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 culture, to rule out parasites and infectious causes.

- 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.

Although ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease.

The simple clinical colitis activity index was created in 1998 and is used to assess the severity of symptoms.

The diagnosis is usually confirmed by biopsies on colonoscopy. Fecal calprotectin is useful as an initial investigation, which may suggest the possibility of IBD, as this test is sensitive but not specific for IBD.

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.

Other diseases may cause an increased excretion of fecal calprotectin, such as infectious diarrhea, untreated coeliac disease, necrotizing enterocolitis, intestinal cystic fibrosis and neoplastic pediatric tumor cells.

Conditions with similar symptoms as Crohn's disease includes intestinal tuberculosis, Behçet's disease, ulcerative colitis, nonsteroidal anti-inflammatory drug enteropathy, irritable bowel syndrome and coeliac disease.

Conditions with similar symptoms as ulcerative colitis includes acute self-limiting colitis, amebic colitis, schistosomiasis, Crohn's disease, colon cancer, irritable bowel syndrome, intestinal tuberculosis and nonsteroidal anti-inflammatory drug enteropathy.

A small bowel follow-through may suggest the diagnosis of Crohn's disease and is useful when the disease involves only the small intestine. Because colonoscopy and gastroscopy allow direct visualization of only the terminal ileum and beginning of the duodenum, they cannot be used to evaluate the remainder of the small intestine. As a result, a barium follow-through X-ray, wherein barium sulfate suspension is ingested and fluoroscopic images of the bowel are taken over time, is useful for looking for inflammation and narrowing of the small bowel. Barium enemas, in which barium is inserted into the rectum and fluoroscopy is used to image the bowel, are rarely used in the work-up of Crohn's disease due to the advent of colonoscopy. They remain useful for identifying anatomical abnormalities when strictures of the colon are too small for a colonoscope to pass through, or in the detection of colonic fistulae (in this case contrast should be performed with iodate substances).

CT and MRI scans are useful for evaluating the small bowel with enteroclysis protocols. They are also useful for looking for intra-abdominal complications of Crohn's disease, such as abscesses, small bowel obstructions, or fistulae. Magnetic resonance imaging (MRI) is another option for imaging the small bowel as well as looking for complications, though it is more expensive and less readily available. MRI techniques such as diffusion-weighted imaging and high-resolution imaging are more sensitive in detecting ulceration and inflammation compared to CT.

A colonoscopy is the best test for making the diagnosis of Crohn's disease, as it allows direct visualization of the colon and the terminal ileum, identifying the pattern of disease involvement. On occasion, the colonoscope can travel past the terminal ileum, but it varies from person to person. During the procedure, the gastroenterologist can also perform a biopsy, taking small samples of tissue for laboratory analysis, which may help confirm a diagnosis. As 30% of Crohn's disease involves only the ileum, cannulation of the terminal ileum is required in making the diagnosis. Finding a patchy distribution of disease, with involvement of the colon or ileum, but not the rectum, is suggestive of Crohn's disease, as are other endoscopic stigmata.

The utility of capsule endoscopy for this, however, is still uncertain. A "cobblestone"-like appearance is seen in approximately 40% of cases of Crohn's disease upon colonoscopy, representing areas of ulceration separated by narrow areas of healthy tissue.

Symptoms suggestive of colitis are worked-up by obtaining the medical history, a physical examination and laboratory tests (CBC, electrolytes, stool culture and sensitivity, stool ova and parasites et cetera). Additional tests may include medical imaging (e.g. abdominal computed tomography, abdominal X-rays) and an examination with a camera inserted into the rectum (sigmoidoscopy, colonoscopy).

An important investigation in the assessment of colitis is biopsy. A very small piece of tissue (usually about 2mm) is removed from the bowel mucosa during endoscopy and examined under the microscope by a histopathologist. It can provide important information regarding the cause of the disease and the extent of bowel damage.

"Indeterminate colitis" is the classification for colitis that has features of both "Crohn's disease" and "ulcerative colitis". Indeterminate colitis' behaviour is usually closer to ulcerative colitis than Crohn's disease.

"Atypical colitis" is a phrase that is occasionally used by physicians for a colitis that does not conform to criteria for accepted types of colitis. It is not an accepted diagnosis "" and, as such, a colitis that cannot be definitively classified.

