Ulcerative Colitis Paper

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that primarily affects the colorectum. The rectum is involved, as is part or all of the colon, and UC is limited to the mucosal layer of the colon. It is one of the two most common disorders under the umbrella of inflammatory bowel diseases, alongside Crohn's disease (CD) (IBD). Some scientists have labeled IBD as "modern society disorders," citing an increase in prevalence since the mid-twentieth century. The majority of the time, the symptomatology is abdominal, with diarrhea, abdominal pain, and hematochezia being the most common clinical symptoms. Despite the postulation of multifactorial and genetic factors, the precise etiology of UC remains unknown. Medical treatment has had a significant impact on the clinical outcome. UC is a life long illness that has profound emotional and social impacts of affected patients. This paper aims to discuss the disease process, pertinent laboratory investigations, and medical treatment, correlation between UC and nutrition, and guidance to patient/family education plan.

Keywords: Ulcerative colitis, Inflammatory Bowel Diseases, Nutrition, Diet

Inflammatory Bowel Disease refers to a group of two main disorders: Crohn’s disease and ulcerative colitis. A third disorder, indeterminate colitis, presents with features similar to both CD and UC.

Nutrition, as define by the World Health Organization, refers to the intake of food, considered in relation to the body’s dietary needs.

Diet is defined by Merriam-Webster dictionary as the food and drink regularly provided or consumed.

Ulcerative Colitis

Ulcerative colitis is an inflammatory bowel disease affecting the colon in a diffuse, continuous and superficial pattern. The Inflammation can extend proximally in variable lengths. The highest incidence rates are in the developed world, however, incidences are increasing in developing countries (Ford, Moayyedi, & Hanauer, 2013). Prevalence worldwide is estimated at 5-500 people per 100000. In the United States, the prevalence among adults is 238 per 100,000 of population (Kappelman et al., 2007).

Lack of definitive etiology notwithstanding, a number of risk factors have been identified; White race (greater risk among Jews), male gender, obesity, gastrointestinal dysbiosis, genetics (risk eight times higher in first-degree relatives of people with the disorder), and age- bimodal distribution with frequencies highest at 15-25 years and 55-65 years of age (Ford et al., 2013). Interestingly, nicotine or smoking appears to be protective against UC (Mahid, Minor, Soto, Hornung, & Galandiuk, 2006).

Lower gastrointestinal tract endoscopy yields a firm diagnosis and secured if colorectal inflammation is confirmed and colorectal biopsies illustrate chronic changes such as crypt distortion, crypt abscesses and lymphocyte infiltrated lamina propria.

The severity of UC can be estimated as (1) mild: Characterized by bleeding per rectum, less than 4 loose motions per day. (2) Moderate: Rectal bleeding, more than 4 loose motions per day and (3) Severe: Defined by the presence of bleeding per rectum, more than 4 loose motions per day, the presence of systemic illness and hypoalbuminemia.

Disease process

The disorder often begins in the rectal area and progresses in a proximal pattern. Two theories or pathogenesis have emerged through studies. (1) There is a dysregulation of the immune system directed against the gut luminal bacteria or their products. (2) Gene-mediated colonic epithelial barrier defects are also implicated. Dysregulation of tight junctions and mucin depletion cause epithelial architectural disruption (Linskens et al., 2002). This facilitates normal commensal bacteria to be identified by dendritic cells and marked out as pathogenic, eliciting a cascade of T-Cell driven immune response with the eventual recruitment of B cells. The inflammatory process and infiltration of inflammation-associated cells (leukocyte, lymphocytes, mast cells, plasma cells) in the lamina propria results in eventual abscess formations, necrosis, and ulceration of the epithelial mucosa (Ordás, Eckmann, Talamini, Baumgart & Sandborn, 2012).

Pertinent Laboratory Investigations

Laboratory studies principally are useful to exclude other diagnoses, assess and monitor disease activity and the patient’s nutritional status. Serological markers, however, can assist in diagnosis.

