Authors: Rita Baron-Faust,Jill Buyon
Crohn’s can create special problems for women. Ulcerations and pain in the perineal area can cause painful sex (leading some women to avoid sexual contact), and some may develop a negative body image. “Women worry about having children, being attractive to the opposite sex, feeling that they are somehow ugly, and scarred, that they will be alone in their lives with this diagnosis,” comments the Mayo Clinic’s Dr. Sunanda Kane. “There are also intimacy issues and worries about sexual performance. Crohn’s disease can be a very disfiguring disease, especially when we are talking about deep ulcers and fistulas, around the perianal area and in the vagina.”
Other issues that can interfere with relationships include diarrhea, sleep disturbances, and fatigue. Women may also have more problems with fecal incontinence, before and after surgery for Crohn’s, or after injury to the anal sphincter during childbirth.
If inflammatory bowel disease begins during childhood or adolescence, it may lead to a delayed puberty, and women may get their first menstrual period later than usual. There are also reports that women experience more severe symptoms around the time of their menstrual periods. There are no clinical studies of premenstrual flares, but a survey of women with irritable bowel and inflammatory bowel disease done by Dr. Kane and colleagues at the University of Chicago found that women with IBD seemed to have more symptoms of PMS. “They polled a group of healthy women, and then compared that to a group of women with inflammatory bowel disease and a group with irritable bowel. The healthy women had premenstrual symptoms, and the group with ulcerative colitis and IBS had the same symptoms but in higher percentages. Of the women with Crohn’s disease, 100 percent had premenstrual symptoms,” remarks Dr. Kane.
Fertility seems to be unaffected when Crohn’s disease is inactive, but if your disease is active you may have some trouble getting pregnant. There are also reports that fertility may be decreased if you’ve had surgery for Crohn’s.
“Two-thirds of women with inactive disease at the time they conceive will do just fine, but perhaps a third may get worse,” says Dr. Kane. “Among women who have active disease at the time of conception, one-third will stay the same, one-third will have worsened disease activity, and one-third will actually get better. We simply don’t know which group a woman will fall into, even if it’s a second or third pregnancy.” Women with severe, active disease of the terminal ileum may have a harder time with pregnancy, she adds.
The goal is to maintain a remission during pregnancy, and most treatments do not pose a risk. So you need to stick with medication. Sulfasalazine can cause nausea, which may worsen morning sickness in the first trimester and may exacerbate heartburn in the later part of pregnancy. “Sulfasalazine does not carry a risk of fetal malformation. It does cross the placenta, but is only minimally found in breast milk. Sulfasalazine does interfere with folic acid metabolism, so we give women an extra milligram of folic acid a day,” says Dr. Kane. Folic acid protects against neural tube defects. “Mesalamine, our first-line medication for both ulcerative colitis and Crohn’s, is a topical anti-inflammatory, and we have not seen any increased risk in pregnant women.” The dose of prednisone should be reduced in nursing mothers, if possible.
Ulcerations in the genital area are a concern seldom discussed. “I have seen a patient who developed a rectovaginal fistula after an episiotomy. What happens is the rectal tissue is inflamed, it doesn’t heal, and a tract starts forming between the vagina and rectum. For women with IBD, episiotomy should not be taken lightly,” adds Dr. Frissora.
Although no harms have been seen for Remicade and Enbrel, risk during pregnancy can’t be ruled out (see
page 51
). Immunosuppressants like azathioprine and 5-ASA drugs should be avoided during pregnancy. (See
pages 251
to
252
for details.)
Crohn’s may worsen during the first trimester and after delivery, but this may be because women go off their medications in order to breast-feed, remarks Dr. Kane. IBD may also occur for the first time during pregnancy or in the postpartum period.
While the course of pregnancy and delivery is usually not affected in most women with Crohn’s disease, you need to have a thorough discussion with your doctors before you start trying to conceive.
Remicade or other biologics can be continued in pregnancy until at least week 20. “We then assess whether disease activity dictates continued therapy, since this is when they start to cross the placenta,” says Dr. Kane.
Colonoscopy and x-ray procedures should be avoided, particularly during the first trimester; sigmoidoscopy can be done to track disease activity, however.
Inflammatory bowel disease is not “inherited” in the same way as a disease like cystic fibrosis (in which inheriting two copies of a defective gene, one from each parent, means you will develop the disease). There are multiple genes involved. Still, not enough is known to predict how many children of women with IBD will be predisposed to Crohn’s (or ulcerative colitis).
Crohn’s disease that develops in midlife and beyond seems to affect more women than men. Women with Crohn’s who have severe menopausal symptoms can consider hormone replacement therapy, says Dr. Kane. “The risks and benefits are the same as for other women.”
