3.4 Inflammatory Bowel Disease & Malabsorption Syndromes
Key Takeaways
- Crohn's disease is characterized by transmural inflammation, skip lesions, non-caseating granulomas, and perianal fistulae, whereas Ulcerative Colitis exhibits continuous mucosal involvement starting from the rectum.
- Primary Sclerosing Cholangitis (PSC) is strongly associated with Ulcerative Colitis (~80% of PSC patients have underlying UC) and increases colorectal cancer risk requiring annual screening colonoscopy.
- Celiac disease is an autoimmune enteropathy triggered by gluten (gliadin) associated with HLA-DQ2/DQ8; anti-tTG IgA is the screening test of choice, and duodenal biopsy showing villous atrophy is diagnostic.
- Whipple disease is caused by Tropheryma whipplei, presenting with malabsorption, arthralgias, hyperpigmentation, and pathognomonic PAS-positive, acid-fast negative macrophages on small bowel biopsy.
Inflammatory Bowel Disease & Malabsorption Syndromes
Inflammatory Bowel Disease (IBD) and Malabsorption Syndromes constitute major gastroenterology topics in UPSC CMS. Exam items test the pathological and clinical distinctions between Crohn's Disease and Ulcerative Colitis, extraintestinal manifestations, Celiac disease serology/biopsy, Tropical sprue, and Whipple disease.
Crohn's Disease vs. Ulcerative Colitis
Inflammatory bowel disease encompasses two primary chronic relapsing idiopathic inflammatory disorders of the gastrointestinal tract.
| Feature | Crohn's Disease (CD) | Ulcerative Colitis (UC) |
|---|---|---|
| Anatomical Distribution | Any segment from mouth to anus; Terminal ileum involved in 70–80%; Rectal sparing common | Restricted to colon; Rectum involved in 95%; extends continuously proximally |
| Pattern of Involvement | Skip lesions (discontinuous areas of inflammation separated by normal mucosa) | Continuous inflammation extending from rectum without skip lesions |
| Depth of Inflammation | Transmural (full thickness of bowel wall) | Mucosal and submucosal only |
| Gross Endoscopic Appearance | Cobblestone mucosa (deep linear ulcers separating edematous mucosa), aphthous ulcers, creeping fat | Diffuse hyperemia, granular friable mucosa, superficial ulcerations, pseudopolyps |
| Histopathology | Non-caseating granulomas (30–50% pathognomonic finding), transmural lymphoid aggregates | Crypt abscesses (neutrophils in crypt lumen), crypt distortion/atrophy |
| Complications | Strictures, intestinal obstruction, fistulae (enterocutaneous, enteroenteric, enterovesical), perianal abscesses | Toxic megacolon (transverse colon diameter $>6\text{ cm}$), severe hemorrhage, Colorectal Carcinoma |
| Serology | ASCA (+) (Anti-Saccharomyces cerevisiae antibodies) | p-ANCA (+) (Perinuclear antineutrophil cytoplasmic antibodies) |
| Smoking Effect | Smoking worsens disease progression and relapse risk | Smoking is protective (ex-smokers have higher risk of UC relapse) |
| Surgical Cure | Non-curable; surgery reserved for complications (segmental resection) | Curable by total proctocolectomy with ileal pouch-anal anastomosis (IPAA) |
Extraintestinal Manifestations of IBD
- Hepatobiliary: Primary Sclerosing Cholangitis (PSC) – strongly associated with Ulcerative Colitis ($70-80%$ of PSC patients have UC). Manifests with concentric onion-skin fibrosis of bile ducts, p-ANCA positivity, and increased risk of cholangiocarcinoma.
- Dermatologic:
- Erythema Nodosum: Painful, tender red subcutaneous nodules on anterior shins; correlates with intestinal disease activity (more common in CD).
- Pyoderma Gangrenosum: Violaceous, necrotic ulceration with undermined purulent edges; independent of intestinal disease activity (more common in UC).
- Ocular: Episcleritis (correlates with bowel inflammation), Uveitis (painful, photophobia, cell & flare on slit-lamp; HLA-B27 associated).
- Musculoskeletal: Peripheral enteropathic arthritis (Type I pauciarticular; Type II polyarticular), Ankylosing Spondylitis (HLA-B27 associated, independent of IBD course).
Pharmacotherapy of IBD
- 5-Aminosalicylates (5-ASA / Mesalamine, Sulfasalazine): First-line induction and maintenance for mild-to-moderate Ulcerative Colitis.
- Corticosteroids (Prednisone, Budesonide): Highly effective for acute flare induction; strictly contraindicated for long-term maintenance due to systemic toxicity.
- Immunomodulators (Azathioprine, 6-Mercaptopurine, Methotrexate): Used for steroid-sparing maintenance in moderate-to-severe IBD. Requires thiopurine methyltransferase (TPMT) testing prior to initiation.
