Crohn's Disease

Crohn's disease is an inflammatory bowel disease (IBD) which involves ongoing inflammation (pain and swelling) of the gastrointestinal tract. Crohn's-related inflammation usually affects the intestines but it may occur anywhere from the mouth to the anus (the end of the rectum).

Typical symptoms of Crohn’s disease include:

• stomach pain
• an urgency to have a bowel movement
• persistent diarrhea
• fatigue

Other symptoms can include rectal pain, fever, anemia, growth failure (in children) recurrent fistulas (abnormal connections of areas within the body, such as between organs), and weight loss. 

The last part of the small intestine (ileum) and the large intestine (colon) are the most common areas where Crohn’s disease is diagnosed. There can be healthy patches of tissue in between diseased areas. Ongoing inflammation causes the intestinal wall to become thick, and can lead to a blockage called a stricture.

There is no cure for Crohn’s disease but many types of medications are available that can ease the symptoms and help you live a more normal life. Surgery may be an option for some people, but is not usually curative.

What is the difference between Crohn’s disease and ulcerative colitis?

Crohn’s disease is not the same medical condition as ulcerative colitis, although both are considered inflammatory bowel diseases.

• In ulcerative colitis, inflammation affects only the large intestine and ulcers develop along the lining of your colon and rectum.
• Symptoms can vary and may include diarrhea, often with blood or pus, stomach cramping, rectal pain or bleeding, difficulties with defecation, weight loss, fatigue, or fever.

How does Crohn’s disease differ from IBS?

Crohn’s disease should also not be confused with irritable bowel syndrome (IBS), a type of functional bowel disease. IBS also only occurs in the colon, but is not considered an inflammatory bowel disease.

• IBS is characterized by cramping, stomach pain, bloating, gas, diarrhea, constipation, or fluctuating diarrhea and constipation.
• IBS does not lead to inflammatory changes of the lining of your large intestine.
• Treatments for inflammatory bowel disease and irritable bowel syndrome are also very different.

What causes Crohn's disease and who is at risk?

While the exact causes that lead to Crohn's disease are unknown, the condition is linked to an interaction between our genetics, immune system, and environmental influences. Normally the immune system helps protect the body from harmful organisms like bacteria, viruses, and fungi. But in patients with Crohn's disease and other types of IBD, the immune system can't tell the difference between normal substances and foreign invaders. The result is an overactive immune response called an autoimmune disorder that leads to the chronic inflammation.

In the U.S., roughly 750,000 people are living with Crohn's disease. The disease may occur at any age, but it usually occurs in adolescents and adults between ages 15 and 35 years. Other risk factors include a family history of Crohn's disease, Jewish ancestry, NSAID use, and smoking.

Types of Crohn's disease

There are five different types of Crohn's disease:

• Ileocolitis is the most common form. It affects the lowest part of the small intestine (ileum) and the large intestine (colon).
• Ileitis affects the ileum.
• Gastroduodenal Crohn's disease causes inflammation in the stomach and in the first part of the small intestine, which is called the duodenum.
• Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine (jejunum).
• Crohn's (granulomatous) colitis only affects the large intestine.

Symptoms of Crohn's disease

Symptoms of Crohn’s disease depend on what part of the gastrointestinal tract is affected. Symptoms range from mild cramping and diarrhea, to more severe disease. Symptoms can come and go with periods of flare-ups and remissions.

The main symptoms of active Crohn's disease typically include:

• Diarrhea
• Stomach cramps
• Lack of appetite
• Weight loss
• Fever
• Fatigue
• Bloody stools
• Mouth sores (aphthous stomatitis)
• Anal pain or sores

Other complications, not all related to the intestine, may include:

• Fissures (tears in the intestinal wall or anus) and ulcers
• Fistulas (a tunnel connecting the intestine with other organs)
• Drainage of pus or mucus from the anus or anal area
• Liver or bile duct inflammation
• Joint pain or arthritis
• Skin rash
• Eye inflammation (uveitis or scleritis)
• Delayed growth and puberty in children
• Increased risk of colorectal cancer

Diagnosis

A description of your symptoms to the doctor and various tests to rule out others conditions, such as infection, will help your healthcare provider to make a correct diagnosis. There is not a specific test to diagnose Crohn's disease.

