Crohn's disease (also spelled Crohn disease) is a chronic inflammatory disease of the intestines. It primarily causes ulcerations (breaks in the lining) of the small and large intestines, but can affect the digestive system anywhere from the mouth to the anus. It is named after the physician who described the disease in 1932. It also is called granulomatous enteritis or colitis, regional enteritis, ileitis, or terminal ileitis.
Crohn's disease is related closely to another chronic inflammatory condition that involves only the colon called ulcerative colitis. Together, Crohn's disease and ulcerative colitis are frequently referred to as inflammatory bowel disease (IBD). Ulcerative colitis and Crohn's disease have no medical cure. Once the diseases begin, they tend to fluctuate between periods of inactivity (remission) and activity (relapse).
Inflammatory bowel disease affects approximately 500,000 to two million people in the United States. Men and women are affected equally. Americans of Jewish European descent are 4 to 5 times more likely to develop IBD than the general population. IBD has historically been considered predominately disease of Caucasians, but there has been an increase in reported cases in African Americans suffering from IBD.
The prevalence appears to be lower among Hispanic and Asian populations. IBD most commonly begins during adolescence and early adulthood (usually between the ages of 15 and 35). There is a small second peak of newly-diagnosed cases after age 50. The number of new cases (incidence) and number of cases (prevalence) of Crohn's disease in the United States are rising, although the reason for this is not completely understood.
Crohn's disease tends to be more common in relatives of patients with Crohn's disease. If a person has a relative with the disease, his/her risk of developing the disease is estimated to be at least 10 times that of the general population and 30 times greater if the relative with Crohn's disease is a sibling. It also is more common among relatives of patients with ulcerative colitis.
While ulcerative colitis causes inflammation only in the colon (colitis) and/or the rectum (proctitis), Crohn's disease may cause inflammation in the colon, rectum, small intestine (jejunum and ileum), and, occasionally, even the stomach, mouth, and esophagus.
The patterns of inflammation in Crohn's disease are different from ulcerative colitis. Except in the most severe cases, the inflammation of ulcerative colitis tends to involve the superficial layers of the inner lining of the bowel. The inflammation also tends to be diffuse and uniform (all of the lining in the affected segment of the intestine is inflamed).
Unlike ulcerative colitis, the inflammation of Crohn's disease is concentrated in some areas more than others, and involves layers of the bowel that are deeper than the superficial inner layers. Therefore, the affected segment(s) of bowel in Crohn's disease often is studded with deeper ulcers with normal lining between these ulcers.
Common symptoms of Crohn's disease include abdominal pain, diarrhea, and weight loss. Less common symptoms include poor appetite, fever, night sweats, rectal pain, and occasionally rectal bleeding. The symptoms of Crohn's disease are dependent on the location, the extent, and the severity of the inflammation.
The different subtypes of Crohn's disease and their symptoms are:
- Crohn's colitis is inflammation that is confined to the colon. Abdominal pain and bloody diarrhea are the common symptoms. Anal fistulae and peri-rectal abscesses also can occur.
- Crohn's enteritis refers to inflammation confined to the small intestine (the first part, called the jejunum or the second part, called the ileum). Involvement of the ileum alone is referred to as Crohn's ileitis. Abdominal pain and diarrhea are the common symptoms. Obstruction of the small intestine also can occur.
- Crohn's terminal ileitis is inflammation that affects only the very end of the small intestine (terminal ileum), the part of the small intestine closest to the colon. Abdominal pain and diarrhea are the common symptoms. Small intestinal obstruction also can occur.
- Crohn's entero-colitis and ileo-colitis are terms to describe inflammation that involve both the small intestine and the colon. Bloody diarrhea and abdominal pain are the common symptoms. Small intestinal obstruction also can occur.
- Crohn's terminal ileitis and ileo-colitis are the most common types of Crohn's disease. (Ulcerative colitis frequently involves only the rectum or rectum and sigmoid colon at the distal end of the colon. These are called ulcerative proctitis and procto-sigmoiditis, respectively.)
Up to one-third of patients with Crohn's disease may have one or more of the following conditions involving the anal area:
- Swelling of the tissue of the anal sphincter, the muscle at the end of the colon that controls defecation.