1. Serological markers

Antinuclear Cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) are the most studied. Perinuclear ANCA (pANCA) is highly associated with UC. ANCA presence is 50% sensitive and 94% specific for UC. 12% of UC patients have positive ASCA values (Linskens et al., 2002). When both are performed, results help differentiate UC, from other IBD- CD and indeterminate colitis.

2. Stool Assays

Stool Assays are recommended to exclude infectious cause and/or complication. Leukocytes, ova and parasitic studies, culture for bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia and E.Coli O157: H7) and Clostridium difficile titer are evaluations done.

3. Inflammatory markers

Erythrocyte sedimentation rate and C-reactive protein levels commensurate with disease activity. Measurement of these and fecal lactoferrin or calprotectin help determine the severity of the intestinal inflammation.

4. Complete blood count and metabolic panel

Electrolyte abnormalities due to diarrhea and dehydration, low albumin, anemia are not uncommon in patients with severe UC. Hemogram and metabolic panels are recommended to monitor cell lines (leukocytes, erythrocytes, and thrombocytes), hemoglobin, serum albumin, potassium, magnesium levels and alkaline phosphatase concentration, which is elevated in UC patients with primary sclerosing cholangitis.

Medical management

The objective of care is to reduce morbidity and prevent complications. A study revealed 50% of affected people are in remission, but, 90% will experience a relapsing and remitting course (Langholz, Munkholm, Davidsen, & Binder, 1994). Thus, no single pharmacotherapeutic agent can offer entire control of symptoms throughout a lifetime of disease. This highlights the importance in tailoring therapy accordingly basing on disease severity, the course of disease during follow-up, and patient's preferences (Kornbluth, Sachar, & Practice Parameters Committee of the American College of Gastroenterology, 2010). Most commonly used medications include; corticosteroids, 5-aminosalicylates, immunosuppressant agents, tumor necrosis factor inhibitors, Antimicrobials and antidiarrheal agents.

Corticosteroids

These decrease inflammation. They are used to induce remission in active moderate to severe UC (Parente et al., 2010). Their role in maintaining remission is very limited. Commonly used corticosteroids are methylprednisolone, prednisolone, budesonide, and hydrocortisone.

Potential side effects include weight gain, hyperglycemia, acne, hirsutism, hypertension and long-term use is associated with bone loss.

5-aminosalicylates

Maintenance of remission is the main role of these agents. They have anti-inflammatory effects as well. Sulfasalazine, Balsalazide, and Mesalamine are the commonly used agents in this class of drugs.

Nausea, headache, abdominal pain, vomiting, skin rash, and diarrhea are the frequently reported side effects.

Tumor Necrosis Factor Inhibitors

Tumor Necrosis Factor is an endogenous cytokine essential in a myriad of immunological responses and functions. These agents block the action of the cytokine consequently curtailing a chain of immunological cascades. Examples include Infliximab, Golimumab, and Adalimumab

Common side effects include a headache, nausea, injection/infusion site reactions, arthralgia, and myalgia. More serious adverse events, albeit rare, include increased the risk of lymphoma, particularly if combined with other immunosuppressants.

Immunosuppressant Agents

These agents affect the activity of the immune system by regulation key elements. They are important in controlling UC that is poorly or non-responsive to corticosteroid therapy. Agents used include azathioprine, Cyclosporine (thiopurine) and 6-mercaptopurine.

Myelosuppression with associated opportunistic infections, hypersensitivity, pancreatitis and lymphoproliferative disorders are some of the potentially serious adverse effects of this class of therapy.

Antidiarrheal Agents

These provide symptomatic relief through prolonging transit time of gut contents, decreasing secretions and reducing visceral pain. Frequently used agents include loperamide and Diphenoxylate hydrochloride.

Adverse effects include sedation, abdominal discomfort, constipation, dry mouth or skin, and rash.

Antimicrobials

Antimicrobials are used in UC management for the purposed of managing complications associated with the illness- infection. Their role in affecting the course of UC specifically has been shown to be very minimal. Used individually or in combination, commonly used agents include metronidazole and ciprofloxacin.

Side effects commonly reported include nausea, headache, abdominal discomfort, rash, and vomiting.

