Ulcerative Colitis
Disease Details
Family Health Simplified
- Description
- Ulcerative colitis is a chronic inflammatory bowel disease that causes long-lasting inflammation and ulcers in the innermost lining of the colon and rectum.
- Type
- Ulcerative colitis is a type of inflammatory bowel disease (IBD). The exact genetic transmission is complex and not fully understood, but it is believed to involve a combination of genetic, environmental, and immune system factors. It is not inherited in a simple Mendelian fashion, but having a family history of the disease can increase one’s risk.
- Signs And Symptoms
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**Signs and Symptoms of Ulcerative Colitis:**
- **Abdominal Pain and Cramping:** Often experienced in the lower abdomen.
- **Diarrhea:** Frequent and urgent need to have a bowel movement, sometimes with blood.
- **Rectal Bleeding:** Presence of blood in stool.
- **Weight Loss and Fatigue:** Unintended weight loss and feeling tired due to malnutrition and blood loss.
- **Fever:** May occur during active disease flare-ups.
- **Tenesmus:** Sensation of an urgent need to move the bowels even when the colon is empty.
- **Growth Failure in Children:** Can occur due to chronic inflammation and malnutrition.
These symptoms may vary in severity and can come and go. - Prognosis
- Poor prognostic factors include: age < 40 years upon diagnosis, extensive colitis, severe colitis on endoscopy, prior hospitalization, elevated CRP and low serum albumin.
- Onset
- The onset of ulcerative colitis typically occurs between the ages of 15 and 30, although it can occur at any age. The exact cause is unknown, but it is believed to be due to a combination of genetic, environmental, and immune system factors. Symptoms can develop gradually or suddenly and may include abdominal pain, diarrhea (often with blood or pus), and rectal bleeding.
- Prevalence
- Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation of the colon and rectum. The prevalence of ulcerative colitis varies geographically. In North America and Europe, it affects approximately 120 to 250 per 100,000 people. The prevalence is generally lower in Asia, Africa, and South America but appears to be increasing in these regions.
- Epidemiology
- Together with Crohn's disease, about 11.2 million people were affected as of 2015. Each year it newly occurs in 1 to 20 per 100,000 people, and 5 to 500 per 100,000 individuals are affected. The disease is more common in North America and Europe than other regions. Often it begins in people aged 15 to 30 years, or among those over 60. Males and females appear to be affected in equal proportions. It has also become more common since the 1950s. Together, ulcerative colitis and Crohn's disease affect about a million people in the United States. With appropriate treatment the risk of death appears the same as that of the general population. The first description of ulcerative colitis occurred around the 1850s.Each year, ulcerative colitis newly occurs in 1 to 20 per 100,000 people (incidence), and there are a total of 5–500 per 100,000 individuals with the disease (prevalence). In 2015, a worldwide total of 47,400 people died due to inflammatory bowel disease (UC and Crohn's disease). The peak onset is between 30 and 40 years of age, with a second peak of onset occurring in the 6th decade of life. Ulcerative colitis is equally common among men and women. With appropriate treatment the risk of death appears similar to that of the general population. UC has become more common since the 1950s.The geographic distribution of UC and Crohn's disease is similar worldwide, with the highest number of new cases a year of UC found in Canada, New Zealand and the United Kingdom. The disease is more common in North America and Europe than other regions. In general, higher rates are seen in northern locations compared to southern locations in Europe and the United States. UC is more common in western Europe compared with eastern Europe. Worldwide, the prevalence of UC varies from 2 to 299 per 100,000 people. Together, ulcerative colitis and Crohn's disease affect about a million people in the United States.As with Crohn's disease, the rates of UC are greater among Ashkenazi Jews and decreases progressively in other persons of Jewish descent, non-Jewish Caucasians, Africans, Hispanics, and Asians. Appendectomy prior to age 20 for appendicitis and current tobacco use are protective against development of UC. However, former tobacco use is associated with a higher risk of developing the disease.
- Intractability
- Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can be difficult to manage and may not respond to standard treatments in some individuals, making it intractable in those cases. However, many patients can achieve remission and manage symptoms effectively with appropriate medication, lifestyle changes, and possibly surgery. The degree of intractability varies from person to person.
- Disease Severity
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Ulcerative colitis is a chronic inflammatory bowel disease primarily affecting the colon and rectum. Disease severity can vary greatly among individuals and is commonly classified into the following categories based on symptoms and extent of colon involvement:
1. **Mild**: Symptoms may include mild diarrhea, occasional blood in stools, and minimal abdominal pain. Patients typically have fewer than four stools per day without significant systemic illness.
