Celiac Disease for USMLE Step 2
Start your One-Week Free Trial
Already subscribed? Log in »
Celiac Disease for USMLE Step 2
Definition
- Celiac Disease (CD): An autoimmune disorder triggered by gluten ingestion (found in wheat, rye, and barley) in genetically predisposed individuals, leading to immune-mediated damage of the small intestine. This primarily affects the duodenum and jejunum, causing malabsorption.
Pathophysiology
- Immune Response to Gluten: In patients with HLA-DQ2 or HLA-DQ8 alleles, gluten peptides (specifically gliadin) are deamidated by tissue transglutaminase (tTG). These modified peptides are presented to CD4+ T cells, which initiate an inflammatory response.
- Villous Atrophy: Chronic inflammation leads to destruction of the villi in the small intestine, reducing the absorptive surface area.
- Crypt Hyperplasia: Compensatory response to villous atrophy, with increased crypt cell production.
- Intraepithelial Lymphocytosis: An influx of T-lymphocytes into the intestinal epithelium due to the immune response.
Genetic Predisposition
- HLA-DQ2/DQ8: Nearly all patients with celiac disease carry these alleles, though only a minority of carriers develop the disease, indicating the role of environmental and additional genetic factors.
Risk Factors
- Family History: A strong risk factor due to the genetic component.
- Autoimmune Diseases: Celiac disease is more common in patients with conditions such as type 1 diabetes, autoimmune thyroid disease, and Sjögren’s syndrome.
Clinical Features
Gastrointestinal (GI) Symptoms
- Chronic Diarrhea: Often pale, greasy, and foul-smelling due to fat malabsorption (steatorrhea).
- Weight Loss: Common in untreated or advanced cases.
- Abdominal Pain and Bloating: Caused by inflammation and fermentation of unabsorbed nutrients.
- Iron Deficiency Anemia: Common, resulting from impaired iron absorption in the duodenum.
Extraintestinal Manifestations
- Dermatitis Herpetiformis: A pruritic, blistering skin rash, pathognomonic for celiac disease, typically found on the extensor surfaces.
- Neurological Symptoms: Peripheral neuropathy, ataxia, and headaches, potentially related to nutrient deficiencies or immune effects.
- Fatigue and Irritability: Often nonspecific symptoms that may improve on a gluten-free diet.
Diagnosis
Serologic Testing
- IgA Anti-Tissue Transglutaminase (tTG) Antibodies: The most sensitive and specific test for celiac disease.
- IgA Deficiency is more common in celiac disease. In such cases, testing for IgG tTG or IgG deamidated gliadin peptides (DGP) is recommended.
- IgA Endomysial Antibodies (EMA): Highly specific but less frequently used due to higher cost and less availability.
Small Bowel Biopsy
- Gold Standard: Endoscopy with biopsy showing villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis confirms the diagnosis.
- Multiple biopsies are taken from the duodenum, as damage can be patchy.
Genetic Testing
- HLA-DQ2/DQ8 Testing: Useful in excluding the diagnosis if both alleles are absent. However, positive results are 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 sources of gluten (wheat, rye, and barley). Even small amounts of gluten can trigger symptoms and cause intestinal damage.
- Symptom Improvement: GI symptoms generally improve within weeks to months, while histological healing may take longer.
- Nutritional Support: Iron, calcium, vitamin D, and folic acid supplementation are often required to correct deficiencies.
- Dietary Education: A dietitian familiar with celiac disease can help patients identify hidden gluten in processed foods and prevent cross-contamination.
Monitoring
- Serologic Testing: Monitoring IgA tTG levels 6–12 months after starting a gluten-free diet can help assess adherence and mucosal healing.
- Repeat Endoscopy: May be necessary in patients with persistent symptoms to evaluate for refractory celiac disease.
Complications
- Refractory Celiac Disease: A rare condition in which symptoms and villous atrophy persist despite strict adherence to a gluten-free diet. It may be classified as RCD Type 1 (responding to immunosuppressive therapy) or RCD Type 2, which is associated with a poor prognosis and risk of progression to enteropathy-associated T-cell lymphoma (EATL).
- Malignancies: Untreated 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 celiac patients.
Key Points
- Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals, leading to small intestinal damage and malabsorption.
- Diagnosis relies on positive serologic tests (IgA tTG) and confirmation by small bowel biopsy showing villous atrophy.
- A gluten-free diet (GFD) is the only effective treatment, resulting in symptom resolution and intestinal healing.
- Complications include refractory celiac disease, increased risk of intestinal malignancies (e.g., EATL), and osteoporosis due to chronic malabsorption.
- Lifelong follow-up with serologic testing and nutritional monitoring is required to ensure adherence and manage complications.