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Inflammatory bowel disease: Clinical practice

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Inflammatory bowel disease: Clinical practice

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A 29-year-old man comes to the office with complaints of frequent loose stools and abdominal pain. He started having these symptoms a month ago, and they did not respond to over-the-counter antidiarrheals. He became concerned when he noticed an increase in urgency and a small amount of blood admixed with mucoid stools yesterday. Past medical history is noncontributory. He has not recently travelled outside the country. Vitals are within normal limits. Physical examination shows mild abdominal tenderness in the left lower quadrant. Colonoscopy shows erythematous rectal mucosa that is friable to touch, along with scattered ulcerations extending up to the distal part of sigmoid colon. The remainder of the colon and ileum are normal. Which of the following is the most appropriate pharmacotherapy for the patient at this stage?  

Transcript

Content Reviewers:

Rishi Desai, MD, MPH

Inflammatory bowel diseases are mainly broken down into two autoimmune conditions - ulcerative colitis and Crohn's disease - both of which cause chronic inflammation in the gastrointestinal tract.

Ulcerative colitis mostly appears in individuals aged from 20 to 30 years old.

The chronic inflammation only involves the mucosal layer of the colon or the rectum and inflammation usually starts in the rectum and goes retrograde through the colon.

Ulcerative colitis can involve only the rectum, in which case it’s called ulcerative proctitis, can involve the rectum and the sigmoid colon - called ulcerative proctosigmoiditis, or can involve the rectum, sigmoid colon and the colon up to the splenic flexure - called distal ulcerative colitis. In some cases, it can also pass the splenic flexure, but spare the cecum - called extensive colitis and finally it can involve the entire colon including the cecum - called pancolitis.

The onset of the disease is gradual and symptoms are progressive over a few weeks. There may be systemic symptoms, such as fatigue, fever, unintentional weight loss, as well as dyspnea and palpitations due to iron deficiency anemia caused by blood loss.

Gastrointestinal symptoms include bloody diarrhea, colicky abdominal pain, and tenesmus.

Extraintestinal manifestations can sometimes occur, and they include arthritis, uveitis and episcleritis, and skin lesions like pyoderma gangrenosum and erythema nodosum, as well as primary sclerosing cholangitis and venous or arterial thromboembolism.

Acute complications of ulcerative colitis include severe gastrointestinal bleeding and fulminant colitis- which is continuous bleeding and over 10 stools per day.

Another complication is toxic megacolon, which is where the nerves and muscles are damaged and the colon becomes atonic and dilated. In severe cases, it can lead to perforation with peritonitis which causes fevers and severe abdominal pain.

Finally, long-term complications of ulcerative colitis include an increased risk for colorectal cancer, as well as strictures from repeated bouts of inflammation, that are usually located in the rectosigmoid colon, and can sometimes lead to bowel obstruction.

Now, let’s switch gears and go over Crohn's disease which also causes chronic inflammation, but in this case it’s transmural, meaning that it involves the full thickness of the gastrointestinal wall, and can happen anywhere in the gastrointestinal tract, from mouth to perianal area.

Systemic symptoms of Crohn’s disease include fatigue, fever and unintentional weight loss.

Gastrointestinal symptoms include crampy abdominal pain, watery diarrhea, and sometimes malabsorption symptoms like steatorrhea.

The transmural inflammation can allow fistulas to form, which are communications between two epithelial organs. They can be enteroenteric meaning from one part of the intestines to another and can feel like a small mass, or can be enterovesical where they go from the intestines to another organ like the bladder where they can cause pneumaturia- which is the passing of gas in the urine. They can also be enterocutaneous fistulas which is where the intestines connect to the skin surface.

Sometimes, a phlegmon can form, which is where there’s a localized area of inflammation in the intestinal wall that can get infected and become an abscess.

Sometimes individuals get perirectal abscesses, fissures, and even cutaneous fistulas around the rectum.

There can be oral involvement, like aphthous ulcers or gingivitis, as well as esophageal symptoms like odynophagia and dysphagia.

There can also be gallstones that lead to biliary colic.

Extraintestinal symptoms are similar to those of ulcerative colitis, those include arthritis, uveitis and episcleritis, and skin lesions like pyoderma gangrenosum and erythema nodosum, as well as primary sclerosing cholangitis and venous or arterial thromboembolism.

Now on top of all of those, Crohn's disease specifically can cause kidney stones as well.

For diagnosing inflammatory bowel disease -both ulcerative colitis and Crohn’s disease- labwork and colonoscopy with biopsy are needed.

Typical lab work includes a CBC that shows anemia, and if there is anemia, then iron studies, vitamin B12, and folate levels are checked to assess for deficiencies. Other common labs are an elevated ESR and CRP, a low albumin, and typically there are electrolyte abnormalities from diarrhea and dehydration.

Typically electrolytes are sent if there’s chronic diarrhea, an AST and ALT to look for evidence of hepatitis, and creatinine and urea nitrogen are sent to assess the kidneys.

Fecal calprotectin levels are typically elevated as well because it’s a protein released in large amounts by neutrophils in the digestive tract during inflammation.

Now, it’s also important to exclude infectious causes. A routine workup includes stool cultures for Salmonella, Shigella, Yersinia, Campylobacter, and E. coli, microscopy for ova and parasites, and antigen testing for Giardia lamblia.

Pathogens associated with specific risk factors include Entamoeba histolytica which is associated with travel to endemic countries, and Clostridium difficile which is associated with recent antibiotic use.

When ulcerative colitis is specifically suspected, testing for sexually transmitted diseases, such as Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus and Treponema pallidum may also be done, especially in individuals with severe rectal symptoms, like tenesmus and fecal incontinence.

The next step is usually imaging, which isn’t needed for the diagnosis, but it can show some abnormal findings for both ulcerative colitis and Crohn’s disease.

One specific imaging test is a double contrast enema. That’s where x-rays are taken of the colon and rectum using barium and air as contrast.

In moderate and severe ulcerative colitis, there can be mucosal thickening and in severe cases, it can show collar button ulcers which are deep mucosal ulcerations that also reach the submucosal layer. The circumferential inflammation can destroy the haustras leading to a smooth section of colon which is called the “lead pipe” sign.

In severely ill individuals, a barium enema shouldn’t be done, because it can precipitate toxic megacolon.

In Crohn’s disease, aphthous ulcers may be seen and these are shallow ulcerations of the mucosa and strictures may also be seen and these allow a tiny stream of contrast material to pass through and that’s called a “string sign”.

To evaluate small intestinal disease in Crohn’s disease, there are a few different imaging techniques that can be done. One option is a wireless capsule endoscopy- this is when the individual ingests a tiny pill that contains an even tinier video camera which can record images as it moves through the small intestine.

Another option is the upper gastrointestinal series with Small Bowel Follow-Through or SBFT- meaning that radiologic images are taken while a barium solution is ingested. This can help identify narrowing of the lumen with nodularity and ulcerations and a “string” sign if the narrowing is advanced, fistulas and a cobblestone appearance may also be seen.

Ultimately the diagnosis of both ulcerative colitis and Crohn’s disease relies on a colonoscopy with biopsy.

In ulcerative colitis there’s typically circumferential inflammation or ulceration that’s continuous throughout an entire section of the rectum or colon. In addition, the mucosa is often so damaged that it’s friable to the touch and can spontaneously bleed. On histology, the damage is limited to the mucosa and submucosa.

In addition, there can be crypt abscesses due to the aggregation of lymphocytes and inflammatory process, that eventually results in crypt atrophy. A bit like lymphocytes having a party in a crypt that gets a bit wild, and then burns out over time.