Inflammatory bowel diseases (Crohn's disease, Ulcerative colitis, gluten enteropathy) – etiology, pathogenesis, and clinical manifestations.
1 Crohn’s disease - a chronic, relapsing, granulomatous inflammatory bowel disease that can affect any part of the gastrointestinal tract from mouth to anus, but most commonly involves the terminal ileum and colon.
Etiology
- Exact cause unknown (multifactorial).
- Genetic predisposition (e.g., NOD2 gene mutations).
- Dysregulated immune response to gut microbiota.
- Environmental triggers (smoking ↑ risk).
Pathogenesis
- Inappropriate immune activation against intestinal microbes - NOD2 mut- This leads to chronic activation of Th1 and Th17 cells, with excessive production of cytokines (e.g., TNF-α, IL-17).
- Transmural (full-thickness) inflammation → granuloma formation - Inflm thru entire wall- from mucosa and serosa, . Non caseating.
- Skip lesions: segments of inflamed bowel separated by normal tissue - cobblestone appearance ” of the mucosa during endoscopy
- Fibrosis, strictures, and fistulas develop over time - Chronic transmural inflammation promotes fibrosis and scarring, which can narrow the intestinal lumen → strictures.
The full-thickness nature allows abnormal connections (fistulas) to form between bowel loops or other organs (e.g., bladder, skin).
Abscesses may form from deep ulcerations
Clinical manifestations
- Diarrhea (often non- bloody).
- Abdominal pain (commonly in right lower quadrant).
- Weight loss, malabsorption.
- Perianal disease (fistulas, fissures).
- Extraintestinal: arthritis, uveitis, erythema nodosum.
2 Ulcerative colitis (UC)
Etiology
- Exact cause unknown.
- Genetic predisposition (e.g., HLA- B27 association).
- Autoimmune mechanisms; abnormal mucosal immune response to gut bacteria.
- Environmental: non- smokers and ex- smokers at higher risk.
Pathogenesis
- Continuous mucosal and submucosal inflammation starting from rectum → extends proximally through the colon (up to cecum). (always continuous, no skip lesions).
- Superficial ulceration, can bleed easily, and crypt abscesses form when neutrophils accumulate inside colonic gland crypts → a hallmark histological feature.
- Longstanding disease → pseudopolyps and increased risk of colorectal carcinoma.
Clinical manifestations
- Bloody, mucous diarrhea.
- Tenesmus (feeling of incomplete evacuation).
- Lower abdominal cramps.
- Severe cases: fever, weight loss.
- Extraintestinal: primary sclerosing cholangitis, arthritis, skin lesions (e.g., pyoderma gangrenosum).
3 Gluten enteropathy (celiac disease)
Etiology
- Autoimmune-mediated reaction to gluten (protein in wheat, barley, rye).
- Genetic predisposition (HLA- DQ2 and DQ8 haplotypes).
Pathogenesis
- Gluten-derived peptide (gliadin) deamidated by tissue transglutaminase ( tTG).
- Presented to T cells → triggers immune response against enterocytes.
- Villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis → malabsorption.
Clinical manifestations
- Chronic diarrhea (steatorrhea: fatty stools).
- Abdominal bloating, flatulence.
- Weight loss, failure to thrive (children).
- Nutritional deficiencies: iron, folate, calcium, vitamin D → anemia, osteoporosis.
- Dermatitis herpetiformis (skin manifestation).