Inflammatory Bowel Disease: Crohn Complete

0:00Welcome to Board Pearls. This is episode two of three of the Inflammatory Bowel Disease chapter, in the Colorectal and Pelvic Floor Disorders module. This episode is Crohn's disease from phenotype through full medical management: the Montreal classification driving risk stratification and the top-down versus step-up choice, Crohn-specific therapy, biologic positioning, and the phenotype-specific algorithms for perianal disease, strictures, and post-operative recurrence.

0:26Crohn's is one disease with many faces, and the face the patient shows you at diagnosis decides most of the therapy. The reason for the heterogeneity is simple: the same transmural immune process can settle in different parts of the gut and progress in different directions, giving one patient a tight ileal stricture, another diffuse colitis, and a third complex perianal fistulas. The phenotype declares itself early and tends to drift toward complications over years, and that drift is why we phenotype at diagnosis, because we're deciding whether to start strong to prevent the drift or start light and escalate only if needed.

1:02The Montreal classification organizes the phenotype in three parts: age at diagnosis, location, and behavior. Age splits at under seventeen, seventeen to forty, and over forty, and younger age is itself a risk marker because the patient accumulates more disease-years and tends toward extensive involvement. Location splits into terminal ileum, colon only, ileocolonic, and upper GI, with upper GI added as a modifier when present. Most patients have terminal-ileum involvement, which is why ileocolonoscopy with terminal-ileum intubation is the diagnostic anchor, and it's also why a high-first-pass steroid that releases in the ileum becomes the natural induction choice for mild-to-moderate disease there. Behavior splits into inflammatory, stricturing, and penetrating, meaning fistulizing or with abscess, with a lowercase-p modifier appended whenever perianal disease coexists. The natural history is the part to keep in front of you: most patients begin inflammatory, but within a decade or two roughly half transition to stricturing or penetrating, and that transition is mechanical, transmural inflammation either fibrosing into a stricture or perforating into a fistula, so the whole point of modern therapy is to prevent it by achieving and sustaining mucosal healing before the wall remodels.

2:23Risk stratification translates the phenotype into the top-down versus step-up decision. The features that predict an aggressive course and push toward early biologic therapy are young age at diagnosis, especially under thirty and most of all under seventeen, deep ulcers on endoscopy, and perianal disease, with smoking, a steroid requirement at presentation, extensive small-bowel involvement, stricturing or penetrating behavior already declared, and prior resection adding to it. So the favored vignette stacks several: a young patient with terminal-ileal Crohn's, deep ulcers, a perianal fistula, a steroid requirement at presentation, and a smoking history is not someone you step up, you start with biologic therapy and consider adding an immunomodulator on top, because combination therapy beats either agent alone in biologic-naive moderate-to-severe Crohn's, and the difference is large enough that combination is the right answer when there's no specific reason to avoid the thiopurine. Low-risk patients sit at the other end, older age, limited ileal disease, inflammatory behavior, no perianal involvement, non-smoker, normal CRP, and mild endoscopic findings, and they can reasonably begin with budesonide and step up only on recurrence. And the classification isn't static: a patient who declares a stricture or fistula at any point moves into the high-risk group, so phenotype drives therapy at every visit, not just at diagnosis.

3:54A note on activity indices: the symptom-based indices quantify how the patient feels, with defined cutoffs for remission through severe disease, but they correlate poorly with what's actually happening in the mucosa, because a patient can be symptomatic with a near-normal mucosa or symptom-quiet with deep ulcers. That mismatch is why the modern treat-to-target framework is built on objective markers, endoscopic mucosal healing, fecal calprotectin, and MR enterography, rather than symptoms alone.

