Crohn's Disease

Crohn's disease, also known as granulomatous enteritis and colitis, is an inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea (which may be bloody if inflammation is at its worst), vomiting, or weight loss,[1][2][3] but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration.[1]

Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation; it is classified as a type of inflammatory bowel disease. There has been evidence of a genetic link to Crohn's disease, putting individuals with siblings afflicted with the disease at higher risk.[4] It is understood to have a large environmental component as evidenced by the higher number of cases in western industrialized nations. Males and females are equally affected. Smokers are three times more likely to develop Crohn's disease.[5] Crohn's disease affects between 400,000 and 600,000 people in North America.[6] Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000.[7] 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.[1]

There is no known pharmaceutical or surgical cure for Crohn's disease.[9] Treatment options are restricted to controlling symptoms, maintaining remission and preventing relapse.


The disease was named for American gastroenterologist Burrill Bernard Crohn, who in 1932, along with two colleagues, described a series of patients with inflammation of the terminal ileum, the area most commonly affected by the illness.[10] For this reason, the disease has also been called regional ileitis[10] or regional enteritis. The condition, however, has been independently identified by others in the literature prior, most notably in 1904 by Polish surgeon Antoni Leśniowski for whom the condition is additionally named (Leśniowski-Crohn's disease) in the Polish literature.


Crohn's disease is one type of inflammatory bowel disease (IBD). It affects the gastrointestinal tract and can be categorized by the area of the gastrointestinal tract which it affects. Ileocolic Crohn's disease, which affects both the ileum (the last part of the small intestine that connects to the large intestine) and the large intestine, accounts for fifty percent of cases. Crohn's ileitis, affecting the ileum only, accounts for thirty percent of cases, and Crohn's colitis, affecting the large intestine, accounts for the remaining twenty percent of cases and may be particularly difficult to distinguish from ulcerative colitis. Gastroduodenal Crohn's disease causes inflammation in the stomach and first part of the small intestine, called the duodenum. Jejunoileitis causes spotty patches of inflammation in the top half of the small intestine, called the jejunum (MedlinePlus 2010). The disease can attack any part of the digestive tract, from mouth to anus. However, individuals affected by the disease rarely fall outside these three classifications, being affected in other parts of the gastrointestinal tract such as the stomach and esophagus.[1]


Crohn's disease may also be categorized by the behavior of disease as it progresses. This was formalized in the Vienna classification of Crohn's disease.[11] There are three categories of disease presentation in Crohn's disease: stricturing, penetrating, and inflammatory. Stricturing disease causes narrowing of the bowel that may lead to bowel obstruction or changes in the caliber of the feces. Penetrating disease creates abnormal passageways (fistulae) between the bowel and other structures such as the skin. Inflammatory disease (or non-stricturing, non-penetrating disease) causes inflammation without causing strictures or fistulae.[11][12]


Gastrointestinal symptoms


Endoscopy image of colon showing serpiginous ulcer, a classic finding in Crohn's disease
Many people with Crohn's disease have symptoms for years prior to the diagnosis.[13] The usual onset is between 15 and 30 years of age but can occur at any age.[14] Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more vague than with ulcerative colitis. People with Crohn's disease will go through periods of flare-ups and remission. [15]


Abdominal pain may be the initial symptom of Crohn's disease. It is often accompanied by diarrhea, especially in those who have had surgery. The diarrhea may or may not be bloody. People who have had surgery or multiple surgeries often end up with short bowel syndrome of the gastrointestinal tract. The nature of the diarrhea in Crohn's disease depends on the part of the small intestine or colon that is involved. Ileitis typically results in large-volume watery feces. Colitis may result in a smaller volume of feces of higher frequency. Fecal consistency may range from solid to watery. In severe cases, an individual may have more than 20 bowel movements per day and may need to awaken at night to defecate.[1][8][16][17] Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but may be seen in the setting of Crohn's colitis.[1] Bloody bowel movements are typically intermittent, and may be bright or dark red in colour. In the setting of severe Crohn's colitis, bleeding may be copious.[8] Flatulence and bloating may also add to the intestinal discomfort.

Symptoms caused by intestinal stenosis are also common in Crohn's disease. Abdominal pain is often most severe in areas of the bowel with stenoses. In the setting of severe stenosis, vomiting and nausea may indicate the beginnings of small bowel obstruction.[8] Although the association is greater in the context of ulcerative colitis, Crohn's disease may also be associated with primary sclerosing cholangitis, a type of inflammation of the bile ducts.[18]

Perianal discomfort may also be prominent in Crohn's disease. Itchiness or pain around the anus may be suggestive of inflammation, fistulization or abscess around the anal area[1] or anal fissure. Perianal skin tags are also common in Crohn's disease.[19] Fecal incontinence may accompany peri-anal Crohn's disease. At the opposite end of the gastrointestinal tract, the mouth may be affected by non-healing sores (aphthous ulcers). Rarely, the esophagus, and stomach may be involved in Crohn's disease. These can cause symptoms including difficulty swallowing (dysphagia), upper abdominal pain, and vomiting.[20]

