Ulcerative Colitis Rachel Gavin

Contents Overview of Ulcerative Colitis. Symptoms and Risks. Diagnosis and Treatment. Types and Severity of the disease. Causes.

Contents Environmental Factors. Treatment. Tests and Therapies. Research. References

Ulcerative Colitis (UC) Inflammatory bowel disease.(1) Chronic disease affecting the mucosa and sub mucosa of the large intestine and colon.(inflammation) Colitis- Ulcers/ Open sores. A variety in the types and degree of ulcerative colitis.(2) Ulcerative colitis likely involves abnormal activation of the immune system in the intestines. The immune system is composed of immune cells and the proteins that these cells produce. These cells and proteins serve to defend the body against harmful bacteria, viruses, fungi, and other foreign invaders. Activation of the immune system causes inflammation within the tissues where the activation occurs.   Ulcerative colitis is a chronic disease, which means that it is on-going and once someone has been diagnosed with UC it means that they will probably always have UC. However, UC generally follows a pattern of active flare or flare-up (periods of active inflammation that causes noticeable symptoms) followed by periods of remission (inflammation has subsided and there are no obvious symptoms).

Symptoms and Risks Rectal Bleeding Abdominal Pain Diarrhea Weight loss Variability of symptoms depending on the part of the intestine inflamed.(3) Colon Cancer.(High Risk Factor)(4) Ulcerative Colitis however is a systemic disease that affects many parts of the body outside the large intestine. It is often confused with Irritable bowl syndrome because it is an inflammatory bowl disease. Generally, patients with inflammation confined to the rectum and a short segment of the colon adjacent to the rectum have milder symptoms and a better prognosis than patients with more widespread inflammation of the colon. The different types of ulcerative colitis are classified according to the location and the extent of inflammation

Symptoms  Variability of symptoms reflects differences in the extent of disease (the amount of the colon and rectum that are inflamed) and the intensity of inflammation. Generally, patients with inflammation confined to the rectum and a short segment of the colon adjacent to the rectum have milder symptoms and a better prognosis than patients with more widespread inflammation of the colon.   Patients with ulcerative colitis can occasionally have ulcers involving the tongue, lips, palate and pharynx. Fig 1 (5)

Types of UC Ulcerative Proctitis- inflamation limited to the rectum. Proctosigmoiditis-inflamation of the rectum and sigmoid colon. Left sided Coilits – Inflamation on left colon. Fulminant Colitis – Rare.(6) Ulcerative proctitis refers to inflammation that is only in the rectum. In many patients with ulcerative proctitis, mild rectal bleeding may be the only symptom. Proctosigmoiditis involves inflammation of the rectum and the sigmoid colon (a short segment of the colon contiguous to the rectum). Symptoms of proctosigmoiditis are also rectal bleeding and cramps. Left-sided colitis involves inflammation that starts at the rectum and extends up the left colon (sigmoid colon and descending colon). Bloody diarrhea, abdominal cramps, weight loss, and left-sided abdominal pain are symptoms of left sided colitis. Fulminant colitis is a rare but severe form of UC. People with fulminant colitis are extremely ill with dehydration severe abdominal pain, protracted diarrhea with bleeding, and even shock. They are at risk of developing colonic rupture. They must be treated in hospital.

Types of UC Fig 2 (7) illustration of the different types of UC.

Severity of Disease Mild Moderate Severe Fulamint UC patients may be characterized according to the severity of their disease. Mild- Patients excrete fewer than 4 stools a day with / without blood. They may experience mild abdominal pain or cramping. Patients may feel that they are constipated but they are experiencing tenesmus which is the constant feeling of the need to empty the bowl. Moderate-  more than four stools daily, but with minimal signs of toxicity. Patients may display anemia (not requiring transfusions), moderate abdominal pain, and low grade fever. Severe-more than six bloody stools a day, and evidence of toxicity as demonstrated by fever, tachycardia and anemia Fulamint- more than ten bowel movements daily, continuous bleeding, toxicity and abdominal tenderness. If untreated Fulamint can lead to death.(8)

Prevalence of UC Affects both men and women. Peak incidence between 15-25 years. Incidence of 10 per 100,000 people annually. Highest incidence in Europe and North America.(9) The cause of ulcerative colitis is unknown. It can develop at any age, but peak 6 incidence is between the ages of 15 and 25 years,with a second, smaller peak between 55 and 65 years. There is no difference between men and women. The worldwide incidence is 0.5~24 new cases per 100 000 individuals, and prevalence is 100~200 cases per 100 000. It is indisputable that the emergence of IBD in various parts of the world is associated with social and economical progress, as initially observed in Northern Europe and North America, then the rest of Europe, South America and Japan, and further the Asian Pacific region.