Other conditions your healthcare provider may rule out in the diagnosis of Crohn’s disease include:

• Irritable Bowel Syndrome
• Lactose Intolerance
• Ulcerative Colitis
• Infectious Colitis
• Diverticulitis
• Perforating Cancer

A physical examination may reveal an abdominal mass or tenderness, skin rash, swollen joints or mouth ulcers. The doctor may use a stethoscope to listen to the belly area. Abdominal sounds (borborygmus, a gurgling or splashing sound heard over the intestine) may be heard.

Tests to help diagnose Crohn's disease:

• Blood tests (i.e., complete blood count) looking for changes in the levels of red or white blood cells, and other markers of inflammation, such as a C-reactive protein (CRP).
• A serum vitamin B12 test, iron test, and vitamin D test.
• Stool testing: to look for occult blood or infections. A fecal calprotectin test can help to differentiate between Crohn’s disease and IBS, and is recommended in the American College of Gastroenterology (ACG) 2018 guidelines. Fecal calprotectin serves as a noninvasive marker of intestinal inflammation.
• Genetic testing is not currently recommended to establish the diagnosis of Crohn’s disease.

Procedures used to diagnose Crohn’s disease:

• Colonoscopy or flexible sigmoidoscopy: Your doctor inserts a thin lighted tube with camera into your colon. A tissue sample (biopsy) may be collected to look for inflammatory cells.
• Capsule endoscopy: You swallow a capsule with a camera inside, and pictures of your intestine are collected, which can be downloaded to a computer which can be viewed for signs of Crohn’s disease. The small capsule and camera is eliminated painlessly in your stool, and no x-ray radiation is involved. You still may need an endoscope to confirm the diagnosis.
• Balloon-assisted enteroscopy: A lighted tube that goes farther into the  small bowel where standard endoscopes don't reach. This technique may be used when the capsule endoscopy shows abnormalities, but the diagnosis is still undetermined.
• Computerized tomography (CT scan): A specialized x-ray that allows detailed visualization of your bowel and surrounding tissues.
• Magnetic resonance imaging (MRI): A special type of imaging technique that uses a magnetic field and radio waves to create detailed images of organs and tissues.

Treatment Options for Crohn’s Disease

The goals of treatment for Crohn’s disease are to treat the acute inflammation, quiet the symptoms (induce clinical remission), and to maintain remission over the long-term. Treatment should ultimately be determined by the recommendations of the healthcare provider and the informed preferences of the patient, considering recent guidelines. Treatment should be tailored to the individual.

Not all patients with Crohn’s disease need ongoing, prescription medications. For those with a low risk of disease progression and positive response with an anti-diarrheal such as loperamide (Imodium A-D) and dietary changes, careful observation for disease progression is acceptable.

For patients who do need medication treatment, improvement in symptoms should be seen in 2 to 4 weeks, with full improvement in 12 to 16 weeks. If symptoms continue, drug dose adjustments, alternative treatments, or step-up therapy for more severe disease should be considered. In many patients, surgery may be needed, but is not curative.

There are five main categories of medications used to treat Crohn’s disease. Treatment will depend upon the severity of the disease, where in the bowel it is located, whether you are considered high or low risk, and prior medications or surgeries.

Drug Therapy Used in Crohn’s Disease

Corticosteroids
Generic Name	Brand Name Examples
budesonide (controlled ileal release)	Entocort EC, Uceris
prednisone	Rayos
prednisolone	Prelone, Orapred ODT
methylprednisolone	Medrol, Medrol Dosepak

Oral corticosteroids can be used as initial anti-inflammatory therapy for patients with mild Crohn’s disease of the ileum and/or proximal colon; oral or intravenous (IV) forms may be used to treat moderate-to-severe and higher risk Crohn's disease. They are used to ease flares of disease activity, and often as a bridge to allow enough time for immunomodulators and/or biologics to take effect.

