Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (5 page)
While immune attacks may produce similar symptoms early on, they don’t always point to a particular disease. Early symptoms can be vague and transitory; illnesses often overlap and mimic each other. For instance, fatigue and joint pain can be symptoms of rheumatoid arthritis, lupus, and thyroid disease.
When doctors talk about diagnosis, they use the terms
signs
and
symptoms
. What’s the difference? Signs are things that can be
seen
during a physical exam, in blood tests, and on x-rays. Symptoms are what you
experience
, which can be very individual.
Sometimes there’s a gap in time between your symptoms and the clinical signs of disease that doctors look for to help make a specific diagnosis. The day you see your doctor your joints may not look swollen and red if you have early rheumatoid arthritis. This may account for a time lag between the actual onset of a disease and a formal diagnosis. And that time lag can be considerable. The signs of autoimmune disease may be misdiagnosed and treated as another condition, such as depression and fatigue in MS or lupus. Or, in women like Cate, fatigue and pain may be mistaken for worsening symptoms of rheumatoid arthritis when they’re actually due to fibromyalgia, a nonautoimmune disorder that often occurs with autoimmune diseases.
Virtually every woman with an autoimmune disease experiences fatigue that can be so debilitating it affects every aspect of life, according to a 2015 online survey by AARDA and the National Coalition of Autoimmune Patient Groups.
Many women suffer infertility, miscarriages, and pregnancy complications because of autoimmune-related problems, even if they don’t have a diagnosable disease. For example, autoantibodies that lead to blood clots in the placenta may cause second-trimester pregnancy loss. These same autoantibodies, called
antiphospholipid antibodies
, are found in women who have lupus or antiphospholipid syndrome, as well as other autoimmune diseases.
Tests for autoantibodies such as
rheumatoid factor (RF)
or
anti-cyclic citrullinated peptides (anti-CCPs)
can help your doctor in making a diagnosis. For instance, a positive test for rheumatoid factor can be one indication of rheumatoid arthritis (and also of Sjögren’s syndrome). It usually takes a combination of blood test results, an assessment of clinical signs and symptoms, and sometimes diagnostic imaging to make a definite diagnosis.
These autoantibodies and inflammatory cytokines may be present long before you start having symptoms and may signal a
preclinical
stage of a disease. An exciting area of research involves ways to figure out which marker (or group of markers) may help predict which women will eventually develop disease and tell them apart from women whose level of biomarkers is benign. The hope is to one day be able to prevent autoimmune disease even before it begins.
As you read each chapter of this book, you’ll learn more about the kinds of tests you need to obtain a correct diagnosis and what the results mean. We’ll also detail the diagnostic criteria doctors use.
If you’re suffering from seemingly vague and unrelated symptoms, we’ll help you sort them out and tell you where to go for help. A survey by the Sjögren’s Syndrome Foundation (SSF) found that as many as three out of four women under age 35 may suffer at least two potential symptoms of Sjögren’s, including dry eyes or dry mouth, yet never tell their doctor, or simply hope the problems will go away. The more quickly you act, the better your chances for a successful treatment.
This book is designed to give you the tools you need to manage your own diagnosis. But, again, be aware that having one autoimmune disease puts you at risk for others that cluster with it. So you need to be alert for other symptoms that can crop up.
We’ll also tell you how autoimmune diseases—and their treatments—can affect you during different stages of your life. Some autoimmune diseases, like antiphospholipid syndrome, can make it hard to sustain a pregnancy. A frequent treatment for autoimmune disease, corticosteroid drugs, may put you at risk for osteoporosis or high cholesterol, especially if you’re older. Corticosteroid drugs can also produce psychological symptoms such as depression and explosions of anger that can be extremely upsetting if you’re not aware that they can occur. They also increase appetite, which can contribute to excessive weight gain.
