Fatigue and Weakness in Scleroderma
Patients
By Jane H. Park,
Ph.D., Vanderbilt University School of Medicine (originally
published in "Scleroderma Voice," 2003 #3)
Editor's note:
This is a long article. You can skip directly to the sections
that interest you, by clicking on these links:
 |
| Jane
H. Park, Ph.D. |
Our studies on scleroderma
started with Dr. Lloyd King, who observed that his scleroderma
patients often felt fatigued and weak.
This lack of energy
was reported by him in patients with diffuse, extensive skin
involvement and also in patients with limited scleroderma,
mainly localized to the hands and face.
Our
Hypothesis
Dr. King thought
this fatigue was the result of a real metabolic problem, and
not just a subjective feeling of the patient.
Therefore, he suggested
to Dr. Nancy Olsen and me that we examine the muscles of scleroderma
patients using MRI (magnetic resonance imaging) techniques,
and look for abnormalities in the energy metabolism during
rest and exercise.
We were anxious to
begin such a study, because fatigue and weakness can definitely
impact the daily activities and lifestyle of patients.
Building
on Previous Work
The investigation
was quite reasonable, since a number of investigators—for
example, Medsger and colleagues, and Clements and associates—had
published work demonstrating weakness and non-specific fatigue
in sizable groups of scleroderma patients.
Our
Findings
Indeed, our studies
did show that biochemical abnormalities were present in muscles
of scle- roderma patients. These abnormalities could account
in part for their reported lack of energy in the activities
of daily living.
Our
Methodology
Our results were
obtained with the MRI machine and can be very simply explained.
The MRI can produce
excellent pictures (images) of muscles. However, more important
for our work, MRI can also measure the concentration of two
essential phosphate compounds, which provide the high energy
required for muscle contraction. These two essential compounds
are called ATP (adenosine triphosphate) and PCr (phosphocreatine).
When the concentrations
of ATP and PCr in muscles are below normal levels, then muscle
contraction becomes impaired, resulting in decreased muscle
strength.
ATP
and PCr in Scleroderma Patients
Our studies showed
that the thigh muscles of scleroderma patients at rest had
an average reduction of 35% in concentrations of both ATP
and PCr compared to normal muscles.
These decreases in
ATP and PCR were present in patients with both diffuse or
limited scleroderma. Thus our initial findings offer a partial
explanation for lack of energy in both types of patients.
During exercise,
the thigh muscles of scleroderma patients proved to be less
efficient than normal muscles in using ATP and PCr. Decreases
in ATP were accentuated in working muscles, which were contracting
for as short a time as 10 minutes.
The recovery period
following exercise is also important. One can see how quickly
trained athletes, such as basketball players, can recover
from strenuous exercise and are eager to leave the bench to
begin playing again.
The recovery period
is also important for each of us during all kinds of daily
tasks. The faster you recovery from a given task, for example
doing the laundry, the sooner you are ready to attack and
complete the next job.
Recovery of muscles
after exercise can be accurately measured in the MRI magnet
by determining the rate at which PCr (phosphocreatine) is
regenerated after exercise.
We noted that the
patients required more than twice as much time to resynthesize
new PCr as the normal controls. Over the course of the day,
this growing deficit in PCr could be a sub- stantial factor
in progressive fatigue.
The
Role of Magnesium
I would like to mention
one other compound, namely, magnesium, which is also essential
for muscle contraction and endurance.
Magnesium is important
because it is required by all the muscle enzymes involved
in energy production.
Magnesium and ATP
always tightly bind together, and ATP is only active in the
presence of proper concentrations of magnesium.
The concentrations
of magnesium are also low in muscles of patients with either
diffuse or localized disease.
During the stress
of exercise, the muscle deficit in magnesium is actually increased.
Thus, reduction of
magnesium provides an additional factor in the explanation
of the well recognized fatigue and weakness in scleroderma.
It's
Not All in the Mind
These biochemical
reductions in ATP, PCr (phosphocreatine), and magnesium are
helpful for patients, family, and friends in understanding
the reasons for fatigue. Lack of energy is not just a simple
problem of attitude, but rather a real metabolic problem.
Implications
for Future Work
We hope these studies
will also suggest some ways to alleviate weakness and fatigue.
For example, many
studies in other laboratories have shown that giving creatine
to both athletes and sedentary people can actually increase
the levels of the high energy PCr (phosphocreatine) and ATP
in muscles.
We are considering
a controlled clinical trial to determine whether similar improvements
can be observed with scleroderma patients.
Magnesium also represents
a possibility for future trials leading to stronger muscles
and increased endurance.
Since scleroderma
is such a complex disease, these biochemical findings and
ideas will necessarily be complemented and enhanced by many
other scientific contributions, which will lead to a more
active and enjoyable lifestyle for patients. |
