Celiac Disease. Symptoms, Causes, Lab Tests, Treatment

Celiac disease is a chronic autoimmune disorder triggered by ingesting gluten, a protein found in wheat, barley, and rye. It affects genetically predisposed individuals and can lead to inflammation and damage of the small intestine, specifically the villi, which is responsible for nutrient absorption.

Celiac Disease Epidemiological Data

Celiac disease is a prevalent autoimmune disorder affecting approximately 1% of the global population. However, its prevalence varies across different regions and populations. The incidence of celiac disease has been increasing globally. This rise is attributed to improved diagnostic methods, heightened awareness, and potential environmental factors. Celiac disease is more common in females than males. While it can develop at any age, certain studies indicate a higher prevalence in children than in adults.

Celiac Disease Symptoms

Celiac disease symptoms vary widely among individuals, ranging from classic gastrointestinal issues to extraintestinal manifestations. Some individuals may even be asymptomatic despite having intestinal damage.

i. Gastrointestinal Symptoms

1. Chronic Diarrhea: Loose, watery stools, often accompanied by urgency.
2. Constipation: Alternating bowel habits can occur.
3. Abdominal Pain: Cramping or general discomfort.
4. Bloating and Gas: Often linked to malabsorption and fermentation of undigested food.
5. Nausea and Vomiting: Can occur after gluten exposure.
6. Steatorrhea: Fatty, pale, foul-smelling stools due to fat malabsorption.

ii. Extraintestinal Symptoms

1. Nutritional Deficiencies
    
   • Iron-deficiency anemia: Fatigue, weakness, pallor.
   • Calcium and Vitamin D Deficiency: Bone pain, fractures, osteoporosis.
   • Folate and Vitamin B12 Deficiency: Neuropathy, glossitis.
2. Neurological Symptoms
    
   • Peripheral neuropathy (tingling or numbness in extremities).
   • Migraines or chronic headaches.
   • Ataxia (loss of balance and coordination).
   • Brain fog and cognitive difficulties.
3. Dermatitis Herpetiformis
    
   • Itchy, blistering rash, typically on elbows, knees, buttocks, and scalp.
   • Often resolves with a gluten-free diet.
4. Mood and Behavioral Symptoms
    
   • Depression, anxiety, irritability.
   • ADHD-like symptoms in children and adults.
5. Chronic Fatigue
    
   • Persistent tiredness, unrelated to activity levels.
6. Growth and Development Issues (in Children)
    
   • Delayed growth or puberty.
   • Short stature or failure to thrive.
   • Behavioral or developmental delays.
7. Infertility and Menstrual Irregularities
    
   • Recurrent miscarriages.
   • Amenorrhea or irregular periods.

Some individuals are "silent" celiac patients, showing no symptoms but still suffering from intestinal damage, detectable through biopsy or serological testing.

For diagnosed individuals adhering to a gluten-free diet, accidental gluten ingestion can lead to:

• Immediate gastrointestinal distress (e.g., diarrhea, cramping).
• Delayed symptoms such as fatigue, brain fog, or joint pain.

Causes of Celiac Disease

A complex interplay of genetic, immunological, and environmental factors causes celiac disease. It occurs in individuals with a genetic predisposition, and its development requires an immune reaction to gluten, a protein found in wheat, barley, and rye.

1. Genetic Factors

HLA-DQ2 and HLA-DQ8 Genes: These genes are found in approximately 95% of individuals with celiac disease (HLA-DQ2) and most remaining cases (HLA-DQ8). However, having these genes does not guarantee disease development—about 30–40% of the general population carry them without ever developing celiac disease.

Family History: First-degree relatives of celiac patients have a significantly higher risk (10–15%) of developing the disease.

2. Gluten Exposure

Gluten is the primary trigger. When ingested, the immune system mistakenly recognizes it as harmful, leading to an inflammatory response.

3. Autoimmune Reaction

Tissue Transglutaminase (tTG): This enzyme modifies gluten peptides in the gut, making them more immunogenic (more likely to provoke an immune response). The immune system produces autoantibodies against tTG, leading to intestinal damage and systemic effects.

Villous Atrophy: Chronic inflammation causes the villi in the small intestine to flatten, resulting in malabsorption.

4. Environmental Triggers

Certain environmental factors can trigger the onset of celiac disease in genetically predisposed individuals, such as infections (mainly gastrointestinal), imbalances in the gut microbiome (dysbiosis), and physical or emotional stress, surgery, or pregnancy.

Laboratory Tests for Celiac Disease Diagnosis and Monitoring

Celiac disease is diagnosed and managed using a combination of serological tests, genetic testing, and intestinal biopsy. Below is a detailed list of the key laboratory tests.

1. Serological Tests (Antibody Tests)

These tests detect specific antibodies produced in response to gluten exposure.

a. Anti-Tissue Transglutaminase Antibodies (tTG)

• tTG-IgA: Most commonly used and highly sensitive/specific for celiac disease. Positive in ~98% of untreated celiac cases.
• tTG-IgG: Used if the patient has IgA deficiency.

