Gastrointestinal

Inflammatory bowel disease: Crohn vs UC diagnosis

Clinical Overview and When to Suspect IBD

— Crohn disease (CD): transmural, skip-lesion inflammation anywhere from mouth to anus, terminal ileum most common

— Ulcerative colitis (UC): mucosal/submucosal inflammation, continuous from rectum proximally, limited to colon

— Young adult with >4 weeks of diarrhea, especially bloody (UC) or with weight loss and RLQ pain (CD)

— Nocturnal diarrhea, urgency, tenesmus, fecal incontinence (inflammatory rather than IBS pattern)

— Unexplained iron-deficiency anemia, growth failure in adolescent, recurrent perianal fistulas/abscesses

— Extraintestinal manifestations: episcleritis, erythema nodosum, large-joint arthritis, primary sclerosing cholangitis

Inflammatory bowel disease (IBD) encompasses two chronic immune-mediated enteropathies:

Bimodal age distribution: peak 15–35 years, second smaller peak 55–65

Risk factors: Ashkenazi Jewish ancestry, family history (strongest single risk factor), smoking increases CD risk but is protective in UC, NSAID use, recent infectious gastroenteritis, appendectomy reduces UC risk

When to suspect IBD on Step 3:

Key distinction: IBS lacks alarm features — no blood, no nocturnal symptoms, normal labs, normal CRP/fecal calprotectin. Step 3 stems testing IBS vs IBD will hinge on fecal calprotectin elevation, anemia, or hematochezia

Ambulatory triage: stable outpatient with suspected IBD → labs + stool studies + GI referral for colonoscopy; toxic appearance, severe bleeding, peritonitis, or obstruction → ED

Board pearl: A 24-year-old smoker with 3 months of crampy RLQ pain, weight loss, and a palpable mass = ileal Crohn until proven otherwise. A 28-year-old nonsmoker with 6 weeks of bloody diarrhea and tenesmus = UC until proven otherwise.

Goals at first visit: confirm diagnosis, classify CD vs UC, assess severity, screen for complications, initiate appropriate induction therapy, and arrange longitudinal GI follow-up — IBD is a chronic disease management topic, exactly the Step 3 wheelhouse.

Presentation Patterns and Key History

— Bloody diarrhea with mucus, urgency, tenesmus (rectal involvement is universal)

— Lower abdominal cramping relieved by defecation

— Gradual onset over weeks to months; flares and remissions

— Systemic symptoms (fever, weight loss) appear in moderate-to-severe disease

— Chronic non-bloody or intermittently bloody diarrhea, RLQ pain, weight loss, low-grade fever

— Postprandial pain or obstructive symptoms (stricturing phenotype)

— Perianal disease: skin tags, fissures, fistulas, abscesses — pathognomonic when present

— Aphthous oral ulcers, odynophagia (upper GI Crohn)

— Duration (>6 weeks favors IBD over infection), nocturnal symptoms, stool frequency/blood

— Travel, antibiotics, sick contacts (rule out infectious mimics)

— NSAID use (can trigger flares and mimic IBD)

— Smoking status — document and counsel

— Family history of IBD, colorectal cancer, celiac

— Extraintestinal: joint pain, eye redness, skin lesions, jaundice/pruritus (PSC)

— Mild: <4 stools/day, no systemic toxicity

— Moderate: 4–6 stools/day, minimal toxicity

— Severe: ≥6 bloody stools/day + fever, tachycardia, anemia (Hgb <10.5), or ESR >30

Ulcerative colitis hallmarks:

Crohn disease hallmarks:

Historical clues to elicit:

Disease activity grading (Truelove-Witts for UC):

CD activity assessed by symptoms + CRP + endoscopy (CDAI in trials, HBI clinically)

Step 3 management: at the intake visit, document stool frequency, presence of blood, nocturnal symptoms, weight change, and extraintestinal review of systems — these drive severity classification and reimbursement-relevant coding

Board pearl: Perianal fistula in a young adult with chronic diarrhea = Crohn; isolated proctitis with bleeding per rectum = UC. Mixed picture with skip lesions on later scope reclassifies as CD even if initial appearance suggested UC ("IBD-unclassified" becomes Crohn).

Physical Exam Findings and Hemodynamic Assessment

— UC: mild diffuse lower abdominal tenderness, no mass; distension + absent bowel sounds + tympany → suspect toxic megacolon

— CD: RLQ tenderness with palpable mass (inflammatory phlegmon or abscess), high-pitched bowel sounds if obstructing

— Peritoneal signs (rebound, guarding) = perforation until proven otherwise → surgical emergency

— Skin tags, fissures (often lateral, multiple — different from typical posterior midline fissures), fistula openings, perirectal fluctuance

— Digital rectal exam: tone, blood, mass; defer if exquisitely tender (abscess)

— Eyes: episcleritis (injected, mild), uveitis (painful, photophobia — urgent ophthalmology)

— Skin: erythema nodosum (tender shins, parallels disease activity), pyoderma gangrenosum (necrotic ulcer, often independent of activity)

— Joints: peripheral (parallels activity) vs axial/sacroiliitis (independent, HLA-B27 associated)

— Mouth: aphthous ulcers

— Liver: hepatomegaly, jaundice (PSC — more common in UC)

— Clubbing in long-standing disease

— HR >100, SBP <100, T >38.5°C

— Orthostasis, mental status change

— Severe abdominal distension or peritonitis

Vital signs first — fever, tachycardia, orthostasis, or hypotension suggest severe flare, sepsis, or perforation

General: cachexia, pallor (anemia), delayed puberty/short stature in adolescents (especially CD)

Abdominal exam:

Perianal exam (mandatory in suspected CD):

Extraintestinal findings:

Hemodynamic red flags requiring inpatient admission:

CCS pearl: In a CCS case with suspected severe UC, the first orders are IVF bolus, CBC, BMP, CRP, lactate, blood cultures, stool studies (including C. difficile), abdominal X-ray for megacolon, and NPO + GI/surgery consult. Do not give antidiarrheals — they precipitate toxic megacolon.