Throughout this book, you’ll learn about the latest scientific and medical research, including research into genetics, environmental and viral triggers,
possible ways of altering immune responses, and potential new therapies such as stem cell transplants and gene therapy. We’ve called on the expertise of immunologists, rheumatologists, endocrinologists, neurologists, hematologists, and gastroenterologists from institutions leading the way in investigating these diseases. Autoimmunity continues to be a rapidly evolving field, but we’ve tried to include the latest information available. Each chapter will feature sections on early signs and symptoms, provide answers to commonly asked questions about fertility and pregnancy management, and detail special considerations for midlife, menopause, and later life.
In this book, you’ll find advice on getting the latest treatments and finding an appropriate specialist in the landscape of the U.S. healthcare system laid out by the Affordable Care Act (ACA) of 2010. In the back of this book you’ll find an extensive list of resources, support groups, and information on the Internet. We’ve also included selected current references for each chapter.
This continues to be an exciting era for autoimmune research. New treatments are emerging that may make these diseases easier to manage and maybe even stop them in their tracks. Basic science is informing clinical decision making every day. Armed with knowledge, you can take charge of your healthcare as understanding of autoimmune diseases continues to evolve.
1
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2
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Front Immunol.
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3
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. 2012;18:42–47.
4
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5
. Campbell AW. Autoimmunity and the gut.
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6
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BMJ
. 2011;342:d35.
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. Scher JU, Abramson SJ. Periodontal disease,
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, and rheumatoid arthritis: what triggers autoimmunity and clinical disease?
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8
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J Immunol.
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9
. Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease.
Front Neuroendocrinol
. 2014;35:347–369.
10
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. 2009;11(5):252–261. doi:10.1186/ar2825.
11
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. 2012;14:R41. doi:10.1186/ar3749.
12
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. 2008;205:1099–1108. doi:10.1084/jem.20070850.
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. Am J Reprod Immunol.
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Trends Immunol
. 2012;33(8):421–427.
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Those Aching Joints—Rheumatoid Arthritis
I was doing a film, Serial Mom (in 1997), and my feet started to swell terribly; all of the shoes that we had bought for the character suddenly seemed painfully small. I thought I must be retaining water or something, even though retaining water didn’t explain the pain. And it hurt terribly. It hurt to put my feet in the shoes, it hurt to put anything on my feet. I would rip the bottoms of the covers off the bed because I couldn’t stand to have the weight of the blanket on my feet. When I finished the film and came home, I found that I couldn’t get into my own shoes. Even sneakers; I had to take the laces out. So I went to the head of podiatry at one of the major New York hospitals and he took x-rays, felt my feet, and told me I needed bigger shoes. He wasn’t very helpful.
Then it went to my neck; I couldn’t turn my head. So I went and had an x-ray of my neck, and the doctors told me that I had lost the curvature of the first four vertebrae, and they had no idea why and there was nothing they could do. Then I couldn’t open my left arm; it was locked in position. So I went to a hotshot doctor, a sports medicine specialist who treats some New York teams, supposed to be the best in the city. He took an MRI as well as an x-ray and couldn’t see anything. He said perhaps we should do exploratory surgery. It was at this point that I got really freaked out. And by then I was feeling so ill, so tired, and so sick—like having the flu all the time. This was over the space of eight or nine months. Back then I wasn’t that aggressive about my own health; I had never had anything seriously wrong with me. But I was frightened.
I didn’t know what was happening to me.
I finally went to my GP, who I’ve been seeing for years and years, and I said, “I think I’m dying and I’m terrified. You’ve got to help me.” He was the first doctor to take blood to be tested. And he called me up the next day and said to get over to his office right away. My rheumatoid factor was sky-high; he didn’t know how I was walking at all. I had access to the best doctors in New York, and he was the one who found the RA. But I was lucky—it only took me a year to get diagnosed. Many women I know take three to five times as long to find out what’s wrong with them.