First-line test for diagnosis; also used to monitor adherence to a gluten-free diet.

b. Anti-Endomysial Antibodies (EMA)

• IgA antibodies target the connective tissue surrounding smooth muscle. They are highly specific but less sensitive than tTG and are often used to confirm a positive tTG result.

c. Deamidated Gliadin Peptide Antibodies (DGP)

DGP-IgA and DGP-IgG: Useful in patients who test negative for tTG but still show symptoms of celiac disease. Deamidated gliadin peptide antibodies are tested for when serum IgA is low, a common occurrence in celiac disease. It can detect early stages of the disease, particularly in children.

d. Total Serum IgA

Screens for IgA deficiency, which occurs in ~2-3% of celiac patients. Low IgA levels may result in false-negative IgA-based tests (e.g., tTG-IgA or EMA-IgA).

2. Genetic Testing

HLA-DQ2 and HLA-DQ8: These genes are necessary for developing celiac disease. A negative result effectively rules out celiac disease. Used in cases with unclear diagnoses (e.g., seronegative celiac disease, patients on a gluten-free diet before testing). Negative tests rule out almost all cases of celiac disease, including those already on a gluten-free diet; negative tests may help clarify the picture when the result of other testing is unclear; and these tests are used to screen close relatives of patients for genetic risk of celiac disease (Coeliac Disease extended Profile, Celiac Disease Genetic Testing, Coeliac Disease Basic Profile).

3. Intestinal Biopsy

The gold standard for diagnosis. A biopsy of the small intestine (duodenum) is performed via endoscopy. Required for confirmation of celiac disease in most cases, especially when antibody tests are positive.

4. Tests for Nutritional Deficiencies

Celiac disease often causes malabsorption, leading to various deficiencies:

• Iron Studies: Serum ferritin and iron are used to check for iron-deficiency anemia.
• Vitamin D and Calcium: To assess bone health.
• Vitamin B12 and Folate: To detect deficiencies related to malabsorption.
• Magnesium, Zinc, and Selenium: To identify other micronutrient imbalances.

5. Monitoring and Follow-Up Tests

• tTG-IgA: To monitor adherence to a gluten-free diet. Antibody levels should normalize after 6–12 months of strict gluten avoidance.

6. Other Specialized Tests

a. Small Intestinal Permeability Test: This test measures the integrity of the intestinal lining ("leaky gut"). It is not a standard diagnostic test but may be used in functional medicine approaches.

b. Fecal Fat Test: Assesses fat malabsorption in persistent diarrhea or steatorrhea cases.

c. Comprehensive Stool Analysis (Enteroscan Comprehensive): Evaluates digestive function, microbiota balance, and inflammation markers.

Conventional Therapies for Celiac Disease

Celiac disease is a chronic autoimmune condition that currently has no cure. The cornerstone of conventional therapy is a strict, lifelong gluten-free diet. This approach helps prevent symptoms, promotes intestinal healing, and reduces the risk of long-term complications. Below are the key components of conventional treatment:

1. Gluten-Free Diet (GFD)

The only effective treatment for celiac disease is the elimination of gluten from the diet. The gluten-free diet excludes all foods that contain wheat (including spelt, triticale, and kamut), rye, and barley. Unless labeled “gluten-free,” oats should be avoided as they can be contaminated with gluten-containing grains. There are many gluten-free alternatives to wheat: amaranth, buckwheat, corn, millet, rice, and quinoa. There are also alternatives to gluten-containing flour, including potato, rice, soy, tapioca, carob, and bean flour.

2. Nutritional Supplementation

Celiac disease often leads to malabsorption, resulting in nutrient deficiencies. Supplementation addresses these deficiencies:

• Iron: For iron-deficiency anemia. Iron-deficiency anemia is one of the most common extraintestinal signs of celiac disease.
• Calcium and Vitamin D: To improve bone density and prevent osteoporosis. In celiac disease, damage to the intestinal lining often leads to calcium malabsorption and decreased serum calcium levels. Vitamin D deficiency is a common problem in celiac disease. One study found low vitamin D levels in 64% of men and 71% of women with celiac disease.
• Folate and Vitamin B12: For macrocytic anemia and neurological symptoms. Folate and vitamin B12 deficiencies are common in celiac disease. Several studies have demonstrated elevated blood levels of homocysteine in celiac patients. Elevated homocysteine is often attributable to a lack of vitamins B12, B6, and folate.
• Magnesium: A study investigated magnesium status in children and adolescents with celiac disease. While all of the patients with classical celiac disease (with malabsorption) were magnesium deficient, only 1 in 5 patients on a gluten-free diet (no malabsorption) and 1 in 5 patients with silent celiac disease (no malabsorption) were low in magnesium.
• Zinc: Zinc deficiency is common in untreated celiac disease, and a gluten-free diet does not always correct this deficiency; zinc supplementation is considered a necessary part of celiac treatment.
• Fat-soluble vitamins (A, D, E, K): Often deficient due to fat malabsorption.
• Probiotics: They may be recommended to restore gut microbiota. Supplementation with Bifidobacterium infantis NLS super strain in untreated celiac disease patients improved indigestion, constipation, and acid reflux.
• Omega-3 Fatty Acids: A study of serum fatty acid composition in adults with newly diagnosed celiac disease found that concentrations of omega-3 fatty acids were significantly lower than those of a control group.

3. Monitoring and Follow-Up

Regular monitoring is critical to assess response to treatment and detect complications:

• Serological Tests: Anti-tTG antibodies: Levels should normalize after 6–12 months of strict gluten avoidance.
• Symptom Monitoring: Evaluate for ongoing symptoms like fatigue, bloating, or diarrhea.
• Nutritional Assessments: Check levels of iron, vitamin D, calcium, and other critical nutrients.