Osteoporosis
is a major concern for all women after menopause, and especially so for women with Crohn’s. “Since Crohn’s causes osteoporosis, we encourage weight-bearing exercise and tell women to take calcium. Some women may need bone-building drugs, depending on how severe the bone loss is,” adds Dr. Kane.
Perhaps 15 percent of patients with inflammatory bowel disease first develop symptoms after age 65. Although the symptoms and course of the disease are similar to that in younger patients, there’s slightly more colon involvement when Crohn’s affects older people. Conditions that can mimic IBD in older age include diverticular disease, colitis caused by medications (especially nonsteroidal anti-inflammatory drugs), infections, cancer, and other diseases. However, medical and treatment options are not different from those for younger women.
Janine’s story continues:
I had started to have severe back pain, and I was lucky to find a really smart orthopedist, who looked beyond just the bones. This doctor really looked at my history. He sees a 46-year-old woman who had a hysterectomy, who has Crohn’s disease, who took prednisone for many years, who is not on estrogen, who has a small frame and is suffering severe back pain. He said it could be osteoporosis and asked me when my last bone density screening was, and
I hadn’t had one yet. I was first put on Fosamax, but it irritated my esophagus, so I was put on Evista. But after years of prednisone the osteoporosis is pretty severe. Now they think about it as soon as they put you on steroids. But years ago they didn’t. And if any woman is on steroids and her doctor doesn’t mention her bones, she should make sure she’s being protected.
In contrast to Crohn’s,
ulcerative colitis
affects only the top layers of the mucus membrane that lines the colon and the rectum, producing inflammation and ulcerations. But the effects of inflammation are the same: the colon empties frequently, causing diarrhea. UC can be difficult to diagnose because the symptoms are similar to irritable bowel syndrome and to Crohn’s. It develops most often between ages 15 and 40 (although children and older people can have it, too). The incidence of UC may be 20 percent higher in men, and it seems to run in families.
Many of the same theories as to what causes Crohn’s disease also apply to ulcerative colitis (see
pages 241
to
243
). It seems likely that in vulnerable people, a reaction to a virus or a bacterium causes ongoing inflammation. Those bacteria could be among those normally found in the gut. Although emotional stress and sensitivities to certain types of food may trigger symptoms, they do not cause the disease itself.
Multiple genes are also likely to be involved in ulcerative colitis. It does tend to run in families; as many as 20 percent of patients have a close relative with ulcerative colitis or, less often, Crohn’s disease. But again, genes tell only part of the story.
The most common symptoms of UC are abdominal pain and bloody diarrhea. You may also experience fatigue, weight loss and loss of appetite, dehydration, and rectal bleeding.
One of the first signs that you may have UC is stools that are looser and softer than usual, often with blood mixed in. You may also feel an intense urge to defecate (called
tenesmus
), and this may result in the accidental passage of a small amount of stool, soiling your underwear. This is due to inflammation of the rectum usually present at the onset of UC and one of the signs that distinguishes it from Crohn’s. Moving your bowels relieves this urge only temporarily, another key sign of UC. You can experience this problem during the night, causing sleep disturbances. Crampy abdominal pain is also common (caused by inflammation in other areas of the bowel). Half of women with UC have only mild symptoms; that’s common if the disease is confined to the lower (
sigmoid
) colon and the rectum.
When inflammation is confined to the rectum, it’s called
ulcerative proctitis
. This may only produce blood and mucus in the stool, and tenesmus. If your disease is more severe and involves large areas of the colon, the symptoms will be more severe and likely to include anemia (from bleeding), weakness, fever, and weight loss.
Because of its inflammatory component, ulcerative colitis may also cause arthritis, eye inflammation, fatty deposits in the liver, and liver disease such as
chronic hepatitis
,
cirrhosis
, and
primary sclerosing cholangitis
(a disease more common in men).
Ankylosing spondylitis, a form of inflammatory arthritis affecting the lower back and spine, affects 2 to 6 percent of people with ulcerative colitis, causing lower back pain, morning stiffness, and sometimes a stooped posture. You may also experience skin rashes, anemia, and kidney stones. Large, circular ulcers called
pyoderma gangrenosa
that eat away at the skin and soft tissues can occur in UC (and, less commonly, in Crohn’s). As with Crohn’s, osteoporosis is a frequent complication. Many of the inflammatory symptoms subside when UC is treated.
Ulcerative colitis is also a clinical diagnosis, requiring a thorough physical exam and two key diagnostic tests:
sigmoidoscopy
and a barium enema.
