Gastrointestinal

Ulcerative colitis: maintenance therapy and surveillance

Clinical Overview and When to Suspect Ulcerative Colitis Maintenance Needs

— Persistent urgency, tenesmus, nocturnal bowel movements, or >3 stools/day above baseline

— Rising fecal calprotectin (>150–250 µg/g) despite symptomatic quiescence

— Recurrent iron deficiency anemia or hypoalbuminemia

— Steroid dependence (cannot taper prednisone below 10 mg without flare within 3 months) or >1 steroid course/year

— Proctitis (≤18 cm): topical mesalamine maintenance often sufficient

— Left-sided (to splenic flexure): oral ± topical 5-ASA

— Extensive/pancolitis: oral 5-ASA ≥2.4 g/day, often advanced therapy

Step 3 management: Any patient who required systemic steroids to achieve remission needs a steroid-sparing maintenance plan in place before discharge — never discharge on a prednisone taper alone without 5-ASA, thiopurine, or biologic bridge planned. Document maintenance regimen, calprotectin baseline, and 8–12 week GI follow-up in the after-visit summary to close the transition-of-care loop.

Ulcerative colitis (UC) is a chronic relapsing-remitting mucosal inflammatory disease of the colon starting at the rectum and extending proximally in continuous fashion

Maintenance therapy is indicated in virtually every patient after induction of remission — UC without maintenance relapses in 60–70% within 1 year vs ~30% with appropriate therapy

When to suspect a maintenance failure or smoldering disease:

Disease extent guides therapy choice:

Risk factors for aggressive course requiring earlier escalation: age <40 at diagnosis, extensive colitis, deep ulcers on endoscopy, need for steroids at diagnosis, elevated CRP/ESR, low albumin, primary sclerosing cholangitis (PSC) comorbidity

Step 3 framing: a primary care or general internist often manages stable UC longitudinally with GI co-management — recognize when to refer back urgently versus continue stable maintenance refills

Presentation Patterns and Key History

— Stool frequency, blood, nocturnal stools (highly specific for active disease), urgency score

— Abdominal pain pattern — new RUQ pain raises concern for PSC or cholangiocarcinoma

— Extraintestinal symptoms: large-joint arthralgia, episcleritis/uveitis, oral ulcers, erythema nodosum, pyoderma gangrenosum

— Adherence to 5-ASA (notoriously poor — ~40% nonadherence drives "treatment failure")

— NSAID use, recent antibiotics (C. difficile risk), travel, new sexual contacts

— >6 bloody stools/day, fever, tachycardia → possible acute severe UC (Truelove–Witts)

— Abdominal distension, decreasing stool output despite worsening pain → toxic megacolon

— Weight loss, jaundice, pruritus → PSC progression or malignancy

Board pearl: Nocturnal bowel movements that wake the patient from sleep are an exam-favorite marker distinguishing organic inflammatory disease from IBS — their presence essentially excludes a functional explanation and mandates objective reassessment (calprotectin, sigmoidoscopy) even if daytime symptoms seem mild.

Key distinction: Worsening symptoms on stable therapy → first rule out superimposed C. difficile and CMV with stool PCR and, if severe, flexible sigmoidoscopy with biopsy before assuming a true UC flare and escalating immunosuppression. Empirically intensifying biologics in undiagnosed C. difficile colitis is a classic Step 3 wrong answer.

Classic UC presentation: bloody diarrhea, urgency, tenesmus, lower abdominal cramping relieved by defecation, often with mucus

In maintenance phase, ask targeted questions at every visit:

Mayo partial score (without endoscopy) tracks at each visit: stool frequency (0–3), rectal bleeding (0–3), physician global (0–3) — remission = total ≤2 with no subscore >1

Red-flag history demanding urgent re-evaluation:

Family history of IBD or colorectal cancer modifies surveillance interval

Vaccination and reproductive history matter: live vaccines contraindicated on biologics; pregnancy planning shifts drug selection

Physical Exam Findings and Hemodynamic Assessment

— Vitals: tachycardia, fever, orthostasis suggest flare or infection (sepsis screen)

— BMI and weight trend: unintentional loss prompts work-up

— Abdomen: tenderness over colonic frame, distension, tympany (megacolon), rebound (perforation)

— Perianal exam: fissures, fistulas, skin tags — extensive perianal disease should prompt reconsideration of Crohn's diagnosis

— Skin: erythema nodosum (pretibial, painful), pyoderma gangrenosum (often parallels disease activity less reliably)

— Eyes: episcleritis (parallels activity), anterior uveitis (independent)

— Joints: peripheral pauciarticular arthritis (parallels gut activity); axial sacroiliitis/AS (independent)

— HEENT: aphthous ulcers, pallor of conjunctiva (anemia)

— Hepatic: hepatomegaly, jaundice → PSC evaluation

— HR >90, T >37.8°C, Hgb <10.5, ESR >30 = Truelove–Witts severe colitis criteria when combined with ≥6 bloody stools/day

— Hypotension or orthostasis → volume resuscitation and admission

Step 3 management: A maintenance-clinic patient who arrives with HR 110, T 38.2°C, 8 bloody stools/day, and abdominal tenderness should be sent directly to the ED, not given oral steroids in clinic. Outpatient escalation is unsafe — they need IV methylprednisolone 60 mg/day, VTE prophylaxis, surgical and GI consults, abdominal imaging to exclude megacolon/perforation, and stool studies including C. difficile PCR. Document the decision and arrange handoff communication.

