Celiac Disease

Detailed Overview

Upon exposure to gliadin (a component of gluten), T-cells in the small intestine launch an immune response leading to crypt hyperplasia and villous blunting. This malabsorption syndrome causes diarrhea, weight loss, and nutritional deficiencies. It strictly requires the presence of HLA-DQ2 or HLA-DQ8. The only effective treatment is a lifelong, strict gluten-free diet.

Epidemiology & Demographics

Prevalence is roughly 1% of the population in North America and Europe. Female to male ratio is 2:1. Often diagnosed in early childhood or the 3rd-4th decade.

Etiological Mechanism

Autoimmune reaction to gliadin, catalyzed by tissue transglutaminase (tTG), in individuals carrying HLA-DQ2 or HLA-DQ8 haplotypes.

Primary Causes

Ingestion of gluten-containing grains: wheat, rye, and barley.

• Genetics: HLA-DQ2 (90-95% of patients) or HLA-DQ8. First-degree relatives have a 10% risk.
• Autoimmune Conditions: High overlap with Type 1 Diabetes and Autoimmune Thyroid disease.

Gluten is digested into gliadin peptides which cross the intestinal epithelium. Tissue transglutaminase (tTG) deamidates gliadin, increasing its affinity for HLA-DQ2/DQ8 receptors on antigen-presenting cells. This activates CD4+ T-cells, releasing IFN-gamma and TNF-alpha, driving tissue inflammation. Intraepithelial CD8+ T-cells directly destroy enterocytes, leading to villous atrophy, crypt hyperplasia, and loss of absorptive surface area in the duodenum/jejunum.

Characteristic Clinical Presentation

• Chronic Diarrhea: Foul-smelling, pale, bulky, greasy stools (steatorrhea).
• Weight Loss: Due to severe malabsorption of calories and nutrients.
• Fatigue: Profound lethargy, often secondary to iron, folate, or B12 deficiency anemia.

Physical Examination Signs

• Dermatitis Herpetiformis
• Muscle Wasting
• Pallor

• Osteoporosis: From malabsorption of Calcium and Vitamin D.
• Enteropathy-Associated T-Cell Lymphoma (EATL): A rare but aggressive small bowel lymphoma in refractory celiac disease.

Diagnostic Criteria & Guidelines

Positive celiac specific serology (IgA anti-tTG) while on a gluten-containing diet, confirmed by upper endoscopy with duodenal biopsies showing villous atrophy, crypt hyperplasia, and increased IELs.

Differential Diagnosis

• Irritable Bowel Syndrome (IBS)
• Crohn Disease
• Non-Celiac Gluten Sensitivity (negative serology/biopsy)

Laboratory Tests & Biomarkers

• IgA anti-Tissue Transglutaminase (tTG): Highly elevated (>10 U/mL, often 10x upper limit of normal). Requires concurrent normal total IgA to avoid false negatives.
• Complete Blood Count: Microcytic anemia (low MCV <80 fL) due to iron deficiency.
• Serum Vitamin D & Calcium: Decreased 25-OH Vitamin D and total calcium.

Imaging Modalities & Findings

• DEXA Scan:

• Marsh I
  Increased intraepithelial lymphocytes (>30 per 100 enterocytes) with normal villi.
• Marsh III
  Villous atrophy (partial to complete), crypt hyperplasia, and heavy inflammatory infiltrate.

Second-Line & Adjunctive Therapy

For Refractory Celiac Disease (persistent atrophy despite strict GFD for 12 months): Budesonide 9 mg PO daily or systemic immunosuppression (Azathioprine).

Surgical & Procedural Management

None, unless complicated by EATL or small bowel adenocarcinoma requiring resection.

Recommended Lifestyle Changes

• Consult a specialized dietitian for GFD education and avoiding cross-contamination.
• Read all labels, as gluten is hidden in many processed foods, sauces, and medications.

Patient Counseling & Advice

Stress that even trace amounts of gluten (e.g., using the same toaster) can trigger mucosal damage, even if asymptomatic.

Follow-Up & Monitoring Schedule

Repeat IgA tTG at 6 and 12 months (should normalize on GFD). Repeat duodenal biopsy in adults at 2 years to confirm mucosal healing.

Preventive Strategies

No primary prevention. Early screening in high-risk groups (Type 1 DM, Down syndrome) prevents complications.

Excellent with strict GFD adherence. Symptoms improve in weeks; mucosal healing takes 1-2 years.