Enigmatic Crohn’s Disease Essays

Enigmatic Crohn’s Disease Essays Enigmatic Crohn’s Disease Paper Enigmatic Crohn’s Disease Paper Physicians and scientists are always in the search for ways of curing diseases which until this time do not have known cure. One of these diseases is called Crohn’s disease which affects the intestinal tract. Its discovery by three outstanding men has enabled scientific, medical, and public communities to understand the mechanism behind this disease. Crohn’s disease has five types, with no known cause and manifests through various symptoms that can be alleviated through medications or surgery, and involves risk factors and complications. Discovery In 1900s, before the Crohn’s disease was given such name, the public identified it as an infectious disease. Specifically, they knew it as intestinal tuberculosis. But by 1930s, there was no proof about the infectious nature of the disease. In addition, the disease became widely known as Crohn’s disease when Burrill Crohn was not able to prove that there was an infectious cause in 1932. As a result, the search for the cause was discontinued. Due largely of these reasons, the research was concentrated in â€Å"immunology† (Paratuberculosis Awareness Research Association, 2003). In 1932, Burrill B. Crohn, along with Leon Ginzburg and Gordon Oppenheimer, published a medical literature which described the features of a disease which is now known as Crohn’s disease. Burrill Crohn was a gastroenterologist, and the disease was named after him because his name appeared first in the landmark paper (Crohn’s and Colitis Foundation of America, 2007). After 60 years, they have deeply studied the manifestations and natural history of Crohn’s disease but they were not able to know the cause yet. During such time, the three men conducted studies and experiments which gave them a lot of information about the inflammatory process in the bowel. In addition, during the times when they were studying the disease, they assumed that the lesions in the intestine were some form of tuberculosis or other chronic infection. Later on the men realized that the lesions did not have acid-fast organisms. They have also taken materials from different specimens and injected them into animals. However, it did not produce the desired results (Prantera Korelitz, 1996, p. 3). During this period, the men were thinking that there could be an infectious cause. During an interview with these men, Crohn firmly stated that the disease was caused by an infectious agent. They have found that a sulfa-containing drug called sulfathaladine had some positive effects on some patients. However, they did not use antibiotics to combat intestinal organisms. When steroids were introduced, they have seen that it was useful for inflammatory bowel disease (IBD). After more than four decades, researchers from the United States, Australia, and other countries started again the search for the cause despite the possibility of coming up with nonexistent findings (Paratuberculosis Awareness Research Association, 2003). Although there was still no known cure, they have found lots of information about Crohn’s disease and the larger group to which it belongs, the inflammatory bowel disease (IBD). Inflammatory Bowel Disease (IBD) Man’s immune system serves as the body’s defense against foreign substances such as bacteria, cancer, and viruses. Researchers have found out that among the people who have Crohn’s disease (CD) and ulcerative colitis (UC), the immune system attacks against the gastrointestinal system. However, they are not sure why this is the behavior of the immune system among Crohn’s patients. When the immune system attacks the GI tract, it becomes inflamed (Warner and Barlo, 2006, p. 2). IBD causes chronic inflammation in the gastrointestinal tract which then leads to various symptoms. When the disease progressed, other organs can also be infected other than the intestines. Once IBD is acquired, it becomes a lifelong disease characterized by periods of active disease and periods of disease control. IBD is different from irritable bowel syndrome (Achkar, 2006). In 2006, there were one million Americans inflicted with IBD. This number is split evenly between CD and UC (Crohn’s. net, n. d. ). The rate by which people acquire this disease is 10 per 100,000 people. Researches have shown that for every year, IBD accounts for more than half a million physician visits and 100,000 cases of hospitalization. This disease also infects young people as it develops between 10 and 30 ages. There are small cases of IBD development between 50 and 60 (Achkar, 2006). In