Lymphocytic and collagenous colitis have both been shown in randomized, placebo-controlled trials to respond well to budesonide, a glucocorticoid. Budesonide formulated to be active in the distal colon and rectum is effective for both active disease and in the prevention of relapse. However, relapse occurs frequently after withdrawal of therapy.

Studies of a number of other agents including antidiarrheals, bismuth subsalicylate (Pepto-Bismol), mesalazine/mesalamine (alone or in combination with cholestyramine), systemic corticosteroids, cholestyramine, immunomodulators, and probiotics have shown to be less effective than budesonide for treating both forms of microscopic colitis.

Anti-TNF inhibitors. split ileostomy, diverting ileostomy, and subtotal colectomy are options for management of steroid-dependent or refractory microscopic colitis. Currently, the need to resort to surgery is limited considering the improvement of drug therapy options. However, surgery is still considered for patients with severe, unresponsive microscopic colitis.

The prognosis for lymphocytic colitis and collagenous colitis is good, and both conditions are considered to be benign. The majority of people afflicted with the conditions recover from their diarrhea, and their histological abnormalities resolve, although relapses commonly occur if maintenance treatment is not continued.

Screening methods for colon cancer depend on detecting either precancerous changes such as certain kinds of polyps or on finding early and thus more treatable cancer. The extent to which screening procedures reduce the incidence of gastrointestinal cancer or mortality depends on the rate of precancerous and cancerous disease in that population. gFOBT (guaiac fecal occult blood test) and flexible sigmoidoscopy screening have each shown benefit in randomized clinical trials. Evidence for other colon cancer screening tools such as iFOBT (immunochemical fecal occult blood test) or colonoscopy is substantial and guidelines have been issued by several advisory groups but does not include randomized studies.

In 2009 the American College of Gastroenterology (ACG) suggest that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a colonoscopy every 10 years in average-risk individuals, beginning at age 50. The ACG suggests that cancer detection tests such as any type of FOB are an alternative that is less preferred, and if a colonoscopy is declined, the FIT (fecal immunochemical test, or iFOBT) should be offered instead. Two other recent guidelines, from the US Multisociety Task Force (MSTF) and the US Preventive Services Task Force (USPSTF), while permitting immediate colonoscopy as an option, did not categorize it as preferred. The ACG and MSTF also included CT colonography every five years, and fecal DNA testing as considerations. All three recommendation panels recommended replacing any older low-sensitivity, guaiac-based fecal occult blood testing (gFOBT) with either newer high-sensitivity guaiac-based fecal occult blood testing (hs gFOBT) or fecal immunochemical testing (FIT). MSTF looked at six studies that compared high sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there was no clear difference in overall performance between these methods.

The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the fecal immunochemical test. Though the FIT test is preferred, even the guaiac FOB testing of average risk populations may have been sufficient to reduce the mortality associated with colon cancer by about 25%. With this lower efficacy, it was not always cost effective to screen a large population with gFOBT.

If colon cancer is suspected in an individual (such as in someone with an unexplained anemia) fecal occult blood tests may not be clinically helpful. If a doctor suspects colon cancer, more rigorous investigation is necessary, whether or not the test is positive.

In 2006, the Australian Government introduced the National Bowel Cancer Program which has been updated several times since; targeted screening will be done of all Australians aged over 50 to 74 by 2017–2018. Cancer Council Australia recommended that FOBT should be done every two years. Gradually government fund disbursement meant that some people are not yet eligible for the national program and should pay for a FOBT by themselves.

The Canadian Cancer Society recommends that men and women age 50 and over have a FOBT at least every 2 years.

In colon cancer screening, using only one sample of feces collected by a doctor performing a digital rectal examination is discouraged.

The use of the M2-PK Test is encouraged over gFOBT for routine screening as it may pick up tumors that are both bleeding and non bleeding. It is able to pick up 80 percent of colorectal cancer and 44 percent for adenoma > 1 centimeter, while gFOBT picks up 13 to 50 percent of colorectal cancers.

Diagnosis may be simple in cases where the patient's signs and symptoms are idiopathic to a specific cause. However this is generally not the case, considering that many pathogens which cause enteritis may exhibit the similar symptoms, especially early in the disease. In particular, "campylobacter, shigella, salmonella" and many other bacteria induce acute self-limited colitis, an inflammation of the lining of the colon which appears similar under the microscope.