Board pearl: A transverse colon diameter >6 cm on KUB + systemic toxicity = toxic megacolon; this is a surgical emergency requiring urgent colectomy if no improvement in 24–72 h with maximal medical therapy.

Diagnostic Workup — Initial Labs, Imaging, and Biomarkers

— CBC: microcytic anemia (iron deficiency from blood loss), leukocytosis, thrombocytosis (acute-phase reactant)

— CMP: low albumin (protein-losing enteropathy, malnutrition), electrolyte derangements from diarrhea

— CRP and ESR: elevated in active disease; CRP more responsive in CD, less reliable in pure UC

— Iron studies, B12 (low in terminal ileal CD or post-ileal resection), folate, vitamin D

— TSH, celiac serology (anti-tTG IgA) — exclude mimics

— HIV, hepatitis B/C serologies (baseline before immunosuppression)

— Quantiferon-TB Gold and CXR (before any anti-TNF)

— C. difficile toxin/PCR (especially before steroids; C. diff can mimic or coexist with flare)

— Stool culture (Salmonella, Shigella, Campylobacter, Yersinia — Yersinia mimics ileal CD)

— Ova and parasites, Giardia antigen, E. coli O157:H7 if bloody

— Fecal calprotectin (>150–250 μg/g strongly suggests IBD; <50 essentially excludes active inflammation, useful to distinguish from IBS)

— Stool lactoferrin alternative

— Plain abdominal radiograph if acute presentation: assess for toxic megacolon (>6 cm transverse colon), free air, obstruction

— CT abdomen/pelvis with contrast in acutely ill or suspected complications: bowel wall thickening, mesenteric stranding, abscess, fistula, obstruction; CT enterography is preferred elective study in CD to map small bowel

Initial laboratory panel (every suspected IBD patient):

Stool studies — mandatory to exclude infection before diagnosing IBD:

Imaging — initial:

Key distinction: Fecal calprotectin distinguishes inflammatory diarrhea (IBD, infectious colitis) from functional diarrhea (IBS) — a Step 3 favorite when the stem describes a young adult with diarrhea and you must choose between scope vs reassurance.

Step 3 management: Never start steroids for a suspected IBD flare without first ruling out C. difficile — coexistent infection is common and steroids worsen outcomes.

Serologic markers (ASCA, p-ANCA) have limited utility — not used for primary diagnosis; reserved for indeterminate colitis classification.

Diagnostic Workup — Endoscopy and Confirmatory Studies

— Continuous inflammation starting at rectum, extending proximally

— Erythema, granularity, friability, loss of vascular pattern, ulcerations, pseudopolyps

— Sharp demarcation between inflamed and normal mucosa

— Rectum always involved (except after topical therapy)

— Disease extent: proctitis, left-sided colitis, extensive/pancolitis (Montreal classification)

— Skip lesions, cobblestoning, aphthous and linear/serpiginous ulcers

— Terminal ileal involvement, rectal sparing

— Strictures, fistulas

— UC: crypt abscesses, crypt distortion, mucosal-limited inflammation, goblet cell depletion

— CD: non-caseating granulomas (only ~30%, but highly specific), transmural inflammation, lymphoid aggregates

— CT enterography or MR enterography — preferred; MRE preferred in young patients to limit radiation exposure (lifelong disease, repeated imaging)

— Capsule endoscopy if cross-sectional imaging negative but suspicion remains (contraindicated if stricture suspected — perform patency capsule first)

— Push enteroscopy or device-assisted enteroscopy for tissue if needed

Ileocolonoscopy with biopsies = gold standard for diagnosis and CD/UC differentiation

UC endoscopic features:

CD endoscopic features:

Histology:

Small bowel evaluation (CD-specific):

Upper endoscopy if upper GI symptoms in CD

MRI pelvis for perianal CD — maps fistulas before surgical/biologic therapy

Board pearl: Granulomas on biopsy = Crohn (but absence does not rule it out). Continuous mucosal disease from rectum + crypt abscesses without granulomas + no terminal ileal disease = UC.

Key distinction: "Backwash ileitis" in UC pancolitis can mimic ileal CD — but it is mild, contiguous with cecal inflammation, and lacks strictures/fistulas/granulomas.

CCS pearl: In acute severe colitis, unprepped flexible sigmoidoscopy with minimal insufflation is preferred over full colonoscopy to reduce perforation risk while still obtaining diagnostic biopsies and ruling out CMV colitis (immunostain biopsies if steroid-refractory).