addition, Caucasians have a higher risk than non-Caucasians. In addition, Caucasians lead the list of racial groups with the highest risk of IBD. Blacks and Hispanics are next in line, while the Asians have low risks of acquiring IBD (Targan, Shanahan, and Karp, 2003, p. 22). Moreover, whites are more prone to acquire IBD than non-whites. Jewish population is also more prone than those of non-Jewish background. Among Jewish people, those of Ashkenazi Jewish decent are at a higher risk of developing IBD (Achkar, 2006). The prevalence of IBD seems to ascend from north to south. In addition, IBD is less common in developed countries (Targan, Shanahan, and Karp, 2003, p. 22). In Western countries, one in 1,000 and one in 1,500 will have ulcerative colitis and Crohn’s disease, respectively. IBD is said to be more common in North America and Europe (Kamm, 1999, p. 2). Around one million Americans have IBD today (Eisenhower Army Medical Center, 2009). Crohn’s disease (CD) and another disease, the ulcerative colitis (UC), are both under a larger group of illnesses called inflammatory bowel disease (IBD) (Crohn’s and Colitis Foundation of America, 2009). However, Crohn’s is also known as IBD (Crohns. net, n. d. ). IBD was rare until the 20th century. By the end of the 20th century, gastroenterologists encountered this illness in the Western countries on a daily basis (Ekbom, 2003). Genetics of IBD Genes is an important factor in the causes of IBD. About 20 to 25% of people have a relative that have either CD or UC. The risk of a person for acquiring either CD or UC is 10 times greater than the general population if the person’s relative has the disease. The risk is 30 times if the relative is a brother or a sister (Crohn’s. net, n. d. ). Past researches have shown that both CD and UC are determined by genetic predisposition and have proven the role of genetic predisposition in acquiring either CD or UC. Genetic predisposition is the best explanation why differences occur between Jewish and non-Jewish populations (Targan, Shanahan, and Karp, 2003, p. 22). Furthermore, empirical data were gathered regarding the familial epidemiology of IBD. The disease seemed to be more common within families. Data also showed that compared to community-wide prevalence, the prevalence of the disease among siblings increases 10 to 30 fold. The prevalence of UC increases among the relatives of those who have UC and the prevalence of CD increases among the relatives of those who have CD. There were also data which suggest the existence of both UC and CD in one family. This incident points to an â€Å"increased frequency higher than just the co-occurrence by chance alone, suggesting an etiologic relationship between UC and CD† (Targan, Shanahan, and Karp, 2003, p. 23). Other studies suggest that a positive family history appears greatly among CD patients than UC patients. In addition, the relatives of those who have CD are at a higher risk of acquiring IBD than those who have UC. This means that in most cases, Crohn’s is often more familial than UC. Moreover, this means that Crohn’s has a more important role in terms of genetic predisposition (Targan, Shanahan, and Karp, 2003, p. 23). Crohn’s Disease Crohn’s disease is one type of IBD whose cause is still unknown (Warner and Barto, 2006, p. 2). According to the outstanding men who conducted extensive study on the disease and whose work gave birth to the term Crohn’s disease, Crohn’s disease cannot be cured, compared to UC which can be cured with surgery (Achkar, 2006). Crohn’s is a chronic disease affecting the gastrointestinal (GI) tract and usually attacks the intestine (ileum) and the large intestine (colon) (Eisenhower Army Medical Center, 2009). It also affects the patches surrounded by healthy tissues in the intestine (University of Maryland Medical Center, 2008). When the disease is not treated sooner, it can affect the gastrointestinal tract from the mouth to the anus (Crohn’s and Colitis Foundation of America, 2009). Causes Until the present time, Crohn’s disease is an enigma to the scientific and medical communities and to the public. There have been many attempts to understand this disease, but there were only few answers. This shows how extensive the nature of Crohn’s disease is. Those who studied Crohn’s assumed that the reason why Crohn’s disease is not fully researched is because it represents many illnesses and its clinical manifestations may be unpredictable. Moreover, researchers attribute the lack of definite causative microorganism to the fact that there is no such microorganism or many microorganisms cause Crohn’s disease (Prantera and