Gastrointestinal

Crohn disease: medical management and complications

Clinical Overview and When to Suspect Crohn Disease

— Chronic (>4–6 weeks) abdominal pain (often RLQ), non-bloody or intermittently bloody diarrhea, weight loss, low-grade fevers, fatigue

— Perianal disease: fistula, abscess, skin tags, fissures — sometimes the presenting feature

— Unexplained iron-deficiency anemia, growth failure in adolescents, recurrent oral aphthous ulcers

— Extraintestinal: episcleritis/uveitis, erythema nodosum, pyoderma gangrenosum, large-joint arthritis, primary sclerosing cholangitis (less than UC)

Board pearl: A young smoker with RLQ pain, chronic diarrhea, weight loss, and a perianal fistula has Crohn disease until proven otherwise — and smoking cessation is itself a disease-modifying intervention you must document at every visit.

Step 3 management: In the ambulatory clinic, the first move when CD is suspected is parallel workup — stool studies to exclude infection, inflammatory markers, iron studies, and GI referral for ileocolonoscopy with biopsy — not empiric steroids.

Crohn disease (CD) is a chronic, transmural, granulomatous inflammatory bowel disease that can affect any segment of the GI tract from mouth to anus, with skip lesions and a predilection for the terminal ileum and right colon (~50% ileocolonic).

Bimodal onset: peak 15–35 years, second smaller peak in 50s–70s. Risk factors: family history (strongest single risk), tobacco use (worsens CD, opposite of UC), Ashkenazi Jewish ancestry, NSAID use, recent enteric infection, and high-income/urban environment.

When to suspect in clinic:

Phenotypes per Montreal classification: age (A1–A3), location (L1 ileal, L2 colonic, L3 ileocolonic, L4 upper GI), behavior (B1 inflammatory, B2 stricturing, B3 penetrating/fistulizing) ± perianal modifier (p).

Natural history: most patients begin as inflammatory (B1) and progress to stricturing or penetrating disease within 10–20 years if undertreated — the rationale for early effective ("top-down") therapy in high-risk patients.

Presentation Patterns and Key History

— Stool frequency, nocturnal stools, blood, urgency (drives activity scoring)

— Weight trajectory, fevers, fatigue

— Tobacco, NSAID, and antibiotic use

— Travel, sick contacts, recent C. difficile exposure (flare mimic)

— Sexual/menstrual history (pregnancy planning, perianal involvement)

— Vaccination status (pre-biologic) and TB/HBV exposure

— Family history of IBD or colorectal cancer

— Functional impact: work, school, quality of life — needed for biologic prior auth

Key distinction: UC = bloody diarrhea, continuous from rectum, mucosal only, non-smoker disease. CD = variable bleeding, skip lesions, transmural, smoking worsens it. Mixing these up is a classic distractor on Step 3.

Ileal/ileocolonic (most common): cramping RLQ pain, postprandial worsening, watery diarrhea, weight loss, B12 deficiency, bile-salt diarrhea. May mimic appendicitis on first presentation.

Colonic CD: bloody diarrhea, urgency, tenesmus — overlaps with UC; perianal disease and rectal sparing favor CD.

Upper GI / gastroduodenal: epigastric pain, nausea, early satiety, dysphagia; can mimic peptic ulcer disease refractory to PPI.

Perianal disease: painful defecation, drainage, recurrent abscesses — present in up to one-third of patients, sometimes years before luminal disease.

Stricturing (B2): postprandial cramping, bloating, vomiting, obstructive symptoms, weight loss without prominent diarrhea.

Penetrating (B3): enteroenteric fistula (often silent), enterovesical (pneumaturia, recurrent polymicrobial UTI), enterocutaneous, enterovaginal, intra-abdominal abscess (fever, mass).

Key history elements to elicit on every Step 3 visit:

Red flags that change the plan today: high fevers, peritoneal signs, obstipation, hematochezia with hemodynamic change, dehydration, new fistula drainage with sepsis features.

Physical Exam Findings and Severity Assessment

— Eyes: episcleritis (injected, non-painful) vs uveitis (painful, photophobic — urgent ophthalmology)

— Skin: erythema nodosum on shins (tracks disease activity), pyoderma gangrenosum (does not), Sweet syndrome

— Joints: peripheral type 1 (pauciarticular, large joint, parallels gut activity) vs type 2 (polyarticular, independent), axial/sacroiliitis

— Oral: aphthous ulcers, angular cheilitis (iron/B12 deficiency)

— Hepatobiliary: jaundice or RUQ tenderness — consider PSC, gallstones (terminal ileal disease)

— Mild: ambulatory, tolerating PO, <10% weight loss, no obstruction/abscess, CRP normal–mildly elevated

— Moderate: failed mild therapy or with fever, significant weight loss, anemia, tender abdomen

— Severe/fulminant: cachexia, high fever, obstruction, abscess, peritonitis, intractable symptoms

CCS pearl: On a CCS case of suspected CD flare, order vitals, orthostatics, abdominal exam, and perianal exam before pulling the trigger on imaging — the exam dictates whether you advance the clock or call surgery first.

