Crohn's disease

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) that may affect any part of the gastrointestinal tract (Pic. 1) from mouth (Pic. 2) to anus. It is classically characterized by skip lesions in which there are discrete areas of diseased bowel separated by normal bowel and typically it spares the rectum. 

Approximately 50% of patients have their disease involving the terminal ileum and colon (Pic. 3), 30% have isolated small bowel disease, 20% have isolated colonic disease (Pic. 4), and up to 25% will also have perianal complications.

Although Crohn’s disease is a global health problem, its pathology remains poorly understood. Nevertheless, it has been established that its etiology is associated with complex interactions between environmental, immune, microbial, and genetic factors, though a number of authors have suggested that the primary defect in Crohn’s disease is one of relative immunodeficiency (full or partial impairment of the immune system).

Crohn’s disease can present in many different ways often based on the underlying disease phenotype (observable characteristic or trait).   

The three classic types of Crohn’s disease include:

• Inflammatory disease (or nonstricturing, nonpenetrating disease) causes inflammation without causing strictures or fistulae.
• Stricturing disease causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces.
• Penetrating (fistulizing) disease creates abnormal passageways (fistulae) between the bowel and other structures, such as the skin.

Signs and symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, and weight loss.

Standard clinical testing to diagnose CD includes blood tests and stool examination for biomarker quantification, endoscopy and biopsy. The diagnosis of inflammatory bowel disease, particularly Crohn’s disease, can be missed or delayed due to the non-specific nature of both intestinal and extra-intestinal symptoms at presentation.

Natural history of disease varies between remission and flares. The mainstay of therapy is pharmacologic management of disease. However, surgery will be necessary in up to 80% of individuals with 50% undergoing a surgery within 10 years from their diagnosis, unlike the surgical management of Crohn’s disease is not curative. Therefore, the types of surgery are dictated by the presenting problem (e.g., stricture or fistula) and a goal of removing the smallest amount of bowel necessary.

Symptoms

Symptoms vary though its common manifestations include persistent diarrhea, rectal bleeding, abdominal cramps, and pain, though fever, extreme fatigue, and weight loss are also common. Constipation is also a frequent symptom and can lead to bowel obstruction and, thus, increase the risk of bowel cancer. Complications involving other than the gastrointestinal (GI) tract include anemia (low oxygen supply), arthritis (joint pain or joint disease), liver disease, eye inflammation, and skin rashes.

Associated diseases

Inflammatory bowel disease

Inflammatory bowel disease (IBD) may be categorized clinically as Crohn’s disease or ulcerative colitis (Pic. 5). The two diseases are both inflammatory conditions but present very differently and involve different parts of the gastrointestinal tract. IBD is an inflammatory disease that is characterized by continuous inflammation of the colonic mucosa (Pic. 6) that extends proximally from the rectum. Unlike with ulcerative colitis, Crohn’s isn’t limited to the GI tract. It may also affect the skin, eyes, joints, and liver. The natural history of the IBD ranges from periods of quiescent remission to flares.

Colon and rectal cancer

Crohn's disease increases the risk of cancer in the area of inflammation. 

Patients with Crohn's disease involving the colon (also known as Crohn's colitis) are at higher risk for developing colorectal cancer (Pic. 7) than the general population. Inflammation of the large intestine can cause continuous turnover of cells in the intestinal lining, causing irregularities. The increased risk of irregularities in intestinal lining may lead to cancer of colon. 

The colorectal cancer in patients with Crohn’s disease has particular characteristics that set it apart from sporadic cancer. Generally diffuse, with multiple characters, it may not be obvious macroscopic observation or involve the entire bowel wall with stricture formation, remaining silent with regard to the symptoms until an advanced stage: at this point is generally manifested by obstructive type symptoms, weight loss and presence of abdominal mass. Sometimes it can occur in association with fistulas or may occur in loops. 

The colorectal cancer in Crohn’s disease frequently affects younger patients (48 vs. 70 years) and is localized preferably in the right colon (45% vs. 20% of cases), compared with the cancers arose de novo.

