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Dr. Bell on ME/CFS Symptom Variation: Illness or Host?

  [ 61 votes ]   [ 3 Comments ]
By David S Bell, MD, FAAP • • March 7, 2012

This information is excerpted from the Nov 1999 issue of the Lyndonville Journal - a bi-monthly newsletter from Dr. Bell's medical office that preceded the Lyndonville News ( It is reproduced here with kind permission,* and offers still-relevant insights, as research to identify proper case definitions, potential ME/CFS subsets, and causes continues.

Symptom Variation: Illness or Host?

Roughly 70% of the persons I see in the office have a pattern of symptoms that is "typical of" chronic fatigue syndrome (CFS). The remaining 30% have variations where doubt can be raised as to the diagnosis. This variation in symptoms is the main reason that researchers may see CFS as a variety of differing illnesses that produce fatigue as a symptom.... But I feel that the vast majority have a single illness, rather than CFS being a mish-mash of different illnesses. The issue here is the debate of illness versus host.

What exactly comes from the cause, and what comes from the host response? To look at this conflict, let us look at chicken pox.

Chicken pox is an everyday, run of the mill, simple illness. Every clinician makes the diagnosis with ease. You seen one chicken pox, you have seen a thousand. It is simple and it is one single illness. That is because it is an illness that affects a distant target organ - the skin. A five-year-old comes in with a fever and little blisters that look like a "dew drop on a rose petal." And that is exactly what a perfect chicken pox looks like. (I have no idea where the chicken part comes in.)

There may be some minor variations. A child may have 30 pox or 300. Some pox (or poxes?) may get infected or scabbed over. Big deal, it is still chicken pox, one illness. The host (or person with the illness) does not affect it much.

But wait. In some cases the host is critical and the illness can be different. Some people have chicken pox without a rash, or have a pneumonia, or worse yet, have a neurologic complication. Is it still chicken pox? Yes, because we are able to culture the virus from the lung or brain, and it is the same as the regular chicken pox in the skin.

In CFS we do not have this luxury. The situation is different.

Whatever CFS is, it affects a very central mechanism within the body, not an end organ like the skin. And this central mechanism, probably the brain, can manifest the symptoms of an insult very differently. With the brain, the same injury or illness causes a variety of symptoms. (Brain tumors, for example. The symptoms of a one-inch area of brain injury depend entirely upon the location of this injury. In one area, there may be minor if any symptoms. In another it might cause arm weakness, in another area, behavior or emotional symptoms.)

Let us suppose for one minute that a single neurotropic virus - one that affects brain tissue - causes CFS. If this virus affects only a small part of the brain, the symptoms will be uniform (post-encephalitic Parkinson's). But if it affects more than one area, then a multitude of symptoms may result, with clear variations from person to person (Post polio syndrome). The issue is the competition between agent specificity and how the host responds to it (host versus illness).

The enormous complexity of both genetic and environmental factors makes people different. By itself, this is an interesting discussion, and probably a good thing. But science would be easier if we were all clones. (We would probably get along better as well.) The complexity of host response, differences in immunity, emotional vulnerability, and environment makes it so that the same injury may cause a variety of responses, particularly if that injury is to a central or primitive part of the brain.

In CFS, we can trace the symptoms to this primitive part of the brain where hormones are produced, where sleep and alertness are regulated, where blood pressure and heart rate are controlled, where pain is modified.

One person with CFS may have asthenia [lack of energy and strength] as the worst symptom. In another, pain is the worse symptom. Are these two illnesses, or are they the same? 

The answer is seen not by looking at one or two symptoms, but by examining the entire symptom pattern. For now, it is reasonable to define CFS broadly without being picky. A clinical, symptom-based diagnosis is appropriate, with the understanding that other fatigue-causing illnesses have been excluded. The pattern of symptoms rather than the specific worst symptom defines the diagnosis. And this pattern may vary from person to person. I do not see this variation as due to differing illnesses. Rather I see the same illness having differing host responses.

The roots of my bias are easy to spot.

