II-2. GI system: inflammatory bowel diseases

消化管：炎症性腸疾患

Inflammatory Bowel Disease (IBD)

Frequent autoimmune GI disorders: ulcerative colitis and Crohn’s disease.

Pathogenesis

Environmental factors, autoimmunity (celiac patients at higher risk), genetic factors (microbiome change + predisposition; many immune-related polymorphisms → pathobiont overpopulation → continuous inflammation).
Microbiome: salt load → ↓Lactobacillus survival + ↑IL-17.

Ulcerative Colitis (UC)

Recurring inflammation limited to the mucosa of the colon; commonly involves rectum; bloody diarrhea attacks lasting weeks (→ anemia); exacerbations alternating with full remission.
Clinical: bloody diarrhea, colicky pain, urgency, tenesmus, incontinence, blood/mucus discharge; systemic (fever, fatigue, weight loss).
Extraintestinal: arthritis (most frequent), skin/ocular lesions (uveitis, episcleritis), hepatobiliary (primary sclerosing cholangitis, fatty liver, autoimmune liver disease), thromboembolism, autoimmune hemolytic anemia.
Diagnosis: chronic diarrhea >4 weeks, active inflammation on endoscopy, biopsy (crypt abscesses, atrophy, ↑lamina propria leukocytes); labs: anemia, ESR ≥30 mm/h, low albumin, electrolyte abnormalities.
Acute complications: severe bleeding (up to 10%), fulminant colitis (>10 stools/day, dehydration), toxic megacolon (colon ≥6 cm or cecum >9 cm + systemic toxicity), perforation (usually from toxic megacolon; peritonitis = 50% mortality).
Chronic complications: benign rectosigmoid strictures (~10%), ↑colorectal cancer risk (extent + duration).

Crohn’s Disease (CD)

Transmural inflammation of GI tract (uncertain etiology); 80% terminal ileum, 50% ileocolitis, 33% perianal, 20% colon-only. Intermittent exacerbations + remission.
Pathogenesis: genetic susceptibility (JAK2, STAT3, Th-17, HLA, NOD2) + environment (smoking 2×, childhood antibiotics, OCP, NSAID, low fiber) + microbiome. Bacterial dysbiosis → intestinal TNF-α; ↑gammaproteobacteria; mucosa-associated invasive E. coli (30%).
Symptoms (hallmarks): occult bleeding (check stool!), weight loss/malabsorption (steatorrhea), prolonged non-bloody diarrhea + crampy pain (distal ileum → RLQ pain), fatigue, fever.
Diagnosis: endoscopy (colonoscopy → focal ulcers, cobblestone; wireless capsule), imaging (MR enterography detects fistulae = gold standard); labs: anemia (iron/B12), ↑WBC, ↑CRP/ESR, stool calprotectin/lactoferrin, hypoalbuminemia; serology (pANCA, anti-OmpC, ↑CRP higher than UC).
DDx: IBS, lactose intolerance, infectious colitis (Shigella, Salmonella, Campylobacter, E. coli O157, C. difficile), UC (rectal involvement, gross bleeding, spares small bowel).

Treatment of IBD

Crohn’s: systemic corticosteroids, methotrexate; biologics — vedolizumab (anti-α4β7 integrin, gut-selective), anti-TNF (infliximab, adalimumab; most potent, used at steroid/MTX resistance).

Irritable Bowel Syndrome (IBS)

Functional GI disorder: chronic cramping abdominal pain + altered bowel habits (diarrhea/constipation/alternating).
No bowel wall structural change; does NOT increase colorectal cancer risk. High healthcare cost (25–50% of GI referrals). Diagnosis = exclusion (no specific test).

一問一答

▶What are the two main inflammatory bowel diseases?

Ulcerative colitis and Crohn's disease — both frequent autoimmune GI disorders.

▶What factors contribute to IBD pathogenesis?

Environmental factors, autoimmunity (higher risk in celiac patients), and genetic factors causing microbiome change → pathobiont overpopulation → continuous inflammation.

▶What is the depth and location of inflammation in ulcerative colitis?

Inflammation is limited to the mucosa of the colon, commonly involving the rectum, with bloody diarrhea attacks and exacerbations alternating with full remission.

▶What are the extraintestinal manifestations of ulcerative colitis?

Arthritis (most frequent), skin/ocular lesions (uveitis, episcleritis), hepatobiliary disease (primary sclerosing cholangitis, fatty liver, autoimmune liver disease), thromboembolism, and autoimmune hemolytic anemia.

▶What are the typical clinical symptoms of ulcerative colitis?

Bloody diarrhea, colicky pain, urgency, tenesmus, incontinence, blood/mucus discharge, plus systemic features (fever, fatigue, weight loss).

▶What are the histological findings of ulcerative colitis on biopsy?

Crypt abscesses, atrophy, and increased lamina propria leukocytes (with active inflammation on endoscopy and chronic diarrhea >4 weeks).

▶What are the hallmark symptoms of Crohn's disease?

Occult bleeding (check stool), weight loss/malabsorption (steatorrhea), prolonged non-bloody diarrhea with crampy pain (distal ileum → RLQ pain), fatigue, and fever.

▶What is the depth and distribution of inflammation in Crohn's disease?

Transmural inflammation anywhere in the GI tract: 80% terminal ileum, 50% ileocolitis, 33% perianal, 20% colon-only, with intermittent exacerbations and remission.

▶What chronic complications arise in ulcerative colitis?

Benign rectosigmoid strictures (~10%) and increased colorectal cancer risk (proportional to extent and duration).

▶What is toxic megacolon and how is it defined in UC?

An acute complication: colon ≥6 cm (or cecum >9 cm) plus systemic toxicity; perforation usually arises from it (peritonitis carries ~50% mortality).

▶What endoscopic findings are characteristic of Crohn's disease?

Focal ulcers and a cobblestone appearance on colonoscopy (wireless capsule for small bowel).

▶Which environmental factors raise Crohn's disease risk?

Smoking (2×), childhood antibiotics, oral contraceptives, NSAIDs, and a low-fiber diet (plus genetic susceptibility: JAK2, STAT3, Th-17, HLA, NOD2).

▶How does Crohn's disease differ from ulcerative colitis on presentation?

UC shows rectal involvement, gross bleeding, and spares the small bowel; Crohn's is transmural, often spares the rectum, and typically has non-bloody diarrhea (and higher CRP).

▶What is the gold-standard imaging for detecting fistulae in Crohn's disease?

MR enterography.

▶What is the role of the microbiome in Crohn's disease?

Bacterial dysbiosis drives intestinal TNF-α; there are increased gammaproteobacteria and mucosa-associated invasive E. coli (in ~30%).

▶What biologics are used to treat Crohn's disease?

Vedolizumab (anti-α4β7 integrin, gut-selective) and anti-TNF agents (infliximab, adalimumab — most potent, used at steroid/MTX resistance); also systemic corticosteroids and methotrexate.

▶What is irritable bowel syndrome (IBS) and does it raise cancer risk?

A functional GI disorder with chronic cramping pain and altered bowel habits; there is no structural bowel wall change and it does NOT increase colorectal cancer risk.

▶How is the diagnosis of IBS made?

By exclusion — there is no specific diagnostic test (it accounts for 25–50% of GI referrals).

▶What laboratory abnormalities support active ulcerative colitis?

Anemia, ESR ≥30 mm/h, low albumin, and electrolyte abnormalities.

▶What infectious causes must be excluded when diagnosing Crohn's disease?

Infectious colitis from Shigella, Salmonella, Campylobacter, E. coli O157, and C. difficile (also consider IBS, lactose intolerance, and UC).