look better?

1.1 is approximately one quarter of 4.1, in other words 25%.

So the advertising of statins tells us that they reduce death rate from CHD by 25%.

This is much more impressive and leads to big sales. But it still means that 100 high-risk men must take a statin for 5 years to delay one death.

There remains the question: 25% of what?

It was more than 20 years ago that the study was performed. Since then the death rate from coronary heart disease has gone down by a factor of 40, from 800 to 20 per 100,000 per year. Therefore it will now require 4000 men (40 x 100) to take a statin for five years to delay one death. This is however kept quiet, the information has been hidden. 

We are still told of the 25% reduction of deaths, but not that it is now 25% of something only one fortieth of what it was 20 years ago. Is it worthwhile?

Beware statistics when expressed as percentages. 

Remember to use olfactorarithmetic - does it smell right?

Is this the beginning of the end of the Cholesterol story?

Everyone knows about cholesterol. Everyone “knows” that it is the cause of heart attacks - because that is what they have been told. Everyone knows that cholesterol comes from fatty food. Everyone knows that fat and cholesterol containing foods must be avoided, the ones that taste so good - why is it that the television cookery programmes are all about cream, eggs and butter?

Everyone knows that we should have our blood cholesterol levels measured, and we expect that if it is “high” then we should take statin tablets to lower it. What we do not know is that “high” means total cholesterol greater than 5.2 mmol/L (200mg/100ml), and that this includes about 85% of the adult population. 

25% of the over 70s in the West Midlands of the UK take statins and 10% of those below the age of 50. It is also suggested “Statins for all by the age of 50” This is all based on the cholesterol-heart story, that cholesterol in the blood causes the arteries to become “furred-up”, thus becoming blocked and precipitating heat attacks, a serious and incorrect oversimplification.

In recent years we have been in the era of “routine” cholesterol measurements, performed on people who are under the impression that they are normal but who turn out to have a condition called “high cholesterol”  (hypercholesterolaemia is the medical term). They are given long-term statin medication and this is the basis of primary prevention of deaths from coronary heart disease.

Change in the USA

But things have suddenly changed, surprisingly in the USA where cholesterol sceptics have not been very obvious and where the diet-cholesterol-heart hypothesis has been most strong.

The new US “Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults” moves away from blood cholesterol concentrations as the basis for prevention! This is a dramatic change and a departure from the first guideline published in 1988, which introduced the 200mg/100ml (5.2mmol/L) threshold, now refined as LDL-cholesterol greater than 190mg/100ml (5mmol/L).

It was obvious from the early clinical trials that the benefit of statins was small but definite. One out of every hundred high risk men treated for five years with a statin each day would have his life prolonged for an uncertain time. But several trials have shown that benefit from statins is not related to either the initial blood level of cholesterol or the degree by which cholesterol is lowered. 

The point is that the benefit of statins appears to be independent of the cholesterol-lowering property, probably an anti-inflammatory action. Statin effect extends well beyond reducing risk of death from heart attack (myocardial infarction, MI), with some anti-cancer properties. 

These clear points  have been avoided in the past years, effectively suppressed by the evangelists of the diet-cholesterol-heart hypothesis, many of whom had considerable vested interests. It looks as though the gravy train is slowing down.

The American College of Cardiology and the American Heart Association are behind this move away from cholesterol, suggesting that prevention of coronary deaths should now be targeted at those at particularly high risk and not at blood levels of cholesterol.

This is a courageous move away from the flawed dogma of the past half-century. It effectively means the beginning of the end of the cholesterol-heart hypothesis. The diet component had been quietly dropped a few years ago: diet is not the cause of heart disease.

And now it is starting to be acknowledged, neither is cholesterol. It is time for medical science to consider what might be the real cause of the epidemic of coronary heart disease.

Cholesterol is involved in the development of coronary heart disease but it is nothing to do with cholesterol in the blood. Cholesterol (as LDL) is part of the tissue inflammatory defensive process and it is in this way that it builds up in the walls of the arteries, probably a response to infection.

Change in the UK ?

How long this change in coronary prevention away from blood cholesterol will take to cross the Atlantic to the UK and Europe remains to be seen.

