Authors: Rita Baron-Faust,Jill Buyon
Unlike lupus, where there are assessment scales to track disease activity by the frequency of certain symptoms, in scleroderma there’s no gold standard to assess increased disease activity and severity to determine when more aggressive treatment is needed.
The Canadian Scleroderma Research Group, a consortium of rheumatologists, basic scientists, and patient representatives, has been working on a
scleroderma activity index for a number of years.
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Among its findings so far, elevated
C-reactive protein (CRP),
a marker of inflammation, may be correlated with disease activity, severity, poor pulmonary function, and shorter survival. CRP is elevated in one-quarter of systemic sclerosis patients, especially in early disease.
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The 51-point modified
Rodnan skin scoring system (mRSS)
for skin thickening is used to monitor disease progression. Higher scores (above 15) on the mRSS indicate more severe skin thickening.
Until a standardized global disease activity scale for scleroderma is developed, Dr. Mayes suggests that several red flags should prompt medical attention:
Karen’s story continues:
It affected me in so many ways. Your sexual life is affected, so you have to make adjustments there. I had always wanted to have kids, but the doctors had advised us not to get pregnant because they really didn’t know what the disease was going to do, and I didn’t want to take any chances. So we decided to adopt a child. Then I got pregnant. But three months into the pregnancy I went into a hypertensive crisis and was in the intensive care unit for 10 days. I almost lost my life and I lost the baby. But the adoption went through when all this was happening. And this child was really a lifeline. Even when I had to have dialysis, I had to shift my focus to taking care of this baby.
Eventually I got off dialysis, my energy came back, and we decided to adopt a second child, and my two girls are my joy. Still, it’s hard sometimes. When I look in the mirror, my face looks so different. This disease changes your whole self-concept. But I have learned to live with this disease; it’s part of my life. I focus on the positive aspects of my life, what’s important. My husband is an exceptional man, but there were times I thought he should bail out. But he said, “I don’t take a vow lightly, and this is not something I’m going to run from.” He has been my strength. I couldn’t have made it without him.
Scleroderma can not only affect a woman’s appearance, but treatments can also affect menstruation and fertility and influence the decision whether to become pregnant.
Scleroderma does not appear to flare premenstrually. However, women with scleroderma may have menstrual and ovulation irregularities, and some of the medications used to treat scleroderma, such as prednisone in very high doses, may also lead to irregular cycles and decreased fertility (but unlike cyclophosphamide, this decrease is temporary not permanent).
“If a woman has a lot of GI involvement and has lost a fair amount of weight, that will affect ovulation and menstrual cycles. A certain amount of body fat is needed to convert the hormones for starting menstruation. You see amenorrhea in women with anorexia because of low estrogen. In scleroderma, if you’ve had a fair amount of weight loss and you’ve lost a great deal of body fat, you may have the same situation,” remarks Dr. Mayes.
Birth control pills do not seem to affect scleroderma. In fact, studies suggest that women taking oral contraceptives may have less skin thickening.
Treatment with cyclophosphamide can cause sterility and trigger an early menopause. The chances of becoming infertile rise with increasing doses given for longer periods of time and with increasing age (even a woman at age 35 is at risk for sterility caused by cyclophosphamide).
Like Karen, almost half of women with scleroderma have their first symptoms before age 40, and childbearing is an important issue.
Early studies reported a high incidence of miscarriages, premature births, and smaller-than-average babies among women with scleroderma. But research led by Dr. Steen found that most women with scleroderma are no more likely than healthy women to suffer these complications of pregnancy.
“We did see a much higher percentage of preterm births in women with early diffuse disease,” remarks Dr. Steen. “Patients who have had diffuse disease for a long time had a significantly greater risk of miscarriage than the other groups.” The majority of patients had no change in their symptoms during pregnancy, but 34 percent experienced a worsening of Raynaud’s, arthritis, and skin thickening.
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“We encourage women to have an early consultation with their rheumatologist to assess the type and activity of their disease. We discourage women with early diffuse disease from becoming pregnant during that period, because of the risk of kidney problems,” says Dr. Steen.
Dr. Mayes advises women newly diagnosed with scleroderma to wait two to three years to see how their illness develops; limited scleroderma may be less risky for a pregnancy than diffuse disease (although there’s some increase in prematurity). The disease must be stable (with no signs of hypertension or
lung problems) because most medications must be stopped before a woman tries to conceive.
While many women with scleroderma have uneventful pregnancies, they should be under the care of an obstetrician who specializes in high-risk pregnancies because of the risk of premature birth. Blood pressure must be carefully monitored. High blood pressure,
preeclampsia
(severe high blood pressure with protein leakage from the kidneys,
proteinuria
), and even more serious kidney damage have been reported more often in women with scleroderma.
