The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (18 page)

Scleroderma gets its name from two Greek words—
sklero
, meaning “hard,” and
derma,
meaning “skin.” However, it can affect not only the skin, but also other sites in the body, including the lungs, esophagus, and kidneys.

In scleroderma, the immune system attacks and damages cells that produce collagen, the substance that makes skin elastic and supports other connective tissues (joints, ligaments, and the capsules that surround internal organs). Collagen is a protein normally made in small amounts by specialized cells, called fibroblasts, and deposited on the outside of cells to support and heal tissues. It’s constantly being made and broken down. If you cut your finger, a clot forms and collagen is laid down along the injured area to fill in the gap and form a scar; scar formation is an essential part of the healing process. Eventually the collagen is broken down, and the scar may become smaller and skin becomes more normal in appearance. But in scleroderma, fibroblasts
start overproducing collagen where there’s no injury to be healed, laying down too much of it and replacing normal tissue.

Scleroderma can be localized, affecting only the collagen-producing cells in the skin, or it can be systemic, affecting collagen-making cells and small blood vessels in other areas of the body, interfering with normal function of organs and tissues.

For example, the esophagus and intestines are less able to contract to move food along because blood flow is reduced or collagen accumulation has affected nerves that control motility. In the lungs, lung cells can’t swap carbon dioxide for oxygen because scar tissue has formed over the thin membrane where this exchange takes place. Systemic scleroderma can be widespread (diffuse) or limited, affecting just a few areas.

The disease is relatively rare, and estimates vary as to how many people have it. According to the Scleroderma Foundation, as many as 300,000 may be affected, one-third with systemic disease.
¹
Around 80 percent of those with scleroderma are women.

The vascular component of scleroderma causes tiny blood vessels in the fingers and other areas of the body to become narrowed. In the kidneys, this can lead to high blood pressure. In the hands, diminished blood supply makes the fingers extremely sensitive to cold, causing
Raynaud’s phenomenon
, exaggerated, painful spasms of the blood vessels when exposed to cold accompanied by color changes (see
pages 131
and
139
).

Raynaud’s occurs in 95 percent of people with scleroderma and also appears alongside RA and lupus, and it can occur in otherwise healthy women.

It’s not known just what triggers the immune reaction that causes collagen production to run amok, says Maureen D. Mayes, MD, MPH, who heads the National Scleroderma Registry at the University of Texas Health Science Center in Houston. “In scleroderma, small blood vessels initially become ‘leaky,’ releasing immune substances that activate the skin to make too much collagen. What causes the blood vessel damage in the first place is still unknown.”

Also unknown: why some women develop localized scleroderma and others suffer systemic disease, sometimes without any visible signs on the skin.

The presence of specific antibodies may provide clues as to which women develop certain complications. “There are probably a host of genetic factors, and potentially toxins or environmental factors that trigger a reaction in
people who are genetically susceptible and prompt the appearance of certain antibodies, which are probably present long before there are any symptoms,” remarks Virginia D. Steen, MD, professor of medicine at Georgetown University in Washington, D.C., who has studied the disease for more than 40 years. “For example, we see certain antibodies in Caucasian women who develop pulmonary hypertension, and another antibody in African American women who develop pulmonary hypertension.”

There are other ethnic differences. African American women are more likely to develop the disease than Caucasian women, and they develop it at an earlier age, says Dr. Steen. “The average age at diagnosis is 40, but in African American women it tends to be earlier. Black women tend to have more diffuse disease and also have more skin pigment changes than Caucasians.”

A 2002 study from Johns Hopkins and the University of Maryland also found that black women have a 60 percent greater risk of dying from scleroderma than white women of the same age with the disease.

Genetics may play a limited role. While Dr. Mayes finds that scleroderma is twice as common in people with a family history, the absolute risk for each family member is actually less than 1 percent.

Some women experience joint pain and puffy hands as the first symptoms of scleroderma, but most often they develop extreme sensitivity to cold and Raynaud’s phenomenon (see
pages 139
to
140
).

Normally when we’re exposed to the cold, the body tries to slow the loss of heat and preserve normal core temperature by sending less blood to arteries near the surface of the skin and moving more blood deep within the body. To divert blood flow, the tiny blood vessels near the skin’s surface (
arterioles
) contract. Everyone has these spasms in blood vessels, causing the hands to feel cold and painful and appear blotchy red. But in Raynaud’s the reaction is intensified, and the color changes are more profound—and distinctive.

“A woman may notice her fingertips tingle and turn pale within a few minutes of cold exposure as blood vessels tighten and keep blood from entering her fingers. The fingers then turn a bluish color from the deoxygenated blood. Then, as the fingers warm up and blood vessels relax, they turn very
red as blood rushes in. This can be extremely painful with exposure to even slight cold, including an air-conditioned room or the freezer section of grocery stores. Women often put up with it for long periods of time,” remarks Dr. Mayes. “But some women may develop little pinpoint-type sores, also called
digital pits
, on their fingertips, because of decreased blood supply. If the decrease in blood supply is more severe, ulcers can develop on the fingertips. They can be quite painful and take weeks to heal. In some cases, the skin on the fingers has already started to become thickened. It’s usually at this point that a woman will see a doctor.”

It’s important to note that up to 5 percent of healthy women have Raynaud’s without any other disease (or
primary Raynaud’s
). The disorder is classified as
secondary Raynaud’s
when it occurs in people with autoimmune disease. Between 85 and 95 percent of women with scleroderma and mixed connective tissue disease, and a third of women with lupus, have secondary Raynaud’s.

