Celiac Disease for USMLE Step 3

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Celiac Disease for USMLE Step 3

Definition

Celiac Disease (CD): A chronic autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. It leads to inflammation and damage of the small intestine, primarily affecting the duodenum and proximal jejunum, causing malabsorption of nutrients.

Pathophysiology

Gluten Sensitivity: Gluten (found in wheat, barley, and rye) is deamidated by tissue transglutaminase (tTG) in the small intestine. In patients with HLA-DQ2 or HLA-DQ8 alleles, deamidated gluten peptides are presented by antigen-presenting cells to T-cells, triggering an immune response.

Villous Atrophy: Chronic immune-mediated inflammation leads to destruction of the villi, causing malabsorption.
Crypt Hyperplasia: Increased crypt cell production as a compensatory response.
Intraepithelial Lymphocytosis: Elevated numbers of T-lymphocytes in the intestinal epithelium due to chronic inflammation.

Risk Factors

Genetics: Presence of HLA-DQ2/DQ8 alleles is necessary but not sufficient for developing celiac disease.
Family History: First-degree relatives of affected individuals have a higher risk.
Associated Autoimmune Diseases: Celiac disease is frequently associated with autoimmune disorders like type 1 diabetes, autoimmune thyroiditis, and Sjögren’s syndrome.

Clinical Features

Gastrointestinal Symptoms

Diarrhea: Chronic, foul-smelling, and greasy due to malabsorption of fat (steatorrhea).
Weight Loss: Often seen in untreated or severe cases due to nutrient malabsorption.
Abdominal Pain and Bloating: Common symptoms due to intestinal inflammation and fermentation of unabsorbed nutrients.
Iron Deficiency Anemia: Frequently caused by impaired iron absorption in the duodenum.

Extraintestinal Manifestations

Dermatitis Herpetiformis: A pathognomonic pruritic, blistering skin rash commonly found on the extensor surfaces (e.g., elbows, knees, buttocks).
Neurological Symptoms: Peripheral neuropathy and ataxia, possibly related to nutrient deficiencies or direct immune-mediated effects.
Fatigue: Nonspecific but common, improving with gluten-free diet.
Infertility: Untreated celiac disease can lead to infertility and adverse pregnancy outcomes, such as miscarriage and preterm delivery.

Diagnosis

Serologic Testing

IgA Anti-Tissue Transglutaminase (tTG) Antibodies: The preferred screening test due to high sensitivity and specificity.

IgA Deficiency: More common in patients with celiac disease, requiring measurement of IgG tTG or IgG deamidated gliadin peptides (DGP) in such cases.

IgA Endomysial Antibodies (EMA): Highly specific but less commonly used due to cost.

Small Bowel Biopsy

Gold Standard: Endoscopy with duodenal biopsy showing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis confirms the diagnosis. Multiple biopsies are recommended due to patchy involvement of the intestine.

Genetic Testing

HLA-DQ2/DQ8 Testing: Helpful in ruling out celiac disease when these alleles are absent. However, their presence is not diagnostic due to their prevalence in the general population.

Management

Gluten-Free Diet (GFD)

Lifelong Gluten-Free Diet: The only effective treatment. Patients must avoid all gluten-containing foods (wheat, rye, barley). Even small amounts of gluten can trigger symptoms and cause intestinal damage.

Symptom Improvement: GI symptoms usually resolve within weeks, but histological healing of the intestinal mucosa may take months to years.

Nutritional Support

Vitamin and Mineral Supplementation: Deficiencies in iron, calcium, vitamin D, and folic acid should be corrected.
Dietary Counseling: Education on hidden sources of gluten and cross-contamination is essential for adherence to the diet.

Monitoring

Serologic Testing: Repeat testing for IgA tTG 6–12 months after initiating a gluten-free diet to assess adherence and mucosal healing.
Repeat Endoscopy: Indicated in patients with persistent symptoms despite strict gluten avoidance to evaluate for refractory celiac disease.

Complications

Refractory Celiac Disease (RCD): Persistent symptoms and intestinal damage despite strict adherence to a gluten-free diet. It can be divided into:

RCD Type 1: Treated with nutritional support and immunosuppressive therapy.
RCD Type 2: Associated with a higher risk of developing enteropathy-associated T-cell lymphoma (EATL).

Malignancies: Long-standing celiac disease increases the risk of gastrointestinal cancers, particularly EATL and small bowel adenocarcinoma.

Osteoporosis: Malabsorption of calcium and vitamin D increases the risk of fractures in untreated patients.

Key Points

Celiac disease is an autoimmune disorder triggered by gluten ingestion, leading to villous atrophy and malabsorption, especially of fats and nutrients like iron, calcium, and fat-soluble vitamins.
Diagnosis is made with positive serologic tests (IgA tTG) and confirmed by small bowel biopsy showing villous atrophy.
Treatment involves a lifelong gluten-free diet, with symptom resolution typically occurring within weeks.
Complications include refractory celiac disease, increased risk of intestinal malignancies, and osteoporosis from chronic malabsorption.
Monitoring includes repeat serologic testing and nutritional follow-up to assess adherence and manage deficiencies.