Risk Stratification and First-Line Management Logic

— Mild–moderate: outpatient management with 5-ASA induction

— Severe (≥6 bloody stools/day, systemic toxicity, Hgb <10.5, ESR >30): hospitalize for IV steroids

— Age <30 at diagnosis

— Extensive disease, deep ulcers on endoscopy

— Perianal/fistulizing disease

— Stricturing behavior

— Prior bowel resection

— Steroid requirement at diagnosis

— Significant weight loss, hypoalbuminemia

— Short-term: symptomatic response, normalize CRP

— Intermediate: clinical remission, normalize fecal calprotectin

— Long-term: endoscopic healing, restored quality of life, normal growth in children

— Inactivated: influenza annually, pneumococcal (PCV15/20 + PPSV23), Tdap, HPV, hepatitis B, COVID-19, recombinant zoster

— Live vaccines (MMR, varicella, live zoster, yellow fever) contraindicated on biologics/immunomodulators — give before starting or during washout

Severity-based stratification drives therapy choice (treat-to-target era: clinical remission + endoscopic healing + normalized biomarkers)

UC severity (Truelove-Witts + endoscopy):

CD risk stratification — high-risk features triggering early biologics ("top-down" approach):

Low-risk CD (limited inflammatory ileitis, mild symptoms): step-up therapy may be reasonable, though modern practice favors early biologics for most

Treatment targets (STRIDE-II):

Step 3 management: A patient achieving symptomatic remission on therapy still needs objective reassessment at 3–6 months — repeat calprotectin, and endoscopy at 6–12 months. Symptom resolution alone is inadequate; mucosal healing predicts long-term outcomes.

Smoking cessation counseling is mandatory in CD (improves outcomes); in UC, do not encourage smoking but use nicotine replacement if patient quits and flares

Vaccination before immunosuppression:

Board pearl: Identifying a high-risk CD phenotype at diagnosis and initiating anti-TNF early (within 12–24 months) reduces surgery rates and disease progression — the era of "top-down" therapy.

Pharmacotherapy — First-Line Drug Regimens

— Mild–moderate distal disease: topical 5-ASA (mesalamine suppositories for proctitis, enemas for left-sided) ± oral 5-ASA

— Mild–moderate extensive disease: oral 5-ASA (mesalamine, sulfasalazine) up to 4.8 g/day

— Moderate–severe: oral prednisone 40–60 mg/day for induction, then taper; bridge to maintenance with biologic or immunomodulator

— Acute severe UC (hospitalized): IV methylprednisolone 60 mg/day; if no response by day 3 → infliximab or cyclosporine rescue vs colectomy

— Maintenance: 5-ASA (mild), thiopurines, anti-TNFs (infliximab, adalimumab, golimumab), anti-integrin (vedolizumab), anti-IL-12/23 (ustekinumab), IL-23 (risankizumab, mirikizumab), JAK inhibitors (tofacitinib, upadacitinib), S1P modulators (ozanimod, etrasimod)

— Mild ileocecal: budesonide 9 mg/day (high first-pass, fewer systemic side effects)

— Moderate–severe: prednisone or biologic; anti-TNF (infliximab, adalimumab) often first-line, especially with high-risk features

— Fistulizing/perianal CD: infliximab + antibiotics (ciprofloxacin/metronidazole) ± surgical seton

— Maintenance: anti-TNF ± thiopurine/methotrexate combination (SONIC trial), vedolizumab, ustekinumab, risankizumab, upadacitinib

Ulcerative colitis induction and maintenance:

Crohn disease induction:

5-ASA is NOT effective for CD maintenance — UC drug only

Steroids never for maintenance — only induction

Pre-biologic checklist: TB screen (Quantiferon + CXR), HBV serologies, HIV, update vaccinations, baseline labs

Thiopurine considerations: Check TPMT and NUDT15 activity before azathioprine/6-MP — homozygous deficiency → severe myelosuppression

Step 3 management: A patient flaring on 5-ASA for UC — first verify adherence and rule out C. diff/CMV, then escalate (add topical 5-ASA if oral alone, then short steroid course, then biologic).

Board pearl: Tofacitinib carries boxed warnings for thrombosis, MACE, malignancy — avoid in patients >50 with CV risk factors or active VTE risk.

Procedures and Surgical Management

— Acute: toxic megacolon refractory to medical therapy, perforation, massive hemorrhage, fulminant colitis failing day-3 rescue therapy

— Elective: medically refractory disease, intolerable side effects, dysplasia or colorectal cancer

— Procedure: total proctocolectomy with ileal pouch-anal anastomosis (IPAA, J-pouch) — preferred in young/healthy

— Alternative: total proctocolectomy with end ileostomy (elderly, sphincter dysfunction, rectal cancer)

— Staged: subtotal colectomy with end ileostomy first in acutely ill, then completion proctectomy + IPAA later

— Strictures with obstruction → strictureplasty (preserve bowel length) or limited resection

— Fistulas refractory to medical therapy, abscesses (drain percutaneously first, then resect)

— Perforation, hemorrhage, medically refractory disease

— Perianal abscess: incision and drainage + seton placement for fistulas; never simply lay open complex CD fistulas

— Cancer/dysplasia

— Hold biologics 1 dosing interval before major surgery if feasible; data suggest anti-TNF safe perioperatively

— Steroids >20 mg prednisone >6 weeks increase post-op infection/anastomotic leak risk — taper or stress-dose appropriately

— Nutritional optimization (preoperative enteral nutrition reduces complications)

Surgery is curative for UC, not for CD — fundamental teaching point

UC surgical indications:

Pouchitis (post-IPAA): inflammation of pouch; treat with ciprofloxacin or metronidazole 2 weeks; chronic pouchitis may need biologics (vedolizumab approved)

Crohn surgical indications (palliative, not curative):

Bowel-sparing principle in CD: preserve length to avoid short bowel syndrome; recurrence at anastomosis is the rule — start post-op prophylaxis (anti-TNF) in high-risk patients with colonoscopy at 6–12 months

Endoscopic balloon dilation for short, accessible CD strictures

Perioperative management:

CCS pearl: A CD patient with high fever, RLQ pain, and CT showing a 5-cm phlegmon/abscess → percutaneous drainage + IV antibiotics first, then delayed elective resection — never operate on hot abscessed bowel if drainable.

