Inflammatory Bowel Disease: Inflammatory Bowel Disease: Ulcerative Colitis

0:00Welcome to Board Pearls. This is episode one of three of the Inflammatory Bowel Disease chapter, in the Colorectal and Pelvic Floor Disorders module. This episode is ulcerative colitis, from the first diagnosis through the hospital. A man with new bloody diarrhea shows how the scope and biopsies separate ulcerative colitis from Crohn disease, how extent is classified, what his history adds, and what's going wrong in his gut. A woman with weight loss and ileal ulcers shows what Crohn disease looks like by comparison. A woman with left-sided colitis that isn't responding shows why the mesalamine formulation matters more than the drug. A man with colitis and swollen knees shows when sulfasalazine is better. And a woman with acute severe colitis shows which criteria mean admission, what happens in the first hours, what decides on day three, and when surgery can't wait.

0:48Here's the first patient. A twenty-four-year-old man has had bloody diarrhea for six weeks, eight times a day, with urgency and tenesmus, the feeling of needing to go when nothing comes. He quit smoking four months ago, and the diarrhea began about two months after that. He has no significant weight loss, no abdominal pain beyond cramps before a bowel movement, and no perianal symptoms. His uncle has Crohn disease. He takes ibuprofen most days for a sore shoulder. His stool infection panel and C. difficile test are negative, and his fecal calprotectin is nine hundred.

1:22Six weeks of bloody diarrhea with urgency and tenesmus, infection excluded, and a calprotectin of nine hundred point to inflammatory bowel disease, IBD. Fecal calprotectin, a neutrophil protein in stool, separates IBD from functional bowel disease at about one hundred fifty to two hundred micrograms per gram. It also tracks mucosal activity over time, so he can later be followed without repeated colonoscopy. C-reactive protein, CRP, and the erythrocyte sedimentation rate, ESR, add support but are less specific.

1:53The first task is deciding which IBD he has, ulcerative colitis or Crohn disease, because they're treated differently. That's answered by colonoscopy and biopsies together. His colonoscopy shows inflammation starting at the rectum and running continuously to the mid descending colon, with no normal patches, and a normal terminal ileum. That's ulcerative colitis: inflammation confined to the mucosa, beginning in the rectum and extending proximally without skip lesions.

2:22His biopsies confirm the pattern. They show distorted crypt architecture, basal plasmacytosis, crypt abscesses, and mucin depletion, confined to the mucosa. The terminal ileum had to be reached, because Crohn disease involves it in about seventy percent of patients. That's why ileocolonoscopy with the ileum intubated is the key diagnostic test.

2:45With the diagnosis made, extent decides his treatment, because the drugs are delivered by distance. The Montreal classification describes it. E1 is proctitis, limited to the rectum. E2 is left-sided colitis, up to the splenic flexure. E3 is extensive colitis or pancolitis, beyond the splenic flexure. His inflammation stops short of the splenic flexure, so he has left-sided ulcerative colitis, Montreal E2.

3:11He doesn't need small bowel imaging. Magnetic resonance, MR, enterography or computed tomography, CT, enterography defines small bowel involvement, fistulas, abscesses, and how tight a stricture is in Crohn disease. His terminal ileum was normal, so it would add nothing.

3:29The second patient shows what his scope would have looked like if he had Crohn disease. A thirty-one-year-old woman who smokes has crampy right lower abdominal pain, non-bloody diarrhea, and fifteen pounds of weight loss over five months, with a perianal skin tag. Her colonoscopy shows a normal rectum, patchy ulcers in the right colon with normal mucosa between them, and deep ulcers in the terminal ileum.

3:54She has Crohn disease. It presents with pain, weight loss, and diarrhea that isn't always bloody, with any mix of inflammatory, stricturing, fistulizing, and perianal disease. The inflammation is transmural and segmental, with skip lesions, anywhere from mouth to anus. Her biopsies show focal cryptitis, deep fissuring ulcers, transmural inflammation, and lymphoid aggregates. Non-caseating granulomas appear in only twenty to thirty percent of Crohn biopsies, so they aren't required for the diagnosis. She needs MR enterography to define small bowel involvement and look for stricture, fistula, or abscess, and stopping smoking is part of her treatment.