Korelitz, 1996, p. 9). However, no one can completely establish the definite cause of Crohn’s disease. Certain theories were made pointing to a faulty immune system, diet, and genes (University of Maryland Medical Center, 2008). Man’s immune system is protected from infections by cells and proteins. One theory about what possibly causes Crohn’s disease indicates that there is an abnormal reaction in the immune system of people with Crohn’s disease, and thus mistakes foods, bacteria and substances as foreign substances (antigens). The normal response of the body’s immune system is to attack these substances. This then leads to white blood cells accumulating in the lining of the intestines. This produces chronic inflammation, which then further leads to bowel injury and ulcerations along the intestines (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Some scientists assumed that antigens either cause or stimulate the body’s defenses in producing inflammation in the GI tract without control. In addition, it was believed that once the immune system of the person with Crohn’s disease is â€Å"turned on,† it does not know how to â€Å"turn off† at the right time. Symptoms of IBD arise because the inflammation has damaged the intestine (Crohn’s and Colitis Foundation of America, 2009). Despite the theories, scientists are not sure if the abnormality existing in the immune system of people who have Crohn’s disease is a cause or a result of CD. Scientists are constantly faced with the findings of studies which showed that the inflammation in the GI tract is connected to three factors including the immune system, inherited genes, and the environment. Studies also showed that antigens, the foreign substances, are present in the environment. Scientists have also assumed that inflammation may be caused by the body’s reaction to the antigens. Others postulated that antigens cause the inflammation. Another theory is that the anti-tumor necrosis factor (TNF), a protein that the immune system produces, causes the inflammation of GI of those who have Crohn’s disease (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Furthermore, researchers assumed that the environmental factors cause the increasing prevalence of Crohn’s disease around the world. The researchers have also noted the countless experiments done with regards to drugs and diets that did not yield the desired results. This indicates that every approach taken is justified because different patients with different illnesses were treated, with only Crohn’s disease as the only thing they have in common. These perspectives can be viewed in two ways. One, Crohn’s disease is a very complex clinical entity that is beyond man’s comprehension. Two, Crohn’s disease is not a distinct clinical entity but â€Å"represents a syndrome with multiple etiologies that are lumped under one heading for lack of sufficient knowledge. † Either way, both medical and scientific communities are faced with the challenge of determining what causes the disease, the mechanisms of the inflammation, and further developing ways to treat the Crohn’s disease (Prantera and Korelitz, 1996, p. 9). In connection to the possibility of microorganisms as causative factors of Crohn’s disease, certain infectious agents have been under examination to determine whether these agents are etiological agents. A long list of bacteria and fungi and viruses ranges from Bacteroids to Y. paratuberculosis (Prantera and Korelitz, 1996, p. 11). Symptoms The symptoms of Crohn’s disease may be mild or severe. The most common among these are persistent diarrhea, abdominal pain, which is usually in the lower right area, rectal bleeding, fever and weight loss (Achkar, 2006). If rectal bleeding is serious and persistent, it can lead to anemia (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Diarrhea, on the other hand, is usually characterized by frequent and watery bowel movements (Crohn’s and Colitis Foundation of America, 2009), sometimes with blood (Rhodes, 2008). Some patients have experienced diarrhea between 10-20 times a day (Rhodes, 2008). In one study, 90% of the patients with Crohn’s disease had diarrhea (Doherty Way, 2005, p. 669). The authors have found out that stools are characterized as semi-solid or liquid. The bloody diarrhea of some patients resembled those of patients with ulcerative colitis (Doherty Way, 2005, p. 669). In abdominal pain, meals initiate mild colic. The pain can be relieved by defecation. The pain is caused by partial blockage in the small bowel, colon, or both. Patients who experienced complete blockage also experienced vomiting, cramping, and abdominal