Inflammatory Bowel Disease¶
Chapter 337 | Part 10: Disorders of the Gastrointestinal System · Part 10 – Gastrointestinal Disorders · Chapter 337
Key Clinical Points¶
- IBD is a chronic idiopathic inflammatory disease of the GI tract, primarily categorized as Ulcerative Colitis (UC) or Crohn's Disease (CD).
- UC is characterized by mucosal/submucosal involvement, continuous distribution in the colon/rectum, and no skip lesions.
- CD is a transmural disease that can affect any part of the GI tract, often presenting with skip lesions and fistulas.
- Smoking has opposing effects: it is protective in UC (OR 0.58) but a risk factor in CD (OR 1.76).
- Genetic factors contribute to ~20% of disease risk; over 60 gene defects are linked to early-onset IBD.
- Granulomas are a specific histopathological feature of CD, not UC.
- Appendectomy is protective for UC (risk reduction 13–26%) but has no protective effect in CD.
- Infections (e.g., C. difficile, Salmonella) must be ruled out before an IBD diagnosis can be confirmed.
- Extraintestinal manifestations (EIMs) vary by system: e.g., joint involvement is most common in Black patients, while skin issues are more common in Latinx patients.
- Management involves a tiered approach based on severity and phenotype, utilizing 5-ASA, immunomodulators, and biologics.
DEFINITION & CLASSIFICATION¶
• Definition (Harrison's 22e): Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease of the gastrointestinal tract. Ulcerative colitis (UC) and Crohn's disease (CD) are the two major types of IBD. • Clinical Subtypes: ◦ Pediatric IBD: ~20–25% of all cases. ◦ Early-onset (EO): <10 years old. ◦ Very-early-onset (VEO): <6 years old; often involves the colon and is resistant to standard medications. ◦ Infantile IBD: <2 years old.
Classification by Morphology¶
• Ulcerative Colitis (UC): ◦ Location: Limited to the colon and rectum. ◦ Continuity: Typically continuous without skip areas. ◦ Depth: Limited to mucosa and submucosa. • Crohn's Disease (CD): ◦ Location: Can affect any part of the GI tract. ◦ Pattern: Often features skip lesions. ◦ Depth: Transmural involvement (all layers of the bowel wall). ◦ Features: Associated with fistulas and granulomas.
EPIDEMIOLOGY¶
• Global Trends: ◦ Prevalence >0.3% in North America, Oceania, and Europe. ◦ Rising incidence in newly industrialized countries (Africa, Asia, South America). ◦ Peak Incidence: 2nd to 4th decades; secondary rise in 7th to 9th decades. • Risk Factors: ◦ Smoking: Protective in UC (OR 0.58) → Risk factor in CD (OR 1.76). ◦ Appendectomy: Protective for UC (risk reduction 13–26%) → Not protective for CD. ◦ Oral Contraceptives: No increased risk in UC; Hazard ratio 2.82 for CD. ◦ Early Life Factors: Infections in the first year of life increase risk by 1.6x (UC) and 3x (CD) by age 10/20. ◦ Dietary Factors: High animal protein, sugar, and \omega-6 fatty acids; low \omega-3 fatty acids linked to increased risk. ◦ Vitamin D: Protective effect on the risk of CD reported.
Genetic Susceptibility¶
• Familial Risk: 5–10% of patients; first-degree relative with disease is the strongest risk factor. ◦ UC: ~4x increased risk for children of affected parents. ◦ CD: ~8x increased risk for children of affected parents. • Twin Studies: ◦ Monozygotic (MZ) twins: 6–18% concordance for UC; 38–58% for CD. ◦ Dizygotic (DZ) twins: 0–2% concordance for UC; 4% for CD. • Genetic Diversity: Over 60 gene defects identified in VEOIBD and infantile IBD via WES.
Phenotypes by Race¶
• Black & Latinx: Tend to have ileocolonic CD distribution. • Asian: Ileocolonic CD is most common (50.5–71%); perianal disease more common than in Whites; older patients (>60) with UC show more aggressive course. • Extraintestinal Manifestations (EIMs): ◦ Black: Joint involvement is predominant (15.7–29.6%). ◦ Asian American: Ocular involvement is common (7.1–13%). ◦ Latinx: Dermatologic manifestations are most common (10–13%).
