| Inflammatory bowel disease | |
|---|---|
| Classification and external resources | |
Micrograph showing inflammation of the large bowel in a case of inflammatory bowel disease. Colonic biopsy. H&E stain. |
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| DiseasesDB | 31127 |
| eMedicine | med/1169 emerg/106 oph/520 |
| MeSH | D015212 |
In medicine, inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.[1][2][3]
Contents |
The main forms of IBD are Crohn's disease and ulcerative colitis (UC).
Accounting for far fewer cases are other forms of IBD, which are not always classified as typical IBD:
The main difference between Crohn's disease and UC is the location and nature of the inflammatory changes. Crohn's can affect any part of the gastrointestinal tract, from mouth to anus (skip lesions), although a majority of the cases start in the terminal ileum. Ulcerative colitis, in contrast, is restricted to the colon and the rectum.[4]
| Pathophysiology in Crohn's disease vs. ulcerative colitis |
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|---|---|---|
| Crohn's disease | Ulcerative colitis | |
| Autoimmune disease | Widely regarded as an autoimmune disease |
No consensus |
| Cytokine response | Associated with Th17[5] | Vaguely associated with Th2 |
Microscopically, ulcerative colitis is restricted to the mucosa (epithelial lining of the gut), while Crohn's disease affects the whole bowel wall ("transmural lesions").
Finally, Crohn's disease and ulcerative colitis present with extra-intestinal manifestations (such as liver problems, arthritis, skin manifestations and eye problems) in different proportions.
Rarely, a definitive diagnosis of neither Crohn's disease nor ulcerative colitis can be made because of idiosyncrasies in the presentation. In this case, a diagnosis of indeterminate colitis may be made. Although a recognised definition, not all centres refer to this.
| Crohn's disease | Ulcerative colitis | |
|---|---|---|
| Defecation | Often porridge-like[6], sometimes steatorrhea |
Often mucus-like and with blood[6] |
| Tenesmus | Less common[6] | More common[6] |
| Fever | Common[6] | Indicates severe disease[6] |
| Fistulae | Common[7] | Seldom |
| Weight loss | Often | More seldom |
Although very different diseases, both may present with any of the following symptoms: abdominal pain, vomiting, diarrhea, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis, weight loss and various associated complaints or diseases like arthritis, pyoderma gangrenosum, and primary sclerosing cholangitis. Diagnosis is generally by colonoscopy with biopsy of pathological lesions.
| Findings in diagnostic workup in Crohn's disease vs. ulcerative colitis |
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|---|---|---|
| Sign | Crohn's disease | Ulcerative colitis |
| Terminal ileum involvement | Commonly | Seldom |
| Colon involvement | Usually | Always |
| Rectum involvement | Seldom | Usually[8] |
| Involvement around the anus |
Common[7] | Seldom |
| Bile duct involvement | No increase in rate of primary sclerosing cholangitis | Higher rate[9] |
| Distribution of Disease | Patchy areas of inflammation (Skip lesions) | Continuous area of inflammation[8] |
| Endoscopy | Deep geographic and serpiginous (snake-like) ulcers | Continuous ulcer |
| Depth of inflammation | May be transmural, deep into tissues[2][7] | Shallow, mucosal |
| Stenosis | Common | Seldom |
| Granulomas on biopsy | May have non-necrotizing non-peri-intestinal crypt granulomas[7][10][11] | Non-peri-intestinal crypt granulomas not seen[8] |
| Management in Crohn's disease vs. ulcerative colitis |
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|---|---|---|
| Crohn's disease | Ulcerative colitis | |
| Mesalazine | less useful[12] | More useful[12] |
| Antibiotics | Effective in long-term[13] | Generally not useful[14] |
| Surgery | Often returns following removal of affected part |
Usually cured by removal of colon |
Optimal treatment of inflammatory bowel disease depends on what form it consists of. For example, mesalazine is more useful in ulcerative colitis than in Crohn's disease.[12] Generally, depending on the level of severity, IBD may require immunosuppression to control the symptom, such as prednisone, TNF inhibition, azathioprine (Imuran), methotrexate, or 6-mercaptopurine. More commonly, treatment of IBD requires a form of mesalazine. Often, steroids are used to control disease flares and were once acceptable as a maintenance drug. In use for several years in Crohn's disease patients and recently in patients with ulcerative colitis, biologicals have been used such as TNF inhibitors. Severe cases may require surgery, such as bowel resection, strictureplasty or a temporary or permanent colostomy or ileostomy. Alternative medicine treatments for bowel disease exist in various forms, however such methods concentrate on controlling underlying pathology in order to avoid prolonged steroidal exposure or surgical excisement.[15]
Usually the treatment is started by administering drugs with high anti-inflammatory effects, such as prednisone. Once the inflammation is successfully controlled, the patient is usually switched to a lighter drug to keep the disease in remission, such as Asacol, a mesalazine. If unsuccessful, a combination of the aforementioned immunosuppression drugs with a mesalazine (which may also have an anti-inflammatory effect) may or may not be administered, depending on the patient.