• These medications lower inflammation and provide short-term control of flare-ups; they do not consistently provide a healing effect. They should be used sparingly, with introduction of steroid-sparing agents as soon as possible.
• They are not recommended for long-term or maintenance use because of their side effects, which can include infection, osteoporosis, bone loss, insomnia, increased appetite, weight gain, high blood pressure, blood glucose changes, acne, glaucoma, skin fragility, insomnia, and mood changes.
• Oral prednisone doses (or equivalent doses) typically should not exceed 60 mg per day.
• Controlled ileal release (CIR) budesonide (9 mg once daily) is effective in inducing remission in ileal and ileocecal Crohn’s disease and is often recommended as a first-line drug in patients with mild-to-moderate active Crohn's disease of the ileum and proximal (right) colon. CIR budesonide has a pH dependent release with high local activity and limited systemic bioavailability of 10% to 20%. Maintenance use is typically limited to 3 months.

Aminosalicylates (5-ASAs)
Generic Name	Brand Name Examples
mesalamine (off-label use)	Apriso, Asacol HD, Delzicol, Lialda, Pentasa
sulfasalazine	Azulfidine, Azulfidine EN-tabs, Sulfazine

The 5-aminosalicylates (5-ASAs) are anti-inflammatory agents that help to control mild-to-moderate, low risk Crohn’s disease. Some forms of the drug are taken by mouth; others must be given rectally by enema or suppository.

• According to 2018 ACG guidelines, sulfasalazine (3 to 6 grams daily) is effective for treating symptoms (but not for healing) of mild-to-moderate active colonic or ileocolonic Crohn's disease, but not in isolated small bowel disease.
• Oral mesalamine should not be used to treat patients with active Crohn's disease due to inconsistent effectiveness for inducing remission or intestinal healing. These drugs remain widely prescribed for Crohn's disease, despite their lack of effectiveness.
• Topical mesalamine (5-ASA suppository and enema preparations) in Crohn's disease is of limited benefit.

Immunomodulators/Thiopurines
Generic Name	Brand Name Examples
azathioprine	Azasan, Imuran
mercaptopurine	Purixan, Purinethol
methotrexate	Trexall, Rheumatrex Dose Pack

Thiopurines like azathioprine or mercaptopurine alter the activity of the immune system to reduce inflammation and can help reduce the need for corticosteroids. They are widely used in the treatment of inflammatory bowel disease for maintenance of remission. Azathioprine is a prodrug of mercaptopurine. Immunomodulators have a relatively slow onset of action (8 to 12 weeks) and do not have a place for short-term induction in active disease.

• These drugs might be used in combination with biologics in patients with moderate-to severe active Crohn’s disease to maintain remission and at lower doses to reduce immunogenicity against biologic therapy.
• Typically these drugs are discontinued after a period of time and long-term maintenance with a biologic is continued.
• In certain circumstances where biologics like anti-TNF drugs cannot be used, they might be used alone for long-term remission.
• Test patients for thiopurine methyltransferase (TPMT) activity before starting treatment with azathioprine or mercaptopurine due to a risk for severe, potentially life-threatening bone marrow toxicity in patients with a deficiency of TPMT.
• Once weekly methotrexate may be considered for symptom relief in patients with steroid-dependent Crohn's disease to maintain remission. Methotrexate is teratogenic, and fetal death can occur when administered to a pregnant woman. See methotrexate warnings for pregnancy.
• Common side effects with these drugs may include: allergic reactions, pancreatitis, nausea, infection, liver toxicity, non-melanoma skin cancer, and lymphoma.