ETIOLOGY & PATHOPHYYSOLOGY¶
• Core Hypothesis: IBD results from a breakdown in the 'supraorganism' balance between: ◦ Commensal microbiota ◦ Intestinal epithelial cells (IECs) ◦ Immune cells • Mechanism: Inappropriate immune response to endogenous commensal microbiota, with or without components of autoimmunity. • Microbiota Dysbiosis: ◦ Increase in Proteobacteria (e.g., E. coli). ◦ Loss of Firmicutes (e.g., Faecalibacterium prausnitzii). • Immune Regulation Failure: ◦ Impaired mucosal tolerance. ◦ Deficient T regulatory cells (FoxP3+). ◦ Reduced anti-inflammatory cytokines (IL-10, IL-35, TGF-β). • Inflammatory Cascade: ◦ Innate sensing → T-cell/B-cell activation → Cytokine production. ◦ Pro-inflammatory cytokines: IL-1, IL-6, IL-12, IL-23, TNF (promote fibrogenesis, tissue damage, and coagulation). ◦ T-cell subsets: ◦ T_H 1: Produce IL-2, IFN-γ; lead to transmural granulomatous inflammation (CD-like). ◦ T_H 2: Produce IL-4, IL-5, IL-13; lead to superficial mucosal inflammation (UC-like). ◦ T_H 9: Produce IL-9; promote allergic-like inflammation. ◦ T_H 17: Produce IL-17, IL-21, IL-22; responsible for neutrophilic recruitment.
Genetic Landscape (Table 3)¶
• Unfolded Protein Response/Autophagy: ATG16L1 (CD), SLC22A5 (CD), IRGM (CD), LRRK2 (CD), LACC1 (CD), ORMDL3 (Both), XBP1 (Both). • Innate Immunity: ITLN1 (CD), NOD2 (CD), PTGER4 (Both), TNFAIP3 (Both), CCR6 (CD), TNFSF15 (Both). • Adaptive/Signaling: IL23R (Both), IL10 (UC), IL12B (Both), PTPN2 (CD), MST1 (Both), JAK2 (Both), STAT3 (Both).
CLINICAL FEATURES¶
• Ulcerative Colitis: ◦ Symptoms: Diarrhea, rectal bleeding, tenesmus, passage of mucus, crampy abdominal pain. ◦ Proctitis specific: Fresh blood/mucus, tenesmus; rarely abdominal pain. • Crohn's Disease: ◦ Macroscopic: Transmural inflammation, skip lesions, fistulas, cobblestoning (Fig 5), transmural wall thickening, and stenosis.
Extraintestinal Manifestations (Table 7)¶
• Rheumatologic: ◦ Peripheral arthritis: Asymmetric/migratory; parallels bowel activity. ◦ Sacroiliitis: Symmetric; independent of bowel activity. ◦ Ankylosing spondylitis: Gradual fusion; independent of bowel activity; 2/3 have HLA-B27. • Dermatologic: ◦ Erythema nodosum: Parallels bowel activity. ◦ Pyoderma gangrenosum: Independent of bowel activity; do not debride or perform colectomy. ◦ Psoriasis: Unrelated to bowel activity. • Ocular: ◦ Anterior uveitis (pain, photophobia): Independent of bowel activity. ◦ Mild burning: Parallels bowel activity. • Hepatobiliary: ◦ Fatty liver: Secondary to illness/meds; reduce steroids. ◦ Cholelithiasis: Common in ileitis or resection; cholecystectomy if symptomatic. ◦ Primary Sclerosing Cholangitis (PSC): 7–10% risk of cholangiocarcinoma; cholecystectomy for polyps. • Other: ◦ Thromboembolic: Increased risk due to inflammation/genetics; use anticoagulation. ◦ Systemic amyloidosis: Secondary in long-standing IBD (especially CD); use colchicine.