Board pearl: Post-ileal resection diarrhea from bile salt malabsorption → cholestyramine; if >100 cm resected → fat malabsorption requiring low-fat diet + MCT oil.

Special Populations — Elderly and Renal/Hepatic Impairment

— ~10–15% of IBD cases; rising incidence

— UC more common than CD in this age group; left-sided UC most frequent

— Must rule out mimics first: ischemic colitis, diverticulitis, NSAID colopathy, microscopic colitis, infection, colon cancer

— Often milder disease but higher complication rates from therapy and disease

— Steroids: higher risk of osteoporosis, hyperglycemia, infection, delirium, cataracts — minimize duration, add calcium/vitamin D and consider bisphosphonate if >3 months

— Thiopurines: increased risk of lymphoma (especially hepatosplenic T-cell with combination therapy in young males, but lymphoma risk higher overall in elderly), nonmelanoma skin cancer — annual dermatology screening

— Anti-TNF: increased serious infection and malignancy risk; screen aggressively for latent TB, HBV

— Vedolizumab and ustekinumab have favorable safety profiles — often preferred first-line biologics in elderly

— JAK inhibitors: avoid in ≥65 with CV risk factors (boxed warning)

— 5-ASA agents (mesalamine, sulfasalazine) can cause interstitial nephritis — monitor creatinine at baseline, 3 months, then annually

— Avoid sulfasalazine in significant CKD

— Dose-adjust methotrexate (avoid if CrCl <30); thiopurines no renal adjustment but monitor counts

— Avoid NSAIDs (worsen IBD and kidneys)

— Methotrexate hepatotoxicity — avoid in significant liver disease, no alcohol, monitor LFTs

— Reactivate hepatitis B with immunosuppression — screen HBsAg/anti-HBc/anti-HBs in all patients before biologics; prophylactic entecavir/tenofovir if HBsAg+ or isolated anti-HBc+ before therapy

— Co-existing PSC (5% of UC) — monitor MRCP and CA 19-9; annual colonoscopy from diagnosis due to colorectal cancer risk

Elderly-onset IBD (≥60 years at diagnosis):

Therapeutic considerations in elderly:

Renal impairment:

Hepatic impairment:

Step 3 management: Before starting a thiopurine in an older patient — check CBC, CMP, TPMT/NUDT15, HBV/HCV/HIV, TB, age-appropriate cancer screening, vaccinations; counsel on skin cancer surveillance and sun protection for life on the drug.

Board pearl: Worsening creatinine in a UC patient on mesalamine = mesalamine-induced interstitial nephritis until proven otherwise — discontinue drug, biopsy if needed.

Special Populations — Pregnancy and Pediatrics

— Aim for ≥3–6 months of remission before conception

— Continue maintenance therapy through pregnancy

— Folate 1 mg/day (2 mg if on sulfasalazine — impairs folate absorption)

— Stop methotrexate ≥3 months before conception in both partners (teratogenic, abortifacient)

— Avoid tofacitinib/upadacitinib in pregnancy

— 5-ASA (mesalamine), sulfasalazine (with folate), thiopurines (continue if needed)

— Anti-TNFs (infliximab, adalimumab) — continue throughout pregnancy; placental transfer in 3rd trimester means avoid live vaccines (rotavirus) in the infant for first 6–12 months

— Vedolizumab, ustekinumab — continue; same infant live vaccine consideration

— Certolizumab pegol has minimal placental transfer (Fc-free) — option in late pregnancy

— Steroids if needed for flare (lowest effective dose)

— ~25% diagnosed before age 20

— CD more common than UC; often more extensive disease

— Growth failure, delayed puberty are red flags — height/weight at every visit

— Exclusive enteral nutrition (EEN) for 6–8 weeks is first-line induction for pediatric CD — as effective as steroids without growth suppression

— Early biologic use to prevent growth impairment and complications

— Avoid thiopurines in young males due to hepatosplenic T-cell lymphoma risk with combination therapy

— Transition-of-care clinic to adult GI at age 18–21

Pregnancy in IBD — core principle: "A healthy mother makes a healthy baby" — active disease at conception/during pregnancy is more harmful than most medications

Preconception counseling:

Safe in pregnancy:

Delivery: vaginal delivery acceptable in most; C-section indicated for active perianal CD to avoid sphincter injury and worsening fistulas

Breastfeeding: compatible with 5-ASA, thiopurines, anti-TNFs, vedolizumab, ustekinumab; avoid methotrexate and JAK inhibitors

Pediatric IBD:

Board pearl: Pregnant patient on infliximab — continue; document plan, communicate with OB and pediatrician about timing of last dose and infant live vaccine avoidance.

Step 3 management: A teenager with new CD and growth failure — start EEN or biologic, not chronic steroids; refer to pediatric GI; involve school for accommodations.

Complications and Adverse Outcomes

— Toxic megacolon (UC > CD): >6 cm transverse colon, systemic toxicity; mortality up to 30% with perforation

— Perforation, massive GI hemorrhage

— Strictures and obstruction (CD, especially ileal)

— Fistulas (CD): enteroenteric, enterocutaneous, enterovesical (recurrent UTI with pneumaturia/fecaluria), enterovaginal, rectovaginal

— Abscesses (CD, perianal and intra-abdominal)

— Malabsorption, weight loss, vitamin deficiencies (B12, D, iron, zinc)

— Short bowel syndrome after repeated CD resections (<200 cm remaining)

— Gallstones (ileal CD, bile salt loss); kidney stones (calcium oxalate from fat malabsorption binding calcium, leaving oxalate to absorb)