General: cachexia, pallor, tachycardia, orthostasis in active flare; document BMI and weight change — both feed into nutrition referral and drug dosing.

Vitals as activity surrogates: HR >90, T >37.8°C, or orthostatic changes suggest moderate–severe flare and shift you from outpatient titration toward admission.

Abdomen: RLQ tenderness, palpable inflammatory mass (phlegmon) in ileocecal disease, distension and high-pitched bowel sounds with stricture/obstruction, peritoneal signs suggest perforation or abscess.

Perianal exam (do not skip): inspect for skin tags ("elephant ears"), fissures (often lateral, multiple — atypical for benign fissure), fistula openings, induration, fluctuance. Digital exam if tolerated; defer if exquisitely tender — suggests abscess needing imaging.

Extraintestinal exam:

Nutritional: glossitis, cheilosis, koilonychia, peripheral neuropathy (B12), bone tenderness (vitamin D, steroid effect).

Severity grading (combined clinical + biomarker):

Diagnostic Workup — Initial Labs, Stool, and Imaging

— CBC: microcytic anemia (iron deficiency, chronic blood loss), macrocytic (B12/folate), thrombocytosis as inflammation marker

— CMP: albumin (nutrition + activity), LFTs (PSC, drug effect, fatty liver), electrolytes (diarrheal losses)

— CRP and ESR: track activity; CRP correlates better with mucosal inflammation but ~20% of active CD has normal CRP

— Iron studies, B12, folate, vitamin D, magnesium, zinc — deficiency is the rule in ileal CD

— TSH if diarrhea workup

— Pre-therapy: HBV (sAg, sAb, cAb), HCV, HIV, TB (IGRA or PPD), VZV titer, MMR, HPV in women, latent strongyloides if endemic exposure — required before biologics/immunomodulators

— C. difficile PCR/toxin — superinfection is the most overlooked cause of "flare"

— Enteric pathogens (Salmonella, Shigella, Campylobacter, Yersinia, E. coli O157, Giardia)

— Fecal calprotectin: highly sensitive for mucosal inflammation; useful to distinguish IBS from active IBD and to monitor response (<150 µg/g = remission in many algorithms)

— Lactoferrin as alternative

— CT enterography (CTE) in acute setting — detects inflammation, stricture, abscess, fistula; preferred when urgency or obstruction

— MR enterography (MRE) preferred for young patients, pregnancy, and serial monitoring — no radiation, superior soft-tissue and perianal detail

— Pelvic MRI is the gold standard for perianal fistula mapping before surgery

— CT abdomen/pelvis with IV contrast if suspected abscess or free air

— Upright CXR / abdominal series if obstruction or perforation suspected

Board pearl: Before starting any biologic or thiopurine, you must screen for latent TB, HBV, and update inactivated vaccines, and ideally give live vaccines (MMR, VZV, zoster) ≥4 weeks before initiation — a frequent Step 3 patient-safety stem.

Initial labs:

Stool studies (mandatory on every flare presentation):

Imaging:

Diagnostic Workup — Endoscopy, Histology, and Confirmatory Studies

— Findings: aphthous ulcers, linear/serpiginous ulcers, cobblestoning, skip lesions, rectal sparing, terminal ileal involvement, strictures

— Biopsy from both diseased and normal-appearing mucosa; histology shows transmural inflammation, focal crypt distortion, and non-caseating granulomas (~25–30% of biopsies, pathognomonic when present)

— CD: skip lesions, rectal sparing, ileal involvement, granulomas, perianal disease, fistula, transmural

— UC: continuous from rectum, mucosal/submucosal only, crypt abscesses without granulomas

— Indeterminate colitis in ~10% — repeat assessment over time

Key distinction: Non-caseating granulomas confirm CD if present, but their absence does not exclude it — diagnosis is clinical/endoscopic/histologic/radiologic synthesis, not a single biopsy finding.

Ileocolonoscopy with intubation of the terminal ileum and segmental biopsies is the diagnostic gold standard.

Upper endoscopy (EGD) when upper GI symptoms, unexplained iron deficiency, or pediatric presentation.

Video capsule endoscopy (VCE) for suspected small-bowel CD when ileocolonoscopy and cross-sectional imaging are nondiagnostic — must exclude stricture first (patency capsule or MRE) to avoid capsule retention.

Balloon-assisted enteroscopy for biopsy or dilation of deep small-bowel lesions.

EUA (exam under anesthesia) with pelvic MRI for complex perianal disease — combined approach improves outcomes.

Serologies (ASCA, anti-OmpC, anti-CBir1, pANCA): adjunctive, not diagnostic. ASCA+/pANCA– pattern favors CD over UC but should not drive therapy.

Differentiating CD from UC at colonoscopy when colitis only:

Activity scoring: CDAI (clinical research), Harvey-Bradshaw Index (clinic-friendly), SES-CD (endoscopic). Target: clinical + biochemical + endoscopic ("deep") remission per STRIDE-II — calprotectin normalization and mucosal healing predict durable remission and reduce surgery.