distention. The usual case is that when both diarrhea and abdominal pain manifest, the patient can experience weight loss, fever, anemia, and fever (Doherty Way, 2005, p. 670). Nausea, vomiting, floating stools (University of Maryland Medical Center, 2008), and fatigue are also associated with Crohn’s disease (Crohn’s and Colitis Foundation of America, 2009). Other less common symptoms include night sweats, abscesses, ulcers, and fissures, and fistulas. Abscesses are collections of pus that develop in the rectal area and can cause tenderness around the anus and fever (Crohns. net, n. d. ). Ulcers and fissures are tears that develop in the lining of the anus. These can cause bleeding and pain during defecation (Crohn’s and Colitis Foundation of America, 2007). Fistulas, on the other hand, are tunnels leading one loop of intestine to another. This loop can also connect the intestine to vagina, bladder, or skin. Fistulas develop around the anal area. When these are present, one can notice a â€Å"drainage of mucus, pus, or stool from the opening† (Crohn’s and Colitis Foundation of America, 2009). Skin problems and arthritis can also manifest. In children, symptoms include delay in growth and sexual development (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). These symptoms can result from complications of Crohn’s disease (Achkar, 2006). There are also other body parts which are affected by Crohn’s disease. Some people can also experience symptoms from other body parts such as redness and itchiness in the eyes, swelling and painful joints, osteoporosis, bumps and other lesions in skin, sores around the mouth, and, in rare cases, cirrhosis and hepatitis. These symptoms involving body parts outside of intestines are called extraintestinal manifestations. These can be the first signs of Crohn’s disease for some people. In some cases, these symptoms appear before a flare up. These symptoms â€Å"come and go. † The time that these symptoms do not manifest can be months or years (Crohn’s and Colitis Foundation of America, 2007). Types of Crohn’s Disease There are different types of Crohn’s disease, depending on the affected area in the GI tract. These types have varying symptoms and complications. The five types are presented below: Ileocolitis. This is the most common of Crohn’s disease which afflicts the ileum and colon (Crohn’s and Colitis Foundation of America, 2007). At least two thirds of those with Crohn’s disease have ileocolitis and ileitis. From a study, many of these patients experienced an indolent course which lasted four years. There were periods of relapses when they use and continue using immunomodulators (Bayless and Hanauer, 2001, p. 339). Diarrhea and abdominal pain are the common symptoms of ileocolitis (Crohns. net, n. d. ). Ileitis. Ileitis generally affects the ileum (Crohns. net, n. d. ). Symptoms that manifest include persistent abdominal cramps or pain, usually at the lower portion of the abdomen. In some cases, a patient may experience diarrhea which can be frequent. Pain is also associated with diarrhea. In addition, fatigue and exhaustion and weight loss can be experienced (Irons, 2006, p. 1). Treatment can include medication, antibiotics or surgery. At times, doctors may recommend a change in the diet (Irons, 2006, p. 2). Complications associated with Ileitis are fistulas and abscess (Crohns. net, n. d. ). Gastroduodenal Crohn’s Disease. This affects the stomach and duodenum. Duodenum is the highest portion of the small intestine (Health Information Publications, 2004, p. 5). At most 13 percent of people that have ileocolonic disease also suffer from gastroduodenal disease. Symptoms that manifest include nausea, vomiting (Bayless and Hanauer, 2001, p421), loss of appetite, and weight loss (Health Information Publications, 2004, p. 5). In addition, patients that suffer from this disease were found to have bleeding in the upper GI tract. There are also fistulas which develop in the ileum (Bayless and Hanauer, 2001, p421). Jejunoileitis. This disease affects jejunum, which is the upper portion of the small intestine (Crohn’s and Colitis Foundation of America, 2007). Jejunoileitis is an unusual manifestation of Crohn’s disease. It usually manifests in young patients. From studies, it was found out that there was a connection between high morbidity and frequent surgical management. In addition, this disease usually coexists with other types of Crohn’s disease. Symptoms include abdominal pain, diarrhea and weight loss (Bayless and Hanauer, 2001, p425). Its symptoms include abdominal pain after meals, malnutrition, and diarrhea (Health Information