4:37Some colitis can't be assigned to either disease, and that changes surgical planning. When colonic inflammation can't be confidently called ulcerative colitis or Crohn disease after endoscopy, biopsy, and imaging, it's IBD-unclassified, sometimes called indeterminate colitis. The label isn't permanent. Over years, perhaps a third of these patients declare one disease, often Crohn disease when small bowel involvement appears.

5:05That uncertainty matters most before a pouch. An ileal pouch lasts less well in Crohn disease than in true ulcerative colitis. So in pancolitis with a normal small bowel and ambiguous histology, when pouch surgery is being considered for refractory colitis, the pouch is considered carefully.

5:22The first patient's history now makes sense, and it changes his care. Smoking has opposite effects in the two diseases. It protects against ulcerative colitis, and patients who quit sometimes flare within months, and he quit four months ago and began bleeding two months later. In Crohn disease, smoking speeds progression, raises the rate of strictures and fistulas, and worsens recurrence after surgery. An appendectomy for true appendicitis before age twenty is mildly protective against ulcerative colitis.

5:53Other exposures matter for both diseases, and one of them is in his medicine cabinet. Early-life antibiotics, city living, and a Western diet, high in fat and low in fiber, are linked to both diseases, and breastfeeding is modestly protective. Nonsteroidal anti-inflammatory drugs, NSAIDs, can trigger flares of established disease, so his ibuprofen stops.

6:17His age and family history fit too. There are two age peaks, a large one between fifteen and thirty-five, where he sits, and a smaller one between fifty and seventy. Both sexes are affected about equally. Incidence rose sharply through the second half of the twentieth century in North America and Northern Europe and is now rising in countries adopting a Western lifestyle. That fits diet, the microbiome, and the environment acting on a baseline genetic risk.

6:44Family history is the strongest single risk factor. A child of one parent with Crohn disease has a five to ten percent lifetime risk of IBD, and the risk is several times higher if both parents are affected. Crohn disease runs in families more often than ulcerative colitis, fitting its larger number of susceptibility genes. His uncle's Crohn disease raises his risk but doesn't decide which disease he has.

7:07What's going wrong in his gut explains why every modern drug works. IBD is a chronic immune disorder in which the intestinal lining loses tolerance for the bacteria in the lumen, in a genetically susceptible person. The epithelial barrier breaks down, bacterial products reach immune cells that can't handle them properly, and a T-helper response takes over. Ulcerative colitis leans toward a Th2 response, and Crohn disease toward Th1 and Th17.

7:36Once the loop starts, both diseases amplify themselves through the same short list of signals. They're tumor necrosis factor alpha, TNF-alpha; the interleukins IL-12, IL-23, and IL-17; and alpha-four beta-seven, the integrin that steers lymphocytes into the gut. Every modern IBD therapy, biologic or small molecule, blocks one of those signals.

8:03More than two hundred IBD genes are known, but few matter for the boards, and they reinforce the same split. NOD2 is the classic Crohn gene. Its loss-of-function variants impair Paneth cell defensin release and macrophage handling of a bacterial wall product, which exaggerates the cytokine response. They predispose to ileal Crohn disease with strictures or fistulas, and they aren't linked to ulcerative colitis. ATG16L1 and IRGM affect autophagy, another Crohn theme.

8:33Ulcerative colitis has its own genes, and one pathway is shared. Ulcerative colitis genes include the human leukocyte antigen gene HLA-DRB1 and IL23R. The IL-23 pathway is shared by both diseases, which is why ustekinumab and risankizumab work in both. Genetic testing isn't part of routine diagnosis.

8:56The third patient has ulcerative colitis that seems not to respond, and the reason is in how the drug is delivered. A thirty-three-year-old woman was diagnosed two months ago with left-sided ulcerative colitis reaching the splenic flexure, Montreal E2. She has four to five bloody stools a day with urgency. Since the diagnosis she's used mesalamine suppositories, one gram nightly, without much change. Her colonoscopy showed friability and erosions through the involved segment. Her creatinine is normal, and she takes no NSAIDs.

