Scleroderma:
What Gets Better, and Why (Part 1 of 2 Parts)
 |
| Lee
Shapiro, M.D., FACP |
By Lee Shapiro,
M.D., FACP, The Center for Rheumatology, LLP, Albany, New
York (originally published in "Scleroderma Voice,"
2002 Issue #4)
Editor's note:
You can skip directly to the subheads that interest you, by
clicking on these links:
This piece was
originally titled Scleroderma: What Gets Better, What Doesn’t,
and Why. After I started writing, I realized I had bit
off more than I could chew. I found there is plenty to say
about what gets better and why, and I will leave the issue
of what doesn’t get better for another day.
Knowledge
Is Power
I truly believe
that with this disease, knowledge is power and ignorance is
not bliss. You need to know what is happening to you and what
could happen to you. The most treatable features of scleroderma
in any part of your body are the early features, and this
is likely always to be the case. The well-informed patient
may not always do well, but he or she will always do better
than those who keep themselves in the dark.
I want to emphasize
the power of knowledge, and the immense relief which understanding
can bring—and thereby make even this article, if possible,
part of the recovery process.
Let’s
Begin at the Beginning
The natural history
of scleroderma starts before the diagnosis is made, sometimes
years before. The individual develops an awareness of altered
bodily function (such as frequent heartburn, shortness of
breath, stiffening or blanching of the fingers) or changed
appearance, but the cause is not yet known to the individual
so afflicted. This period of uncertainty may be prolonged.
Denial of symptoms—or
simply fear—may lead to delay in pursuing medical attention;
and the first encounters with a physician may not lead to
diagnosis. This isn’t due to physician ineptitude, but
to the often-subtle onset of the disease and the often-meager
physical findings early in the disease.
As in so many illnesses,
the answer becomes more apparent over time. But unfortunately,
even when the diagnosis is ultimately made, instead of relief
at discovery of an answer, the patient’s unease persists,
and may worsen because of uncertainty as to one’s fate.
In this day and age, a diagnosis often leads to self-directed
Internet research which may overwhelm an individual, introduce
someone to all the potential complications of the disease,
and yet fail to provide information pertinent to the searcher’s
future.
Thus a diagnosis
of scleroderma is not sufficient knowledge to allay anxiety,
nor is it sufficient, by itself, to assist the patient and
his or her physician in anticipating future events.
The
Physician Has Several Responsibilities to You, the Scleroderma
Patient
We, your physicians,
need to provide you with knowledge relevant to you, and greater
peace of mind.
The physician has
multiple tasks, and it is a challenge—but a necessity—to
complete them rapidly and accurately.
Obtaining
an Accurate, Detailed Medical History
From you, we must
obtain an accurate and complete history. We must know what
problems have already occurred, how they have affected your
functional abilities: your normal home and work activities.
We must get a sense
of the pace of disease progression. Have you had Raynaud’s
phenomenon for the past 15 years, or did hand swelling and
stiffness develop just in the past few weeks. Diffuse disease
is sometimes misdiagnosed as limited disease on a first visit,
such as in an individual with puffy hands and Raynaud’s
phenomenon, because this time element is ignored.
What
Is Your Support System?
We must get some
sense of the support system available to you. Are you on your
own, or is there a spouse or companion to help you with difficult
tasks?
How
Are You Adjusting Psychologically?
We should also
try to explore the psychological impact of your illness. Fear,
anger, insomnia, and hopelessness are issues that must be
addressed.
Properly handled,
this “adjustment disorder” can be the first part
of the illness to improve. Dissolving fear and apprehension
is for me, the most gratifying of all medical tasks. From
now on, you won’t be alone, you won’t be without
a clue as to what is happening to you, and you will gain in
confidence in your coping skills.
Conducting
a Careful Physical Examination
Then the physician
must examine you physically with equal care, with a focus
on the skin. This may seem peculiar to you, but the extent
of skin thickening and the changes in skin thickening over
time are as important as any blood test in telling us about
your disease and your response to therapy.