4:23Now the medical therapy. The severity escalation looks like UC, but the drug selection differs, because Crohn's inflammation is transmural, the location is heterogeneous, and mesalamine does most of its work on the colonic surface rather than the small bowel. The starting question is mechanical: is the disease amenable to a local high-first-pass steroid, meaning is it ileal or right-colonic where budesonide releases? If yes, budesonide; if no, systemic steroids for induction. Budesonide at nine milligrams daily is the favored induction steroid for mild-to-moderate ileal or right-colonic disease, and the reason it's the answer over prednisone is that it undergoes extensive first-pass hepatic metabolism, so systemic exposure is low while mucosal exposure in the terminal ileum and right colon is high, sparing the bone, metabolism, and mood. It outperforms mesalamine and matches prednisolone for induction in ileocecal disease, but it doesn't work for left-sided colonic disease because the capsule doesn't deliver distally, and it's not effective as maintenance beyond about six months, so the temptation to keep someone on a low budesonide dose because they feel well is the trap. Systemic prednisone at forty to sixty milligrams daily is induction for extensive or severe disease, tapered over six to eight weeks, and the teaching isn't the dose, it's the tipping point: steroid dependence, meaning you can't taper below ten milligrams without a flare, and steroid refractoriness both mandate escalation, because long-term steroid exposure carries infection, mortality, and bone risk, and the maintenance role belongs to an immunomodulator or biologic, not a continued steroid. Mesalamine has limited efficacy in Crohn's, with a small benefit for sulfasalazine in mild colonic disease through its sulfa moiety and even less for mesalamine, and no meaningful effect on small-bowel disease, so it shouldn't be the answer for induction or maintenance in a Crohn's vignette except when a question specifically tests whether it has any role at all in mild colonic disease.

6:24Immunomodulators are the maintenance agents when a biologic isn't chosen and the add-on when one is. The thiopurines, azathioprine and 6-mercaptopurine, act through purine-analog metabolites that inhibit proliferating lymphocytes, with slow onset over a couple of months, which is why they're for maintenance after another agent induces remission, not for induction. The screening before starting is non-negotiable: TPMT genotype or activity testing, because low activity leads to cytotoxic metabolite accumulation and severe myelosuppression, with absent activity a contraindication and intermediate activity warranting half-dose, plus NUDT15 testing in Asian, Hispanic, and Native American populations because those variants also predict toxicity and aren't caught by TPMT. The allopurinol interaction is worth knowing: allopurinol shifts thiopurine metabolism toward the active pool and away from the hepatotoxic one, so a low-dose thiopurine plus allopurinol can convert a non-responder into a responder, though it requires expertise. The adverse-effect profile is the high-yield trap: myelosuppression, hepatotoxicity, early idiosyncratic pancreatitis requiring permanent discontinuation, infection, non-melanoma skin cancer needing sun protection, and a modest increase in lymphoma, with the signal to memorize being hepatosplenic T-cell lymphoma, rare and devastating, clustering in young men on combination thiopurine plus anti-TNF, which the boards use both to drive you toward methotrexate as the anti-TNF partner in young men and to test whether you can hold that rare risk against the much larger risk of undertreated Crohn's, with routine blood-count and liver monitoring mandatory. Methotrexate, given by injection weekly with a lower maintenance dose and folic acid to mitigate the cytopenias and stomatitis, is an effective induction and maintenance immunomodulator when thiopurines fail or are contraindicated, with two things to keep in mind: it's teratogenic and absolutely contraindicated in pregnancy or with conception planned within several months, and oral absorption is unreliable in inflamed bowel so the answer is subcutaneous or intramuscular, and its practical advantage is the patient with concurrent peripheral arthritis, which it treats at the same time while pairing cleanly with anti-TNF in young men.

8:36Now the biologics, organized by mechanism, with anti-TNF the broadly effective foundation and the newer agents matching or exceeding it in selected scenarios with differentiated safety. Infliximab is intravenous at five milligrams per kilogram at weeks zero, two, and six then every eight weeks, escalated to ten per kilogram or shortened intervals for inadequate response; adalimumab is subcutaneous with a loading sequence then every two weeks; certolizumab is subcutaneous and Crohn-only because the UC trials missed endpoint, while golimumab is the opposite, UC-only, the indications following the trial data rather than a deeper biological reason. The screening before any anti-TNF is tested reliably: latent tuberculosis with an interferon-gamma release assay or skin test plus chest film, a positive screen mandating treatment before starting, and hepatitis B screening, with chronic carriers needing concurrent antiviral therapy, while hepatitis C is screened but doesn't contraindicate. The class risks beyond viral reactivation are serious bacterial infection, invasive fungal infection in endemic areas, drug-induced lupus, demyelinating disease making it wrong in multiple sclerosis, worsening heart failure making it wrong in advanced heart failure, and the lymphoma signal, with biosimilars clinically equivalent.

