by Alison Berry
I wrote my senior thesis for school a little earlier this year when all the research came out. I wouldn't encourage anyone to just copy it and use it for school, but it has a lot of useful info in there if anyone wants to use my research as a reference or just to learn more about this disease!!!
Crohn’s disease (CD) is an inflammatory bowel disease (IBD) of an undetermined cause. CD afflicts more than 500,000 people in the United States and is not biased in regards to whom it strikes. People unlucky enough to get CD include the rich as well as poor, children, women, and men of white, black, and Asian descent. Crohn’s primarily attacks the lower parts of the small intestine (ileum), near the appendix, and the large intestine (colon), but may occur in any section of the gastrointestinal tract. Although Crohn’s disease afflicts all age groups, initial diagnosis generally occurs before the age of thirty.
Throughout historical medical literature, during the 19th century, various cases were reported by physicians describing what is known as Crohn’s disease today. Although it was not named until 1932, the first reported case of Crohn’s was in 1806 by doctors Combe and Sanders to the Royal College of Physicians in London, England (CD History, 2001). Seventeen years later an Edinburgh physician by the name of John Abercrombie documented 144 cases in which there was a clearly outlined difference in ileal and colonic diseases. In comparison to known facts of CD today, the Edinburgh physician was most likely describing Crohn’s and ulcerative colitis, another inflammatory bowel disease.
Almost a hundred years later, in 1913, there was surgical evidence of the disease as reported in the paper ‘Chronic Intestinal Enteritis’ written by Dr. Kennedy Dalziel, a Scottish physician working at the Western Infirmary in Glasgow. The most famous report did not come until 1932 from research done at Mount Sinai Hospital in New York. Dr. Burrill B. Crohn first presented a paper titled ‘Terminal Ileitis’ to the 83rd Annual Session of the American Medical Association. The paper listed information on fourteen surgical cases mostly operated on by surgeon, Dr. A. A. Berg. The paper prompted more medical research in the area which lead to the three man team of gastroenterological Drs. Burrill B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer. The three doctors studied the disease of the ileum that was once thought to be intestinal tuberculosis (NFIC, 1983). Crohn, Ginsberg, and Oppenheimer later presented their paper ‘Regional Ileitis.’ The threesome recorded cases of "non specific granulomas of the intestine" (CD History, 2001).
There was no appropriate medical terminology to describe the many manifestations of the disease. It was in England that the name Crohn’s was widely used by local physicians (CD History, 2001). In the western world, the disease was called "Terminal Ileitis" for many years. The name involving the word ‘terminal’ frightened patients although the disease was not fatal with treatment (NFIC, 1983). Later, the name "Regional Ileitis" came into use, but as it was discovered that the disease could in fact involve any area of the gastrointestinal tract, not just the terminal ileum, the name Crohn’s was gradually used widespread (CD History, 2001). The disease is referred to as Crohn’s due to the fact that Burrill B. Crohn’s name was the first listed in the landmark paper (Researchers, 2001). Dr. Berg unfortunately did not want his name published on the important paper, if he had, Crohn’s would be known by a different name today (CD History, 2001).
It wasn’t till May 2001 that the first gene for Crohn’s disease was identified. The discovery was made by a team of IBD researches led by Dr. Judy Cho, an assistant professor of medicine and a researcher in the Martin Boyer Laboratories at the University of Chicago, and Dr. Gabriel Nuňez, an assistant professor of pathology at the University of Michigan (Researchers, 2001). To collaborate the findings of the American based scientists, an independent research team in France released their findings showing that they had found the same gene. The French research team was lead by Dr. Jean-Pierre Hugot and Dr. Gilles Thomas.
The researchers were able to identify an abnormal mutation in a gene known as Nod2. This mutation occurs twice as frequently in Crohn’s patients as in the general population. This finding connects the disease with an arm of the immune system known as the innate immune system. Nod2 is responsible for encoding a protein that helps the innate immune system recognize and respond to a component of some types of bacteria. This component, found in the outer membrane of the bacteria, is known as lipopolysaccharides (LPS). In the mutated form of Nod2, about three percent of the protein is missing, making it much more difficult for the Nod2 to recognize LPS and respond to bacterial invaders (Researchers, 2001).
It was always believed that both genetic and environmental factors played a role in inflammatory bowel diseases, now it brings some relief to the scientists because they can finally begin to understand how the two factors work together to cause the disease. Dr. Nuňez said it best when he stated, “It has been known for a long time that there is an important link between bacteria residing in the gut and genetic factors for the development of CD. The discovery of Nod2 may explain this missing-link connection between genes and bacteria" (Researchers, 2001).
