352.1 🎓 醫孞生版

352.1.0.1 📌 䞀頁重點

352.1.0.1.1 Celiac Disease

352.1.1 Epidemiology

  • ~ 1% Caucasian / European
  • Lower in Asian (~ 0.5%); rising
  • Female 2:1 vs male
  • Family clustering
  • HLA-DQ2 (95%) + HLA-DQ8 (5%) — necessary but not sufficient

352.1.2 Pathogenesis

  • Gluten (wheat, barley, rye) → gliadin
  • HLA-DQ2/DQ8 presents to T cells
  • T-cell mediated villous atrophy
  • Tissue transglutaminase autoantibody
  • Inflammatory damage

352.1.3 Clinical Spectrum

Classic Celiac: - Diarrhea (sometimes steatorrhea) - Malabsorption - Weight loss - Failure to thrive (pediatric) - Bloating, gas

Non-Classic Celiac: - Iron deficiency anemia (most common) - Osteoporosis - Vitamin D, K deficiency - Infertility, miscarriage - Dermatitis herpetiformis (pathognomonic; IgA deposits) - Neurologic (ataxia, neuropathy, encephalopathy) - Fatigue, depression - Aphthous stomatitis - Dental enamel defects

Silent Celiac: - Asymptomatic - Found on screening (family screening, T1DM, etc.)

352.1.4 Associated Conditions

  • Type 1 Diabetes Mellitus (5-10% T1DM have celiac)
  • Autoimmune thyroid disease (Hashimoto, Graves)
  • IgA deficiency (10-fold higher; tTG IgG needed)
  • Down syndrome
  • Turner syndrome
  • Williams syndrome
  • Selective IgA deficiency
  • Microscopic colitis
  • Liver disease (PBC, autoimmune hepatitis)
  • Sjögren syndrome

352.1.5 Diagnosis

Serology (Critical): - Anti-tissue transglutaminase IgA (anti-tTG IgA) — preferred initial screen - Total serum IgA — check for deficiency - If IgA deficient: anti-tTG IgG, anti-DGP IgG - Anti-endomysial antibody (EMA) — confirmatory, expensive - Anti-gliadin antibodies (older, less specific)

Duodenal Biopsy (Gold Standard): - During EGD - 4-6 samples from distal duodenum + bulb - Marsh classification: - Marsh 1: intraepithelial lymphocytosis (IEL) - Marsh 2: + crypt hyperplasia - Marsh 3a-c: + villous atrophy (partial, subtotal, total) - Must be on gluten diet for valid testing (challenge or while on gluten)

Genetic Testing (HLA-DQ2/DQ8): - Negative predictive value high (rules out) - Positive doesn’t confirm - Useful for family screening, ambiguous cases, IgA deficiency

Diagnostic Criteria (ESPGHAN 2020 Pediatric): - High anti-tTG IgA (> 10x ULN) + EMA + HLA-DQ2/DQ8: can avoid biopsy - Otherwise biopsy

352.1.6 Treatment

Gluten-Free Diet (GFD) — Lifelong: - Strict avoidance of wheat, barley, rye - Oats: usually safe but cross-contamination risk - Dietitian guidance - Reading food labels (gluten-free certification < 20 ppm) - 70-80% improve histologically; 90%+ symptom improvement

Refractory Celiac: - Persistent symptoms + histology despite GFD ≥ 12 months - Type I (no clonal IEL) vs Type II (clonal IEL — risk for EATL — enteropathy-associated T-cell lymphoma) - Workup: rule out gluten contamination, other diagnoses - Treatment: budesonide, AZA, biologics, autologous SCT

Emerging Therapies: - Latiglutenase (ALV003): gluten-degrading enzymes - Larazotide acetate (AT-1001): tight junction modulator - Cell-based therapies: investigational

Vaccinations + Adjunctive: - Pneumococcal (functional asplenia) - Vitamin + mineral supplementation - DEXA scan - Liver function periodic

352.1.6.0.1 Other Malabsorption Syndromes

352.1.7 Tropical Sprue

  • Tropical countries (esp Asia)
  • Bacterial overgrowth + nutritional
  • Diarrhea + weight loss + folate/B12 deficiency
  • Treatment: tetracycline + folate + B12

352.1.8 Whipple Disease

  • Tropheryma whipplei (rare)
  • Multi-systemic
  • Arthralgia → GI → neurologic
  • Diagnosis: PAS-positive macrophages in lamina propria; PCR
  • Treatment: IV ceftriaxone × 2-4 weeks → TMP-SMX × 1 year

352.1.9 AIDS Enteropathy

  • HIV + opportunistic infections
  • Cryptosporidium, microsporidia, MAC
  • Treatment of opportunistic + ART