Risk Stratification and Treatment Strategy Logic

— Age <30 at diagnosis

— Extensive small-bowel involvement

— Deep ulcers on endoscopy

— Perianal/penetrating disease

— Stricturing behavior

— Prior bowel resection

— Steroid requirement at diagnosis

— Active smoker

— Significant weight loss or hypoalbuminemia

— Short term: symptomatic response within 2–4 weeks, steroid-free clinical remission by 3 months

— Intermediate: normalization of CRP and fecal calprotectin

— Long term: endoscopic healing, restoration of quality of life, normal growth (peds), prevention of disability/surgery

Step 3 management: A 24-year-old smoker with newly diagnosed ileocolonic CD, deep ulcers, perianal tag, and CRP 45 → initiate anti-TNF (± immunomodulator) as first-line maintenance, not azathioprine monotherapy or repeated steroid courses.

Step 3 expects you to stratify by risk of disabling disease at diagnosis and choose therapy accordingly — not reflexively use a step-up ladder.

High-risk features (favor early biologic / "top-down"):

Low-risk: limited ileocolonic inflammatory disease, mild symptoms, no perianal involvement, older age — reasonable to start with budesonide ± conventional step-up.

Treatment goals (STRIDE-II):

Treat-to-target with objective reassessment every 3–6 months; do not rely on symptoms alone — they correlate poorly with mucosal inflammation.

Induction vs maintenance: corticosteroids and exclusive enteral nutrition induce but never maintain. Biologics, immunomodulators, and small molecules do both.

5-ASAs (mesalamine): minimal benefit in CD despite their UC role — do not use as maintenance monotherapy in CD on the exam.

Smoking cessation: counseled at every visit; reduces flares, postoperative recurrence, and biologic failure. Document in the chart — Step 3 loves this.

Pharmacotherapy — Induction and Maintenance Regimens

— Budesonide 9 mg daily (controlled ileal release) for mild–moderate ileal/right-colonic CD — first-pass metabolism limits systemic effects

— Prednisone 40–60 mg daily for moderate–severe or non-ileal disease; taper over 8–12 weeks

— IV methylprednisolone for severe flares inpatient

— Never use as maintenance; bridge to a steroid-sparing agent. Co-prescribe calcium + vitamin D, assess bone density if prolonged courses.

— Azathioprine 2–2.5 mg/kg/day or 6-MP 1–1.5 mg/kg/day — check TPMT or NUDT15 genotype/activity before starting; monitor CBC and LFTs at 2, 4, 8, 12 weeks then quarterly

— Methotrexate 25 mg SQ weekly induction, 15 mg weekly maintenance — alternative when thiopurines contraindicated; add folate; contraindicated in pregnancy

— Anti-TNF: infliximab (IV, dose by weight, often combined with thiopurine for synergy and lower immunogenicity), adalimumab (SC), certolizumab — best evidence for fistulizing disease

— Anti-integrin: vedolizumab (gut-selective, favorable safety, slower onset)

— Anti-IL-12/23: ustekinumab — good for anti-TNF failures, strong safety

— Anti-IL-23: risankizumab, mirikizumab — newer, effective in moderate–severe CD

— Upadacitinib (JAK1 inhibitor) — oral, effective in moderate–severe CD; check lipids, screen for MACE/VTE risk, herpes zoster vaccination

Board pearl: Combination infliximab + azathioprine outperforms either alone for induction/maintenance in moderate–severe CD (SONIC trial logic) — but balance against the rare risk of hepatosplenic T-cell lymphoma in young males.

Corticosteroids (induction only):

Immunomodulators:

Biologics:

Small molecules:

Antibiotics: ciprofloxacin + metronidazole for perianal disease and abscess adjunct, not as primary CD therapy.

Pre-biologic checklist (Step 3 favorite): TB screen, HBV serologies, HIV, varicella/zoster status, age-appropriate cancer screening, update inactivated vaccines (influenza, pneumococcal PCV20, Tdap, HPV, recombinant zoster ≥19, COVID); live vaccines before starting.

Procedures, Surgery, and Disease-Specific Interventions

— Medically refractory disease

— Fibrostenotic stricture with obstruction (not inflammatory — inflammatory strictures may respond to biologics)

— Abscess (drain percutaneously first, then optimize medically, then resect if needed)

— Enterocutaneous, enterovesical, or symptomatic enteroenteric fistula

— Perforation, massive hemorrhage

— Dysplasia/cancer

— Growth failure in children

— Ileocecal resection — most common; laparoscopic preferred; resect minimal necessary length to preserve bowel

— Stricturoplasty for short, multiple small-bowel strictures — bowel-sparing

— Endoscopic balloon dilation for short (<4 cm), accessible anastomotic or primary strictures without ulceration

— Seton placement for complex perianal fistulas — drains sepsis while biologics work; definitive repair (LIFT, advancement flap) after disease control

— Percutaneous drainage of intra-abdominal abscess >3 cm, then antibiotics, then planned resection

— Risk factors: smoking, penetrating phenotype, prior resection, young age, short disease duration before surgery

— High-risk patients: start anti-TNF or other biologic within 4 weeks of surgery

— All patients: colonoscopy at 6–12 months post-op; intensify therapy for Rutgeerts score ≥i2

CCS pearl: A CD patient with fever, RLQ mass, and CT showing a 5-cm abscess — the order set is IV antibiotics + IR-guided drainage + hold biologics/steroids for sepsis, with surgical consultation; do not take them straight to laparotomy or escalate immunosuppression during active infection.