The Nod2 gene is found primarily in monocytes, simple defensive cells of the innate immune system. The monocytes’ inability to recognize bacteria may lead to an exaggerated inflammatory response of another part of the immune system, known as the adaptive immune system. The adaptive immune system reacts more slowly but produces stronger, targeted responses to specific invaders. It has been suggested in other studies that a breach in this "first line of defense" plays a role in the inflammatory response, and the mutated form of Nod2 may be the link to identifying other "breaches" or weaknesses (Researchers, 2001).
Dr. Cho believes that with the discovery of the Nod2 mutations, the process of finding additional Crohn’s disease associated mutations will be easier to the clues as linked with the disease pathways and subsequently related proteins (Researchers, 2001).
The Nod2 gene is located on chromosome 16 (Associated, 2001). Having the Nod2 mutation increases a person’s chance by 25 percent to get the disease, but not every person with the mutation will develop the disease over their lifetime (Associated, 2001).
Scientists have always hypothesized Crohn’s disease was a genetic disorder so the investigators studied a total of 416 families in the United States in which 797 individuals had the disease (Researchers, 2001). Considering that the appearance of the same type of disease was higher among members of the same family lines was a good indication that the IBD was indeed a genetic disorder. Scientists had studies the genome for years looking for IBD susceptible genes, but it wasn’t until 1996 did researches identify chromosome 16 as the general location for the gene mutation(s) (Researchers, 2001). Not being able to identify the specific gene at the time, Drs. Cho and Nuňez broke the chromosome down and labeled its regions. “Nod2 is located at the peak region of IBD1. Nod2 became a logical target of study given its genomic location and the potential role of Nod proteins in recognizing bacterial components" (Researchers, 2001). Further research is being done now to find new treatments on the new discovery of the Nod2 gene.
A new development has also been released about Crohn’s. Johne’s disease, identified over a century ago, is alleged to affect "at least one in every five U.S. herds" of cattle (Brasher, 2001). Scientists are studying its possible link to Crohn’s disease. "Its [Crohn’s] link with Johne’s is hotly debated by scientists. The bacterium M. paratuburculosis that causes Johne’s is found in many – but not all- Crohn’s patients" Brasher, 2001). The main symptoms of diarrhea and weight loss are similar in both humans and cattle.
Because scientists are not sure that Johne’s bacteria are destroyed when milk is pasteurized, it is a concern that the disease could be transmitted into humans as Crohn’s. Another concern is consumption of the bacteria by undercooked meats, unpasteurized dairy products, or fecal contamination of underground water supplies (Brasher, 2001). Due to the possible connection and harm to humans, the National Milk Producers Federation is asking congress for 1.3 billion dollars to identify and destroy all infected cattle (Brasher, 2001).
The symptoms of Crohn’s disease a person gets is determined by the subtype of the disease they have. There are five subtypes of CD: gastroduodenal Crohn disease, jejunoileitis, ileitis, ileocolitis, and Crohn colitis (also called granulomatous colitis (Zonderman, 2000).
Gastroduodenal Crohn disease is known to affect the stomach and duodenum (beginning section of the small intestines). The main symptoms for this subtype of Crohn’s include a loss of appetite and weight loss, nausea, vomiting, and pain in the upper middle of the abdomen. Doctors initially diagnose this condition as ulcer disease. Correct diagnosis occurs when treatment for the ulcers has been unsuccessful or when the disease affects another part of the intestinal tract (Zonderman, 2000).
Jejunoileitis is a disease of the jejunum. The jejunum is the largest section of the small intestine which is located between the duodenum and the ileum (last part of the small intestine) (Zonderman, 2000). Major symptoms include mild-to-intense abdominal pain and cramping after meals. Weight loss and malnutrition can occur due to diarrhea and malabsorption of nutrients normally absorbed in the region of the jejunum. Fistulas, "abnormal connections of the inflammation that spreads beyond the confines of the bowel wall and penetrates to adjacent loops of bowel, to other organs such as the bladder, vagina, or to the skin surface," may arise in this subset of CD (NFIC, 1983).
Ileitis affects the ileum. "The main symptoms are diarrhea and cramping or pain in the right lower-middle part of the abdomen, especially after meals. Malabsorption of vitamin B12 can lead to the peripheral neuropathy (tingling of fingers and toes) and folate deficiency can hinder red blood cell development" (Zonderman, 2000). The intestines sometimes inflame so greatly that a large mass becomes apparent in the right lower abdomen. Fistulas are also common with Ileitis.
Ileocolitis is the most common subtype of CD. If affects the ileum as well as the colon. " Often the diseased areas of the ileum and colon are contiguous and involve the ileocecal valve, which sits at the junction of the ileum and cecum – the first section of the colon – and keeps the waste contents for the colon from backflushing into the small intestine" (Zonderman, 2000). Ileitis and ileocolitis have essentially the same symptoms with the addition of weight loss.