Biologics Used for Crohn's Disease
Generic Name	Brand Name Examples
adalimumab	Humira
adalimumab-adaz (biosimilar to Humira)	Hyrimoz
adalimumab-atto (biosimilar to Humira)	Amjevita
adalimumab-adbm (biosimilar to Humira)	Cyltezo
adalimumab-bwwd (biosimilar to Humira)	Hadlima
certolizumab pegol	Cimzia
infliximab	Remicade
infliximab-dyyb (biosimilar to Remicade)	Inflectra
infliximab-abda (biosimilar to Remicade)	Renflexis
infliximab-qbtx (biosimilar to Remicade)	Ixifi
natalizumab	Tysabri
ustekinumab	Stelara
vedolizumab	Entyvio

Biologic therapy is used to treat patients with moderate-to-severe Crohn's disease or disease that does not respond to most other types of medications, including immunomodulators and corticosteroids. These drugs help block various immune system chemicals that promote inflammation.

Biologic therapy is used to reduce symptoms and induce and maintain remission in Crohn’s disease, and for mucosal healing. Biologics may also help reduce the need for long-term steroid treatment to control symptoms; they may also be used in combination with immunomodulators to help prevent anti-drug antibody formation which can lower effectiveness of the biologic. Combined therapy with an immunomodulator is recommended when possible. The combination of infliximab plus a thiopurine has been shown to be more effective than either treatment alone.

Biologic monoclonal antibodies used in the treatment of Crohn’s disease include:

• Tumor necrosis factor-alpha (TNF) blockers: TNF inhibitors (anti-TNF agents) suppress the immune system by blocking the activity of tumor necrosis factor (TNF), a substance in the body that can cause inflammation. TNF inhibitors include: adalimumab (Humira) and biosimilars, certolizumab pegol (Cimzia), and infliximab (Remicade) and biosimilars. Clinical effect can be rapid, often within 2 weeks. Response rates are higher if given early in disease (typically in the first 2 years). Infliximab is indicated for fistulizing Crohn's disease. Side effects with TNF blockers may include: infections, reactivation of latent tuberculosis, and risk of lymphoma.
• Anti-integrin therapy: Includes natalizumab (Tysabri) and vedolizumab (Entyvio) which block the action of integrin on cells in the immune system to lower inflammation. These agents are used with or without an immunomodulator. The clinical use of natalizumab is limited due to the risk of serious and fatal progressive multifocal leukoencephalopathy (PML) caused by JC virus. Vedolizumab, with or without immunomodulator, is effective for induction, remission, and mucosal healing. Side effects with anti-integrin therapy may include: nasopharyngitis (cold), joint pain, headache, nausea.
• Anti-IL12/23 therapy: Ustekinumab (Stelara) targets interleukin (IL)-12 and IL-23 cytokines, which play a key role in inflammatory and immune responses. Ustekinumab is used to induce and maintain response in those who fail most therapies, including anti-TNF agents; however it can be used in patients who have never used anti-TNF agents but not had an adequate response with corticosteroids or immunomodulators. Common side effects include: vomiting, common cold, injection site reactions, yeast infection, bronchitis, itching, urinary tract infection, and sinusitis.

Broad spectrum antibiotics may also be prescribed for abscesses or fistulas that can occur with Crohn’s disease. In the past, antibiotics were used for the treatment of Crohn's disease symptoms, but that is no longer recommended.

Surgery for Crohn’s Disease

In some patients with Crohn’s disease, medications may not be adequate to control their symptoms and they may eventually need surgery. According to the Crohn's and Colitis Foundation of America, up to 75% of patients with Crohn's disease will require surgery. However, unlike ulcerative colitis, surgery for Crohn’s is not curative, except in some instances where only the colon, rectum, and anus are affected. Most people need to continue drug treatment to control symptoms over the long-term. According to the ACG 2018 guidelines, Crohn's disease can reoccur after surgery in up to 50% of people.