DIFFERENTIAL DIAGNOSIS¶
• Infectious Mimics (Table 6): ◦ Bacterial: Salmonella, Shigella, E. coli, Campylobacter, Yersinia, C. difficile, Gonorrhea, Chlamydia. ◦ Mycobacterial: Tuberculosis, M. avium. ◦ Viral: Cytomegalovirus, Herpes simplex, HIV. ◦ Parasitic: Amebiasis, Isospora, Trichuris trichiura. ◦ Fungal: Histoplasmosis, Candida, Aspergillus. • Noninfectious Mimics: ◦ Inflammatory: Appendicitis, Diverticulitis, Ischemic colitis. ◦ Neoplastic: Lymphoma, Carcinoma of the ileum. ◦ Drugs/Chemicals: NSAIDs, Phenothiazole (not listed but implied), Chemotherapy (not listed). ◦ Other: Behçet's syndrome, Graft-versus-host disease, Neutropenic colitis.
DIAGNOSTIC APPROACH¶
- Infection Exclusion: Rule out infectious etiologies (Bacterial, Viral, Parasitic) before confirming IBD diagnosis.
- Endoscopic Evaluation:
- Colonoscopy: Assess for erythema, friability, and exudate (UC) or cobblestoning and skip lesions (CD).
- Capsule Endoscopy: Utilize to visualize small bowel mucosa for ulcerations/narrowing.
- Imaging Studies:
- MRI (T2-weighted with fat saturation): Identify wall thickening, fistulas, abscesses, and luminal narrowing (stenosis).
- Histopathology:
- UC: Look for continuous mucosal inflammation, crypt atrophy, and basal lymphoplasmacytosis.
- CD: Look for transmural inflammation, granulomas, and architectural distortion.
- Surveillance: Identify low-grade dysplasia in chronic UC (Fig 12) to monitor for progression to cancer.
MANAGEMENT & TREATMENT¶
- Initial/Induction Therapy:
- Use of corticosteroids (Prednisone, Hydrocortisone, Solumedrol) for induction of remission only.
- Maintenance Therapy (based on severity):
- Mild to Moderate CD:
- Budesonide oral.
- Upadacitinib (45 mg PO qd; 8 weeks for UC, 12 weeks for CD, then 15 or 30 mg qd).
- Biologics (Infliximab, Vedolizumab, Risankizumab) ± MP/AZA/MTX.
- Moderate to Severe CD:
- Biologics (Infliximab, Vedol12, Risankizumab) ± MP/AZA/MTX.
- Specialized Management for Fistulizing CD:
- Biologic ± MP/AZA/MTX.
- Abscess drainage and antibiotics.
- Total parenteral (TPN) or exclusive enteral nutrition (EEN) and bowel rest.
- Pharmacological Agents & Dosing (Table 8 & 9):
- 5-ASA Preparations:
- Azo-Bond (Sulfasalazine/Balsalazide): 3–6 g (acute); 2–4 g (maintenance).
- Delayed-Release (Mesalamine): 400, 800 mg.
- Controlled-Release (Mesalamine): 250, 500, 1000 mg.
- Biologics:
- Infliximab: 5 mg/kg (0, 2, 6 weeks), then every 8 weeks; or 160mg/80mg/40mg regimen.
- Vedolizumab: 300 mg (0, 2, 6 weeks), then every 8 weeks.
- Risankizumab: 600 mg IV (x3) then 180 or 360 mg SC every 8 weeks.
- Upadacitinib: 45 mg PO qd (initial); then 15 or 30 mg qd.
- Surgical Indications (Table 10):
- UC: Intractable disease, Fulminant disease, Toxic megacolon, Colonic perforation, Massive colonic hemorrhage, Extracolonic disease.
- CD: Small intestine stricture/obstruction, Refractory fistula, Abscess, Perianal disease unresponsive to medical therapy.
Management of Fistulizing CD (Flowchart 1)¶
Step 1: Identify Fistulizing CD → Step 2: Options include: - Biologic ± MP/AZA/MTX. - Abscess drainage and antibiotics. - Total parenteral and bowel rest.