The goal of this
history-taking and physical examination is to help the physician
categorize your illness, specifically as to whether you have
so-called “limited” or “diffuse” disease,
or whether you have scleroderma overlapping with another connective
tissue disorder, such as lupus or polymyositis.
Ordering
Appropriate Tests
To help make a
proper diagnosis, antibody studies are helpful.
Anticentromere
antibody is strongly associated with limited scleroderma,
and Scl70 antibody is seen with diffuse disease—but the
antibodies are not in themselves diagnostic, and they are
not always present even in the face of obvious disease.
EKG, echocardiogram,
chest x-ray, pulmonary function studies, muscle enzymes, and
barium studies of the gastrointestinal tract are done to help
us define the extent of your disease.
If we can categorize
your illness accurately, we can provide you with a forecast
of what the future may bring, what monitoring is required,
and—just as important—we can tell you that many
of your worries may be misplaced.
Bad news always
seems to have more impact than good news, and bad things may
have happened to someone else with scleroderma, but don’t
think or assume this will be your fate.
Physicians’
Attitudes Toward Scleroderma Have Changed
Something else
of a general nature has gotten better in recent years, and
that is how most physicians themselves respond to a patient
with scleroderma.
As recently as
1987, in a rheumatology journal, a physician wrote, “most
physicians dread the prospect of caring for patients with
systemic sclerosis because of the multitude of difficulties
these patients present and the heretofore generally unsatisfactory
therapeutic armamentarium available.”
This was one of
medicine’s dirty little secrets. Doctors used to be terrified
by the diagnosis of scleroderma, and they conveyed this sense
of terror to their patients.
Happily, this is
rapidly changing. There is an enormous and growing interest
in the treatment of scleroderma—but no doubt, there are
many doctors yet unaware of how very treatable many of the
most troublesome aspects of scleroderma have now become.
There is also increasing
awareness that some features of scleroderma may improve over
time, even without treatment. This knowledge came from careful
long-term observation of individuals just like you.
Scleroderma
Can Get Better Over Time
Scleroderma was
once thought, and not so very long ago, to be a disease which
progressed relentlessly. The disease was called progressive
systemic sclerosis.
But then two observations
were made. First, it was noted that many individuals with
the CREST syndrome or the limited form of the systemic sclerosis
showed no evidence of disease progression over years or even
decades.
And as individuals
with diffuse disease were closely observed, we learned that
the disease doesn’t endlessly progress. Skin thickening
peaks after anywhere from two to five years, and then the
skin stabilizes and often thins. Sometimes, though sadly in
only the small minority, the skin thinning is so complete
that the disease appears to have disappeared entirely.
In 1986, Dr. Carol
Black, who directs a large scleroderma clinic in London, published
a paper entitled Regressive Systemic Sclerosis, a report of
four patients with diffuse scleroderma, each of whom initially
worsened over a course of two to four years. But then regression
occurred over a period of eight to 30 years, leading to resolution.
To mention only
one case: at age 30, four years after onset of disease, the
female patient had advanced fibrotic changes involving her
fingers, hands, arms, feet, legs, face, neck, and chest wall.
The knees were fixed in 90 degrees flexion, the fingers clawed,
the skin tight and shiny. She was unable to walk and largely
confined to bed and chair.
From this point
on, with no medication apart from analgesics, she slowly and
steadily improved. Twenty years later the skin thickening
had resolved, the fingers flexed and extended almost completely,
her knees could straighten, she could walk upstairs, and resumed
a normal life.
Such complete spontaneous
improvement remains the exception, not the rule. But in almost
everyone with diffuse disease, progression of skin thickening
does stop after a few years; and in the majority, detectable
though not complete skin thinning does occur.
A
Case from My Own Practice
Let me share a
similar story that occurred in the Capital District of New
York. In 1998, a 52-year-old woman, who had been in excellent
health, experienced the abrupt onset of numbness involving
the digits of each hand.
Over a period of
a few weeks she developed progressive swelling of her hands
and feet, diffuse muscle aches, intense itching, insomnia,
and profound fatigue. She developed pain and restricted motion
at her shoulders, hands, knees, and feet.
