Chron's disease is a type of inflammatory bowel disease (IBD). It is a chronic disease that causes inflammation of the gastrointestinal (GI) tract. The disease is characterized by alternating periods of flare-ups (active disease) and remissions (few or no symptoms). The disease may affect any part of the GI tract from the mouth to the anus, however it most commonly affects the last part of the small intestine (ileum) or the large intestine (colon). Chron’s disease is classified into subtypes according to the affected part of the GI tract. The subtypes are ileocolitis, ileitis, gastroduodenal Chron's disease, jejunoileitis and Crohn's (granulomatous) Colitis.

Chron’s is an idiopathic disease with an unknown cause. Scientists believe a complex interaction between genetic factors, an abnormal immune response, microbial, and environmental factors may lead to Chron’s disease.

The risk factors that may influence susceptibility to Chron’s disease include genetic factors such as family history of Chron’s, environmental factors such as living in urban areas, a microbial imbalance between the harmful and helpful bacteria in the gut and a dysfunction in the immune system causes it to attack the cells in the intestine.

Chron’s disease arises when defects in the epithelial barrier of the intestinal cells cause the cells of the immune system to infiltrate an area around the crypt cells (cells in the intestine). These immune cells produce chemicals called cytokines which cause inflammation and recruit other kinds of immune cells that also release substances damaging to the lining of the intestine. This leads to ulceration of superficial mucosa (the lining of the intestine). Later the immune cells keep moving deeper into the deep mucosal layers lining the intestine, spreading inflammation.

Symptoms of Chron’s may range from mild to severe. Typical symptoms include diarrhea, abdominal pain and fever. Patients with severe disease usually display symptoms outside the GI tract such as pain in the joints or inflammation of eyes and skin.

In order to diagnose Chron’s disease, the doctor performs a physical exam to examine the patient’s abdomen and uses laboratory studies in addition to imaging studies to confirm a diagnosis of Chron’s. Laboratory studies that may be used include blood and stool tests to check for anemia and rule out infections. Imaging studies commonly used include abdominal CT or magnetic resonance (MR) enterography.

Chron’s disease does not have a cure. The goals of treatment are to decrease the inflammation in the GI tract, prevent flare ups and extend the time spent in remission. Lifestyle changes and medication are treatment options for Chron’s disease. The different medications used to treat Chron’s disease include aminosalicylates, corticosteroids (steroids), immunomodulators and biologics. Sometimes, surgery may be necessary to treat complications.  

Complications caused by Chron’s disease may affect the intestines or other parts of the body. The complications include osteoporosis, anemia, malnutrition, strictures, fistulas, ulcers and an increased risk for colorectal cancer.

Since the exact cause of Chron’s disease is unknown, prevention is not possible. For patients with Chron’s, prevention involves reducing the severity of the symptoms and extending the amount of time in remission. This is obtained through lifestyle changes in combination with the treatment. These changes include quitting smoking, avoiding alcohol, learning how to manage stress, eating smaller, more frequent meals and avoiding foods that are spicy or high in fiber.

If the disease is managed properly, patient’s with Chron’s are able to have a reasonable quality of life. The majority of people with Chron’s disease enjoy normal life spans.

North America and Europe have the highest incidence rates of Chron’s disease. An article in the World Journal of Gastroenterology, an American publication, reported worldwide rates of Chron’s disease to be between 0.1-16 per 100,000 people.

Chron's disease is a chronic, idiopathic (unknown cause) disease that causes inflammation of the gastrointestinal (GI) tract. It is one of the most common types of inflammatory bowel disease (IBD). The disease may affect any part of the GI tract from the mouth to the anus, however it most commonly affects the last part of the small intestine (ileum) or the large intestine (colon).  The disease is characterized by alternating periods of flare-ups (active disease) and remissions (few or no symptoms).