— Colorectal cancer: risk ↑ with disease extent and duration; surveillance colonoscopy starting 8 years after diagnosis of extensive colitis (every 1–3 years); PSC + UC: start at PSC diagnosis, annually

— Small bowel adenocarcinoma in long-standing CD

— Cholangiocarcinoma in PSC

— Lymphoma with thiopurines (especially young men on combo therapy — hepatosplenic T-cell lymphoma)

— Nonmelanoma skin cancer (thiopurines), melanoma (anti-TNF)

— Osteoporosis (steroid use + inflammation + malabsorption) — DEXA in patients on chronic steroids

— VTE: IBD increases venous thromboembolism risk 3-fold, especially during flares and hospitalization — all hospitalized IBD patients need pharmacologic DVT prophylaxis even with rectal bleeding

— Anemia (iron deficiency, anemia of chronic disease, B12 deficiency)

— Depression, anxiety

— Steroid: osteoporosis, hyperglycemia, AVN, cataracts, infection

— Anti-TNF: infection (reactivation TB, HBV, opportunistic), demyelination, drug-induced lupus, infusion reactions, paradoxical psoriasis

— Vedolizumab: gut-selective, very favorable safety

Disease-related complications:

Cancer risk:

Extraintestinal complications:

Therapy-related:

Key distinction: Rectal bleeding in active IBD does not contraindicate VTE prophylaxis — VTE risk outweighs bleeding risk in inpatients. Step 3 will test this.

Board pearl: Recurrent calcium oxalate kidney stones in a CD patient = enteric hyperoxaluria from fat malabsorption — treat with low-oxalate, low-fat diet, calcium supplementation with meals (binds oxalate in gut), hydration.

When to Escalate Care — Inpatient Triage and Consultation

— Severe UC (Truelove-Witts: ≥6 bloody stools/day + systemic toxicity)

— Inability to tolerate PO, dehydration, electrolyte derangement

— Severe abdominal pain, suspected obstruction, abscess, or perforation

— Hemodynamic instability, sepsis

— Hgb <8 or transfusion need

— Failure of outpatient steroid/biologic escalation

— IV access × 2, IVF resuscitation (NS or LR), strict I/O, daily weights

— NPO if obstruction/megacolon; otherwise low-residue diet as tolerated

— Labs: CBC, CMP, CRP, lactate, blood cultures, type and screen

— Stool C. difficile testing, stool cultures

— Abdominal X-ray (megacolon/perforation); CT if pain or suspected complication

— IV methylprednisolone 60 mg/day (for severe UC); equivalent prednisolone

— VTE pharmacologic prophylaxis (enoxaparin 40 mg SQ daily) — even with hematochezia

— Avoid: NSAIDs, opioids (mask exam), anticholinergics, antidiarrheals (megacolon risk)

— Nutrition consult, GI consult on admission, surgical consult on day 1 for severe UC

— Flexible sigmoidoscopy within 24–48 h with CMV staining

— Stool frequency, CRP, albumin predict colectomy risk

— Travis criteria: >8 stools/day OR 3–8 stools + CRP >45 on day 3 = 85% colectomy risk

— Initiate rescue therapy: infliximab 5–10 mg/kg or cyclosporine OR proceed to colectomy

— Reassess again by day 5–7; if no response, colectomy

— GI: always

— Colorectal surgery: severe UC, obstruction, abscess, fistula

— Interventional radiology: drainable abscess

— Nutrition: malnourished or NPO >5–7 days (TPN if no enteral access)

— Ophthalmology: uveitis

— Dermatology: pyoderma gangrenosum

Admission criteria for IBD flare:

Initial inpatient orders (CCS-style):

Day 3 reassessment for acute severe UC:

Consultations:

CCS pearl: In acute severe UC, the clock starts on admission — day 3 decision point is non-negotiable. Delaying surgery in steroid-refractory disease increases postoperative mortality. Order surgery consult on day 1, not day 4.

Step 3 management: Discharge criteria — tolerating diet, stool frequency improving, off IV steroids on oral taper, follow-up arranged within 1–2 weeks with GI, biologic plan in place.

Key Differentials — Same-Category (GI/Colitis) Causes

— C. difficile: prior antibiotics, healthcare exposure; can coexist with IBD flare; toxin/PCR on stool

— Salmonella, Shigella, Campylobacter, EHEC O157:H7 — acute bloody diarrhea, often self-limited; stool culture

— Yersinia enterocolitica — terminal ileitis mimicking CD; mesenteric adenitis, pseudoappendicitis

— Entamoeba histolytica — travel history, flask-shaped ulcers; treat before steroids (steroids worsen amebiasis)

— CMV colitis — in immunosuppressed IBD; suspect in steroid-refractory flare; biopsy with immunostain

— Tuberculous enteritis — endemic exposure, ileocecal, caseating granulomas (vs non-caseating in CD); ALWAYS rule out before anti-TNF

— Elderly, vascular risk factors, watershed (splenic flexure) involvement

— Sudden-onset bloody diarrhea + abdominal pain

— CT: segmental thickening; colonoscopy: pale mucosa with hemorrhage

— Older women, chronic watery non-bloody diarrhea, normal endoscopic appearance, diagnosis on biopsy

— Associations: NSAIDs, PPIs, SSRIs, celiac

— Treatment: stop offending drug, budesonide

— Sigmoid involvement with diverticula; mimics left-sided UC

Infectious colitis — must exclude before diagnosing IBD:

Ischemic colitis:

Microscopic colitis (lymphocytic, collagenous):

Diverticulitis/SCAD (segmental colitis associated with diverticulosis):

Radiation colitis: prior pelvic radiation

NSAID enteropathy: ulcers, strictures, diaphragm-like lesions

Celiac disease: chronic diarrhea, malabsorption, iron deficiency — anti-tTG IgA + duodenal biopsy

Behçet disease: oral and genital ulcers, uveitis, ileocolonic ulcers — can closely mimic CD

Diversion colitis: segment of colon out of fecal stream; treat with SCFA enemas or reanastomosis

Key distinction: Yersinia enterocolitis vs ileal Crohn — both cause RLQ pain, terminal ileitis, fever. Yersinia is self-limited, positive culture/serology; CD persists, has granulomas, skip lesions, perianal disease.