Alpha 4 Integrin Inhibitors

An emerging treatment regimen for managing patients with moderate to severe UC that poorly respond to majority of the other regimens or showing dependence on corticosteroids. These agents are monoclonal antibodies that act to inhibit migration of leukocytes (T-lymphocytes) into the gastrointestinal tissues. Vedolizumab is an example.

Adverse effects most commonly associated to these agents include headache, nasopharyngitis, arthralgia, nausea and pyrexia.

Educating the newly diagnosed patient (and family)

It is imperative to discuss the diagnosis of UC and its treatment with a patient and the patient’s family or support unit. Elements of the patient education plan should include;

• Explain what ulcerative colitis is and that the cause is incompletely understood.
• Explain why the patient is experiencing symptoms they suffer
• Explain that UC is a lifelong disorder; however, symptoms wax and wane.
• Explain to the patient the disorder is manageable on medication and provide information on modality of treatment, its use, common side effects associated and drug interactions concerns, if the patient is taking any medication.
• To the pregnant patient, it is essential to reassure her that the health of the fetus shall not be affected by the use of 5-aminosalicyclates.
• Provide information on foods that may make symptoms worse and other dietary changes that may be needed. Encourage patients to adapt the use of a food journal.

Foods that may flare symptoms include; caffeinated drinks, fruit, and juice, fried/fatty/spicy foods, whole grain, and multigrain bread, alcohol, dairy products, red meat, beans, artificial colors/flavors/sweeteners, and condiments.

• Inform the patient of the usually nutritional deficiencies and the need to individualized meals and probable mineral/vitamin supplements.
• Provide information on support groups for long term coping with the disease, websites (such as Crohn's&colitisfoundation.org) for more information.
• Provide recommendations to specialist care (dietician, nutritionist, gastroenterologist)

Ulcerative Colitis and Nutrition

Nutritional deficiencies

Nutritional deficiencies are not uncommon in Ulcerative Colitis. Reduced intake is associated with disease activity and mediated by proinflammatory agents such as tumor necrosis factor alpha. Reduction in food intake analogously in some sufferers of UC is due to self-imposed abstinence from particular foods for fear of eliciting a flare. Malabsorption, increased energy expenditure and gastrointestinal protein loss and/or adverse effects of treatment regimens such as corticosteroids also contribute to deficiency. Common nutritional deficiencies in UC include

• Folate and Vitamin B12. Absorption is usually affected by medication such as sulfasalazine
• Iron. Chronic blood loss results in a progressively lowering iron levels
• Magnesium, Potassium, and Zinc; deficiencies in these two micronutrients results from profuse diarrhea often associated with the illness.
• Calcium and Vitamin D. Deficiency of calcium can occur from decreased intake such as reduced use of dairy products due to fear of exacerbating symptoms, use of corticosteroids long term suppress calcium and Vitamin D absorption.
• Protein(albumin): the chronic inflammatory milieu of UC increases energy demands and increased protein breakdown

Mineral Supplements plus diverse and nutrient-rich meals are encouraged for patients with UC to correct protein and micronutrient deficiencies.

Dietary recommendations

There is no special dietary recommendation for patients with Ulcerative colitis. A nutritionally balanced diet however is essential in managing symptoms and complications of UC. Caloric needs are largely similar to individuals without the disorder. The World Health Organization recommends a healthy diet for an adult comprises of;

• Fruits, vegetables, legumes and whole grains
• At least 400g (5 portions) of fruits and vegetables daily
• Less than 10% of total energy intake from free sugars for a person of healthy body weight consuming about 2000 calories per day.
• Less than 30% of total energy intake from fats, with unsaturated fats preferable to saturated fats.
• Less than 5g of salt per day. Iodized salt is favored.