K
ATHLEEN
T
URNER
(
DIAGNOSED AT AGE
42)
U
nlike the charismatic actress Kathleen Turner, rheumatoid arthritis (RA) may not have much stage presence in the beginning. It may come on so gradually that you can’t even remember when the aching and stiffness in your joints began. Or it may announce itself loudly, with a sudden outburst of swelling and joint pain. But the character of RA is revealed in its symmetry—the immune system attack on the joint lining usually affects the same joints on both sides of the body.
The Arthritis Foundation (AF) estimates that rheumatoid arthritis affects some 1.5 million Americans, almost three times more women than men. RA usually strikes in the prime of life but can also affect children (as juvenile RA) and the elderly.
Arthritis is derived from the Greek word
arthron
, meaning “joint,” and the suffix
itis
, meaning “inflammation.” But inflammation itself doesn’t start out to be destructive; it is actually the body’s defense mechanism. When there’s an injury or invasion, the immune system sends specialized white blood cells to the area to destroy anything foreign and repair damage. For example, when you get a cut, the immune system dispatches a repair crew of white blood cells to the scene to destroy harmful bacteria and heal the damaged tissue. The work done by the repair cells initially makes things red and swollen—inflamed. When the repairs are done, the area heals and the redness and inflammation go away. But if an attack becomes constant, the inflammation doesn’t cease. And it eventually becomes chronic and destructive.
A joint (the place where two bones meet) is surrounded by a protective capsule. The ends of the bones are covered by a layer of rubbery material
called
cartilage
, which acts as a shock absorber and enables the bones to move against each other smoothly (cartilage breaks down from wear and tear in another common form of arthritis,
osteoarthritis
). The joint capsule is lined with a thin layer of tissue called the
synovial membrane
, which produces a clear fluid that lubricates the joint. The synovium also acts as a filter to bring nutritional materials from the blood into the joint and the cartilage, which does not have a blood supply. So the synovium is very important for maintaining function of the joint.
In rheumatoid arthritis, immune cells for reasons still unknown mistakenly attack the synovium, setting off a destructive cascade of events. As white blood cells pour into the synovium, extra fluid is produced and antibodies and inflammatory molecules (
cytokines
) inflame the joint lining. Eventually, this synovitis results in the warmth, redness, swelling, and pain that are the classic symptoms of rheumatoid arthritis.
As the inflammation continues to percolate, synovial cells start to grow and divide abnormally, thickening a membrane that was once just three or four cells thick. As RA progresses, new blood vessels form to feed the growing mass of abnormal synovial cells and immune cells, which form a sheet (
pannus
) that
spreads over the cartilage in the joint. This tissue begins to eat into the cartilage and also erodes and destroys the bone adjacent to the cartilage. This weakens the muscles, ligaments, and tendons that help support and stabilize the joint. When the support system is damaged, it can lead to pain, stiffness, and deformity.
How RA Affects Joints
This damage can begin during the first year or two of the disease, long before symptoms start to appear, and by the time RA is diagnosed the disease may have already become destructive. That’s one reason that early diagnosis and treatment are so critical.
In women, RA often starts in the fingers of both hands and progresses to the wrist joints and beyond, or it can begin in the feet (as in Kathleen Turner’s case). The disease can affect any joint in the body, including those in the spine. Once it’s set off, the inflammatory process takes on a life of its own and can reach beyond the joints. Inflammatory cytokines can cause reduced levels of erythropoietin, a hormone that stimulates the bone marrow to make red blood cells; if fewer red blood cells are produced, the result is anemia. Antibodies and inflammation in the eyes, mucous membranes, and salivary glands frequently cause dry eyes and mouth (
Sjögren’s syndrome
). Inflammation may also affect the blood vessels (
vasculitis
) as well as the lining of the lungs (
pleuritis
) and the sac around the heart (
pericarditis
).
The inflammatory process of RA differs from woman to woman. In some, acute inflammation lasts only a few months or a year or two, then subsides without appreciable damage. Others have mild disease that periodically worsens (or flares) and then improves. And in others the disease can be aggressive and permanently deform joints so that they no longer function.