Crohn colitis, otherwise known as granulomatous colitis, involves only the colon. Symptoms of this subtype include rectal bleeding, diarrhea, and pain. Crohn colitis is often misdiagnosed for ulcerative colitis up to twenty percent of the time. Crohn’s colitis is distinguishable from ulcerative colitis by presence of disease around the anus which includes fistulas and abscesses (Zonderman, 2000). Abscesses are a localized collection of inflammatory cells (puss) that can occur in acute or chronic infections. In those with IBD, it tends to occur outside the bowel walls or around the anal canal (Zonderman, 2000). Additional symptoms most common of Crohn colitis include the extra intestinal symptoms of joint pain and skin lesions.
Although each subtype of Crohn’s disease carries unique symptoms, common to all patients are the following: low grade to high fever, persistent chronic pain in the abdomen, moderate to severe diarrhea, weakness, fatigue, and weight loss. In some cases patients develop sores on their bodies and arthritis in their joints.
Diagnosis of CD can be difficult. In many cases it took years of suffering
before the correct diagnosis was made. Because CD is hard to distinguish between many gastrointestinal illnesses, doctors must put each patient through rigorous testing most of which are very unpleasant.
The first thing a doctor does is takes the medical history of his or her patient. He looks for persistent, recurrent diarrhea, pain, fever, and asks about family lineage since Crohn’s is genetically linked. Other signs of CD can take place well before what is known as a flare up (active CD in the intestinal tract). These include reddening and inflammation of the eyes, joint pains, skin lesions, sores inside the mouth called aphthous ulcers, and of course weight loss (Zonderman, 2000).
Upon completion of the history the doctor will issue a physical exam focusing extra attention on the abdomen for tenderness as well as inflammatory masses and the anorectal area. In an active CD case there is, on occasion, a palpable inflammatory mass caused by an acute inflammation usually found at the ileum. This is often diagnosed as appendicitis because due to the location and severity of pain (Kishner, 1988). Because the colon may be involved, the doctor will feel along the colon for tender spots that signal signs of acute inflammation (Zonderman, 2000).
Next, a series of lab tests and diagnostic procedures are administered to add evidence to or eliminate the possibility of having an inflammatory bowel disease. Blood tests and stool cultures are among the first items sent to the lab. In most CD patients "the hemoglobin in the red calls as well as the hemotocrit ( the ratio of red blood cells to whole blood) may be lower than normal, indicating anemia, which is due to malabsorption of iron, excessive bleeding, or chronic illness" (Zonderman, 2000).
The physician will then order a series of diagnostic procedures. Most commonly preformed are the sigmoidoscopy, colonoscopy, barium enema X-ray, barium upper-GI series with small bowel follow-through, and an endoscopic exam of the esophagus and stomach thru the mouth (Zonderman, 2000).
Looking for irregularities, the doctor performs a sigmoidoscopy most likely with a flexible fiber-optic tube containing a light source and camera lens at the end of the tube. The sigmoidoscope is inserted into the anus and moves through the rectum into the descending colon. With active CD, the doctor will see ulceration, a loss of "normal vascularity" to the bowel lining, and a granular texture of the lining (granularity), and friability (easy brusing) (Zonderman, 2000).
A colonoscopy is a more thorough examination of the large intestine and terminal ileum. Because it allows more visualization of the entire colon it is helpful for distinguishing CD from ulcerative colitis (Zonderman, 2000). In comparison to a sigmoidoscope, a colonoscope is much longer and uses electronic imaging making use of microchips and screen projections. During this procedure, biopsies are taken for further lab tests.
Barium is a contrast agent commonly used in X-rays to help show the lining of the intestinal walls. A barium enema is inserted by a tube up the rectum. A series of X-rays (usually by CT scan) are taken. Barium X-rays are often a definitive test in the diagnosis of CD (Zonderman, 2000).
To pinpoint the exact location and severity of tissue damage associated with Crohn’s disease, and upper-GI X-ray with small bowel follow-through is done. Barium is swallowed by the patient and time passes by to allow the chalk-like substance to line the esophagus, stomach, and entire intestinal tract. A series of X-rays are once again taken (Zonderman, 2000).
With the combination of history, physical exams, lab and diagnostic testing, a correct diagnosis can generally be made and a drug therapy can begin.
In the 1930s, surgery seemed to be the only option for patients with CD because there were no effective drugs available. Today, surgery is the last resort in dealing with this menacing disease. Corticosteroids with immunosuppressant abilities were developed in the 1950s and proved to be responsible for the dramatic remission of Crohn’s disease (CD History, 2001). Prednisone and Prednisolone are the most commonly used corticosteroid therapy (NFIC, 1983). They are highly effective in reducing the inflammation caused by the onset of CD. The biggest draw back to using steroids is the inability to use them in the long run. Whenever the intake of steroids are reduced or nullified, the return of CD symptoms seems inevitable (CD History, 2001).