Causes of UC Although UC has no known cause, there is a presumed genetic component to susceptibility. The disease may be triggered in a susceptible person by environmental factors. Although dietary modification may reduce the discomfort of a person with the disease, UC is not thought to be caused by dietary factors. Although UC is treated as though it were an autoimmune disease, there is no consensus that it is such. A large number of unrelated environmental factors are considered risk factors for UC, including smoking , diet, drugs such as oral contraceptives.(10)

Diagnosis No single test. Clinical History. Stool specimens. Blood tests. Colonoscopy. Tissue Biopsy. There is no single test which can establish the presence of ulcerative colitis. A diagnosis is usually made through a combination of tests and examinations including blood and stool sample tests, physical and rectal examinations, colonoscopy/sigmoidoscopy (a procedure where a camera is passed into the colon) and biopsy (taking a sample of the inner lining of the colon). In patients with suspected ulcerative colitis, the most important laboratory studies are stool examinations for ova and parasites, stool culture, and testing for Clostridium difficile toxin to help eliminate other causes of chronic diarrhea.(11)

Colonoscopy Healthy colon-no lesions or Ulcers. Ulcerative colon- inflamation and ulcers. Fig 3 (12)

Treatment of UC Dietary Modification.(13) Surgery- Colonectomy (Severe Cases) Medication. Corticosteroids.(14) Biologics.(14) Immunosuppressants.(14) Bacterial recolonization Probiotics may have benefit. Ulcerative colitis is a lifelong disease.. It can also affect a person’s social and psychological wellbeing, if poorly controlled. Patients with the disease can experience relapses. Around 50%of people with ulcerative colitis will have at least one relapse per year.146 About 80% of these are mild to moderate and about 20% are severe. Approximately 25% of people with ulcerative colitis will have one or more episodes of acute severe colitis in their life. 29% of these cases will have to get a colonectomy. Rectal therapy with 5-aminosalicylic acid compounds is used for proctitis. More extensive disease requires treatment with oral 5-aminosalicylic acid compounds and oral corticosteroids. The side effects of steroids limit their usefulness for chronic therapy. Patients who do not respond to treatment with oral corticosteroids require hospitalization and intravenous steroids. Biologics (such as infliximab, adalimumab and Golimumab) are powerful medications used for people with moderate-to-severe ulcerative colitis when other treatments have been unsuccessful.

Tests and Therapies Predicting UC associated Colon Cancer using reverse transcription polymerase chain analysis.(15) Peripheral Blood mononuclear cells are useful to differentiate UC and Crohns Disease.(16) Biomarkers can predict potential clinical responders to DIMS0150 a toll-like receptor 9 agonist in ulcerative colitis patients.(17) Genetic alterations are present not only in ulcerative colitis (UC)-associated neoplastic lesions but also in the adjacent normal colonic mucosa. Genetic changes in nonneoplastic mucosa might be effective markers for predicting the development of UC related Cancer. A predictive model was built for the development of UC-Cancer based on gene expression levels measured by reverse-transcription polymerase chain reaction analysis in nonneoplastic rectal mucosa. The predictive model developed shows that is it possible to identify patients who are likely to develop Colon Cancer. Biomarkers to distinguish between the two diseases have not yet been discovered. In this investigation protein profiles of peripheral blood mononuclear cells were analysed to discover a biomarker. Further investigation of the proteins, which distinguished between the two diseases, could promote elucidation of the pathophysiology of UC and CD. Using specific steroid response biomarkers, Glucorticosteroids refractory UC patients most likely to benefit from this treatment could be identified and illustrates the usefulness of a personalized treatment approach.

