Celiac Disease for the ABIM
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Celiac Disease for American Board of Internal Medicine Exam
Definition
- Celiac Disease (CD): A chronic autoimmune disorder where ingestion of gluten (found in wheat, rye, and barley) triggers an immune-mediated response that leads to inflammation and damage of the small intestine, primarily affecting the proximal small bowel (duodenum and jejunum). This results in malabsorption of nutrients.
Pathophysiology
- Immune-Mediated Response: In genetically predisposed individuals (those carrying HLA-DQ2 or HLA-DQ8 alleles), gluten peptides (specifically gliadin) are deamidated by tissue transglutaminase (tTG) in the small intestine. These modified peptides are presented by antigen-presenting cells to CD4+ T-cells, initiating an inflammatory response.
- Villous Atrophy: Chronic inflammation leads to the destruction of the villi in the small intestine, resulting in villous atrophy and loss of surface area, which impairs nutrient absorption.
- Crypt Hyperplasia: Compensatory increase in crypt cell production, but the lack of functional villi leads to malabsorption.
- Genetic Predisposition: Almost all patients with celiac disease carry the HLA-DQ2 or HLA-DQ8 genes. However, not all carriers of these genes develop the disease, suggesting additional environmental or genetic factors play a role.
Risk Factors
- Genetics: A strong family history of celiac disease increases the risk.
- Autoimmune Diseases: There is a higher prevalence of celiac disease in individuals with other autoimmune conditions, such as type 1 diabetes, autoimmune thyroiditis, and Sjögren’s syndrome.
- Environmental Factors: Early childhood infections and timing of gluten introduction in infants may play a role, but data are inconclusive.
Clinical Features
Celiac disease presents with a wide spectrum of symptoms, ranging from classic malabsorptive symptoms to non-GI manifestations.
Gastrointestinal (GI) Manifestations
- Diarrhea: Chronic, often foul-smelling and greasy due to fat malabsorption (steatorrhea).
- Weight Loss: Common in more advanced disease due to malabsorption.
- Abdominal Pain and Bloating: Resulting from inflammation and fermentation of unabsorbed nutrients.
- Nutrient Deficiencies: Malabsorption can lead to deficiencies in iron, calcium, vitamin D, and folate, resulting in:
- Iron Deficiency Anemia: Most common presentation due to impaired absorption in the duodenum.
- Fat-Soluble Vitamin Deficiencies: Can lead to osteoporosis (vitamin D deficiency) and coagulopathy (vitamin K deficiency).
Extraintestinal Manifestations
- Dermatitis Herpetiformis: A pathognomonic, pruritic rash that presents with symmetrical vesicles, commonly on the extensor surfaces (e.g., elbows, knees, buttocks). It reflects gluten sensitivity and responds to a gluten-free diet.
- Neurological Manifestations: Peripheral neuropathy, ataxia, and headaches can occur, potentially linked to vitamin deficiencies or direct immune-mediated effects.
- Infertility and Recurrent Miscarriages: Common in untreated celiac disease.
- Fatigue and Irritability: Common, non-specific symptoms that often improve on a gluten-free diet.
Diagnosis
Serologic Testing
- IgA Anti-Tissue Transglutaminase Antibodies (IgA tTG): The most sensitive and specific initial test for celiac disease.
- False negatives can occur in patients with IgA deficiency, which is more common in celiac patients. In these cases, IgG tTG or IgG deamidated gliadin peptide (DGP) antibodies are useful.
- IgA Endomysial Antibodies (EMA): Highly specific but less commonly used due to cost.
- IgG Deamidated Gliadin Peptides (DGP): Used in cases of IgA deficiency or when tTG testing is inconclusive.
Small Bowel Biopsy
- Gold Standard for Diagnosis: Endoscopy with duodenal biopsy is required for definitive diagnosis.
- Findings include villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis.
- Multiple biopsies are recommended, as the damage may be patchy.
Genetic Testing
- HLA-DQ2 and HLA-DQ8 Testing: Useful in excluding celiac disease, as absence of both genes makes the diagnosis unlikely. However, presence of these genes is not diagnostic, as they are also found in the general population.
Gluten Challenge
- For patients already on a gluten-free diet but without a confirmed diagnosis, a gluten challenge may be performed. The patient resumes a gluten-containing diet for several weeks before repeat serology or biopsy.
Management
Gluten-Free Diet (GFD)
- Lifelong Gluten-Free Diet: The mainstay of treatment. Patients must avoid all foods containing wheat, rye, barley, and their derivatives. Even small amounts of gluten can trigger symptoms and intestinal damage.
- Label Reading: Patients must be educated on identifying hidden sources of gluten in processed foods, medications, and supplements.
- Nutritional Counseling: A dietitian experienced in managing celiac disease is essential for dietary education and ensuring balanced nutrition.
- Symptom Resolution: Most patients experience improvement in GI symptoms and energy levels within weeks of starting the diet. However, histological healing of the small intestine may take months to years.
Refractory Celiac Disease
- Non-Responsive Celiac Disease: Symptoms persist despite adherence to a strict gluten-free diet. Common causes include inadvertent gluten exposure, concurrent disorders like small intestinal bacterial overgrowth (SIBO), or irritable bowel syndrome.
- Refractory Celiac Disease (RCD): A rare but serious form where symptoms and villous atrophy persist despite a strict GFD for over 12 months.
- RCD Type 1: Treated with nutritional support and immunosuppressants.
- RCD Type 2: Carries a poor prognosis due to the risk of progression to enteropathy-associated T-cell lymphoma (EATL). Treatment involves more aggressive immunosuppression or chemotherapy.
Complications
- Malignancy: Patients with celiac disease are at increased risk for intestinal malignancies, including:
- Enteropathy-Associated T-Cell Lymphoma (EATL): A rare but aggressive small bowel lymphoma associated with long-standing, untreated celiac disease.
- Small Bowel Adenocarcinoma: Another rare complication.
- Osteoporosis: Due to malabsorption of calcium and vitamin D.
- Infertility: Particularly in women, untreated celiac disease can lead to infertility and complications during pregnancy, including miscarriage and preterm delivery.
Monitoring
- Follow-Up Serology: Measurement of IgA tTG or EMA levels 6–12 months after starting a gluten-free diet is recommended to assess adherence and mucosal healing.
- Repeat Biopsy: In patients with persistent symptoms despite a strict GFD, repeat endoscopy and biopsy may be warranted to evaluate for refractory disease.
Key Points
- Celiac disease is an autoimmune disorder triggered by gluten ingestion, leading to small intestinal damage, malabsorption, and a wide range of systemic manifestations.
- Diagnosis is confirmed by serologic testing (IgA tTG) and duodenal biopsy, showing villous atrophy and crypt hyperplasia.
- The mainstay of treatment is a lifelong gluten-free diet, which resolves symptoms and prevents complications.
- Refractory celiac disease is rare but should be considered in patients who do not improve on a gluten-free diet. Complications include osteoporosis and intestinal malignancies such as EATL.
- Lifelong follow-up with serologic testing and nutritional counseling is essential to ensure adherence to the diet and manage complications.