Celiac disease or gluten sensitive enteropathy (GSE) is non-allergic immune-mediated sensitivity to gluten or storage proteins found in wheat, barley and rye as well as close relatives of these specific grains such as spelt and triticale in genetically susceptible individuals.

Epidemiology

• Incidence - affects 0.5 to 1.0 percent of the general population of the United States
• Sex - F>M
• Ethnic - mainly affects Caucasians (North European ancestry)
• Age - median 20-30 years

Risk Factors

• HLA DQ2 allele (90-95%)
• HLA DQ8 (5-10%)
• 75% concordance in monozygotic twins

Pathophysiology

• Inappropriate immune response to ingested wheat gluten proteins and related proteins in barley and rye
• Celiac lesion is characterized by villous atrophy, crypt hyperplasia, and a dense infiltration of lymphocytes in the epithelium and lamina propria
• tTG has been identified as the major target autoantigen of the endomysial smooth muscle antibody (EMA).
• tTG is an enzyme that catalyzes the replacement by primary amines (cross-linking) as well as the hydrolysis (deamidation) of amide groups of protein and peptide-bound glutamine residues
• Gliadin, a glutamine-rich protein, has been identified as a specific substrate for tTG, and deamidation of gliadin has been reported to improve the overall diagnostic performance of the conventional antigliadin antibody assays

Clinical Presentation

• Clinical manifestations are extremely varied and tend to differ by age group
  • General - anemia, fatigue, weight loss
  • Pediatrics - diarrhea, abdominal distention, or symptoms of malnutrition such as short stature, anemia, defects in dentition, failure to thrive, or developmental delay
  • Adults - abdominal pain, flatulence, diarrhea, and, in severe cases, steatorrhea
    • Extraintestinal features among adults include fatigue and malaise, which may occur independently of anemia
  • Neurologic - psychiatric problems
  • Associated conditions
    • Dermatitis herpetiformis
    • Increased risk of lymphoma
• Additional clinical presentations include neuromuscular abnormalities, infertility and mouth ulcers

Treatment

• Gluten-free diet may control GSE and associated risks

Diagnosis

• Laboratory testing
  • Tissue transglutaminase (tTg) antibodies (IgA and IgG) by ELISA.
    • Has been reported to have equivalent diagnostic utility as EMA IgA by IFA for celiac disease
  • Deaminated gliadin antibodies (IgG and IgA) by ELISA
    • Higher sensitivity/specificity than conventional antigliadin antibody tests
  • IgA deficiency
    • If IgA deficiency is suspected, determination of IgA levels prior to antibody testing is recommended
    • If patient is IgA deficient, all antibody testing will need to be performed using IgG tests to prevent underdiagnosis of celiac disease
  • In some cases, tTg and/or deamidated gliadin IgG antibodies maybe present despite detectable levels of IgA
    • Thus, if suspicion for celiac disease is strong and tTg IgA is negative, testing for DPG IgA, tTG and DPG IgG antibodies may be clinically relevant
  • HLA testing is usually unnecessary for diagnosing Celiac disease
  • F-actin IgA - presence of antibodies indicates intestinal villus atrophy
• Tissue diagnosis
  • Duodenal biopsy
• Criteria for diagnosis
  • Positive EMA or tTG IgA serologic test
  • Positive tissue biopsy
  • Complete resolution of clinical symptoms and/or a seronegative response following a gluten-free diet (GFD)
    • Gluten rechallenge not necessary except in patients who had no initial biopsy or uncharacteristic biopsy

Disease monitoring

• Antibody titers
  • Usually wane after patient adheres to diet
  • Will become elevated again if gluten reintroduced