Colonoscopy and proctosigmoidoscopy
are needed to determine the extent of the disease and the mucosal changes common in UC, including ulcerations. (For details on colonoscopy and sigmoidoscopy, see
pages 247
to
249
.) Proctosigmoidoscopy examines the rectum using the same fiber-optic scope.
Sigmoidoscopy
can often easily distinguish ulcerative colitis from Crohn’s; UC is not patchy, and there will be continuous areas of inflammation and ulcerations. In ulcerative proctitis, there will be a clear separation between red, inflamed tissue and normal bowel above it.
During periods of remission, ulcerations in the lining of the colon may heal to such an extent that the colon will appear close to normal during sigmoidoscopy or a barium x-ray.
Stool testing
can reveal bleeding or infection in the colon or rectum. Since rectal bleeding or blood in the stool can also be a sign of colon cancer, further tests may be needed (such as colonoscopy with a biopsy).
Stool tests can also find infections such as
Clostridium difficile (C. difficile)
, which is increasing among patients with UC, and
Escherichia coli (E. coli)
, both of which can cause severe diarrhea.
Infectious colitis
can also produce bloody diarrhea, as can parasites. A mucosal biopsy may be needed to distinguish this from ulcerative colitis.
A
complete blood count (CBC,
see
page 33
) can pick up anemia, which can be a sign of bleeding in the colon or rectum. A high white blood cell count is a sign of inflammation.
Erythrocyte sedimentation rate (SED rate)
will be normal in mild to moderate UC, and elevated in severe disease. (For a complete explanation of a SED rate, see
page 32
.)
The following disease activity classifications were updated in 2010 by the American College of Gastroenterology (ACG) and are used to help select or adjust treatment.
These classifications, based on clinical and endoscopic findings, do not take into account symptoms including abdominal pain, nighttime bowel movements, urgency, or “the dreadful fear of episodes of incontinence, which are often the patients’ greatest concerns,” the ACG notes in its Practice Guidelines.
22
Unless your disease is very severe, it’s likely you’ll be given medication. In many cases, medications can bring about long periods of remission, from months to years, where the mucosal lining of the colon heals and virtually returns to normal. Unfortunately, your symptoms are likely to return eventually. If the disease is severe, you may need to have the entire colon removed.
In cases of severe symptoms, such as extensive bleeding or diarrhea causing dehydration, you may need to be hospitalized. In that event, you’ll be given medications to stop the diarrhea and bleeding and replace lost fluids and electrolytes. If the colon is severely inflamed, you may need a special diet or intravenous feeding.
Ulcerative colitis is a chronic disease (the only cure is radical surgery) that requires long-term medical care, and you need to be followed closely by a gastroenterologist.
According to ACG guidelines, patients with mild to moderate distal colitis may be treated with oral aminosalicylates, topical mesalamine, or topical steroids, depending on the patient’s preference, since both types of therapies are effective.
17
Aminosalicylates
are given orally or rectally (or both) to suppress inflammation in the rectum and colon. Oral medications include
sulfasalazine
and
5-aminosalicylic acid (5-ASA)
drugs (
mesalamine
,
olsalazine
, and
balsalazide
), which are generally used in mild to moderate ulcerative colitis, and as maintenance therapy once remission is achieved. In cases of extensive but mild disease, only oral sulfasalazine or 5-ASA medications are used. If disease is moderate and extensive, azathioprine or 6-MP may be added.
Side effects of oral 5-ASA drugs include nausea, vomiting, heartburn, diarrhea, and headache (see
page 251
for more about sulfasalazine and 5-ASA drugs). Topical 5-ASA agents in suppository form or suspension
enemas (Rowasa)
can cause hemorrhoids, itching, and allergic reactions (rashes) in some people. They can also stain your clothing.
Combining oral and topical aminosalicylates is more effective than either alone. In patients who don’t respond to oral aminosalicylates or topical corticosteroids, mesalamine enemas or suppositories may still be effective. In rare cases where there’s no improvement with all of those therapies, or if there’s a systemic illness, patients may need oral
corticosteroids
such as prednisone or
infliximab (Remicade)
.
Sulfasalazine, 5-ASA drugs, and infliximab
are used in patients with more extensive mild to moderate UC.
Prednisone and other corticosteroids
like
methylprednisolone (Medrol, Depo-Medrol)
can be given orally, intravenously, through an enema, or in suppository form, depending on where the inflammation is located. These medications are used in UC patients with moderate to severe disease. Systemic corticosteroids carry a risk of osteoporosis and can cause side effects like weight gain, acne, facial hair, mood swings, high blood pressure, diabetes, and an increased risk of infection.
