1. 1. Definition
   1. Autoimmune disorder
   2. Trigger: Gluten (wheat, rye, barley)
   3. Permanent intolerance
   4. Affects proximal small intestine - mucosa flattening
   5. Genetically susceptible individuals
   6. presentation: 6m - 2y
2. 2. normally
   1. ⚙️ Gluten proteins contains
      1. Glutenin (easily digested)
      2. Gliadin (has difficult digested amino acids)
   2. gluten from diet
      1. small intestin lamina propria
         1. digested in dendritic cells and deamidated by tissue transglutaminase II
3. 3. Celiac Pathophysiology
   1. innate immune system activation
      1. IL-15 is released
   2. dendritic cells recognize gluten as a foreign body
      1. gluten presented via HLA-DQ2/DQ8
         1. T-helper cells activated
            1. produce cytokines and activate B-Cells
            2. produce antibodies to gluten
            3. villous atrophy
            4. crypt hyperplasia
            5. surface epithelium damage
            6. systemic inflammatory response
4. 4. Associated Conditions
   1. 1. 🧬 IgA Deficiency
   2. 2. 🏥 Hyposplenism
   3. 3. 🧪 Abnormal Liver Function Tests
   4. 4. 🔄 Autoimmune Disorders
      1. **Type 1 Diabetes Mellitus**
      2. **Hypothyroidism**
      3. **Primary Biliary Cirrhosis**
      4. **Microscopic Colitis**
   5. 5. 🧠 Down Syndrome
5. 3. Epidemiology
   1. 95% have HLA-DQ2 / DQ8
   2. Higher prevalence in women
   3. ↑ Risk in:
      1. 1st-degree relatives (10–20%)
      2. Monozygotic twins (75%)
   4. Rare in Japanese population
6. 4. Clinical Presentations
   1. A. Typical
      1. GI symptoms: Diarrhea, constipation, failure to thrive, anemia, vitamin deficiencies, behavioral changes
      2. Celiac crisis in infants (rare)
   2. B. Atypical
      1. Extraintestinal: Dermatitis herpetiformis, Dental enamel hypoplasia, anemia, delayed puberty, hepatitis, arthritis, osteiopnea, psychiatric & neurological issues
   3. C. Silent
      1. No symptoms but mucosal damage and positive serology
   4. D. Potential
      1. Positive serology, normal mucosa, may progress
   5. E. Latent
      1. History of gluten-sensitive enteropathy, normal mucosa
7. 5. Differential Diagnosis
   1. Cystic fibrosis
   2. Milk protein enteropathy
   3. IBD
   4. Giardiasis
   5. Pancreatic enzyme deficiency
   6. Immunodeficiency
   7. Neuroblastoma
   8. Toddler’s diarrhea
   9. Lymphoma
   10. Carcinoid syndrome
8. 6. Diagnosis 🧪
   1. A. Serology (1st-line)
      1. Anti-tTG (IgA): High sensitivity/specificity
      2. EMA (IgA): Confirm equivocal tTG
      3. AGA (IgG/IgA): Useful in <18 months
      4. DGP: Better for IgA deficiency/ most reliable test
   2. B. Genetics
      1. HLA-DQ2/DQ8 → Rule out if negative
   3. C. Endoscopy + Biopsy (Gold Standard)
      1. ≥4 duodenal biopsies
      2. Endoscopic findings: scalloping, mosaic pattern, loss of folds, prominence of the submucosa blood vessels, nodular pattern to the mucosa
   4. D. Other Tests
      1. DEXA scan
      2. CBC, iron studies
      3. Thyroid function test
   5. E. Histology (Marsh Classification)
      1. Type 0 to Type 3c: Progressive damage
9. 7. Treatment
   1. Lifelong gluten-free diet
   2. Monitor antibodies for compliance
   3. Vitamin/mineral supplementation
   4. Enzyme therapy (future)
   5. Refractory cases: Immunosuppressants
10. 8. Complications
    1. Osteoporosis
    2. Anemia
    3. Pregnancy issues
    4. GI malignancies (EATL)
    5. Refractory celiac disease
11. 9. Prognosis ✅
    1. Excellent with strict diet
    2. Symptoms and labs normalize within months