Nancy Klimas, MD, is Professor of Medicine at
the University of Miami VA Medical
Center, where she conducts research on immunologic abnormalities in chronic fatigue syndrome (CFS).
Wallace, MD, a board-certified internist, is Assistant Professor of Medicine and Healthcare Sciences at
George Washington University Hospital in Washington, D.C.
(Excerpted with permission from
an article published in the June 2000 issue of The Journal of Women's Health & Gender-Based Medicine.
For information on obtaining reprints of the full article, call the publisher at 914/834-3100.)
How can the primary care physician properly diagnose
One sign of the illness is orthostatic
intolerance (OI), which causes autonomic dysfunction. This may happen early, or it may be a result of
deconditioning. An estimated 60% of women with CFS will have OI.
A typical example is the woman
who goes shopping and must stop 15 minutes into the activity because she feels a sudden need to
down. This is not a fainting spell, dizziness or fatigue. Rather, the patient is experiencing a bradycardic
hypotensive moment, and she sits or lies down to prevent symptoms from worsening.
this as the “cognitive cloud of fatigue” because they are going along fine when an abrupt wave of symptoms,
such as total body pain or aches, forces them to stop.
Hand in hand with the drop in blood pressure
comes a host of nonautonomic symptoms, such as swollen lymph nodes, sore throat, total body pain, myalgia
and arthralgia. The presence of OI can and should be tested by a tilt-table test. I caution primary care
physicians to have a tilt-table test performed by a cardiologist who has experience with CFS because these
patients are at high risk for cardiac complications.
That said, there is a very straightforward
workup to exclude other common illnesses that occur with fatigue. Most important is a symptom-driven physical
examination with a complete blood count (CBC), Chem23, sedimentation rate, ANA, and TSH,
T3 and T4
A classic case will be very obvious.
There is little else that can cause such an abrupt change in function and the accepted complex of symptoms.
As with migraines, a good medical history is key, as there are no definitive tests available to confirm
The physician needs to rule out other plausible causes of the symptoms such as sleep
disorders, chronic infection, depression, malignancy, systemic illnesses and adrenal insufficiency, based
on a thorough history and physical exam.
The process of diagnosis can take months, and as new symptoms
or a change in symptoms arises, the diagnosis should be reviewed. As time goes on, I look for more esoteric
causes, such as porphyria or
What is the recommended approach to treatment?
It is important to approach management
of CFS with the understanding that these patients do not metabolize drugs normally, typically demonstrating
a low tolerance for any kind of medication. It is essential to use very small doses and begin one or two
drugs at a time to monitor the effect and, after four to six weeks, to introduce additional medication
I focus my treatment in five major areas:
Patients are treated as if they have a diminished blood volume and are dehydrated. The theory is
that too much blood pools in their lower extremities. To counteract this, patients are instructed to increase
their fluids to two to three quarts a day and to increase salt through intake in food, salt tablets and
occasionally intravenous saline. If this is not sufficient, I may prescribe fludrocortisone to increase
Another approach is the use of vasoconstrictors. For this, I prescribe the newly
approved drug Midodrine. Although these measures are not always effective, it is all some patients need
to regain substantial functioning. Beta-blockers and clonidine are also useful adjuncts that blunt inappropriate
Sleep. A drug that seems most effective is Ambien, which works well
for a specific sleep disorder often seen in CFS and fibromyalgia patients—alpha intrusion into delta sleep.
Although it has some potential for addiction, Klonopin is a very good sleep drug because it also helps
with pain. I use the smallest dose possible. Another effective sleep drug is Neurontin, which also helps
Tricyclic antidepressants (TCAs) can aid sleep, but if I use them, I use tiny doses
(5 to 10 mg). The caution with TCAs is that they can cause low blood pressure and tachycardia.
Although controversial, I believe that long-acting narcotics are needed to relieve pain among these patients.
Because there is no inflammation causing the pain, NSAIDs are not likely to be effective. Anticonvulsant
drugs, such as Neurontin, can be useful.
General Support. To help with cognitive
problems, I rely on stimulating drugs, such as Ritalin, Welbutrin and a new drug, Provigil, which tend
to wake up the brain.
For energy levels, there are several complementary preparations I use as
adjuncts. I often begin with vitamin B12 injections (up to 5,000 mg three times/week). Other preparations
I recommend include NADH, evening primrose oil (up to 5,000 mg/day) and glutathione by injection.
skills. It is essential to work with patients to accept their limitations. I encourage my CFS
patients to do some muscle toning and some light physical activity [as they are able].
techniques, such as yoga or meditation, can be useful, but women should be cautious about yoga, which
can reduce blood pressure, a preexisting problem for some patients.
Certainly, if concomitant depression
is present, it should be treated, in which case the patient’s mood is likely to improve but the chronic
fatigue syndrome will not.
I begin with sleep, borrowing from the research
on sleep dysfunction in fibromyalgia. The most effective drugs are TCAs in low doses, preferably Sinequan
elixir, which gives patients eight hours of sleep and simultaneously reduces pain. I begin with
5 mg and work up to 20 to 25 mg.
Next I deal with pain. More often than not, patients arrive with
a great deal of pain medication, most of which are short-acting, as-
the patient is having withdrawal symptoms as the pain medication is wearing off, I wean the person from
their current regimen and then look for nonpharmacological alternatives, such as massage, stretching and
physical therapy (whirlpool, hot tubs).
These ancillary options, along with NSAIDS, seem to work
for all but 4% to 5% of patients. For the few who require pain medication, I choose the long-acting, 24-hour
opiates at a low dose.
When autonomic dysfunction is present, the goal is to increase plasma volume.
Generally, if the patient has a positive
tilt-table test and increasing salt and water makes her feel
better for a few weeks, the kidneys become efficient at getting rid of the extra sodium, at which time
the patient should be prescribed fludrocortisone (Florinef).
Another route is to prescribe alpha1-agonists,
such as pseudoephedrine. The most selective alpha1-agonist is Midodrine.
The third option, often
used in combination with one of the other drugs, is to use a beta-blocker to reduce the pulse, allowing
for a longer fill time and slowing of the impulses to the stretch receptors.
axis (HPA) interventions have not been well studied. Only cortisol has been looked at on a limited basis,
and the results were inconsistent. The danger is that cortisol may have to be given lifelong. Thus, it
is premature to recommend this drug until we have a better understanding of its efficacy.
regard to the immune system, we have a system that is hyperactive but not working properly. There is some
controversy about using SSRIs as immunomod-ulators. Anecdotally, I recommend limiting their use to nondepressed
CFS patients and giving a four to five month trial to assess improvement.
Are there any alternative treatments contraindicated
I try to discourage my patients from
trying expensive, unproven treatments, such as chelation therapy and mercury detoxification (dental fillings
Dr. Klimas: Licorice
root works like Florinef but
also has some adverse effect, which is hypokalemia. Symptoms of low potassium are nearly the same as that
of CFS. Thus, physicians should monitor potassium levels.
Dehydroepiando-sterone (DHEA) is popular
and has its advantages as well as hazards. It affects estrogen and testosterone
levels, among other
hormones. The problem is that patients may feel good on a small dose (i.e., 25 mg) and then increase it
to feel even better, but there is concern about this preparation increasing the risk of breast cancer
and other hormone-induced cancers.
St. John’s wort is a natural SSRI and should not be taken with
other SSRIs. Some effective and safe supplements include a multivitamin with a great deal of the B complex
vitamins, vitamin E and eicosapentanoic acid (EPA).