Approximately 50% of CD patients require surgery within 10 years; surgery is not curative — recurrence rates 30–50% at the anastomosis within 1 year endoscopically.

Indications for surgery:

Procedures:

Postoperative recurrence prevention:

Nutrition optimization before elective surgery: correct albumin, anemia, vitamin D; wean steroids if possible — high steroid dose at surgery increases leak and infection risk.

Special Populations — Elderly, Renal, and Hepatic Considerations

— More colonic, inflammatory (B1) phenotype; less penetrating disease

— Higher infection, malignancy, and steroid complication risk (osteoporosis, hyperglycemia, delirium, cataracts)

— Polypharmacy and NSAID use are common flare triggers — review meds explicitly

— Prefer vedolizumab or ustekinumab over anti-TNF when safety dominates (lower serious infection rate)

— Avoid thiopurines if possible: increased lymphoma and non-melanoma skin cancer risk in older adults

— Age-appropriate cancer screening must be current; screen for HBV, TB, latent infections more carefully

— 5-ASAs: nephrotoxicity (interstitial nephritis) — monitor creatinine annually; not a primary CD agent anyway

— Methotrexate: renally cleared — avoid if CrCl <30, dose-reduce if 30–60

— Biologics (monoclonal antibodies): no renal dose adjustment

— Hydration during flares — diarrhea + dehydration can precipitate AKI; cautious NSAID avoidance

— Thiopurines: monitor for hepatotoxicity (cholestatic, hepatocellular, nodular regenerative hyperplasia) — check LFTs serially; obtain 6-TGN/6-MMP metabolites if poor response or toxicity

— Methotrexate: cumulative hepatotoxicity — avoid in chronic liver disease, screen for fatty liver

— HBV reactivation risk with biologics/JAKs — give entecavir or tenofovir prophylaxis in HBsAg+ or isolated anti-HBc+ patients before/throughout therapy

— Concurrent PSC: surveillance colonoscopy annually for dysplasia

Board pearl: In an older Crohn patient needing escalation, vedolizumab is often the safest pick — gut-selective, low systemic immunosuppression, minimal infection signal — a high-yield Step 3 answer for the multimorbid elder.

Elderly-onset CD (>60):

Bone health: DEXA at baseline for any patient on ≥3 months steroids or postmenopausal; supplement calcium 1200 mg + vitamin D 800–1000 IU; bisphosphonate if T-score ≤ −1.5 with steroids.

Cardiovascular: JAK inhibitors (upadacitinib) carry MACE/VTE warnings — avoid in ≥65 with cardiovascular risk factors or smoking history when alternatives exist.

Renal impairment:

Hepatic impairment:

Special Populations — Pregnancy, Pediatrics, and Fertility

— Continue: mesalamine, sulfasalazine (add folate 2 mg/day), thiopurines (azathioprine/6-MP), anti-TNF (infliximab, adalimumab, certolizumab), vedolizumab, ustekinumab — benefits of disease control outweigh risks

— Certolizumab has minimal placental transfer — preferred when starting de novo in pregnancy

— Other anti-TNFs cross placenta in T3 — consider holding last dose in early T3; avoid live vaccines in the infant for the first 6 months if exposed in utero (notably rotavirus)

— Stop: methotrexate (teratogenic) — discontinue ≥3 months before conception in both partners; JAK inhibitors (limited data, avoid); thalidomide

— Corticosteroids: use lowest effective dose; risk of cleft palate (T1), gestational diabetes, hypertension

— Often more extensive and aggressive; growth failure and delayed puberty are unique outcomes

— Exclusive enteral nutrition (EEN) for 6–8 weeks is first-line induction in children — efficacy equal to steroids without growth suppression

— Early anti-TNF for high-risk phenotype improves growth and reduces complications

Step 3 management: Pregnant patient on infliximab in remission — continue the biologic, schedule MFM co-management, plan delivery mode by perianal exam, and defer infant rotavirus and BCG until 6 months.

Preconception counseling is the most important step: active disease at conception is the strongest predictor of poor pregnancy outcome (preterm birth, low birth weight, pregnancy loss). Aim for ≥3 months of remission before conception.

Medication safety in pregnancy:

Mode of delivery: vaginal delivery is fine; active perianal disease or rectovaginal fistula → cesarean to prevent sphincter injury.

Breastfeeding: compatible with biologics, thiopurines, mesalamine; avoid methotrexate and JAKs.

Fertility: CD itself does not impair fertility in remission; sulfasalazine causes reversible male oligospermia (switch to mesalamine if conception planned); pelvic surgery (especially proctectomy/IPAA) may reduce female fertility.

