Tuesday 24 February 2015

CFS, ME - now SEID

Chronic fatigue syndrome CFS or Myalgic encephalomyelitis ME

This has always been a controversial illness. It has been recognised medically for only about forty years, but it is still not universally accepted by doctors. There is always the suspicion that it is somehow imaginary, that the sufferers might be frauds.

A new name has recently been suggested in the USA and I think this is a good move. The new name is Systemic Exertion Intolerance Disease - SEID.

I have had a clinical I interest in fatigue syndromes for more than twenty years. I just happened to see sufferers, but see them with an open mind as many doctors had not taken them seriously. I listened carefully to their stories (the basis of clinical medicine, as I had been taught) and a pattern seemed to emerge. I ultimately became the consultant lead within Lancashire and south Cumbria in the north-west of England, with a population of 1.5 million. The condition is rare but I gained great experience and saw more than 400 sufferers from CFS as I called it then. I learned from the patients.

The patients would report that they felt "tired", "exhausted", or "fatigued", hence the development of the term chronic fatigue syndrome. But normal observers would often say: "But I feel tired / exhausted / fatigued as well, implying that the patients / sufferers were frauds or malingerers, that they were effectively normal but just used a medical escape from work or domestic responsibilities.

It is true that normal people can feel tired, exhausted, fatigued. The problem was that the sufferers did not have the language to express what they were experiencing. There was not a suitable non-medical term that could be used - at least in English but I have no information concerning other languages.

The pattern is that the muscle and the brain are affected. Heart, liver, kidneys, intestines, blood production and other organs function normally. But the muscle do not. In very severe cases the muscles are not strong enough to support the body sitting in an upright position for more than a a few minutes, with the necessity of lying down, but this would be extremely rare. Usually maintaining a supported sitting posture would be satisfactory, but standing for more than a few minutes would be impossible. Walking for more than a few steps or a short distance would similarly not be possible. If at this point the sufferer would be unable to sit down then collapse would occur. The problem is clearly that of "exertion or exercise intolerance" or "exercise-induced muscle weakness". Once such a term is used, the nature of the illness becomes clear.

There is another illness characterised by exercise-induced muscle weakness, and that is myasthenia gravis. It is different and rather more dramatic. Double vision, drooping of the eyelids and slurring of speech are typical.

In SEID / CFS / ME brain function is also disturbed. This is a failure of concentration and the recording of memory. Conversation becomes very exhausting. Reading a book is impossible: when the bottom of the page has been reached, what was at the top of the page has been forgotten. Storylines of television or films cannot be followed.

We can see the advantage of the new term  Systemic Exertion Intolerance Syndrome. "Systemic" implies a wide-spread illness with perhaps more than one body system involved (muscles and brain. Exertion or exercise intolerance is now self-explanatory. The use of the term "Disease" is interesting, but it does give significant medical acceptance of the condition.

In general I use the term "disease" to describe an illness in which there is an obvious abnormality of anatomy, the structure of the body. This would include cancers, heart attacks (myocardial infarction), pneumonia and many others that we know. A "disorder" can be viewed as an illness in which part of the body does not function in a normal way but the structure appears to be normal. We use the term functional bowel disorder as an alternative to irritable bowel syndrome. But when we understand the biochemical aspect of a condition, such as a high blood sugar in diabetes, we tend to use the term disease. I have usually viewed SEID / CFS as a "disorder" as the muscle biopsies usually show normal appearances and the pathophysiology, the nature of the abnormal function, is not clear.

But with SEID there is some understanding of the nature of the disturbance within the body.

This will be the subject of another post shortly.

Tuesday 10 February 2015

High cholesterol may not be bad for you - lesson from the liver

Primary biliary cirrhosis

Continuing the theme that the misinformation that we are given that cholesterol is somehow toxic is wrong....

By "toxic" I mean that a chemical substance that causes damage to us in a way that is related to dose and time-span of exposure. We are told that he greater the amount of cholesterol in the blood, and for a longer period of time, the more damaging it is. This assertion is not just over-simplistic but it is in defiance of the evidence. It is clear but generally unstated that it is only in men below the age of 50 that blood cholesterol is an indicator of risk of future manifestations of coronary heart disease (CHD). Above the age of 60, the age after which the vast majority of the deaths from CHD occur, a high blood cholesterol is a positive indicator of better survival.

Therapy is aimed at reducing the cholesterol level in the blood, but can this really be expected to be of any benefit? It does not appear to help.

Nature supplies us with a natural experiment by which we can investigate the effect of a high level of cholesterol in the blood. It is a liver disease called primary biliary cirrhosis (PBC).

PBC is a chronic disease of the liver that affects mainly middle-aged women. It has nothing to do with alcohol. The cause is unknown but it is generally classified as an auto-immune disease. In older women it tends to be a curiosity that is picked up incidentally from "routine" blood tests, but in younger women it is likely to be progressive and serious. There is no cure for this condition but it might lead to liver transplantation.

In PBC there is characteristically a very high level of cholesterol in the blood, and this has been recognised for more than half a century. This has given plenty of time for research.

The large amount of cholesterol in the blood in PBC might be deposited in the skin, creating fat patches that are called  xanthomas, or xanthelasma if there are many of them. They tend to occur on the inner parts of the eyelids, on the knees and in the creases of the palms of the hands.

According to what we are told this would make people with PBC particularly susceptible to early death from CHD. They might be expected to have a large amount of cholesterol deposited in the walls of the arteries causing blockage, but this does not happen.

People with an exceptionally high level of cholesterol can be recognised as having familial hypercholesterolaemia (FH), of which we learn more in a Post to follow shortly. It is however interesting to compare the fortunes of those with PBC and those with FH as both have similarly high levels of blood cholesterol.

Those with PBC have a fundamental disadvantage in that they have a serious liver disease. It is only in recent years that liver transplantation has become available as otherwise the younger ones would die early because of liver failure. Transplantation has proved to be every effective in this condition although it can sometimes recur in the new liver.

During the 20th century people with FH have been at a considerable disadvantage in respect of CHD with premature death. However it is now clear that in contrast people with PBC are not at any disadvantage. They do not develop premature CHD and this has been demonstrated in a number of studies. The conclusion of one study is that "(in people with primary biliary cirrhosis) marked hypercholesterolaemia ....is not associated with an excess risk of cardiovascular disease."

If CHD were due to a high blood cholesterol with simple deposition of cholesterol from the blood then we would expect people with PBC to be very much at risk. But we can see that this is not so. This natural experiment casts serious doubt on the widely-accepted model of CHD. It indicates that CHD is not simply due to large amounts of cholesterol in the blood being deposited in the tissues.

We have seen in a recent Post that cholesterol in the wall of the arteries is not the result of simple deposition from the blood. It is an integral part of body defence mechanism and an important part of the inflammatory reaction.

Longo M et al.
Hyperlipidaemic state and cardiovascular risk in primary biliary cirrhosis.
GUT 2001 51 265-269.