In well-maintained UC the exam is often normal — a reassuring exam does not exclude mucosal inflammation; objective biomarkers and endoscopy are required

Targeted exam at maintenance visits:

Hemodynamic red flags requiring same-day escalation:

Digital rectal exam: stool color, blood, masses; do not skip in new bleeding

Diagnostic Workup — Initial Labs, Imaging, and Biomarkers in Maintenance

— CBC (anemia, leukocytosis), CMP (albumin, LFTs — PSC screen, drug toxicity)

— CRP and ESR — imperfect but rising trend correlates with flare

— Iron studies, ferritin, B12, folate, vitamin D — chronic losses and malabsorption

— Fecal calprotectin — most useful noninvasive activity marker; <150 µg/g supports remission, >250 strongly suggests active inflammation

— 5-ASA: annual creatinine (rare interstitial nephritis)

— Thiopurines: CBC and LFTs every 3 months; TPMT/NUDT15 genotype before starting

— Anti-TNF: TB (IGRA), HBV serologies pre-treatment; periodic drug levels and antibodies

— JAK inhibitors (tofacitinib, upadacitinib): lipid panel at 8 weeks, CBC, LFTs, lipid + CV risk assessment

— C. difficile PCR/toxin (UC patients have higher incidence and worse outcomes)

— Bacterial culture, ova/parasites if travel/exposure

— Consider CMV if steroid-refractory

— Plain abdominal radiograph for suspected megacolon (transverse colon >6 cm)

— CT for complications (perforation, abscess); not used to diagnose UC itself

— MRCP if cholestatic LFTs → screen all UC patients with persistently elevated alk phos for PSC

Board pearl: Fecal calprotectin is the maintenance-phase workhorse — a value <50 µg/g has high NPV for mucosal healing and can defer colonoscopy; >250 µg/g warrants endoscopic reassessment even if the patient feels well. Use it to confirm true symptomatic remission represents biologic remission, the deeper treatment target championed by STRIDE-II (clinical + biomarker + endoscopic healing).

Maintenance monitoring labs (every 3–6 months on stable therapy; more often after changes):

Drug-specific monitoring (covered deeper in chunk 7–8):

Stool studies whenever symptoms change:

Imaging:

Diagnostic Workup — Endoscopy, Histology, and Surveillance Strategy

— Begin surveillance colonoscopy 8 years after symptom onset for extensive or left-sided colitis

— Begin immediately at diagnosis if concomitant PSC, then annually for life

— Interval: every 1–3 years based on risk (PSC, family hx CRC, prior dysplasia, strictures, ongoing inflammation, pseudopolyps)

— Technique: high-definition chromoendoscopy with targeted biopsies preferred; if standard WLE, take random 4-quadrant biopsies every 10 cm (≥33 samples)

— Visible, well-circumscribed dysplasia → endoscopic resection + intensified surveillance

— Invisible or multifocal high-grade dysplasia, or dysplasia with stricture → total proctocolectomy

Step 3 management: A 32-year-old with UC + PSC diagnosed today needs surveillance colonoscopy now, not in 8 years, and annually thereafter. Also start ursodeoxycholic acid only if specific indication (not routinely for CRC prevention — high-dose UDCA actually increased colon cancer risk in trials). Refer to hepatology and discuss eventual transplant trajectory.

Colonoscopy with ileal intubation and segmental biopsies is the gold standard for diagnosis, disease extent, activity assessment, and dysplasia surveillance

Endoscopic findings in active UC: continuous erythema, loss of vascular pattern, granularity, friability, erosions, ulcers — graded by Mayo endoscopic subscore (0 normal, 1 mild, 2 moderate, 3 severe)

Mucosal healing (Mayo 0–1) is the modern treatment target — associated with reduced relapse, hospitalization, colectomy, and cancer

Histology: crypt architectural distortion, basal plasmacytosis, cryptitis, crypt abscesses; histologic remission (Nancy or Geboes score) is an emerging deeper target

Dysplasia surveillance — high-yield Step 3 content:

Management of dysplasia:

Sigmoidoscopy (unprepped, no sedation) is preferred in acute severe colitis to limit perforation risk

Risk Stratification and Maintenance Therapy Selection Logic

— Low-risk: limited extent (proctitis/left-sided), mild endoscopic activity, no steroid dependence, no hospitalization, normal CRP/albumin, age >40 at diagnosis

— High-risk: extensive colitis, deep ulcers, age <40, hospitalization, steroid requirement, high CRP, low albumin, EIMs, PSC

— Mild proctitis: mesalamine suppository 1 g nightly as maintenance after induction

— Mild-moderate left-sided/extensive: oral 5-ASA ≥2.0–2.4 g/day, often combined with topical 2–3×/week

