Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (30 page)
Tough to Digest—Inflammatory Bowel Disease (Crohn’s Disease and Ulcerative Colitis), Celiac Disease, and Pernicious Anemia
I was diagnosed with Crohn’s when I was 20. But, looking back, I’d had symptoms ever since I was a child. I would have these strange periods of a week or two where I would have fevers, abdominal pain, and such fatigue and exhaustion that I couldn’t move. But my pediatrician used to tell my parents, “She’s just trying to get out of going to school. Don’t take it seriously.” And then during stressful times, I would get really sick. Like during exams or the week of my high school graduation. It took a long time to figure out what was wrong with me. I was going to lots of doctors. I was going to a gynecologist, I was seeing my family doctor, and they were all saying different things. One said I was developing an ulcer and I should reduce the stress in my life, and I needed to take acid reducers. My gynecologist said I had ovarian cysts and that’s what was causing the pain. I was told I had irritable bowel syndrome . . . I was put on antibiotics . . . but no matter what they did, nothing helped. When I was at my sickest, I dropped around 20 pounds. I was also having fevers and night sweats, which are all classic symptoms of Crohn’s during a flare. But it still took a long time to be diagnosed. And that only happened because I was so sick my gynecologist decided to admit me to the hospital to find out what was wrong. Once I was put in the hospital, they ran some CAT scans and barium tests and they
found the Crohn’s. But that was only after the pain and inflammation were so bad, and my small intestine became so inflamed that it burst through my bladder. So I had to have a whole section of my intestines removed. If they had caught it early, maybe I could have just had medication and been fine.J
ANINE
, 26
A
s Janine found out, diagnosing
inflammatory bowel disease (IBD)
is rarely quick or simple. The two types of IBD—
Crohn’s disease
and
ulcerative colitis
—are often mistaken for each other, and their early symptoms of diarrhea and cramping are frequently confused with a nonautoimmune problem called
irritable bowel syndrome (IBS)
. Sometimes they even occur together.
However, IBS and IBD are not the same, even though the abbreviations are similar. In Crohn’s disease and ulcerative colitis, it’s as if something is eating at you, destroying the parts of your body needed to extract vital nutrition from food and protect you from bacteria in the gut. Both are technically “foreign” antigens, and for our intestines to be tolerant of food and protect against invasion by bacteria, the thin mucosal lining must have a tightly regulated immune system. In IBD and
celiac disease
(another autoimmune disease that affects the intestines), this system fails, disrupting normal digestion.
The process of digestion can be likened to an assembly line, with the various parts of the gastrointestinal system moving food along on a conveyor belt powered by smooth muscle tissue. Food is first chopped up into manageable pieces as we chew, moistened by saliva (which also contains enzymes that begin to break down carbohydrates), and, after a minute or two, is loaded onto the conveyor belt with each swallow. The muscles in the esophagus contract (this is called
peristalsis
) to push food down into the stomach, where it’s mixed with acid and digestive juices produced by the stomach lining (which help break down proteins). Your stomach continuously churns as it breaks down and mixes food into a semiliquid consistency, and after two to four hours sends it into the many loops of the small intestine.
This part of the GI conveyor belt has three sections: the
duodenum
(the part that connects directly to the stomach), the
jejunum
(the section just below it), and the
ileum
(which connects to the
colon
, or large intestine). In the duodenum, liver enzymes and
bile salts
(produced by the gallbladder)
break down fats, and digestive enzymes from the pancreas continue the breakdown of carbohydrates and proteins. The final breakdown of food is carried out by glands in the lining of the small intestine, and nutrients are extracted by tiny fingerlike projections from the inner lining called
villi
; the layer of cells just beneath the lining helps nutrients pass into the bloodstream.
The Digestive System
This process takes anywhere from one to four hours. Finally, the conveyor moves food into the colon. Here, the lining has indentations called
crypts
, which extract most of the water. The solid waste that’s left over is moved out of the body as feces. This is actually the longest part of the process, taking anywhere from 10 hours to a couple of days.
The inflammation of IBD speeds up the passage of food, so the intestines empty more frequently, causing diarrhea. Because your body doesn’t get enough time to absorb food properly, calories pass out of the system before you can use them, so you start to lose weight.
