Celiac Disease and Chronic Malabsorption — Examination Question Bank

Pathogenesis, Genetics & Clinical Presentation

Question	Answer
1. What is the fundamental immunopathogenesis of Celiac Disease?	Celiac Disease (Gluten-Sensitive Enteropathy) is a chronic, immune-mediated systemic disorder triggered by the ingestion of dietary gluten (specifically the alcohol-soluble gliadin fraction of wheat, and homologous prolamins: secalin in rye, hordein in barley) in genetically susceptible individuals carrying HLA-DQ2 or HLA-DQ8. - Luminal digestion of gliadin yields resistant 33-mer peptide fragments that pass through the epithelial barrier. - In the lamina propria, the enzyme tissue transglutaminase 2 (tTG-2) deamidates neutral glutamine residues into negatively charged glutamic acid. - This deamidation creates a high-affinity binding motif for the positively charged peptide-binding groove of HLA-DQ2/DQ8 on antigen-presenting cells (APCs). - APCs present deamidated gliadin to CD4+ T helper cells, triggering the release of pro-inflammatory cytokines (IFN-gamma, TNF-alpha), driving mucosal destruction, and inducing B cells to produce antibodies against tTG, endomysium, and deamidated gliadin peptides (DGP). - Simultaneously, stress-induced epithelial IL-15 reprograms CD8+ intraepithelial lymphocytes (IELs) into natural killer-like killer cells expressing NKG2D, which lyse enterocytes expressing MIC-A/B, causing total villous atrophy, crypt hyperplasia, and mucosal destruction.
2. Detail the HLA genetics of Celiac Disease and its clinical utility.	- $>90-95\%$ of celiac patients express the HLA-DQ2.5 heterodimer encoded by the alleles DQA105:01* and DQB102:01* (in cis on DR3-DQ2 or in trans on DR11-DQ7 / DR7-DQ2). - The remaining $5-10\%$ carry HLA-DQ8 encoded by DQA103:01* and DQB103:02. - Clinical Utility:* The presence of HLA-DQ2/DQ8 has very poor positive predictive value because $30-40\%$ of the healthy general population carry these alleles. - However, the negative predictive value of HLA-DQ2 and HLA-DQ8 is almost 99-100%. Absence of both HLA-DQ2 and DQ8 virtually excludes the diagnosis of celiac disease!
3. What are the classic vs non-classic vs silent vs potential forms of Celiac Disease?	- Classical Celiac Disease: Presents with gastrointestinal malabsorptive symptoms: chronic diarrhea, steatorrhea, abdominal distension, failure to thrive, anorexia, and muscle wasting. - Non-Classical Celiac Disease: Gastrointestinal complaints are absent or atypical; presents with extraintestinal manifestations: refractory iron deficiency anemia, short stature, recurrent aphthous stomatitis, dental enamel hypoplasia, osteopenia/rickets, transaminitis, or chronic constipation. - Silent / Asymptomatic Celiac Disease: No recognizable symptoms, but serology positive and small intestinal biopsy demonstrates villous atrophy (often discovered during screening of high-risk cohorts: T1DM, Down syndrome, first-degree relatives). - Potential Celiac Disease: Positive celiac serology (anti-tTG IgA), but small bowel mucosal architecture is histologically normal (Marsh 0 or 1).