Histoplasma produces toxins that cause intestinal disease called histoplasmosis that is a “serious consideration” in an immunocompromised patient with signs and symptoms of IBD. Antifungal drugs such as nystatin (a broad spectrum gut antifungal) and either itraconazole (Sporanox) or fluconazole (Diflucan) have been suggested as a treatment for IBD disorders such as Crohn’s disease and ulcerative colitis that all share the same symptoms such as diarrhea, weight loss, fever, and abdominal pain.[16]
| Complications of Crohn's disease vs. ulcerative colitis |
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|---|---|---|---|
| Crohn's disease | Ulcerative colitis | ||
| Nutrient deficiency | Higher risk | ||
| Colon cancer risk | Slight | Considerable | |
| Prevalence of extraintestinal complications[17] |
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| Iritis/uveitis | Females | 2.2% | 3.2% |
| Males | 1.3% | 0.9% | |
| Primary sclerosing cholangitis |
Females | 0.3% | 1% |
| Males | 0.4% | 3% | |
| Ankylosing spondylitis |
Females | 0.7% | 0.8% |
| Males | 2.7% | 1.5% | |
| Pyoderma gangrenosum |
Females | 1.2% | 0.8% |
| Males | 1.3% | 0.7% | |
| Erythema nodosum | Females | 1.9% | 2% |
| Males | 0.6% | 0.7% | |
While IBD can limit quality of life because of pain, vomiting, diarrhea, and other socially unacceptable symptoms, it is rarely fatal on its own. Fatalities due to complications such as toxic megacolon, bowel perforation and surgical complications are also rare.
While patients of IBD do have an increased risk of colorectal cancer, this is usually caught much earlier than the general population in routine surveillance of the colon by colonoscopy, and therefore patients are much more likely to survive.
New evidence suggests that patients with IBD may have an elevated risk of endothelial dysfunction and coronary artery disease[18]
The goal of treatment is toward achieving remission, after which the patient is usually switched to a lighter drug with fewer potential side effects. Every so often, an acute resurgence of the original symptoms may appear; this is known as a "flare-up". Depending on the circumstances, it may go away on its own or require medication. The time between flare-ups may be anywhere from weeks to years, and varies wildly between patients - a few have never experienced a flare-up.
The following treatment strategies are not used routinely, but appear promising in most forms of inflammatory bowel disease.
Initial reports[19] suggest that "helminthic therapy" may not only prevent but even control IBD: a drink with roughly 2,500 ova of the Trichuris suis helminth taken twice monthly decreased symptoms markedly in many patients. It is even speculated that an effective "immunization" procedure could be developed—by ingesting the cocktail at an early age.
Prebiotics and probiotics are showing increasing promise as treatments for IBD[20] and in some studies have proven to be as effective as prescription drugs.[21]
In 2005 New Scientist published a joint study by Bristol University and the University of Bath on the apparent healing power of cannabis on IBD. Reports that cannabis eased IBD symptoms indicated the possible existence of cannabinoid receptors in the intestinal lining, which respond to molecules in the plant-derived chemicals. CB1 cannabinoid receptors – which are known to be present in the brain – exist in the endothelial cells which line the gut, it is thought that they are involved in repairing the lining of the gut when damaged. The team deliberately damaged the cells to cause inflammation of the gut lining and then added synthetically produced cannabinoids; the result was that gut started to heal: the broken cells were repaired and brought back closer together to mend the tears. It is believed that in a healthy gut, natural endogenous cannabinoids are released from endothelial cells when they are injured, which then bind to the CB1 receptors. The process appears to set off a wound-healing reaction, and when people use cannabis, the cannabinoids bind to these receptors in the same way. Previous studies have shown that CB1 receptors located on the nerve cells in the gut respond to cannabinoids by slowing gut motility, therefore reducing the painful muscle contractions associated with diarrhoea. The team also discovered another cannabinoid receptor, CB2, in the guts of IBD sufferers, which was not present in healthy guts. These receptors, which also respond to chemicals in cannabis, appear to be associated with apoptosis – programmed cell death – and may have a role in suppressing the overactive immune system and reducing inflammation by mopping up excess cells.[22]
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