3.4 Celiac Disease & Irritable Bowel Syndrome

1. Celiac Disease (Gluten-Sensitive Enteropathy)

Pathophysiology & Genetics

• Autoimmune enteropathy triggered by ingestion of dietary gluten (specifically the gliadin peptide fraction found in wheat, rye, and barley).
• Strongly associated with Human Leukocyte Antigens HLA-DQ2 (95%) and HLA-DQ8 (5%).

Clinical Manifestations

• Gastrointestinal: Chronic osmotic/secretory diarrhea, steatorrhea (pale, bulky, foul-smelling stools), flatulence, abdominal bloating, and weight loss.
• Extraintestinal / Malabsorptive: Refractory iron deficiency anemia, premature osteopenia/osteoporosis (calcium/vitamin D malabsorption), aphthous stomatitis, elevated transaminases, peripheral neuropathy, and ataxia.
• Dermatitis Herpetiformis: Pathognomonic cutaneous manifestation characterized by intensely pruritic, grouped, polymorphic erythematous papules and vesicles distributed symmetrically over the extensor surfaces (elbows, knees, buttocks, scalp, upper back).
  • Diagnosis: Direct immunofluorescence (DIF) of perilesional skin punch biopsy demonstrates granular IgA deposition in the dermal papillae.
  • Treatment: Strict lifelong gluten-free diet and oral Dapsone (must check baseline G6PD level to prevent acute hemolytic anemia).

Diagnostic Evaluation

1. Step 1 — Serologic Testing:
   • Order serum IgA Tissue Transglutaminase (tTG-IgA) antibody PLUS Total Serum IgA.
   • The Total IgA Pitfall: Patients with Celiac disease have a 10- to 15-fold higher prevalence of Selective IgA Deficiency. In patients with IgA deficiency ($\text{total IgA} < 20\text{ mg/dL}$), tTG-IgA will be falsely negative. In this setting, order IgG-based testing: Deamidated Gliadin Peptide IgG (DGP-IgG) or tTG-IgG.
2. Step 2 — Confirmatory Endoscopy & Histopathology:
   • EGD with multiple duodenal mucosal biopsies (1–2 biopsies from the duodenal bulb and $\ge 4$ biopsies from the second/third portion of the duodenum).
   • Marsh Classification Hallmark Findings:
     1. Intraepithelial lymphocytosis ($>25$ intraepithelial lymphocytes per 100 enterocytes).
     2. Crypt hyperplasia.
     3. Blunting and total atrophy of intestinal villi (villous flattening).
3. Long-Term Management & Complications:
   • Strict lifelong Gluten-Free Diet (eliminate wheat, barley, rye; pure uncontaminated oats are generally safe in moderation).
   • Monitor adherence by checking tTG-IgA serology at 6 and 12 months post-dietary initiation.
   • Perform baseline DEXA scan for metabolic bone disease; replenish iron, folate, B12, vitamin D, and zinc.
   • Malignancy Risk: Increased risk of Enteropathy-Associated T-Cell Lymphoma (EATL) and small bowel adenocarcinoma in patients with refractory or poorly controlled disease.

2. Irritable Bowel Syndrome (IBS)

Irritable Bowel Syndrome (IBS) is a disorder of gut-brain interaction characterized by recurrent abdominal pain associated with altered bowel habits.

Rome IV Diagnostic Criteria

Recurrent abdominal pain on average at least 1 day per week in the last 3 months, with symptom onset at least 6 months prior, associated with $\ge 2$ of the following features:

1. Related to defecation (either improved or worsened by defecation).
2. Associated with a change in the frequency of stool.
3. Associated with a change in the form (appearance) of stool (according to the Bristol Stool Form Scale).

IBS Subtypes (Bristol Stool Scale)

• IBS-D (Diarrhea-predominant): $>25\%$ stools Bristol types 6–7 (loose/watery) and $<25\%$ Bristol types 1–2 (hard/lumpy).
• IBS-C (Constipation-predominant): $>25\%$ stools Bristol types 1–2 and $<25\%$ Bristol types 6–7.
• IBS-M (Mixed): $>25\%$ stools Bristol types 1–2 AND $>25\%$ Bristol types 6–7.

Red Flag Alarm Features (Requiring Organic Workup / Colonoscopy)

• Age $\ge 50$ years at symptom onset without prior CRC screening.
• Unexplained unintentional weight loss.
• Nocturnal diarrhea waking the patient from sleep.
• Overt rectal bleeding or melena.
• Unexplained iron deficiency anemia.
• Family history of colorectal cancer, IBD, or celiac disease.
• Palpable abdominal mass or lymphadenopathy.

Evidence-Based Pharmacotherapy