Diagnostic Criteria & Histopathology

Question	Answer
4. Explain the updated ESPGHAN Guidelines (2020) for diagnosing Celiac Disease, including the "No-Biopsy" approach.	The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2020 guidelines allow a biopsy-free diagnosis in pediatric patients who fulfill all of the following criteria: 1) Quantitative Serum Total IgA: Must be measured concurrently to rule out selective IgA deficiency. 2) Serum Anti-tTG IgA Level: Must be $\ge 10 imes$ the Upper Limit of Normal ($\ge 10 imes$ ULN) of the laboratory assay. 3) Positive Anti-Endomysial Antibodies (EMA-IgA): Must be confirmed on a second, independent blood sample drawn on a separate occasion. 4) If both criteria are met, the positive predictive value exceeds $99\%$, and a diagnostic duodenal biopsy is NOT required. Note on HLA testing: ESPGHAN 2020 removed HLA typing from the required routine diagnostic algorithm for the no-biopsy approach.
5. How do you approach diagnosis if Total Serum IgA is deficient?	Selective IgA deficiency occurs in $2-3\%$ of celiac patients (10 to 15 times higher than the general population). - If total serum IgA is $<0.2 ext{ g/L}$ (below age-specific cutoffs), all IgA-based serologies (anti-tTG IgA, EMA IgA) will yield false-negative results. - Protocol: Test for IgG-based serologies: specifically Anti-Deamidated Gliadin Peptide IgG (anti-DGP IgG) and/or Anti-tTG IgG. - In IgA-deficient children, an upper gastrointestinal endoscopy with multiple duodenal biopsies is mandatory.
6. Describe the Marsh-Oberhuber Histopathological Classification.
7. How many biopsies must be taken, and from where?	A minimum of 4 to 6 oriented endoscopic biopsies must be obtained: - At least 1 to 2 biopsies from the duodenal bulb (at 9 o'clock and 12 o'clock positions, because villous atrophy can be patchy and confined solely to the bulb in up to $10\%$ of children). - At least 4 biopsies from the second and third parts of the duodenum (D2/D3).

Management, Complications & Viva Traps

Question	Answer
8. Detail the Gluten-Free Diet (GFD) prescription and monitoring.	- Strict Lifelong Elimination: Total exclusion of all foods, medications, and products containing wheat, barley, rye, and triticale. - Safe Grains: Rice, corn (maize), millet (ragi, bajra, jowar), sorghum, buckwheat, amaranth, quinoa, soy, and certified gluten-free uncontaminated oats. - Threshold: Safe gluten threshold is $<20 ext{ ppm}$ ($<20 ext{ mg/kg}$) according to Codex Alimentarius. - Monitoring: - Clinical: Rapid symptom resolution (irritability resolves within 48-72 hours; stool normalization in 2-4 weeks; catch-up growth within 3-6 months). - Serological: Recheck anti-tTG IgA titers at 6 months and 12 months; titers should fall progressively and normalize within 12-24 months.
9. VIVA TRAP: What is a "Celiac Crisis" and how is it managed in emergency?	Celiac Crisis is a rare, life-threatening acute presentation of celiac disease characterized by severe explosive watery diarrhea, hypokalemia, profound metabolic acidosis, hypoproteinemia with anasarca, and cardiovascular instability. - Emergency Management: 1) Resuscitation: IV isotonic fluids ($0.9\%$ Normal Saline) to restore intravascular volume. 2) Electrolyte Correction: Correct hypokalemia with IV potassium chloride (max $40 ext{ mEq/L}$ via peripheral line). Correct hypomagnesemia and hypocalcemia. 3) Nutritional Support: Parenteral nutrition or hydrolyzed elemental formula. 4) Systemic Corticosteroids: IV Methylprednisolone ($1-2 ext{ mg/kg/day}$) or oral Prednisolone ($1-2 ext{ mg/kg/day}$) for 1-2 weeks, which dramatically induces enterocyte brush border reconstitution and arrests secretory loss, followed by a slow taper once strict GFD is instituted.
10. VIVA TRAP: What are the high-risk screening groups for Celiac Disease?	Routine active screening using anti-tTG IgA is mandatory in: 1) Type 1 Diabetes Mellitus ($5-10\%$ prevalence). 2) Autoimmune Thyroiditis (Hashimoto) and Autoimmune Hepatitis. 3) Down Syndrome ($7-16\%$ prevalence), Turner Syndrome ($5\%$), and Williams Syndrome. 4) First-degree relatives of biopsy-proven celiac patients ($10-15\%$ prevalence). 5) Selective IgA Deficiency.