COMPLICATIONS & PROGNOSIS¶
• Complications: ◦ Fistulas (common in CD). ◦ Abscesses (common in CD). ◦ Perianal disease. ◦ Colonic obstruction/stenosis. ◦ Cancer: Risk of colorectal cancer in chronic UC; risk of cholangiocarcinoma in PSC. ◦ Extraintestinal Manifestations (EIMs): See Table 7 for specific risks like heart attack, stroke, and pulmonary issues.
Prognosis¶
• General: Prognosis depends on the severity of disease and presence of complications. ◦ Early-onset IBD (VEO/Infantile) often requires more intensive management due to resistance to standard medications.
SPECIAL POPULATIONS¶
• Pediatric Patients: ◦ VEO and infantile cases are often resistant to standard meds. ◦ High risk of rapid progression in certain genetic-linked cases.
Pregnancy & Pregnancy Management¶
• Monitoring: Use MRI (T2-weighted) to evaluate CD during pregnancy (Fig 9). ◦ Safety: Ensure fetal safety while managing active inflammation.
KEY PEARLS & HIGH-YIELD POINTS¶
• Rule of Thumb: UC = Mucosa/Continuous; CD = Transmural/Skip. • Smoking Paradox: Protects UC, harms CD. • Appendectomy: Protective for UC, neutral for CD. • Granulomas: Pathognomonic for CD (not present in UC). • Surgical Triggers: Surgery is indicated for 'emergency' conditions like perforation or toxic megacolon in UC; and for 'refractory' issues like fistulas/abscesses in CD. • Biologic Selection: Vedolizumab has no increased risk of systemic infection; Infliximab requires TB/Hep B screening.
Reference Tables¶
TABLE 337-1 Epidemiology of IBD Age of onset¶
Harrison's 22e, p.2551
| ULCERATIVE COLITIS | CROHN’S DISEASE | |
|---|---|---|
| Age of onset | Second to fourth decades and seventh to ninth decades |
Second to fourth decades and seventh to ninth decades |
| Female-to-male ratio | 0.51–1.58 | 0.34–1.65 |
| May prevent disease (odds ratio 0.58) |
||
| Oral contraceptives | No increased risk | Hazard ratio 2.82 |
| Protective (risk reduction 13–26%) |
||
| Monozygotic twins | 6–18% concordance | 38–58% concordance |
| 0–2% concordance | ||
| Infections in the first year of life |
1.6 and 3 times the risk of developing IBD by age 10 and 20 years |
|
| 337 | Inflammatory Bowel Disease Sonia Friedman, Richard S. Blumberg |
TABLE 337-2 Primary Genetic Disorders Associated with¶
Harrison's 22e, p.2553
| NAME | GENETIC ASSOCIATION | PHENOTYPE |
|---|---|---|
| Turner’s syndrome | Loss of part or all of X chromosome |
Associated with UC and colonic CD |
| Autosomal recessive disorder genes involved in the biogenesis of lysosome- related organelles or adaptor protein-3 complex |
||
| Wiskott-Aldrich syndrome (WAS) |
X-linked recessive disorder, loss of WAS protein function |
Colitis, immunodeficiency, severely dysfunctional platelets, and thrombocytopenia |
| Autosomal recessive disorder of SLC37A4 resulting in deficiency of the glucose-6-phosphate translocase |
||
| Immune dysregulation polyendocrinopathy, enteropathy X-linked (IPEX) |
Loss of FoxP3 transcription factor and T regulatory cell function |
UC-like autoimmune enteropathy, with endocrinopathy (neonatal type 1 diabetes or thyroiditis), dermatitis |
| Deficient IL-10 and IL-10 receptor function |
TABLE 337-3 Some Genetic Loci Associated with Crohn’s Disease and/or Ulcerative Colitis CHROMOSOME Unfolded Protein…¶
Harrison's 22e, p.2554
| CHROMOSOME | PUTATIVE GENE |
GENE NAME | PROTEIN FUNCTION | CD | UC |
|---|---|---|---|---|---|
| Unfolded Protein Response, Autophagy, and Metabolism | |||||
| 2q37 | ATG16L1 | ATG16 autophagy related 16-like 1 | Autophagy | + | |