- Biologic Therapies:
- Anti-TNF-$\alpha$ agents: Infliximab, Adalimumab.
- Anti-integrin ($\alpha_4\beta_7$): Vedolizumab (gut-selective).
- Anti-IL-12/IL-23: Ustekinumab.
Malabsorption Syndromes
Malabsorption is impaired mucosal absorption of nutrients from the small intestine.
1. Celiac Disease (Gluten-Sensitive Enteropathy)
- Pathogenesis: Immune-mediated enteropathy triggered by ingestion of dietary gluten (specifically gliadin peptides found in wheat, rye, and barley) in genetically susceptible individuals expressing HLA-DQ2 ($95%$) or HLA-DQ8 ($5%$).
- Clinical Manifestations: Chronic diarrhea, abdominal distension, failure to thrive, iron-deficiency anemia refractory to oral iron, dermatitis herpetiformis (intensely pruritic papulovesicular rash on extensor surfaces).
- Diagnostic Protocol:
- Serology (Initial Screening): IgA anti-Tissue Transglutaminase (anti-tTG IgA) antibody + Total serum IgA level (to exclude selective IgA deficiency). Quantitative IgA anti-endomysial antibodies (EMA IgA) provide near 100% specificity.
- Duodenal Biopsy (Gold Standard): Multiple endoscopic mucosal biopsies of the second/third portion of the duodenum demonstrating Marsh Criteria:
- Marsh 1: Increased Intraepithelial Lymphocytes (IELs $>25$ per 100 enterocytes).
- Marsh 2: Crypt hyperplasia.
- Marsh 3: Partial, subtotal, or total villous atrophy.
- Treatment: Lifelong strict Gluten-Free Diet (GFD).
- Malignancy Risk: Long-term untreated disease increases the risk of Enteropathy-Associated T-Cell Lymphoma (EATL) and small bowel adenocarcinoma.
2. Tropical Sprue
- Chronic malabsorptive disorder affecting residents of or visitors to tropical areas (e.g., India, Southeast Asia, Caribbean).
- Involves the entire small intestine (duodenum, jejunum, and ileum), leading to dual Vitamin $\text{B}_{12}$ and Folate deficiency $\rightarrow$ severe megaloblastic anemia.
- Histopathology shows blunting of villi (less severe than Celiac disease).
- Treatment: Oral Tetracycline (or Doxycycline) 250 mg QID PLUS Folic acid 5 mg daily for 3 to 6 months.
3. Whipple Disease
- Rare systemic infectious disease caused by the Gram-positive actinomycete Tropheryma whipplei.
- Classic Clinical Quadrad: Malabsorption (diarrhea, weight loss), Migratory Large Joint Arthralgias, Hyperpigmentation, and Low-grade Fever/Lymphadenopathy (may cause culture-negative endocarditis and CNS cognitive symptoms).
- Pathognomonic Histopathology: Small bowel duodenal biopsy showing PAS-positive (Periodic acid-Schiff), acid-fast negative macrophages filling the lamina propria and compressing lymphatic lacteals.
- Treatment: Intravenous Ceftriaxone (or Penicillin G) for 2–4 weeks followed by oral Trimethoprim-Sulfamethoxazole (TMP-SMX) for 12 months.
A 28-year-old male presents with chronic bloody diarrhea, lower abdominal cramping, and tenesmus. Colonoscopy discloses continuous inflammation with friable, erythematous mucosa and pseudopolyps beginning at the anal verge and extending up to the splenic flexure. Mucosal biopsies confirm crypt abscesses. What feature would strongly distinguish Crohn's Disease from Ulcerative Colitis in this clinical scenario?
A 32-year-old female presents with chronic watery diarrhea, abdominal bloating, and severe fatigue. Laboratory studies reveal microcytic anemia with a serum ferritin of 6 ng/mL (ref 15-150 ng/mL). Serological screening demonstrates an anti-tissue transglutaminase (anti-tTG) IgA level of 180 U/mL (ref < 10 U/mL). What is the gold-standard diagnostic procedure to confirm the diagnosis?
A 44-year-old male with a 10-year history of Ulcerative Colitis presents with progressive jaundice, generalized pruritus, and right upper quadrant discomfort. Laboratory testing discloses a serum alkaline phosphatase of 620 U/L (ref 40-130 U/L) and positive p-ANCA serology. Magnetic resonance cholangiopancreatography (MRCP) reveals multifocal strictures and segmental dilatations of intrahepatic and extrahepatic bile ducts ('beaded appearance'). What is the diagnosis?
A 48-year-old male presents with chronic diarrhea, weight loss, migratory polyarthritis affecting the knees and wrists, low-grade fever, and hyperpigmentation of sun-exposed skin. Endoscopic biopsy of the small intestine demonstrates dense infiltration of the lamina propria by abundant Periodic Acid-Schiff (PAS)-positive, acid-fast negative macrophages. What is the diagnosis and appropriate long-term antimicrobial regimen?