3.4 Celiac Disease & Irritable Bowel Syndrome
Key Takeaways
- Tissue transglutaminase IgA testing requires a simultaneous total IgA level, because selective IgA deficiency is over-represented in celiac disease and produces false-negative results.
- Serology and biopsy are only interpretable while the patient is consuming gluten; a gluten-free diet before testing invalidates both.
- Dermatitis herpetiformis is the cutaneous manifestation of celiac disease and is itself sufficient to establish the diagnosis in the right serologic context.
- Irritable bowel syndrome is diagnosed from recurrent abdominal pain related to defecation or a change in stool form or frequency, in the absence of alarm features.
- Alarm features including onset after age 50, weight loss, nocturnal symptoms, bleeding, anemia or a family history of colorectal cancer or inflammatory bowel disease mandate further evaluation.
Last updated: August 2026
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
[!WARNING] Patients MUST be on a gluten-containing diet (at least 1–2 slices of wheat bread daily for 6–8 weeks) at the time of serologic and histologic testing. Testing while on a gluten-free diet causes false-negative results.
- 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 ($ ext{total IgA} < 20 ext{ mg/dL}$), tTG-IgA will be falsely negative. In this setting, order IgG-based testing: Deamidated Gliadin Peptide IgG (DGP-IgG) or tTG-IgG.
- 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:
- Intraepithelial lymphocytosis ($>25$ intraepithelial lymphocytes per 100 enterocytes).
- Crypt hyperplasia.
- Blunting and total atrophy of intestinal villi (villous flattening).
- 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:
- Related to defecation (either improved or worsened by defecation).
- Associated with a change in the frequency of stool.
- 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
| IBS Subtype | First-Line & Dietary Interventions | Targeted Pharmacotherapy Options |
|---|---|---|
| All Subtypes | • Low-FODMAP diet (Fermentable Oligo-, Di-, Monosaccharides, and Polyols)<br/>• Soluble Fiber (Psyllium / Ispaghula husk 20–30 g/day; avoid insoluble bran which worsens gas/bloating) | • Tricyclic Antidepressants (TCAs): Amitriptyline, Desipramine (10–50 mg qhs for visceral pain neuromodulation via anticholinergic and central analgesic effects). |
| IBS-D | • Dietary avoidance of lactose, caffeine, artificial sweeteners | • Loperamide (2–4 mg prn 30 min before meals)<br/>• Antispasmodics: Dicyclomine (10–20 mg QID), Hyoscyamine<br/>• Rifaximin: 550 mg TID for 14 days (non-absorbable antibiotic, can be repeated up to 2 times for recurrent symptoms)<br/>• Eluxadoline: Mixed $\mu$-opioid receptor agonist (100 mg BID; contraindicated in patients without a gallbladder, history of pancreatitis, or alcohol excess due to risk of sphincter of Oddi spasm). |
| IBS-C | • Increased fluid intake, regular aerobic exercise | • Osmotic Laxative: Polyethylene Glycol (PEG 3350, 17 g daily)<br/>• Secretagogues:<br/> - Lubiprostone: Chloride channel (ClC-2) activator (8 mcg BID for women)<br/> - Linaclotide: Guanylate cyclase-C agonist (72–290 mcg daily)<br/> - Plecanatide: Guanylate cyclase-C agonist (3 mg daily)<br/>• Prokinetic: Prucalopride (selective 5-HT4 receptor agonist, 1–2 mg daily). |
Test Your Knowledge
A 34-year-old man presents with chronic watery diarrhea, bloating, a 12-lb weight loss, and an intensely pruritic vesicular rash symmetrically distributed over his extensor elbows and knees. Laboratory evaluation reveals a total serum IgA level of 8 mg/dL (reference range: 70–400 mg/dL) and a negative serum IgA tissue transglutaminase (tTG-IgA) antibody titer. What is the most appropriate next step in establishing the diagnosis?
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D