| 5q31 | SLC22A5 | Solute carrier family 22, member 5 | β-Carnitine transporter | + | |
| 5q33 | IRGM | Immunity-related GTPase family, M | Autophagy | + | |
| 7p21 | AGR2 | Anterior gradient 2 | Unfolded protein response | + | + |
| 12q12 | LRRK2 | Leucine-rich repeat kinase 2 | Autophagy | + | |
| 13q14 | LACC1 | Laccase domain containing 1 (FAMIN) | Immunometabolic regulator | + | |
| 17q21 | ORMDL3 | Orosomucoid related member 1-like 3 | Unfolded protein response and lipid synthesis | + | + |
| 22q12 | XBP1 | X-box binding protein 1 | Unfolded protein response | + | + |
| Innate Immunity | |||||
| ITLN1 | Intelectin 1 | Bacterial binding | + | ||
| NOD2 | Nucleotide-binding oligomerization domain containing 2 | Bacterial sensing and autophagy activation | + | ||
| Adaptive Immunity | |||||
| 1p31 | IL23R | Interleukin 23 receptor | T17 cell stimulation H |
+ | + |
| 1q32 | IL10 | Interleukin 10 | Treg-associated cytokine | + | |
| 5q33 | IL12B | Interleukin 12 subunit beta | IL-12 p40 chain of IL-12/IL-23 | + | + |
| 18p11 | PTPN2 | Protein tyrosine phosphatase, nonreceptor type 2 | T-cell regulation | + | |
| Inflammation and Healing | |||||
| MST1 | Macrophage Stimulating 1 | Macrophage activation | + | ||
| PTGER4 | Prostaglandin E receptor 4 | PGE receptor 2 |
+ | ||
| TNFAIP3 | Tumor necrosis factor, alpha-induced protein 3 (A20) | Toll-like receptor regulation | + | ||
| CCR6 | Chemokine (C-C motif) receptor 6 | Dendritic cell migration | + | ||
| JAK2 | Janus kinase 2 | IL-6R and IL-23R signaling | + | ||
| TNFSF15 | Tumor necrosis factor–like cytokine 1A (TL1A) | Promotes inflammation and fibrosis | + | ||
| STAT3 | Signal transducer and activator of transcription 3 | IL-6R, IL-23R, and IL-10R signaling | + |
TABLE 337-4 Montreal Classification of Extent and Severity of Ulcerative Colitis (UC) EXTENT E1: Ulcerative proctitis…¶
Harrison's 22e, p.2557
| EXTENT | ANATOMY |
|---|---|
| E1: Ulcerative proctitis | Involvement limited to the rectum |
| E3: Extensive UC (pancolitis) | Involvement extends proximal to the splenic flexure |
| SEVERITY | DEFINITION |
| S0: Clinical remission | Absence of symptoms |
| S2: Moderate disease activity | ≥4 stools/d but minimal signs of systemic toxicity |
TABLE 337-5 Vienna and Montreal Classifications of Crohn’s Disease Age at diagnosis¶
Harrison's 22e, p.2558
| VIENNA | MONTREAL | |
|---|---|---|
| Age at diagnosis | A1: <40 years A2: >40 years |
A1: <16 years A2: Between 17 and 40 years A3: >40 years |
| L1: Ileal L2: Colonic L3: Ileocolonic L4: Upper |
||
| Behavior | B1: Nonstricturing, nonpenetrating B2: Stricturing B3: Penetrating |
B1: Nonstricturing, nonpenetrating B2: Stricturing B3: Penetrating p: Perianal disease modifierb |
TABLE 337-6 Diseases That Mimic IBD Infectious Etiologies Bacterial¶
Harrison's 22e, p.2560
| Infectious Etiologies | ||
|---|---|---|
| Bacterial | Mycobacterial | Viral |
| Salmonella | Tuberculosis | Cytomegalovirus |
| Shigella | Mycobacterium avium | Herpes simplex |
| Toxigenic | Parasitic | HIV |
| Escherichia coli | Amebiasis | Fungal |
| Campylobacter | Isospora | Histoplasmosis |
| Yersinia | Trichuris trichiura | Candida |
| Clostridioides difficile | Hookworm | Aspergillus |
| Gonorrhea | Strongyloides | |
| Chlamydia trachomatis | ||
| Noninfectious Etiologies | ||
| Inflammatory | Neoplastic | Drugs and Chemicals |
| Appendicitis | Lymphoma | NSAIDs |
| Diverticulitis | Metastatic | Phosphosoda |
| Diversion colitis | Carcinoma | Cathartic colon |