Preeclampsia may arise in scleroderma because of thickening and narrowing of blood vessels in the placenta, which hampers delivery of oxygen and nutrients to the fetus and the removal of wastes. If untreated, it can progress to eclampsia (seizures), which can result in maternal death. Preeclampsia develops most often in the third trimester. If blood pressure cannot be managed, the baby may have to be delivered early. If untreated, it can progress to eclampsia, which can cause seizures and death. ACE inhibitors are not given during pregnancy unless other medications fail to control high blood pressure. If a woman develops preeclampsia and her blood pressure doesn’t respond to medication, cesarean delivery is required.
The most common symptoms of pregnancy—morning sickness in the early months, and heartburn as the pregnancy progresses—are more pronounced in women with scleroderma.
Menopause is still largely uncharted territory in scleroderma, and its effects on the disease itself are unclear.
Menopause in all women is associated with some skin thinning and collagen loss due to low estrogen. Studies find a 1 to 2 percent decline in collagen per year after menopause. One recent study suggests that menopause has a substantial effect on skin thickening in diffuse systemic sclerosis, with postmenopausal women having a lower mean
mRSS
compared to premenopausal women.
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Canadian researchers find that estrogen supplementation in postmenopausal women may increase skin scores by increasing collagen content in the skin.
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“I have no problem prescribing hormones for women who are
experiencing hot flashes, because my data does not suggest there’s a problem with taking hormones,” comments Dr. Steen.
The atrophy of vaginal tissues that occurs as estrogen levels drop in menopause can also occur independently in women with scleroderma and Sjögren’s syndrome (see
page 148
). “Perhaps 10 percent of women with scleroderma have true autoimmune Sjögren’s syndrome. Probably 30 to 40 percent of women with scleroderma have overlapping symptoms with Sjögren’s, but when their parotid glands are examined, they are fibrotic,” says Dr. Steen. Anti-Ro and La antibodies point toward Sjögren’s syndrome.
In both cases, vaginal tissues may feel dry; there may be itching, burning, and irritation as well as painful sex. If the problem is due to menopause, oral estrogen therapy or estrogen cream can help relieve vaginal dryness. (If you have an intact uterus you need to take progestin to protect against endometrial hyperplasia.) Vaginal dryness can also be relieved by special moisturizers. (See
pages 191
to
192
.)
Systemic estrogen does carry the risk of blood clots, is not advisable for women with vascular or clotting problems, and is not recommended for the secondary prevention of heart disease. So a woman needs to discuss the pros and cons with her physician. One study did suggest a slightly increased risk of Raynaud’s among women taking estrogen therapy.
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“In general, we have not seen an increased risk of osteoporosis in scleroderma patients as there is with rheumatoid arthritis,” adds Dr. Steen.
In any chronic illness, there’s a higher risk of depression. This can affect sexuality, as can a negative body image from the changes caused by scleroderma. The fatigue of scleroderma can interfere with having an active sex life, and uncomfortable vaginal dryness can cause some women to avoid sex altogether.
However, a 2009 study of 101 women with scleroderma found that 60 percent remained sexually active despite their disease. And the main causes of inactivity could be helped, the researchers say.
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The most common symptoms reported by the group that influenced sexual function were fatigue (60 percent), vaginal dryness (42 percent), body pain (40 percent), depression, and vaginal discomfort (38.3 percent). Among those women who reported decreased sexual function, the problems of vaginal
dryness, vaginal discomfort, Raynaud’s phenomenon, and depression were more common; more than 28 percent of the women reported depression.
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If you’re suffering depression along with sexual problems, a combination of counseling and medication can help.
The hands can be severely affected early in scleroderma. Skin thickening and contracture can cause loss of flexibility in the fingers, loss of wrist motion, and a decline in fine motor skills, such as writing. Women, particularly those with diffuse scleroderma, need to do range-of-motion exercises to help slow or avoid loss of motion. Such exercises include stretching the tiny joints of the fingers by using the palm of one hand to press down the back of the finger joints of the other hand, flexing and extending the wrist, and doing rotations, two to three times a day. Women are often sent to an occupational therapist to help with exercising.
“There are also some individuals who will have a true arthritis with joint inflammation that contributes to the hand and wrist decreased range of motion in scleroderma,” says Dr. Mayes. “It’s sometimes difficult to figure whether the pain and swelling in the hand are due to the general puffiness that goes along with scleroderma, or to true arthritis joint inflammation that’s making the joint swollen. Ultrasound examination of the joints of the hands and wrists can be very helpful in identifying true joint inflammation from the soft tissue swelling from leaky blood vessels.”
The arthritis that can occur in scleroderma is treated with the same anti-inflammatories and arthritis drugs used to treat RA, like methotrexate. There may be a potential for gastric bleeding with some pain medications, so the
COX-2 inhibitor celecoxib (Celebrex)
may prescribed.
Psoriasis
is a chronic, inflammatory skin disease diagnosed in 150,000 people each year. According to the National Institutes of Health, as many as 7.5 million Americans in every racial group are affected (2.6 percent of Caucasians), and it is slightly more common in women than men.