We know that at the present time the death rate from coronary heart disease has dropped dramatically, the epidemic being almost over about 90 years since it started. The reduction of deaths in the UK has been so great that it will be difficult to identify high risk individuals in the future. The prevention of one coronary death by statins has become very expensive.

It is however a great sense of relief to read of the US change and the dropping of cholesterol screening of the general population. Hopefully things will change soon on the UK, but there will be considerable resistance from the pharmaceutical industry, and those individuals and departments who benefit. 

The wind of change approaches.

http://www.bmj.com/content/347/bmj.f7110

Is there really an epidemic of coeliac disease?

Only a few years ago very few people would have heard of coeliac disease but things are different today. Most people have heard of it and many people have it or suspect that they have it. In my clinical practice of hospital gastro-enterology it used to be very rare but now barely a week goes by without me seeing a newly diagnosed patient. 

But we must always be cautious about epidemics. Is it a true epidemic, that is a real increase in the frequency of a disease resulting from natural or environmental factors? Influenza epidemics for example are obvious, but not epidemics of diseases that are not generally considered to be of a non-microbial cause.

An epidemic can be spurious, false, being a reflection of medical definition and the result of deliberations by a committee. There is supposed to be a present epidemic of diabetes, but is this might be just a result of case-finding in people who consider themselves to be normal. But in addition the definition of diabetes is changing so as to include more people, a greater proportion of the population.

The definition of a disease can change, and so can the behaviour of doctors to diagnose it.  It is only when a disease is fatal that the diagnosis is usually clear, but even then terminology can change. There has been a clear epidemic of coronary heart disease during the 20th century and international death statistics have defined it. When the epidemic developed there was a great increase in the total number of heart deaths, this excluding just a change in terminology.

We must be aware of these factors when we contemplate whether there is a true epidemic of coeliac disease.

Samuel Gee

It was first recognised in children. The clinical picture was that of looseness of the bowel with fatty stools and either weight loss or failure to gain weight. The “pot belly”  appearance of the children gave the name coeliac disease. It was first described by the English physician Samuel Gee, but its cause was completely unknown. 

Identification of the cause

The clue to the cause was a result of the famine in the Netherlands during the Second World War. Whereas the health of the general population deteriorated with tragic results, that of children known to have coeliac disease surprisingly improved. Towards the end of the war the Netherlands was liberated and its food production was restored to its population. The famine was relieved but the children with coeliac disease became ill once again. 

The cause of coeliac disease clearly lay in the diet but what it was remained far from clear. By using a nutritious food that was not in the European diet, empirical experimentation led to a diet of bananas being being identified as effective in restoring good health for these children. They became known as “banana babies”, a term now almost beyond memory. 

Re-introduction of a variety of normal European foods led to the recognition of wheat as the cause, and a wheat-free diet became the treatment. Further investigation identified the true culprit to be gluten, a protein component of wheat flour, and now known to be present in other cereal flours. There is however no gluten in rice flour and people with coeliac disease can eat rice without ill-effect. 

It is gluten that makes dough sticky, and so rice flour with no gluten is not sticky. The bread made from rice flour (and this is what gluten-free flour actually is, combined with potato flour) is very crumbly and in this respect it is not very pleasant. There is a way around this. A small amount of egg-white can be added to gluten-free rice flour to act as a binding agent, as in other forms of cookery. 

The increased awareness of coeliac disease has brought about a widespread availability of gluten-free flour and prepared foods.

The Chinese would not have had coeliac disease as their diet was based on rice and they did not have wheat. When Marco Polo visited China he was introduced to noodles, which were and still are made from rice flour with egg-white as a binding agent. Egg noodles are available in our shops and supermarkets today. On his return to Venice, Marco Polo introduced the idea of noodles to Italy, and it was later realised that wheat flour could be used without the need for egg due to the presence of gluten. Lasagne sheets had been used in Italy for the preservation of wheat during the winter, but spaghetti and other forms of pasta became a new way to preserve and a way to eat wheat. Although pasta is excluded from a coeliac disease diet, egg noodles are perfectly acceptable.

