Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (34 page)
About 5 percent of people with UC develop colorectal cancer, and the risk increases the longer you have UC and with the extent and location of the disease. For example, if the entire colon is involved, your risk of cancer may
be as high as 32 times the norm; if UC involves only the lower colon and rectum, your risks are not higher than normal.
Ulcerative colitis can lead to precancerous changes called dysplasia in the cells lining the colon. Signs of dysplasia can be picked up during colonoscopy and biopsy.
Guidelines for colon cancer screening (endorsed by the American Cancer Society, the American College of Gastroenterology, the American Society of Colon and Rectal Surgeons, and the Crohn’s & Colitis Foundation of America) advise that people who have had IBD throughout their colon for at least eight years, and those who have had IBD in only the left colon for at least 15 years, should have a colonoscopy every one to two years to check for dysplasia. Recent studies show that colonoscopy is the most effective way of finding colon cancer in its earliest, most curable stage.
As with Crohn’s disease, ulcerative colitis can affect women during their reproductive years.
Fertility among women with ulcerative colitis seems to be unaffected by the disease itself. However, women who undergo removal of their colon may have trouble conceiving after the surgery. A study from Denmark compared fertility rates of women with UC to women without the condition. Those women who had not undergone colectomy had an equal or higher fertility rate compared with women without ulcerative colitis. Those women who underwent colectomy had a significantly lower fertility rate and an increased use of in vitro fertilization.
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Another study found that women who had anal ileal pouch anastomosis had three times the risk of infertility after the procedure.
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Around a third of women with active ulcerative colitis who become pregnant will improve, and a third will worsen, notes the Mayo Clinic’s
Dr. Sunanda Kane. UC can also occur during pregnancy and the postpartum period. However, sulfasalazine is safe to use during pregnancy, and the 5-ASA agents also appear safe.
Osteoporosis is a major concern for women taking corticosteroids, especially later in life. Corticosteroids tend to complicate and worsen diabetes, high blood pressure, and other age-related diseases. Women with UC may need antiresorptive agents called bisphosphonates, such as
alendronate (Fosamax)
or
risedronate (Actonel)
to stem bone loss. (For more on these drugs, see
page 58
.)
One form of colon inflammation, called
ischemic colitis
, can occur in later life and is caused by poor circulation and can mimic the symptoms of IBD. One study found that 75 percent of people with colitis after the age of 50 actually had ischemic colitis, and neither form of IBD. Older women may also develop an antibiotic-associated colitis.
I was diagnosed with celiac disease as a child. Apparently it runs in my family. My grandmother later told me one of her sisters died of diarrhea and dehydration as a baby; they thought it was colic. But I thought it was something you outgrew. . . . I found out by accident that you don’t really outgrow it. I never had a digestive system that worked properly, from what I can tell. Once every few weeks, I’d have what they called a “stomach virus.” I thought I was just susceptible to that. No matter how much I ate, I felt full. If I didn’t eat, I’d drop five pounds. If I looked at my stool, I’d see whole pieces of undigested food, and globs of fat. I’d think, “I’m not digesting my food.”
I didn’t know anything about celiac. Except they made you live on nothing when you were a kid, then they thought you outgrew it and you were fine. I made an appointment with an internist and told him I don’t know that much about celiac disease, but maybe there’s a relationship between that and what’s going on with my digestive system. I said, “I think you need to do a stool analysis because I’m not digesting my food.” And he said no. Celiac disease has nothing to do with it. This was in 1975 when this happened. I was 18 or 19. I thought I was being completely logical. But he dismissed it.
He gave me a blood test of some kind, which showed nothing. So I figured celiac had nothing to do with it, and I gave up. I didn’t pursue it until much later on.R
ONNIE
, 45
Celiac disease is an autoimmune disease that damages the small intestine and interferes with absorption of nutrients. In celiac disease, the immune system mounts an inflammatory reaction against
gluten
, a protein found in wheat (similar proteins are found in rye and barley), in the process destroying the numerous tiny
villi
in the lining of the small intestine and establishing a state of chronic inflammation in the intestine.
You’ll recall that villi absorb nutrients from food; without villi you become malnourished, no matter how much you eat. Celiac disease can affect the entire small intestine or localized areas, such as where iron and calcium are absorbed. So most people with celiac have iron-deficiency anemia and bone loss. The disease also destroys cells in the intestinal lining containing the receptors for vitamins A, D, E, K, and B
12
. Vitamin B
12
deficiency results in another form of anemia, macrocytic anemia (in which abnormally enlarged red blood cells crowd out normal cells).
Celiac disease runs in families, and genes play a role. It was once thought to be relatively rare in this country compared to Ireland and Italy, but recent research indicates it is much more common, affecting as many as one percent of people in Western countries, and is on the rise in Asia, where wheat products are replacing rice as a dietary staple.
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In the United States there is a very low rate of diagnosis, only 17 percent of that one percent, partly because some physicians may not be aware of celiac and because the symptoms are so varied.
While men and women are affected, women are diagnosed three times more often than men, partly because the symptoms are similar to irritable bowel syndrome and partly because women tend to visit doctors more often, so there’s more opportunity for a diagnosis.
Celiac disease is associated with a tenfold increased chance of acquiring other autoimmune disorders. Some autoimmune diseases share a very high
rate of being associated with celiac disease. These include type 1 diabetes, Sjögren’s syndrome, and primary biliary cirrhosis.
Celiac typically arises during early childhood, but it can also be triggered (or become active for the first time) after surgery, pregnancy, childbirth, viral infections, or even severe emotional stress. Like Ronnie, people were once thought to “outgrow” celiac disease. But we now know that’s not true. And untreated celiac disease can have serious complications, including an increased risk of certain types of cancers.