Board pearl: Steroid-refractory UC — always biopsy for CMV before declaring biologic failure; treat CMV with ganciclovir if positive.

Key Differentials — Other-Category (Non-Colitis) Causes

— Functional, no inflammation

— Rome IV: recurrent abdominal pain ≥1 day/week × 3 months + ≥2 of (related to defecation, change in stool frequency/form)

— No alarm features: no weight loss, no nocturnal symptoms, no blood, no anemia, normal calprotectin

— Step 3 favorite: young woman with cramping/diarrhea relieved by defecation, normal labs, normal calprotectin → IBS, not IBD

Irritable bowel syndrome (IBS):

Celiac disease: chronic diarrhea, weight loss, iron deficiency, anti-tTG IgA, duodenal villous atrophy

Lactose/fructose intolerance: bloating, diarrhea after specific foods; H2 breath test

Bile acid diarrhea: post-cholecystectomy or ileal resection; responds to cholestyramine

Hyperthyroidism: diarrhea, weight loss, tachycardia — check TSH

Carcinoid syndrome: flushing, diarrhea, wheezing; elevated 5-HIAA

VIPoma, gastrinoma (Zollinger-Ellison): secretory diarrhea

Chronic pancreatitis: steatorrhea, weight loss, abdominal pain; check fecal elastase

Whipple disease: middle-aged man with diarrhea, weight loss, arthralgia, neuro symptoms; PAS-positive macrophages

HIV enteropathy and opportunistic infections (Cryptosporidium, Microsporidia, MAC, CMV): check HIV status

Colorectal cancer: older patient with rectal bleeding, change in bowel habits, iron deficiency anemia — colonoscopy mandatory

Endometriosis: cyclical GI symptoms with menses; can cause bowel involvement

Eosinophilic gastroenteritis: peripheral eosinophilia, mucosal eosinophil infiltration

Graft-versus-host disease: post-transplant, diarrhea, rash

Factitious diarrhea: laxative abuse — stool osmotic gap, stool laxative screen

Key distinction: A 45-year-old with new-onset bloody diarrhea — even if IBD is plausible, colonoscopy must evaluate for colorectal cancer, not just biopsy for IBD. Age and red flags drive workup.

Board pearl: Recurrent UTIs with pneumaturia or fecaluria in a CD patient = enterovesical fistula — CT cystogram or cystoscopy confirms; surgical repair after disease control.

Secondary Prevention, Discharge Medications, and Long-Term Plan

— Steroid taper plan written explicitly (e.g., prednisone 40 mg with 5–10 mg weekly taper over 6–8 weeks)

— Maintenance therapy initiated or escalated (no patient should leave on steroids without a steroid-sparing plan)

— Calcium 1200 mg + vitamin D 800–1000 IU daily while on steroids

— Pneumocystis prophylaxis (TMP-SMX) if triple immunosuppression (steroid + thiopurine + biologic)

— PPI if on chronic steroids with NSAID exposure or peptic ulcer risk (selectively)

— Iron repletion (oral if mild; IV if severe deficiency or active inflammation impairing oral absorption)

— B12 supplementation if ileal CD or resection

— Antidepressant if comorbid depression/anxiety (common, treat actively)

— UC: 5-ASA, thiopurine, biologic, or small molecule per severity

— CD: biologic ± immunomodulator; never 5-ASA alone for CD maintenance

— Avoid NSAIDs lifelong (flares); acetaminophen for pain

— Colonoscopy with chromoendoscopy or high-definition white light + targeted biopsies every 1–3 years starting 8 years after diagnosis of extensive colitis (UC or Crohn colitis)

— PSC: annual colonoscopy from PSC diagnosis

— Annual skin exam (NMSC risk on thiopurines/anti-TNF)

— Annual cervical cancer screening with HPV co-testing in women on immunosuppression

— Influenza yearly (inactivated)

— Pneumococcal (PCV15/20 + PPSV23)

— Recombinant zoster ≥18 years on immunosuppression (≥50 universally)

— HPV through age 26 (consider through 45)

— Hepatitis A and B if not immune

— COVID-19 per current guidance

— Avoid live vaccines on immunosuppression

Discharge checklist after IBD flare:

Maintenance pharmacotherapy reminders:

Cancer surveillance:

Vaccinations (annual review):

Bone health: DEXA baseline if chronic steroids, repeat every 2 years

Cardiovascular: IBD is a CV risk factor — control BP, lipids, diabetes

Smoking cessation (especially CD): counsel every visit, offer pharmacotherapy

Step 3 management: Discharge summary must communicate to PCP — current meds, taper, vaccinations needed, surveillance schedule, GI follow-up date, red-flag symptoms warranting ED return.

Board pearl: Triple immunosuppression (steroid + thiopurine + anti-TNF) → start TMP-SMX for PJP prophylaxis.