The pathology, the nature of the disease

It was in the 1960s that the pathology of coeliac disease became established. The disease process was in the jejunum, the upper part of the small intestine. The jejunum has the function of the absorption of food, a remarkably rapid process, and damage in coeliac disease leads to impairment of absorption - malabsorption. The result is a failure of absorption of essential nutriments, fats in particular.

An alternative and more accurate name for coeliac disease is Gluten Enteropathy, implying that there is intestinal disease caused by gluten.

Normal jejunal mucosa, tall villi and short crypts

The surface of the normal jejunum is covered with finger-like villi, and this arrangement increases many-fold the surface area available for the absorption of nutrients. In coeliac disease gluten causes damage that results in the villi becoming shorter (partial villous atrophy) or absent (total villous atrophy). These changes can be seen on microscopy.

However the term “atrophy” (= wasting) is not really appropriate. Each of the villi (singular villus, adjective villous) has an associated crypt (a “pit”). The change in coeliac disease is that as the villi become shorter (partial villous atrophy) the crypts become deeper. When in more severe coeliac disease the villi flattened it is called total villous atrophy flattened. The crypts are then very deep. In other words coeliac disease is more of a hypertrophy than an atrophy. The villi have a surface of single cells which have the absorptive function. These cells are formed in the crypts and then travel up the villi and fall off the top. This journey normally takes three days but in coeliac disease it can take only twelve hours. This is indeed hypertrophy of the mucosa, excess growth, or more strictly hyperplasia, an increase in cell turnover.

The process of diagnosis

Identification of pathology relies on biopsy specimens and this was the challenge, to biopsy the lining of the jejunum without the need for potentially dangerous invasive surgery. 

Crosby capsule

The answer lay in the Crosby capsule. This was an ingenious device about the size of a 500mg medical capsule. It was swallowed and on the end of a fine tube it slowly passed though the stomach and into the jejunum, identified on X-ray. When correctly positioned it was fired by negative pressure from a syringe and then withdrawn, containing a small biopsy specimen.

Crosby capsule located in jejunum

Jejunal biopsy using a Crosby capsule was a tedious process taking a full morning and not always being successful. I remember it well from when I was in early years of training. But it meant that very few biopsies could be undertaken, and only in patients in whom there was a very strong suspicion of the diagnosis. 

Things changed in the late 1970s with the wide-spread use of gastroscopy. Most people will be aware of this, a method of examining the stomach and duodenum with a fibre-optic scope. it also allows biopsies to be taken, and this includes duodenal biopsies (from as far into the duodenum as possible) for the purpose of diagnosing coeliac disease. Although the process would take only about ten minutes, it was still minimally invasive and uncomfortable to the patient. However it enabled a much greater number of such biopsies than was possible using Crosby capsule biopsy, and therefore a greater number of people with coeliac disease were able to be diagnosed.

But then at about the year 2000 came a non-invasive test, a simple blood test, the immunological detection of antibodies.  This is now used very frequently, particularly by family doctors and there is no restriction on testing. It is just a matter of the doctor or nurse ticking the box on the blood sample request form.  It is usual to follow a positive blood test with a biopsy and there is a strong correlation between the two.

It has enabled a vast increase in the number of people to be tested for coeliac disease and the number of positive tests has been far greater than expected. The coeliac disease blood test is now performed with little discrimination and on people with, traditional standards, no realistic probability of coeliac disease, for example in people with just recent diarrhea.

Is a biopsy always necessary?

In practice the diagnosis of coeliac disease is based on any three of four criteria:

• a good clinical story
• positive blood test
• abnormal biopsy
• good response to a gluten free diet.

We will see that a good clinical story is not always present. The blood test can be bypassed if a biopsy is performed.

Many people are very reluctant to have a biopsy, the gastroscopy being rather unpleasant. If the patient has symptoms and a positive blood test, then a good response to a gluten free diet will clinch the diagnosis. It is when there is uncertainty that a biopsy is essential. The uncertainties can be a vague story, an equivocal blood test, and uncertainty about response to diet.

There will be further short posts on the subject of coeliac disease.