| Collagenous/lymphocytic colitis |
Carcinoma of the ileum Carcinoid Familial polyposis |
Gold Oral contraceptives Cocaine Immune checkpoint inhibitor colitis Mycophenolate mofetil |
| Ischemic colitis | ||
| Radiation colitis/enteritis | ||
| Solitary rectal ulcer syndrome |
||
| Eosinophilic gastroenteritis |
||
| Neutropenic colitis | ||
| Behçet’s syndrome | ||
| Graft-versus-host disease |
TABLE 337-7 Extraintestinal Manifestations CATEGORY Rheumatologic Disorders (5–20%) Peripheral arthritis Sacroiliitis…¶
Harrison's 22e, p.2562
| CATEGORY | CLINICAL COURSE | TREATMENT |
|---|---|---|
| Rheumatologic Disorders (5–20%) | ||
| Peripheral arthritis | Asymmetric, migratory Parallels bowel activity |
Reduce bowel inflammation |
| Sacroiliitis | Symmetric: spine and hip joints Independent of bowel activity |
Steroids, injections, methotrexate, anti-TNF |
| Ankylosing spondylitis | Gradual fusion of spine Independent of bowel activity Two-thirds have HLA-B27 antigen |
Physical therapy, steroids, injections, methotrexate, anti- TNF, IL-17 inhibitors, JAK inhibitors |
| Metabolic Bone Disorders (up to 40% of patients) | ||
| Risk increased by glucocorticoids, cyclosporine, methotrexate, total parenteral nutrition, malabsorption, and inflammation Fracture rates highest in the elderly (age >60) |
||
| Death of osteocytes and adipocytes and eventual bone collapse; affects hips more than knees or shoulders; risk factor is steroid use |
||
| Dermatologic Disorders (10–20%) | ||
| Erythema nodosum | Hot, red, tender, nodules/extremities Parallels bowel activity |
Reduce bowel inflammation |
| Pyoderma gangrenosum | Ulcerating, necrotic lesions on extremities, trunk, face, stoma Independent of bowel activity |
Antibiotics, steroids, cyclosporine, infliximab, dapsone, azathioprine, intralesional steroids; not debridement or colectomy |
| Psoriasis | Unrelated to bowel activity | Topical steroids, light therapy, methotrexate, infliximab, adalimumab, ustekinumab, risankizumab, JAK inhibitors |
| Pyoderma vegetans | Intertriginous areas Parallels bowel activity |
Evanescent; resolves without progression |
| Pyostomatitis vegetans | Mucous membranes Parallels bowel activity |
Evanescent; resolves without progression |
| Metastatic Crohn’s disease (CD) |
CD of the skin Parallels bowel activity |
Reduce bowel inflammation |
| Sweet syndrome | Neutrophilic dermatosis Parallels bowel activity |
Reduce bowel inflammation |
| Aphthous stomatitis | Oral ulcerations Parallels bowel activity |
Reduce bowel inflammation/topical therapy |
| Ocular Disorders (1–11%) | ||
| Ocular pain, photophobia, blurred vision, headache Independent of bowel activity |
||
| Mild ocular burning Parallels bowel activity |
||
| Hepatobiliary Disorders (10–35%) | ||
| Fatty liver | Secondary to chronic illness, malnutrition, steroid therapy | Improve nutrition, reduce steroids |
| Cholelithiasis | Patients with ileitis or ileal resection Malabsorption of bile acids, depletion of bile salt pool, secretion of lithogenic bile |
Reduce bowel inflammation; cholecystectomy in symptomatic patients |
| Primary sclerosing cholangitis (PSC) |
Intrahepatic and extrahepatic Inflammation and fibrosis leading to biliary cirrhosis and hepatic failure 7–10% cholangiocarcinoma Small-duct PSC involves small-caliber bile ducts and has a better prognosis |
Cholecystectomy in patients with gallbladder polyps due to the high incidence of malignancy |
| Urologic | ||
| Less Common Extraintestinal Manifestations | ||