Immunosuppressants
used to treat ulcerative colitis include
azathioprine (Imuran)
,
6-mercaptopurine (6-MP)
, and
cyclosporine (Neoral)
. These drugs dampen immune activity and keep immune cells from provoking inflammation. They are usually given orally to patients who have not responded to aminosalicylates or corticosteroids. Azathioprine or 6-MP may also be used in combination with corticosteroids (they also allow lower doses to be used) in moderate and extensive disease. It can take up to three months before benefits are seen with these drugs. Intravenous cyclosporine may be given for severe disease. The oral immunomodulator
tacrolimus (Prograf)
, used in transplant patients, is also approved to treat UC.
23
The first-line therapy is still the 5-ASA drugs. If the disease involves only the rectum or the rectum and the sigmoid colon, we use topical agents such as 5-ASA enema or, in some cases, cortisone enemas. And that can control distal disease. For mild disease, usually the oral 5-ASAs are effective. For flares, steroids are used a little more often, but we try to avoid their use, or use them only for very short periods. As with Crohn’s disease,
other drugs may be given to relieve pain, diarrhea, or infection (see
pages 254
to
255
).
Golimumab (Simponi)
is a newer
TNF
α
blocker approved for treating adults with moderate to severe UC who’ve have become dependent on corticosteroids or who have had an inadequate response (or can’t tolerate) oral aminosalicylates, corticosteroids, azathioprine, or 6-MP. Golimumab improves the mucosal lining of the colon and helps achieve and maintain remission.
An initial subcutaneous injection of 200 mg is followed by a 100 mg at week 2 and then 100 mg every month afterward. You can learn to inject it yourself (or have a family member learn) at home.
24
Two other
TNF
α
drugs used for Crohn’s disease,
infliximab (Remicade)
and
adalimumab (Humira)
are also approved for treating UC. Infliximab is given to patients with severe UC. (See
pages 252
to
253
.)
8
The integrin receptor antagonist
vedolizumab (Entyvio)
is also approved to treat people with moderate to severe ulcerative colitis who have not responded adequately to corticosteroids, immunomodulators, or
TNF
α
blockers.
10
Recent studies suggest that biologics are safer, more effective, and have more sustained benefits as maintenance therapy than the immunomodulators tacrolimus or 6-MP.
25
If the disease cannot be controlled with medication, or if there’s extensive bleeding, rupture, or the threat of colon cancer, surgery may be recommended.
Until recently, radical surgery to remove the entire colon and rectum (
colectomy
), with an
ileostomy
and an external bag to collect solid waste, had been the only “cure” for ulcerative colitis. However, newer surgical techniques allow for the colon to be removed without the need for an ileostomy.
The
ileoanal anastomosis
(commonly called a pull-through operation) preserves part of the rectum and allows patients to have normal bowel movements. In this procedure, the diseased part of the colon and the inside of the rectum are removed, leaving the outer muscles of the rectum intact. The ileum is attached to the inside of the rectum and the anus, creating a pouch that stores waste, which is passed in the usual manner. Inflammation of the
pouch and more frequent, watery bowel movements are possible complications.
The type of surgery depends on the severity and extent of the disease; you need to get as much information as possible to make an informed decision.
A number of new treatment approaches for ulcerative colitis are now in clinical trials.
Epithelial growth factors are being tested; they may speed healing of the colon lining and prevent infiltration of inflammatory cells.
Another experimental drug being used is an antibody to a molecule dubbed
alpha4beta7
that has been shown to contribute to inflammation in IBD. Preliminary clinical trials involving 28 patients found the drug LDP-20 induced remissions in 40 percent of patients, compared to those on a placebo. Further clinical trials are under way in ulcerative colitis and in Crohn’s.
Thalidomide (Thalomid)
, a once-banned drug, has found a new use in fighting IBD. Thalidomide was given as an antinausea drug to pregnant women and caused catastrophic birth defects; it was banned in the 1960s. But in recent years, it has been tested against ulcerative colitis, Crohn’s, and other diseases.
26
Side effects include sedation, numbness, and dry skin.
Tests are also being conducted of other forms of thalidomide called
selective cytokine inhibitory drugs
, which inhibit an enzyme that spurs production of tumor necrosis factor. These drugs seem to be more potent at dampening inflammation than thalidomide, and animal tests have not shown any birth defects.
It’s an odd occurrence that smoking seems to be protective in ulcerative colitis, so nicotine is being studied as a potential therapy, mostly in nicotine patches. But it has not been approved as a therapy for UC.