A 33-year-old man has a history of intermittent bloody diarrhea, tenesmus, fever, fatigue, and lower abdominal cramps for the past 2 weeks. On physical examination, he is lethargic and appears lean and pale. He has aphthous stomatitis, red congested conjunctiva, and tender swollen joints. At the doctor’s office, his pulse is 114/min, blood pressure is 102/76 mm Hg, respirations are 20/min, and his temperature is 39.4°C (102.9°F). There is vague lower abdominal tenderness and frank blood on rectal examination. Laboratory studies show: Hemoglobin 7.6 g/dL Hematocrit 33% Total leucocyte count 22,000/mm3 Stool assay for C.difficile is negative Abdominal X-ray shows no significant abnormality He is symptomatically managed and referred to a gastroenterologist, who suggests a colonoscopy and contrast (barium) study for the diagnosis. Which of the following is the most likely combination of findings in his colonoscopy and barium study?

Colonoscopy: Continuous ulcerated lesions involving the mucosa and submucosa, granular mucosa, crypt abscess, and pseudopolyps, Barium study: Lead pipe colon appearance

Colonoscopy: Multiple vascular malformations that resemble telangiectasias on the colon wall, Barium study: Normal

Colonoscopy: Patches of mucosal erosions with pseudomembrane formation, Barium study: Cobblestone appearance with strictures

Colonoscopy: Discontinuous transmural ‘skip lesions’ with aphthoid linear ulcers and transverse fissures, non-caseating granulomas, and strictures, Barium study: Cobblestone appearance with strictures

Colonoscopy: Normal, Barium study: Lead pipe colon appearance

A 28-year-old man comes to the physician because of a 6-month history of progressive fatigue and intermittent diarrhea. During this time, he has had a 6-kg (13-lb) weight loss. Physical examination shows pale conjunctivae. Abdominal examination shows tenderness to palpation in the lower quadrants. An image from a colonoscopy of the descending colon is shown. Further evaluation is most likely to show which of the following findings?

Perinuclear antineutrophil cytoplasmic antibodies

PAS-positive cytoplasmic granules

Anti-Saccharomyces cerevisiae antibodies

Positive lactose hydrogen breath test

Anti-tissue transglutaminase antibodies

A 42-year-old woman comes to the physician because of increasing fatigue and difficulty concentrating at work for the last 2 months. She has hypertension and a 22-year history of Crohn disease. She has been hospitalized and treated for acute exacerbations, sometimes involving strictures, multiple times in the past. She has not had significant gastrointestinal symptoms in over a year. Current medications include mesalamine, thiazide, and bisoprolol. Her temperature is 37.2°C (99°F), pulse is 72/min, and blood pressure is 140/90 mm Hg. Examination shows a soft abdomen and pale conjunctivae. Rectal examination is unremarkable. Laboratory studies show: Hemoglobin 9.4 g/dL Mean corpuscular volume 112 fL Mean corpuscular hemoglobin 37.2 pg/cell Leukocyte count 8,700 /mm3 Platelet count 150,000 /mm3 Erythrocyte sedimentation rate 42 mm/h Serum Ferritin 88 ng/mL Iron 117 μg/dL Thyroid-stimulating hormone 3.2 μU/mL Thyroxine 7 μg/dL Further evaluation of this patient is most likely to reveal which of the following findings?

Impaired vision in her right eye

A 23-year-old female presents with a seven-day history of abdominal pain, and now bloody diarrhea that brings her to her primary care physician. Review of systems is notable for a 12-pound unintentional weight loss and intermittent loose stools. She has a family history notable for a father with CAD and a mother with primary sclerosing cholangitis. Upon further workup, she is found to have the following on colonoscopy and biopsy, Figures A and B respectively. Serum perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) is positive. This patient's disease is likely to also include which of the following features?

Continuous progression beginning in the rectum

Worse disease severity near the ileocecal valve

Fistulae and stricture formation

A 31-year-old woman comes to the emergency department because of a 4-day history of fever and diarrhea. She has abdominal cramps and frequent bowel movements of small quantities of stool with blood and mucus. She has had multiple similar episodes over the past 8 months. Her temperature is 38.1°C (100.6°F), pulse is 75/min, and blood pressure is 130/80 mm Hg. Bowel sounds are normal. The abdomen is soft. There is tenderness to palpation in the left lower quadrant with guarding and no rebound. She receives appropriate treatment and recovers. Two weeks later, colonoscopy shows polypoid growths flanked by linear ulcers. A colonic biopsy specimen shows mucosal edema with distorted crypts and inflammatory cells in the lamina propria. Which of the following is the most appropriate recommendation for this patient?