The estimated calorie need for adults (18+ years) is 2400- 3200 calories (Dietary Guidelines for Americans, 2015). This need varies with age and level of activity. In patients of UC, however, increase in calories (250-500 more calories per day) in times of inflammatory flares is advised. Guidelines to eating, forwarded by the Crohn’s & Colitis Foundation Of America (2013), for individuals with UC during periods of flares involve eating smaller meals, having frequent meals, avoiding trigger foods, limiting food with insoluble fibre, eating in relaxed environments and lowing the amount of fried/greasy foods consumed. Generally, developing a diet tailored to patient is influenced by factors such as symptoms (diarrhea, abdominal pain, and flatulence), the severity of disease, presence of a flare or whether the individual is in remission, presence of a specific nutrient deficiency and history of surgeries for the disorder. In the event a flare trigger food is identified, it should be eliminated from the diet and substituted with another food that provides the same nutrient. These are called elimination diets. Food journals help keep track of food consumed, symptoms and can facilitate identification of foods provoking or exacerbating symptoms.

Dietary intakes and examples of a meal plan for patients with ulcerative colitis are shown in table 1 and table 2 respectively in appendices.

References

Ford, A. C., Moayyedi, P., & Hanauer, S. B. (2013). Ulcerative colitis. BMJ, 346, f432. https://doi.org/10.1136/bmj.f432

Kappelman, M. D., Rifas-Shiman, S. L., Kleinman, K., Ollendorf, D., Bousvaros, A., Grand, R. J., & Finkelstein, J. A. (2007). The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 5(12), 1424–1429. https://doi.org/10.1016/j.cgh.2007.07.012

Kornbluth, A., Sachar, D. B., & Practice Parameters Committee of the American College of Gastroenterology. (2010). Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. The American Journal of Gastroenterology, 105(3), 501–523; quiz 524. https://doi.org/10.1038/ajg.2009.727

Langholz, E., Munkholm, P., Davidsen, M., & Binder, V. (1994). Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology, 107(1), 3–11.

Linskens, R. K., Mallant-Hent, R. C., Groothuismink, Z. M. A., Bakker-Jonges, L. E., van de Merwe, J. P., Hooijkaas, H., Meuwissen, S. G. M. (2002). Evaluation of serological markers to differentiate between ulcerative colitis and Crohn's disease: pANCA, ASCA and agglutinating antibodies to anaerobic coccoid rods. European Journal of Gastroenterology & Hepatology, 14(9), 1013–1018.

Mahid, S. S., Minor, K. S., Soto, R. E., Hornung, C. A., & Galandiuk, S. (2006). Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clinic Proceedings, 81(11), 1462–1471. https://doi.org/10.4065/81.11.1462

Ordás, I., Eckmann, L., Talamini, M., Baumgart, D. C., & Sandborn, W. J. (2012). Ulcerative colitis. The Lancet, 380(9853), 1606–1619. http://dx.doi.org/10.1016/S0140-6736(16)32126-2

Parente, F., Molteni, M., Marino, B., Colli, A., Ardizzone, S., Greco, S., Gallus, S. (2010). Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis?: a prospective study. The American journal of gastroenterology, 105(5), 1150–1157. doi:10.1038/ajg.2009.672

Langham R.Y. (2013). Food to Eat With Ulcerative Colitis. Retrieved April 9, 2017, from http://www.livestrong.com/article/285609-food-to-eat-with-ulcerative-colitis/

Ulcerative Colitis - Disease Process, Symptoms, Diagnostic Tests, Treatments at Medi-Info. (n.d.). Retrieved from http://www.medi-info.com/ulcerative-colitis/

Ulcerative Colitis Diet Plan. (n.d.). Retrieved April 9, 2017, from http://drbenkim.com/articles-ulcerative-colitis-diet.htm

WHO | Healthy diet. (n.d.). WHO. Retrieved April 12, 2017, from http://www.who.int/mediacentre/factsheets/fs394/en/

Parente, F., Molteni, M., Marino, B., Colli, A., Ardizzone, S., Greco, S., Gallus, S. (2010). Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis?: a prospective study. The American journal of gastroenterology, 105(5), 1150–1157. doi:10.1038/ajg.2009.672

Appendices

Table 1

Dietary recommendations in ulcerative disease

Pregnant women on sulfasalazine should take 2mg of Folic Acid daily

Table 2

Three-day meal plan for patient with ulcerative colitis