Ulcerative Colitis; Causes, Symptoms, Diagnosis, Treatment

Ulcerative Colitis








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Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. It causes irritation and swelling called inflammation. Eventually, that leads to sores called ulcers in the lining there. It is a chronic inflammation of the large intestine (colon). The colon is the part of the digestive system where water is removed from the undigested material, and the remaining waste material is stored. The rectum is the end of the colon adjacent to the anus. In patients with ulcerative colitis, ulcers and inflammation of the inner lining of the colon lead to symptoms of abdominal pain, diarrhea, and rectal bleeding.

Types of Ulcerative Colitis

According to the location and the extent of inflammation

Ulcerative proctitis – refers to inflammation that is limited to the rectum. In many patients with ulcerative proctitis, mild intermittent rectal bleeding may be the only symptom. Other patients with more severe rectal inflammation may, in addition, experience rectal pain, urgency (sudden feeling of having to defecate and a need to rush to the bathroom for fear of soiling), and tenesmus (ineffective, painful urge to move one’s bowels caused by the inflammation).

Proctosigmoiditis – involves inflammation of the rectum and the sigmoid colon (a short segment of the colon contiguous to the rectum). Symptoms of proctosigmoiditis, like that of proctitis, include rectal bleeding, urgency, and tenesmus. Some patients with proctosigmoiditis also develop bloody diarrhea and cramps.

Left-sided colitis – involves inflammation that starts at the rectum and extends up the left colon (sigmoid colon and descending colon). Symptoms of left-sided colitis include bloody diarrhea, abdominal cramps, weight loss, and left-sided abdominal pain.

Pancolitis or universal colitis  – refers to inflammation affecting the entire colon (right colon, left colon, transverse colon, and the rectum). Symptoms of pancolitis include bloody diarrhea, abdominal pain and cramps, weight loss, fatiguefever, and night sweats.

Fulminant colitis – is a rare but severe form of pancolitis. Patients with fulminant colitis are extremely ill with dehydration, severe abdominal pain, protracted diarrhea with bleeding, and even shock. They are at risk of developing toxic megacolon (marked dilatation of the colon due to severe inflammation) and colonic rupture (perforation)

According to 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). Mild abdominal pain or cramping may occur. 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, a colonic perforation may ensue. Unless treated, the fulminant disease will soon lead to death.

Causes of Ulcerative Colitis

No direct causes for ulcerative colitis are known, but many possible factors such as genetics and stress play a role.

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

Twelve regions of the genome 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 has been consistently shown to be at fault, suggesting that the disorder is influenced by 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.

Environmental factors

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. Few studies have investigated such an association; 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 – Some reports of the protection of breastfeeding in the development of inflammatory bowel disease contradict each other. One Italian study showed a potential protective effect.
  • One study of isotretinoin  – found a small increase in the rate of ulcerative colitis.

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. 

Symptoms of Ulcerative Colitis

Extent of involvement

The disease is classified by the extent of involvement, depending on how far 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.

Extraintestinal features 

The frequency of such extraintestinal manifestations has been reported as anywhere between 6 and 47 percent, and include the following

Aphthous ulcer of the mouth

Ophthalmic

  • Iritis or uveitis, which is inflammation of the eye’s iris
  • Episcleritis

Musculoskeletal

Cutaneous (related to the skin)

  • 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

Associate more symptoms

Diagnosis of Ulcerative Colitis

The initial diagnostic workup for ulcerative colitis includes the following
  • A complete blood count – is done to check for anemia; thrombocytosis, a high platelet count, is occasionally seen
  • Electrolyte studies and renal function tests – are done, as chronic diarrhea may be associated with hypokalemia, hypomagnesemia and pre-renal failure.
  • Liver function tests  – are performed to screen for bile duct involvement, primary sclerosing cholangitis.
  • X-ray
  • Urinalysis
  • Stool test – the doctor examines your stool for blood, bacteria, and parasites.
  • Endoscopy – the doctor uses a flexible tube to examine your stomach, esophagus, and small intestine.
  • Biopsy – A surgeon removes a tissue sample from your colon for analysis.
  • CT scan -This is a specialized X-ray of your abdomen and pelvis.
  • Erythrocyte sedimentation rate – can be measured, with an elevated sedimentation rate indicating that an inflammatory process is present.
  • C-reactive protein – can be measured, with an elevated level being another indication of inflammation.
  • Sigmoidoscopy a type of endoscopy -which can detect the presence of ulcers in the large intestine after a trial of an enema.
  • Colonoscopy – This test allows your doctor to view your entire colon and at the very end of your ileum using a thin, flexible, lighted tube with an attached camera. During the procedure, your doctor can also take small samples of tissue for laboratory analysis, which may help confirm a diagnosis.
  • Magnetic resonance imaging (MRI) –  An MRI scanner uses a magnetic field and radio waves to create detailed images of organs and tissues.
  • Capsule endoscopy – For this test, you swallow a capsule that has a camera in it. The camera takes pictures of your small intestine, which are transmitted to a recorder you wear on your belt. The images are then downloaded to a computer, displayed on a monitor and checked for signs of ulcerative colitis.
  • Balloon-assisted enteroscopy – For this test, a scope is used in conjunction with a device called an overtube. This enables the doctor to look further into the small bowel where standard endoscopes don’t reach. This technique is useful when capsule endoscopy shows abnormalities, but the diagnosis is still in question.