Inflammation also breaks down the thin layer of cells lining the intestines (
epithelial cells
). This one-cell-thick sheet of cells and the layer of
mucin
they produce to lubricate and shield them from digestive chemicals serves as the only barrier against normal bacteria (
flora
) and toxins in the bowel. Without it, we’d be overwhelmed by infections.
Some T cells are found in the epithelial layer, but the immune system of the intestines only allows a certain amount of other white blood cells into the gut to take care of viruses or excess bacteria (we need a certain amount of bacteria for normal functioning, and they must constantly be kept in a delicate balance). Immune cells in the gut must be programmed for tolerance of food antigens and to react against anything else foreign. As inflammation breaks down the lining of the intestine, normal immune function of the gut breaks down as well, leading to overgrowth of bacteria and infections.
Erosion of the intestinal lining by inflammation causes
ulcerations
or cracks (
fissures
) that can bleed. The disease also triggers overgrowth of smooth muscle cells in the intestine wall, which thickens the wall and narrows the opening through which food passes. In some cases, the narrowing is so severe it blocks food from moving along (
strictures
). Inflammation can also spread outside the bowel wall, penetrating to an adjacent area of the intestine, sometimes causing sections of bowel to stick together (
adhesions
).
Crohn’s disease typically affects the lower part of your small intestine (the
terminal ileum
), but it can produce inflammation and ulcerations along any part of the digestive conveyor belt, from the mouth to the anus (as well as nearby tissues) and can cause symptoms in other parts of the body (see
pages 245
to
246
). The terms
ileitis
and
proctitis
refer to inflammation in the ileum and rectal areas. In
ulcerative colitis (UC)
, inflammation usually occurs only in the lower colon and in the rectum, but may spread to the entire colon.
IBD is actually the second most common chronic inflammatory disorder after rheumatoid arthritis. Crohn’s and ulcerative colitis commonly occur between ages 12 and 28, and spikes again after age 50. Opinions are divided as to whether women are more prone to Crohn’s disease; some studies show women are two to three times more likely to develop it. Crohn’s is a lifelong, chronic disease, but new treatments have made lengthy remissions possible; UC can be cured with surgery to remove the affected area of bowel.
According to the Crohn’s & Colitis Foundation of America (CCFA), Crohn’s disease and ulcerative colitis affect as many as 1.4 million Americans.
1
Crohn’s disease seems to stem from a combination of genetic and environmental causes, especially bacterial infections. Around 5 to 20 percent of people with Crohn’s have a close family member with inflammatory bowel disease. If you have a parent or sibling with IBD, your chances of developing it are increased. “With one affected parent the risk is 3 to 7 percent; with two affected parents it goes up to 33 percent for the child,” remarks Sunanda V. Kane, MD, professor of medicine, gastroenterology, and hepatology at the Mayo Clinic in Rochester, Minnesota. Crohn’s is also more common in Caucasians and among people of Jewish descent.
Back in 2001, scientists at three U.S. universities and in Europe identified the first genetic abnormality that increases susceptibility to Crohn’s disease. Today upwards of 70 genes have been found.
Discovery of that first Crohn’s gene proved pivotal. The gene involves a protein called
NOD2/CARD15
, which helps immune cells called
macrophages
target bacterial invaders by recognizing a key component of their cell membrane. Macrophages, the Pac-Man-like cells of the immune system, engulf
and break down bacteria they encounter, then display crumbs of their meal on their surface as a signal to other immune cells to join in the fight. This signal also helps the other immune cells “remember” their prey. In flawed forms of the
NOD2/CARD15
gene, a small portion of the protein is missing, making it less effective in recognizing the bacteria.
2
How this triggers the inflammation of Crohn’s disease isn’t yet clear. Researchers speculate that if macrophages are less efficient in sensing bacteria initially, then the other immune cells that are eventually activated and react to the bacteria may produce an exaggerated, prolonged inflammatory response.
As many as 20 percent of people with Crohn’s disease in North America and Europe may have a damaged form of the
NOD2/CARD15
. Having just one copy of a defective
NOD2/CARD15
gene may double the risk of developing Crohn’s; having two copies could increase risk 15 to 20 times, according to the CCFA.
While
NOD2/CARD15
is only one of many genes that increase risk, the finding gives an important clue as to how bacteria, even those that normally live in the gut (the
microbiome
) could contribute to Crohn’s disease.