9:29She has mild to moderate left-sided colitis. Mesalamine is five-aminosalicylic acid, five-ASA, the foundation of treatment for mild to moderate ulcerative colitis. It acts locally on the colon lining, blocking prostaglandin synthesis, scavenging reactive oxygen species, dampening nuclear factor kappa B signaling, and activating peroxisome proliferator-activated receptor gamma.

9:55Because it acts only where it touches inflamed mucosa, the formulation matters more than the molecule. The formulation decides where the drug is released, so it's chosen by matching it to the Montreal extent.

10:07Topical forms come first in distal disease, because oral tablets can't reliably saturate the rectum, and each reaches a different distance. Mesalamine suppositories, one gram nightly, reach the last fifteen to twenty centimeters, for proctitis. Mesalamine enemas, usually four grams nightly, spread up to the splenic flexure, for proctosigmoiditis and left-sided colitis. Hydrocortisone foam and budesonide foam are alternatives for patients who can't tolerate or don't respond to topical mesalamine, but topical mesalamine works better than topical steroids in direct comparisons.

10:43Her disease reaches the splenic flexure, but a suppository covers only the last fifteen to twenty centimeters, so most of her inflamed colon has never seen the drug. She hasn't failed mesalamine. She's failed a formulation that couldn't reach her disease.

10:57Her new plan adds oral therapy at the right dose. In distal and left-sided disease, oral plus topical five-ASA together works better than either alone. It's the preferred induction for E1 and E2 disease that hasn't responded to topical treatment. For moderate disease, induction is four point eight grams a day, which randomized data favored over two point four grams, with similar safety and a faster mucosal response. She switches to mesalamine enemas four grams nightly and adds oral mesalamine four point eight grams a day.

11:30Her oral tablet is chosen by where it releases the drug. Delayed-release pH-dependent tablets release in the terminal ileum and colon. Pentasa, a controlled-release form, releases throughout the small bowel and colon, which makes it the only oral mesalamine with any rationale for small bowel Crohn disease. Multimatrix, MMX, mesalamine and Apriso are designed for once-daily colonic delivery, which improves adherence. The prodrugs sulfasalazine, balsalazide, and olsalazine attach five-ASA to a carrier through an azo bond that only colonic bacterial enzymes can break, so the drug is released in the colon.

12:10Her response is judged against a target. Her colonoscopy showed friability and erosions, an endoscopic Mayo subscore of two. The target is mucosal healing, an endoscopic Mayo subscore of zero or one, because healing predicts steroid-free remission, fewer hospitalizations, and less colectomy, and calprotectin follows it without repeated scopes. Within six weeks she has one or two formed stools a day without blood, and her calprotectin has fallen. Once that holds, her oral dose steps down to the maintenance dose of two point four grams a day.

12:46Five-ASA has a time limit, whatever the extent. For extensive colitis, E3, the starting plan is oral mesalamine four point eight grams a day with topical therapy added at the start. No response within four to eight weeks means escalation to systemic corticosteroids or an advanced therapy, a biologic or a small molecule. Oral budesonide MMX, nine milligrams a day, works for mild to moderate disease in a patient who can't tolerate or doesn't respond to mesalamine. Most of it is cleared by the liver on first pass, which limits systemic exposure.

13:21Her monitoring is set by the side effects. They're usually idiosyncratic rather than dose-dependent, so a lower dose won't prevent them. Interstitial nephritis is the most important, so creatinine is checked at baseline and periodically, because the reaction is reversible when caught early. Rarely, colitis gets acutely worse soon after starting five-ASA, a hypersensitivity reaction treated by stopping the drug, not raising the dose. Pancreatitis, pericarditis, hepatitis, and pneumonitis are rare hypersensitivity reactions. Five-ASA is mainly an ulcerative colitis drug, with limited efficacy in Crohn disease.

14:01The fourth patient shows when the older prodrug is the better choice. A forty-two-year-old man with moderate ulcerative colitis has swollen, painful knees and ankles that flare with his bowel symptoms. Sulfasalazine joins five-ASA to sulfapyridine. The five-ASA treats the colon, and the sulfapyridine adds an anti-inflammatory effect on the joints that pure five-ASA lacks. So in a patient with peripheral arthritis, sulfasalazine is preferred over a non-sulfa five-ASA, because the joints respond.