Pediatric CD:

Complications and Adverse Outcomes

— Strictures → small-bowel obstruction (postprandial pain, vomiting, distention); inflammatory strictures may respond to biologics, fibrotic ones require dilation or resection

— Fistulas: enteroenteric, enterocutaneous, enterovesical (recurrent polymicrobial UTI, pneumaturia, fecaluria), enterovaginal, rectovaginal

— Abscess (intra-abdominal, perianal): fever, focal pain, leukocytosis — image and drain

— Perforation (less common than UC, but high mortality)

— Toxic megacolon (rare in CD vs UC) — colonic dilation >6 cm with systemic toxicity

— Massive GI hemorrhage (uncommon)

— Vitamin B12 deficiency with terminal ileal disease/resection — lifelong parenteral B12

— Bile salt malabsorption → choleretic diarrhea (treat with cholestyramine); also predisposes to cholesterol gallstones

— Fat malabsorption → steatorrhea, fat-soluble vitamin (ADEK) deficiency

— Calcium oxalate kidney stones (enteric hyperoxaluria) — unbound oxalate absorbed when calcium binds fat

— Short bowel syndrome after extensive resection

— Iron, folate, zinc, magnesium deficiencies; osteoporosis

— Colorectal cancer: increased risk with long-standing colonic CD (>30% colonic involvement, >8 years duration, PSC) — surveillance colonoscopy every 1–3 years

— Small-bowel adenocarcinoma: rare but elevated risk

— Lymphoma (thiopurine + anti-TNF), non-melanoma skin cancer (thiopurines), melanoma (anti-TNF) — counsel sun protection and annual dermatology

Key distinction: Toxic megacolon is classically UC; small-bowel obstruction is classically CD. Both share VTE risk during flares — anticoagulate hospitalized IBD patients prophylactically regardless of mild hematochezia.

Luminal/structural:

Malabsorption/nutritional:

Malignancy:

Thromboembolism: IBD flare is a prothrombotic state — VTE prophylaxis for all admitted IBD patients, even with rectal bleeding.

Extraintestinal: uveitis (vision-threatening), PSC, AA amyloidosis (rare, late).

Psychosocial: depression, anxiety prevalent — screen at visits.

When to Escalate — ICU, Surgical Consult, and Inpatient Triage

— Severe flare with inability to maintain hydration/nutrition orally

— Tachycardia, fever, orthostasis, significant weight loss in short interval

— Suspected obstruction, abscess, perforation, or massive bleeding

— Failure of outpatient steroid taper after 3–5 days

— New fistula with systemic toxicity

— NPO or clear liquids depending on obstruction risk; IV fluids (LR), correct K/Mg

— VTE prophylaxis (enoxaparin 40 mg SC daily) — yes, even with hematochezia in most cases

— IV methylprednisolone 40–60 mg/day (or hydrocortisone equivalent) for severe flare after infection excluded

— Stool C. difficile, enteric pathogen panel, blood cultures if febrile

— CT abdomen/pelvis with IV contrast to rule out abscess/obstruction before steroid escalation

— Hold NSAIDs, narcotics minimized (mask obstruction, increase ileus); avoid anti-diarrheals if any concern for toxic megacolon

— Nutrition consult; consider enteral nutrition preferentially, TPN only if gut not usable

— Surgical consultation early for any abscess, obstruction, perforation, or refractory disease

— GI consultation for endoscopy and biologic decision

— Hemodynamic instability (sepsis, massive bleeding, perforation)

— Toxic megacolon

— Respiratory compromise from massive distention

CCS pearl: Sequence on a severe CD admission is fluids → labs/cultures → imaging → steroids (only after infection excluded) → surgical consult if no improvement in 3–5 days. Skipping the imaging step before steroids on an abscess patient is the classic CCS penalty move.

Admit for:

Initial CCS inpatient order set:

Indications for ICU:

Rescue therapy in steroid-refractory severe CD: infliximab induction after infection ruled out; if no response in 3–5 days → surgery.

Discharge criteria: afebrile 24 h, tolerating PO, pain controlled, stable hemoglobin, clear maintenance plan, follow-up within 1–2 weeks, biologic/immunomodulator plan documented, vaccinations addressed.

Key Differentials — Other GI Causes

— Continuous inflammation from rectum proximally, mucosal only, bloody diarrhea prominent, no perianal disease, no granulomas, smoking is protective

— Indeterminate colitis when overlap exists

— C. difficile — must rule out at every flare; can also superinfect known IBD

— Salmonella, Shigella, Campylobacter, Yersinia enterocolitica (mimics ileal CD with RLQ pain, "pseudoappendicitis")

— E. coli O157:H7 — bloody diarrhea, HUS risk

— Entamoeba histolytica — travel history, can cause flask-shaped ulcers

— Intestinal tuberculosis — ileocecal, granulomas, but caseating; critical to exclude before anti-TNF in endemic areas

— CMV colitis in immunosuppressed

Key distinction: Intestinal TB vs ileocecal CD — both cause terminal ileal stricturing, RLQ mass, fistula. TB has caseating granulomas, AFB on biopsy/culture, transverse ulcers, fewer/larger granulomas; CD has noncaseating granulomas, longitudinal ulcers. Treat TB before any biologic.

Ulcerative colitis:

Infectious colitis/enteritis:

Ischemic colitis: older, vascular risk factors, watershed areas (splenic flexure), thumbprinting on imaging.

Microscopic colitis (lymphocytic/collagenous): chronic watery non-bloody diarrhea, normal endoscopy, abnormal biopsy; NSAID and PPI association.