Endoscopic findings in ulcerative colitis include the following

  • Loss of the vascular appearance of the colon
  • Erythema (or redness of the mucosa) and friability of the mucosa
  • Superficial ulceration, which may be confluent, and
  • Pseudopolyps.

Histologic

  • Biopsies of the mucosa are taken to definitively diagnose UC and differentiate it from Crohn’s disease, which is managed differently clinically.
  • Microbiological samples are typically taken at the time of endoscopy. The pathology in ulcerative colitis typically involves distortion of crypt architecture, inflammation of crypts (cryptitis), frank crypt abscesses, and hemorrhage or inflammatory cells in the lamina propria.
  • In cases where the clinical picture is unclear, the histomorphologic analysis often plays a pivotal role in determining the diagnosis and thus the management.
  • By contrast, a biopsy analysis may be indeterminate, and thus the clinical progression of the disease must inform its treatment.

Differential diagnosis

The following conditions may present in a similar manner as ulcerative colitis and should be excluded

  • Infectious colitis  – which is typically detected on stool cultures > Pseudomembranous colitis, or Clostridium difficile-associated colitis, bacterial upsets often seen following administration of antibiotics
  • Ischemic colitis – inadequate blood supply to the intestine, which typically affects the elderly
  • Radiation colitis – in patients with previous pelvic radiotherapy
  • Chemical colitis – resulting from the introduction of harsh chemicals into the colon from an enema or other procedure.
  • Malignancy Cancer may present as acute flare of colitis or vice versa. It is important to rule out malignancy especially when the colitis is refractory to the treatment.

Treatment of Ulcerative Colitis

  • Antibiotics – may be used when infections—such as abscesses—occur in ulcerative colitis. They can also be helpful with fistulas around the anal canal and vagina.  Antibiotics used to treat bacterial infection in the GI tract include metronidazole, ampicillin, ciprofloxacin, fistulas, strictures, or prior surgery may cause bacterial overgrowth. Doctors will generally treat this by prescribing ampicillin, sulfonamide, cephalosporin, tetracycline, or metronidazole others.
  • Drugs to control mild diarrhea – for example, diphenoxylate, loperamide, codeine, and anticholinergics may help to reduce the number of bowel movements and relieve the feeling of bowel urgency. However, you should avoid these drugs if you have severe diarrhea because of inflammatory bowel disease. They should not be used if a fever is present.
  • Cholestyramine – an agent that binds bile salts, helps to control diarrhea associated with Crohn’s disease, particularly in people who have had a portion of their small intestine removed. Dicyclomine may relieve intestinal spasms.
  • Anti-inflammation drugs – the doctor will most likely start with mesalamine (Sulfasalazine), which helps control inflammation.
  • Corticosteroids – Prednisone and methylprednisolone help treat the inflammation in moderate or severe ulcerative colitis by helping to suppress the body’s immune system. Because they can trigger both short- and long-term effects, people shouldn’t use them continuously.
  • Immunosuppressant drugs – these drugs reduce the patient’s immune response. The doctor may prescribe 6-mercaptopurine or a related drug, azathioprine. Side effects include vomiting, nausea, and a weaker resistance to infection.
  • Mercaptopurine  & Azathioprine –  shown here in tablet form, is a first line steroid-sparing immunosuppressant
  • Azathioprine and 6-mercaptopurine (6-MP) – are the most commonly used immunosuppressants for maintenance therapy of Crohn’s disease. They are purine anti-metabolites, meaning that they interfere with the synthesis of purines required for inflammatory cells. They have a duration of action of months (slow-acting). Both drugs are dosed at 1.5 to 2.5 mg/kg, with literature supporting the use of higher doses.
  • Aminosalicylates (5-ASA) – Usually prescribed for people with a mild or moderate type of Crohn’s, these medications—which include sulfasalazine, mesalamine, olsalazine, and balsalazide—work by decreasing inflammation in the lining of the GI tract. Although they aren’t specifically approved by the Food and Drug Administration (FDA) to treat ulcerative colitis they can help prevent a flare-up, according to the Crohn’s & Colitis foundation.
  • Immunomodulators – If aminosalicylates and corticosteroids haven’t helped quell the inflammation, doctors may prescribe immunomodulators, including 6-mercaptopurine(6-MP), azathioprinecyclosporine, and methotrexate. These medications also work by suppressing the immune system and may take several weeks or months to start working.
  • Biologics – For people who haven’t responded to other forms of ulcerative colitis treatment, doctors may prescribe newer medications called biologics, which target certain inflammation-causing proteins in the body. These drugs include certolizumab, & are following
  • Adalimumab – Adalimumab, like infliximab, is an antibody that targets tumor necrosis factor. It has been shown to reduce the signs and symptoms of and is approved for treatment of, moderate to severe ulcerative colitis in adults who have not responded well to conventional treatments and who have lost response to or are unable to tolerate infliximab
  • Natalizumab – Natalizumab is an anti-integrin monoclonal antibody that has shown utility as induction and maintenance treatment for moderate to severe ulcerative colitis. Natalizumab may be appropriate in patients who do not respond to medications that block tumor necrosis factor-alpha, such as infliximab.
  • Ustekinumab – Ustekinumab is a monoclonal antibody that suppresses cytokines IL-12 and IL-23. Originally designed to treat psoriasis, Ustekinumab was FDA approved for the treatment of ulcerative colitis in 2016. Evidence from four quality randomized control trials suggest that Ustekinumab is effective for induction of clinical remission and clinical improvement in patients with moderate to severe ulcerative colitis
  • Infliximab – Infliximab is a mouse-human chimeric antibody that targets tumor necrosis factor alpha (TNFα), a cytokine in the inflammatory response. It is a monoclonal antibody that inhibits the pro-inflammatory cytokine TNFα. It is administered intravenously and dosed per weight starting at 5 mg/kg and increasing according to the character of the disease.
  • Subsequent therapy — Patients with fulminant ulcerative colitis who fail to improve by the third day of intensive treatment should be managed as patients with steroid-refractory ulcerative colitis with either cyclosporine or infliximab, or undergo colectomy. However, the threshold to undergo colectomy in patients who fail to respond to cyclosporine or infliximab is lower.