14:34Its dose and side effects come from the sulfa part. The dose is up to four grams a day, with daily folic acid, because sulfasalazine blocks folate absorption. The sulfa part causes most side effects: hypersensitivity, hemolysis, especially with glucose-6-phosphate dehydrogenase, G6PD, deficiency, and the rare interstitial nephritis, pneumonitis, pancreatitis, and pericarditis it shares with five-ASA.

15:02One side effect needs a conversation before he starts. Sulfasalazine causes reversible low sperm counts in about sixty percent of men. If he and his partner hope to conceive, that belongs in the discussion now, not after a year of trying.

15:17The last patient's colitis has crossed into the severe range. A forty-seven-year-old woman with extensive ulcerative colitis, Montreal E3, diagnosed three years ago and maintained on oral mesalamine, has had ten bloody stools a day for a week, with cramps and urgency. Her temperature is thirty-eight point two, her heart rate one hundred eight, her hemoglobin nine point eight, her ESR forty-two, her albumin two point six, and her CRP is high. Her abdomen is tender but not distended.

15:49She has a severe flare, and severity decides everything downstream, from outpatient escalation to hospitalization to colectomy. The Mayo score adds four parts, each scored zero to three: stool frequency above the patient's baseline, rectal bleeding, the endoscopic appearance, and the physician's overall assessment, for a total of zero to twelve. Remission is about two or less, with no part above one. Mild disease is around three to five, moderate six to ten, and severe eleven to twelve.

16:20The endoscopic part is the most useful single piece. Zero is normal mucosa. One is redness and a decreased vascular pattern. Two is friability with erosions. Three is spontaneous bleeding and ulceration. A proposed American College of Gastroenterology severity index adds CRP, ESR, hemoglobin, and fecal calprotectin alongside the Mayo subscore and the Ulcerative Colitis Endoscopic Index of Severity, UCEIS, and those markers work best as treatment targets.

16:50Whether she's admitted is decided by the Truelove and Witts criteria for severe colitis. They require more than six bloody stools a day plus at least one sign of systemic illness: a temperature over thirty-seven point eight, a heart rate over ninety, a hemoglobin under ten point five, or an ESR over thirty. She has ten stools and all four signs, though one would have been enough. So she has acute severe ulcerative colitis and is admitted.

17:17Speed matters because of what the colon is doing. In acute severe colitis the inflammation goes deeper than the mucosa, the colon can distend and shed its lining, and the systemic inflammation drives the fever, fast heart rate, and abnormal labs. It can perforate or progress to toxic megacolon within days, so the decision points are set in advance.

17:38Her first hours follow a fixed plan, starting with what would make steroids dangerous. Infection is excluded first, with a stool C. difficile test and a flexible sigmoidoscopy with limited air insufflation for cytomegalovirus, CMV, biopsies. The abdomen is imaged for megacolon, a transverse colon wider than five and a half to six centimeters, and for perforation. Her C. difficile test and CMV biopsies are negative, and her transverse colon is four and a half centimeters, with no free air.

18:11Treatment then starts, with three rules that surprise people. Intravenous steroids start: methylprednisolone forty to sixty milligrams a day, or hydrocortisone one hundred milligrams every six to eight hours. She eats, with no need to fast. Antimotility drugs, loperamide and opioids, are avoided because they can precipitate megacolon. And prophylactic anticoagulation starts, because acute severe ulcerative colitis markedly raises the risk of venous clots despite the rectal bleeding.

18:41Day three is the scripted decision point. Under the Travis criteria, also called the Oxford rule, steroid failure by day three of intravenous steroids is more than eight stools a day, or three to eight stools with a CRP over forty-five milligrams per liter. About eighty-five percent of patients meeting the rule need colectomy during that admission if steroids alone continue. So the answer is salvage therapy, not a higher steroid dose. On day three she still has nine stools a day.

19:14Her salvage drug is infliximab or cyclosporine, which are roughly equivalent at avoiding colectomy at one year. Infliximab is five milligrams per kilogram. With very low albumin, a higher induction dose of ten milligrams per kilogram or accelerated dosing is considered, because a severely inflamed colon leaks protein, and the antibody is lost with it.