The main goals of surgery for Crohn’s disease are to conserve as much bowel as possible, help treat or avoid complications, and to boost the quality of life for the patient.

The most frequently performed surgeries for Crohn’s disease are:

• Resection and Anastomosis: This surgery involves removal of part of the intestine (resection) and rejoining the two healthy ends after the diseased portion is removed (anastomosis). Partial colectomy is an example of this surgery. With an anastomosis, bowel movements are usually not affected and can still occur through the anus.
• Ostomy: If the two ends of the intestine cannot be reconnected, the surgeon will create an ostomy (ileostomy or colostomy), where the intestine is connected to an opening in the abdomen. For most people, the ostomy can be reversed in a few months, but some people require a permanent ostomy. You will attach a plastic bag to the ostomy opening and your bowel movements will empty here. You can empty the waste from the bag as needed. An ostomy nurse will teach you how to care for your skin and how to empty the ostomy bag. Most people can lead a normal life once they are trained and receive support on the care for their ostomy.
• Strictureplasty: Ongoing inflammation can cause the intestinal walls to thicken or form scar tissue, which may lead to an intestinal blockage called a stricture. This procedure opens strictures that may occur, and may be done during other surgeries, like a resection. Several strictures may be treated in one surgery. Nausea and vomiting or constipation may be signs of a stricture.

Diet and Lifestyle Changes for Crohn’s Disease

Eating a healthy amount of calories, vitamins, and protein is important to avoid malnutrition and weight loss with Crohn’s disease. Specific food problems may vary from person to person during a flare. Consulting with a dietician will help you to understand your best food choices for optimal nutrition, during a flare and when you are in remission.

Some people may find that eating several small meals a day may be better for their symptoms than 2 or 3 large meals. Be sure to drink plenty of fluids. Drinking 8 to 10 eight ounce cups of fluids daily, such as water, broth, tomato juice, and diluted sports drinks.

Certain foods may worsen symptoms like cramping, bloating and diarrhea. You may need to limit some foods with a more severe flare or if you have a stricture.

Examples of foods you may need to avoid include:

• Raw fruits and vegetables, whole nuts, whole grains, and other insoluble fiber foods may need to be eliminated temporarily.
• Lactose (milk sugar) found in dairy products.
• Non-absorbable sugar alcohols (sorbitol, mannitol) that may be found in candy, chewing gum, ice cream or some juices
• Foods high in sugar like pastry or juices
• Foods high in fat
• Alcohol or caffeine
• Spicy food

Regular exercise is always important, including for patients with Crohn’s disease. Consult with your doctor about appropriate exercises, especially if you’ve had recent intestinal surgery.

Smoking is dangerous for everyone. But if you smoke and have Crohn’s disease, it is especially  important that you quit. Smoking can worsen your symptoms, and may increase your chances for surgery or complications. Speak to your healthcare provider about a successful smoking cessation plan that you can start.

Crohn’s disease can increase your risk for colon cancer. Talk to your doctor about appropriate intervals for colon cancer screening, such as a colonoscopy, based on your risk profile and family history.

NSAID use in Crohn's disease

Avoid the use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil, Motrin) or naproxen (Aleve) which can worsen Crohn’s disease. These drugs are commonly used to treat pain or headaches. Some NSAIDs are available without a prescription but others may be prescribed. According to 2018 AGC guidelines, studies have shown that the selective COX-2 inhibitor NSAIDs such as celecoxib (Celebrex) do not exacerbate ulcerative colitis, but studies in Crohn's disease are not available.

Examples of common NSAIDs include:

• ibuprofen (Advil, Motrin)
• naproxen (Aleve)
• diclofenac (Voltaren, Cambia, Cataflam)

Call your doctor if:

• You have symptoms of Crohn's disease.
• You have already been diagnosed with Crohn's disease and your symptoms have worsened or have not improved with treatment.
• You have already been diagnosed with Crohn's disease and you develop new symptoms.