Celiac disease: chronic diarrhea, weight loss, iron deficiency — check tTG-IgA with total IgA; can coexist with CD.

Diverticulitis / segmental colitis associated with diverticulosis (SCAD): older, sigmoid predominant.

Appendicitis: acute RLQ pain, hours-to-days, leukocytosis — but recurrent or chronic ileitis-mimicking presentation suggests CD.

Intestinal lymphoma, small-bowel adenocarcinoma, GIST, carcinoid: rare but mimic strictures; biopsy any suspicious lesion.

Behçet disease: ileocecal ulcers + oral/genital ulcers + uveitis — overlap with CD; check for HLA-B51, pathergy.

NSAID enteropathy: small-bowel ulcers and strictures (diaphragm disease) — get a medication history.

Key Differentials — Extraintestinal and Non-GI Mimics

Board pearl: A young woman with cyclic RLQ pain and dyschezia but normal calprotectin and colonoscopy — think endometriosis, not Crohn. Calprotectin is your gatekeeper to avoid invasive workup of functional disorders.

Functional / IBS-D: chronic abdominal pain and altered bowel habits without alarm features (weight loss, nocturnal symptoms, bleeding, anemia, elevated CRP/calprotectin). Fecal calprotectin <50 µg/g essentially excludes active IBD — a critical Step 3 cost-effective screen.

Lactose intolerance / bile-acid diarrhea: postprandial bloating and diarrhea; bile-acid diarrhea responds to cholestyramine and can coexist with ileal CD post-resection.

Endometriosis: cyclic abdominal pain, dyschezia, hematochezia during menses; can mimic CD, especially in young women with RLQ pain. Pelvic exam, MRI, gynecology referral.

Ovarian pathology: cyst, torsion, neoplasm; pregnancy must be excluded.

Urolithiasis: especially calcium oxalate stones in CD itself — colicky flank-to-groin pain, hematuria.

Pelvic inflammatory disease / tubo-ovarian abscess: sexually active young women with fever and pelvic pain.

Mesenteric ischemia: pain out of proportion, vascular risk, lactic acidosis, postprandial pain (chronic mesenteric ischemia).

Vasculitis: IgA vasculitis (Henoch-Schönlein) in children — palpable purpura, arthralgia, abdominal pain, intussusception; polyarteritis nodosa — mesenteric microaneurysms.

Hypothyroidism / hyperthyroidism: weight change and altered bowel habits.

Carcinoid syndrome: flushing, secretory diarrhea, right heart valvular disease; 24-h urine 5-HIAA.

Eosinophilic gastroenteritis: peripheral eosinophilia, allergic history, biopsy with eosinophilic infiltration.

Common variable immunodeficiency / chronic granulomatous disease: recurrent infections + IBD-like phenotype; consider in atypical young patients with low immunoglobulins.

Radiation enteritis: prior pelvic radiation, strictures and fistulas mimic CD.

Secondary Prevention, Discharge, and Long-Term Plan

— Defined steroid taper with end date (e.g., prednisone 40 mg → taper 5 mg/week)

— Steroid-sparing maintenance started or scheduled (biologic/immunomodulator) — never discharge on steroids alone

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

— PPI if on steroids + NSAIDs (avoid NSAIDs ideally)

— VTE prophylaxis consideration if persistent risk

— Bowel regimen, anti-emetics PRN

— Iron repletion (oral or IV based on tolerance and severity)

— B12 IM monthly if ileal disease/resection

— Annual influenza (inactivated), PCV20 or PCV15→PPSV23, Tdap, HPV through age 45, recombinant zoster ≥19 years on immunosuppression, COVID per current guidance, hepatitis B series if non-immune

— Live vaccines (MMR, varicella, yellow fever) contraindicated on biologics, thiopurines, high-dose steroids, JAKs — give before starting or during sustained off-therapy windows

— Colonoscopy 8 years after diagnosis if colonic involvement, then every 1–3 years (annual if PSC)

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

— Cervical cancer screening annually for women on immunosuppression

— Tobacco cessation — disease-modifying; offer pharmacotherapy + behavioral support

— Mediterranean-style diet; specific carbohydrate or low-FODMAP for symptom control

— Mental health screening (PHQ-9/GAD-7); CBT referral for chronic-illness coping

— Reproductive counseling and contraception (oral contraceptive absorption may be reduced with diarrhea/short bowel)

Step 3 management: Every CD discharge order set should include a steroid taper, a maintenance therapy, calcium/vitamin D, vaccination plan, smoking cessation, and a 2-week follow-up appointment — incomplete discharge orders are a frequent point loss on CCS.

Discharge medication checklist after a CD admission:

Vaccinations (verify and update):

Cancer surveillance:

Bone health: DEXA at baseline if ≥3 months steroids, postmenopausal, or low-trauma fracture history; repeat every 1–2 years.