— Steroid-dependent or 5-ASA failure: step up to thiopurine + anti-TNF combo, or vedolizumab, ustekinumab, JAK inhibitor, or S1P modulator (ozanimod) monotherapy

— Acute severe UC responsive to IV steroids: maintain with infliximab, vedolizumab, or tofacitinib; thiopurine monotherapy inadequate

— Short term: symptom relief, normalize CRP/calprotectin

— Intermediate: corticosteroid-free clinical remission

— Long term: endoscopic healing (Mayo 0–1), restoration of QoL, prevention of disability

Key distinction: Steroids are never appropriate maintenance therapy in UC — neither oral prednisone nor budesonide MMX. If a patient cannot taper off steroids without flaring, they are steroid-dependent by definition and need a steroid-sparing agent (thiopurine, biologic, or JAK inhibitor) added now, not another taper attempt. This is a perennial Step 3 stem.

Stratify each patient as low-risk vs moderate-to-high-risk to choose maintenance:

Therapy choice flow:

Treat-to-target (STRIDE-II):

Reassess at 3 months and intensify if targets unmet — do not "wait and see" indefinitely on a failing regimen

Consider colectomy referral for medically refractory disease, dysplasia, or patient preference — proctocolectomy with IPAA (ileal pouch–anal anastomosis) is curative for the colonic disease

Pharmacotherapy — 5-ASA, Thiopurines, and Biologic Maintenance

— Oral mesalamine 2.0–4.8 g/day; topical 1 g suppository (proctitis) or enema (left-sided)

— Combined oral + topical superior to either alone for left-sided disease

— Once-daily dosing equals divided dosing for efficacy and improves adherence

— Adverse effects: headache, dyspepsia, interstitial nephritis (annual Cr), rare paradoxical worsening

— Sulfasalazine: add folic acid 1 mg/day; check G6PD; causes reversible oligospermia

— Check TPMT and NUDT15 genotype/activity before starting — homozygous deficiency contraindicates use; intermediate requires dose reduction

— Monitor CBC and LFTs weekly × 4, then monthly × 3, then every 3 months

— Adverse: myelosuppression, hepatotoxicity, pancreatitis, lymphoma (especially HSTCL in young males on anti-TNF combo), nonmelanoma skin cancer (sun protection, annual derm)

— Pre-treatment: TB (IGRA), HBV serologies, update vaccines including inactivated influenza/pneumococcal/recombinant zoster; avoid live vaccines on therapy

— Therapeutic drug monitoring: trough infliximab >5 µg/mL targets; check antibodies if loss of response

— Combine infliximab + thiopurine (UC SUCCESS) for higher remission, weigh malignancy risk

Board pearl: Patients on any immunosuppressive maintenance need annual influenza, pneumococcal (PCV15→PPSV23 or PCV20), and recombinant zoster vaccines, and HPV through age 45 — administered ideally before immunosuppression starts. Live vaccines (MMR, varicella, yellow fever, live zoster, intranasal flu) are contraindicated on biologics and JAKi.

5-Aminosalicylates (mesalamine, sulfasalazine, balsalazide, olsalazine) — first-line for mild-moderate UC

Thiopurines (azathioprine 2–2.5 mg/kg, 6-MP 1–1.5 mg/kg) — steroid-sparing maintenance, slow onset (3–4 months)

Anti-TNFs: infliximab (IV), adalimumab (SC), golimumab (SC)

Vedolizumab (gut-selective α4β7): excellent safety, slower onset, no TB reactivation risk

Ustekinumab (IL-12/23): once q8 weeks SC after IV induction

JAK inhibitors (tofacitinib, upadacitinib): rapid onset; boxed warnings — MACE, VTE, malignancy, serious infections — reserve for prior anti-TNF failure or age <50 nonsmokers per FDA labeling

Ozanimod (S1P modulator): check baseline ECG (bradycardia), ophthalmology (macular edema), LFTs

Surgical Management and Advanced Therapy Sequencing

— Emergency: toxic megacolon, perforation, uncontrolled hemorrhage, fulminant colitis refractory to medical rescue

— Elective: medically refractory disease, intolerable side effects, dysplasia/cancer, growth failure (peds), patient preference

— 2-stage: colectomy + IPAA with diverting loop ileostomy → ileostomy takedown

— 3-stage (preferred in severely ill or on biologics/steroids): subtotal colectomy with end ileostomy → completion proctectomy + IPAA → ileostomy takedown

— Pouchitis — most common complication (up to 50% lifetime); ciprofloxacin or metronidazole 2 weeks; chronic antibiotic-refractory pouchitis may respond to vedolizumab

— Cuffitis (retained rectal cuff inflammation) — topical mesalamine

— Pouch failure, fertility reduction in women (~30% relative reduction), nocturnal seepage

— Annual pouchoscopy if PSC or prior dysplasia

— Generally first-line biologic: infliximab or vedolizumab

— Switching within class (anti-TNF → anti-TNF) for immunogenicity loss-of-response with adequate drug level but antibodies

— Switching out-of-class for primary nonresponse or adequate level without response

— Sequence considerations: prior anti-TNF exposure reduces ustekinumab and vedolizumab efficacy modestly but they remain valid

CCS pearl: For a CCS case of acute severe UC failing 3–5 days of IV methylprednisolone, the correct next orders are simultaneous surgical consult AND medical rescue (infliximab 5–10 mg/kg or IV cyclosporine 2 mg/kg/day) — not one then the other. Continue VTE prophylaxis with LMWH despite rectal bleeding (UC is prothrombotic; bleeding is rarely the limiting factor).