Complications

The major significant complications of Crohn's disease (Pic. 8) include bowel obstruction, abscesses (collections of pus), malnutrition, pregnancy complications, free perforation and hemorrhage (bleeding), which in rare cases may be fatal.

Bowel obstruction

Obstruction typically occurs from strictures or adhesions that narrow the lumen, blocking the passage of the intestinal contents. A fistula (an abnormal connection between two hollow spaces) can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin.  

Abscesses

Abscesses are walled off concentrations of infection, which can occur in the abdomen or in the perianal area. 

Malnutrition

Individuals with Crohn's disease are at risk of malnutrition for many reasons, including decreased food intake and malabsorption (poor intestinal absorption of nutrients). The risk increases following resection of the small bowel. Such individuals may require oral supplements to increase their caloric intake, or in severe cases, total parenteral nutrition (TPN). Most people with moderate or severe Crohn's disease are referred to a dietitian for assistance in nutrition.

Pregnancy

Crohn's disease can be problematic during pregnancy, and some medications can cause adverse outcomes for the fetus or mother. Consultation with an obstetrician and gastroenterologist about Crohn's disease and all medications facilitates preventative measures. In some cases, remission occurs during pregnancy. Certain medications can also lower sperm count or otherwise adversely affect a man's fertility.

Hemorrhage

Although Crohn’s disease is often associated with mild gastrointestinal (GI) bleeding, severe GI hemorrhage is a rare complication. The site of bleeding commonly follows the distribution of disease and is best localized with angiography or endoscopy.

Risk factors

Age

Crohn's disease tends to present initially in the teens and twenties, with another peak incidence in the fifties to seventies, although the disease can occur at any age. 

Genetic risk

About half of the overall risk is related to genetics with more than 70 genes found to be involved. 

Smoking

Tobacco smokers are twice as likely to develop Crohn’s disease as nonsmokers. It also often begins after gastroenteritis (inflammation of the gastrointestinal tract).

Prevention

Crohn's disease cannot be prevented; nevertheless, patient can take steps to reduce the severity of the disease, such as avoiding bulky grains, hot spices, alcohol, smoking and milk products which may increase diarrhea and cramping.

Female fertility

In active phase, women may have problems getting pregnant if they are underweight and eating poorly. Additionally, severe inflammation in the small intestine can affect normal function of ovaries, thus affecting fertility. Some research studies have found that women with active Crohn’s may have lower levels of a hormone associated with “ovarian reserve” (egg cells capable of being fertilized), especially if they are over 30. Inflammatory bowel disease can also cause adhesions (bands of scar tissue) that affect the fallopian tubes. However, women should have no more difficulty becoming pregnant than those without a Crohn’s disease in remission phase.

Male fertility

In general, male fertility is not affected by Crohn’s disease. However, 70%-90% of CD patients will need a surgical intervention at some point in the course of their disease. As the consequence of surgery, sexual dysfunction may occur. Sexual dysfunction is one of the etiologies of male infertility, and it includes erectile dysfunction (inability to get or keep an erection) and ejaculatory dysfunction (variety of ejaculatory disorders) such as retrograde ejaculation (entry of semen into the bladder instead of going out through the urethra during ejaculation) and anejaculation (no ejaculation). Certain medications can also lower sperm count and cause abnormal sperm anatomy or otherwise adversely affect a man's chance of fertilize naturally.

Crohn's disease is a chronic condition for which there is no known cure. It is characterized by periods of improvement followed by episodes when symptoms flare up. With treatment, most people achieve a healthy weight, and the mortality rate for the disease is relatively low. It can vary from being benign to very severe and people with CD could experience just one episode or have continuous symptoms. It usually reoccurs, although some people can remain disease free for years or decades.

Most people with Crohn's live a normal lifespan. However, Crohn's disease is associated with a small increase in risk of small bowel and colorectal carcinoma (bowel cancer). 

It’s best to conceive when Crohn’s symptoms are under control. Patient should be free of flares for the past 3 to 6 months and are not taking corticosteroids. Most medications to treat Crohn’s have been proven safe for pregnant women. However, some may cause birth defects.