Chron’s disease is classified into subtypes depending on the area of the GI tract affected

Ileocolitis

It affects the ileum (end of the small intestine) and the large intestine (colon). This is the most common type of Chron’s disease

Ileitis

In this type, only the ileum is affected

Gastroduodenal Chron’s disease

In this type, the stomach and the beginning of the small intestine (duodenum) are affected

Jejunoileitis

In this type, intermittent areas of inflammation appear in the upper half of the small intestine (the jejunum)

Crohn's (granulomatous) colitis

In this type, only the colon is affected

The exact cause of Chron’s disease has yet to be identified. Researchers believe it may be result of a complex interaction between genetic factors, an abnormal immune response, microbial, and environmental factors

The risk factors that may influence susceptibility to Chron’s disease include:

Age

Crohn's is more common between the ages of 15 and 35 years

Genetics

Developments in genetic testing have allowed researchers to identify several genes that may be associated with an increased risk of irritable bowel syndrome. A family history of irritable bowel syndrome also increases the risk of developing Chron’s disease 9. Caucasians and Jewish people displayed an increased risk of Chron’s disease

Environmental factors

Environmental risk factors including dietary habits, use of medication, stress, smoking and geographic location are examples of environmental risk factors that may increase the possibility of Chron’s disease.

•      Former and active smokers are both at a higher risk of developing Chron’s disease, with the latter being at a higher risk.

•      Low vitamin D is a possible risk factor for Chron’s disease

•      Using high doses of NSAIDs frequently and for an extended period of time is linked to an increased risk of Chron’s disease

•      The use of antibiotics may increase the risk due to their effect on the microorganisms normally living inside the body .

•      High levels of stress increase the risk

•      Air pollution may contribute to the risk of Chron’s disease  

•      Using oral contraceptive pills may cause a marginally increased risk, particularly with prolonged use. Further research is needed to confirm the risk .

•      Living in an urban area increases the risk of developing Chron’s disease .

•      Family Size and Birth

o     Living in a small household and being born last increase the risk of Chron’s disease

•      High sugar intake in the diet

•      Perinatal infections (a period of time from the 20th week of pregnancy to the 28th day of newborn life) in mother or child increase the risk of Chron’s disease .

Microbial

Researchers believe that a microbial imbalance (dysbiosis) between the harmful and helpful bacteria in the gut is associated with the development of Chron’s diseas . This hypothesis is strengthened by observations of decreased diversity and stability of the gut flora of patients with Chron’s disease .

Several factors may contribute to causing this imbalance, thus increasing the risk of developing Chron’s disease such as acute gastroenteritis which may be caused by Salmonella and Campylobacter, and exposure to certain bacteria like Listeria monocytogenes and Yersinia enterocolitica .

Immunological factors

A dysfunction in the immune system causes it to attack the intestinal cells, causing symptoms of Chron’s disease to appear.

Several risk factors lead to defects in the epithelial barrier of the intestinal cells, insufficiencies in autophagy (destruction of cells), deficiencies in innate pattern recognition receptors, and problems with lymphocyte differentiation (specialization of lymphocytes, which are immune cells) .

Innate pattern recognition receptors belong to the innate immune system. They are proteins expressed by the cells of the innate immune system to identify microbial pathogens or cells that are damaged or dead.

Microscopically, the initial damage starts because of infiltration of immune system cells in a limited area around the intestinal crypt cells. These immune cells release substances called cytokines which cause inflammation and recruit other kinds of immune cells that also release inflammatory substances that damage the lining of the intestine. This leads to ulceration of superficial mucosa (the most superficial inner lining of the intestine).Later the immune cells keep moving deeper into the deep mucosal layers lining the intestine, spreading inflammation.  As they move deeper, the immune cells begin to organize into non-necrotizing granulomas (cluster of immune cells). A non-necrotizing granuloma is an area of inflammation where the tissue is not dead15. The granulomas spread through all the layers of the intestinal wall and into the mesentery (a membrane that attaches the intestine to the abdominal wall) and the regional lymph nodes.

The neutrophils (another type of immune cells) move into the intestinal crypt cells, forming crypt abscesses (lesions in the crypt cells) which causes destruction of these cells and wasting of the colon.

These microsocopic changes in the intestinal mucosa appear as hyperemia (an excess of blood in the vessels) and edema (swelling) of the affected mucosa. Later detached superficial ulcers form over lymphoid aggregates (a cluster of immune cells). They may be visualized as red spots or depressions in the mucosa. These ulcers may become deep and serpiginous (having a wavy margin), causing the mucose to appear like cobblestone. The lesions (ulcerations) are usually segmental, with healthy areas in between the ulcerated areas, giving them the name skip lesions.