Indications for colectomy in UC:

Procedure of choice in most: total proctocolectomy with ileal pouch–anal anastomosis (IPAA), typically staged

Post-IPAA long-term issues to manage in primary care/GI co-care:

Advanced therapy positioning when 5-ASA fails:

Stop-therapy decisions: generally continue maintenance indefinitely; de-escalation only in select sustained deep remission with shared decision-making — relapse risk ~40% within 2 years

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher infection risk on immunosuppression — vedolizumab and ustekinumab preferred over anti-TNF or thiopurines due to favorable safety

— Avoid tofacitinib/upadacitinib if age ≥65, smokers, or CV risk factors — ORAL Surveillance showed increased MACE, VTE, malignancy

— Thiopurines: higher lymphoma and nonmelanoma skin cancer risk in elderly — generally avoid as new starts

— Steroids: high risk of osteoporosis, hyperglycemia, delirium, infection — minimize duration; co-prescribe calcium/vitamin D and consider bisphosphonate if >3 months

— Polypharmacy review: NSAIDs (flare trigger), anticoagulants (bleeding), drug-drug interactions

— Cancer screening up to date (colon surveillance per UC protocol still applies)

— 5-ASA: monitor Cr at baseline, 3 months, then annually — stop if Cr rises unexplained (interstitial nephritis)

— Avoid NSAIDs entirely

— Anti-TNF, vedolizumab, ustekinumab: no dose adjustment, generally safe

— JAK inhibitors: dose reduce in moderate-severe renal impairment; tofacitinib 5 mg daily if CrCl <30

— Thiopurines: caution; avoid in Child-Pugh C

— Methotrexate: avoid in significant hepatic disease

— Anti-TNFs: monitor LFTs; rare drug-induced hepatitis with infliximab

— Tofacitinib: not recommended in severe hepatic impairment

— Ozanimod: contraindicated in moderate-severe hepatic impairment

Step 3 management: A 72-year-old with UC requiring escalation beyond 5-ASA should preferentially receive vedolizumab — gut-selective, no significant systemic immunosuppression, no TB reactivation, and the strongest safety profile in older adults. This is the high-yield "elderly + IBD" answer choice.

Elderly UC patients (onset >60 or aging cohort): account for ~15% of cases; bimodal incidence

Renal impairment:

Hepatic impairment (often PSC-related):

Bone health: DEXA at baseline for steroid-exposed or elderly patients; repeat every 1–2 years

Special Populations — Pregnancy, Pediatrics, and Reproductive Care

— Continue mesalamine (avoid sulfasalazine-containing brands with high dibutyl phthalate; supplement folate 2 mg/day)

— Continue azathioprine/6-MP — extensive registry data support safety; do NOT start de novo in pregnancy

— Continue infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab — IgG biologics cross placenta in T3 (certolizumab minimally due to pegylated Fab structure)

— Avoid live vaccines in infants exposed to biologics in utero for first 6 months (rotavirus is the practical issue)

— Stop methotrexate ≥3 months before conception in both partners — teratogenic and abortifacient

— Avoid tofacitinib/upadacitinib and ozanimod in pregnancy (animal teratogenicity)

— More often extensive (pancolitis ~80%); growth and pubertal monitoring essential

— Mesalamine, thiopurines, infliximab, adalimumab, vedolizumab, ustekinumab approved

— Vaccinations including HPV on schedule; live vaccines before immunosuppression when possible

— Transition-of-care to adult GI typically late adolescence with structured handoff

Board pearl: Sulfasalazine causes reversible male infertility via oligospermia — switch to a non-sulfa 5-ASA (mesalamine) 3 months before attempting conception. Female fertility on UC medications is preserved; IPAA surgery itself reduces female fertility ~3-fold due to pelvic adhesions — discuss before elective colectomy in women of reproductive age.