In some patients, a form of arthritis—psoriatic arthritis—can develop over a period of years. Both can also occur with other autoimmune diseases (such as Crohn’s disease). For this reason, we’ve decided to include both diseases in this book.
Psoriasis is frequently diagnosed in a woman’s late twenties to midthirties, but it can develop at any time, from childhood to old age. In some cases, skin injury, infections, stress, and certain drugs may trigger psoriasis.
Heredity may also play a role. One out of three women with psoriasis has a family history of the disease, says noted psoriasis researcher Mark Lebwohl, MD, professor and chairman of the department of dermatology at the Mount Sinai School of Medicine in New York City. “If one parent has it, the likelihood a woman may also develop psoriasis is around 10 percent. If both parents have it, there’s a 30 to 50 percent risk,” he says. “Different genes may cause psoriasis. What we call psoriasis probably can be thought of as a group of very closely related disorders. But the genetic abnormalities lead to the same pathway. That’s why there are different patterns, and why some treatments work for some people and not others.”
No one knows exactly what causes psoriasis; specific autoantibodies have yet to be identified.
“What we can say is that psoriasis is a disorder of the immune system in which T lymphocytes are activated in response to some yet to be identified antigen, and then cytokines cause skin cells to multiply too quickly and cause inflammation,” explains Dr. Lebwohl. A normal skin cell matures around every 28 days and is then shed from the skin’s surface. “In psoriasis, skin cells can turn over every two to four days.”
Some studies show stress may play a role in the onset and exacerbation of psoriasis and, for some people, living with a chronic skin condition can lead to depression and anxiety.
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As many as 30 percent of women with psoriasis (usually moderate or severe) will develop
psoriatic arthritis
. Like RA, psoriatic arthritis (PsA) causes inflammation and stiffness in the soft tissue around joints, often involving the fingers and toes, as well as the wrists, neck, lower back, knees, and ankles. In severe cases, psoriatic arthritis can cause joint destruction and disability. PsA may develop as long as 10 years after a diagnosis of psoriasis. It can come on slowly or quickly, with more severe symptoms.
Psoriatic arthritis is classified as a
spondyloarthritis
(
spondyloarthritides
), a family of inflammatory arthritic diseases that usually involve the spine, the
sacroiliac
joints in the pelvis, and areas where ligaments and tendons attach to bone (
entheses
).
Psoriatic arthritis is characterized by swelling, tenderness, and inflammation in areas where ligaments attache to bone (
enthesitis
) like your Achilles tendon, often with a gradual onset of pain that improves with activity and gets worse with rest. “Inflammatory arthritis that affects the spine is called
spondylitis
, which occurs in PsA,” he explains. “So one of the things we look for is inflammatory back pain, characterized by pain that improves with activity and gets worse with rest, lasting longer than three months,” he explains. There can also be
sacroiliitis
, inflammation of the sacroiliac joints (located on either side of your tailbone) seen best on MRI.
There are several forms of psoriasis. The most common,
plaque psoriasis
, is characterized by red, inflamed patches of skin topped by a layer of silvery white scales.
Other forms of psoriasis include:
Plaques can be limited to a few patches on the elbows or knees, or they may involve more extensive areas of the skin, including the scalp, nails, palms, soles, torso, genital area, and, in rare cases, the face. Plaques may be symmetrical, in the same place on the right and left sides of the body.
For many people, the disease tends to be mild, but in some cases it can be disabling and even deadly. “In the more severe forms of psoriasis, the erythrodermic and the pustular forms, some patients will literally be covered by lesions overnight. Generalized erythrodermic and pustular psoriasis can be life threatening because they can affect 90 to 100 percent of the body surface, and people lose the protective functions of the skin,” says Dr. Lebwohl.
The skin is actually an organ that serves as the body’s first defense against infection and helps regulate body temperature. But when large areas of skin are affected in severe psoriasis, these functions are lost. “People lose protein and nutrients through the skin. They lose fluid, so their blood pressure can fall. They lose heat, so they can have low body temperature or develop fevers. In rare cases, a bacterial infection can cause death,” says Dr. Lebwohl. According to the National Psoriasis Foundation (NPF), as many as 400 people die of complications related to psoriasis each year.
Because each form of psoriasis has a characteristic appearance, a physical examination by a dermatologist is needed to make a diagnosis. However, the first signs of psoriasis may not cause concern, allowing plaques to become more extensive. “Some people with mild psoriasis will treat scaly patches with moisturizers and never mention it to their physician,” remarks Dr. Lebwohl. “There’s no marker of who’s likely to get psoriasis. Women with Crohn’s disease may be unaware of the increased risk, and psoriasis plaques may not be noticed by a gastroenterologist.”
Psoriatic arthritis can develop years before or after psoriasis. If you have joint pain and psoriasis you need to be evaluated by a rheumatologist.