Celiac Disease Overview and Genetics

Study Notes

Genetic predisposition plays a major role
The MHC class II association accounts for about 40% of the genetic component.
HLA-DQ2 is positive in 90% of patients; HLA-DQ8 is positive in the remaining 10%
Environmental factors, such as gluten ingestion, trigger the celiac enteropathy.
Gluten, specifically gliadin and glutenin proteins, are digestion-resistant and provoke an immune response

Globally, Celiac Disease affects approximately 1% of the population
Prevalence varies geographically with higher prevalence in Western and Southeastern Europe, and in North and South America.
Prevalence in areas of the developing world is lower, particularly those with less wheat consumption, though is increasing in some areas.
The Saharawi population of Algeria shows the highest prevalence.

Historically, mostly a pediatric disease, with gastrointestinal symptoms like diarrhea, abdominal pain, distended abdomen (potbelly in children) and weight loss.
Nowdays, more adults are diagnosed.
A wide range of extra-intestinal manifestations are common, including anemia, neurological problems (ataxia, peripheral neuropathy, epilepsy), psychiatric disorders, reduced fertility, miscarriages, low birth weight babies, delayed puberty, short stature and complications like osteoporosis, dental enamel hypoplasia, skin conditions (Dermatitis Herpetiformis) and various types of chronic intestinal inflammation.

Non-invasive techniques: Serology (tests for IgA antibodies against gliadin and endomysium, and to tissue transglutaminase)
Invasive techniques: Small intestinal biopsy. Microscopy showing villous atrophy and increased intraepithelial lymphocytes.
HLA-DQ2/DQ8 testing can help rule celiac disease out.
Criteria for diagnosing celiac disease without biopsy may vary based on criteria like those used in ESPGHAN 2012 in children.

Lifelong gluten-free diet is the cornerstone of treatment
Strict avoidance of wheat, rye, barley, oats, and their derivatives is essential
Careful consideration of processed foods, medications, and other substances that may contain gluten is necessary
Follow-up and monitoring is critical to ensure the gluten-free diet is being followed appropriately and to track for complications.

Poor absorption: Can result in malnutrition, bone loss (osteoporosis), dental defects, and other nutrient deficiencies.
Increased risk of lymphoma and other cancers: Particularly within the small intestine
Mental Health disorders: Depression, Anxiety and Irritable Bowl Syndrome
Nutritional deficiencies: Iron deficiency anemia, low vitamin D levels, etc.

A complex interplay of genetic and environmental factors
Gluten peptides trigger an inappropriate immune response in genetically susceptible individuals, leading to inflammation and damage to the intestines.
This involves tissue transglutaminase and an activation of T-helper cells.
The intestinal barrier is compromised, which triggers an inflammatory response.

Infections: Adenovirus and Rotavirus can influence intestinal permeability.
Early childhood feeding: Prolonged breastfeeding before gluten introduction may be protective.

Monitoring: Patients should be monitored regularly for compliance with the gluten-free diet and development of complications
Failure to respond: Continued symptoms despite a gluten-free may suggest other conditions and necessitate further evaluation to rule out complications, additional dietary considerations or non-gluten allergies.
Immunosuppressive Therapy: Necessary in severe or refractory cases of celiac disease and is usually not for short-term management.