Preconception counseling is essential: disease activity at conception is the strongest predictor of pregnancy outcome — aim for ≥3–6 months of remission before conception

Medication safety in pregnancy/lactation (key Step 3 content):

Flares in pregnancy: treat aggressively — untreated active disease harms fetus more than medications; steroids, biologics as needed

Delivery: vaginal generally fine; cesarean preferred for active perianal disease or after IPAA to protect sphincter

Breastfeeding compatible with 5-ASA, thiopurines, anti-TNFs, vedolizumab, ustekinumab

Pediatric UC:

Complications and Adverse Outcomes

— Toxic megacolon (transverse colon >6 cm on imaging + systemic toxicity) — surgical emergency; mortality ~20% if perforation

— Severe hemorrhage, perforation, stricture (uncommon — strictures in UC should raise cancer suspicion)

— Colorectal cancer: cumulative risk ~2% at 10 years, 8% at 20, 18% at 30 — drivers are duration, extent, inflammation severity, PSC, family hx

— Venous thromboembolism: 3× baseline risk, even higher during flares — prophylax all hospitalized UC patients with LMWH regardless of rectal bleeding

— Parallel disease activity: peripheral arthritis (type 1, pauciarticular), episcleritis, erythema nodosum, oral ulcers

— Independent of activity: axial spondyloarthritis/ankylosing spondylitis (HLA-B27), uveitis, pyoderma gangrenosum, PSC (5% of UC, but 75% of PSC patients have IBD)

— Hepatobiliary: PSC → cholangiocarcinoma (annual MRCP + CA 19-9), gallbladder cancer

— Metabolic bone disease, iron deficiency, B12 deficiency (post-ileal pouch)

— Steroids: osteoporosis, cataracts, glucose intolerance, adrenal suppression, infection, mood

— Thiopurines: myelosuppression, hepatotoxicity, pancreatitis, lymphoma, NMSC

— Anti-TNF: infusion reactions, reactivation TB/HBV, demyelination, drug-induced lupus, melanoma slight increase

— JAKi: VTE, MACE, herpes zoster (vaccinate first), malignancy

— Post-IPAA: pouchitis, cuffitis, infertility (women), pouch failure

Key distinction: Pyoderma gangrenosum often does not parallel UC activity and may persist or appear after colectomy — treat with topical/intralesional steroids, systemic steroids, cyclosporine, or infliximab (works even in colectomized patients); avoid surgical debridement which triggers pathergy.

Disease-related complications:

Extraintestinal manifestations (EIMs):

Treatment-related complications:

Psychosocial: depression and anxiety prevalence ~30%; screen with PHQ-2/GAD-2 annually

When to Escalate Care — Inpatient, ICU, Surgical Consult

— IV methylprednisolone 60 mg/day or hydrocortisone 100 mg IV q6h

— IV fluids, electrolyte repletion (K, Mg)

— VTE prophylaxis with LMWH even with bleeding

— Stool C. difficile, bacterial pathogens, CMV PCR on biopsy

— Flexible sigmoidoscopy without full prep within 24 hours (limited insufflation) to assess severity, exclude CMV

— Plain film daily to monitor for megacolon while severe

— NPO if megacolon/considering surgery; otherwise low-residue diet

— Avoid opioids, anticholinergics, antidiarrheals, NSAIDs (precipitate megacolon)

— Early surgical consult day 1

— Nutrition consult; enteral nutrition preferred over TPN

— New steroid requirement, loss of response to maintenance biologic, recurrent C. difficile, dysplasia, new EIM, abnormal LFTs (PSC eval)

CCS pearl: In an ASUC CCS case, do not advance the clock 5 days waiting for steroids to work before considering rescue or surgery — assess on day 3. Failing to act on day 3 is a graded error. Move case time deliberately: orders → 24 hours → reassess vitals/stools/CRP → 48 hours → repeat → day 3 decision point with both medical rescue and surgical pathways activated in parallel.

Acute severe UC (ASUC) by Truelove–Witts: ≥6 bloody stools/day PLUS any of HR >90, T >37.8°C, Hgb <10.5, ESR >30 — admit, do not manage outpatient

Inpatient ASUC bundle (CCS-style orders):

Day 3 assessment (Oxford/Travis criteria): if >8 stools/day, OR 3–8 stools with CRP >45 mg/L → 85% colectomy risk — start medical rescue (infliximab or cyclosporine) AND maintain active surgical option

ICU criteria: hemodynamic instability, megacolon, perforation, severe electrolyte derangement, transfusion needs, organ dysfunction

Outpatient escalation triggers (urgent GI referral within days, not weeks):

Key Differentials — Other Inflammatory and Infectious Colitides

— Patchy/segmental, skip lesions, rectal sparing, ileal involvement, transmural ulcers, granulomas, fistulas, perianal disease

— Smoking worsens Crohn's, may paradoxically improve UC (do NOT recommend smoking — net harm)

— Distinction matters because IPAA outcomes worse in Crohn's; indeterminate colitis 10–15% of cases — manage based on phenotype

— C. difficile — test on every flare; metronidazole inadequate for severe — use oral vancomycin 125 mg QID × 10 days or fidaxomicin

— CMV colitis — suspect in steroid-refractory disease; diagnose by tissue PCR/immunohistochemistry, not blood PCR alone; treat with ganciclovir

— Bacterial: Shigella, Salmonella, Campylobacter, enterohemorrhagic E. coli, Yersinia, Aeromonas

— Parasitic: amebiasis (do not steroid-treat without excluding in endemic exposure — fatal megacolon risk), giardiasis

— Sexually transmitted proctitis: gonorrhea, chlamydia (LGV), syphilis, HSV — receptive anal intercourse history

Key distinction: Always retest C. difficile at every UC flare — UC patients have higher prevalence, often without the classic risk factors (no antibiotic exposure necessary), and superimposed CDI dramatically worsens outcomes. Treating CDI without intensifying immunosuppression often resolves the "flare."