Unlike other autoimmune diseases, in celiac the immune system doesn’t attack self-antigens. The attack is actually directed against water-insoluble proteins, or
prolamins
, in grains as they pass through the digestive system. Toxic peptides found in these proteins—
gliadin
(found in wheat),
secalin
(from rye), and
hordein
(contained in barley)—trigger an inflammatory reaction in the small intestines of genetically susceptible individuals.
When the immune system senses a prolamin, it sends white blood cells to attack it. These lymphocytes infiltrate the lining of the small intestine, and the resulting inflammation causes overgrowth of the valleys (
crypts
) between the villi, and eventually the destruction of the villi themselves.
“It’s not a case of mistaken identity or molecular mimicry. The villi are not the targets; they are innocent bystanders,” remarks Peter H. R. Green, MD, the Phyllis and Ivan Seidenberg Professor of Medicine and director of the Celiac Disease Research Center at Columbia University. “Celiac disease is a unique autoimmune disease because we know what the environmental antigen is.” What isn’t known is why any individual may lose his or her tolerance to gluten. In people who are genetically susceptible to celiac disease, “tolerance” to gluten is lost.
Technically, all the foods we eat are “foreign” antigens. But as we gradually start eating solid foods as babies, the immune system becomes programmed to tolerate them. The immune system has to reach a certain maturity before it can do this, however. That’s one reason breast-feeding is beneficial. Breast milk not only contains a perfect balance of proteins, carbohydrates, and fat to nourish an infant, but because these nutrient antigens come from the mother, they are less likely to set off an immune reaction. Breast milk also contains many important antibodies that help an infant fight off infections, and it creates a protective environment in the intestines. Baby formulas contain cow’s milk that’s been altered to closely resemble human milk (but it lacks the key antibodies). In families where food allergies or lactose intolerance is common, soy baby formula is used. In the case of milk allergies, babies are fed protein
hydrolysate
formulas, which contain cow’s milk proteins broken down in a way that mimics digestion and is less likely to provoke allergic reactions. (Allergic reactions also involve the immune system and often occur in people with autoimmune disease.) The first solid food babies eat is rice cereal, which does not contain gluten.
Recent large placebo-controlled European studies of the role of breast-feeding and timing of gluten introduction have debunked current thinking. These two studies of around 1,500 children, who were at high risk of developing celiac disease because of having family members with celiac disease, show that breast-feeding was not protective against developing celiac. In addition, giving small amounts of gluten between four to six months, as is the recommended practice (at least in Europe) did not provide protection against celiac.
Neither was delaying gluten introduction to after the child was a year old. Their only risk factor: the number of at-risk genes.
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A majority of people with celiac disease produce antibodies against gliadin, the product in the toxic grains, and other antibodies, setting off a process that leads to production of autoantibodies. These include
anti-gliadin peptide tissue transglutaminase antibodies (tTG)
and
antiendomysium antibodies (EMAs)
, which react against components of smooth muscle tissue in the esophagus and the upper part of the small intestine
(jejunum)
.
Celiac disease is closely associated with other autoimmune diseases, including type 1 diabetes, thyroid disease, and Sjögren’s syndrome, which are often the initial diagnosis in adults with celiac. “It’s thought that you get the celiac disease first, then you get these autoantibodies to other organs, and then you get the other organ disease, and much later the celiac gets diagnosed,” explains Dr. Green. “If you take a bunch of kids with celiac disease, they will often have autoantibodies to the pancreas or to the thyroid. If you put them on a gluten-free diet, those autoantibodies go away. So maybe if you can diagnose celiac early enough, you may prevent these other autoimmune diseases.”
Genes also play a major role in celiac disease. Among identical twins (who share identical genes), if one twin has celiac there’s only a 70 percent chance the other twin will have it too. Among nonidentical twins, this concordance rate is 40 percent. In the study of high-risk children fed gluten before six months of age or later, the deciding factor for developing celiac seemed to be genes rather than when they were exposed to gluten.
However, sharing the same
human leukocyte antigens (HLAs)
may not be the only factor that predisposes people to celiac disease. Environmental causes can play a role, as well.
“We now know that there are about 40 different genes associated with the development of celiac disease. Celiac is associated with specific HLA genes, but they are also common in the general population,” observes Dr. Green.
It’s not clear whether female (or male) hormones play a role in celiac disease. “We have looked at male-female differences in celiac disease, and men seem to have more severe manifestations than women. Men have lower bone density and lower total cholesterol, suggesting more malabsorption. But more women get it than men,” remarks Dr. Green. “Hormones have not been looked at closely in women with celiac disease, but in men you have low testosterone levels. There’s a circulation of estrogen within the liver that gets
secreted in bile and then reabsorbed. So potentially, you don’t get reabsorption of secreted estrogen. Women may well have lowered testosterone, too. But it hasn’t been studied.”
Ronnie’s story continues:
I actually learned about celiac disease from a free magazine I got in a health food store . . . the article talked about all the symptoms I had been having for years. It mentioned a book, and I ordered it. It told you what to eat and not to eat. So I tried eliminating all the gluten in my diet. I went to a bookstore that had a medical text section and found two books that had something on celiac and took notes. That’s how I learned everything . . . the tests that diagnose it, which does include a stool analysis to look for evidence of undigested fat . . . and they described all the damage to the villi. I did go to see another doctor who didn’t want to hear about anything I had learned. She just wanted to run tests. She got very huffy and said, “You think you know so much . . . I’m the doctor.” I have other problems along with the celiac. I’ve had chronic fatigue . . . I had fibromyalgia . . . on both sides of my family there’s diabetes, and I am very prone to hypoglycemia. But aside from avoiding gluten and fat, I figured there was nothing the medical profession could really do for me.