Ulcerative colitis

Definition:
Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD). Ulcerative colitis is a form of colitis, a disease of the colon (the largest portion of the large intestine), that includes characteristic ulcers, or open sores. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset. IBD is often confused with irritable bowel syndrome (IBS).
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It is a disease that causes inflammation and sores (ulcers) in the lining of the large intestine (colon ). It usually affects the lower section (sigmoid colon) and the rectum. But it can affect the entire colon. In general, the more of the colon that’s affected, the worse the symptoms will be.

CLICK & SEE THE PICTURE OF  CHRONIC ULCERARIVE COLITIS

Ulcerative colitis shares much in common with Crohn’s disease, another form of IBD, but Crohn’s disease can affect the whole gastrointestinal tract while ulcerative colitis only attacks the large intestine, and while ulcerative colitis can be treated by performing a total colectomy (i.e., removing the entire large intestine), surgery for Crohn’s disease involves removing the damaged parts of the intestine and reconnecting the healthy parts, which does not cure Crohn’s, as it can recur after surgery, mostly at the site of the intestinal anastomosis (connection) or in other areas. Ulcerative colitis is an intermittent disease, with periods of exacerbated symptoms, and periods that are relatively symptom-free. Although the symptoms of ulcerative colitis can sometimes diminish on their own, the disease usually requires treatment to go into remission. Ulcerative colitis has an incidence of 1 to 20 cases per 100,000 individuals per year, and a prevalence of 8 to 246 per 100,000 individuals.

The disease is more prevalent in northern countries of the world, as well as in northern areas of individual countries or other regions. Rates tend to be higher in more affluent countries, which may indicate the increased prevalence is due to increased rates of diagnosis. It may also indicate that an industrial or Western diet and lifestyle increases the prevalence of this disease, including symptoms which may or may not be related to ulcerative colitis. 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, ulcerative colitis is not thought to be caused by dietary factors.

Ulcerative colitis, like its sister condition Crohn’s disease, is treated as an autoimmune disease. Treatment is with anti-inflammatory drugs, immunosuppression, and biological therapy targeting specific components of the immune response. Colectomy (partial or total removal of the large bowel through surgery) is occasionally necessary if the disease is severe, does not respond to treatment, or if significant complications develop. A total proctocolectomy (removal of the entirety of the large bowel and rectum) can cure ulcerative colitis (extraintestinal symptoms will remain), as the disease only affects the large bowel and rectum. While extra intestinal symptoms will remain, complications may develop.

Symptoms:
As ulcerative colitis is believed to have a systemic (i.e., autoimmune) origin, patients may present with comorbidities leading to symptoms and complications outside the colon. The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent. These include the following:

*Aphthous ulcer of the mouth
*Ophthalmic (involving the eyes):
*Iritis or uveitis, which is inflammation of the iris Episcleritis

*Musculoskeletal:
#Seronegative arthritis, which can be a large-joint oligoarthritis (affecting one or two joints), or may affect many small joints of the hands and feet
#Ankylosing spondylitis, arthritis of the spine
#Sacroiliitis, arthritis of the lower spine

*Cutaneous (related to the skin):CLICK & SEE
#Erythema nodosum, which is a panniculitis, or inflammation of subcutaneous tissue involving the lower extremities
#Pyoderma gangrenosum, which is a painful ulcerating lesion involving the skin

*Deep venous thrombosis and pulmonary embolism
*Autoimmune hemolytic anemia
*Clubbing, a deformity of the ends of the fingers.
*Primary sclerosing cholangitis, a distinct disease that causes inflammation of the bile ducts

Gastrointestinal:
The clinical presentation of ulcerative colitis depends on the extent of the disease process. Patients usually present with diarrhea mixed with blood and mucus, of gradual onset that persists for an extended period (weeks). They may also have weight loss and blood on rectal examination. The inflammation caused by the disease along with chronic loss of blood from the GI tract leads to increased rates of anaemia. The disease may be accompanied with different degrees of abdominal pain, from mild discomfort to painful bowel movements or painful abdominal cramping with bowel movements.

Ulcerative colitis is associated with a general inflammatory process that affects many parts of the body. Sometimes these associated extra-intestinal symptoms are the initial signs of the disease, such as painful arthritic knees in a teenager and may be seen in adults also. The presence of the disease may not be confirmed immediately, however, until the onset of intestinal manifestations.