Publications, 2004, p. 5). Crohn’s (granulomatous) Colitis. This disease affects the colon only (Health Information Publications, 2004, p. 5). It is characterized by deep ulcers from rectum to cecum (Kouklakis et. al, 2007). Symptoms include rectal bleeding, diarrhea, ulcer, abscess, and fistulas. Skin lesions and joint pains are also associated with this disease (Crohns. net, n. d. ). The symptoms can vary from person to person, and patients should know which treatment options are effective in alleviating these symptoms. Treatments include medications such as Aminosalicylates (5-ASA), Corticosteroids, Antibiotics, Immuno-modulators, and biologic therapies, and surgery. Treatment Although there is no cure for Crohn’s disease, there have been recommended treatment to ease the symptoms. Treatment can be in the form of medications, diet, and surgery. These treatment options aim to restrain the inflammatory response (Crohn’s and Colitis Foundation of America, 2009), relieve symptoms, and alleviate nutritional deficiencies. In addition, treatments can help control any recurrence. Treatment would also depend on complications, severity of the disease, and the body’s response to previous medications (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Thus, treatment approach would vary from person to person (Crohn’s and Colitis Foundation of America, 2007). Because Crohn’s disease is chronic, or on-going, sometimes long-term treatment is required (Achkar, 2006). There are several medical therapies that can help alleviate Crohn’s disease. The categories for medications include Aminosalicylates, corticosteroids, antibiotics, immuno-modulators, and biologic therapies (Patel, 2007, p. 2). Aminosalicylates (5-ASA). Aminosalicylates contain sulfasalazine and mesalamine. Mesalamine can control inflammation (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). The most active component of Aminosalicylates is called 5-aminosalicylic acid, or ASA. 5-ASA functions to lessen inflammation in the GI wall. Most of the drugs under 5-ASA are pills taken orally, but there are also suppository forms (Achker, 2006). Patients that have mild to moderate symptoms are recommended this drug, which includes Pentasa, Asacol, Canasa Enemas, Colazal, and Rowasa Enemas. Other forms of this durg, such as Rowasa and Canasa, can be administered rectally (Crohn’s and Colitis Foundation of America, 2009). Side effects of these drugs can range from nausea to headache. In some cases, cramps and gas and heartburn occur. But if aminosalicylates are effective, they can bring the symptoms under control and can prevent recurrences (National Institute of Diabetes and Digestive and Kidney Diseases, 2006) Corticosteroids. This group of drugs can treat moderate to severe symptoms and can substitute for aminosalicylates if the latter is not effective (Patel, 2007, p. 3). Some people consider corticosteroids as very effective (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Prednisone, hydrocortisone, and prednisolone are the ones commonly used (Patel, 2007, p. 3). Doctors usually prescribe a large dose of prednisone when symptoms are at their worse. When these symptoms are under control, the dosage is lowered (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Unlike 5-ASA, corticosteroids need no direct contact with inflammation. Corticosteroids function to create an anti-inflammatory reaction to body areas, even the affected intestine. However, doctors found out that this group of drugs does not maintain remission or control flare ups (Patel, 2007, p. 3). There can be multiple side effects which develop due to high dosages and long duration of therapies. Mood changes, sleep disturbances, increased blood sugar levels, irritability, and increased appetite are early common side effects. Cataracts, acne, round face, osteoporosis are side effects associated with long-term use (Achkar, 2006). Other common side effects include swelling in the legs, susceptibility to infections, depression, blurred vision and hair growth (Crohns. net, n. d. ). Antibiotics. Antibiotics suppress bacterial overgrowth in the small intestine (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Flagyl is the commonly used antibiotics in IBD. Flagyl can treat infections that parasites and bacteria cause. Flagyl is also used for anal fistulas (Patel, 2007, p. 3). Other commonly used antibiotics are ciprofloxacin, metronidazole, ampicillin (Crohn’s and Colitis Foundation of America, 2009). Metronidazole is usually used to manage perineal Crohn’s disease (Mayo Clinic, 2009). However, the bad thing about antibiotics is that they kill good and bad