| Thromboembolic disorders | Increased risk of venous and arterial thrombosis; factors responsible include abnormalities of the platelet-endothelial interaction, hyperhomocysteinemia, alterations in the coagulation cascade, impaired fibrinolysis, involvement of tissue factor–bearing microvesicles, disruption of the normal coagulation system by autoantibodies, and a genetic predisposition |
Anticoagulation; control of inflammation |
| Cardiopulmonary | Endocarditis, myocarditis, pleuropericarditis, interstitial lung disease | Treatment is varied; stop 5-ASA agents as they can rarely cause interstitial lung disease |
| Systemic amyloidosis | Secondary (reactive) in long-standing IBD, especially CD | Colchicine and referral to specialty center |
| Pancreatitis | Duodenal fistulas, ampullary CD, gallstones, PSC, drugs (MP, azathioprine, 5-ASAs), autoimmune, primary CD of the pancreas |
Treatment is varied; stop offending medication; diagnose and treat with ERCP and/or cholecystectomy |
TABLE 337-8 Oral 5-Aminosalicylic Acid (5-ASA) Preparations PREPARATION Azo-Bond Sulfasalazine (500 mg) (Azulfidine)…¶
Harrison's 22e, p.2564
| PREPARATION | FORMULATION | DELIVERY | DOSING PER DAY |
|---|---|---|---|
| Azo-Bond | |||
| Sulfasalazine (500 mg) (Azulfidine) Balsalazide (750 mg) (Colazal) |
Sulfapyridine-5-ASA Aminobenzoyl-alanine–5-ASA |
Colon Colon |
3–6 g (acute) 2–4 g (maintenance) 6.75–9 g |
| Delayed-Release | |||
| Eudragit S (pH 7) MMX mesalamine (SPD476) |
Distal ileum-colon Ileum-colon |
||
| Controlled-Release | |||
| Mesalamine (250, 500, 1000 mg) (Pentasa) |
Ethylcellulose microgranules | Stomach-colon | 2–4 g (acute) 1.5–4 g (maintenance) |
| Delayed- and Extended-Release | |||
| Intellicor extended-release mechanism | Ileum-colon |
TABLE 337-9 Biologic and Small-Molecule Agents in the Treatment of Inflammatory Bowel Disease MEDICATION Infliximab¶
Harrison's 22e, p.2568
| MEDICATION | DOSAGE | INDICATION | SERIOUS TOXICITIES | OTHER COMMON SIDE EFFECTS |
TESTING |
|---|---|---|---|---|---|
| Infliximab | 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks; may increase dose to 10 mg/kg every 4 weeks depending on trough levels Intensive dosing for hospitalized corticosteroid- refractory patients |
Moderate to severe Crohn’s disease and ulcerative colitis Fistulizing Crohn’s disease |
Increased risk of infections (bacterial and fungal), tuberculosis (TB) reactivation, hepatitis B reactivation, lymphoma (controversial), psoriasis, melanoma and nonmelanoma skin cancers, drug-induced lupus Contraindicated in multiple sclerosis, class III/IV congestive heart failure |
Infusion reactions | Prior to infusion: TB testing Hepatitis B testing (HBsAb, HBsAg, HBcAb) Maintenance: Skin check yearly Influenza, pneumococcal vaccinations Hepatitis B vaccine if not immune |
| 160 mg day 0, 80 mg day 14 and then 40 mg every 14 days; may increase to 40 mg every 7 days depending on trough levels |
Moderate to severe Crohn’s disease and ulcerative colitis Fistulizing Crohn’s disease |
As above | Injection site reactions (better with citrate-free preparation) |
||
| Certolizumab | 400 mg on days 0 and 14, then 400 mg every 28 days |
Moderate to severe Crohn’s disease |
As above | As above | As above |
| 200 mg on day 0, 100 mg on day 14, then 100 mg every 28 days |
Moderate to severe ulcerative colitis |
As above | As above | ||
| Vedolizumab | 300 mg at 0, 2, and 6 weeks, then every 8 weeks; may increase dose to 300 mg every 4 weeks |