The transmural inflammation (spans the entire depth of the intestinal wall) characteristic of Chron’s disease causes the wall of the intestine to thicken, leading to a narrowing of the lumen (the inside space of the intestine). Progression of the disease causes obstruction (blockage) or deep ulceration. This results in fistulization (the creation of an abnormal passage), adhesions (scar tissue that joins 2 parts of tissue that are not normally tied together), formation of abscesses (collections of pus), microperforation (small holes), and malabsorption (intestine is unable to absorb enough nutrients and fluids).

Bowel obstruction (blockage of the intestine) results from the swelling (edema) of the mucosa. Initially, the obstruction is irregular and may be resolved. As the disease progresses the obstruction becomes chronic as a result of narrowing of the lumen, the formation of strictures (narrowing of a section of the intestine) and fibrosis (the formation of excess fibrous connective tissue as part of the healing process).

Usually patients with Chron’s disease initially display the following symptoms

•      Diarrhea

•      Fever

•      Abdominal pain.

o     Usually, the pain usually is insidious (gradual), affects the lower right quarter, and appears soon after a meal.

•      Fatigue

•      Anal fissures – small tears in the lining of the anus which results in pain during bowel movements.

•      Inflamed and sore mouth

•      Unintended weight loss

Other symptoms could include

•      Less commonly, blood in the stool

•      Inflammation of eyes and skin

•      Inflammation of the bile ducts or liver.

•      Arthritis (pain and swelling in the joints)

Chron’s disease may be mild or severe. The smaller the number of bowel motions, the milder the disease.

Characteristics of mild Crohn's disease include:

•      Patient may not complain of abdominal pain or the pain may be mild.

•      Complications outside the GI tract are minimal, or even absent. 

•      When examining the abdomen, the doctor does not detect any mass.

•      The patient does not have fistulas, abscesses, or other chronic complications.

•      The patient’s sense of comfort and health are normal or close to normal

•      The patient is not underweight

•      The patient’s red blood cell count is normal or nearly normal.

Characteristics of severe Crohn's disease include21 :

•      Bowel movements are very frequent, requiring strong anti-diarrheal medication to control them.

•      The abdominal pain is severe.

•      The patient’s red blood cell count is low

•      The patient experiences complications outside the GI tract (joint pain) or chronic complications (fistulas)

•      The patient’s has a poor sense of comfort and health.

The doctor usually performs a physical exam and then uses a combination of laboratory studies and imaging tests to confirm the diagnosis of Chron’s disease.

Physical exam

The doctor checks for abdominal bloating, signs of an enlarged liver or spleen and listens to sounds within the abdomen.

Imaging tests

•      Colonoscopy

o     A colonoscopy is used to look inside the rectum and colon. During the colonoscopy a biopsy may be taken. This test is helpful for determining the presence of granulomas, which aid in confirming the diagnosis of Crohn's.

•      Upper GI x-ray

o     The patient uses an orally ingested contrast material such as barium that allows the intestines to appear on x-rays. This test enables the doctor to identify the presence of any ulcerations or fistulas. The deep ulcerations in the mucosa of the intestine gives it a cobblestone appearance on the x-ray.

•      Video capsule enteroscopy

o     The patient swallows a capsule that contains a camera. The camera captures photos of the small intestine. The test may show the presence of any superficial ulcers.

•      Abdominal CT, CT enterography or magnetic resonance (MR) enterography

o     These imaging tests enable detailed visualization of the intestines. They are used to identify the presence of obstruction, fistulas, strictures, abscesses or the separation of bowel loops as a result of edema.

•      Upper GI endoscopy

o     This test allows the doctor to look at the upper part of the GI tract.

•      Balloon-assisted enteroscopy or other types of enteroscopy.

o     In an enteroscopy, a long endoscope is used to examine the small intestine. In a balloon-assisted enteroscopy, small balloons assist the movement of the endoscope into the intestine.

Lab Tests

Lab tests used to aid in the diagnosis of Chron’s disease include blood tests, liver function tests and stool tests.

A blood sample will be collected from the patient and used to check for signs of inflammation or infection, anemia, low albumin (a protein in the blood), electrolyte abnormalities, and certain markers (specific antibodies) that are commonly associated with Chron’s disease .

The stool test is usually used to rule out other possible causes of gastrointestinal disease, particularly infections and can be tested for the presence of blood.