For example,
Escherichia coli (E. coli)
bacteria are normally present in the intestines, but if you eat or drink food or water contaminated by fecal matter, certain strains of
E. coli
can cause a diarrheal infection. People with Crohn’s are often infected with the bacteria. French researchers reported in 2002 that
E. coli
infection causes cells lining the intestine to produce molecules called
MICA
, which activate natural killer T cells. The T cells then release a chemical signal that causes inflammation. One theory of how inflammatory bowel disease develops is that bacteria may constantly stimulate the mucosal lining of the intestines, and the resulting activation of immune cells and production of inflammatory cytokines (like
tumor necrosis factor alpha, TNF
α
) lead to chronic inflammation that eventually breaks down these tissues.
3
So a big surge in MICA molecules in the intestines due to an
E. coli
infection could set off an immune response that causes Crohn’s disease. Or, people with a defective
NOD2/CARD15
gene may be genetically “programmed” to mount a prolonged immune response to the infection, causing chronic inflammation of the intestines that leads to Crohn’s. It may also be that toxins produced by
E. coli
(or other bacteria) could also damage the intestinal lining.
One bacterium linked to Crohn’s is
Mycobacterium paratuberculosis
, which has been found in biopsies of intestinal tissue from Crohn’s patients. Crohn’s
has been confused with intestinal tuberculosis, and one of the drugs used to treat TB is
para-aminosalicylic acid
, an aspirin-like drug closely related to
5-aminosalicylic acid
, a component of
sulfasalazine (Azulfidine)
, which is used to treat Crohn’s disease.
The persistent idea that the measles virus (
Rubeola
) may play a role in Crohn’s disease has been largely disproven.
Disruption of the normal balance of gut bacteria (
dysbiosis
), caused by toxins, bacteria, and even stress may lead to Crohn’s. As previously mentioned, more than 500 species of bacteria, along with yeast and other organisms, live in the gut. When dysbiosis occurs, the normally “tight junctions” between the epithelial cells lining the intestines may become “leaky,” so inflammatory cells and harmful bacteria can get through and cause an abnormal immune reaction.
4
The theory is that inflammation triggers changes in the lining of the gut that eventually lead to Crohn’s and other autoimmune diseases such as rheumatoid arthritis.
5
Smoking is a major risk factor for Crohn’s and for developing symptoms outside the gut.
6
But ironically, smoking seems to be protective in ulcerative colitis. One of the theories is that in ulcerative colitis, nicotine may stimulate mucin production, and mucin acts as a barrier to help prevent bacteria in the gut from invading the intestinal wall and stimulating the immune system. In Crohn’s disease it seems to be the opposite—mucin production is reduced. However, it’s not clear whether it’s the nicotine or something else in cigarette smoke that’s causing this effect.
I think I must have had this disease my whole life . . . I remember when I was in second grade, I was in a gifted class, and when we would have tests I would have severe stomach pains. I would be doubled over; I was in the bathroom all the time. But when my parents took me to a doctor, they were told I had a “spastic colon,” a “nervous stomach.” That’s what I was told all my life.
I’ve been living on diarrhea medicines since I was a kid. At times the pain would be so bad I thought I had appendicitis. It was only after I had my second child in 1990 that my doctor said, “I think it’s time you got this checked out.” I went to a gastroenterologist, who did a colonoscopy—and that’s how I found out I had Crohn’s. But there had been other signs. In 1985 I suddenly started bleeding vaginally. I went to my gynecologist and found that
I had an ulcer in the vagina that was bleeding. He tried cauterizing it, but no matter what he did nothing worked. Then one night I started to hemorrhage. The ulcer had exposed an artery, and they had to tie it off. That was in 1985. It kept happening. I must have had around 10 to 12 different surgeries for vaginal ulcers. They would seem to heal, then a month or two later another one would open. They lasered them . . . twice they used placental tissue for a graft . . . but it wasn’t really that successful. They thought maybe it was Behçet’s disease, but I didn’t meet all the criteria for that. Then, as suddenly as it started it just seemed to go away . . . years later, after I developed another one and it was biopsied, we confirmed that they were Crohn’s ulcers.L
AURA
, 46