The most frequently used treatment for CD are sulfasalazine, a two part system of sulfa preparation (sulfapyridine) and an aspirin-like drug called acetylsalicylic acid (NFIC, 1983). The combination of the two medicines appear to very successful in the suppressing the inflammatory reactions in the tissues of the colon.
Before any of the above medicines are administered, doctors usually give patients Flagyl and Cipro, two forms of drugs that kill any and all bacterium in the gut. Only after the harmful bacteria are vanquished can the drug therapies work to the best of their abilities.
In more severe cases of CD when fistulas are predominant, the intravenous drug treatment of Remicade is used (Remicade, 2001). Administered every eight to twelve weeks Remicade helps heal the lining of the intestines. Remicade blocks a substance known as TNF-alpha from the bloodstream. Overproduction of TNF-alpha is associated with many diseases that cause inflammation (Remicade, 2001).
As a very last resort, surgery is used. Because short bowl syndrome can be an effect of surgical procedures, surgery is used sparingly (CD History, 2001). Surgery can be seen as an emergency for performation, toxic megacolon, bleeding, and sudden total obstruction. Elective surgery is undertaken when chronic partial obstruction occurs, when a patient has persistent fistulas, or when drug therapies fail and the qualities of one’s life is severely impaired (Zonderman, 2000).
The most common form of surgery is a partial intestinal resection with reanatomosis (reconnection) (Zonderman, 2000). The damaged section of the small or large intestine is removed and the healthy parts are sewn back together.
Another form of surgery is a colectomy, or total removal of the colon and rectum (Zonderman, 2000). Upon completion of the colectomy, an ileostomy (external bag fitted to the side of the abdomen where wastes can drain and collect) is created by sewing the end portion of the small intestine through the abdomen wall in order for the bag to attach (Zonderman, 2000). Again, surgical procedures are generally used only as a last resort.
Patients can learn to live with this disease over time. It is very unsettling not knowing when or where one is going to develop a sudden flare up so psychological damage sometimes happens. CD patients should have a support group or counselor whom they can speak with. A nutritionalist can create a specific diet on a patient to patient basis, but nothing can really prevent the onset of the disease. The patient’s doctor becomes their best friend as the years pass by. It is very important to have a doctor one is comfortable with and whom they trust completely.
During times of a flare up, patients learn that they are limited to such foods as broth, Gatorade, jello, and water since eating anything solid is very painful and can make their symptoms feel ten times worse. Doctors tell patients to stay away from dairy products, nuts, meats, and raw vegetables as well as fruits in the event of a flare up because the body cannot digest them as easily as other foods.
CD patients learn to live with their lifelong chronic disease and live normal lifestyles. There are two sorts of Crohn’s patients. First, we have the patient that only stays at home feeling sorry for himself. He has no goals in life since he has a chronic disease. Then there’s this other patient… he has accepted his disease and takes one step at the time. He has goals and does everything to reach them. For the most part, people with Crohn’s have families, jobs, and participate in everyday activities. With today’s medicine, support groups (both online and in person), and family, CD patients can lead happy, long lives.
The Crohn’s and Colitis Foundation of America provide support both psychologically for patients and monetarily for future research. Although there is no current cure for CD, with combined efforts of researchers worldwide the possibility of finding a cure is closely approaching and hopefully Crohn’s disease will only be known as a insignificant disease of the past.
Works Cited
Associated Press. "Crohn’s Disease Lined to Bad Gene." Wilmington Morning Star 22 May. 2001: 5A
Brasher, Philip. "Dairy Farmers Asking For Help To Wipe Out Johne’s In Herds."
Wilmington Morning Star 28 May. 2001: 4A
"Crohn’s Disease, History and Treatments." 2001, June 4. Australian Crohn’s and Colitis
Association. http://www.acca.net.au
Janowitz, Henry D., M.D. Inflammatory Bowel Disease: A Personal View.
Field, Rich and Associates. U.S.A., 1985.
Kirsner, Joseph B., M.D., Ph.D. and Roy G. Shorter, M.D. Inflammatory
Bowel Disease. Lea & Febiger. Philadelphia, 1988.
Moses, P.L., B.R. Moore, and N. Ferrentino. "Inflammatory Bowel Disease:
Origins, Presentation, and Course". Postgrad Med. 1998" 103(5): 77-84.
NFIC. The Crohn’s Disease and Ulcerative Colitis Fact Book. Charles Scribner’s Sons.
New York, 1983.
"Remicade For Crohn’s." 2001, May 21. Remicade Infliximab.
http://www.remicade-crohns.com/
"Researchers Find First Gene For Crohn’s Disease." 2001, May 21.
Crohn’s and Colitis Foundation of America. http://www.ccfa.org
Zonderman, Jon and Ronald Vender, M.D. Understanding Crohn Disease
and Ulcerative Colitis. University Press of Mississippi. Jackson,
2000.
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