For many women, RA improves during pregnancy and worsens in the postpartum period (initially leading many scientists to believe female hormones and/or glucocorticoids play a protective role in the disease since hormones such as estrogen and progesterone increase dramatically during pregnancy but fall postpartum). RA can become chronic and severe, causing serious joint damage and disability. But in recent years new drugs have been developed to block specific inflammatory molecules, slowing or even stopping the damage caused by rheumatoid arthritis.
RA appears to be caused by a combination of genetic vulnerability, environmental triggers (possibly infections), hormonal influences, and perhaps joint injury.
A number of genes are associated with RA, and they’re found in healthy people and in women with other autoimmune diseases. The genes encode human leukocyte antigens (HLAs), which are proteins that contain instructions for the cell to be labeled self or nonself. Women with rheumatoid arthritis may have the genes encoding the particular HLA
allele
(form of the gene) DR4, which may cause healthy tissues to be labeled as foreign. Different versions of the HLA-DR4 genes are associated with an increased risk of rheumatoid arthritis (and other autoimmune diseases that cluster with it, such as thyroid disease). “DR4 also predisposes to developing more severe disease. We don’t quite understand why and how that occurs, but if you acquire rheumatoid arthritis, and you have this DR4 molecule, you may develop more severe disease,” explains William P. Arend, MD, Distinguished Professor Emeritus/Division of Rheumatology at the University of Colorado, Denver School of Medicine. Other genes linked to RA regulate the inflammatory cytokines like
tumor necrosis factor (TNF)
and
interleukin-1 (IL-1)
, leading to overproduction of these molecules, he adds.
But genes alone don’t tell the story; some women with rheumatoid arthritis have no known RA-linked genes, while some who have these genes never develop RA. Even among identical twins (who share identical genes), if one twin has rheumatoid arthritis the other doesn’t automatically develop it; the
concordance
(mutual occurrence) rate among identical twins is only about 12 to 15 percent.
Genetically vulnerable people need to encounter other factors, a combination of several “hits” required to set a disease in motion, says Dr. Arend. Those “hits” could include viral or bacterial infections, such as Epstein-Barr virus (EBV), which causes infectious mononucleosis, or
Chlamydia trachomatis (C. trachomatis)
, the most common sexually transmitted infection in the United States. A 2013 study found evidence of a past chlamydial infection in the joints of almost a third of people with reactive arthritis.
1
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS),
reactive arthritis
is an autoimmune joint inflammation caused by an infection in other areas of the body (including urinary tract infections). It may occur more often in people carrying a specific gene (HLA-B27). Symptoms of pain and joint swelling may appear two to four weeks after an infection and may last only a few weeks or months. However, reactive arthritis may return in a more serious form.
An estimated 2.86 million cases of
C. trachomatis
are reported annually. The study found that dual antibiotic treatment not only eliminated the bacterium from joints but also improved arthritis.
1
Food-borne gastrointestinal infections can also trigger reactive arthritis, including
Salmonella
,
Shigella
,
Yersinia
, and
Campylobacter
, caused by eating contaminated food, such as meats or cold cuts that are not refrigerated properly.
Other suspect bacteria include
Escherichia coli (E. coli)
, responsible for urinary tract infections;
Helicobacter pylori
, which causes gastrointestinal ulcers; and
Borrelia burgdorferi
, the corkscrew-shaped bacterium carried by ticks that causes Lyme disease. Lyme disease triggers inflammation around the body with joint pain and can cause an arthritis similar to RA (it’s often misdiagnosed as rheumatoid arthritis).
New research suggests that even the normal bacteria that live in our digestive system may provoke an autoimmune reaction that leads to RA.
2
As we mentioned in
Chapter 1
, the structure of a virus or bacteria (or proteins they carry) and the structure of some cells and proteins in the body may appear similar, and immune cells react to both, a case of “molecular mimicry.” Studies show that T cells from the joints of patients with RA react to proteins on the Epstein-Barr virus.
