The Clinical Management of Patients with
Chronic Fatigue Syndrome and/or Fibromyalgia - An "Essay"

By: Burton A. Waisbren, Sr., M.D., F.A.C.P., F.I.D.S.A

My practice has gradually evolved to try to find solutions for patients who have been told there is nothing to do.  There has been a trend over the past 10 years for patients of this type to appear with either the chronic fatigue syndrome or fibromyalgia.  In this essay, I will share with colleagues and patients, the approach and methods that have apparently helped some individuals. I will then describe the background upon which the treatment program is based and the specific modalities that I have found to be worthwhile.  An experienced physician should be able to decide whether the history fits the description of the chronic fatigue syndrome, fibromyalgia, or whether the history better fits another disease.

The main characteristics of the chronic fatigue syndrome have been well described.  In my experience, the fatigue itself is the best thing to consider.  This fatigue becomes overpowering when the patient reaches a certain level of exertion, and each patient can usually describe this level.

The second prominent feature is difficulty in concentration and memory.  These symptoms are the first to improve when a treatment program is working.  However, the physician should be watching for cases, which I would call narcissistic chronic fatigue.  In this syndrome, the patients fall "in love" with this disease.  These patients usually spend the entire session focusing on their need for Social Security Disability.  Patients of this type are very hard to handle and to treat.

There are two features of the history I have found to be of particular importance.  These are that the chronic fatigue syndrome can follow hepatitis B vaccination and that masked hypothyroidism will also mimic this condition.  Masked hypothyroidism presents itself with a strong family history of thyroid problems and the presence of anti-thyroid antibodies.
The physical examination in my experience is usually non-revealing with perhaps slight enlargement of the tonsils and/or adenoids.  Palpable organs or generalized lymphadenopathy should alert the clinician to turn his attention to other diagnoses.  The well-known tender points of fibromyalgia should be tested for in chronic fatigue patients because these diseases often develop together.

The laboratory studies I find most important are the search for antibodies to the Epstein-Barr virus, the Cytomegalovirus, Herpes VI virus, and Herpes I virus.  Antibodies to one of these viruses and/or having a history of infectious mononucleosis appear to be the most positive serological findings.

Laboratory tests to rule out other diseases should also be done.  In an endemic area, a Lyme disease test should be performed.  However, the clinician must remember that a negative test does not rule out this disease.  Thyroid autoantibodies as well as T3, T4, and TSH levels should be determined since as mentioned above masked hypothyroidism is always a consideration.  Of course, hidden neoplasms and the usual autoimmune diseases should be ruled out by the proper tests.  If these diseases are found they should be treated appropriately.

We also investigate possible sleep disorders as a cause of the fatigue.  We ask the patients partner about snoring and get sleep studies if it occurs.

We have gotten away from tilt table studies and attempts to document foramen magnum (Chiari syndrome) as a cause of CFS since neither has been proven to be of much help in our hands. 

When I conclude that the patient does indeed have chronic fatigue syndrome or fibromyalgia, I reassure him/her that what they have does occur, and that it is not a sign of emotional distress.  I do this because often they have been told "it is all in your mind," and that tranquilizers are what they need.  I tell them that there must be a way to help them, and that we will search for it.

I then tell the patient that we should start a sequential therapeutic program that might help.  I emphasize that I am not trying to prove anything, but I feel that multiple reasonable therapies are worth trying.  I also emphasize that in the traditional framework of organized medicine, that none of the treatment I propose have been proven to help.

Numerous articles and literature suggest an immunologic and/or viral etiology of this condition. The numerous immunologic abnormalities described in medical literature may be the result of an immune deficiency or the cause of it.  I am not sure how productive it is to follow abnormal immunologic findings on an individual basis.  Similarly, I do not feel that it would be productive to subject patients with chronic fatigue to single treatment modalities in order to prove their efficacy.  As we have found in cancer and most severe infections, more than one modality must often be given to obtain optimum results in a particular disease.  I think the best way to evaluate the treatment is let the patient tell you if it is helping.  If the patient tells you that he is being helped, he probably is.

With the above as a frame of reference, a medication routine that can be reasonably used on a sequential basis can be started.  I know of no objective laboratory way to evaluate the efficacy of this program.  In patients that I think are helped, the first subjective sign of improvement has been an improved mental acuity.  This is followed by a rise in the ceiling that restricts their activity by the appearance of extreme fatigue that often lasts for several days after too much exertion has been attempted. Later on, sleep patterns appear to improve and finally a graded exercise program can be tolerated.