Follow-Up, Monitoring Parameters, and Counseling

— Active disease/new diagnosis: GI visit 2–4 weeks after starting therapy, then every 1–3 months until remission

— Stable remission: GI every 6–12 months

— PCP every 6–12 months for vaccines, depression screening, lipids, BP, cancer screening

— CBC, CMP, CRP every 3 months on most therapies; more often early after biologic initiation

— Fecal calprotectin every 3–6 months as objective surrogate for mucosal inflammation

— Thiopurines: CBC and LFTs at weeks 2, 4, 8, then every 3 months; check 6-TGN levels if subtherapeutic response or toxicity

— Methotrexate: CBC, LFTs every 1–3 months

— Anti-TNF: therapeutic drug monitoring — check drug trough and anti-drug antibodies in loss of response (proactive monitoring increasingly standard)

— Vedolizumab, ustekinumab: similar TDM available

— Reassess mucosa 6–12 months after induction to confirm endoscopic healing (treat-to-target)

— Surveillance per cancer schedule

— Repeat MR enterography in CD as clinically indicated (every 1–2 years if active or stricturing)

— No universal "IBD diet"; Mediterranean or CD-TREAT/specific carbohydrate diet may help symptoms

— Avoid low-fiber only during obstructive symptoms

— Lactose, FODMAP individualized

— Limit ultra-processed foods, emulsifiers (emerging data)

— Screen for depression/anxiety annually (PHQ-9, GAD-7); CBT and gut-directed hypnotherapy effective

— Address fatigue (multifactorial: anemia, inflammation, sleep, depression)

— Symptom diary, calprotectin home kits emerging

— Action plan: who to call for flare, when to go to ED

— Pregnancy planning conversations

Follow-up cadence:

Monitoring labs:

Endoscopic monitoring:

Imaging:

Nutritional counseling:

Mental health:

Patient self-management:

Step 3 management: Treat-to-target with objective markers (CRP, calprotectin, endoscopy) — symptom-based care alone misses persistent inflammation and increases long-term complications.

Board pearl: Persistent diarrhea in a UC patient with normal calprotectin + normal scope = consider bile acid diarrhea, IBS overlap, or pouchitis if post-IPAA — not active UC.

Ethical, Legal, and Patient Safety Considerations

— Discuss serious infection (including reactivation TB, HBV, opportunistic), malignancy risk (lymphoma, NMSC, melanoma), demyelination, infusion reactions, infertility considerations (rare)

— Document conversation; provide written materials

— Shared decision-making between step-up vs top-down strategy in moderate disease — use decision aids

— Pediatric-to-adult GI transition is a high-risk window — medication nonadherence, loss to follow-up, increased flares and hospitalizations

— Structured transition programs starting age 14, formal handoff by age 18–21

— Confidentiality boundaries for adolescents (in many states, ≥14 can consent confidentially to STI/mental health care)

— Patients commonly stop medications during pregnancy out of fear → flares

— Document preconception counseling; involve maternal-fetal medicine for high-risk patients

— Respect autonomy if patient declines therapy, but document risks

— Sulfasalazine causes reversible oligospermia — switch to mesalamine if planning conception

— Methotrexate teratogenic — both partners off ≥3 months before conception; reliable contraception while on it

— Live vaccines contraindicated on immunosuppression — verbal and written warning before starting therapy

— Infants exposed to biologics in utero should not receive rotavirus vaccine (live) in first 6 months

— Hospital discharge after severe flare: medication reconciliation, explicit steroid taper, GI follow-up within 1–2 weeks, clear communication to PCP about monitoring needs

— Avoid duplicate or omitted immunosuppressants across providers

— Patient portal access for results, written action plan

— Biologics are expensive; engage social work, manufacturer assistance programs

— Address food insecurity, transportation, mental health access

— Cancer reporting via tumor registry

— Mandatory TB reporting if reactivation occurs

Informed consent for biologics and immunosuppressants:

Adolescents and transition of care:

Pregnancy decision-making:

Reproductive considerations:

Vaccine safety:

Transitions of care (high-yield Step 3 safety theme):

Health disparities and access:

Mandatory considerations:

Step 3 management: A patient on combination immunosuppression for IBD wishes to attend a wedding in a yellow fever-endemic country — yellow fever vaccine is live and contraindicated; counsel on avoiding travel or holding immunosuppression with ID/GI input. Document discussion.

Board pearl: Failure to screen for latent TB before anti-TNF is the classic preventable harm — boxed warning, malpractice exposure, and exam favorite.

High-Yield Associations and Rapid-Fire Clinical Facts

Smoking: harmful in CD, protective in UC — never recommend smoking; ensure NRT during cessation

Appendectomy reduces UC risk

NSAIDs trigger flares in both — avoid

Antibiotic exposure in childhood ↑ IBD risk

OCP use modestly ↑ IBD risk

Stress and infection trigger flares

Anti-Saccharomyces cerevisiae antibodies (ASCA): Crohn

p-ANCA: ulcerative colitis

Granulomas: Crohn (non-caseating)

Crypt abscesses: UC (not specific)

String sign on small bowel imaging: Crohn ileal stricture

Cobblestoning: Crohn

Lead-pipe colon: chronic UC with loss of haustra

Backwash ileitis: UC pancolitis

Rectal sparing + skip lesions: Crohn

Continuous disease from rectum: UC

Perianal fistula: Crohn

Toxic megacolon: UC > CD

Primary sclerosing cholangitis: UC > CD; ↑ cholangiocarcinoma and colorectal cancer

Erythema nodosum: parallels disease activity

Pyoderma gangrenosum: independent of activity

Peripheral arthritis (type 1, pauciarticular): parallels activity

Axial arthritis/ankylosing spondylitis: independent, HLA-B27

Uveitis: urgent ophthalmology

Kidney stones: calcium oxalate (CD with fat malabsorption); uric acid (dehydration, ileostomy)