Moderate to severe ulcerative colitis (more effective than adalimumab as first- line therapy in one study) Moderate to severe Crohn’s disease. |
No increased risk of serious systemic or opportunistic infections No increased risk of malignancy |
Nasopharyngitis, headache, arthralgias, nausea |
Prior to infusion: TB testing Hepatitis B testing (HBsAb, HBsAg, HBcAb) Maintenance: Influenza, pneumococcal vaccinations Hepatitis B vaccine if not immune |
| 6 mg/kg IV, then 90 mg every 8 weeks; may increase dose to 90 mg every 4 weeks |
Moderate to severe Crohn’s disease and ulcerative colitis |
Reversible posterior leukoencephalopathy syndrome (presents with headaches, seizures, confusion, and visual disturbances), anaphylaxis, and angioedema |
Nasopharyngitis, upper respiratory tract infection, fatigue, headache |
||
| Risankizumab | 600 mg IV every 4 weeks × 3 doses then 180 mg or 360 mg SC every 8 weeks |
Moderate to severe Crohn’s disease |
Reversible posterior leukoencephalopathy syndrome (presents with headaches, seizures, confusion, and visual disturbances), anaphylaxis, and angioedema |
Nasopharyngitis, upper respiratory tract infection, fatigue, headache |
TB testing Hepatitis B testing (HBsAb, HBsAg, HBcAb) Maintenance: Influenza, pneumococcal vaccinations Hepatitis B vaccine if not immune |
| 10 mg bid; can decrease to 5 mg bid when patient in remission |
Moderate to severe ulcerative colitis |
Increased risk of heart attack, stroke, cancer, blood clots, and death. Patients who are at risk for cardiovascular disease, are current or past smokers, and/or are over the age of 50 should consider alternative therapies. Increased risk of viral infections, including herpes zoster, and bacterial and invasive fungal infections |
Elevated lipids, neutropenia, anemia, elevated liver enzymes |
||
| Upadacitinib | 45 mg PO qd × 8 weeks for ulcerative colitis; 45 mg PO qd × 12 weeks for Crohn’s disease, then 15 or 30 mg qd |
Moderate to severe ulcerative colitis or Crohn’s disease |
Increased risk of heart attack, stroke, cancer, blood clots, and death. Patients who are at risk for cardiovascular disease, are current or past smokers, and/or are over the age of 50 should consider alternative therapies. Increased risk of viral infections, including herpes zoster, and bacterial and invasive fungal infections |
Elevated lipids, neutropenia, anemia, elevated liver enzymes |
Prior to infusion: First dose of Shingrix recommended, TB testing Hepatitis B testing (HBsAb, HBsAg, HBcAb) Maintenance: Influenza, pneumococcal vaccinations Hepatitis B vaccine if not immune |
| 0.23 mg PO days 1–4, 0.46 mg PO days 5–7, 0.92 mg PO thereafter |
Moderate to severe UC |
Bradycardia, atrioventricular conduction delay, increased blood pressure, macular edema, posterior reversible encephalopathy syndrome |
Infections, elevated liver enzymes |
TABLE 337-10 Indications for Surgery¶
Harrison's 22e, p.2569
| ULCERATIVE COLITIS | CROHN’S DISEASE |
|---|---|
| Intractable disease | Small Intestine |
| Fulminant disease | Stricture and obstruction |
| Toxic megacolon | unresponsive to medical therapy |
| Colonic perforation | Massive hemorrhage |
| Massive colonic hemorrhage | Refractory fistula |
| Extracolonic disease | Abscess |
| Colonic obstruction | Colon and rectum |
| Colon cancer prophylaxis | Intractable disease |
| Colon dysplasia or cancer | Fulminant disease |
| Perianal disease unresponsive to medical therapy |
|
| Refractory fistula | |
| Colonic obstruction | |
| Cancer prophylaxis | |
| Colon dysplasia or cancer |