In women with scleroderma, the inside of the blood vessel wall becomes
fibrotic
because of excess collagen deposits, and the thickening of skin in the surrounding area causes an increased demand for oxygen in the tissues. When cells lining the blood vessels are damaged, they produce a substance called
endothelin
, which acts as a potent vasoconstrictor, causing an increased tendency to spasm. Ulcers can occur as a complication of restricted blood flow (
ischemia
). In severe or prolonged cases, the tips of the fingers may become shorter, and the bone may even become damaged from lack of blood supply.

Raynaud’s may initially appear along with puffy hands, but it’s the skin thickening that’s the primary symptom of scleroderma. Skin thickening in the fingers is called
sclerodactyly
and usually starts from the middle joints out to the fingertips.

The thickened skin isn’t red or bumpy—it’s smooth and shiny with few wrinkles. The swelling and skin thickening can make the fingers feel stiff, because the joints don’t bend normally. The skin covering the finger joints can become so tight and inelastic that the fingers do not extend and are forced to bend inward (
joint contracture
). In severe cases, they may eventually become “frozen” in this position.

At the nail folds, the area where the nail meets the cuticle, the capillaries may be enlarged, show tiny hemorrhages, or may even be missing altogether.

Other skin problems include itching caused by inflammation; pigment changes (darker or lighter patches of skin); ulcerations due to poor
circulation, injury, or tearing of tight skin at joints and pressure points; and red spots caused by enlargement (
dilation
) of small blood vessels in the skin (
telangiectasias
), usually on the face and hands.

There may be hair loss in areas of thickened skin, due to both excess collagen around hair follicles and reduced blood supply (hair loss on the scalp can occur, but it’s more common in lupus). Later in the illness, tiny calcium deposits can form (
calcinosis
), which feel like firm bumps under the skin; these can become very painful and inflamed, and can become infected.

In the esophagus, the movements that normally push food into the stomach (
peristalsis
) are decreased because of scarring of nerve tissue and reduced blood flow, so you may have an uncomfortable sensation of food sticking in the throat or chest. The valve that’s supposed to keep acid in the stomach becomes weakened, allowing acid to back up or
reflux
, leading to chronic heartburn and
gastroesophageal reflux disease (GERD)
. Heartburn doesn’t just happen after meals but can occur at other times as well, especially when lying down at night.

This constellation of symptoms in limited systemic scleroderma has been called
CREST
—an acronym for
c
alcinosis,
R
aynaud’s,
e
sophageal problems,
s
clerodactyly, and
t
elangiectasias. However catchy the acronym, it was an imprecise term and is now used less often. Not every woman will have all of the external symptoms. Some may have internal involvement limited to the esophagus. Some may have limited cutaneous scleroderma with damage in the intestines and lungs.

Excess collagen deposits can also limit contractions of the bowel needed to move food and waste along. As a result, bacteria begin to overgrow in the small intestine, which interferes with the absorption of nutrients and fat, causing diarrhea and weight loss. When the large intestine is affected, it can cause constipation.

Most of the time, the earliest signs of systemic scleroderma may be dismissed as a minor complaint. “Many women say they had symptoms for two or three or even four years and sought help from a physician, but no clear diagnosis was made,” comments Dr. Mayes.

It’s a different story with diffuse scleroderma. Symptoms may come on suddenly and often do not include Raynaud’s. A woman may have swollen hands and feet, swollen and/or painful joints, extreme fatigue, or a sudden, severe rise in blood pressure (due to blood vessel spasm in the kidney, which
causes severe headaches, shortness of breath, a stroke, or even kidney failure). A woman may then have progression of thickened skin beyond the hand that spreads up over the arms, legs, and trunk over a short period.

Other organ involvement includes the small intestines and the lungs. In the lungs, excess collagen interferes with the normal exchange of carbon dioxide for oxygen across the thin membrane that separates the tiny capillaries and the air sacs (
alveoli
). It’s not clear what triggers the process, but activated immune cells and damaged blood vessels play a role. There’s also inflammation in the air sacs, called
alveolitis
, which leads to scarring (
pulmonary fibrosis
) and breathing problems.

Pulmonary fibrosis might also be linked to reflux; there’s some speculation that microscopic particles of stomach acid could be inhaled when a patient lies down during sleep. The primary symptoms of lung involvement are a chronic cough and shortness of breath.

In rare cases (about 5 percent of cases), women may have a condition called
scleroderma sine sclerosis
, or scleroderma without skin thickening. “She will have Raynaud’s phenomenon, but there’s often a long period of time between the onset of Raynaud’s and other problems, leading to a delay in diagnosis, because the most visible and characteristic sign, thickening of the skin, is not present,” says Dr. Mayes.

Occasionally, diffuse scleroderma can have a very rapid course, progressing quickly to affect the kidneys, lungs, heart, and other organs, and can even be fatal. Fortunately, this is uncommon. Most women with scleroderma have a relatively normal life span.

In localized scleroderma, patches of thickened, pigmented skin are called
morphea
. Localized skin thickening can also appear as a band or line down the face or an arm or leg (
linear scleroderma
), which may extend deep into the skin and muscle. Around 20 percent of women with localized scleroderma may develop joint pain (sometimes before skin changes appear, causing confusion with rheumatoid arthritis). Localized scleroderma may be self-limiting, with symptoms subsiding after a few years.

Karen’s story continues:

The third rheumatologist I saw took one look at my hands and said I had scleroderma. He said that some people don’t test positive for the antibodies for scleroderma, and to this day I don’t test positive. There were times this
disease really consumed me. I would lie on the couch far 14 to 16 hours a day. I had no energy at all; it was an effort to get up and walk to the bathroom. And I had been a pretty high-energy person, so this was very disturbing. I would sleep 10 or 11 hours a night and still wake up exhausted. Having a doctor to help me through it made all the difference. You need hope and good medical care.