352.1.10 Pancreatic Insufficiency

  • Chronic pancreatitis, CF, pancreatic cancer
  • Steatorrhea + malabsorption
  • Fecal elastase < 200 ÎŒg/g
  • Treatment: pancreatic enzyme replacement (PERT) + ADEK vitamins

352.1.11 Bile Salt Deficiency

  • Cholestasis (cirrhosis, PBC)
  • Ileal resection / disease
  • Bacterial overgrowth
  • Fat malabsorption
  • Treatment: address underlying; cholestyramine for bile acid diarrhea

352.1.12 Lymphangiectasia

  • Intestinal lymphatic dilatation
  • Protein-losing enteropathy
  • Hypoalbuminemia, edema
  • Treatment: low-fat MCT diet

352.1.13 Short Bowel Syndrome

  • Resection of significant bowel
  • Malabsorption
  • TPN, special diets, teduglutide (GLP-2 analog)
352.1.13.0.1 Small Intestinal Bacterial Overgrowth (SIBO)

352.1.14 Pathophysiology

  • Excessive bacterial colonization of small bowel
  • Usually > 10^5 organisms/mL
  • Causes: small bowel stasis (motility issues), structural (diverticula, surgery), achlorhydria

352.1.15 Risk Factors

  • Diabetes (autonomic neuropathy)
  • Scleroderma
  • Post-bariatric surgery
  • Roux-en-Y gastric bypass
  • Diverticula (small bowel)
  • Crohn’s disease
  • Achlorhydria (PPI, autoimmune gastritis)
  • Cirrhosis
  • Elderly

352.1.16 Clinical

  • Bloating
  • Diarrhea (sometimes steatorrhea)
  • Abdominal pain
  • Weight loss
  • Vitamin B12 deficiency (some)
  • Iron deficiency
  • Malabsorption

352.1.17 Diagnosis

  • Hydrogen breath test (lactulose or glucose) — most common
  • Methane breath test (methanogens)
  • Jejunal aspirate culture (gold standard, rarely done)
  • Clinical context

352.1.18 Treatment

  • Rifaximin (550 mg TID × 14 days) — first-line
  • Alternatives: norfloxacin, metronidazole, ciprofloxacin
  • Recurrent (50%+): re-treatment + address underlying
  • Treat underlying motility / structural issues
  • Prokinetics (metoclopramide, prucalopride)
  • Diet (low FODMAP for some)
352.1.18.0.1 Lactose Intolerance

352.1.19 Definition

  • Lactase deficiency → unmetabolized lactose
  • Fermentation by colonic bacteria → gas, bloating, diarrhea

352.1.20 Subtypes

  • Primary lactase deficiency (most common — Asians, African, Native American descent)
  • Secondary (post-gastroenteritis, celiac, Crohn’s, after antibiotics)
  • Congenital (rare; infant)

352.1.21 Diagnosis

  • Hydrogen breath test
  • Lactose tolerance test (less common)
  • Lactose elimination + reintroduction
  • Genetic testing (lactase persistence variants)

352.1.22 Treatment

  • Lactose restriction
  • Lactose-free dairy
  • Lactase enzyme supplements (Lactaid)
  • Yogurt (live cultures) often tolerated
352.1.22.0.1 Specific Malabsorption Workup

352.1.23 Steatorrhea

  • Fecal fat > 7-9 g/day
  • Sudan stain (qualitative)
  • 72-h quantitative
  • Causes: pancreatic insufficiency, bile salt deficiency, mucosal disease

352.1.24 Carbohydrate Malabsorption

  • Lactose, fructose, sorbitol
  • Breath tests

352.1.25 Protein Malabsorption

  • Less common
  • Alpha-1 antitrypsin clearance (protein-losing enteropathy)
  • Hypoalbuminemia

352.1.26 Vitamin Deficiencies

  • B12 (terminal ileum, gastric, IF deficiency)
  • Folate (jejunum)
  • Iron (duodenum, jejunum)
  • Vitamin A, D, E, K (fat-soluble — bile + pancreas)

352.1.26.1 🩺 床邊速查

  • Celiac: anti-tTG IgA + total IgA + duodenal biopsy (villous atrophy); HLA-DQ2/DQ8; lifelong GFD
  • Refractory celiac: rule out gluten contamination + workup; Type II → EATL risk
  • Dermatitis herpetiformis: pathognomonic for celiac
  • SIBO: hydrogen breath test; rifaximin 550 TID × 14 d
  • Lactose intolerance: hydrogen breath test; lactose restriction + Lactaid
  • Pancreatic insufficiency: fecal elastase + PERT + ADEK vitamins
  • Whipple: PAS-positive macrophages + IV ceftriaxone → TMP-SMX 1 year
  • Tropical sprue: tetracycline + folate + B12