Gallstones: ileal CD (bile salt loss)

B12 deficiency: ileal CD or resection

Vitamin D, iron deficiency: common in both

Anti-TNF: infliximab, adalimumab, certolizumab, golimumab

Anti-integrin: vedolizumab (gut-selective, safe)

Anti-IL-12/23: ustekinumab; Anti-IL-23: risankizumab, mirikizumab

JAK inhibitors: tofacitinib (UC), upadacitinib (UC, CD) — boxed warnings

S1P modulators: ozanimod, etrasimod (UC) — check ECG (bradycardia), ophthalmology (macular edema)

EEN (exclusive enteral nutrition): first-line pediatric CD induction

CMV colitis: consider in steroid-refractory UC

C. diff: test in every flare

Surveillance colonoscopy: 8 years after extensive colitis diagnosis; annually if PSC

Step 3 management: When a stem highlights ANY single fact above, it usually anchors the diagnosis — recognize the pattern.

Board pearl: "Cobblestone mucosa + non-caseating granuloma + perianal fistula" = Crohn, regardless of other distractors.

Board Question Stem Patterns

— "28-year-old nonsmoker with 8 weeks of bloody diarrhea, urgency, tenesmus, lower abdominal cramping. Colonoscopy shows continuous erythema and friability from rectum to splenic flexure. Biopsy: crypt abscesses, no granulomas."

— Diagnosis: left-sided UC; next step: 5-ASA oral + topical, GI follow-up

— "23-year-old smoker with 6 months of RLQ pain, non-bloody diarrhea, 8-kg weight loss, perianal fistula. CT enterography: terminal ileal wall thickening with skip lesions."

— Diagnosis: ileocolonic CD with perianal disease; next step: ileocolonoscopy + biopsies, MRI pelvis, anti-TNF induction

— "26-year-old with UC, 10 bloody stools/day, T 38.6, HR 112, Hgb 9.2, CRP 80."

— Next steps: admit, IVF, IV methylprednisolone, stool C. diff, flex sig, surgery consult, VTE prophylaxis despite hematochezia

— Severe UC on IV steroids, day 3: still 9 stools/day, CRP 60 → infliximab or cyclosporine, or colectomy

— UC patient, abdominal distension, transverse colon 8 cm on KUB, T 39, WBC 18k → NPO, NGT, IV steroids + broad-spectrum abx, urgent surgery consult; avoid antimotility agents

— UC patient develops rising creatinine after starting mesalamine → interstitial nephritis, stop drug

— CD patient on infliximab planning pregnancy → continue therapy; counsel on infant rotavirus vaccine

— Patient about to start adalimumab → Quantiferon, CXR, HBV serologies, HIV, vaccinations

— UC flare not improving on IV steroids → check stool C. diff and CMV biopsy before escalating

— UC × 10 years, extensive disease → colonoscopy with biopsies every 1–3 years; PSC + UC → annual

— CD with pneumaturia → enterovesical fistula (CT cystogram)

— CD post-ileal resection with diarrhea → bile acid diarrhea, treat with cholestyramine

— CD with recurrent calcium oxalate stones → enteric hyperoxaluria

— Young woman, crampy diarrhea, no blood, no weight loss, normal calprotectin → IBS, reassure

Classic UC stem:

Classic CD stem:

Severe UC requiring hospitalization:

Day 3 rescue:

Toxic megacolon:

Mesalamine adverse effect:

Pregnancy:

Pre-biologic screening:

C. diff coexistence:

Surveillance:

Crohn complications:

IBS vs IBD:

Step 3 management: When the stem provides timeline, biomarkers, and endoscopic findings, map to severity and select the corresponding step (induction vs maintenance vs rescue vs surgery).

Board pearl: "Steroid-refractory severe UC on day 3" = infliximab/cyclosporine OR colectomy — never just continue steroids.

One-Line Recap

Crohn disease is a transmural, skip-lesion, mouth-to-anus disease with non-caseating granulomas, perianal fistulas, and a stricturing/fistulizing phenotype, whereas ulcerative colitis is a continuous mucosal disease starting at the rectum with bloody diarrhea and crypt abscesses — and Step 3 success hinges on excluding C. difficile and infection first, classifying severity precisely, choosing risk-stratified induction (5-ASA, steroids, or biologic), confirming endoscopic healing, surveilling for colorectal cancer, and managing the chronic-disease longitudinal arc.

— Fecal calprotectin + ileocolonoscopy with biopsies + cross-sectional imaging (MR/CT enterography for CD)

— Always exclude C. difficile and other infections; consider CMV in steroid-refractory disease

— Granulomas = CD; rectal involvement + continuous disease = UC; perianal fistulas = CD

— UC: 5-ASA → steroids → biologics/small molecules → colectomy (curative)

— CD: early biologics for high-risk; surgery is palliative (preserve bowel)

— Acute severe UC day-3 rule: rescue therapy or colectomy if no response to IV steroids

— Pre-biologic: TB, HBV, HIV, vaccines; live vaccines contraindicated on immunosuppression

— Treat-to-target with calprotectin and endoscopic healing, not symptoms alone

— Surveillance colonoscopy starting 8 years after extensive colitis (annual if PSC)

— Smoking cessation in CD; bone health, vaccinations, mental health, pregnancy planning

— Hospitalized IBD patients need VTE prophylaxis even with rectal bleeding

Diagnosis essentials:

Management essentials:

Longitudinal essentials:

Step 3 differentiator: Think outpatient cadence, transitions of care, perioperative planning, preconception counseling, and safety screening — exam rewards the longitudinal, system-aware physician.