bacteria. When metronidazole and alcohol are taken together, it can cause severe side effects such as nausea, headache, and vomiting. Some of the uncommon side effects include loss of appetite, rash, permanent nerve damage (Crohns. net, n. d. ). Immuno-modulators. This class of drugs can help decrease costicosteroid dosage and heal anal fistulas. In addition, they can help in maintaining remission (Crohn’s and Colitis Foundation of America, 2009). Immuno-modulators include 6-MP (6-Mercaptopurine), Methotrexate, and Azathioprine. These drugs can substitute corticosteroids when the latter are not effective. Reducing immune cells and obstructing protein cells can lessen inflammation (Patel, 2007, p. 3). 6-MP and azathioprine are taken orally. Their effects are not immediate. Thus, steroids are taken on a short-term duration to help control the disease during the first stages of taking 6-MP and azithioprine. Their side effects include pancreatitis, allergic reactions (Achkar, 2006), inflammation of the liver, and bone marrow toxicity (Patel, 2007, p. 3). Other side effects include susceptibility to infections, loss of appetite and nausea (Crohns. net, n. d. ). Methotrexate, on the other hand, functions by reducing the activity of the body’s immune system. It can also help bring Crohn’s disease into remission. Methotrexate can also be taken orally, although it can also be injected under the skin. Side effects associated with Methotrexate are infections, inflammation of the liver, and scarring in the lungs on rare occasions (Achkar, 2006). Biologic therapies. In 1998, the Food and Drug Administration (FDA) introduced a new biologic therapy in the form of Remicade (Infliximab) (Patel, 2007, p. 4). Remicade contains antibody which prevents the immune system from producing tumor necrosis factor (TNF). TNF is a chemical that worsens inflammation (Crohn’s and Colitis Foundation of America, 2009). Remicade is used for patients who have moderate to severe IBD. It is used when other medications are not effective and is given intravenously (Rhodes, 2008). In addition, Remicade works by blocking TNF, which is a part of the immune system. Through this blockage, inflammation in the intestine can be reduced. From clinical studies, it was found out that one or three infusions can bring inflammation into remission state and allow fistulas to heal (Achkar, 2006). Another biologic therapy is adalimumab, which FDA approved in 2007. It is a man-made protein which blocks TNF. Adalimumab attaches itself to TNF and blocks its effects. Natalizumab is another antibody which â€Å"inhibits certain types of white blood cells. † The latest addition to the biologic therapies is Certolizumab which the FDA approved on April 2008. It aims to reduce signs and symptoms of Crohn’s disease (Crohn’s and Colitis Foundation of America, 2009). Side effects of using Remicade include fever, chills, abdominal pain, itching, chest pain, nasal congestion, sore throat, nausea, vomiting, fainting and cough. Less common side effects are skin rash, low or high blood pressure, back pain, pain, diarrhea, and white patches in mouth or tongue. In rare occasions, a patient may experience weight loss, constipation, abscess, and stomach pain (Crohns. net, n. d. ). Surgery The three indications for surgery are perforation, stricture, and bleeding (Norton, Barie, Bollinger, Chang, and Lowry, 2008, p. 1021). In addition, surgery is needed when Crohn’s disease is in a very serious state and the medications were not effective (Achkar, 2006). Other indications for surgery are recurrence of symptoms, worsening of symptoms, occurrence of complications, intestinal blockage, hemorrhage, growth retardation, and carcinoma (Norton, Barie, Bollinger, Chang, and Lowry, 2008, p. 1021). Seventy percent of those who have Crohn’s disease will be required to undergo surgery to remove some part of their digestive tract Achkar, 2006). In some cases, surgery can repair fissures or fistulas. In addition, surgery is required especially if there is an intestinal blockage or intestinal abscess (Crohn’s and Colitis Foundation of America, 2007). Conservative resection is usually the preferred surgical procedure. Surgeries are seen to preserve the intestinal length. However, surgery is only limited to the area where complications arise (Doherty and Way, 2005, p. 672). When the diseased segment of bowel is removed, this is referred to as resection. The process of joining two healthy bowel ends is called anastomosis. Ileostomy can also be preferred if the diseased area is the colon. When colon is removed, surgeons attach the small bowel to the skin in order for waste