A medical history, physical examination and tests such as blood counts, stool cultures, CT scans, MRIs, PCRs, colonoscopies and upper endoscopies may be used in order to perform a differential diagnosis. A biopsy may be required to obtain a sample for histopathology.

Symptoms of pouchitis include Increased stool frequency, urgency, incontinence, nocturnal seepage, abdominal cramping, pelvic discomfort, and arthralgia.

Symptom severity does not always correlate with severity of endoscopically- or histologically-evaluated pouch inflammation. Additionally, these symptoms are not necessarily specific for pouchitis, asthey may arise from other inflammatory or functional pouch disorders such as Crohn's disease of the pouch, cuffitis, pouch sinus, or irritable pouch syndrome. The most reliable tool for diagnosis is endoscopy combined with histologic features (derived from tissue biopsies obtained during endoscopy).

Budesonide, in colonic release preparations, has been shown in randomized controlled trials to be effective in treating this disorder. It helps control the diarrheal symptoms and treatment is usually given for several weeks. Sometimes it is used to prevent frequent relapses.

Over-the-counter antidiarrheal drugs may be effective for some people with lymphocytic colitis. Anti-inflammatory drugs, such as salicylates, mesalazine, and systemic corticosteroids may be prescribed for people who do not respond to other drug treatment. The long-term prognosis for this disease is good with a proportion of people suffering relapses which respond to treatment.

Treatment of collagenous colitis is often challenging. Typically, one or more of the following therapeutic agents are used:

- Bismuth agents, including Pepto-Bismol

- 5-aminosalicylic acid

- Budesonide

- Immunosuppressants, including azathioprine

- Corticosteroids

Pilot-scale studies have shown some evidence of possible benefit for both "Boswellia serrata" extract and specific strains of probiotics in the treatment of collagenous colitis, although larger sample sizes are needed to confirm the results.

Chemical colitis is a type of colitis, an inflammation of the large intestine or colon, caused by the introduction of harsh chemicals to the colon by an enema or other procedure. Chemical colitis can resemble ulcerative colitis, infectious colitis and pseudomembranous colitis endoscopically.

Prior to 1950, hydrogen peroxide enemas were commonly used for certain conditions. This practice will often result in chemical colitis.

Soap enemas may also cause chemical colitis.

Harsh chemicals, such as compounds used to clean colonoscopes, are sometimes accidentally introduced into the colon during colonoscopy or other procedures. This can also lead to chemical colitis.

Chemical colitis may trigger a flare of ulcerative colitis or Crohn's colitis. Symptoms of colitis are assessed using the Simple Clinical Colitis Activity Index.

Pancolitis or universal colitis is a very severe form of ulcerative colitis. This form of ulcerative colitis is spread throughout the entire large intestine including the right colon, the left colon, the transverse colon, descending colon, and the rectum. A diagnosis can be made using a number of techniques but the most accurate method is direct visualization via a colonoscopy. Symptoms are similar to those of ulcerative colitis but more severe and affect the entire large intestine. Patients with ulcerative colitis generally exhibit symptoms including rectal bleeding as a result of ulcers, pain in the abdominal region, inflammation in varying degrees, and diarrhea (often containing blood). Pancolitis patients exhibit these symptoms and may also experience fatigue, fever, and night sweats. Due to the loss of function in the large intestine patients may lose large amounts of weight from being unable to procure nutrients from food. In other cases the blood loss from ulcers can result in anemia which can be treated with iron supplements. Additionally, due to the chronic nature of most cases of pancolitis, patients have a higher chance of developing colon cancer.