In Lyndonville, many persons developed severe fatigue and other symptoms due to something. Because this took place in an isolated rural community, I feel that it must have been a single event. [The 1985 'Lyndonville outbreak' of CFS affected 210 persons, 60 of whom were children, a patient group that Dr. Bell continues to track.(1)] I do not think that 15 different cause of CFS hit all at the same time. For this reason, the variation of symptom severity and even emphasis must be due to host responses rather than cause.

Two children in the same family become ill: One has acute onset, one gradual; one with fatigue as the worst symptom, one with headache. But it is too much of a coincidence that these would be different illnesses within the same family at the same time.

As an aside the CFC has stated that CFS does not run in families. This is because all may not fit the CDC research criteria. But most clinicians feel that there is a clear familial component. If three family members develop chronic fatigue at the same time, host response is more likely to explain the differences in symptoms than the possiblity of separate illnesses.

At the time of the CFS 'outbreak' in Lyndonville, there were those with viral infections that caused two months of fatigue. Lucky individuals. And there were siblings who got full-blown CFS. My hunch is that it is the same initiating event expressing itself differently in separate individuals.

We will know the answer to host versus illness only when an an underlying cause is known in a few persons. Then we can see if the others have evidence of the same underlying cause. This was the case with HIV infection. Some persons would have cancer, some bad pneumonias. Only when a specific initiating event was found was it possible to understand the full spectrum of HIV infection.

So now we have to wait. We can create a definition, and start from there. It is my hunch that we will soon define appropriate subgroups of CFS. And it remains to be seen whether these subgroups are artificial or will accurately define different causes of CFS.

But until this occurs, persons with CFS should not be denied appropriate diagnosis, treatment, or disability benefits if warranted. The definition of CFS now must be broad. Whether due to host response or initiating cause will be answered eventually with research.

I am going to put my money on:

• A few different initiating events,

• Causing a specific physiological injury,

• In persons with varying host response.

And I keep wondering why I am broke.

- Dr. David S Bell, MD, FAAP, Nov 1999


1. See Dr. Bell's presentation on his tracking of the Lyndonville outbreak patients ("25 Year Follow-up on Chronic Fatigue Syndrome: Rising Incapacity,"), delivered Apr 16, 2011 as part of the Massachusetts CFIDS/ME & FM Association's lecture series. (Allow ample time for the video download.) He discusses symptom variation, and theorizes that 'fibromyalgia' is a term people use when they're able to be up and around, but their pain is considerable.

* Reproduced with kind permission of the author from the paper archives of the Lyndonville Journal, © Bell, Pollard, Robinson, 2000. All rights reserved. See Dr. Bell’s website to sign up for its e-successor, the Lyndonville News (

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Article Comments Post a Comment

Excellent Article
Posted by: Mikie
Mar 7, 2012
First, Dr. Bell has seen a cluster event and followed the patients and observed the differences in symptoms first hand. Those of us who have CFIDS/ME and talk to others here with this condition know that not all of us are identical and that no one treatment helps us all. His likening this to Chicken Pox and AIDS helps to make his point in an easy-to-understand manner.

What muddies the waters has always been that the infections, which many glom onto to and call the cause, eventually fail the test. Many, but not all of us, have several chronic infections, none of which are likely the "cause" of what ails us. The cluster outbreak in Punta Gorda, FL in the 50's occured following a govt. spraying "for insects." No one has ever been able to find out what was in the spray.

So, the debate continues as to whether it is one pathogen or exposure to a toxin which causes all cases of CFIDS/ME or whether various events can bring on this illness. I agree with him that CFIDS/ME is one illness and he made his point well. Still, I'm not convinced that there is "one cause." Only time and research will tell.

Reply Reply

Dr. Bell agrees
Posted by: Narey63
Mar 7, 2012
He wrote that he would put his money on "a few different initiating events."


Dr Bell
Posted by: Elisa
Mar 7, 2012
Brilliant medical thinker and investigator!
Reply Reply
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