  • Cyclosporine — Intravenous cyclosporine has a role in the induction of remission in patients with severe or fulminant colitis but is not effective and/or safe for long-term use. Cyclosporine is used as a short-term “bridge” to therapy with the slower onset, longer acting medications, including azathioprine (AZA) or 6-mercaptopurine (6-MP). The role of cyclosporine in steroid-refractory ulcerative colitis is discussed in detail separately

  • Aminosalicylates – 5-ASA compounds, such as mesalazine and sulfasalazine, have shown to be of very little efficacy in the treatment of ulcerative colitis either for induction or for maintenance of remission. Current guidelines do not advise the use of 5-ASA compounds in ulcerative colitis.
  • Disease-modifying agents – such as and adalimumab are used in the treatment of active moderate-to-severe ulcerative colitis that has not responded to other medications. These medications act by disrupting the inflammatory process. Their use is somewhat restricted because they are expensive.
  • Small bowel resection – People with ulcerative colitis or those who develop an obstruction in the small intestine (from, for example, the accumulation of scar tissue) may need to undergo small bowel resection surgery to remove part of the intestine.
  • Anti-diarrheal and fluid replacements – when the inflammation subsides, diarrhea usually becomes less of a problem. However, sometimes the patient may need something for diarrhea and abdominal pain.
  • Methotrexate – is a folate anti-metabolite drug that is also used for chemotherapy. It is useful in the maintenance of remission for those no longer taking corticosteroids.
  • Thalidomide – has shown efficacy in reversing endoscopic evidence of disease.
  • Cannabis – may be used to treat ulcerative colitis because of its anti-inflammatory properties. Cannabis and cannabis-derived drugs may also help to heal the gut lining and may reduce the need for surgery and other medications.
  • Non-steroidal anti-inflammatory drugs (NSAIDs) –  such as ibuprofen and naproxen, can cause flares of inflammatory bowel disease in approximately 25% of patients. These flares tend to occur within one week after starting regular use of the NSAID.
  • Iron supplements – If you have chronic intestinal bleeding, you may develop iron deficiency anemia and need to take iron supplements.
  • Vitamin B-12 shots –  Crohn’s disease can cause vitamin B-12 deficiency. Vitamin B-12 helps prevent anemia, promotes normal growth and development, and is essential for proper nerve function.
  • Calcium and vitamin D supplements – ulcerative colitis and steroids used to treat it can increase your risk of osteoporosis, so you may need to take a calcium supplement with added vitamin D.
  • Consider multivitamins – Because ulcerative colitis can interfere with your ability to absorb nutrients and because your diet may be limited, multivitamin and mineral supplements are often helpful. Check with your doctor before taking any vitamins or supplements.
  • Helminthic therapy – In an experimental idea called helminthic therapy, moderate hookworm infections have been demonstrated to have beneficial effects on hosts suffering from diseases linked to overactive immune systems. This may be explained by the hygiene hypothesis. Hookworm therapy is currently in the trial stage at the University of Nottingham. Due to the unconventional nature of this therapy, it is not widely used.
  • In contrast – acetaminophen (paracetamol) and aspirin appear to be safe. Celecoxib, a cox-2 inhibitor, also appears to be safe, at least in short-term studies of patients in remission and on medication for their Crohn’s disease.
  • Dehydration – caused by profuse diarrhea may need to be treated by giving fluids through a drip. Medications to relieve pain and diarrhoea may also be given. Antibiotics may be required if the infection is present in the colon.