Crohn's colitis — the critical same-category differential

Infectious colitis:

Microscopic colitis (collagenous, lymphocytic): nonbloody watery diarrhea, normal endoscopy, diagnosis on biopsy; treat with budesonide

Ischemic colitis: elderly, watershed (splenic flexure), acute LLQ pain then bleeding, self-limited; thumbprinting on imaging

Radiation proctitis: history of pelvic radiation, telangiectasias on endoscopy

NSAID colitis, diversion colitis, diverticular colitis

Key Differentials — Functional, Neoplastic, and Systemic Mimics

— Up to one-third of UC patients in remission have overlapping IBS-like symptoms

— Distinguish via objective markers: normal CRP, calprotectin <50–150, normal endoscopy

— Treat IBS symptoms (low-FODMAP, antispasmodics, neuromodulators) — do not escalate IBD therapy for IBS overlap

— UC patients have elevated baseline risk; new anemia, weight loss, change in caliber, or new stricture in a UC patient should prompt urgent colonoscopy

— Surveillance schedule already discussed

Board pearl: Checkpoint inhibitor colitis in an oncology patient mimics UC endoscopically and histologically; first-line is high-dose corticosteroids, escalating to infliximab or vedolizumab if no response within 3–5 days. Recognizing this and not delaying biologic rescue is the classic Step 3 oncology-GI crossover question.

Irritable bowel syndrome (IBS):

Colorectal cancer:

Diverticulitis / SCAD (segmental colitis associated with diverticulosis) — typically older, sigmoid-localized

Celiac disease — anemia, weight loss, diarrhea; check tissue transglutaminase IgA + total IgA

Bile acid diarrhea — particularly after ileal resection or in IPAA patients; trial cholestyramine

Hyperthyroidism — diarrhea, weight loss; check TSH

Vasculitides: Behçet's (oral and genital ulcers, uveitis, ileocecal ulcers), polyarteritis nodosa, IgA vasculitis (Henoch-Schönlein)

Medication-induced colitis: mycophenolate, checkpoint inhibitors (ipilimumab > nivolumab/pembrolizumab) — manage with steroids ± infliximab/vedolizumab

Eosinophilic colitis, GVHD (post-HSCT), Behçet, SLE enteritis

Anorectal disorders: hemorrhoids and fissures can mimic UC bleeding — examine carefully

Secondary Prevention, Discharge Planning, and Long-Term Maintenance

— Written taper plan for steroids (e.g., prednisone 40 mg → taper 5 mg/week)

— Maintenance therapy in hand at discharge — never discharge on steroids alone without a steroid-sparing plan

— VTE prophylaxis duration: continue prophylactic LMWH through hospitalization; extended prophylaxis post-discharge case-by-case (ASUC, prior VTE)

— Calcium 1200 mg + vitamin D 800–1000 IU daily; consider bisphosphonate if prolonged steroids

— PPI if steroids + anticoagulation or peptic history

— PCP appointment within 1–2 weeks; GI within 4–8 weeks; repeat calprotectin at 6–8 weeks

— Annual inactivated influenza

— Pneumococcal: PCV20 alone OR PCV15 followed by PPSV23

— Recombinant zoster vaccine (Shingrix) for all immunosuppressed patients ≥18 (off-label <50 but recommended by AGA)

— HPV through age 45

— Tdap, COVID-19 boosters

— Hepatitis B series if nonimmune (especially before anti-TNF)

— Live vaccines (MMR, varicella, yellow fever, live zoster, intranasal flu) contraindicated while on biologics/JAKi/thiopurines — administer ≥4 weeks before starting or 3 months after stopping

— Surveillance colonoscopy on schedule

— Annual dermatology exam on thiopurines or anti-TNF (skin cancer surveillance)

— Cervical cancer screening per guidelines (annual cytology if immunosuppressed per some guidance)

— Smoking cessation, sun protection, BMI optimization

Step 3 management: Build a structured annual "IBD health maintenance" visit — vaccines, derm exam, DEXA if indicated, depression screen, smoking cessation, calprotectin, surveillance colonoscopy scheduling. This bundled visit is high-yield ambulatory Step 3 content and mirrors AGA quality measures.

Discharge after a flare (after ED or hospital):

Vaccinations (verify and update at every visit):

Cancer prevention:

Bone health, cardiovascular risk, mental health screening annually

Iron repletion: IV iron preferred during active disease (oral worsens GI symptoms)

Follow-Up, Monitoring Parameters, and Patient Counseling

— Clinic visit every 3–6 months in remission, every 4–8 weeks during induction/escalation

— Labs: CBC, CMP, CRP every 3–6 months; thiopurines need CBC/LFTs q3 months; biologics per agent

— Fecal calprotectin every 3–6 months even in symptomatic remission to detect subclinical inflammation

— Therapeutic drug monitoring for anti-TNFs at week 14 (induction completion) and reactively at loss of response