Extent of Involvement:
Ulcerative colitis is normally continuous from the rectum up the colon. The disease is classified by the extent of involvement, depending on how far up the colon the disease extends:

*Distal colitis, potentially treatable with enemas:
#Proctitis: Involvement limited to the rectum.
#Proctosigmoiditis: Involvement of the rectosigmoid colon, the portion of the colon adjacent to the rectum.
#Left-sided colitis: Involvement of the descending colon, which runs along the patient’s left side, up to the splenic flexure and the beginning of the transverse colon.

*Extensive colitis, inflammation extending beyond the reach of enemas:
#Pancolitis: Involvement of the entire colon, extending from the rectum to the cecum, beyond which the small intestine begins.

Severities of the diseases:..>...click & see   
In addition to the extent of involvement, people may also be characterized by the severity of their disease.

#Mild disease correlates with fewer than four stools daily, with or without blood, no systemic signs of toxicity, and a normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). There may be mild abdominal pain or cramping. Patients may believe they are constipated when in fact they are experiencing tenesmus, which is a constant feeling of the need to empty the bowel accompanied by involuntary straining efforts, pain, and cramping with little or no fecal output. Rectal pain is uncommon.

#Moderate disease correlates with 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, 38 to 39 °C (100 to 102 °F).
Severe disease, correlates with more than six bloody stools a day or observable massive and significant bloody bowel movement, and evidence of toxicity as demonstrated by fever, tachycardia, anemia or an elevated ESR or CRP.

#Fulminant disease correlates with more than ten bowel movements daily, continuous bleeding, toxicity, abdominal tenderness and distension, blood transfusion requirement and colonic dilation (expansion). Patients in this category may have inflammation extending beyond just the mucosal layer, causing impaired colonic motility and leading to toxic megacolon. If the serous membrane is involved, colonic perforation may ensue. Unless treated, fulminant disease will soon lead to death.
Causes:
Experts aren’t sure what causes it. They think it might be caused by the immune system overreacting to normal bacteria in the digestive tract. Or other kinds of bacteria and viruses may cause it.

Some factors are indicative:
Genetic factors:
*A genetic component to the etiology of ulcerative colitis can be hypothesized based on the following:

#Aggregation of ulcerative colitis in families.
#Identical twin concordance rate of 10% and dizygotic twin concordance rate of 3%
#Ethnic differences in incidence
#Genetic markers and linkages

There are 12 regions of the genome that may be linked to ulcerative colitis, including, in the order of their discovery, chromosomes 16, 12, 6, 14, 5, 19, 1, and 3, but none of these loci have been consistently shown to be at fault, suggesting that the disorder arises from the combination of multiple genes. For example, chromosome band 1p36 is one such region thought to be linked to inflammatory bowel disease.

Some of the putative regions encode transporter proteins such as OCTN1 and OCTN2. Other potential regions involve cell scaffolding proteins such as the MAGUK family. There may even be human leukocyte antigen associations at work. In fact, this linkage on chromosome 6 may be the most convincing and consistent of the genetic candidates.

Multiple autoimmune disorders have been recorded with the neurovisceral and cutaneous genetic porphyrias including ulcerative colitis, Crohn’s disease, celiac disease, dermatitis herpetiformis, diabetes, systemic and discoid lupus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, Sjogren’s disease and scleritis. Physicians should be on high alert for porphyrias in families with autoimmune disorders and care must be taken with potential porphyrinogenic drugs, including sulfasalazine.

Environmental factors:
Many hypotheses have been raised for environmental contributants to the pathogenesis of ulcerative colitis. They include the following:

#Diet: as the colon is exposed to many dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis of both ulcerative colitis and Crohn’s disease. There have been few studies to investigate such an association, but one study showed no association of refined sugar on the prevalence of ulcerative colitis. High intake of unsaturated fat and vitamin B6 may enhance the risk of developing ulcerative colitis. Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages. Specifically, sulfur has been investigated as being involved in the etiology of ulcerative colitis, but this is controversial. Sulfur restricted diets have been investigated in patients with UC and animal models of the disease. The theory of sulfur as an etiological factor is related to the gut microbiota and mucosal sulfide detoxification in addition to the diet.

#Breastfeeding: There have been conflicting reports of the protection of breastfeeding in the development of inflammatory bowel disease. One Italian study showed a potential protective effect.

Several scientific studies have posited that Accutane is a possible trigger of Crohn’s disease and ulcerative colitis in some individuals. Three cases in the United States have gone to trial thus far, with all three resulting in multi-million dollar judgements against the makers of isotretinoin.