9:53Vedolizumab is the gut-selective anti-integrin, targeting the integrin that traffics lymphocytes specifically to gut mucosa, so systemic immunosuppression is minimal and safety sits near placebo, dosed intravenously at weeks zero, two, and six then every eight weeks with a subcutaneous maintenance option, and the price for that clean profile is slower onset, often six to ten weeks, which is why it's not the first choice for acute severe disease. It's effective in both diseases, with the small-bowel signal possibly weaker in Crohn's, and it outperformed adalimumab in moderate-to-severe UC in the head-to-head trial, and it doesn't carry the brain-infection risk of the broader integrin blocker because its target is gut-selective, with the trade-off that it has minimal effect on extraintestinal manifestations, so a patient with prominent skin, joint, or eye involvement may need a more systemic agent. Ustekinumab targets the shared subunit of IL-12 and IL-23 and is approved for both diseases, weight-based intravenous induction then ninety milligrams subcutaneously every eight weeks, effective in anti-TNF failures with low immunogenicity and no boxed warning. Risankizumab and mirikizumab are the more selective IL-23 inhibitors now carrying both UC and Crohn indications, with intravenous induction and subcutaneous maintenance, the advantage of selective blockade being preservation of IL-12 signaling and possibly a better infection profile, and the shared IL-23 pathway being why they work across both diseases.

11:25The JAK inhibitors are the oral small molecules: tofacitinib, a pan-JAK inhibitor for UC, induction ten milligrams twice daily then maintenance five, and upadacitinib, JAK1-selective and approved for both, induction forty-five milligrams daily then maintenance fifteen or thirty. The class carries a boxed warning from rheumatoid-arthritis data, serious infection with a striking herpes zoster signal, major cardiovascular events, malignancy, thrombosis, and mortality, so the recombinant zoster vaccine is recommended before starting in older adults and ideally before any IBD biologic in that group, with lipid and blood-count monitoring, and the trade-off the class buys is rapid onset within days to weeks, oral dosing, and effectiveness in anti-TNF failures. Choosing among them: efficacy data put anti-TNF and upadacitinib near the top in UC and ustekinumab and adalimumab with parallel data in Crohn's, then safety filters narrow it, avoiding anti-TNF in heart failure or demyelinating disease, avoiding JAK inhibitors with clot risk or in older cardiac patients, and avoiding the sphingosine-1-phosphate modulators with conduction abnormalities, with pregnancy data most reassuring for anti-TNF, vedolizumab, and ustekinumab. So the favored selection vignettes pair vedolizumab to the patient with infection or malignancy concerns, a JAK inhibitor to the anti-TNF failure who wants oral therapy with no clot risk, and ustekinumab or risankizumab to the Crohn's patient after anti-TNF failure.

13:00But Crohn's management doesn't reduce to picking the right biologic, and the rest of the episode proves it, because phenotype-specific algorithms drive perianal disease, strictures, and the post-operative state, and you switch into the matching algorithm the moment the phenotype is recognized.

13:15Perianal Crohn's is the multidisciplinary scenario tested most directly, transmural inflammation extending into the perianal tissues to produce fistulas, abscesses, fissures, and eventually incontinence, clustering in patients with colonic and rectal involvement. The diagnostic anchor is pelvic MRI, which defines the tract anatomy, distinguishes simple from complex, and identifies abscesses and the relationship to the sphincters better than ultrasound in branching disease, and examination under anesthesia by a colorectal surgeon defines the anatomy from inside, drains any abscess, and places setons, the non-absorbable sutures that sit through the tract for controlled drainage to prevent abscess re-formation. The sequence is the high-yield, non-negotiable teaching: drain the abscess, place setons, then start medical therapy, because starting a biologic on top of an undrained abscess is how the patient becomes septic. So in a patient with perianal pain, fever, and an unexamined collection on imaging, dose-optimized infliximab is the wrong first move, and the operating room is the right one. Medical therapy pairs antibiotics with anti-TNF: metronidazole with or without ciprofloxacin for several weeks to reduce the bacterial load in drained tracts, and infliximab as the biologic of choice because the fistula-healing evidence is strongest for it, typically dose-optimized, with combination anti-TNF plus an immunomodulator improving outcomes, and local mesenchymal stem cell injection for refractory complex fistulas. Setons come out once medical therapy has reduced the inflammation, and refractory severe disease may need fecal diversion or rarely proctectomy.