2. **Moderate**: Patients experience more pronounced symptoms such as frequent diarrhea (up to six stools per day), moderate abdominal pain, significant blood in stools, and possible signs of systemic involvement like low-grade fever or anemia.
3. **Severe**: Characterized by more severe symptoms including frequent diarrhea (over six stools per day), severe abdominal pain, marked weight loss, fever, and significant systemic symptoms like tachycardia and anemia. Hospitalization may be required for management.
4. **Fulminant**: The most intense form, involving continuous and severe symptoms, often with complications such as high fever, severe abdominal pain, rapid heart rate, and anemia. There is a high risk of severe complications like toxic megacolon or perforation of the colon. Immediate intensive care and possibly surgical intervention may be necessary.
Disease severity in ulcerative colitis has crucial implications for treatment decisions and long-term management strategies. - Healthcare Professionals
- Disease Ontology ID - DOID:8577
- Pathophysiology
- An increased amount of colonic sulfate-reducing bacteria has been observed in some people with ulcerative colitis, resulting in higher concentrations of the toxic gas hydrogen sulfide. Human colonic mucosa is maintained by the colonic epithelial barrier and immune cells in the lamina propria (see intestinal mucosal barrier). The short-chain fatty acid n-butyrate gets oxidized through the beta oxidation pathway into carbon dioxide and ketone bodies. It has been shown that n-butyrate helps supply nutrients to this epithelial barrier. Studies have proposed that hydrogen sulfide plays a role in impairing this beta-oxidation pathway by interrupting the short chain acetyl-CoA dehydrogenase, an enzyme within the pathway. Furthermore, it has been suggested that the protective effect of smoking in ulcerative colitis is due to the hydrogen cyanide from cigarette smoke reacting with hydrogen sulfide to produce the non-toxic isothiocyanate, thereby inhibiting sulfides from interrupting the pathway. An unrelated study suggested that the sulfur contained in red meats and alcohol may lead to an increased risk of relapse for people in remission.Other proposed mechanisms driving the pathophysiology of ulcerative colitis involve an abnormal immune response to the normal gut microbiota. This involves abnormal activity of antigen presenting cells (APCs) including dendritic cells and macrophages. Normally, dendritic cells and macrophages patrol the intestinal epithelium and phagocytose (engulf and destroy) pathogenic microorganisms and present parts of the microorganism as antigens to T-cells to stimulate differentiation and activation of the T-cells. However, in ulcerative colitis, aberrant activity of dendritic cells and macrophages results in them phagocytosing bacteria of the normal gut microbiome. After ingesting the microbiome bacterium, the APCs release the cytokine TNFα which stimulates inflammatory signaling and recruits inflammatory cells to the intestines, leading to the inflammation that is characteristic of ulcerative colitis. The TNF inhibitors, including infliximab, adalimumab and golimumab, are used to inhibit this step during the treatment of ulcerative colitis. After phagocytosing the microbe, the APCs then enter the mesenteric lymph nodes where they present antigens to naive T-cells while also releasing the pro-inflammatory cytokines IL-12 and IL-23 which lead to T cell differentiation into Th1 and Th17 T-cells. IL-12 and IL-23 signaling is blocked by the biologic ustekinumab and IL-23 is blocked by guselkumab, mirikizumab and risankizumab, medications that are used in the treatment of ulcerative colitis. From the mesenteric lymph node, the T-cells then enter the intestinal lymphatic venule which provides transport to the intestinal epithelium where they mediate further inflammation characteristic of ulcerative colitis. The T-cells exit the lymphatic venule via the adhesion protein mucosal vascular addressin cell adhesion molecule 1 MAdCAM-1, the ulcerative colitis biologic treatment vedolizumab inhibits T-cell migration out of the lymphatic venules by blocking binding to MAdCAM-1. While the medications ozanimod and etrasimod inhibit the sphingosine-1-phosphate receptor to prevent T-cell migration into the efferent lymphatic venules. Once the mature Th1 and Th17 T-cells exit the efferent lymphatic venule, they travel to the intestinal mucosa and cause further inflammation. T-cell mediated inflammation is thought to be driven by the JAK-STAT intracellular T-cell signaling pathway, leading to the transcription, translation and release of inflammatory cytokines. This T-cell JAK-STAT signaling is inhibited by the medications tofacitinib, filgotinib and upadacitinib which are used in the treatment of ulcerative colitis.
- Carrier Status
- Ulcerative colitis is not a condition with a carrier status. It is a chronic inflammatory bowel disease affecting the colon and rectum.
- Mechanism
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Ulcerative colitis is a chronic inflammatory condition of the colon and rectum. Its mechanisms and molecular mechanisms involve a complex interplay of genetic, environmental, microbial, and immune factors.
