Crohn’s disease is a chronic, relapsing–remitting, transmural inflammatory bowel disease that tends to progress over time from purely inflammatory disease to stricturing or penetrating complications.^[1][2] Disease location is usually stable, but up to half of patients develop a stricture, internal fistula, or perianal complication within 20 years of diagnosis, and contemporary population-based cohorts show that roughly 1 in 5 patients with uncomplicated disease progress and about 1 in 4 require resection within 10 years.^[2][3] Major complications include bowel obstruction from strictures, fistulae, intra-abdominal and perianal abscesses, extraintestinal manifestations, nutritional deficiencies, treatment-related toxicity, and an increased risk of small bowel and colorectal adenocarcinoma.^[1][4] There is no cure. Long-term mortality is modestly higher than in the background population, and patients with Crohn’s colitis need risk-stratified colonoscopic surveillance for colorectal cancer.^[5][6]

• Most patients follow a chronic intermittent course. In North American population-based cohorts, about 13% had continuously active (unremitting) disease and about 10% had prolonged remission.^[7]
• Symptoms and bowel damage are often discordant. Structural damage can accumulate silently despite symptomatic remission.^[1]

• At diagnosis, ileal, colonic, and ileocolonic disease each account for roughly one-third of cases. Location stays stable in most patients, and only about 6–14% extend anatomically.^[2]
• Most patients present with non-stricturing, non-penetrating (inflammatory, Montreal B1) disease. Behavior then progresses to stricturing (B2) or penetrating (B3) disease in up to half of patients within 20 years.^[2]
• Contemporary inception cohorts show lower early progression rates than historical series:
  • In the European Epi-IBD cohort, 14% of patients with B1 disease progressed to stricturing and/or penetrating disease within 5 years, 22% underwent surgery, and 36% were hospitalized.^[8]
  • At 10 years, rates were about 20% for progression to complicated disease, 24% for surgery, and 41% for hospitalization. Outcomes were similar despite earlier use of advanced therapy in Western Europe.^[3]
• In US claims data, more than one-quarter of newly diagnosed patients progressed within 3 years. Intestinal obstruction/stenosis was the most common complication, and much of the risk accrued within the first 6 months, reflecting diagnostic delay or complications present at diagnosis.^[9]

• Surgical rates have fallen over time:
  • In the Copenhagen County cohort (diagnosed 1962–1987), the cumulative probability of surgery was 62% at 10 years and 71% at 20 years, plateauing near 74% by 40–50 years. Over half of operated patients needed two or more operations.^[5]
  • In contemporary cohorts, about 24% undergo resection by 10 years.^[3]
• Stricturing or penetrating disease at diagnosis, progression of disease behavior, and former smoking were associated with intestinal resection in the 10-year Epi-IBD cohort.^[3]

• Patients with these features are considered candidates for early effective (advanced) therapy.^[2] Whether early aggressive therapy durably changes the long-term progressive phenotype remains uncertain. In Epi-IBD, earlier advanced therapy did not translate into different 10-year outcomes.^[3]

• Strictures and obstruction may be inflammatory (potentially reversible) or fibrostenotic (fixed). They present with post-prandial pain, bloating, nausea, and vomiting.^[1]
  • CT enterography or MR enterography help distinguish inflammatory from fibrotic strictures.^[1]
  • Symptomatic small-bowel or anastomotic strictures not amenable to medical therapy or endoscopic dilation are an indication for surgery.^[11]
• Fistulae may be enteroenteric, enterovesical (fecaluria, pneumaturia, recurrent urinary tract infections), enterocutaneous, or rectovaginal.^[1]
• Intra-abdominal abscess and phlegmon arise from penetrating disease.^[11]
  • They may be managed with antibiotics with or without drainage, followed by interval resection or medical therapy.^[11]
  • Corticosteroids should be avoided when a penetrating complication is suspected.^[12]
• Perianal disease ranges from skin tags and fissures to complex fistulizing disease with abscess. Cumulative incidence is roughly 18–20% at 10 years and 20–25% at 20 years in adult cohorts. Pelvic MRI is the reference imaging study.^[13][1]
• Free perforation and severe hemorrhage are uncommon. Impending or actual perforation, or severe acute colitis unresponsive to medical therapy, requires surgery.^[11]
• Short bowel syndrome and intestinal failure can follow repeated resections.
  • The 10-year cumulative incidence of intestinal failure in Denmark fell from 2.7% before 1980 to 0.2% after 2000.^[14]
  • Affected patients had a standardized mortality ratio of 3.66.^[14]