Systemic symptoms


Crohn's disease, like many other chronic, inflammatory diseases, can cause a variety of systemic symptoms.[1] Among children, growth failure is common. Many children are first diagnosed with Crohn's disease based on inability to maintain growth.[21] As Crohn's disease may manifest at the time of the growth spurt in puberty, up to 30% of children with Crohn's disease may have retardation of growth.[22] Fever may also be present, though fevers greater than 38.5 ˚C (101.3 ˚F) are uncommon unless there is a complication such as an abscess.[1] Among older individuals, Crohn's disease may manifest as weight loss. This is usually related to decreased food intake, since individuals with intestinal symptoms from Crohn's disease often feel better when they do not eat and might lose their appetite.[21] People with extensive small intestine disease may also have malabsorption of carbohydrates or lipids, which can further exacerbate weight loss.[23]


Extraintestinal symptoms


Erythema nodosum on the back of a person with Crohn's disease.


Pyoderma gangrenosum on the leg of a person with Crohn's disease.

In addition to systemic and gastrointestinal involvement, Crohn's disease can affect many other organ systems.[24] Inflammation of the interior portion of the eye, known as uveitis, can cause eye pain, especially when exposed to light (photophobia). Inflammation may also involve the white part of the eye (sclera), a condition called episcleritis. Both episcleritis and uveitis can lead to loss of vision if untreated.

Crohn's disease is associated with a type of rheumatologic disease known as seronegative spondyloarthropathy. This group of diseases is characterized by inflammation of one or more joints (arthritis) or muscle insertions (enthesitis). The arthritis can affect larger joints such as the knee or shoulder or may exclusively involve the small joints of the hand and feet. The arthritis may also involve the spine, leading to ankylosing spondylitis if the entire spine is involved or simply sacroiliitis if only the lower spine is involved. The symptoms of arthritis include painful, warm, swollen, stiff joints and loss of joint mobility or function. [15]


Crohn's disease may also involve the skin, blood, and endocrine system. One type of skin manifestation, erythema nodosum, presents as red nodules usually appearing on the shins. Erythema nodosum is due to inflammation of the underlying subcutaneous tissue and is characterized by septal panniculitis. Another skin lesion, pyoderma gangrenosum, is typically a painful ulcerating nodule. Crohn's disease also increases the risk of blood clots; painful swelling of the lower legs can be a sign of deep venous thrombosis, while difficulty breathing may be a result of pulmonary embolism. Autoimmune hemolytic anemia, a condition in which the immune system attacks the red blood cells, is also more common in Crohn's disease and may cause fatigue, pallor, and other symptoms common in anemia. Clubbing, a deformity of the ends of the fingers, may also be a result of Crohn's disease. Finally, Crohn's disease may cause osteoporosis, or thinning of the bones. Individuals with osteoporosis are at increased risk of bone fractures.[7]

Crohn's disease can also cause neurological complications (reportedly in up to 15% of patients).[25] The most common of these are seizures, stroke, myopathy, peripheral neuropathy, headache and depression.[25]

Crohn's patients often also have issues with small bowel bacterial overgrowth syndrome, which has similar symptoms.[26]



Complications


Endoscopic image of colon cancer identified in the sigmoid colon on screening colonoscopy for Crohn's disease.

Crohn's disease can lead to several mechanical complications within the intestines, including obstruction, fistulae, and abscesses. Obstruction typically occurs from strictures or adhesions which narrow the lumen, blocking the passage of the intestinal contents. Fistulae can develop between two loops of bowel, between the bowel and bladder, between the bowel and vagina, and between the bowel and skin. Abscesses are walled off collections of infection, which can occur in the abdomen or in the perianal area in Crohn's disease sufferers.

Crohn's disease also increases the risk of cancer in the area of inflammation. For example, individuals with Crohn's disease involving the small bowel are at higher risk for small intestinal cancer. Similarly, people with Crohn's colitis have a relative risk of 5.6 for developing colon cancer.[27] Screening for colon cancer with colonoscopy is recommended for anyone who has had Crohn's colitis for at least eight years.[28] Some studies suggest that there is a role for chemoprotection in the prevention of colorectal cancer in Crohn's involving the colon; two agents have been suggested, folate and mesalamine preparations.

Individuals with Crohn's disease are at risk of malnutrition for many reasons, including decreased food intake and malabsorption. 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.[30]


Crohn's disease can cause significant complications including bowel obstruction, abscesses, free perforation and hemorrhage.[31]



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 allows preventative measures to be taken. In some cases, remission can occur during pregnancy. Certain medications can also impact sperm count or may otherwise adversely affect a man's ability to conceive.[32]


Cause

Although the exact cause of Crohn's disease is still unknown, a combination of environmental factors and genetic predisposition seems to cause the disease.[33] The genetic risk factors have now more or less been comprehensively elucidated, making Crohn's disease the first genetically complex disease of which the genetic background has been resolved.[34] The relative risks of contracting the disease when one has a mutation in one of the risk genes, however, are actually very low (approximately 1:200). Broadly speaking, the genetic data indicate that innate immune systems in patients with Crohn's disease malfunction, and direct assessment of patient immunity confirms this notion.[35] This had led to the notion that Crohn's disease should be viewed as innate immune deficiency, chronic inflammation being caused by adaptive immunity trying to compensate for the reduced function of the innate immune system.[36]