### Mechanism:
1. **Immune Response**: The primary mechanism of ulcerative colitis involves an inappropriate immune response against the gut's own tissue. This is characterized by an excessive inflammatory response in the colon.
2. **Loss of Tolerance**: There is a loss of immune tolerance to the gut microbiota or other luminal antigens, leading to continuous inflammation.
3. **Epithelial Barrier Dysfunction**: Disruption of the epithelial barrier of the colon, which normally prevents gut bacteria from entering the underlying tissue, exacerbates the condition.
### Molecular Mechanisms:
1. **Genetic Factors**: Certain genetic polymorphisms have been associated with susceptibility to ulcerative colitis. Notable genes include NOD2, IL23R, and HLA variants.
2. **Cytokines and Chemokines**: Key cytokines such as TNF-α (Tumor Necrosis Factor-alpha), IL-17, IL-23, and interferons play crucial roles in sustaining inflammation.
3. **Signal Transduction Pathways**: Signaling pathways such as the NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) pathway are persistently activated, leading to the production of inflammatory mediators.
4. **T-cell Dysregulation**: An imbalance between regulatory T cells (Tregs) and effector T cells (Th17 cells) contributes to the chronic inflammation. Th17 cells, in particular, secrete IL-17 and other pro-inflammatory cytokines.
5. **Microbiome Alterations**: Dysbiosis, or imbalance in the gut microbiota, plays a role in triggering and perpetuating inflammation. Certain harmful bacteria may be overrepresented, while beneficial bacteria are reduced.
6. **Reactive Oxygen Species (ROS)**: ROS production increases within the inflamed gut mucosa, leading to further damage and perpetuation of the inflammatory cycle.
Understanding these mechanisms is crucial in developing targeted therapies to manage and treat ulcerative colitis effectively. - Treatment
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Ulcerative colitis is typically treated through a combination of medication, lifestyle changes, and sometimes surgery.
Medications include:
1. Anti-inflammatory drugs: Aminosalicylates (e.g., mesalamine), corticosteroids.
2. Immunosuppressants: Azathioprine, cyclosporine.
3. Biologics: Infliximab, adalimumab, vedolizumab.
Lifestyle changes involve:
- Diet modifications: Avoiding trigger foods, eating smaller, more frequent meals, and staying hydrated.
- Stress management techniques: Such as exercise, meditation, and counseling.
Surgical options may be considered for severe cases and involve:
- Proctocolectomy with ileal pouch-anal anastomosis (J-pouch): Removal of the colon and rectum, followed by creating a pouch from the end of the small intestine.
- Total proctocolectomy with ileostomy: Removal of the colon, rectum, and anus with an opening (stoma) created in the abdomen for waste to pass.
Regular follow-ups with a healthcare provider are essential for managing the disease effectively. - Compassionate Use Treatment
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For ulcerative colitis, compassionate use and off-label or experimental treatments may be considered in severe cases or when standard treatments fail. These can include:
1. **Fecal Microbiota Transplantation (FMT):** Though still under investigation, FMT involves transplanting fecal bacteria from a healthy donor to restore the colonic microbiota balance.
2. **Tofacitinib:** Originally an arthritis drug, this JAK inhibitor may be used off-label for ulcerative colitis.
3. **Vedolizumab:** This biologic targets the gut-specific integrin and is approved but may be used in complicated cases where other treatments have failed.
4. **Stem Cell Therapy:** Experimental treatments using mesenchymal stem cells are being explored for their regenerative properties.
5. **Ustekinumab:** Typically used for conditions like psoriasis and Crohn's disease, this biologic targeting IL-12 and IL-23 is being studied for ulcerative colitis.
6. **Risankizumab:** Another IL-23 inhibitor primarily used for psoriasis, being explored in experimental contexts for ulcerative colitis.
Always consult healthcare providers for the most suitable and safest options for treatment. - Lifestyle Recommendations
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Lifestyle recommendations for managing ulcerative colitis include:
1. **Dietary Adjustments**:
- Consume a balanced diet rich in fruits, vegetables, lean proteins, and whole grains.
- Identify and avoid trigger foods that exacerbate symptoms. Common triggers can include spicy foods, dairy products, high-fiber foods, and sugary items.
- Eat smaller, more frequent meals to reduce the burden on the digestive system.
2. **Hydration**:
- Drink plenty of water to stay well-hydrated, especially if experiencing diarrhea.
3. **Stress Management**:
- Practice stress-reducing techniques such as yoga, meditation, or deep-breathing exercises.
- Consider seeing a therapist or counselor to manage stress and anxiety effectively.
4. **Regular Exercise**:
- Engage in regular physical activity, such as walking, swimming, or low-impact aerobic exercises, to help reduce stress and maintain overall health.