Six months after
onset of her illness, when I first saw her, she had diffuse
skin thickening (skin score of 25). She had to abandon her
job and needed help with many routine activities.
For a year, the
itching persisted and the extent and severity of skin thickening
worsened (peaking at a skin score of 44).
But then, with
no therapy other than a brief course of penicillamine, the
itching stopped and the skin started to thin. Now, four years
later, her skin thickening has nearly completely resolved,
and is confined to her fingers.
So the skin can
thin—and if the skin thins, then joints, muscles, and
tendons may also operate more easily.
How
Common is This Improvement?
Doctors Steen and
Medsger recently reviewed the enormous database of patients
seen at the University of Pittsburgh. They looked at data
on patients with early diffuse scleroderma who were reevaluated
two years later. Sixty-three percent showed an improvement
in their skin thickening of more than 25% of their peak score.
Spontaneous
Improvement Must Be Taken Into Account in Medication Studies
In the group with
improvement, most patients demonstrated continued improvement
over an additional five years of followup. Not only that,
but patients who showed skin improvement also did better over
all: they had less severe internal-organ involvement.
One surprising
finding in the Steen-Medsger study was that patients who had
a rapid increase in skin thickening were more likely to have
later skin improvement. Those with slower development of diffuse
skin thickening were less likely to improve.
So spontaneous
skin thinning can occur. This finding must be considered when
reading reports of uncontrolled series of patients treated
with methotrexate or minocycline.
[In other words,
patients in these studies may see improvement of their symptoms,
but this may not be due to the medication. The improvement
may be spontaneous, and the medication may have nothing to
do with it. —Editor’s note.]
In a recent controlled
study of high-dose versus low-dose penicillamine, both groups
improved. The mean (average) improvement in skin score was
30%. This study has generated continued controversy because
we don’t know if this was spontaneous improvement or,
as those who are penicillamine advocates would like to believe,
that both low- and high-dose penicillamine could be effective.
Why
Does Spontaneous Improvement Occur in Some Skin Areas and
Not Others?
The pattern of
improvement is not random. Skin thinning almost always begins
in areas that have been affected last—usually the upper
chest, abdomen, and upper arms. The areas first involved—the
fingers and hands—are the last and the least likely to
improve.
Why should this
be so? One answer is that the body has enzymes that can digest
collagen, but these enzymes work most effectively on collagen
that has been recently produced. Mature collagen is more resistant
to enzymatic digestion, because the collagen fibers form crosslinks
which weave them together more tightly.
In addition, recent
studies from Switzerland have shown that low tissue oxygen
tension may in itself be a trigger for activating fibroblasts,
the cells which produce collagen. In scleroderma, the fingers
suffer first from deficient blood supply and this poor digital
blood supply is a persistent problem. This may explain why
skin thickening usually starts on the fingers and persists
there, even as other skin areas improve.
How
White Cells, Mast Cells, and Fibroblasts Function in Scleroderma
In an individual
with early diffuse disease, a skin biopsy from an area of
newly thickened skin will usually show not just bundles of
extra collagen and diminished blood vessels, but also collections
of white cells. These white cells have been identified as
activated T-lymphocytes.
We now know that
these cells produce signals, which in turn activate fibroblasts
to over-produce collagen.
These white cells
are present only in the early inflammatory phase of scleroderma,
the phase when the hands are puffy, the joints most achy,
and the itching most severe.
Not just lymphocytes
infiltrate the skin, but also mast cells. These cells probably
account for much of the itching, due to their release of histamines.
In later disease,
the lymphocytes and mast cells disappear from the skin, and
the swelling subsides and the itching resolves or decreases.
Unfortunately,
the fibroblasts that were activated continue to over-produce
collagen. The signals that transformed them have a long-lasting
effect.
Therefore, if we
are to treat the skin effectively, we must either do so early,
when the process is more one of inflammation than of fibrosis,
or we must develop better ways of turning off fibroblasts
or accelerating the activity of enzymes which digest collagen.
We must do so in ways that don’t poison normal fibroblasts,
thin normal skin, or weaken all the internal structures in
which collagen is an integral part.
Part
2 of 2 |
