Crohn’s Disease: Causes and Treatments?>

Crohn’s Disease: Causes and Treatments

by UCB Health & Wellness Publications

About 780,000 people in the United States have Crohn’s disease—and the incidence is rising. Crohn’s disease is a chronic inflammatory disorder that can affect any segment of the digestive tract, from the mouth, esophagus, and stomach to the small and large intestines. Most commonly, it affects the ileum (the last part of the small intestine) and the cecum (the first part of the large intestine). It is a systemic illness that in 25 to 35 percent of cases can also affect other body parts. Of these other body parts, joints are the most commonly affected, but skin, eye, and liver problems can also occur. Most of these problems usually improve with control of the underlying bowel inflammation.

Causes of Crohn’s disease

Despite extensive research, the causes of Crohn’s disease are poorly understood. Three factors likely play a role. Genetics is one of them: Certain people inherit a susceptibility to the disease. Caucasians (particularly American Jews of European descent), followed by African Americans, are more likely to get Crohn’s disease than are Hispanics and Asians, but the incidence of Crohn’s disease is significantly increasing in the Asian population.

The other factors are environmental and immunologic. For example, if a pathologic bacteria enters the intestinal tract, there is an immune response that counters the bacteria by sending inflammatory cells to get rid of the infection. When that task has been accomplished, this immune response shuts off, and the intestine returns to normal. In Crohn’s disease, the immune response does not cease, and inflammatory cells remain, damaging the intestine.

Symptoms of Crohn’s disease

Crohn’s disease causes chronic inflammation in the affected part of the bowel. The affected segment becomes swollen and develops erosions and ulcerations, which can affect the entire thickness of the intestine. These inflammatory changes usually result in abdominal pain and a change in bowel pattern—and, occasionally, bloody diarrhea. The chronic inflammation can also lead to complications such as peritonitis, abscesses, fistulas (abnormal connections between two organs), and strictures (narrowing of part of the intestine).

Symptoms of Crohn’s disease usually begin in the teen or young adult years but can occur at any age. Once individuals develop the disease, they have it for life. That said, some people have symptom-free periods that can last for months to years. Symptom-free periods are longer because of today’s treatment options. A reappearance of symptoms is referred to as a flare-up.

Diagnosis of Crohn’s disease

The tests used to diagnose Crohn’s disease depend on where your doctor thinks the inflammation is occurring. A computed tomography (CT) scan or magnetic resonance (MR) enterography (a type of magnetic resonance imaging, or MRI, performed with contrast material) is used to detect upper gastrointestinal Crohn’s disease. Looking at the upper portion of the gastrointestinal tract with an endoscope, passed through the mouth while a patient is under sedation, can sometimes be helpful.

Crohn’s disease of the small intestine can also be studied using capsule endoscopy, which is increasingly being used for diagnosis. Before going forward with a capsule endoscopy, doctors will perform tests to determine if a stricture is suspected because the capsule could get stuck if a stricture is present.

Colonoscopy, sigmoidoscopy, CT, and MRI can be used to detect Crohn’s disease of the large intestine. These studies have replaced barium enemas as the preferred diagnostic tests. Fistulas are best evaluated by CT or MRI. Genetic tests and blood tests for detecting Crohn’s disease are currently in development. It is important to distinguish Crohn’s disease from other possible disorders, including infections, drug-induced injury, inadequate blood flow to a part of the intestine, cancer, and ulcerative colitis.

How Crohn’s disease is treated

No drug or surgical procedure can cure Crohn’s disease. Treatment is aimed at improving symptoms and preventing and treating flare-ups and complications. Mesalamine-containing drugs are considered ineffective for treating Crohn’s disease unless the person has very mild disease located in the ileum or the ileum and colon. Depending upon the location and severity of disease, corticosteroids, immunomodulators (also referred to as immunosuppressants), or drugs known as biologics are used for treatment, often given in combination. Immunomodulators have a generalized, nonspecific effect on immunity. Biologics are made from living tissue and target specific parts of the immune system.

When Crohn’s disease involves the end of the ileum or the cecum, budesonide (Entocort EC) can be used as long as there aren’t complications such as a stricture or fistula. Budesonide is a safer corticosteroid than prednisone and can be taken for three months, then slowly tapered. If there is a recurrence, treatment can be repeated.