The program used is as follows:

  1. Gamma globulin 4 cc. intramuscularly first twice a week, then weekly, and then less frequently, seems to be an effective treatment in some cases. Patients can often tell how often they need this injection.  Intramuscular gamma globulin is cheaper and safer than intravenous gamma globulin. Theoretically the gamma globulin provides blocking antibodies that block out a theoretical autoimmunity that is evolving.
  2. Acyclovir or Valtrex. These are used in relatively high doses. A dose of either Acyclovir 1600 mg or Valtrex 2000 mg is given daily. They are well tolerated, safe and are used because of the hypothetical viral component of this disease.
  3. Naltrexone 50 mg daily. I started using this drug after I read an article that showed
    abnormal monocyte functioning in cells from patients with the chronic fatigue syndrome. These normalized after naltrexone was added to an in vitro monocyte function test. I corresponded with Dr. Prieto, the author of the article, who was in Pamplona, Spain, and asked him if he had tried naltrexone on patients. He said that he had and that he thought it had helped. Accordingly, I give naltrexone to chronic fatigue syndrome and fibromyalgia patients who are not responding to gamma globulin and Valtrex. At first many of these patients have violent gastrointestinal reactions to a 50 mg dose and often we have to start with a dose of 5 mg a day and work our way up. Theoretically, the patients who respond may be narcotizing themselves by excessive endorphins or endogenous material stimulated by an autoimmune reaction. It is know that naltrexone neutralizes opiate-like compounds. Whatever the physiology I can share with colleagues that this drug if judiciously given might help some but not all patients.
  4. I have found that Provigil, the drug used for narcolepsy has helped the fatigue in some patients. This was suggested to me by the report that the drug Provigil helped the fatigue felt by some multiple sclerosis patients.
  5. Another thing that that has been used with some success is Isoprinosine. There have been several cases in which there seemed to be a very definite response. However, some patients did not respond.  Theoretically, Isoprinosine improves T-cell function.
  6. Recently, we have leaned toward more consideration of sleep deprivation and sleep apnea. It is often helpful to prescribe a sleeping aid in CFS patients that complain of insomnia.  It seems that a C-Pap program will help some CFS patients actively overcome their problems even when sleep studies are equivocal.
  7. When a person has no response to any of the above, what might be done next?  In several cases, I have used the immunologic techniques we have used in cancer.  This consists of mixed bacterial vaccine, transfer factor, BCG and lymphoblastoid lymphocytes. The discussion of this treatment is available on this website.  In several instances, the results have been encouraging but the expense and the fact that the third parties are reluctant to finance this sort of approach makes it impractical at present.

While CFS and fibromyalgia are in many ways similar and in some cases fibromyalgia does respond to measures we have described above, fibromyalgia presents some unique problems.  Some patients we have seen “who hurt all over” may well suffer from Somatization syndrome, which is described as severe generalized pain without known organic cause.   One help in coming to this diagnosis is that these patients pain breaks out of the boundaries so characteristic of fibromyalgia.  We have tried but have not helped patients of this type.

Another complicating feature in fibromyalgia is that a number of patients with this syndrome have become addicted to narcotics.  Often this is not their doing but a result of valiant doctors trying to help them.  Our position with these patients is that they must first be detoxified, often in an inpatient service or sophisticated pain clinic before we would try to help them.  We never go further than Ultram and modest doses of Neurontin for fibromyalgia. 

Finally, the internet seems to be becoming a double edge sword in regard to fibromyalgia.  Treating this disease appears to be becoming a big business with claims of sure cures becoming common on websites and chat rooms.  The red flags that must be watched for in this regard are claims of guaranteed results.  Here the peer review function of sophisticated internet users should come into play.          

One part of the covenant that should be made with a patient with chronic fatigue syndrome and fibromyalgia is that new treatments reported on the Internet and in traditional medical literature will be researched and considered. Q-10 and guaifenesin have been touted for treatment of chronic fatigue syndrome but they have not helped my patients.

At this point, the patient should be asking, "How can a practicing clinician who fancies himself a careful scientist share treatment strategies with his colleagues that have not proven effictive in the classic sense?” My answer to this is that I believe that if this program is followed, that some patients may be helped by it.  Perhaps more importantly, I am trying to make several points. First, when a patient shares with a physician that he is sick and tired, he probably is, and it is vital that the physician do something about it.  Statements to the effect that there is nothing to do cancels out one of the most important things that a physician can give to his patients, that being hope.  Finally, I believe there is always something to do to help a patient.  With the Medline and worldwide web at their disposal, the physician should be able to find something reasonable to try for patients not responding to usual treatments.  All reasonable proposals that are not toxic should be shared with patients and with their consent; a program can be started.  It is in this frame of reference that the above has been written.


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