Coeliac disease

Gluten-sensitive enteropathy

Pathogenesis:

• Autoimmune disorder triggered by gluten in genetically-predisposed individuals

Clinical manifestations

• Classic symptoms related to malabsorption:
  • Diarrhoea
  • Steatorrhoea
  • Weight loss
  • Nutrient or vitamin deficiencies
• Majority have only minor GIT complaints
• Associated conditions:
  • Dermatitis herpetiformis (grouped intensely pruritic papules and vesicles, mostly on elbows, dorsal forearms, knees, scalp, back and buttocks)
  • Atrophic glossitis
  • Metabolic bone disease
  • Iron deficiency anaemia (UTD says coeliac disease is found in up to 10% of patients presenting for investigation of IDA)
  • Selective IgA deficiency
  • Other conditions with autoimmune components
  • Increased risk for lymphoma and GIT cancer (unclear if the incidence of cancer is affected by good management of coeliac disease)

Risk factors:

• First and second degree relative with confirmed coeliac disease
• T1DM
• Autoimmune thyroiditis
• Down and Turner syndromes
• Pulmonary haemosiderosis

Investigation:

• Serologic tests
  • Tissue transglutaminase-IgA is the single preferred test
  • Serum tissue transglutaminase IgA and endomysial IgA have similar sensitivities
  • Sensitivity depends on severity of disease
  • Tests may become negative within weeks of adherence to gluten-free diet
  • Positive serology generally mandates a small bowel biopsy to confirm diagnosis
  • Serologic tests can give a false negative in: IgA deficiency, gluten-free diet, and mild disease
• Gastroscopy with small bowel biopsy
  • Look for:
    • Atrophic appearing mucosa with loss of folds
    • Visible fissures
    • Nodularity
    • Scalloping
    • Prominent submucosal vascularity
    • However, endoscopic visual features alone have a low sensitivity (60-90%)
    • Features can also be seen with giardiasis, autoimmune enteropathy, and HIV infection
  • Biopsy:
    • At least four biopsies of post-bulbar duodenum
    • Some advocate for bulb biopsies too, but these are probably not necessary, and if taken should be sent separately and labelled as such to avoid the false-positive finding of villous atrophy on those samples
    • I don't THINK it makes a difference whether they are on gluten for that part

Diagnosis

• Diagnostic criteria:
  • Duodenal biopsy samples showing increased intraepithelial lymphocytes with crypt hyperplasia or also with villous atrophy, in a patient with positive coeliac serology
• Patients on a gluten-containing diet:
  • Low disease probability (absence of symptoms or signs of malabsorption such as chronic diarrhoea/steatorrhoea or weight loss; absence of family history; chinese, japanese or sub-saharan african descent)
    • Serologic testing
      • Negative test for an individual with low risk of coeliac disease has a high negative predictive value and obviates the need for small bowel biopsy
    • If positive, gastroscopy with small bowel biopsy
  • High disease probability (clinical presentation highly suggestive for coeliac disease, such as chronic diarrhoea/steatorrhoea with weight loss; both risk factors and consistent symptoms/signs)
    • Both serologic testing and small bowel biopsy
• Patients on a gluten-free diet
  • Do serologic testing anyway
  • If negative, do HLA-DQ2/DQ8 testing
    • If negative coeliac disease excluding
    • If positive, give them gluten for 8 weeks then repeat serology and small bowel biopsy
• Positive serology and nondiagnostic biopsies:
  • False-positive tTg - see UTD
  • False-negative biopsy - can have a patchy distribution or initially be confined to duodenal bulb
  • Can do further tests like HLA-DQ2/DQ8 genotyping - would refer to gastro, I guess
• Negative serology and abnormal small bowel biopsy
  • Genetic testing
  • If positive, gluten free diet for 12-24 months and monitor clinical response