Pancolitis is a kind of inflammatory bowel disease (IBD) that affects the entire internal lining of the colon. The precise causes of this inflammatory disorder are unclear, although physicians currently believe that autoimmune diseases and genetic predispositions might play a role in its progress. Genes that are known to put individuals at risk for Crohn’s disease have been shown to also increase risk of other IBD including pancolitis. Furthermore, an individual may also develop pancolitis if ulcerative colitis of only a small portion of the colon is left untreated or worsens. Current treatment of pancolitis is focused on forcing the disease into remission, a state where the majority of the symptoms subside. Ultimately, the goal is to reach an improved quality of life, reduction in need for medicine, and minimization of the risk of cancer. Medication utilized in treatment includes anti-inflammatory agents and corticosteroids to alleviate inflammation and immunomodulators which act to suppress the immune system. Immunomodulators are used in severe cases of ulcerative colitis and often utilized to treat patients with pancolitis who have shown little improvement with anti-inflammatories and corticosteroids. However, in this case it can further expose the patient to other diseases due to the compromised immune system. A final option of treatment is available in the form of surgery. Generally, this option is reserved for only the cases in which cancer development is highly suspected or major hemorrhaging from ulcers occurs. In this case the entire colon and rectum are removed which both cures the pancolitis and prevents any chance of colon cancer. Patients who undergo surgery either must have their stool collect in a reservoir made in place of the rectum or have the end of the small intestine attached to the anus. In the latter case the diseased portion of the anus must be removed, but the muscles are left intact, allowing bowel movement to still take place.

Multiple disorders are found in patients with radiation enteropathy, so guidance including an algorithmic approach to their investigation has been developed. This includes a holistic assessment with investigations including endoscopies, breath tests and other nutritional and gastrointestinal tests. Full investigation is important as many cancer survivors of radiation therapy develop other causes for their symptoms such as colonic polyps, diverticular disease or hemorrhoids.

The diagnosis of CMV colitis is based on serology, CMV antigen testing and colonscopy with biopsy.

Clinical suspicion should be aroused in the setting of immunocompromised patient but it is much rarer in immunocompetent patient.

Although it is known that CMV colitis is almost always caused by reactivation of latent CMV infection in immunocompromised patients, new infection of CMV or reinfection of different strain of CMV can cause colitis in immunocompetent hosts.

Because asymptomatic CMV viremia and viruria is common and about 1/3 of symptomatic CMV infection is caused by reinfection of different strain of CMV, the diagnosis of CMV colitis needs more direct causality. It is practically achieved by colonoscopy or sigmoidoscopy tissue sampling and pathological evidence of CMV infection under microscope. Positive CMV IgG doesn't necessarily mean that it is reactivation of latent infection because of the possibility of reinfection of different strain.

On colonoscopy, the mucosa of the colon typically looks normal, but biopsies of affected tissue usually show deposition of collagen in the lamina propria, which is the area of connective tissue between colonic glands. Radiological tests, such as a barium enema are also typically normal.

Doctors can diagnose proctitis by looking inside the rectum with a proctoscope or a sigmoidoscope. A biopsy is taken, in which the doctor scrapes a tiny piece of tissue from the rectum, and this tissue is then examined by microscopy. The physician may also take a stool sample to test for infections or bacteria. If the physician suspects that the patient suffers from Crohn's disease or ulcerative colitis, colonoscopy or barium enema X-rays are used to examine areas of the intestine.

PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:

- serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months;

- cholangiography demonstrating biliary strictures or irregularity consistent with PSC; and,

- liver biopsy consistent with PSC (if available).

Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its non-invasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.

Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear anti-neutrophil cytoplasmic antibodies; however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients and, likewise, are not specific for the disease but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).

Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent.

The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation non-anastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, response to treatment, and risks of disease progression.

An extensive literature has examined the clinical value of FOBT in iron deficiency anemia.

Mild cases usually do not require treatment and will go away after a few days in healthy people. In cases where symptoms persist or when it is more severe, specific treatments based on the initial cause may be required.

In cases where diarrhoea is present, replenishing fluids lost is recommended, and in cases with prolonged or severe diarrhoea which persists, intravenous rehydration therapy or antibiotics may be required. A simple oral rehydration therapy (ORS) can be made by dissolving one teaspoon of salt, eight teaspoons of sugar and the juice of an orange into one litre of clean water. Studies have shown the efficacy of antibiotics in reducing the duration of the symptoms of infectious enteritis of bacterial origin, however antibiotic treatments are usually not required due to the self-limiting duration of infectious enteritis.

Lymphocytic colitis is a subtype of microscopic colitis, a condition characterized by chronic non-bloody watery diarrhea. The colonoscopy is normal but histology of the mucosal biopsy reveals an accumulation of lymphocytes in the colonic epithelium and connective tissue (lamina propria). Collagenous colitis shares this feature but additionally shows a distinctive thickening of the subepithelial collagen table. The peak incidence of lymphocytic colitis is in persons over age 50; the disease affects women and men equally. Lymphocytic colitis was first described in 1989.