- Development of ulcers and fissures (long ulcers) within the anal sphincter. These ulcers and fissures can cause bleeding and pain with defecation.
- Development of anal fistulae (abnormal tunnels) between the anus or rectum and the skin surrounding the anus). Mucous and pus may drain from the openings of the fistulae on the skin.
- Development of peri-rectal abscesses (collections of pus in the anal and rectal area). Peri-rectal abscesses can cause fever, pain and tenderness around the anus.
The cause of Crohn's disease is unknown. Some scientists suspect that infection by certain bacteria, such as strains of mycobacterium, may be the cause of Crohn's disease. To date, however, there has been no convincing evidence that the disease is caused by infection per se. Crohn's disease is not contagious. Although diet may affect the symptoms in patients with Crohn's disease, it is unlikely that diet is responsible for the disease.
Activation of the immune system in the intestines appears to be important inIBD. The immune system is composed of immune cells and the proteins that these immune cells produce. Normally, these cells and proteins defend the body against harmful bacteria, viruses, fungi, and other foreign invaders. Activation of the immune system causes inflammation within the tissues where the activation occurs. (Inflammation is an important mechanism of defense used by the immune system.)
Normally, the immune system is activated only when the body is exposed to harmful invaders. In individuals with IBD, however, the immune system is abnormally and chronically activated in the absence of any known invader. The continued abnormal activation of the immune system results in chronic inflammation and ulceration. The susceptibility to abnormal activation of the immune system is genetically inherited.
Thus, first degree relatives (brothers, sisters, children, and parents) of people with IBD are more likely to develop these diseases. Recently a gene called NOD2 has been identified as being associated with Crohn's disease. This gene is important in determining how the body responds to some bacterial products. Individuals with mutations in this gene are more susceptible to developing Crohn's disease.
Other genes are still being discovered and studied which are important in understanding the pathogenesis of Crohn's disease including autophagy related 16-like 1 gene (ATG 16L1) and IRGM, which both contribute to macrophage defects and have been identified with the Genome-Wide Association study2.
In this regard, there have also been studies which show that in the intestines of individuals with Crohn's disease, there are higher levels of a certain type of bacterium, E. coli, which might play a role in the pathogenesis1. One postulated mechanism by which this could occur is though a genetically determined1 defect in elimination of the E. coli, by intestinal mucosal macrophages. The exact roles that these various factors play in the development of this disease remain unclear.
The symptoms and severity of Crohn's disease vary among patients. Patients with mild or no symptoms may not need treatment. Patients whose disease is in remission (where symptoms are absent) also may not need treatment.
Crohn's disease medications
There is no medication that can cure Crohn's disease. Patients with Crohn's disease typically will experience periods of relapse (worsening of inflammation) followed by periods of remission (lessening of inflammation) lasting months to years. During relapses, symptoms of abdominal pain, diarrhea, and rectal bleeding worsen. During remissions, these symptoms improve. Remissions usually occur because of treatment with medications or surgery, but occasionally they occur spontaneously without any treatment.
Since there is no cure for Crohn's disease, the goals of treatment are to 1) induce remissions, 2) maintain remissions, 3) minimize side effects of treatment, and 4) improve the quality of life. Treatment of Crohn's disease and ulcerative colitis with medications is similar though not always identical.
Medications for treating Crohn's disease include
- anti-inflammatory agents such as 5-ASA compounds and corticosteroids,
- topical antibiotics,
Selection of treatment regimens depends on disease severity, disease location, and disease-associated complications. Various guidelines recommend that approaches be sequential - initially to induce clinical remission, and then to maintain remissions. Initial evidence of improvement should be seen within 2 to 4 weeks and maximal improvement should be seen in 12 to 16 weeks.
The classic approach to therapy in Crohn's disease has been a "step-up" approach starting with the least toxic agents for mild disease, and increasingly more aggressive treatment for more severe disease, or patients who have not responded to less toxic agents. More recently the field has been moving toward a "top-down" approach (early aggressive management) which might decrease exposure to anti-inflammatory agents and increase exposure to agents that enhance mucosal healing that might prevent future complications.