Lifestyle:

Follow-Up, Monitoring, and Counseling

— After flare or new therapy: 2 weeks, 6 weeks, then every 3 months until stable remission

— Stable remission: every 6 months with labs

— Telephone/portal check-ins as needed; consider remote calprotectin monitoring

— Symptom review (Harvey-Bradshaw), weight, BMI

— Adherence and adverse effects

— Tobacco status (every visit, document)

— Mental health (PHQ-9, GAD-7 at least annually)

— Vaccination updates

— Reproductive plans

— Baseline and every 3–6 months: CBC, CMP, CRP, fecal calprotectin

— Thiopurines: CBC and LFTs at weeks 2, 4, 8, 12, then every 3 months; consider 6-TGN/6-MMP levels

— Methotrexate: CBC and LFTs monthly initially, then every 3 months

— Biologics: periodic drug-level and antibody testing if loss of response (therapeutic drug monitoring) — therapeutic trough thresholds vary by agent

— JAK inhibitors: lipids at 8 weeks, CBC, LFTs, CPK; periodic VTE/MACE assessment

— Vitamin B12, D, iron, ferritin annually

— Colonoscopy or MR enterography 6–12 months after initiating new therapy

— Fecal calprotectin every 3–6 months as a non-invasive proxy

— Sick-day rules: increase steroid dose during major infection/surgery (stress-dose if chronic ≥5 mg/day prednisone equivalent >3 weeks)

— Avoid NSAIDs; acetaminophen first-line for pain

— Travel: vaccines well in advance, traveler's diarrhea plan (azithromycin), avoid live vaccines if endemic exposure

— Patient support: Crohn's & Colitis Foundation, peer groups

CCS pearl: When a CD patient reports loss of response to infliximab, order infliximab trough level and anti-drug antibodies before switching — sub-therapeutic without antibodies → dose intensify; antibodies present → switch within or out of class.

Visit cadence:

Each visit covers:

Lab monitoring:

Objective reassessment of mucosal healing:

Counseling points:

Quality measures: documented vaccination, smoking status, bone health, colorectal surveillance, depression screening — common on Step 3 quality/safety stems.

Ethical, Legal, and Patient Safety Considerations

— Discuss serious infection (including reactivation of TB/HBV), malignancy (lymphoma, NMSC, melanoma), infusion/injection reactions, demyelinating disease risk with anti-TNFs in patients with personal/family MS history

— JAK inhibitors: explicit discussion of MACE, VTE, malignancy, and herpes zoster; document shared decision-making, especially in patients ≥50 with cardiovascular risk

— For young men starting combination thiopurine + anti-TNF: counsel on hepatosplenic T-cell lymphoma rare but fatal risk

— Structured transition from pediatric to adult IBD care between ages 18–21

— Address adherence, mental health, substance use, reproductive counseling, insurance continuity

— Failed transition is a leading cause of flare and hospitalization in young adults

Board pearl: A CD patient on infliximab inadvertently scheduled for live yellow fever vaccine before travel — recognize this as a near-miss, cancel the live vaccine, and arrange alternative travel risk mitigation. This is the prototype patient-safety vignette.

Informed consent for biologics/immunosuppressants:

Adolescent transitions of care (high-yield Step 3):

Reproductive counseling and confidentiality: adolescents and young adults — discuss teratogens (methotrexate, JAKs), contraception, and pregnancy planning; respect confidentiality within state law.

Capacity and shared decision-making in severe flare: surgery vs continued medical therapy in steroid-refractory patient — document capacity, alternatives, and risk/benefit; involve surgery and GI together to avoid fragmented consent.

Vaccination safety: live vaccine error in immunosuppressed patient is a sentinel patient-safety event — verify status before starting biologic; communicate with PCP and pharmacy.

Medication reconciliation at every transition: NSAIDs, opioids, antibiotics (C. diff risk), and OCP absorption are common discharge errors.

Disability and workplace accommodation: CD is a recognized disability under the ADA — patients may need bathroom access, flexible scheduling; provide letters.

Health-system equity: prior authorization delays for biologics are a documented harm — appeal with peer-to-peer; document medical necessity. Be alert to step-therapy mandates that conflict with high-risk treat-early evidence.

Mandatory reporting: suspected child neglect when growth failure is unaddressed due to caregiver nonadherence.

High-Yield Associations and Rapid-Fire Facts

Key distinction: Memorize the CD vs UC contrast pair (location, depth, smoking, perianal, granuloma, surgery curative) — at least one comparison question is nearly guaranteed.

Smoking worsens CD; smoking is protective in UC — opposite directionality is a perennial test item.

Terminal ileum disease/resection → B12 deficiency, bile-salt diarrhea, gallstones, oxalate kidney stones.

Non-caseating granulomas = CD; caseating granulomas = TB; crypt abscesses without granulomas = UC.

Perianal fistula = think CD (and image with pelvic MRI, treat with anti-TNF + seton).

String sign on small-bowel imaging = terminal ileal stricture.

Cobblestoning, skip lesions, rectal sparing = CD endoscopic hallmarks.

Pyoderma gangrenosum course independent of bowel disease; erythema nodosum parallels activity.

Episcleritis parallels disease; uveitis does not — uveitis is the urgent ophthalmology referral.

Primary sclerosing cholangitis is more associated with UC than CD but occurs in both; annual colonoscopy required when present.

Anti-TNF + thiopurine combo is most effective for moderate–severe CD but has highest immunosuppression burden.

