Scleroderma: What Gets Better, and Why (Part 1 of 2 Parts)

By Lee Shapiro, M.D., FACP, The Center for Rheumatology, LLP, Albany, New York (originally published in "Scleroderma Voice," 2002 Issue #4)

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