Introduction of Inflammatory Bowel Disease:
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Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. The term IBD is commonly used for two bowel diseases having many similarities but the conditions usually have a distinctive morphological appearance. These two conditions are ulcerative colitis and Crohn’s disease.
- Ulcerative colitis: This condition causes long-lasting inflammation and sores (ulcers) in the innermost lining of the large intestine (colon) and rectum. Classically, ulcerative colitis begins in the rectum, and in continuity extends upwards into the sigmoid colon, descending colon, transverse colon, and sometimes may involve the entire colon. The colonic contents may rarely backflow in the terminal ileum in continuity, causing ‘backwash ileitis’ in about 10% of cases.
- Crohn’s disease: Crohn’s disease may involve any portion of the gastrointestinal tract but affect most commonly 15-25 cm of the terminal ileum which may extend into the caecum and sometimes into the ascending colon. Both ulcerative colitis and Crohn’s disease usually involve severe diarrhea, abdominal pain, and fatigue, and weight loss.
Causes of Inflammatory Bowel Disease:
1. Immunological factors: The exact cause of IBD is unknown, but IBD is the result of a defective immune system. A properly functioning immune system attacks foreign organisms, such as viruses and bacteria, to protect the body. In IBD, the immune system responds incorrectly to environmental triggers, which causes inflammation of the gastrointestinal tract.
2. Genetic factors:
- There is about 3 to 20 times higher incidence of occurrence of IBD in first-degree relatives. This is due to a genetic defect causing diminished epithelial barrier function.
- There is approximately a 50% chance of development of IBD (Crohn’s disease about 60%, ulcerative colitis about 6%) in monozygotic twins. However, there is no clear link between the abnormal genes and IBD.
3. Exogenous factors:
i) Microbial factors: Microbial factors (bacteria, viruses, protozoa, and fungi) have been suspect but without definite evidence.
ii) Psychosocial factors: It has been observed that individuals who are unduly sensitive, dependent on others, and unable to express themselves, or some major life events such as illness or death in the family, divorce, interpersonal conflicts, etc. suffer from the irritable colon or have an exacerbation of symptoms.
iii) Smoking: The role of smoking in the causation of Crohn’s disease has been reported.
iv) Oral contraceptives: An increased risk to develop Crohn’s disease with long-term use of oral contraceptives have been found in some studies but there is no such increased risk of ulcerative colitis.
Pathophysiology of Inflammatory Bowel Disease:
The location and appearance of inflammatory lesions differ between the two forms. In Crohn’s disease, inflammatory lesions extend through the bowel wall and develop simultaneously in separate areas. Granuloma formation occurs first, followed by ulceration and abscess formation, fistula may form between the affected areas and the bladder, vagina, or rectum. With repeated episodes, the gut wall assumes a cobblestone appearance, with permanent scarring and constriction. The characteristic lesion of UC is the crypt abscess, pus-filled, a necrotic lesion that starts at the bases of any of the tubular glands of the intestinal mucous membrane. These lesions ulcerate and bleed during flares, then heal with scarring and constriction.
In a normal individual, there is a lack of immune responsiveness to dietary antigens and commensal flora in the intestinal lumen. The mechanism responsible for this is by activation of CD4+T cell secreting cytokines inhibitory to inflammation (IL-10, TGF-β) which suppress inflammation in the gut wall. In IBD, this immune mechanism of suppression of inflammation is defective and thus results in uncontrolled inflammation. In both types of IBD, activated CD4+T cells are present in the lamina propria and the peripheral blood. These cells either activate other inflammatory cells macrophages and B cells. There are two main types of CD4+T cells in IBD.
- TH1 cells secrete proinflammatory y cytokines IFN-γ and TNF which induce transmural granulomatous inflammation seen in Crohn’s disease. IL-12 initiates the TH1 cytokine pathway.
- TH2 cells secrete IL-4, IL-5, and IL-13 which induce superficial mucosal inflammation characteristically seen in ulcerative colitis.
Crohn’s disease begins with crypt inflammation and abscesses, which progress to tiny focal aphthoid ulcers. These mucosal lesions may develop into deep longitudinal and transverse ulcers with intervening mucosal edema, creating a characteristic cobblestoned appearance to the bowel.
Transmural spread of inflammation leads to lymphedema and thickening of the bowel wall and mesentery. Mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge. Extensive inflammation may result in hypertrophy of the muscular mucosae, fibrosis, and stricture formation, which can lead to bowel obstruction. Abscesses are common, and fistulas often penetrate adjoining structures, including other loops of the bowel and the bladder. Fistulas may even extend to the skin of the anterior abdomen or flanks. Independently of intra-abdominal disease activity, perianal fistulas and abscesses occur in 25 to 33% of cases; these complications are frequently the most troublesome aspects of Crohn’s disease.
Non-caseating granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the bowel wall. Although pathognomonic (a characteristic sign or symptom of a disease that can be used to diagnose) when present, granulomas are not detected in about half of patients with Crohn’s disease. The presence of granulomas does not seem to be related to the clinical course.