Autoimmune disease:
Ulcerative colitis is an autoimmune disease characterized by T-cells infiltrating the colon. In contrast to Crohn’s disease, which can affect areas of the gastrointestinal tract outside of the colon, ulcerative colitis usually involves the rectum and is confined to the colon, with occasional involvement of the ileum. This so-called “backwash ileitis” can occur in 10–20% of patients with pancolitis and is believed to be of little clinical significance. Ulcerative colitis can also be associated with comorbidities that produce symptoms in many areas of the body outside the digestive system. Surgical removal of the large intestine often cures the disease.

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Alternative theories:
Levels of sulfate-reducing bacteria tend to be higher in persons with ulcerative colitis. This could mean that there are higher levels of hydrogen sulfide in the intestine. An alternative theory suggests that the symptoms of the disease may be caused by toxic effects of the hydrogen sulfide on the cells lining the intestine.

Pathophysiology:
An increased amount of colonic sulfate-reducing bacteria has been observed in some patients 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. N-butyrate, a short-chain fatty acid, 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 benefit of smoking in ulcerative colitis is due to the hydrogen cyanide from cigarette smoke reacting with hydrogen sulfide to produce the nontoxic isothiocyanate, thereby inhibiting sulfides from interrupting the pathway. An unrelated study suggested that the sulphur contained in red meats and alcohol may lead to an increased risk of relapse for patients in remission.

Diagnosis:
The doctor will likely diagnose ulcerative colitis after ruling out other possible causes for your signs and symptoms. To help confirm a diagnosis of ulcerative colitis, he or she may want to have one or more of the following tests and procedures:

*Blood tests.The doctor may suggest blood tests to check for anemia — a condition in which there aren’t enough red blood cells to carry adequate oxygen to the patient’s tissues — or to check for signs of infection.

*Stool sample. White blood cells in  stool can indicate ulcerative colitis. A stool sample can also help rule out other disorders, such as infections caused by bacteria, viruses and parasites.

*Colonoscopy. This exam allows the doctor to view the entire colon using a thin, flexible, lighted tube with an attached camera. During the procedure,the doctor can also take small samples of tissue (biopsy) for laboratory analysis. Sometimes a tissue sample can help confirm a diagnosis.

*Flexible sigmoidoscopy.The doctor uses a slender, flexible, lighted tube to examine the sigmoid, the last portion of the patient’s colon. If the colon is severely inflamed, the doctor may perform this test instead of a full colonoscopy.

*X-ray. If the patient have severe symptoms, the doctor may use a standard X-ray of the abdominal area to rule out serious complications, such as a perforated colon.

*CT scan. A CT scan of your abdomen or pelvis may be performed if the doctor suspects a complication from ulcerative colitis or inflammation of the small intestine. A CT scan may also reveal how much of the colon is inflamed.

Treatment:
Treatment for ulcerative colitis depends on the severity of the disease. Most people are treated with medication. If there is significant bleeding, infection, or complications, surgery may be required to remove the diseased colon. Surgery is the only cure for ulcerative colitis.

Ulcerative colitis may affect patients in different ways, and treatment is adjusted to meet the needs of the specific patient. Emotional and psychological support is also important.

The symptoms of ulcerative colitis come and go. Periods of remission, in which symptoms resolve, may last for months or years before relapsing. Patients and physicians need to decide together whether medications will be continued during remission times. In some patients, it may be the case that the medications keep the disease under control, and stopping them will cause a relapse.

Ulcerative colitis is a lifelong illness and cannot be ignored. Routine medical check-ups are necessary and scheduled colonoscopies are important to monitor the health of the patient and to make certain that the ulcerative colitis is under control and not spreading.

Modern medication:
Ulcerative colitis can be treated with a number of medications including 5-ASA drugs such as sulfasalazine and mesalazine. Corticosteroids such as prednisone can also be used due to their immunosuppressing and short term healing properties, but due to the risks outweighing the benefits, they are not used long term in treatment. Immunosuppressive medications such as azathioprine, and biological agents such as infliximab and adalimumab are given lastly, only if people cannot achieve remission with 5-ASA and corticosteroids, due to their possible risk factors, including, but not limited to increased risk of cancers in teenagers and adults, TB and new or worsening heart failure (these side effects are rare). A formulation of budesonide was approved by the FDA for treatment of active ulcerative colitis in January 2013.The evidence on methotrexate does not show a benefit in producing remission in those with ulcerative colitis.

Alternative medicine and experimental treatment avenues:
About 21% of inflammatory bowel disease patients use alternative treatments. A variety of dietary treatments show promise, but they require further research before they can be recommended.

In vitro research, animal evidence, and limited human study suggest that melatonin may be beneficial.

