Crohn's disease; an immune-related disease

Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract from the mouth to the anus. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension, and weight loss.
Other complications outside the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and fatigue. The skin rashes may be due to infections as well as pyoderma gangrenosum or erythema nodosum. Bowel obstruction may occur as a complication of chronic inflammation, and those with the disease are at greater risk of colon cancer and small bowel cancer.
While the precise causes of Crohn's disease are unknown, it is believed to be caused by a combination of environmental, immune, and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system defends the gastrointestinal tract, possibly targeting microbial antigens. While Crohn's is an immune-related disease, it does not appear to be an autoimmune disease (in that the immune system is not being triggered by the body itself). The exact underlying immune problem is not clear; however, it may be an immunodeficiency state.
About half of the overall risk is related to genetics, with more than 70 genes having been found to be involved. Tobacco smokers are twice as likely to develop Crohn's disease as nonsmokers. It also often begins after gastroenteritis. Diagnosis is based on a number of findings, including biopsy and appearance of the bowel wall, medical imaging, and description of the disease. Other conditions that can present similarly include irritable bowel syndrome and Behçet's disease.
There are no medications or surgical procedures that can cure Crohn's disease. Treatment options are intended to help with symptoms, maintain remission, and prevent relapse. In those newly diagnosed, a corticosteroid may be used for a brief period of time to rapidly improve symptoms, alongside another medication such as either methotrexate or a thiopurine used to prevent recurrence. Stopping smoking is recommended in people with Crohn's disease. One in five people with the disease is admitted to the hospital each year, and half of those with the disease will require surgery for the disease at some point over a ten-year period. While surgery should be used as little as possible, it is necessary to address some abscesses, certain bowel obstructions, and cancers. Checking for bowel cancer via colonoscopy is recommended every few years, starting eight years after the disease has begun.
Crohn's disease affects about 3.2 per 1,000 people in Europe and North America. It is less common in Asia and Africa. It has historically been more common in the developed world. Rates have, however, been increasing, particularly in the developing world, since the 1970s. Inflammatory bowel disease resulted in 47,400 deaths in 2015, and those with Crohn's disease have a slightly reduced life expectancy. It tends to start in the teens and twenties, though it can occur at any age. Males and females are equally affected. The disease was named after gastroenterologist Burrill Bernard Crohn, who in 1932, together with two colleagues at Mount Sinai Hospital in New York, described a series of patients with inflammation of the terminal ileum of the small intestine, the area most commonly affected by the illness.
Symptoms
Many people with Crohn's disease have symptoms for years before the diagnosis. The usual onset is in the teens and twenties, but can occur at any age. Because of the 'patchy' nature of the gastrointestinal disease and the depth of tissue involvement, initial symptoms can be more subtle than those of ulcerative colitis. People with Crohn's disease experience chronic recurring periods of flare-ups and remission. Abdominal pain is a common initial symptom of Crohn's disease, especially in the lower right abdomen. It is often accompanied by diarrhea, which may or may not be bloody. Inflammation in different areas of the intestinal tract can affect the quality of the feces. Ileitis typically results in large-volume, watery feces, while 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. Visible bleeding in the feces is less common in Crohn's disease than in ulcerative colitis, but is not unusual. Bloody bowel movements are usually intermittent, and may be bright or dark red in color. In severe Crohn's colitis, bleeding may be copious. Flatulence, bloating, and abdominal distension are additional symptoms and may also add to the intestinal discomfort.
Diagnosis
The diagnosis of Crohn's disease can sometimes be challenging, and a number of tests are often required to assist the physician in making the diagnosis. Even with a full battery of tests, it may not be possible to diagnose Crohn's with complete certainty; a colonoscopy is approximately 70% effective in diagnosing the disease, with further tests being less effective. Disease in the small bowel is particularly difficult to diagnose, as a traditional colonoscopy allows access to only the colon and lower portions of the small intestines; introduction of the capsule endoscopy aids in endoscopic diagnosis. Giant (multinucleate) cells, a common finding in the lesions of Crohn's disease, are less common in the lesions of lichen nitidus.
Medication
Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce inflammation (normally aminosalicylate anti-inflammatory drugs and corticosteroids). When symptoms are in remission, treatment enters maintenance, with a goal of avoiding the recurrence of symptoms. Prolonged use of corticosteroids has significant side-effects; as a result, they are, in general, not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority are able to maintain the treatment, and many require immunosuppressive drugs. It has been also suggested that antibiotics change the enteric flora, and their continuous use may pose the risk of overgrowth with pathogens such as Clostridium difficile. Medications used to treat the symptoms of Crohn's disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine (given as the prodrug for 6-mercaptopurine), methotrexate, infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab, and natalizumab. Hydrocortisone should be used in severe attacks of Crohn's disease. Biological therapies are medications used to avoid long-term steroid use, decrease inflammation, and treat people who have fistulas with abscesses. The monoclonal antibody ustekinumab appears to be a safe treatment option, and may help people with moderate to severe active Crohn's disease. The long term safety and effectiveness of monoclonal antibody treatment is not known. The monoclonal antibody briakinumab is not effective for people with active Crohn's disease and it is no longer being manufactured.
Best Regards,
Alex John
Submit manuscript at: https://www.scholarscentral.org/submissions/clinical-experimental-neuroimmunology.html
An e-mail attachment at: manuscripts@omicsonline.com