products to be emptied into a pouch in the abdomen. This type of surgery is done when rectum has been diseased (Crohn’s and Colitis Foundation of America, 2007). Another type of surgery is colectomy, wherein the entire colon is removed when Crohn’s disease has affected the large intestine (Crohn’s and Colitis Foundation of America, 2009). Although surgery can allow symptom-free years, it is not a cure for Crohn’s disease. In addition, certain patients need to have more than one operation because inflammation appears near the area where the affected intestine was removed (National Institute of Diabetes and Digestive and Kidney Diseases, 2006). Furthermore, those who are considering surgery should first weigh its benefits and risks. Surgery is also not appropriate for every patient. Thus, it is of importance to consult their doctors who had experience regarding Crohn’s disease. Risk Factors Several risk factors have been associated with Crohn’s disease, as shown in Table 1. Risk factors refer to those that make a person more inclined to getting a disease (Warner Barto, 2006, p. 204). Table 1. Risk Factors that are Associated with Crohn’s Disease. Familial aggregation Stressful events Nicotine Early life exposures Smoking Weaning Oral moist snuff Hygiene Oral contraceptives Infections Diet Dairy products Refined sugar Passive smoking Cereals (cornflakes) â€Å"Sheltered child† â€Å"Fast food† Infections Margarine Mycobacteria Baker’s yeast Measles Physical activity Nonspecific virus infections Socioeconomic status Source: Prantera Korelitz, 1996. Familial aggregation. As mentioned previously, those who have relatives with Crohn’s disease are at a higher risk of developing the disease. Previous analytical studies have established familial aggregation as the most established risk factor. There were countless documented cases which established the positive history of IBD in 23% of Ashkenazi Jews in California. There were also studies of monozygotic twins which showed that there was a 58. 3% concordance rate for developing the disease. The same level of concordance rate for Crohn’s disease was found in diabetes and bronchial asthma. The concordance rate was lower for dizygotic twins. The reason why the concordance rate for monozygotic twins is higher is because of genetic and not environmental factors. Additionally, the concordant twin siblings developed Crohn’s disease within two years of each other (Prantera and Korelitz, 1996, p. 63). Smoking. A person’s history of smoking is said to be the â€Å"most established† (Prantera Korelitz, 1996, p. 63) and the â€Å"most important† (Michetti, 2005, p. 50) environmental and external risk factor for the disease. Past researches found out that smoking can worsen symptoms (University of Maryland Medical Center, 2008). Additionally, those who smoke are more likely to develop Crohn’s disease than the non-smokers. There were also empirical data to support the finding that smokers have an aggressive form of Crohn’s disease than non-smokers. However, researchers were not able to determine the exact effects that cigarette smoking has on the GI tract (Achkar, 2006). From the past researches, it was found out that there was no consistent increased risk among those who smoke. This means that smoking is a promoting factor of Crohn’s disease. Smokers who have Crohn’s disease are also seen to be more prone to relapses, surgery, hospitalization, diarrhea, and pain compared to former smokers or nonsmokers. And as smoking is associated with lung cancer, those who smoke and have Crohn’s disease are at a higher risk of experiencing respiratory malignancies. However, there was no association found from the studies done in relation to cancer morbidity and mortality. This added to doubts regarding the smoking’s etiological attributable fraction in Crohn’s disease (Prantera Korelitz, 1996, p. 63). The association between Crohn’s disease and smoking is further complicated because smokers have a lower risk of developing ulcerative colitis and former smokers are at a higher risk. The opposite results of studies regarding the role of smoking in both Crohn’s disease and ulcerative colitis prompted researchers and experts to assume the possibility of smoking as a determinant of either Crohn’s or colitis developing in an individual (Prantera Korelitz, 1996, p. 63). Oral contraceptives. This is another risk factor of Crohn’s disease, wherein women who take oral contraceptives are more likely to develop the disease (Crohn’s. net, n. d. ). However, there were other studies whose results showed that the causality of oral contraceptive is weak (Crohns. org, n. d. ). One such