Involvement of the upper part of the small intestine is more serious and requires treatment with a steroid such as prednisone and usually a biologic, often taken with an immunomodulator. Involvement of the ileum, colon, and rectum, other than for very mild disease, is often treated with a steroid, but usually will also require a biologic. Steroids should not be given as sole treatment for repeated flare-ups, and ideally, they should not be used for more than three months because of their serious side effects. Also, steroids are not as effective in correcting intestinal damage as immunomodulators and biologics.

The immunomodulators usually given are mercaptopurine, also called 6-MP (Purinethol), or azathioprine (Imuran); both are taken orally every day. An enzyme called TPMT should be measured with a blood test before starting these drugs in order to minimize the danger of liver and bone marrow injury. As with all immunosuppressants, there is an increased risk of infection. There is also a very small increased risk of lymphoma, more so in young and older men. Another immunomodulator that may be used is methotrexate, self-injected once a week.

Severe disease and significant flare-ups usually require hospital treatment, which may involve intravenous nutrition and fluids to allow the bowel to rest. To reduce inflammation, an intravenous corticosteroid such as methylprednisolone may be given, and in all likelihood, a biologic drug will also be used, if this is not already part of the treatment. Surgery may be needed if medications are ineffective.

Five biologic drugs are currently used for the treatment of Crohn’s disease. Three of these—infliximab (Remicade), adalimumab (Humira), and certolizumab pegol (Cimzia)—are tumor necrosis factor (TNF) inhibitors, meaning they stop the immune system protein TNF from causing inflammation. All three are equally effective. Ustekinumab (Stelara) works by inhibiting a different part of the immune system that causes inflammation (interleukin-12 and -23). Vedolizumab (Entyvio) blocks the entrance of inflammatory cells at the intestinal site. Because vedolizumab has less of an effect on immunity outside the intestinal tract, it has the potential for fewer side effects.

Infliximab and vedolizumab are injected intravenously. Adalimumab, certolizumab pegol, and ustekinumab are self-injected under the skin. All of these drugs can result in significant clinical improvement and can also lead to a complete remission. If effective and tolerated, the drug being used should be continued on a regular basis, even if there are no further symptoms. Stopping usually leads to a flare-up. The main significant side effect of these drugs is an increased risk of infection.

In 2016, the FDA began approving the first anti-TNF biosimilar drugs to treat severe Crohn’s disease and ulcerative colitis. These biosimilars, like the drugs they mimic, are TNF inhibitors acting directly on the immune system by blocking the production of excess amounts of inflammatory proteins. In general, they are as safe, effective, and tolerable as the original drugs. But these, too, carry the risk of serious infection. The newer medications are Amjevita and Cyltezo, which are biosimilars for adalimumab, and Inflectra, Ixifi and Renflexis, which are biosimilars for infliximab. Biosimilars can be used when biological therapy is initiated. They should not be substituted for an existing drug of the same class that is already effective and tolerated without both the doctor’s and the patient’s approval.

Before biologics are used, patients need to be tested for prior exposure to tuberculosis or hepatitis B. If either is present and not treated before starting a biologic drug, serious illness and death can occur. Also, routine vaccinations, including those for flu and pneumonia, should be given before starting treatment.

With any Crohn’s disease medication, quitting smoking is extremely important. Smoking not only reduces the effectiveness of drug treatment, it also makes it more likely that disease will recur.

When is surgery needed?

Surgical removal of a section of the bowel is required if you develop problems such as an intestinal obstruction due to strictures, fistulas, or abscesses that don’t respond to medication. In this surgery, the affected portion of the small or large intestine is removed and the two ends are reattached. The procedure is not a cure for Crohn’s disease, since the remaining bowel is still susceptible to the disease.

It is also possible that a part of the intestine may need to be brought through an opening made in the skin, called a stoma, which allows intestinal contents to empty into a removable bag that is affixed to the skin. The stoma may be temporary but can also be permanent in certain situations. Using an immunomodulator or a biologic postoperatively may be recommended to prevent recurrent disease.

This article first appeared in the 2019 UC Berkeley Digestive Disorders White Paper, medically reviewed by Steven Jacobsohn, MD.

Also see Ulcerative Colitis: Finding Relief and Remission.