19:36Cyclosporine has a narrower place. It's a continuous infusion at two milligrams per kilogram a day, aiming for levels of one hundred fifty to two hundred fifty nanograms per milliliter. After response it's switched to oral cyclosporine, four to eight milligrams per kilogram a day, with a thiopurine started as a bridge. It carries kidney, nerve, and blood pressure risks and can't be long-term maintenance, so infliximab is more often chosen in centers without a cyclosporine pathway. Tofacitinib has emerging data as oral salvage. Her albumin is two point six, so she gets infliximab ten milligrams per kilogram.

20:12Surgery has its own rules, set before salvage begins. Salvage is a single attempt. No response to infliximab or cyclosporine within five to seven days means colectomy, usually a subtotal colectomy with an end ileostomy, leaving the rectal stump so a pouch can be built later. Moving from one salvage drug to the other carries a high infection rate and is generally avoided. And perforation, uncontrolled hemorrhage, or toxic megacolon that doesn't improve within twenty-four to forty-eight hours means emergency colectomy regardless of the medical response.

20:48Colectomy is less common than it was, but acute severe colitis still drives most of it. Since two thousand, the ten-year colectomy risk in ulcerative colitis is about thirteen to fifteen percent, lower than before biologics, with acute severe colitis accounting for most of the surgery.

21:04She responds. By day seven she has three stools a day with little blood, and her CRP is falling. She goes home on infliximab maintenance, with calprotectin to follow her.

21:15Here are the traps the boards set in these patients. Granulomas aren't needed to diagnose Crohn disease. Continuous inflammation from the rectum isn't Crohn disease, and skip lesions with a normal rectum aren't ulcerative colitis. Quitting smoking can unmask ulcerative colitis. NOD2 isn't an ulcerative colitis gene. The terminal ileum isn't skipped at colonoscopy. A patient with IBD doesn't stay on daily NSAIDs. And a pouch isn't rushed in IBD-unclassified.

21:46The mesalamine traps follow. Suppositories for disease reaching the splenic flexure don't count as mesalamine failure. Topical mesalamine is preferred over a topical steroid. Moderate disease isn't started at two point four grams. Colitis that worsens right after starting mesalamine means stopping it, not raising the dose. Creatinine monitoring isn't forgotten, and neither are folic acid and low sperm counts with sulfasalazine. And mesalamine isn't continued for months after it has failed.

22:18The acute severe colitis traps close the list. C. difficile and CMV are tested before steroids. Loperamide and opioids aren't given. Anticoagulation isn't held because of rectal bleeding. The steroid dose isn't raised on day three when salvage is needed. The standard infliximab dose isn't enough with very low albumin. A second salvage drug isn't tried. And medical therapy doesn't continue despite perforation, uncontrolled bleeding, or persistent megacolon.

22:47So, start to finish. Bloody diarrhea with a high calprotectin and no infection points to IBD, and ileocolonoscopy with biopsies decides which. Ulcerative colitis is continuous mucosal inflammation from the rectum upward, classified by Montreal extent. Crohn disease is segmental and transmural, most often in the terminal ileum, with granulomas in only a minority.

23:11Smoking protects against ulcerative colitis and worsens Crohn disease. IBD is lost tolerance to gut bacteria in a susceptible host, amplified through cytokines that modern drugs each target.

23:24Five-ASA works only where it touches the mucosa, so match the formulation to the extent, combine oral and topical therapy, induce moderate disease at four point eight grams, and aim for mucosal healing. Use sulfasalazine when peripheral arthritis coexists. No response in four to eight weeks means steroids or an advanced therapy.

23:42Acute severe colitis is more than six bloody stools a day with a systemic sign. Exclude C. difficile and CMV, image for megacolon, give intravenous steroids and clot prophylaxis, let her eat, and avoid antimotility drugs.

23:58On day three, more than eight stools, or three to eight with a CRP over forty-five, means one salvage attempt with infliximab, higher dosed if albumin is low, or cyclosporine. No response in five to seven days means subtotal colectomy, and perforation, uncontrolled bleeding, or persistent megacolon mean surgery regardless.

24:19Episode two is Crohn disease: classifying it, who needs early biologic therapy, how the advanced therapies are chosen, and what to do with perianal disease, strictures, and recurrence after surgery.

24:32For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of three of chapter fourteen, and I'll see you in the next one.