While recent population studies have also turned up links between RA and some environmental toxins, such as pesticides, your biggest risk may come from tobacco smoke.
Smoking is an established risk factor for RA, and your risk rises each year with every cigarette smoked—even if you’re only an “occasional” smoker.
3
Compared to never smoking, the risk of RA more than doubles with long-term heavy smoking.
4
Not only does tobacco smoke contain toxins such as nicotine, hydrocarbons, and carbon monoxide that may themselves trigger an immune attack, but exposure to these toxins may compound your genetic risk.
In recent years, researchers have come to label some foods as “inflammatory” and suggest that some may
increase
the risk of RA, among them, coffee. Is coffee a
real
risk? It’s worth examining because the issue keeps percolating in the popular media.
The debate was first stirred up in 2000, when Swedish researchers reported that people who drank four or more cups of coffee a day were more likely to have rheumatoid factor (a marker for RA) in their blood and an increased risk of rheumatoid arthritis.
5
In contrast, an update from the Iowa Women’s Health Study in 2002 found that those who drank four or more cups of
decaffeinated
coffee a day were more than twice as likely to develop RA as women who drank regular coffee.
6
Adding to the controversy: among the 31,336 women in the study, those ages 55 to 69 who drank three or more cups of
tea
each day had a 60 percent
reduction
in their risk of RA. Researchers from Harvard reported the next year that they found
no
association between coffee (decaf or regular) or tea and RA risk.
7
These were all population studies, which cannot prove cause and effect. So there’s simply no
definitive
evidence. The Arthritis Foundation does
not
tell people to avoid coffee, just to consume it in moderation.
8
On the other hand, some foods may help dampen inflammation and improve RA. Notably, the omega-3 fatty acids, found in cold-water fish such as salmon, mackerel, and sardines, have been shown to relieve symptoms of RA (see
page 45
). In general, experts recommend an overall healthy and balanced diet.
Being overweight or obese may also increase the risk of RA, especially in younger women, according to a study of more than 200,000 American women.
9
Previous studies have also suggested that overweight and obese people with RA may experience higher disease activity and pain, and may even respond less well to medications.
Then there’s the question of hormones. The fact that rheumatoid arthritis improves in many women during pregnancy (when estrogen levels are very high) and worsens after delivery (when estrogen levels drop) has led some
researchers to believe there’s a hormonal factor in RA. As we’ve mentioned, estrogen can influence the activity of immune cells in a number of ways. However, the peak onset of rheumatoid arthritis is between ages 40 and 60, when estrogen levels are declining. So it’s still unclear what role estrogen may actually play.
Kathleen’s story continues:
I was about two years into the RA, and I kept on working despite the pain.
I had no choice. If I didn’t keep working my career would be over. I was offered a play,
Indiscretions,
and I thought I’d be able to do it because the character was a diabetic, and the first and the third acts took place in her bedroom . . . I figured I’d be lying around a lot. It didn’t turn out that way.In the second act of the play, there was a three-story spiral staircase that went up to a catwalk. . . . We would sit up there until we heard the cues and start back down. By the time I got up to the catwalk I was sobbing every night—the pain was so terrible. So I kept tissues, powder, and a lipstick and a mirror up there so I could fix my face before I went back down. I only missed a few performances in the run. I didn’t make my disease public at the time . . . because we didn’t know at this point how much I was going to recover and if I was going to recover. And people don’t understand rheumatoid arthritis. I was put on a whole cocktail of drugs, and that was almost worse than the RA. I was on Plaquenil, I was on gold salts, I was on methotrexate, I was on prednisone, large doses of prednisone. It blew up my body, blew up my face. And the press had a field day—they decided that I had a drinking problem because I was so puffy. And I didn’t even care if people thought I had an alcohol problem. I mean, they hire drunks, they hire repeat drug offenders every day in this business. But I knew they wouldn’t hire me if they knew I had this disease.
