Celiac Disease

Celiac Basics - Gluten's Gut Grudge

• Chronic small intestinal immune-mediated enteropathy triggered by dietary gluten.
• Genetic Susceptibility: Primarily HLA-DQ2 (90-95%) and HLA-DQ8 (5-10%).
• Trigger: Gluten (gliadin protein) in Wheat, Rye, Barley. (📌 Mnemonic: Avoid B.R.O.W. - Barley, Rye, Oats*, Wheat. *Oats often contaminated).
• Pathophysiology:
  • Ingested gluten (gliadin) is deamidated by tissue transglutaminase (tTG).
  • Deamidated gliadin presented by APCs (via HLA-DQ2/DQ8) to CD4+ T-cells.
  • Leads to mucosal inflammation: villous atrophy, crypt hyperplasia, ↑Intraepithelial Lymphocytes (IELs).

⭐ Strongest genetic association is with HLA-DQ2.5.

Symptom Spectrum - The Celiac Chameleon

• Gastrointestinal (GI) - Common in younger children:
  • Chronic diarrhea (steatorrhea: pale, foul, bulky stools)
  • Failure to Thrive (FTT), weight loss
  • Abdominal distension, pain, bloating
  • Vomiting, anorexia
  • Constipation (less common, may occur in older children)
• Extra-intestinal Manifestations (EIMs) - "The Chameleon", esp. older children/adolescents:
  • Iron Deficiency Anemia (IDA) - often refractory to oral iron
  • Short stature, delayed puberty
  • Dermatitis Herpetiformis (DH) - intensely itchy vesicles (elbows, knees, buttocks)
  • Dental enamel defects (permanent dentition)
  • Recurrent aphthous stomatitis
  • Osteopenia/Osteoporosis, arthralgia
  • Elevated transaminases (unexplained)
• Silent/Latent Celiac Disease:
  • Asymptomatic or minimal symptoms despite positive serology/histology.

⭐ Dermatitis herpetiformis is a highly specific skin manifestation; biopsy of unaffected perilesional skin shows granular IgA deposits at the dermoepidermal junction.

Diagnostic Drill‑Down - Confirming Celiac

• Initial Serology (on gluten diet):
  • IgA anti-tissue Transglutaminase (IgA-tTG) - preferred.
  • Total IgA (rule out IgA deficiency).
  • If IgA deficient: IgG-tTG, IgG-Deamidated Gliadin Peptide (DGP).
• ESPGHAN Guidelines (2020) - Symptomatic Children:
  • IgA-tTG > 10x ULN: Confirm with IgA Endomysial Antibody (EMA) (2nd sample).
    • If both positive + HLA-DQ2/DQ8 positive (supportive) → Diagnosis without biopsy.
  • IgA-tTG < 10x ULN or EMA negative → Duodenal biopsy.
• Duodenal Biopsy:
  • Gold standard; multiple samples (D2/D3, bulb).
  • Histopathology: Marsh-Oberhuber Classification.
    • Marsh 0: Normal.
    • Marsh I: ↑IELs (>25/100 enterocytes).
    • Marsh II: Crypt hyperplasia.
    • Marsh III (a,b,c): Villous atrophy (mild, marked, total).

  ⭐ Marsh IIIc (total villous atrophy) is classic in symptomatic celiac disease.

• Genetic Testing:
  • HLA-DQ2/DQ8: High negative predictive value (rules out if negative).

Treatment & Troubles - Gluten‑Free & Beyond

• Gluten-Free Diet (GFD): Cornerstone
  • Lifelong, strict: No Wheat, Rye, Barley, Oats (📌 WRBO: We Read Big Outs).
  • Safe: Rice, Corn, Millets, Soya, Potato.
  • Beware: Hidden gluten (processed foods, meds). Dietician vital.
• Nutritional Support:
  • Correct deficiencies: Fe, Folate, B12, Vit D, Ca, Zn.
  • Lactose intolerance: Often transient.
• Monitoring & Follow-up:
  • Clinical improvement: Weeks.
  • Serology (tTG-IgA): Normalizes in 6-12 months.
  • Assess growth & GFD adherence.
• Troubles & Associations:
  • Persistent symptoms: Poor GFD adherence commonest.

    ⭐ Poor GFD adherence: #1 cause of non-response.

  • Refractory Celiac Disease (RCD): Rare.
  • Long-term risks: Osteoporosis, anemia, infertility, malignancy (EATL), autoimmune (T1DM, thyroiditis).
  • Vaccination: Pneumococcal (due to hyposplenism risk).

High‑Yield Points - ⚡ Biggest Takeaways

• Celiac disease: Immune reaction to gluten in genetically susceptible individuals (HLA-DQ2/DQ8).
• Presents with chronic diarrhea, malabsorption, weight loss, or anemia; failure to thrive in children.
• Dermatitis herpetiformis is a highly specific skin manifestation.
• Serology: IgA anti-tTG is the preferred initial test; IgA EMA for confirmation.
• Duodenal biopsy showing villous atrophy, crypt hyperplasia, and ↑IELs is diagnostic.
• Lifelong strict gluten-free diet (GFD) is the only treatment.
• Untreated: ↑ risk of lymphoma (e.g., EATL).