Vedolizumab = gut-selective α4β7 integrin blocker — safest biologic in elderly/multimorbid.

Ustekinumab = anti-IL-12/23; risankizumab/mirikizumab = anti-IL-23; upadacitinib = JAK1.

Methotrexate is teratogenic; stop ≥3 months before conception in both partners.

Certolizumab has minimal placental transfer — preferred to start in pregnancy.

TPMT/NUDT15 genotyping before thiopurines.

Pre-biologic screen: TB, HBV, HCV, HIV, varicella, age-appropriate vaccines.

Fecal calprotectin <50 essentially excludes active IBD; >250 suggests active inflammation.

Colorectal cancer surveillance: start 8 years after diagnosis (or at PSC diagnosis), every 1–3 years.

Postoperative recurrence: colonoscopy at 6–12 months; Rutgeerts ≥i2 → intensify therapy.

VTE prophylaxis for all hospitalized IBD patients, even with rectal bleeding.

Exclusive enteral nutrition = first-line pediatric induction.

Surgery is not curative in CD — recurrence is the rule.

Board Question Stem Patterns

— Answer: Infliximab + azathioprine (combination therapy for high-risk phenotype); not mesalamine, not steroids alone.

— Answer: Stool C. difficile and enteric pathogens before escalating immunosuppression. Add cross-sectional imaging if pain or mass.

— Answer: Stop methotrexate ≥3 months before conception, switch to pregnancy-compatible agent (e.g., certolizumab or continue azathioprine).

— Answer: Check TB (IGRA), HBV serologies, vaccination status, give inactivated vaccines, defer live vaccines.

— Answer: Pelvic MRI for mapping, EUA with seton placement, anti-TNF therapy. Not immediate fistulotomy (risk of incontinence).

— Answer: Smoking cessation + anti-TNF within 4 weeks, colonoscopy at 6–12 months.

— Answer: Low oxalate diet, increased fluids, calcium with meals to bind oxalate; treat malabsorption.

— Answer: Check trough level and anti-drug antibodies; dose-intensify if low without antibodies, switch if antibodies present.

— Answer: Rule out abscess/CMV/C. diff, then rescue infliximab or surgery.

— Answer: Patient-safety event, monitor for live-vaccine illness, root-cause analysis, system fix.

Step 3 management: Pattern recognition — the question is almost always asking you to either rule out infection first, screen before biologic, or choose treat-early therapy for high-risk phenotype.

Stem 1 — Newly diagnosed CD, choose maintenance: 26-year-old smoker, ileocolonic disease, deep ulcers, perianal tag, CRP 60, hypoalbuminemia. Best maintenance therapy?

Stem 2 — Flare workup before escalation: Known CD on adalimumab presents with worsening diarrhea and fever. Next step?

Stem 3 — Pregnancy counseling: Patient on methotrexate planning pregnancy.

Stem 4 — Pre-biologic safety: About to start infliximab.

Stem 5 — Perianal fistula: Patient with draining perianal fistula and known CD.

Stem 6 — Postoperative recurrence prevention: After ileocecal resection in a smoker.

Stem 7 — Kidney stone: CD patient with calcium oxalate stones.

Stem 8 — Loss of response to infliximab:

Stem 9 — Severe inpatient flare, no improvement on IV steroids day 4:

Stem 10 — Vaccination error: CD patient on infliximab received MMR.

One-Line Recap

Crohn disease is a transmural, skip-lesion, smoking-worsened inflammatory bowel disease where Step 3 success means risk-stratifying early, choosing biologic-based steroid-sparing maintenance for high-risk phenotypes, ruling out infection and abscess before escalating immunosuppression, and building a longitudinal plan that includes vaccinations, surveillance, nutrition, smoking cessation, and reproductive counseling.

Board pearl: If you remember only one principle, remember treat-to-target with objective remission (clinical + calprotectin + endoscopic) using early effective therapy in high-risk patients — that single concept anchors most Step 3 Crohn questions.

Diagnose: ileocolonoscopy + biopsy, MR/CT enterography, fecal calprotectin, infection exclusion (C. diff every flare).

Treat: steroids/budesonide or EEN to induce; biologic ± immunomodulator to maintain — never steroids as maintenance, never mesalamine as CD monotherapy on the exam.

Prevent harm: pre-biologic TB/HBV/vaccination screen, VTE prophylaxis when admitted, DEXA on chronic steroids, smoking cessation at every visit.

Surveil: calprotectin every 3–6 months, mucosal reassessment at 6–12 months, colorectal cancer screening 8 years after colonic diagnosis (annual with PSC), annual skin/cervical exams on immunosuppression.

Operate when indicated: stricture, abscess (drain first), refractory disease, fistula — but surgery is not curative; start anti-TNF within 4 weeks postoperatively in high-risk patients and recolonoscope at 6–12 months.

Special populations: methotrexate and JAKs out in pregnancy; certolizumab preferred new-start in pregnancy; vedolizumab safest in elderly/multimorbid; EEN first-line in pediatric induction.

CCS rhythm: vitals → labs/stool → imaging → infection exclusion → steroids → surgical/GI consult → discharge with maintenance, taper, vaccinations, and 2-week follow-up.