Extraintestinal manifestations (EIMs) occur in up to roughly half of patients. They may precede, parallel, or run independently of luminal activity, and one EIM increases the likelihood of others.^[1][15]

^[1][15]

• Other systemic complications:
  • Venous thromboembolism risk is about 3-fold higher, and higher still with active disease, hospitalization, and surgery.^[2]
  • Metabolic bone disease and osteoporosis are associated with both Crohn’s disease and corticosteroid use.^[10]
  • Cholelithiasis, nephrolithiasis, and aphthous stomatitis also occur.^[2]

• Malnutrition, iron deficiency anemia, and deficiencies of vitamin B12, vitamin D, folate, and zinc are common and worsen outcomes.^[15]
  • B12 deficiency is predictable after terminal ileal resection (classically >20 cm).^[15]
  • Folate deficiency is promoted by sulfasalazine or methotrexate.^[15]
  • Zinc losses rise with high-output stomas or fistulae.^[15]
• In children, growth failure and delayed puberty are disease-specific complications of active Crohn’s disease.^[1]

• Corticosteroids do not maintain remission.^[12]
• Even short courses carry risks of serious infection, accelerated bone loss, hyperglycemia, glaucoma, increased VTE risk, and cardiovascular disease.^[12]
• Roughly 15% of patients become steroid-dependent.^[12]
• Patients should be weaned from glucocorticoids before elective surgery because of the higher risk of postoperative infectious complications.^[11]

• Colorectal cancer (CRC):
  • In meta-analysis, the relative risk was 2.5 overall, 4.5 with colonic disease, and 1.1 with isolated ileal disease.^[4]
  • The cumulative risk was about 2.9% at 10 years, and the relative risk has declined over the past 30 years.^[4]
  • Risk rises with disease extent and duration, persistent inflammation, concomitant PSC, colonic stricture, dense post-inflammatory polyposis, family history of CRC, and young age at diagnosis.^[6][11]
• Small bowel adenocarcinoma:
  • Relative risk is markedly increased (33.2 in meta-analysis), although absolute risk is low.^[4]
  • No routine surveillance strategy exists. A new stricture or abrupt symptom change in long-standing, stable small-bowel disease should raise suspicion.^[6]
• Other cancers: long-term population data also show an increased risk of rectal, anal, respiratory, and skin cancers compared with the background population.^[5]

• Crohn’s disease is a lifelong condition with no cure. The aim of care is to induce and maintain remission and prevent irreversible bowel damage.^[10]
• Mortality: in the Copenhagen County inception cohort followed for up to 56 years, mortality was higher than in the matched background population.^[5] Mortality is substantially higher in the subgroup that develops intestinal failure.^[14]
• Surgery is not curative:
  • Repeat resection is common; most operated patients in long-term cohorts needed more than one operation.^[5]
  • Postoperative medical therapy should be considered to treat residual disease or maintain remission.^[11]
• Secular trends: contemporary cohorts have lower rates of surgery and intestinal failure than historical ones. The relative risk of CRC has also declined, likely reflecting better inflammation control and surveillance.^[3][14][4]
• Modifiable prognostic factors:
  • Smoking cessation improves disease outcomes and may reduce postoperative morbidity.^[10][11]
  • Other levers are sustained control of mucosal inflammation, avoidance of corticosteroid dependence, correction of nutritional deficiencies, attention to bone health, VTE prophylaxis during hospitalization, and adherence to CRC surveillance.^[2][12]

• Ileal and ileocolonic disease progress fastest to stricturing or penetrating complications.^[2]
• Symptoms underestimate structural damage. Objective reassessment with endoscopy and/or cross-sectional imaging is needed to judge progression.^[1]
• A new stricture or abrupt change in long-standing small-bowel disease should prompt evaluation for small bowel adenocarcinoma.^[6]
• PSC changes surveillance: colonoscopy should start at PSC diagnosis and be repeated annually.^[16]
• Pyoderma gangrenosum should not be debrided.^[15]