A cure for Chron’s disease has yet to be found. Treatment of Chron’s disease aims at reducing the inflammation in the GI tract, preventing flare ups (periods where the symptoms are active) and extending the time spent in remission. Treatment is comprised of managing diet and nutrition, using medication to alleviate the symptoms and prevent flare-ups and surgery in case the patient stops responding to medication and lifestyle changes.

Medications

Drug therapy in Chron’s disease aims to alleviate the symptoms and bring about remission in patients with active disease and maintain remission by preventing flare-ups. The severity of disease determines the type of medication prescribed. The different medications used to treat Chron’s disease include:

Aminosalicylates, are medication that help regulate inflammation. This class of medication is used to treat newly diagnosed patients and people with mild symptoms. Examples of aminosalicylates used include:

•      Olsalazine

•      Balsalazide

•      Sulfasalazine

•      Mesalamine

Corticosteroids (steroids) are medication that help reduce immune system activity, leading to a reduction in inflammation. They may be prescribed for patients who display moderate or severe symptoms. These drugs are generally used short-term to induce remission, not during long term maintenance therapy due to their severe side effects.

Examples of corticosteroids used include:

•      Methylprednisone

•      Budesonide

•      Prednisone

•      Hydrocortisone

Immunomodulators are medication that help decrease the activity of the immune system, which results in a decrease in inflammation. These medications may be prescribed for patients who do not respond to other treatments. They may be used to help induce remission and as part of long term maintenance therapy. Examples of immunomodulators used include:

•      6-mercaptopurine, or 6-MP

•      Azathioprine

•      Methotrexate

Biologics are medication that target tumor necrosis factor (TNF), a protein created by the immune system. These medication nullify TNF, reducing inflammation in the GI tract. They are used in the treatment of moderate to severe drugs to quickly cause remission, particularly if the patient isn’t responding to other medications.

Examples of biologics used include:

•      adalimumab  and adalimumab-atto

•      infliximab and infliximab-dyyb

•      certolizumab

•      vedolizumab

•      natalizumab

•      ustekinumab

Other medication used to treat patients with Chron’s disease could include:

•      Acetaminophen – to treat mild pain. Chron’s disease patients should try not to use ibuprofen, naproxen, and aspirin since these medications can aggravate their symptoms.

•      Antibiotics - such as ciprofloxacin or metronidazole, may be used to treat abscesses and fistulas.

•      Loperamide – helps reduce or stop diarrhea. Only given over short periods of time.

Nutrition

Bowel rest

For some patients that may be suffering from severe symptoms of Chron’s disease, the doctor may recommend bowel rest. Bowel rest involves not eating or drinking anything or drinking only specific liquids for a period of time ranging from a few days to several weeks. During that time period the patient may be given nutrients intravenously, or through a feeding tube inserted into the stomach or intestines.

Diet

Patients with Chron’s disease frequently suffer from malabsorption which could cause malnutrition. Ensuring adequate nutritional intake to reverse malnutrition is important, particularly in children. Some patients report that certain foods worsen their symptoms, despite the absence of scientific evidence linking diet to Crohn's disease. Dietary suggestions given to patients of Chron’s disease as part of their treatment includes:

•      Avoiding carbonated drinks

•      Avoiding high-fiber foods (vegetable skins, popcorn, nuts, etc)

•      Increasing liquid intake

•      Eating small, frequent meals.

•      Using a food diary to identify foods that affect the patient's symptoms

•      Some Chron’s disease  patients become lactose intolerant and should avoid high lactose foods

•      Avoiding spicy foods.

•      Avoid fried foods and those high in fat

•      Avoid or limit alcohol and caffeine consumption.

Surgery

Despite medication, most Chron’s disease  patients will eventually need surgery. Surgery will not cure Chron’s disease  but it can treat complications like obstructions and may alleviate the symptoms.

Surgery is recommended in the following cases:

•      If a patient has obstructions in the intestine

•      If a patient has perforations (tears)

•      life threatening bleeding

•      side effects from medicines when they threaten your health

•      The patient is not responding to other forms of treatment

•      If a patient has fistulas (abnormal passageway that links two organs or vessels that are not normally connected)

Different surgical procedures may be used to treat Chron’s disease , depending on the severity of the disease or the location of the diseased intestinal segment:

Strictureplasty

Strictureplasty is used to open up strictures, parts of the intestine that have narrowed. 

