Celiac disease

Summary

Celiac disease (also called gluten-sensitive enteropathy or celiac sprue) is an autoimmune disorder of the small intestine triggered by gluten in genetically predisposed individuals (HLA-DQ2 or HLA-DQ8).

• It mainly damages the distal duodenum and proximal jejunum, leading to malabsorption and steatorrhea.
• Patients present with chronic diarrhea, bloating, weight loss, iron deficiency anemia, or failure to thrive in children.
• It is strongly associated with dermatitis herpetiformis, low bone density, and a small increased risk of enteropathy-associated T-cell lymphoma (EATL).
• Histology shows the classic triad: villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.
• Treatment is a strict lifelong gluten-free diet plus correction of nutrient deficiencies.

Epidemiology

• More common in North America, Europe, the Middle East, and Australia.
• Prevalence ~1% of the general population; many cases remain undiagnosed.
• Two peaks of presentation:
  • Infants (6 months – 2 years): shortly after gluten is introduced into the diet — classic GI symptoms.
  • Adults (30s–40s): often with subtle or extraintestinal symptoms (e.g., isolated iron deficiency anemia).
• Female predominance (~2:1).
• Strong genetic link: nearly all patients carry HLA-DQ2 (~90%) or HLA-DQ8 (~5–10%).
• Higher prevalence in patients with Down syndrome, Turner syndrome, type 1 diabetes, and first-degree relatives of celiac patients.

Etiology and Pathogenesis

Celiac disease is an autoimmune reaction triggered by gluten, a storage protein found in:

• Wheat
• Rye
• Barley
• Oats (cross-contamination; pure oats tolerated by most)

Step-by-step pathogenesis

1. Dietary gluten is partially digested to gliadin in the gut lumen.
2. Gliadin crosses the intestinal epithelium and is deamidated by the enzyme tissue transglutaminase (tTG) in the lamina propria.
3. Deamidated gliadin is presented by HLA-DQ2 or HLA-DQ8 on antigen-presenting cells to CD4+ T helper cells.
4. Activated T cells release pro-inflammatory cytokines (IFN-γ) that recruit intraepithelial lymphocytes and damage the mucosa → villous atrophy.
5. B cells produce autoantibodies: anti-tTG IgA, anti-endomysial IgA (EMA), and anti-deamidated gliadin peptide (DGP).

The end result is loss of absorptive surface area → malabsorption of nutrients, fats, and vitamins.

Associated condition: Selective IgA deficiency is the most commonly linked immunodeficiency — important because it can cause false-negative IgA-based serology.

Clinical Features

Celiac disease has a wide range of presentations — from classic GI symptoms in children to silent or extraintestinal disease in adults. See the multisystem clinical manifestations table for a complete organ-system breakdown.

Gastrointestinal symptoms

• Chronic diarrhea ± steatorrhea (bulky, foul-smelling, greasy, floating stools).
• Abdominal pain, bloating, flatulence.
• Weight loss in adults; failure to thrive in children.
• Nausea, vomiting, or constipation (less common).

Extraintestinal manifestations

• Dermatitis herpetiformis — intensely pruritic, grouped papulovesicles on extensor surfaces (elbows, knees, buttocks). Seen in 10–25% of patients. Caused by IgA deposits in the dermal papillae.
  
• Iron deficiency anemia — often the only sign in adults; may not respond to oral iron due to duodenal malabsorption.
  
• Osteopenia / osteomalacia — from vitamin D and calcium malabsorption.
• Atrophic glossitis, aphthous stomatitis.
• Easy bruising — vitamin K deficiency → prolonged PT/INR.
• Peripheral neuropathy, depression, anxiety.
• Short stature, delayed puberty in children.

Features of Malabsorption

Because the proximal small bowel is the main site of nutrient absorption, celiac disease leads to a wide variety of deficiencies. Each missing nutrient produces a distinct clinical sign — see also the full malabsorption reference table and the nutrient deficiency overview.

Diagnosis

Diagnosis follows a stepwise approach. The patient must be on a gluten-containing diet during testing — otherwise results may be falsely negative. See the celiac disease symptoms, signs & diagnosis table.

Step 1 — Serology (screening)

• Anti-tissue transglutaminase IgA (anti-tTG IgA) → first-line, most sensitive & specific.
• Anti-endomysial antibody (EMA) IgA → highly specific confirmatory test.
• Total serum IgA → always check to rule out IgA deficiency (causes false-negative tTG).
• If IgA deficient → switch to IgG-based tests: deamidated gliadin peptide IgG (DGP-IgG) or tTG-IgG.

