Chronic ulcerative colitis is a potential risk factor for cancer.
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A 23-year-old American Jewish woman comes to the emergency department due to a 4-day history of fever, left lower quadrant pain, and abdominal distention. Her medical history is relevant for Hashimoto's hypothyroidism, situational anxiety, and positive family history of inflammatory bowel disease. The patient currently takes levothyroxine, vitamin C/zinc supplement, and alprazolam. Upon further questioning, the patient mentions that she has increasing bowel movements (every hour) and has small amounts of watery-mucousy red stools. Physical exam shows distended abdomen and tympanitic, drum-like sounds over her right upper and left upper quadrant. Her temperature is 38.6°C (101.48°F), pulse is 121/min, respirations are 18/min, blood pressure is 80/70 mmHg. Upon hospital admission, the patient's clinical condition deteriorates despite antibiotic therapy and steroids. An abdominal radiograph is obtained and shown below.
Which of the following is the most likely cause of this patient's condition?
Content Reviewers:Rishi Desai, MD, MPH
Inflammatory bowel disease can cause inflammation in the small and large intestine, in other words...inflammation of the bowel.
Colitis refers specifically to inflammation in the colon, or the large intestine. Ulcerative colitis is a type of inflammatory bowel disease that tends to form ulcers along the inner-surface or lumen of the large intestine, including both the colon and the rectum.
These ulcers are spots in the mucosa where the tissue has eroded away and left behind open sores or breaks in the membrane.
Sometimes there is a flare which means that new damage has occurred, and then there are periods of remission when the tissue starts to heal up.
Ulcerative colitis is actually the most common type of inflammatory bowel disease, not that there are that many, but this one causes inflammation and ulcers in the mucosa and submucosa of the large intestine only, which is an important point that sets it apart from Crohn disease, another inflammatory bowel disease.
Now although certain environmental factors like diet and stress were once thought to be the culprit behind these ulcers forming in the gut, now it’s thought that these are more secondary, meaning they seem to make symptoms worse, but ulcerative colitis is now ultimately thought to be autoimmune in origin.
In fact, cytotoxic T cells from the immune system are often found in the epithelium lining the colon, so the thought is that inflammation and ulceration in the large intestine is caused by T cells destroying the cells lining the walls of the large intestine, leaving behind these eroded areas or ulcers.
It’s unclear what exactly these T cells are meant to be targeting though.
Some patients have p-ANCAs in their blood, or perinuclear antineutrophilic cytoplasmic antibodies, which are a kind of antibodies that target antigens in the body’s own neutrophils.
Although not completely understood, some theories suggest this may be partly due to an immune reaction to gut bacteria that have some structural similarity to our own cells, allowing antibodies to those gut bacteria, or p-ANCAs, to “cross-react” with neutrophils.
Patients also seem to have a higher proportion of gut bacteria that produce sulfides, and often high sulfide production is correlated with periods of active inflammation as opposed to remission.
Ultimately, though, these are mostly correlations and theories, and we’ve yet to nail down the precise mechanism behind mucosal destruction; the cause is ultimately some combination of environmental stimuli, perhaps the sulfide-producing bacteria, mixed with a genetic predisposition, because patients with a family history of ulcerative colitis are more likely to develop the disease themselves.
It also seems to be more common in young women from the teens to 30s, with more prevalence among caucasians and eastern european jews.