— Surveillance colonoscopy per stratified interval

— If clinical remission + biomarker remission → continue

— If symptoms persist or calprotectin elevated → endoscopic reassessment and escalation

— Adherence emphasis — non-adherence is the most common cause of relapse on 5-ASA

— Avoid NSAIDs; acetaminophen is preferred analgesic

— Smoking: cessation overall benefits health; counsel that UC may flare on quitting but do not advise smoking

— Diet: no universal IBD diet; Mediterranean-style favored; identify individual triggers; lactose intolerance more common

— Stress and sleep affect symptom perception; CBT, gut-directed hypnotherapy adjuncts

— Travel: vaccinations, traveler's diarrhea plan (do not use antimotility in active flare), drug refills

— Pregnancy planning conversation early in reproductive-age patients

CCS pearl: When a stable UC patient reports symptoms suggestive of flare, the correct virtual/CCS sequence is: stool studies including C. difficile → fecal calprotectin → flexible sigmoidoscopy if biomarkers elevated → then adjust therapy. Jumping to oral prednisone without objective confirmation and infection exclusion is a graded misstep.

Monitoring cadence on stable maintenance:

Treat-to-target reassessment at 3 months after any change:

Patient counseling pearls:

Care coordination: shared GI + PCP model; rheumatology, dermatology, hepatology, ophthalmology referrals as EIMs dictate

Patient-reported outcome tools: SCCAI, IBD-Q for QoL trending

Ethical, Legal, and Patient Safety Considerations

— Boxed warnings: serious infections, TB reactivation, malignancy (especially lymphoma, NMSC), HBV reactivation, demyelination (anti-TNF), MACE/VTE (JAKi)

— Risks vs. benefits compared to undertreated disease and colectomy

— Long-term commitment, monitoring requirements, cost

— Document conversation in chart with patient teach-back

— Hospital discharge for ASUC: medication reconciliation, steroid taper instructions, biologic infusion scheduled, GI follow-up within 2–4 weeks, PCP within 1–2 weeks, return precautions in writing

— Avoid "discharge with prednisone, follow up with GI in 3 months" — that is the wrong-answer stem; high relapse and readmission risk

— Pediatric-to-adult transition: structured handoff visit, written summary, transition readiness assessment

— Patient's values about ostomy, pouch function, fertility, quality of life

— Surgeon-patient discussion of staged approach, pouch failure rates (~5–10%)

— Reproductive counseling for women — fertility implications of pelvic surgery

Step 3 management: A UC patient on infliximab found to have a positive IGRA but normal CXR has latent TB. Start isoniazid + B6 for 9 months (or rifampin 4 months, or 3HP weekly × 12 weeks); you may begin or continue infliximab after 1 month of LTBI therapy — do not delay months. Report per state law.

Informed consent for biologics and JAK inhibitors must include:

Transition-of-care safety — the highest-yield Step 3 safety scenario:

Shared decision-making for colectomy:

Adolescent autonomy and confidentiality: discuss sexual activity, substance use, mental health privately; respect minor consent laws by state for STI testing and contraception

Mandatory reporting: occupational exposure to TB; reportable communicable diseases (e.g., new TB on IGRA pre-biologic screening must be reported and treated before starting therapy)

Pharmacy and insurance navigation: biologic prior authorizations are leading cause of treatment delay; document medical necessity, use specialty pharmacy patient assistance programs

Medication safety: never co-prescribe live vaccines on biologics; verify TPMT/NUDT15 before thiopurines; check HBV before anti-TNF — failure constitutes a sentinel safety event

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: A young man with UC develops fatigue, pruritus, and alk phos 3× ULN — order MRCP for PSC, not RUQ ultrasound first. ERCP only if MRCP positive or therapy needed; brushings for cholangiocarcinoma if dominant stricture.

PSC + UC: 75% of PSC patients have IBD (mostly UC); UC with PSC requires annual surveillance colonoscopy from diagnosis, often right-sided dysplasia/cancer predominance, annual MRCP + CA 19-9 for cholangiocarcinoma

Backwash ileitis in UC: mild ileal inflammation contiguous with pancolitis — does not equal Crohn's

p-ANCA positive in ~70% of UC (vs ASCA more often Crohn's) — not used clinically for diagnosis but classic test trivia

Smoking: protective in UC, harmful in Crohn's — never recommend smoking; nicotine patches studied with modest effect, not standard

Appendectomy before age 20 for true appendicitis is associated with lower risk of developing UC

HLA-B27 → axial spondyloarthritis association

Erythema nodosum and peripheral arthritis parallel disease activity; uveitis, AS, PSC do NOT parallel activity

Pyoderma gangrenosum: pathergy phenomenon — do not debride; treat with steroids, cyclosporine, or infliximab

Toxic megacolon precipitants: hypokalemia, opioids, anticholinergics, antidiarrheals, barium enema, colonoscopy in severe disease

Truelove–Witts severity criteria (memorize): ≥6 bloody stools + ≥1 of T >37.8, HR >90, Hgb <10.5, ESR >30

STRIDE-II targets: clinical + biomarker remission short-term, endoscopic healing long-term