14:53Stricturing Crohn's has its own algorithm, and the principle is to preserve bowel length, because repeated resections add up to short bowel syndrome. The stricturoplasty techniques are a longitudinal incision closed transversely for shorter strictures, a side-to-side anastomosis for longer ones, and an isoperistaltic technique for very long strictures, all contraindicated by active inflammation at the stricture, abscess, dysplasia, or a colonic location where resection is preferred. Endoscopic balloon dilation is an alternative for short accessible strictures without active inflammation, fistula, or dysplasia, with a reasonable initial response but frequent recurrence within a year, and the point of judgment is that active inflammation around a stricture should be treated medically before any mechanical intervention, because a mixed inflammatory-fibrotic stricture may resolve with medical therapy alone.

15:43Post-operative recurrence is the third phenotype and the most underappreciated, because without preventive therapy the disease comes back as a rule: endoscopic lesions at the neoterminal ileum are near-universal within a year, with clinical symptoms and then repeat surgery climbing over the following years. Risk stratification at surgery determines prevention: high-risk features are smoking, young age, fistulizing or penetrating behavior, two or more prior resections, perianal disease, and a short interval since the last surgery, and those patients should start prophylactic anti-TNF within four weeks of surgery, while low-risk patients, older, first surgery for short fibrostenotic disease, non-smoker, long disease duration, can be observed and assessed by colonoscopy at six to twelve months. The Rutgeerts score grades the neoterminal ileum at that scope, from no lesions, through a few aphthous lesions, to more numerous lesions or lesions at the anastomosis, to diffuse ileitis, to diffuse inflammation with larger ulcers or stricturing, and the clinical threshold that predicts recurrence and triggers escalation is the middle grade or higher. That scope at six to twelve months is universal regardless of risk, because the Rutgeerts grade drives the next decision more reliably than any clinical signal. And smoking cessation deserves its own sentence: it's the single modifiable factor that meaningfully reduces recurrence, so when a vignette asks what one intervention reduces recurrence in a smoker undergoing ileocolectomy, smoking cessation is the answer, with anti-TNF within four weeks the most effective drug prophylaxis and thiopurines or metronidazole the alternatives.

17:20Pregnancy in Crohn's deserves brief placement: the dominant threat to outcomes is active disease, not active medication, so most IBD drugs continue through pregnancy, the exceptions being methotrexate, absolutely contraindicated, and the JAK inhibitors, avoided. Sulfasalazine continues with folic acid, thiopurines continue when needed, and the anti-TNF agents other than certolizumab cross the placenta in the third trimester, while certolizumab crosses less and is sometimes preferred in late pregnancy, with infant live vaccines deferred until the baby clears the transferred biologic.

17:54So the coherent Crohn's map: phenotype the patient with the Montreal classification at diagnosis, read the risk features off the phenotype and history, decide top-down or step-up, match the drug to location and severity for induction, escalate steroid-dependent or refractory disease to a maintenance immunomodulator or biologic, and pick the biologic by mechanism, screening, safety, and the patient's filters. Then switch into the phenotype-specific algorithm whenever perianal disease, a stricture, or a recent resection is in front of you, and the unifying decision the phenotyping enables is whether to prevent the next complication or wait for it.

18:31Episode three turns to the long-term complications and the maintenance work over decades: pouchitis and cuffitis and the Crohn's-like pouch after restorative surgery, dysplasia surveillance with chromoendoscopy, the extraintestinal manifestations, nutrition, and vaccines, and keeping biologic therapy running through pregnancy.

18:51For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode two of three of chapter fourteen, and I'll see you in the next one.