Surgery of Ulcerative Colitis

There are three main surgical techniques for the treatment of ulcerative colitis.

Total proctocolectomy and ileostomy – involves removing the entire colon and rectum. The end of the small intestine is brought out onto the wall of the abdomen. A collection bag is placed over the opening and faecal matter will pass into it. The bag is emptied by the person as required. The ileostomy is permanent.  This type of surgery offers a permanent cure for ulcerative colitis.

Sub-total colectomy and ileorectal anastomosis – is where most of the colon is removed, but the rectum is retained. The lower end of the small intestine is joined to the upper end of the rectum.

Ileoanal anastomosis (“Pouch operation”) – involves removing the entire colon and rectum. A section of the small intestine is used to make a small pouch where faecal matter can be stored. The pouch is then attached to the anus. This surgical technique does not require a permanent ileostomy.

Alternative medicine

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.

  • Melatonin – may be beneficial according to in vitro research, animal studies, and a preliminary human study.
  • 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.
  • 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 and 1500 mg/day are recommended for other conditions, most commonly cardiac. Fish oil also contains vitamin D, of which many people with IBD are deficient.
  • Short chain fatty acid (butyrate) enema – The epithelial cells in the colon uses 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 significantly decreased rate of relapse when the medication was used in conjunction with oral 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.
  • Curcumin (turmeric) therapy – in conjunction with taking the medications mesalamine or sulfasalazine, may be effective and safe for maintaining remission in people with quiescent ulcerative colitis. The effect of curcumin therapy alone on quiescent ulcerative colitis is unknown.
  • Fecal bacteriotherapy – involves the infusion of human probiotics through fecal enemas. Ulcerative colitis typically requires a more prolonged bacteriotherapy treatment than Clostridium difficile infection to be successful, possibly due to the time needed to heal the ulcerated epithelium. The response of ulcerative colitis is potentially very favorable with one study reporting 67.7% of sufferers experiencing complete remission. It suggests that the cause of ulcerative colitis may be a previous infection by a still unknown pathogen.
  • Probiotics  – have demonstrated the potential to be helpful in the treatment of ulcerative colitis. Specific types of probiotics such as Escherichia coli Nissle have been shown to induce remission in some patients for up to a year. Another type of probiotic that is said to have a similar effect is Lactobacillus acidophilus. The probiotics are said to work by calming some of the ongoing inflammation that causes the disease, which in turn allows the body to mobilize dendritic cells, otherwise known as messenger immune cells. These cells then are able to produce other T-cells that further aid in restoring balance in the intestines by rebalancing systematic inflammation.
  • Leukocyte apheresis – A type of leukocyte apheresis, known as granulocyte and monocyte adsorptive apheresis, still requires large-scale trials to determine whether or not it is effective. Results from small trials have been tentatively positive.
  • Iron supplementation – The gradual loss of blood from the gastrointestinal tract, as well as chronic inflammation, often leads to anemia, and professional guidelines suggest routinely monitoring for anemia with blood tests repeated every three months in active disease and annually in quiescent disease. Adequate disease control usually improves anemia of chronic disease, but iron deficiency anemia should be treated with iron supplements.
  • Nicotine – Unlike Crohn’s disease, ulcerative colitis has a lesser prevalence in smokers than non-smokers. Studies using a transdermal nicotine patch have shown clinical and histological improvement. In one double-blind, placebo-controlled study conducted in the United Kingdom, 48.6% of patients who used the nicotine patch, in conjunction with their standard treatment, showed complete resolution of symptoms. Another randomized, double-blind, placebo-controlled, single-center clinical trial conducted in the United States showed that 39% of patients who used the patch showed significant improvement, versus 9% of those given a placebo

References

Ulcerative Colitis

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