Step 2 — Duodenal biopsy (gold standard)

An EGD with ≥4 biopsies from the distal duodenum (+ 1–2 from the bulb) confirms the diagnosis. Histology shows the classic triad:

• Villous atrophy — flattened villi reduce absorptive surface.
  
• Crypt hyperplasia — elongated crypts (compensatory proliferation).
• Intraepithelial lymphocytosis — >25 lymphocytes per 100 enterocytes (earliest finding).
  

The presence of Brunner glands in the biopsy confirms the duodenal location of the sample.

Step 3 — Response to gluten-free diet

Resolution of symptoms, normalization of antibodies, and improved villous architecture on follow-up biopsy confirm the diagnosis.

Differential Diagnosis

Many GI conditions mimic celiac disease. The combination of chronic diarrhea + nutrient deficiencies + positive serology + villous atrophy on biopsy distinguishes celiac from the alternatives below. For patients with diarrhea-predominant symptoms, also see the malabsorption syndromes comparison.

Causes of steatorrhea — reference table

Treatment

See the management of celiac disease — full table for a complete reference.

1. Strict, lifelong gluten-free diet (cornerstone)

• Avoid wheat, rye, barley. Most patients tolerate pure oats.
• Safe alternatives: rice, corn, potatoes, quinoa, buckwheat.
• Patients should read all food labels — gluten hides in sauces, processed meats, and some medications.
• Symptoms usually improve within weeks; mucosal healing takes months to years.

2. Correct nutrient deficiencies

• Iron, folate for anemia (most common deficiencies).
• Calcium + vitamin D for bone health; order a DXA scan at diagnosis to screen for osteomalacia/osteoporosis.
• Vitamin K, A if clinically deficient.

3. Specific therapies

• Dermatitis herpetiformis → gluten-free diet ± dapsone for rapid skin relief.
  
• Pneumococcal vaccination — celiac patients have functional hyposplenism.
• Follow-up serology (anti-tTG IgA) at 6 and 12 months to confirm dietary adherence.

4. Refractory celiac disease

Persistent symptoms despite a strict gluten-free diet → work through the differential systematically:

Complications and Associated Conditions

Complications

• Iron deficiency anemia — most common complication overall.
• Osteoporosis / osteomalacia — from calcium and vitamin D malabsorption → increased fracture risk.
• Infertility, recurrent miscarriage — reversible with gluten-free diet.
• Growth failure and delayed puberty in children.
• Enteropathy-associated T-cell lymphoma (EATL) — rare but feared; risk increases with poor dietary compliance.
• Small bowel adenocarcinoma — slightly increased risk.
• Ulcerative jejunitis, refractory sprue.

Associated autoimmune disorders

• Type 1 diabetes mellitus — shared HLA associations; screen celiac patients and vice versa.
• Autoimmune thyroid disease (Hashimoto, Graves).
• Selective IgA deficiency — remember: can cause false-negative serology.
• Down syndrome, Turner syndrome — increased prevalence; screen routinely.
• Primary biliary cholangitis, autoimmune hepatitis.

Dermatitis herpetiformis — the skin manifestation

Skin conditions and associated systemic diseases — DH is the pathognomonic skin finding of celiac disease, caused by granular IgA deposits at dermal papillae. Biopsy of perilesional skin with direct immunofluorescence showing granular IgA is diagnostic.

Mnemonics

Key Points for Exams – نقاط مهمة للامتحانات

• Trigger: Gluten (wheat, rye, barley) → BROW.
• Genetics: HLA-DQ2 (~90%) or HLA-DQ8.
• Site affected: Distal duodenum / proximal jejunum.
• Histology triad: Villous atrophy + crypt hyperplasia + intraepithelial lymphocytosis.
• Earliest histologic finding: Intraepithelial lymphocytosis (>25 lymphocytes per 100 enterocytes).
• Best initial test: Anti-tTG IgA (+ total serum IgA to rule out IgA deficiency).
• Gold standard: Duodenal biopsy while patient is on a gluten-containing diet.
• Classic skin sign: Dermatitis herpetiformis → treat with gluten-free diet ± dapsone.
• Adult presentation clue: Iron deficiency anemia not responding to oral iron.
• Treatment: Lifelong gluten-free diet + vitamin/mineral replacement + pneumococcal vaccine.
• Malignancy risk: Enteropathy-associated T-cell lymphoma (EATL).
• Associations: Type 1 DM, autoimmune thyroid disease, IgA deficiency, Down syndrome, Turner syndrome.

Celiac disease — comprehensive reference table · Risk factors, symptoms, diagnosis & treatment