5-ASA is for UC primarily; minimal role in Crohn's despite historical use

Sulfasalazine causes reversible oligospermia; supplement folate

Tofacitinib black box: MACE, VTE, malignancy — avoid in age ≥65, smokers, CV risk

Vedolizumab — gut-selective, safest in elderly and infections risk

Infliximab dose intensification: 10 mg/kg or q4-week dosing if low trough

Pouchitis treatment: ciprofloxacin or metronidazole; recurrent → rifaximin, VSL#3-type probiotics, vedolizumab

Iron deficiency in IBD: IV iron preferred during active disease

Board Question Stem Patterns

Key distinction: When the stem says "feels well but calprotectin 600," the answer is endoscopic reassessment, not reassurance — STRIDE-II targets demand objective remission, not just symptomatic.

Stem 1 — Steroid dependence: "A 28-year-old with UC has flared each time prednisone is tapered below 15 mg over the past year." → Best next step: start a steroid-sparing maintenance agent (azathioprine if mild, infliximab/vedolizumab if moderate-severe). Wrong answers: another steroid taper, continue prednisone indefinitely, budesonide MMX as maintenance.

Stem 2 — Flare on stable 5-ASA: "Increased stool frequency and bleeding after 2 years of remission." → Stool studies including C. difficile PCR first, then calprotectin, then sigmoidoscopy. Wrong: empiric prednisone, immediate biologic.

Stem 3 — UC + abnormal LFTs: "Alk phos 480, GGT elevated." → MRCP for PSC. Wrong: RUQ US first as the answer, hepatitis serologies alone.

Stem 4 — Surveillance timing: New UC diagnosis with PSC. → Colonoscopy now and annually. Wrong: 8 years from symptom onset.

Stem 5 — Acute severe UC day 3: IV steroids failing. → Infliximab or cyclosporine rescue AND surgical consult. Wrong: continue steroids 5 more days, switch to oral prednisone.

Stem 6 — Pregnancy: UC in remission on infliximab, planning pregnancy. → Continue infliximab; avoid live vaccines in infant first 6 months. Wrong: stop biologic.

Stem 7 — Elderly + escalation: 70-year-old needs beyond 5-ASA. → Vedolizumab. Wrong: tofacitinib, azathioprine.

Stem 8 — Vaccination before biologic: → Update inactivated influenza, pneumococcal, recombinant zoster, HBV, HPV; live vaccines ≥4 weeks before. Wrong: live MMR after biologic started.

Stem 9 — Dysplasia management: Visible polypoid low-grade dysplasia resected completely. → Intensified surveillance. Wrong: immediate colectomy. Invisible high-grade or multifocal LGD → colectomy.

Stem 10 — VTE prophylaxis with rectal bleeding: ASUC inpatient. → LMWH prophylaxis still indicated. Wrong: hold anticoagulation due to bleeding.

Stem 11 — Pyoderma gangrenosum post-colectomy: → Infliximab or systemic steroids; avoid debridement (pathergy). Wrong: surgical debridement.

One-Line Recap

Ulcerative colitis management is a lifelong, treat-to-target endeavor: induce remission, maintain it with a steroid-sparing agent matched to disease extent and risk, monitor with calprotectin and surveillance colonoscopy, vaccinate and screen for cancers/EIMs/PSC, escalate promptly when targets are missed, and never substitute steroids for true maintenance.

Board pearl: The unifying Step 3 thread is outpatient longitudinal stewardship — every UC patient needs a maintenance regimen, a calprotectin trend, a surveillance schedule, an updated vaccine record, and a written escalation plan; the wrong answers on the exam are almost always "another prednisone taper," "live vaccine on biologic," or "wait 8 years to scope a UC-PSC patient."

Maintenance choice by stratification: mild proctitis → topical mesalamine; mild-moderate left-sided/extensive → oral ± topical 5-ASA ≥2.4 g/day; steroid-dependent or moderate-severe → thiopurine, anti-TNF, vedolizumab, ustekinumab, JAK inhibitor, or ozanimod — vedolizumab preferred in elderly; combine infliximab with thiopurine in selected high-risk patients

Treat-to-target (STRIDE-II): symptomatic remission → biomarker remission (CRP, calprotectin <150–250) → endoscopic healing (Mayo 0–1); reassess at 3 months and intensify if missed; clinical remission alone is insufficient

Surveillance and prevention: dysplasia colonoscopy starting 8 years from symptom onset (or immediately with PSC, then annually), high-definition chromoendoscopy preferred; annual flu, pneumococcal, recombinant zoster, HBV, HPV, derm exam on immunosuppression; bone health, depression screening, smoking cessation, NSAID avoidance; stool C. difficile at every flare; treat-to-target with calprotectin; VTE prophylaxis when hospitalized regardless of bleeding; never discharge on steroids without a steroid-sparing plan in place

Acute severe UC: Truelove–Witts criteria → admit, IV methylprednisolone, LMWH, sigmoidoscopy, surgical consult on day 1, day-3 decision point for medical rescue (infliximab/cyclosporine) versus colectomy — failing to assess at day 3 is the graded error