Small bowel resection

This surgery is used in patients with intestinal obstruction or severe Crohn’s disease. The surgeon removes the affected section of the small intestine.

Proctocolectomy or Colectomy

A proctocolectomy (removal of the colon and rectum) or colectomy (removal of the large intestine (colon)) are performed in patients with severe Crohn’s disease. After the proctocolectomy the surgeon creates an opening in the abdomen from part of the ileum (ileostomy). That opening is connected to a removable external collection pouch. Contents of the intestine empty through the stoma into external collection pouch instead of passing through the anus. The ileostomy is permanent.

Other surgical procedures

To repair fistulas that do not respond to medication and to drain abscesses.

Complications caused by Chron’s disease include:

•      Intestinal strictures

    A stricture is the narrowing of a section of the intestine due to accumulation of scar tissue caused by inflammation.

•      Abscess formation

    Occur anywhere in the GI tract but particularly around the anus. An abscess is a swelling filled with pus.

•      Fistulas

    A fistula is an abnormal passageway between an organ and the skin or between two organs. Large fistulas could get infected and cause other problems

•      Anal fissures

    Anal fissures are small tears in the anus. These tears could cause bleeding, itching or pain.

•      Ulcers

    Ulcers or open sores may appear in the mouth, perineum (the area between the anus and the scrotum or vulva), anus or intestines.

•      Malnutrition

    The intestines are unable to absorb enough nutrients due to cell death, which eventually leads to malnutrition as the body does not get enough nutrients to meet its needs.

•      Inflammation in other parts of the body .

    Inflammation may affect the eyes, joints, and skin.

•      Toxic megacolon

•      If the inflammation affects the deep layers of the large intestine (colon), it swells and stops working. This complication may be life-threatening in severe cases where the colon is at risk of rupturing and could requiring immediate surgery.

•      Colorectal cancer

•      Patients with Chron’s disease have an increased risk of colorectal cancer .

•      Osteoporosis

•      Chron’s disease and some medication used to treat it such as corticosteroids may cause osteopenia or osteoporosis.

•      Impaired growth and development in children

    Children may suffer from impaired growth and delayed puberty.

•      Anemia

    Anemia may result because of internal bleeding from the ulcers in the intestine combined with the malabsorption resulting from the disease.

•      Liver and gallbladder problems

    Chron’s disease patients have a higher risk of developing gallstones and mild liver problems.

•      Blood clots

    Chron’s disease patients have a higher risk of g blood clot formation, especially in their legs.

•      Kidney and urinary tract problems

    Chron’s disease patients are more likely to get kidney stones. Infections in the urinary tract are also common. Patients may also suffer from a rare condition called amyloidosis where amyloid (a protein) accumulates in the kidney.

•      Emotional problems

    Patients may become afraid to eat because of the resulting abdominal pain. Frequent diarrhea could result in the patient feeling humiliated which could cause low self-esteem and may drive the patients to isolate themselves from society.

Since Chron’s disease is an idiopathic disease (no known cause), prevention is not possible. In Chron’s disease patients, prevention involves reducing the severity of the symptoms and extending the amount of time in remission. This can be achieved through lifestyle changes in combination with the treatment. These changes include:

•      Stop smoking

    Chron’s disease patients who smoke may experience more severe symptoms and more complications, they are more likely to need surgery and are also more likely to require higher doses of medication to treat their disease.

•      Avoid alcohol

    Alcohol may increase cramping and diarrhea.

•      Learn how to manage stress

    Such as exercise and breathing techniques. Stress may cause flare-ups and worsen the severity of the symptoms.

•      Dietary management

    Keeping a food diary to record which foods, if any, may cause flare-ups or worsen the symptoms.

    Eat small, frequent meals.

    Avoid spicy foods, foods high in fiber (such as raw vegetables, wholegrains), fried foods and those high in fat since they may increase diarrhea and cramping.

Appropriate management of Chron’s disease could allow the patient to enjoy a reasonable quality of life. The disease is rarely a direct cause of death, and the majority of patients enjoy a normal lifespan.

Incidence rates of Chron’s disease are highest in Europe and North America while Africa, South America and Asia report lower incidence rates. The disease appears more frequently in developed countries. An article in the World Journal of Gastroenterology, an American publication, reported worldwide rates of Chron’s disease to be between 0.1-16 per 100,000 people.