Research in UC Animal research in experimental ulcerative colitis in rats and Marine animals(18) Smoking reduces UC risk.(19) Possible Heriditary linkage. GLA is a fatty acid found in vegetable oils,black currant seed oil, and evening primrose oil, and it also occurs naturally in the body. Animal research suggests that it has anti-ulcer properties and may help to reduce inflammation in the gut. Smoking has been demonstrated to be protective in Ulcerative Colitis. Dendritic Cells play an important role in T-cell activation and differentiation . Cigarette smoke was examined on dendritic cells of patients with Ulcerative Colitis and Crohns disease.

Prognosis With Medication and a correct diet the outlook for people with UC is very good. No change in life expectancy. Regular check-ups. 50% of people experience mild symptoms only.

References 1-3-Canadian Digestive Health Foundation. understanding Ulcerative Colitis 2014 [15 April 2014]. http://www.cdhf.ca/bank/disorder_pdf_en/17-ulcerative-colitis.pdf 5-Stemcellstcm.com. Disease Severity in Ulcerative Colitis | Stem Cell Transplantation Center 2014 [14 April 2014]. http://www.stemcellstcm.com/disease-severity-in-ulcerative-colitis.html 6,8-Hoffman R. Crohn’s disease and ulcerative colitis . Drhoffman.com. 2014 [21 April 2014].: http://drhoffman.com/article/crohns-disease-and-ulcerative-colitis-2/ 7-Ecologyhealthcenter.net. Nutrition News . 2014 [11 May 2014]. http://ecologyhealthcenter.net/book/export/html/4 9-Langan R, Gotsch P, Krafczyk M, Skillinge D. Ulcerative colitis: diagnosis and treatment. American family physician. 2007;76-(9) http://www.aafp.org/afp/2007/1101/p1323.html 10-Camperi M, Gionetchi P. Bacteria as the cause of ulcerative colitis. Gut 2001 [7 April 2014];48(1):132- 135. http://gut.bmj.com/content/48/1/132.full 11- Longstrength G. Ulcerative colitis: MedlinePlus Medical Encyclopedia Nlm.nih.gov. 2012 [16 April 2014].: http://www.nlm.nih.gov/medlineplus/ency/article/000250.htm

References 12-Ecologyhealthcenter.net. Nutrition News . 2014 [11 May 2014]. http://ecologyhealthcenter.net/book/export/html/4 14-Plevy S. Emerging Therapies in Ulcerative Colitis. Medscape]. 2012 [6 April 2014];. Available from: http://www.medscape.org/viewarticle/769356 15- Watanabe T, Kobunai T, Yamamoto Y, Ikeuchi H, Matsuda K, Ishihara S et al. Predicting ulcerative colitis-associated colorectal cancer using reverse-transcription polymerase chain reaction analysis. Clinical colorectal cancer. 2011;10(2):134--141. http://www.ncbi.nlm.nih.gov/pubmed/2185956 16-Burczynski M, Peterson R, Twine N, Zuberek K, Brodeur B, Casciotti L et al. Molecular classification of Crohn's disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells. The journal of molecular diagnostics. 2006;8(1):51--61. http://www.ncbi.nlm.nih.gov/pubmed/16436634 17-Kuznetsov N, Zargari A, Gielen A, von Stein O, Musch E, Befrits R et al. Biomarkers can predict potential clinical responders to DIMS0150 a toll-like receptor 9 agonist in ulcerative colitis patients. BMC gastroenterology. 2014;14(1):79. http://www.ncbi.nlm.nih.gov/pubmed/24758565 18-Tolstanova G, Khomenko T, Deng X, Chen L, Tarnawski A, Ahluwalia A et al. Neutralizing anti-vascular endothelial growth factor (VEGF) antibody reduces severity of experimental ulcerative colitis in rats: direct evidence for the pathogenic role of VEGF. Journal of Pharmacology and Experimental Therapeutics. 2009;328(3):749--757. http://www.ncbi.nlm.nih.gov/pubmed/19060224 19-Ueno A, Jijon H, Traves S, Chan R, Ford K, Beck P et al. Opposing effects of smoking in Ulcerative Colitis and Crohn's Disease may be explained by differential effects on Dendritic Cells. Inflammatory bowel diseases. 2014;20(5):800--810. http://www.ncbi.nlm.nih.gov/pubmed/24691114