5. **Quit Smoking**:
- If you smoke, seek resources and support to quit, as smoking can worsen symptoms.
6. **Adequate Sleep**:
- Ensure you get enough sleep to help your body heal and maintain energy levels.
7. **Medication Adherence**:
- Take prescribed medications as directed by your healthcare provider and attend regular check-ups to monitor your condition.
8. **Probiotic Supplements**:
- Consider taking probiotics to support gut health, but consult with your healthcare provider before starting any new supplements.
These lifestyle modifications can complement medical treatment and help manage symptoms more effectively. - Medication
- The first-line maintenance medication for ulcerative colitis in remission is mesalazine (also known as mesalamine or 5-ASA). For patients with active disease limited to the left colon (descending colon) or proctitis, mesalazine is also the first-line agent, and a combination of suppositories and oral mesalazine may be tried. Adding corticosteroids such as prednisone is also common in active disease, especially if remission is not achieved through mesalazine monotherapy, but they are not used in long-term treatment as their risks then outweigh their benefits. Immunosuppressive medications such as azathioprine and biological agents such as infliximab, adalimumab, ustekinumab, or vedolizumab are given in severe disease or if a patient cannot achieve remission with mesalazine and corticosteroids. As an alternative to mesalazine, one of its prodrugs such as sulfasalazine may be chosen for treatment of active disease or maintenance therapy, but the prodrugs have greater potential for serious side effects and have not been demonstrated to be superior to mesalazine in large trials.A formulation of budesonide was approved by the U.S. Food and Drug Administration (FDA) for treatment of active ulcerative colitis in January 2013. In 2018, tofacitinib was approved for treatment of moderately to severely active ulcerative colitis in the United States, the first oral medication indicated for long term use in this condition. The evidence on methotrexate does not show a benefit in producing remission in people with ulcerative colitis. Cyclosporine is effective for severe UC and tacrolimus has also shown benefits. Etrasimod was approved for medical use in the United States in October 2023.
- Repurposable Drugs
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There are several drugs that have been studied for potential repurposing in the treatment of ulcerative colitis. Some of these include:
1. **Thalidomide**: An immunomodulatory drug that has shown potential in reducing inflammation.
2. **Metformin**: Commonly used for diabetes, but has anti-inflammatory properties that could be beneficial.
3. **Naltrexone (low-dose)**: Originally used for opioid addiction, but may help reduce inflammation in low doses.
4. **Statins**: Typically used for lowering cholesterol, but they have immunomodulatory and anti-inflammatory effects.
5. **Azithromycin**: An antibiotic that also has anti-inflammatory properties.
These drugs are still under investigation, and their efficacy and safety for ulcerative colitis need to be validated through clinical trials. Always consult a healthcare provider before considering any off-label use of medications. - Metabolites
- Ulcerative colitis is a chronic inflammatory bowel disease that primarily affects the colon. While specific metabolites directly associated with ulcerative colitis can vary, common markers include increased levels of calprotectin and lactoferrin in the stool, as well as elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the blood. These metabolites are used to assess inflammation and disease activity in affected individuals.
- Nutraceuticals
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Nutraceuticals, which are food-derived products with health benefits, are being explored for the management of ulcerative colitis, an inflammatory bowel disease. Some of the nutraceuticals studied include:
1. **Curcumin**: This active compound in turmeric has anti-inflammatory properties that may reduce symptoms.
2. **Probiotics**: These beneficial bacteria can help restore gut flora balance and may reduce inflammation.
3. **Omega-3 Fatty Acids**: Found in fish oil, these have anti-inflammatory effects and may help in reducing flare-ups.
4. **Aloe Vera**: Known for its soothing properties, aloe vera may help alleviate gastrointestinal inflammation.
5. **Resveratrol**: An antioxidant found in grapes, it has anti-inflammatory properties that may benefit the gut lining.
While these nutraceuticals have shown promise in some studies, it’s important to consult a healthcare provider for personalized advice and treatment for ulcerative colitis. - Peptides
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Ulcerative colitis is a chronic inflammatory condition affecting the colon and rectum. Peptides are short chains of amino acids that can play roles in signaling and immune response in the body. Recent research has explored the potential of peptide-based therapies to reduce inflammation and promote healing in ulcerative colitis. These peptides may help modulate immune responses and repair tissue, offering a novel avenue for treatment.
As for the application of nanotechnology ("nan"), it holds promise in ulcerative colitis treatment through the targeted delivery of drugs. Nanoparticles can be engineered to deliver therapeutic agents directly to the inflamed sites in the colon, potentially increasing treatment efficacy while minimizing side effects. This targeted approach can enhance the precision and effectiveness of treatments, offering hope for better management of the disease.