Dietary fiber, meaning indigestible plant matter, has been recommended for decades in the maintenance of bowel function. Of peculiar note is fiber from brassica, which seems to contain soluble constituents capable of reversing ulcers along the entire human digestive tract before it is cooked. Oatmeal is also commonly prescribed.

Fish oil, and eicosapentaenoic acid (EPA) derived from fish oil, inhibits leukotriene activity, the latter which may be a key factor of inflammation. As an IBD therapy, there are no conclusive studies in support and no recommended dosage. But dosages of EPA between 180 to 1500 mg/day are recommended for other conditions, most commonly cardiac.

Short chain fatty acid (butyrate) enema. The colon utilizes butyrate from the contents of the intestine as an energy source. The amount of butyrate available decreases toward the rectum. Inadequate butyrate levels in the lower intestine have been suggested as a contributing factor for the disease. This might be addressed through butyrate enemas. The results however are not conclusive.

Herbal medications are used by patients with ulcerative colitis. Compounds that contain sulfhydryl may have an effect in ulcerative colitis (under a similar hypothesis that the sulfa moiety of sulfasalazine may have activity in addition to the active 5-ASA component). One randomized control trial evaluated the over-the-counter medication S-methylmethionine and found a significant decreased rate of relapse when the medication was used in conjunction with oral sulfasalazine.

Boswellia is an Ayurvedic (Indian traditional medicine) herb. One study has found its effectiveness similar to sulfasalazine.
helminthic therapy is the use of intestinal parasitic nematodes to treat ulcerative colitis, and is based on the premises of the hygiene hypothesis. Studies have shown that helminths ameliorate and are more effective than daily corticosteroids at blocking chemically induced colitis in mice, and a trial of intentional helminth infection of rhesus monkeys with idiopathic chronic diarrhea (a condition similar to ulcerative colitis in humans) resulted in remission of symptoms in 4 out of 5 of the animals treated. A randomised controlled trial of Trichuris suis ova in humans found the therapy to be safe and effective, and further human trials are currently on going. Yoga and meditation may help a lot.

CLICK TO SEE : Homeopathic treatment of ulcerative colitis

Research:
Helminthic therapy using the whipworm Trichuris suis has been shown in a randomized control trial from Iowa to show benefit in patients with ulcerative colitis. The therapy tests the hygiene hypothesis which argues that the absence of helminths in the colons of patients in the developed world may lead to inflammation. Both helminthic therapy and fecal bacteriotherapy induce a characteristic Th2 white cell response in the diseased areas, which was unexpected given that ulcerative colitis was thought to involve Th2 overproduction.

Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger RNA through Watson-Crick base pair interactions in order to subdue expression of ICAM-1. ICAM-1 propagates an inflammatory response promoting the extravasation and activation of leukocytes (white blood cells) into inflamed tissue. Increased expression of ICAM-1 has been observed within the inflamed intestinal mucosa of ulcerative colitis sufferers, where ICAM-1 over production correlated with disease activity. This suggests that ICAM-1 is a potential therapeutic target in the treatment of ulcerative colitis

Prognosis:
Ulcerative colitis is a form of inflammatory bowel disease for which there is no cure. For the first 10 years after diagnosis, the prognosis for most people with ulcerative colitis is good — the rate of colectomy is low, and most patients achieve remission.

Patients with ulcerative colitis usually have an intermittent course, with periods of disease inactivity alternating with “flares” of disease. Patients with proctitis or left-sided colitis usually have a more benign course: only 15% progress proximally with their disease, and up to 20% can have sustained remission in the absence of any therapy. Patients with more extensive disease are less likely to sustain remission, but the rate of remission is independent of the severity of disease.

Other long-term features and Mortality:
Changes that can be seen in chronic ulcerative colitis include granularity, loss of the vascular pattern of the mucosa, loss of haustra, effacement of the ileocecal valve, mucosal bridging, strictures and pseudopolyps.

Research has not revealed any difference in overall risk of dying in patients with Ulcerative colitis from that of the background population. The cause-of-death distribution may be different from that of the background population. It is thought that the disease primarily affects quality of life, and not lifespan.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.webmd.com/ibd-crohns-disease/ulcerative-colitis/ulcerative-colitis-topic-overview
http://en.wikipedia.org/wiki/Ulcerative_colitis
http://www.emedicinehealth.com/ulcerative_colitis/page6_em.htm
http://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/basics/treatment/con-20043763
http://ibdcrohns.about.com/od/ucbeyondbasics/f/ulcerative-colitis-prognosis.htm

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