Start annual colonoscopy starting in 8 years

Obtain barium follow-through radiography in 1 year

Obtain glutamate dehydrogenase antigen immunoassay now

Start annual magnetic resonance cholangiopancreatography screening in 10 years

A 65-year-old man comes to the physician because of a 2-week history of dizziness, fatigue, and shortness of breath. He has noticed increased straining with bowel movements and decreased caliber of his stools over the past 3 months. He has no history of medical illness and takes no medications. He appears pale. Physical examination shows mild tachycardia and conjunctival pallor. Test of the stool for occult blood is positive. His hemoglobin concentration is 6.4 g/dL, and mean corpuscular volume is 74 μm3. A double-contrast barium enema study in this patient is most likely to show which of the following?

Filling defect of the rectosigmoid colon

Thumbprint sign of the transverse colon

String sign in the terminal ileum

Diverticula in the sigmoid colon

Lead pipe sign of the descending colon

A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?

"Can you tell me more about the symptoms you have been experiencing?"

"Does the diarrhea typically precede the constipation, or vice-versa?"

"Is the diarrhea foul-smelling?"

"Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"

"Are the symptoms worse in the morning or at night?"

Diagnostic approach to IBD for USMLE Step 3: High-Yield Internal Medicine Lessons

Initial Workup - Spotting the Flames

Clinical Picture: Suspect in patients with chronic (>6 weeks) diarrhea, abdominal pain, weight loss, and/or signs of malabsorption.
Lab Panel:
- CBC for anemia (microcytic) & thrombocytosis.
- CMP for ↓albumin, electrolyte issues.
- Inflammatory markers: ↑ESR, ↑CRP.
Stool Studies:
- Rule out infectious causes (esp. C. difficile).
- Inflammatory markers: Fecal calprotectin or lactoferrin.

⭐ Fecal calprotectin is a highly sensitive non-invasive marker of intestinal inflammation, key for differentiating IBD from IBS and justifying endoscopy.

Endoscopy & Biopsy - The Gold Standard

Crohn's vs. Ulcerative Colitis: Clinical & Endoscopic

Colonoscopy with ileoscopy is the definitive procedure. Multiple biopsies from both inflamed and normal-appearing mucosa are crucial for diagnosis and dysplasia surveillance.

Crohn's Disease (CD) Findings:
- Endoscopy: Skip lesions (discontinuous), aphthous to deep linear ulcers, cobblestoning, strictures.
- Biopsy: Transmural inflammation, lymphoid aggregates.
Ulcerative Colitis (UC) Findings:
- Endoscopy: Continuous, circumferential inflammation starting from rectum; edema, friability, pseudopolyps.
- Biopsy: Inflammation limited to mucosa/submucosa, crypt abscesses, crypt distortion.

⭐ Non-caseating granulomas on biopsy are pathognomonic for Crohn's Disease, though found in <30% of specimens.

Serology & Stool Tests - Helpful Clues

Serology (Antibody Tests): Not for primary diagnosis, but can provide supportive clues.
- p-ANCA (perinuclear anti-neutrophil cytoplasmic Ab): More common in Ulcerative Colitis (~65%).
- ASCA (Anti-Saccharomyces cerevisiae Ab): More common in Crohn's Disease (~65%).
- 📌 Mnemonic: ASCA for Crohn's.
Stool Markers (Inflammatory):
- Fecal Calprotectin & Lactoferrin: Neutrophil-derived proteins that are ↑ with intestinal inflammation.
- Key use: Differentiating IBD from non-inflammatory etiologies (e.g., IBS).
- Also valuable for monitoring disease activity.

⭐ Fecal calprotectin has a high negative predictive value; a normal level makes IBD very unlikely, effectively helping to rule it out in patients with chronic diarrhea.

Imaging - A Deeper Look

MRE/CTE (Enterography): Preferred for small bowel assessment in Crohn's.
- Key Crohn's Findings:
  - Bowel wall thickening (>3 mm) & mural enhancement
  - Strictures, fistulas, abscesses
  - "Comb sign" (mesenteric hypervascularity)
  - "Creeping fat" (fibrofatty proliferation)
Barium Studies (Historical/Classic):
- Crohn's: "String sign" of Kantor (severe terminal ileum narrowing), cobblestoning, fistulas.
- UC: "Lead pipe" colon (loss of haustra), fine ulcerations.

⭐ Pearl: MRE is preferred over CTE to limit cumulative radiation exposure, a key consideration in young IBD patients who require serial imaging.

High-Yield Points - ⚡ Biggest Takeaways

Initial workup includes stool studies (calprotectin, infection), CBC, and inflammatory markers (CRP/ESR).

Colonoscopy with biopsy is the gold standard for diagnosis and differentiation.

UC features continuous, superficial colonic inflammation and is often p-ANCA positive.

Crohn's disease has transmural, skip lesions from mouth to anus, is ASCA positive, and shows non-caseating granulomas.

CT or MR enterography evaluates small bowel involvement and complications like fistulas, especially in Crohn's.

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