Sign and Symptoms:
Inflammatory bowel disease symptoms vary, depending on the severity of inflammation and where it occurs. Symptoms may range from mild to severe. Signs and symptoms that are common to both Crohn’s disease and ulcerative colitis include Diarrhoea, fever, and fatigue, abdominal pain, and cramping, blood in stool, reduced appetite, unintended weight loss. Other symptoms may include: Constipation, sores or swelling in the eyes, draining of pus, mucus, or stools from, around the rectum or anus (fistula), joint pain and swelling, mouth ulcers, rectal bleeding and bloody stools, swollen gums, tender, red bumps (nodules) under the skin which may turn into skin ulcers.
Diagnosis of Inflammatory Bowel Disease:
Crohn’s disease is diagnosed through a medical history, physical exam, imaging tests to look at the intestines, and lab tests.
General investigation: Physical examination includes, checking for signs such as paleness (caused by anemia) or tenderness in the abdomen, skin rash, swollen joints, or mouth ulcers, and tenderness in the stomach (caused by inflammation) and recording of patient’s history.
Blood tests: To look for changes in
- Red blood cells: When red blood cells are fewer or smaller than normal, a patient may have anemia.
- White blood cells: When the white blood cell count is higher than normal, a person may have inflammation or infection somewhere in the body.
- Blood tests are also helpful to find antibodies. The presence of certain antibodies can sometimes help diagnose a type of inflammatory bowel disease i.e. Crohn’s disease or ulcerative colitis.
- Stool tests: A stool test is the analysis of a sample of stool, to rule out other causes of GI diseases.
- Upper gastrointestinal (UGI) series: It examines the upper part of the digestive tract.
- Upper gastrointestinal endoscopy: It looks at the interior lining of the esophagus, stomach, and duodenum.
- Colonoscopy or flexible sigmoidoscopy: Colonoscopy is often the preferred test because it can be used to examine the entire colon. Sigmoidoscopy reaches only the lowest part of the colon.
- Abdominal X-ray: This test can show possible obstructions in the abdomen.
- Barium enema: This test looks at the large intestine (colon).
- Computed tomography (CT) scan: Computerized tomography scans use a combination of X-rays and computer technology to create images. CT scans can diagnose both Crohn’s disease and the complications seen with the disease.
- Magnetic resonance imaging (MRI): MRI uses a magnetic field and pulses of radio wave energy to provide pictures of organs and structures inside the body. The pathologic entities of a fistula, a sinus tract, and an abscess can be detected in the static anorectal region by using MRI.
- Barium enema: This diagnostic test allows evaluating the entire large intestine with an X-ray. Barium, a contrast solution, is placed into the bowel using an enema. Sometimes air is added as well. The barium coats the lining, creating a feature of the rectum, colon, and a portion of the small intestine. This test is rarely used anymore, and it can be dangerous because the pressure required to inflate and coat the colon can lead to rupture of the colon. For people with severe symptoms, flexible sigmoidoscopy combined with a CT scan is a better alternative.
Treatment for IBD depends on the seriousness of the disease. Most people are treated with medication. Some people whose symptoms are triggered by certain foods can control the symptoms by avoiding foods that upset their intestines, like highly seasoned foods or dairy products. Each person may experience ulcerative colitis differently, so treatment is adjusted for each individual. Emotional and psychological support is also important.
The main aims of treatment are to:
- Reduce symptoms, known as inducing remission (a period without symptoms),
- Maintain remission.
Anti-inflammatory drugs are often the first step in the treatment of inflammatory bowel disease. They include:
(i) Aminosalicylates (ASAs): Such as Sulfasalazine, Mesalamine, Balsalazide and Olsalazine are medications that help to reduce inflammation and effective in ulcerative colitis.
(ii) Corticosteroids: These drugs, which include prednisone and hydrocortisone are a more powerful type of medication used to reduce inflammation. They can be used with or instead of ASAs to treat a flare-up if ASAs alone are not effective.
(iii) Immunosuppressants: Immunosuppressants such as Azathioprine, 6-mercaptopurine, methotrexate, cyclosporine are often used and can make a marked improvement at a low dose with few side effects. Other drugs may be given to relax the patient or to relieve pain, diarrhea, or infection. Occasionally, symptoms are severe enough that the person must be hospitalized.
Additional medications are required to manage specific symptoms of ulcerative colitis.
(i) Antibiotics: People with ulcerative colitis who run fevers will likely take antibiotics to help prevent or control infection. (e.g., Metronidazole, Ciprofloxacin, Rifaximin etc.)
(ii) Antidiarrhoeal medications: For severe diarrhea, loperamide may be effective. Use antidiarrhoeal medications with great caution, however, because they may increase the risk of toxic megacolon.
(iii) Iron supplements: In chronic intestinal bleeding, a person may develop iron deficiency anemia and be given iron supplements.
(iv) Bowel rest: Sometimes Crohn’s disease symptoms are severe and a person may need to rest bowel for a few days to several weeks. Bowel rest involves drinking only clear liquids or having no oral intake. Nutritions are provided to the patient intravenously through a special catheter, or tube, inserted into a vein in the patient’s arm.
(v) Surgery: Even with medication treatments, up to 20% of people will need surgery to treat their Crohn’s disease. Although surgery will not cure Crohn’s disease, it can treat complications and improve symptoms.
Table: Different clinical features
|Blood in stool||Yes||Occasionally|
|Small intestine obstruction||No||Frequently|
|Response to antibiotic||No||Yes|
|Recurrence after surgery||NO||Yes|
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